Influence of CYP2D6 genotype on the disposition of the enantiomers of venlafaxine and its major metabolites in postmortem femoral blood

Venlafaxine (VEN) is an antidepressant drug mainly metabolized by the cytochrome P450 (CYP) enzyme CYP2D6 to the active metabolite O-desmethylvenlafaxine (ODV). VEN is also metabolized to N-desmetylvenlafaxine (NDV) via CYP3A4. ODV and NDV are further metabolized to N,O-didesmethylvenlafaxine (DDV). VEN is a racemic mixture of the S- and R-enantiomers and these have in vitro displayed different degrees of serotonin and noradrenaline reuptake inhibition. The aim of the study was to investigate if an enantioselective analysis of VEN and its metabolites, in combination with genotyping for CYP2D6, could assist in the interpretation of forensic toxicological results in cases with different causes of deaths. Concentrations of the enantiomers of VEN and metabolites were determined in femoral blood obtained from 56 autopsy cases with different causes of death. The drug analysis was done by liquid chromatography tandem mass spectrometry (LC/MS/MS) and the CYP2D6 genotyping by PCR and pyrosequencing. The mean (median) enantiomeric S/R ratios of VEN, ODV, NDV and DDV were 0.99 (0.91), 2.17 (0.93), 0.92 (0.86) and 1.08 (1.03), respectively. However, a substantial variation in the relationship between the S- and R-enantiomers of VEN and metabolites was evident (S/R ratios ranging from 0.23 to 17.6). In six cases, a low S/R VEN ratio (mean 0.5) was associated with a high S/R ODV ratio (mean 11.9). Genotyping showed that these individuals carried two inactive CYP2D6 genes indicating a poor metabolizer phenotype. From these data we conclude that enantioselective analysis of VEN and ODV can predict if a person is a poor metabolizer genotype/phenotype for CYP2D6. Knowledge of the relationship between the S- and R-enantiomers of this antidepressant drug and its active metabolite is also important since the enantiomers display different pharmacodynamic profiles.     

Transfer of academic research: uncovering the grey zone

In this study, we respond to calls for further investigation on why and how scientists choose to commercialize their research. Mowery (University entrepreneurship and technology transfer: process design, and intellectual property, Elsevier, Oxford 2005), in his criticism of the US-system, emphasizes the need for multiple channels between university and industry. His argument makes the case of Sweden interesting, where the researchers own the intellectual property of their research. Sweden thus constitutes a unique case where data can be found on which choices researchers make in a setting where a variety of channels for transfer are available. Our empirical data, collected through case studies, allowed for the expansion of the typology for mechanisms for transfer of academic research as well as the development of a typology for determinants for researchers’ choice to engage in transfer of research. Apart from those contributions to the theoretic discussion, the data also provided policy implications.     

Uncertainty,risk, and trust: The Swedish—German general staff negotiations of 1910

Despite a protracted and well‐established policy of neutrality, in 1910, Sweden decided to enter into negotiations with Germany concerning military collaboration in case of a Russian attack against Germany and Sweden. This article argues that behind the Swedish decision to enter into the talks was Swedish trust towards Germany to the effect that Germany would not exploit the talks for its own interests. The article discusses the phenomenon of inter‐state trust in terms of risk and uncertainty, and analyzes the Swedish decision process leading to the general staff negotiations.     

Direct Democracy and its Critics: Support for Direct Democracy and ‘Stealth’ Democracy in Finland

In this article support for direct democracy and for stealth democracy in Finland is analysed. Stealth democracy represents a step towards a democracy in which there would be even less citizen involvement than in the representative form of today's democracy. The authors found that both options gained significant support among the Finnish electorate. Additionally, they found that it is mostly the same variables that contribute to the probability of citizens being supporters of either direct democracy or stealth democracy. It is the people with less education, who do not know much about politics and who feel that the current system does not respond to citizens' needs, that want change. The direction of change appears to be a matter of secondary interest. Political ideology affects which of the two options respondents favour. Right-wing citizens are more likely to favour stealth democracy. Citizens leaning to the left are more interested in direct democracy.     

Silencer or Amplifier? The European Union Presidency and the Nordic Countries

How did the three Nordic European Union member states approach their periods as holders of the European Union (EU) Council Presidency? Two radically different predictions about the impact of the Presidency on member state behaviour can be found in the literature. Some maintain that the position functions as an amplifier, strengthening the already existing tendency to propagate national concerns. Others argue that the Presidency functions as a silencer, subordinating national material interests to the benefit of common European concerns. In this article we analyse the ways in which Finland, Sweden and Denmark actually performed the Presidency role. Which of the competing interpretations is most appropriate? Was the Presidency role performed differently by the three countries? Our main finding is that the Presidency generally functioned as an amplifier during the Nordic presidencies. There are, however, interesting differences between the three states, Denmark being the least constrained in using the Presidency to further national interests whereas Finland was most anxious not to violate norms of impartiality and neutrality, even in cases where such behaviour ran contrary to national interests.     

