Residual effects of esmirtazapine on actual driving performance: overall findings and an exploratory analysis into the role of CYP2D6 phenotype

INTRODUCTION: Esmirtazapine is evaluated as a novel drug for treatment of insomnia. PURPOSE: The present study was designed to assess residual effects of single and repeated doses of esmirtazapine 1.5 and 4.5 mg on actual driving in 32 healthy volunteers in a double-blind, placebo-controlled study. Treatment with single doses of zopiclone 7.5 mg was included as active control. METHODS: Treatments were administered in the evening. Driving performance was assessed in the morning, 11 h after drug intake, in a standardized on-the-road highway driving test. The primary study parameter was standard deviation of lateral position (SDLP), a measure of "weaving". All subjects were subjected to CYP2D6 phenotyping in order to distinguish poor metabolizers from extensive metabolizers of esmirtazapine. RESULTS: Overall, esmirtazapine 1.5 mg did not produce any clinically relevant change in SDLP after single and repeated dosing. Driving impairment, i.e., a rise in SDLP, did occur after a single-dose administration of esmirtazapine 4.5 mg but was resolved after repeated doses. Acute driving impairment was more pronounced after both doses of esmirtazapine in a select group of poor metabolizers (N = 7). A single-dose zopiclone 7.5 mg also increased SDLP as expected. CONCLUSION: It is concluded that single and repeated doses of 1.5 mg esmirtazapine are generally not associated with residual impairment. Single-dose administration of 4.5 mg esmirtazapine was associated with residual impairment that generally resolved after repeated administration. Exploratory analysis in a small group of poor CYP 2D6 metabolizers suggested that these subjects are more sensitive to the impairing effects of esmirtazapine on car driving

Strategic Group Performance and Dynamics under Different Economic Conditions

We analyse strategic groups in the German insurance market. We use cluster analysis to subdivide insurance groups into strategic groups. Furthermore, we analyse whether strategic group affiliation can affect the performance of the insurance groups' property-liability subsidiaries. In addition, we examine the consequences of the financial crisis of 2008 on the competitive situation in the German insurance sector and examine whether changes in strategic group affiliation can be considered as a consequence of the financial crisis. Using a data set of 829 firm-year observations for the years 2004-2012, our results indicate the existence of three strategic group in the German insurance sector. In addition, we find that performance differences at the subsidiary level can be attributed to strategic group affiliation. Furthermore, we do not find evidence that the financial crisis induced changes in strategic group affiliation

Insurability of Climate Risks

The IPCC 2007 report noted that both the frequency and strength of hurricanes, floods and droughts have increased during the past few years. Thus, climate risk, and more specifically natural catastrophes, are now hardly insurable: losses can be huge (and the actuarial pure premium might even be infinite), diversification through the central limit theorem is not possible because of geographical correlation (a lot of additional capital is required), there might exist no insurance market since the price asked by insurance companies can be much higher than the price householders are willing to pay (short-term horizon of policyholders), and, due to climate change, there is more uncertainty (and thus additional risk). The first idea we will discuss in this paper, about insurance markets and climate risks, is that insurance exists only if risk can be transferred, not only to reinsurance companies but also to capital markets (through securitization or catastrophes options). The second one is that climate is changing, and therefore, not only prices and capital required should be important, but also uncertainty can be very large. It is extremely difficult to insure in a changing environment. The Geneva Papers (2008) 33, 91–109. doi:10.1057/palgrave.gpp.2510155

Reinsurance Brokers and Advice Quality: Is There a Need for Regulation?

Brokers play an increasing role in the distribution of reinsurance. In order to analyse reinsurance brokers' advice quality, we employ a model in which a monopoly broker advises cedents to buy a particular one out of similar reinsurance policies that cost the same but differ in details. The broker decides on how much to invest in his advice quality and on the price to charge for his service. We find that the broker's advice quality is generally lower and the price for his service higher than in the social optimum, even in the presence of a potential new entrant. The Geneva Risk and Insurance Review (2009) 34, 20–46. doi:10.1057/grir.2008.14

Statistical approaches to evaluate the aquatic ecosystem qualities of a significant mining area: Emet stream basin (Turkey)

WOS: 000330992400017Emet Stream is one of the most important branches of Uluabat Lake (Ramsar area) and also one of Turkey's most important river systems. In addition to the geologic structure of the basin, Harmancik Chromium Mines are one of the most important inorganic pollution sources for the basin and also for Uluabat Lake. In the present study, water, sediment and fish (Squalius cii, Capoeta tinca and Barbus oligolepis) samples were collected seasonally from eight stations (one of them was on the Kinik Stream where the Harmancik Chromium Mines is located on and one of them was on the Dursunbey Stream) on the Emet Stream Basin. Some limnological parameters (pH, conductivity and total hardness) in water and Cr, Ca, Mg, Ni and Mn levels in biotic (muscle, gill, liver and kidney tissues of fishes) and abiotic (water and sediment) components of basin were determined to evaluate the effects of Harmancik Chromium Mines on the system. Cluster Analysis, Factor Analysis, Pearson Correlation Index, One Way Anova Tests, Scatter dot Comparing and Matrix plot Distribution Diagrams were applied to the results in order to estimate the data properly. Water samples were evaluated according to the water quality criteria for Turkey and sediment samples were evaluated according to the sediment quality criteria. According to data obtained, statistically significance differences were identified between Kinik and Emet Streams according to Cr and Ni accumulations in water and sediment. Chromium levels of Kinik Stream were extremely higher an average of 153 times for water and 10 times for sediment than uncontaminated stations. Water and sediment quality of Emet Stream were decreasing after falling the Kinik Stream and increasing after falling the Dursunbey Stream. It was also determined that, the amount of chromium in muscle tissues of three fish species were much higher than the limit value of 0.15 mg kg(-1) that FAO identified