Optimal insurance contracts without the non-negativity constraint on indemnities: revisited

In the literature on optimal indemnity schedules, indemnities are usually restricted to be non-negative. Keeler [1974] and Gollier [1987] show that this constraint might well bind: insured could get higher expected utility if insurance contracts would allow payments from the insured to the insurer at some losses. This paper extends Collier’s findings by allowing for negative indemnity payments for a broader class of insurers’ cost functions and argues that the indemnity schedule derived here is more appropriate for practical applications (e.g. in health insurance). Copyright Springer Science + Business Media, LLC 2006Optimal insurance, Indemnity, Deductible, Co-insurance,

Optimal insurance contract under a value-at-risk constraint

This study develops an optimal insurance contract endogenously under a value-at-risk (VaR) constraint. Although Wang et al. [2005] had examined this problem, their assumption implied that the insured is risk neutral. Consequently, this study extends Wang et al. [2005] and further considers a more realistic situation where the insured is risk averse. The study derives the optimal insurance contract as a single deductible insurance when the VaR constraint is redundant or as a double deductible insurance when the VaR constraint is binding. Finally, this study discusses the optimal coverage level from common forms of insurances, including deductible insurance, upper-limit insurance, and proportional coinsurance. Copyright Springer Science + Business Media, LLC 2006Value-at-risk, Optimal insurance, Deductible, Policy limit, Coinsurance,

P6348Phospholamban antisense oligonucleotides drive the reversal of cardiac dysfunction and multiple heart failure parameters during murine dilated cardiomyopathy

Abstract Background Mice lacking muscle LIM protein (Mlp/Cspr3 −/−) develop dilated cardiomyopathy (DCM). Previous work established this model to be amenable to improvements in cardiac function by genetic ablation of phospholamban (PLN). Purpose To test the hypothesis that therapeutic reductions of PLN would similarly improve cardiac function, Mlp KO mice were administered an antisense oligonucleotide (ASO) targeting PLN. Methods Echocardiography measurements of ejection fraction (EF), end-diastolic volume (EDV) and end-systolic volume (ESV) were performed before and after treatment. In addition, global transcriptome profiling using 3'RNA-seq was performed to identify gene expression changes in diseased Mlp KO mice and following PLN ASO treatments. Mlp KO mice with ejection fraction (EF%) of less than 45% (median, 37.6%; interquartile range, 32.2–42.0%) were treated with vehicle (n=10) or PLN ASO (n=9) for 4 weeks. Results Three subcutaneous injections of PLN ASO were administered to Mlp KO mice resulting in 50–70% PLN reductions. Echocardiography performed at study end revealed improvements of EF (60±8 vs. 46±12%), ESV (31±11 vs. 56±21μl) and EDV (79±22 vs. 100±25μl) with PLN ASO treatment. Corrected for baseline values, PLN ASO treatment improved all echocardiographic measurements (p&lt;0.001). Transcriptional analyses revealed that PLN ASO treatment reduced expression of heart failure related markers, such as Myh7 (−70%), Nppa (−72%), Nppb (−71%), Acta1 (−84%) and Ankrd1 (−40%), p&lt;0.05 vs. vehicle. In addition, genes not previously known to be dysregulated in this model, Edn3 and Xirp2, were identified and shown to be reduced following PLN ASO treatment by 71% and 67%, respectively (p&lt;0.001). Bioinformatic analysis suggested improvement of known and novel heart failure associated pathways by PLN inhibition in this model. In conclusion, antisense inhibition of PLN reduced functional and transcriptional indices of heart failure in a DCM model. In view of the failed CUPID trials, a gene therapy approach to improve SERCA2a activity, targeting PLN with ASO may be advantageous due to a likely more robust pharmacological profile. </jats:sec

Business as a Regulatory Leader for Risk Governance? The Compact Initiative for Liability and Redress under the Cartagena Protocol on Biosafety

In March 2008, the six world leading agro-biotechnology companies, presented a private, international instrument for liability and redress to cover the environmental damage caused by genetically modified organisms. The proposal was rejected by governments, who instead adopted a binding supplementary liability and redress protocol to the Cartagena Protocol on Biosafety, with no content transfer from the business initiative. Elaborating on this case study, it is explained how powerful business proposals can turn into a policy failure. Business conflicts are identified as one major explanatory factor. The fragmentation of business interests and the lackof business support for the six major firms’ initiative have discredited the role of corporations as regulatory leaders. Business unity is found to be a decisive, necessary condition for the endorsement of corporate proposals by policymakers