This study develops a contingent-claim framework for valuing a reinsurance contract and examines how a reinsurance company can increase the value of a reinsurance contract and reduce its default risk ...by issuing catastrophe (CAT) bonds. The results also show how the changes in contract values and default risk premium are related to basis risk, trigger level, catastrophe risk, interest rate risk, and the reinsurer’s capital position.
This article develops a contingent claim model to price a default-risky, catastrophe-linked bond. This model incorporates stochastic interest rates and more generic loss processes and allows for ...practical considerations of moral hazard, basis risk, and default risk. The authors compute default-free and default-risky CAT bond prices by using the Monte Carlo method. The results show that both moral hazard and basis risk drive down the bond prices substantially; these effects should not be ignored in pricing the CAT bonds. The authors also show how the bond prices are related to catastrophe occurrence intensity, loss volatility, trigger level, the issuing firm's capital position, debt structure, and interest rate uncertainty.
Common cancer biomarkers Basil, Christopher F; Zhao, Yingdong; Zavaglia, Katia ...
Cancer research,
03/2006, Letnik:
66, Številka:
6
Journal Article
Recenzirano
Odprti dostop
There is an increasing interest in complementing conventional histopathologic evaluation with molecular tools that could increase the sensitivity and specificity of cancer staging for diagnostic and ...prognostic purposes. This study strove to identify cancer-specific markers for the molecular detection of a broad range of cancer types. We used 373 archival samples inclusive of normal tissues of various lineages and benign or malignant tumors (predominantly colon, melanoma, ovarian, and esophageal cancers). All samples were processed identically and cohybridized with an identical reference RNA source to a custom-made cDNA array platform. The database was split into training (n = 201) and comparable prediction (n = 172) sets. Leave-one-out cross-validation and gene pairing analysis identified putative cancer biomarkers overexpressed by malignant lesions independent of tissue of derivation. In particular, seven gene pairs were identified with high predictive power (87%) in segregating malignant from benign lesions. Receiver operator characteristic curves based on the same genes could segregate malignant from benign tissues with 94% accuracy. The relevance of this study rests on the identification of a restricted number of biomarkers ubiquitously expressed by cancers of distinct histology. This has not been done before. These biomarkers could be used broadly to increase the sensitivity and accuracy of cancer staging and early detection of locoregional or systemic recurrence. Their selective expression by cancerous compared with paired normal tissues suggests an association with the oncogenic process resulting in stable expression during disease progression when the presently used differentiation markers are unreliable.
To investigate the association of DNA nucleotide excision repair (NER) defects with neurological degeneration, cachexia and cancer, we performed autopsies on 4 adult xeroderma pigmentosum (XP) ...patients with different clinical features and defects in NER complementation groups XP-A, XP-C or XP-D.
The XP-A (XP12BE) and XP-D (XP18BE) patients exhibited progressive neurological deterioration with sensorineural hearing loss. The clinical spectrum encompassed severe cachexia in the XP-A (XP12BE) patient, numerous skin cancers in the XP-A and two XP-C (XP24BE and XP1BE) patients and only few skin cancers in the XP-D patient. Two XP-C patients developed internal neoplasms including glioblastoma in XP24BE and uterine adenocarcinoma in XP1BE. At autopsy, the brains of the 44 yr XP-A and the 45 yr XP-D patients were profoundly atrophic and characterized microscopically by diffuse neuronal loss, myelin pallor and gliosis. Unlike the XP-A patient, the XP-D patient had a thickened calvarium, and the brain showed vacuolization of the neuropil in the cerebrum, cerebellum and brainstem, and patchy Purkinje cell loss. Axonal neuropathy and chronic denervation atrophy of the skeletal muscles were observed in the XP-A patient, but not in the XP-D patient.
These clinical manifestations and autopsy findings indicate advanced involvement of the central and peripheral nervous system. Despite similar defects in DNA repair, different clinicopathological phenotypes are seen in the four cases, and therefore distinct patterns of neurodegeneration characterize XP-D, XP-A and XP-C patients.
•Summary of recent significant research on developing revolutionary sustained gene delivery carriers.•Synthetic nonviral systems have innate biocompatibility and tunable surface properties in gene ...therapy.•Customization for controlled release profiles circumvents the need for repeated administration while maintaining high transfection efficiency.•Recombination of multicomplex polymers endows with novel properties for advanced therapeutic applications.
Sustained gene delivery is of particular importance today because it circumvents the need for repeated therapeutic administration and provides spatial and temporal control of the release profile. Better understanding of the genetic basis of diseases and advances in gene therapy have propelled significant research on biocompatible gene carriers for therapeutic purposes. Varied biodegradable polymer-based architectures have been used to create new compositions with unique properties suitable for sustained gene delivery. This review presents the most recent advances in various polymeric systems: hydrogels, microspheres, nanospheres and scaffolds, having complex architectures to encapsulate and deliver functional genes. Through the recombination of different existing polymer systems, the multicomplex systems can be further endowed with new properties for better-targeted biomedical applications.
Human toll-like receptor 4 (TLR4) is an important receptor in innate immunity, particularly against gram-negative bacterial infection (GNBI). In our study, we evaluated associations of TLR4 single ...nucleotide polymorphisms (SNPs) with GNBI in Han Chinese neonates.
Polymorphisms in TLR4 were genotyped in 201 neonates with GNBI and 279 gestational age and birth weight-matched controls without GNBI. Polymorphism analyses were applied to allele frequencies of the detected TLR4 SNPs and their associations with various clinical entities, including premature birth and GNBI were assessed.
A total of six SNPs with more than 5% frequency were found in several promoter sequences, including rs10759931, rs2737190, rs10116253, rs10983755, rs1927914, and rs10759932. Mutation allele frequencies ranged from 23 to 41%. There were no SNPs with a frequency greater than 5% in exon analyses. Allele G rs2737190 mutations and GGCGGC haplotypes were more frequent among preterm GNBI neonates (odds ratio OR, 1.32; 95% confidence interval CI, 1.02-1.71 and OR, 1.89; 95% CI, 1.19-3.00, respectively). No specific alleles or haplotypes were associated with GNBI status among term neonates.
In this study population of Han Chinese, there was a significant association between an ethnical unique SNP in the TLR4 promoter region and preterm neonatal GNBIs.
T-DNA tagging lines are useful for analyzing the functions of genes and regulatory elements. We have previously generated approximately 100,000 insertional mutants in japonica rice (
Oryza sativa
), ...using T-DNA vectors carrying the promoter-less
GUS
reporter gene. In this study, we conducted GUS assays of seedlings from 430 lines in which TDNA was inserted into transcription factor genes. Among the 75 lines that showed GUS signals, nine displayed an endospermpreferential expression pattern; two lines demonstrated GUS signals in both endosperm and roots; 21 lines had GUS expression mainly in leaves; 19 lines showed GUS signal in both leaves and roots; and 24 lines expressed GUS predominantly in the roots. Co-segregation analyses of 49 homozygous lines indicated that the GUS expression patterns observed from 38 lines were due to the T-DNA insertion. We also identified fusion transcripts between tagged genes and the
GUS
reporter in six lines. Quantitative RT-PCR confirmed that the GUS expression patterns of those tagged lines indeed represent organ- and tissue-preferential expression of the tagged genes. The
GUS
-tagged transcription factor lines identified here will be useful for functional analysis of these candidates.
Financial reforms and capital adequacy are probably the most critical issues for the banking industry in the world. This study examines the effectiveness of financial reforms carried out in Taiwan ...recently and measures the adequacy of the deposit insurance fund (DIF), including financial restructuring fund and Designated Reserve Ratio (DRR) strategy in Taiwan. We have improved on the methodology of Episcopoc (2004) and report estimates of the cost of deposit insurance and implied reserves for each bank or financial holding company. Estimates of the implicit cost of government guaranty of the DIF are also included. To stabilize its financial environment in 2000, the Taiwanese government amended many bank regulations, including the enactment of the Financial Holding Company Act (FHC Act) of 2001 and the Financial Restructuring Fund Statute. Our evidence shows lower volatilities and average unit cost of deposit insurance for seven sampled FHCs compared to sixteen sampled banks, even though the FHCs are larger. These results indicate the effectiveness of the financial reforms put forward by the Taiwanese government. When implied reserves are compared with the Designated Reserve Ratio (DRR) strategy of 2%, imposed by the Central Deposit Insurance Corporation (CDIC) in 2007, we find that the DIF would have been sufficient in 2006, but not in 2000. The results imply that the fixed target ratio for the DIF may not be appropriate. In addition, the details of financial reforms in Taiwan starting in 2001 are provided and demonstrate resolve in implementing financial reforms. Finally, financial reforms of Taiwan and the calculations of DRR and estimates of the implicit cost of government guaranty of the DIF can be used as lessons for other countries.
•We estimate the cost of deposit insurance and implied reserves of banks in Taiwan.•We examine the effectiveness of financial reforms carried out in Taiwan.•This study examines the adequacy of the fixed target ratio set in the DIF.•The experience of Taiwan provides a lesson to resolve bank failure.
Abstract Objective To characterize blood glucose fluctuation during hemodialysis in patients with end stage diabetic nephropathy (ESDN) by a continuous glucose monitoring system (CGMS), and aim to ...improve blood glucose control in this patient population. Methods Forty-six patients with or without type 2 diabetes mellitus (T2DM), receiving hemodialysis, were recruited in this study. Thirty-six patients had end stage diabetic nephropathy (ESDN group), the other ten patients had end stage renal disease without diabetes (ESRD group). A continuous glucose monitoring system (CGMS) was employed to monitor glycemic fluctuation for 72 hours. Blood samples were collected and analyzed. Results Mean, standard deviation (SD), maximum, and mean amplitude glycemic excursion (MAGE) of blood glucose and the ratio of blood glucose readings that was greater than 13.9 mmol/L of ESDN group, were significantly greater than those of ESRD group (p < 0.01 for all) during 72 hours of observation. The mean blood glucose was significantly lower, while SD and MAGE were significantly higher in ESDN group on hemodialysis day than on days off hemodialysis (p < 0.05), while these were not been observed in ESRD group. Though mean, SD, and MAGE of blood glucose during hemodialysis were significantly lower than those of peri-hemodialysis in both groups (p < 0.01 or p < 0.05, respectively), they were significantly higher in ESDN group than that in ESRD group (p < 0.05). The mean blood glucose value calculated from HbA1c did not reflect the actual mean blood glucose measured by CGM in both groups, and gave an inaccurate impression of a significantly lower mean glucose. Conclusions ESDN patients had larger glycemic fluctuations as compared with ESRD patients. Hemodialysis caused reduction in mean, SD, and MAGE, which in turn caused bigger glycemic fluctuations on hemodialysis day. The HbA1c in ESDN patients gave an inaccurate value, which did not truly reflect blood glucose status for a prolonged period.
Childhood adiposity is increasingly recognized as a significant predictor of cardiometabolic risks in later life. The aim of this study was to investigate factors associated with longitudinal changes ...in weight during childhood and the development of metabolic disease risk factors. Four hundred twenty-four children from DaQing city, China, were recruited at 5 y old and followed up for 5 y. Birth weight, television (TV) viewing time at 5 y old, blood pressure, anthropometric measurements, fasting plasma insulin (FI), and triglycerides (TG) levels were measured at 5 and 10 y old. Both birth weight and TV viewing time at 5 y old significantly correlated with percentage of ideal weight for height (WFH) at 5 y old (WFH5; p = 0.0032 and p = 0.01), but only TV time was significantly correlated with WFH at 10 y old (WFH10; p < 0.0001). Blood pressures, FI, homeostasis model assessment for insulin resistance (HOMA-IR), and TG at 10 y old were significantly greater in those children who had greater change in WFH from 5 to 10 y old (ΔWFH). We concluded that TV viewing time was the stronger determinant of later childhood adiposity. A greater ΔWFH was associated with increased cardiometabolic risk factors at 10 y old.
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