European security and early warning systems: from risks to threats in the European Union’s health security sector

This article critically examines a poorly understood aspect of the European security landscape: early warning systems (EWSs). EWSs are socio-technical systems designed to detect, analyse, and disseminate knowledge on potential security issues in a wide variety of sectors. We first present an empirical overview of more than 80 EWS in the European Union. We then draw on debates in Critical Security Studies to help us make sense of the role of such systems, tapping into conceptual debates on the construction of security issues as either “threat” or “risk” related. Finally, we study one EWS – the Early Warning and Response System for infectious diseases – to understand how it works and how it reconciles risk – versus threat-based security logics. Contrary to assumptions of a clear distinction between risk- and threat-based logics of security, we show that EWSs may serve as a “transmission belt” for the movement of issues from risk into threats.     

Collective Political Action as Civic Voluntarism: Analysing Ethnic Associations as Political Participants by Translating Individual-level Theory to the Organizational Level

This article presents and empirically evaluates an analytical experiment in which we seek to translate individual-level explanations of differences in political participation to an organizational level. Utilizing the Civic Voluntarism Model, we analyse the consequences of voluntary associations’ politically valuable ‘resources’, ‘motivation’, and ‘recruitment networks’. Using data from a survey of ethnic associations in Stockholm, Sweden, results suggest that the overall logic of how associational-level political participation is encouraged resembles corresponding mechanisms on the individual level. We conclude that both our theoretical argument and empirical findings merit further analyses of civil society actors’ political participation with the approach taken in this study.     

Housing as a Social Right: Implications for Welfare State Theory

The article contributes to two central and interrelated discourses in welfare state theory and housing policy. One concerns the meaning of a 'right to housing' , and the other concerns the meaning of the dichotomy 'universal'–'selective' in housing policy . The right to housing is best seen as a political 'marker of concern' pointing out housing as an area for welfare state policy. The more precise meaning of the idea is always defined socially, in a specific national context of relations between state, citizen, and markets in housing provision. Two alternative interpretations of a right to housing are suggested, each related to a certain logic of housing provision. In a selective housing policy, the state provides a 'protected' complement to the general housing market, and the right to housing implies some legalistic minimum rights for households of lesser means. In a universal housing policy, the state provides correctives to the general housing market in order to make housing available to all types of households, and the right to housing is best seen as a social right in Marshall's meaning of an obligation of the state towards society as a whole. The concepts of 'universal' and 'selective' may be applied to either the political discourse or the social outcome of policies. Furthermore, they may refer to different political levels (e.g. welfare state level, sector level, and policy instrument level). If the dichotomy is not specified in those two respects, the distinction between a universal and a selective policy will always be seriously blurred.     

Uncertainty, risk, and trust: The Swedish—German general staff negotiations of 1910

Despite a protracted and well-established policy of neutrality, in 1910, Sweden decided to enter into negotiations with Germany concerning military collaboration in case of a Russian attack against Germany and Sweden. This article argues that behind the Swedish decision to enter into the talks was Swedish trust towards Germany to the effect that Germany would not exploit the talks for its own interests. The article discusses the phenomenon of inter-state trust in terms of risk and uncertainty, and analyzes the Swedish decision process leading to the general staff negotiations.     

Empowering Members of Ethnic Organisations: Tracing the Political Integration Potential of Immigrant Associations in Stockholm

The voluminous participation literature notwithstanding, knowledge is still scarce on how voluntary associations more precisely provide their members with politically significant human and social capital. This article focuses on the capacities of immigrant organisations to promote the political integration of ethnic minority members. Analysing a unique dataset, based on face-to-face interviews with representatives of 106 organisations of four different immigrant groups in Greater Stockholm, the study empirically investigates what the authors refer to as an association's ' political integration potential ' (PIP) – the possibility of a given ethnic association to promote the inclusion of its members in the political community of the host society. As elements of PIP, the article examines associational-level political activity as well as support and mobilisation of individual members, and analyses how the former may be induced by the latter. Furthermore, the article tries to explain why some types of organisations do better than others in these respects. It finds that size and diversification of associations have an important impact on PIP, thus explaining observed differences between associations of the ethnic categories included in this study.