The impact of parameter uncertainty in insurance pricing and reserve with the temperature‐related mortality model

Changes in mortality rates have an impact on the life insurance industry, the financial sector (as a significant proportion of the financial markets is driven by pension funds), governmental agencies, and decision makers and policymakers. Thus the pricing of financial, pension and insurance products that are contingent upon survival or death and which is related to the accuracy of central mortality rates is of key importance. Recently, a temperature‐related mortality (TRM) model was proposed by Seklecka et al. (Journal of Forecasting, 2017, 36(7), 824–841), and it has shown evidence of outperformance compared with the Lee and Carter (Journal of the American Statistical Association, 1992, 87, 659–671) model and several others of its extensions, when mortality‐experience data from the UK are used. There is a need for awareness, when fitting the TRM model, of model risk when assessing longevity‐related liabilities, especially when pricing long‐term annuities and pensions. In this paper, the impact of uncertainty on the various parameters involved in the model is examined. We demonstrate a number of ways to quantify model risk in the estimation of the temperature‐related parameters, the choice of the forecasting methodology, the structures of actuarial products chosen (e.g., annuity, endowment and life insurance), and the actuarial reserve. Finally, several tables and figures illustrate the main findings of this paper.     

Vpx relieves inhibition of HIV-1 infection of macrophages mediated by the SAMHD1 protein

Macrophages and dendritic cells have key roles in viral infections, providing virus reservoirs that frequently resist antiviral therapies and linking innate virus detection to antiviral adaptive immune responses. Human immunodeficiency virus 1 (HIV-1) fails to transduce dendritic cells and has a reduced ability to transduce macrophages, due to an as yet uncharacterized mechanism that inhibits infection by interfering with efficient synthesis of viral complementary DNA. In contrast, HIV-2 and related simian immunodeficiency viruses (SIVsm/mac) transduce myeloid cells efficiently owing to their virion-associated Vpx accessory proteins, which counteract the restrictive mechanism. Here we show that the inhibition of HIV-1 infection in macrophages involves the cellular SAM domain HD domain-containing protein 1 (SAMHD1). Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein. Mutations in SAMHD1 cause Aicardi-Goutières syndrome, a disease that produces a phenotype that mimics the effects of a congenital viral infection. Failure to dispose of endogenous nucleic acid debris in Aicardi-Goutières syndrome results in inappropriate triggering of innate immune responses via cytosolic nucleic acids sensors. Thus, our findings show that macrophages are defended from HIV-1 infection by a mechanism that prevents an unwanted interferon response triggered by self nucleic acids, and uncover an intricate relationship between innate immune mechanisms that control response to self and to retroviral pathogens.     

Mortality effects of economic fluctuations in selected eurozone countries

Socioeconomic status is commonly conceptualized as the social standing or well‐being of an individual or society. Higher socioeconomic status has long been identified as a contributing factor for mortality improvement. This paper studies the impact of macroeconomic fluctuations (having gross domestic product (GDP) as a proxy) on mortality for the nine most populous eurozone countries. Based on the statistical analysis between the time‐dependent indicator of the Lee and Carter (Journal of the American Statistical Association, 1992, 87(419), 659–671) model and GDP, and adaptation of the good features of the O'Hare and Li (Insurance: Mathematics and Economics, 2012, 50, 12–25) model, a new mortality model including this additional economic‐related factor is proposed. Results for male and female from ages between 0 and 89, and similar for unisex data, are provided. This new model shows a better fitting and more plausible forecast among a significant number of eurozone countries. An in‐depth analysis of our findings is provided to give a better understanding of the relationship between mortality and GDP fluctuations.     

Multiple newly identified loci associated with prostate cancer susceptibility

Prostate cancer is the most common cancer affecting males in developed countries. It shows consistent evidence of familial aggregation, but the causes of this aggregation are mostly unknown. To identify common alleles associated with prostate cancer risk, we conducted a genome-wide association study (GWAS) using blood DNA samples from 1,854 individuals with clinically detected prostate cancer diagnosed at 相似文献