Systemic Sovereign Credit Risk: Lessons from the U.S. and Europe

We study the nature of systemic sovereign credit risk using CDS spreads for the U.S. Treasury, individual U.S. states, and major European countries. Using a multifactor affine framework that allows for both systemic and sovereign-specific credit shocks, we find that there is considerable heterogeneity across U.S. and European issuers in their sensitivity to systemic risk. U.S. and Euro systemic shocks are highly correlated, but there is much less systemic risk among U.S. sovereigns than among European sovereigns. We also find that U.S. and European systemic sovereign risk is strongly related to financial market variables. These results provide strong support for the view that systemic sovereign risk has its roots in financial markets rather than in macroeconomic fundamentals.

Does religion make a difference? : assessing the effects of Christian affiliation and practice on marital solidarity and divorce in Britain, 1985-2005

Marital breakdown rates were examined among 15,714 adults from the British Social Attitudes dataset for 1985-2005. Separation and divorce peaked at around 50 years of age, and increased significantly over the period of study. Ratios of separation or divorce were compared between respondents who had no religious affiliation and (a) Christian affiliates who attended church at least once a month, (b) Christian affiliates who attended church, but less than once a month, and (c) Christian affiliates who never attended church. The results showed that active Christians were 1.5 times less likely to suffer marital breakdown than non-affiliates, but there was no difference between affiliates who never attended church and those of no religion. Christians who attended infrequently were 1.3 times less likely to suffer marital breakdown compared to non-affiliates, suggesting that even infrequent attendance at church may have some significance for predicting the persistence of martial solidarity

Dermatology life quality index (DLQI) as a psoriasis referral triage tool

Most primary care psoriasis referrals in the UK are triaged as ‘routine’, in part because of the prioritisation of skin cancer. As a result, patients with severe psoriasis may wait several months to be seen, enduring quality of life (QoL) impairment that could have been reduced. Furthermore some patients may spontaneously improve by the time they are seen by a specialist, making the appointment unnecessary at that time. Therefore, following approval from the local ethics committee, we conducted a prospective study to evaluate the usefulness of Dermatology Life Quality Index (DLQI) scores in triaging patients with psoriasis referred to our dermatology secondary health care services

NorthStar, a support tool for the design and evaluation of quality improvement interventions in healthcare

Background: The Research-Based Education and Quality Improvement (ReBEQI) European partnership aims to establish a framework and provide practical tools for the selection, implementation, and evaluation of quality improvement (QI) interventions. We describe the development and preliminary evaluation of the software tool NorthStar, a major product of the ReBEQI project. Methods: We focused the content of NorthStar on the design and evaluation of QI interventions. A lead individual from the ReBEQI group drafted each section, and at least two other group members reviewed it. The content is based on published literature, as well as material developed by the ReBEQI group. We developed the software in both a Microsoft Windows HTML help system version and a web-based version. In a preliminary evaluation, we surveyed 33 potential users about the acceptability and perceived utility of NorthStar. Results: NorthStar consists of 18 sections covering the design and evaluation of QI interventions. The major focus of the intervention design sections is on how to identify determinants of practice (factors affecting practice patterns), while the major focus of the intervention evaluation sections is on how to design a cluster randomised trial. The two versions of the software can be transferred by email or CD, and are available for download from the internet. The software offers easy navigation and various functions to access the content. Potential users (55% response rate) reported above-moderate levels of confidence in carrying out QI research related tasks if using NorthStar, particularly when developing a protocol for a cluster randomised trial Conclusion: NorthStar is an integrated, accessible, practical, and acceptable tool to assist developers and evaluators of QI interventions

Exploiting the neoantigen landscape for immunotherapy of pancreatic ductal adenocarcinoma

Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases. Our findings reveal that: (a) nearly all PDAC samples harbor potentially targetable neoantigens; (b) T cells are present but generally show a reduced activation signature; and (c) markers of efficient antigen presentation are associated with a reduced signature of markers characterizing cytotoxic T cells. These findings suggest that despite the presence of tumor specific neoepitopes, T cell activation is actively suppressed in PDAC. Further, we identify iNOS as a potential mediator of immune suppression that might be actionable using pharmacological avenues

Trichostatin A Blocks Aldosterone-Induced Na+ Transport And Control Of Serum- And Glucocorticoid-Inducible Kinase 1 In Cortical Collecting Duct Cells

Background and Purpose: Aldosterone stimulates epithelial Na+ channel (ENaC)-dependent Na+ retention in the cortical collecting duct (CCD) of the kidney by activating mineralocorticoid receptors that promote expression of serum and glucocorticoid-inducible kinase 1 (SGK1). This response is critical to BP homeostasis. It has previously been suggested that inhibiting lysine deacetylases (KDACs) can post-transcriptionally disrupt this response by promoting acetylation of the mineralocorticoid receptor. The present study critically evaluates this hypothesis. Experimental Approach: Electrometric and molecular methods were used to define the effects of a pan-KDAC inhibitor, trichostatin A, on the responses to a physiologically relevant concentration of aldosterone (3 nM) in murine mCCDcl1 cells. Key Results: Aldosterone augmented ENaC-induced Na+ absorption and increased SGK1 activity and abundance, as expected. In the presence of trichostatin A, these responses were suppressed. Trichostatin A-induced inhibition of KDAC was confirmed by increased acetylation of histone H3, H4, and α-tubulin. Trichostatin A did not block the electrometric response to insulin, a hormone that activates SGK1 independently of increased transcription, indicating that trichostatin A has no direct effect upon the SGK1/ENaC pathway. Conclusions and Implications: Inhibition of lysine de-acetylation suppresses aldosterone-dependent control over the SGK1–ENaC pathway but does not perturb post-transcriptional signalling, providing a physiological basis for the anti-hypertensive action of KDAC inhibition seen in vivo

A Basin Redox Transect at the Dawn of Animal Life

Multiple eukaryotic clades make their first appearance in the fossil record between ~810 and 715 Ma. Molecular clock studies suggest that the origin of animal multicellularity may have been part of this broader eukaryotic radiation. Animals require oxygen to fuel their metabolism, and low oxygen levels have been hypothesized to account for the temporal lag between metazoan origins and the Cambrian radiation of large, ecologically diverse animals. Here, paleoredox conditions were investigated in the Fifteenmile Group, Ogilvie Mountains, Yukon, Canada, which hosts an 811 Ma ash horizon and spans the temporal window that captures the inferred origin and early evolution of animals. Iron-based redox proxies, redox-sensitive trace elements, organic carbon percentages and pyrite sulfur isotopes were analyzed in seven stratigraphic sections along two parallel basin transects. These data suggest that for this basin, oxygenated shelf waters overlay generally anoxic deeper waters. The anoxic water column was dominantly ferruginous, but brief periods of euxinia likely occurred. These oscillations coincide with changes in total organic carbon, suggesting euxinia was primarily driven by increased organic carbon loading. Overall, these data are consistent with proposed quantitative constraints on Proterozoic atmospheric oxygen being greater than 1% of modern levels, but less than present levels. Comparing these oxygen levels against the likely oxygen requirements of the earliest animals, both theoretical considerations and the ecology of modern oxygen-deficient settings suggest that the inferred oxygen levels in the mixed layer would not have been prohibitive to the presence of sponges, eumetazoans or bilaterians. Thus the evolution of the earliest animals was probably not limited by the low absolute oxygen levels that may have characterized Neoproterozoic oceans, although these inferred levels would constrain animals to very small sizes and low metabolic rates.Earth and Planetary SciencesOrganismic and Evolutionary Biolog