Underwriting and investment risks in the property-liability insurance industry: Evidence prior to the 9-11 event

Underwriting and investment are two important and related business activities of insurance companies. However, studies on the interrelation between underwriting and investment risks of Property-Liability (P-L) insurance companies are sparse in the literature. Using a sample of US P-L insurers, this article conducts an empirical investigation of how these two risks are associated with each other in the 1994-2000 period (before the September 11th terrorist attack in 2001). Our results, robust to various estimations, suggest that there is no significant relationship between the underwriting and investment risks among our sample firms. Such results based on pre 9-11 event period provide some support for the conjecture of Achleitner et al. (Geneva Pap Risk Insur Issues Pract 27:275-282, 2002) that many insurance companies may have failed to take an integrated approach to risk management. This resulted in a heavy loss due to dual exposures in both underwriting and investment in the 9-11 event. In the aftermath of the recent global financial crisis, risk taking and risk management of financial institutions have received more attention and increasing scrutiny. We believe the current paper provides some useful insights in this vein. © 2010 Springer Science+Business Media, LLC.postprin

Analysis of independent cohorts of outbred CFW mice reveals novel loci for behavioral and physiological traits and identifies factors determining reproducibility

Combining samples for genetic association is standard practice in human genetic analysis of complex traits, but is rarely undertaken in rodent genetics. Here, using 23 phenotypes and genotypes from two independent laboratories, we obtained a sample size of 3,076 commercially available outbred mice and identified 70 loci, more than double the number of loci identified in the component studies. Fine-mapping in the combined sample reduced the number of likely causal variants, with a median reduction in set size of 51%, and indicated novel gene associations, including Pnpo, Ttll6 and GM11545 with bone mineral density, and Psmb9 with weight. However replication at a nominal threshold of 0.05 between the two component studies was low, with less than a third of loci identified in one study replicated in the second. In addition to overestimates in the effect size in the discovery sample (Winner's Curse), we also found that heterogeneity between studies explained the poor replication, but the contribution of these two factors varied among traits. Leveraging these observations we integrated information about replication rates, study-specific heterogeneity, and Winner's Curse corrected estimates of power to assign variants to one of four confidence levels. Our approach addresses concerns about reproducibility, and demonstrates how to obtain robust results from mapping complex traits in any genome-wide association study

Factors associated with failed treatment : an analysis of 121,744 women embarking on their first IVF cycles

Peer reviewedPublisher PD

Sparsest factor analysis for clustering variables: a matrix decomposition approach

We propose a new procedure for sparse factor analysis (FA) such that each variable loads only one common factor. Thus, the loading matrix has a single nonzero element in each row and zeros elsewhere. Such a loading matrix is the sparsest possible for certain number of variables and common factors. For this reason, the proposed method is named sparsest FA (SSFA). It may also be called FA-based variable clustering, since the variables loading the same common factor can be classified into a cluster. In SSFA, all model parts of FA (common factors, their correlations, loadings, unique factors, and unique variances) are treated as fixed unknown parameter matrices and their least squares function is minimized through specific data matrix decomposition. A useful feature of the algorithm is that the matrix of common factor scores is re-parameterized using QR decomposition in order to efficiently estimate factor correlations. A simulation study shows that the proposed procedure can exactly identify the true sparsest models. Real data examples demonstrate the usefulness of the variable clustering performed by SSFA

Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses

FATP4 missense and nonsense mutations cause similar features in Ichthyosis Prematurity Syndrome

<p>Abstract</p> <p>Background</p> <p>Ichthyosis Prematurity Syndrome (IPS) is an autosomal recessive disorder characterized by premature birth, non-scaly ichthyosis and atopic manifestations. The disease was recently shown to be caused by mutations in the gene encoding the fatty acid transport protein 4 (FATP4) and a specific reduction in the incorporation of very long chain fatty acids (VLCFA) into cellular lipids.</p> <p>Findings</p> <p>We screened probands from five families segregating IPS for mutations in the <it>FATP4 </it>gene. Four probands were compound heterozygous for four different mutations of which three are novel. Four patients were heterozygous and one patient homozygous for the previously reported non-sense mutation p.C168X (c.504c > a). All patients had clinical characteristics of IPS and a similar clinical course.</p> <p>Conclusions</p> <p>Missense mutations and non-sense mutations in <it>FATP4 </it>are associated with similar clinical features suggesting that missense mutations have a severe impact on FATP4 function. The results broaden the mutational spectrum in <it>FATP4 </it>associated with IPS for molecular diagnosis of and further functional analysis of FATP4.</p

Recent translational research: stem cells as the roots of breast cancer

Common phenotypes of cancer and stem cells suggest that breast cancers arise from stem cells. Breast epithelial cells with stem cell phenotypes have been shown to be more susceptible to immortalization and neoplastic transformation. Breast tumor stem cells with CD44(+)/CD24(-/low)Lineage(- )markers have been isolated. The role of these cells in tumor progression and clinical outcome is not clear. The relationship between breast stem cell and tumor stem cell may be elucidated by further studies of carcinogenesis of nonadherent mammosphere cells with stem cell features and by derivation of CD44(+)/CD24(-/low )cells from an adherent breast epithelial stem cell type

The non-coding landscape of head and neck squamous cell carcinoma

published_or_final_versio

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs