This paper addresses the arguments in favour of both the decentralization and centralization of public policy making. It points out that the same arguments are sometimes used to advance either claim and that in different countries opposite arguments are used to support the same claim. Clearly, the inherent features of centralization and decentralization are far from obvious. A closer look at the attention given to the issue by political parties at the national level in four European countries reveals that decentralization becomes an issue in these countries at different periods and as a cause of different arguments, which rather reflect the dominant values in the political culture than refer to inherent properties of decentralization itself. An analysis of opinions of local elites points at the relation between their opinion on decentralizing responsibilities in a specific field and the support for existing institutional arrangements, their own influence in the policy field and the predisposition towards decentralization tendencies. This results in the conclusion that the support for decentralization tendencies is more closely related to existing specific institutional arrangements, and to the degree to which it is expected to influence one's own position, than to its inherent merits.
Background and ObjectivesTwo phase I drug interaction studies were performed with oral enzalutamide, which is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC).MethodsA parallel-treatment design (n = 41) was used to evaluate the effects of a strong cytochrome P450 (CYP) 2C8 inhibitor (oral gemfibrozil 600 mg twice daily) or strong CYP3A4 inhibitor (oral itraconazole 200 mg once daily) on the pharmacokinetics of enzalutamide and its active metabolite N-desmethyl enzalutamide after a single dose of enzalutamide (160 mg). A single-sequence crossover design (n = 14) was used to determine the effects of enzalutamide 160 mg/day on the pharmacokinetics of a single oral dose of sensitive substrates for CYP2C8 (pioglitazone 30 mg), CYP2C9 (warfarin 10 mg), CYP2C19 (omeprazole 20 mg), or CYP3A4 (midazolam 2 mg).ResultsCoadministration of gemfibrozil increased the composite area under the plasma concentration–time curve from time zero to infinity (AUC∞) of enzalutamide plus active metabolite by 2.2-fold, and coadministration of itraconazole increased the composite AUC∞ by 1.3-fold. Enzalutamide did not affect exposure to oral pioglitazone. Enzalutamide reduced the AUC∞ of oral S-warfarin, omeprazole, and midazolam by 56, 70, and 86 %, respectively; therefore, enzalutamide is a moderate inducer of CYP2C9 and CYP2C19 and a strong inducer of CYP3A4.ConclusionsIf a patient requires coadministration of a strong CYP2C8 inhibitor with enzalutamide, then the enzalutamide dose should be reduced to 80 mg/day. It is recommended to avoid concomitant use of enzalutamide with narrow therapeutic index drugs metabolized by CYP2C9, CYP2C19, or CYP3A4, as enzalutamide may decrease their exposure.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-015-0283-1) contains supplementary material, which is available to authorized users.
Public sector reform: an overview of recent literature and research on NPM and alternative paths Michiel De Vries Juraj Nemec Article information: To cite this document: Michiel De Vries Juraj Nemec , (2013),"Public sector reform: an overview of recent literature and research on NPM and alternative paths"If you would like to write for this, or any other Emerald publication, then please use our Emerald for Authors service information about how to choose which publication to write for and submission guidelines are available for all. Please visit www.emeraldinsight.com/authors for more information. About Emerald www.emeraldinsight.comEmerald is a global publisher linking research and practice to the benefit of society. The company manages a portfolio of more than 290 journals and over 2,350 books and book series volumes, as well as providing an extensive range of online products and additional customer resources and services.Emerald is both COUNTER 4 and TRANSFER compliant. The organization is a partner of the Committee on Publication Ethics (COPE) and also works with Portico and the LOCKSS initiative for digital archive preservation. AbstractPurpose -The purpose of this article is to discuss the idea that new public management (NPM) would be passé. Design/methodology/approach -The article is based on a review of existing theories. Findings -The article argues that NPM has two dimensions, namely the minimization of the role of government vis-à -vis society and the improvement of the internal performance of the public sector. Whereas the first dimension is indeed more and more disputed nowadays this does not imply this also goes for the second dimension. The conclusion of this article calls for explanatory empirical research in order to explain the increasing variance in reforms among countries, by investigating which factors are determinative for decisions by governments to turn one way or the other. Practical implications -It is far from certain which way the public sector is heading in the so-called post-NPM era. Some countries are still implementing NPM-kind of reforms, either by downsizing or by introducing performance management. Other countries have chosen alternative paths. All this implies an increased variance between countries in the direction public sector reforms take. It requires quite different support from administrative sciences compared to the one-size-fits-all recommendations for public sector reforms -in conformity with the maxims of NPM -as witnessed in the past decades. Originality/value -The article contributes to the discussion about the role of NPM today. It presents original conclusions about diverging developments based on the unique comprehensive literature review on the topic.
