Portfolio risk analysis of excess of loss reinsurance

Consider a catastrophe insurance market in which primary insurers purchase excess of loss reinsurance to transfer their higher-layer losses to a reinsurer. We conduct a portfolio risk analysis for the reinsurer. In doing so, we model the losses to the primary insurers by a mixture structure, which effectively integrates three risk factors: common shock, systematic risk, and idiosyncratic risk. Assume that the reinsurer holds an initial capital Cn that is in accordance with its market size n. When expanding its business, the reinsurer needs to comply with a certain VaR-based solvency capital requirement, which determines an infimal retention level rn according to the initial capital Cn. As our main results, we find the limit of rn as n→∞ and then establish a weak convergence for the reinsurance portfolio loss. The latter result is applied to approximate the distortion risk measures of the reinsurance portfolio loss. In our numerical studies, we examine the accuracy of the obtained approximations and conduct various sensitivity tests against some risk parameters

Insurance risk analysis of financial networks vulnerable to a shock

We conduct a risk analysis of non-core insurance business of selling protection to financial firms against investment losses due to a shock. A static structural model is constructed, composed of a network of firms who cross-hold each other, a financial market consisting of multiple primitive assets that are vulnerable to a shock, and an insurer who resides external to the network and assesses the opportunity to sell protection to the financial firms. Assume that each firm in the network is rational and able to decide how much protection to purchase to optimize its portfolio according to the mean-variance principle. As a result, the shock may impact on the insurer but indirectly through the network. In view of the robust-yet-fragile nature of financial networks that has been discovered, both empirically and theoretically, by various recent works, one expects that the network integration and the shock play an intertwined role in the insurance risk. Our study forms a theoretical confirmation of this surmise: Depending on the shock size, there are three mutually exclusive scenarios in which an increase in the network integration can either reduce or amplify the impact of the shock on the insurance risk

Blockage of transdifferentiation from fibroblast to myofibroblast in experimental ovarian cancer models

<p>Abstract</p> <p>Background</p> <p>Tumour stromal myofibroblasts can promote tumour invasion. As these cells are genetically more stable than cancer cells, there has been enormous interest in developing targeted molecular therapies against them. Chloride intracellular channel 4 (CLIC4) and reactive oxygen species (ROS) have been linked with promoting stromal cell transdifferentiation in various cancers, but little is known of their roles in ovarian cancer. In this study, we examined the functional roles that both CLIC4 and ROS play in the process of ovarian cancer cell-stimulated or TGF-β1 induced fibroblast-to-myofibroblast transdifferentiation. We also examine whether it is possible to reverse such a process, with the aim of developing novel therapies against ovarian cancer by targeting activated transdifferentiated myofibroblasts.</p> <p>Results</p> <p>We demonstrate that TGF-β1 induced or CM^SKOV3activate transdifferentiated myofibroblasts (fibroblasts). These fibroblasts mimic "reactive" stromal myofibroblasts and demonstrate significant up-regulation of CLIC4 expression and increased level of ROS production. Blocking the production of ROS with an antioxidant consequently reduces the expression of CLIC4, and is accompanied by disappearance of <it>α</it>-smooth-muscle actin (α-SMA), a myofibroblast marker, suggesting ROS acts as a signalling molecule that promotes and enhances CLIC4 activities in the myofibroblast transdifferentiaton process. Down-regulation of CLIC4 with a generic agent or specific siRNA both significantly reduces the expression of factors related to the phenotypes and functions of myofibroblasts, such as α-SMA, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF), thus reversing the myofibroblast phenotype back to fibroblasts. These results convincingly show that ROS and CLIC4 are responsible for TGF-β1 induced fibroblast-to-myofibroblast transdifferentiaton and down-regulation of both is sufficient to block transdifferentiated myofibroblasts.</p> <p>Conclusion</p> <p>Molecular targeting of ROS and CLIC4 has the potential to develop novel therapies for ovarian cancer.</p

Epitranscriptomics for Biomedical Discovery

Epitranscriptomics is a newly burgeoning field pertaining to the complete delineation and elucidation of chemical modifications of nucleotides found within all classes of RNA that do not involve a change in the ribonucleotide sequence. More than 140 diverse and distinct nucleotide modifications have been identified in RNA, dwarfing the number of nucleotide modifications found in DNA. The majority of epitranscriptomic modifications have been identified in ribosomal RNA (rRNA), transfer RNA (tRNA), and small nuclear RNA (snRNA). However, in total, the knowledge of the occurrence, and specifically the function, of RNA modifications remains scarce. Recently, the rapid advancement of next‐generation sequencing and mass spectrometry technologies have allowed for the identification and functional characterization of nucleotide modifications in both protein‐coding and non‐coding RNA on a global, transcriptome scale. In this chapter, we will introduce the concepts of nucleotide modification, summarize transcriptome‐wide RNA modification mapping techniques, highlight recent studies exploring the functions of RNA modifications and their association to disease, and finally offer insight into the future progression of epitranscriptomics

Magnesium Intake and Risk of Type 2 Diabetes: Meta-analysis of prospective cohort studies

Emerging epidemiological evidence suggests that higher magnesium intake may reduce diabetes incidence. We aimed to examine the association between magnesium intake and risk of type 2 diabetes by conducting a meta-analysis of prospective cohort studies

Second-Trimester Placental and Thyroid Hormones Are Associated With Cognitive Development From Ages 1 to 3 Years

Adequate maternal thyroid hormone (TH) is necessary for fetal brain development. The role of placental human chorionic gonadotropin (hCG) in ensuring the production of TH is less well understood. The objective of the study was to evaluate 1) associations of placental hCG and its subunits, and maternal TH in the second trimester, and 2) the single and joint effects of TH and placental hormones on cognitive development and communication at ages 1 and 3 years. Fifty individuals (5%) were selected from the CANDLE (Conditions Affecting Neurocognitive Development and Early Learning) pregnancy cohort in Memphis, Tennessee, with recruitment from 2006 to 2011, to equally represent male and female fetuses. Participants were 68% Black and 32% White. Hormones measured were maternal thyroid (thyrotropin [TSH] and free thyroxine [FT4]) and placental hormones (hCG, its hyperglycosylated form [hCG-h], and free alpha- [hCG alpha] and beta-subunits [hCG beta]) in maternal serum (17-28 weeks). The primary outcome measurement was the Bayley Scales of Infant and Toddler Development. All forms of hCG were negatively associated with FT4 and not associated with TSH. hCG alpha was associated with cognitive development at age 1 year and jointly interacted with TSH to predict cognitive development at age 3 years. This pilot study added insight into the thyrotropic actions of hCG in the second trimester, and into the significance of this mechanism for brain development. More research is warranted to elucidate differences between hCG alpha, hCG beta, and hCG-h in relation to TH regulation and child brain function.Peer reviewe