Background and ObjectivesOral enzalutamide (160 mg once daily) is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This article describes the pharmacokinetics of enzalutamide and its active metabolite N-desmethyl enzalutamide.MethodsResults are reported from five clinical studies.ResultsIn a dose-escalation study (n = 140), enzalutamide half-life was 5.8 days, steady state was achieved by day 28, accumulation was 8.3-fold, exposure was approximately dose proportional from 30–360 mg/day, and intersubject variability was ≤30 %. In a mass balance study (n = 6), enzalutamide was primarily eliminated by hepatic metabolism. Renal excretion was an insignificant elimination pathway for enzalutamide and N-desmethyl enzalutamide. In a food-effect study (n = 60), food did not have a meaningful effect on area under the plasma concentration–time curve (AUC) of enzalutamide or N-desmethyl enzalutamide, and in an hepatic impairment study, AUC of the sum of enzalutamide plus N-desmethyl enzalutamide was similar in men with mild (n = 6) or moderate (n = 8) impairment (Child–Pugh Class A and B) versus men with normal hepatic function (n = 14). In a phase III trial, an exposure-response analysis of steady-state predose (trough) concentrations (Ctrough) versus overall survival (n = 1103) showed that active treatment Ctrough quartiles for 160 mg/day were uniformly beneficial relative to placebo, and no threshold of Ctrough was associated with a statistically significant better response.ConclusionsEnzalutamide has predictable pharmacokinetics, with low intersubject variability. Similar efficacy was observed in patients across the concentration/exposure range associated with a fixed oral dose of enzalutamide 160 mg/day.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-015-0271-5) contains supplementary material, which is available to authorized users.
Eager to learn from private sector trends, practitioners in (semi)public organizations across the world have recently turned their eyes to the concept of work engagement to improve employee performance. Studies in the private sector show that work engagement is a more robust predictor of performance than, for example, satisfaction. The goal of this study is to find out whether the effects of work engagement on attitudinal, behavioral, and performance outcomes within the semipublic and public sector are also as high as expected and whether these relationships differ between the public, semipublic, and private sector. The results of the cross-sectoral meta-analysis of 130 studies showed that the most noticeable significant sectoral differences can be found in the mean work engagement and the effects of work engagement on the level of attitudinal outcomes (job satisfaction and commitment) and behavioral outcomes (workaholism and turnover intention).
In the past 20 years, decentralization has been proposed as a strategy for enhancing public participation. Aid-providing organizations, such as the World Bank, stimulated decentralization processes in several countries in the hope that this would promote civic empowerment, diminish corruption, enhance efficiency, and improve public service delivery. This assumption forms the basis for a comparative analysis into the relation between decentralization and participation at the local level in Brazil, Japan, Russia and Sweden. A multi-level regression analysis using the data of the Democracy and Local Governance Project was undertaken in order to test the `one size fits all' and the `diversity in development' hypotheses. The results show that the second hypothesis was corroborated. Perceived autonomy had a different impact on openness to participation depending on the country considered; in one country (Japan), perceived autonomy diminished public officials' willingness to be open to public participation.
Ritodrine is a beta 2-adrenoceptor agonist used for the management of preterm labour. It is inactivated by conjugation with sulphate and glucuronic acid. There is more ritodrine sulphate than ritodrine glucuronide in urine from the newborn whereas equal amounts of ritodrine glucuronide and sulphate are excreted in maternal urine [Clin. Pharmacol. Ther 44, 634-641, 1988]. We show that, in the mid-gestational human fetal liver, ritodrine sulphotransferase is well expressed, whereas the glucuronidation of ritodrine is little developed compared to the adult liver. The average sulphotransferase activity was 308 pmol.min-1 per mg protein in fetal (N = 48) and 145 pmol.min-1 per mg protein in adult (N = 32) liver. The rates of ritodrine sulphation in fetal gut, lung and kidney were higher than in the corresponding adult tissues. The development and tissue distribution patterns of ritodrine sulphotransferase are consistent with those of dopamine sulphotransferase. Ritodrine and dopamine are sulphated by thermolabile enzymes. The activity of glucuronyl transferase was measurable in only 5 of the 48 foetal livers assayed, and in those in which could be assayed, the average activity was 44.6 pmol.min-1 per mg protein, one-tenth of that in adult livers (524 pmol.min-1 per mg protein).
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