Forecasting Cross-Sections of Frailty-Correlated Default

We propose a novel econometric model for estimating and forecasting cross-sections of time-varying conditional default probabilities. The model captures the systematic variation in corporate default counts across e.g. rating and industry groups by using dynamic factors from a large panel of selected macroeconomic and financial data as well as common unobserved risk factors. All factors are statistically and economically significant and together capture a large part of the time-variation in observed default rates. In this framework we improve the out-of-sample forecasting accuracy associated with conditional default probabilities by about 10-35 % in terms of Mean Absolute Error, particularly in years of default stress

Macro, industry and frailty effects in defaults: The 2008 credit crisis in perspective

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Hawking radiation in different coordinate settings: Complex paths approach

We apply the technique of complex paths to obtain Hawking radiation in different coordinate representations of the Schwarzschild space-time. The coordinate representations we consider do not possess a singularity at the horizon unlike the standard Schwarzschild coordinate. However, the event horizon manifests itself as a singularity in the expression for the semiclassical action. This singularity is regularized by using the method of complex paths and we find that Hawking radiation is recovered in these coordinates indicating the covariance of Hawking radiation as far as these coordinates are concerned.Comment: 18 pages, 2 figures, Uses IOP style file; final version; accepted in Class. Quant. Gra

Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n=41) and advanced SM (advSM, n=67). Organomegaly was measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen. In multivariate analysis of all patients, an increased spleen volume greater than or equal to450?ml (hazard ratio [HR], 5.2; 95% confidence interval [CI], [2.1–13.0]; P=0.003) and an elevated alkaline phosphatase (AP; HR 5.0 [1.1–22.2]; P=0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P<0.0001), for patients with 0 (low-risk, n=37), 1 (intermediate-risk, n=32) or 2 (high-risk, n=39) parameters. For advSM patients with fully available clinical and molecular data (n=60), univariate analysis identified splenomegaly greater than or equal to1200?ml, elevated AP and mutations in the SRSF2/ASXL1/RUNX1 (S/A/R) gene panel as significant prognostic markers. In multivariate analysis, mutations in S/A/R (HR, 3.2 [1.1–9.6]; P=0.01) and elevated AP (HR 2.6 [1.0–7.1]; P=0.03) remained predictive adverse prognostic markers for OS. The 3-year OS was 76% and 38%, respectively (P=0.0003), for patients with 0-1 (intermediate-risk, n=28) or 2 (high-risk, n=32) parameters. We conclude that splenomegaly, elevated AP and mutations in the S/A/R gene panel are independent of the WHO classification and provide the most relevant prognostic information in SM patient

An Isolated Water Droplet in the Aqueous Solution of a Supramolecular Tetrahedral Cage

Water under nanoconfinement at ambient conditions has exhibited low-dimensional ice formation and liquid-solid phase transitions, but with structural and dynamical signatures which map onto known regions of waters phase diagram. Using THz absorption spectroscopy and ab initio molecular dynamics, we have investigated the ambient water confined in a supramolecular tetrahedral assembly, and determined that a distinct network of 9-10 water molecules is present within the nanocavity of the host. The low-frequency absorption spectrum and theoretical analysis of the water in the $Ga_4$$L_6$$^{-12}$ host demonstrate that the structure and dynamics of the encapsulated droplet is distinct from any known phase of water. A further inference is that the release of the highly unusual encapsulated water droplet creates a strong thermodynamic driver for the high affinity binding of guests in aqueous solution for the $Ga_4$$L_6$$^{-12}$ supramolecular construct

Measurement of the Transverse Beam Spin Asymmetry in Elastic Electron Proton Scattering and the Inelastic Contribution to the Imaginary Part of the Two-Photon Exchange Amplitude

We report on a measurement of the asymmetry in the scattering of transversely polarized electrons off unpolarized protons, A$_\perp$, at two Q$^2$ values of \qsquaredaveragedlow (GeV/c)$^2$ and \qsquaredaveragedhighII (GeV/c)$^2$ and a scattering angle of $30^\circ < \theta_e < 40^\circ$. The measured transverse asymmetries are A$_{\perp}$(Q$^2$ = \qsquaredaveragedlow (GeV/c)$^2$) = (\experimentalasymmetry alulowcorr $\pm$ \statisticalerrorlow$_{\rm stat}$ $\pm$ \combinedsyspolerrorlowalucor$_{\rm sys}$) $\times$ 10$^{-6}$ and A$_{\perp}$(Q$^2$ = \qsquaredaveragedhighII (GeV/c)$^2$) = (\experimentalasymme tryaluhighcorr $\pm$ \statisticalerrorhigh$_{\rm stat}$ $\pm$ \combinedsyspolerrorhighalucor$_{\rm sys}$) $\times$ 10$^{-6}$. The first errors denotes the statistical error and the second the systematic uncertainties. A$_\perp$ arises from the imaginary part of the two-photon exchange amplitude and is zero in the one-photon exchange approximation. From comparison with theoretical estimates of A$_\perp$ we conclude that $\pi$N-intermediate states give a substantial contribution to the imaginary part of the two-photon amplitude. The contribution from the ground state proton to the imaginary part of the two-photon exchange can be neglected. There is no obvious reason why this should be different for the real part of the two-photon amplitude, which enters into the radiative corrections for the Rosenbluth separation measurements of the electric form factor of the proton.Comment: 4 figures, submitted to PRL on Oct.

Evidence for Strange Quark Contributions to the Nucleon's Form Factors at Q2Q^2 = 0.108 (GeV/c)2^2

We report on a measurement of the parity violating asymmetry in the elastic scattering of polarized electrons off unpolarized protons with the A4 apparatus at MAMI in Mainz at a four momentum transfer value of $Q^2$ = \Qsquare (GeV/c)$^2$ and at a forward electron scattering angle of 30$^\circ < \theta_e < 40^\circ$. The measured asymmetry is $A_{LR}(\vec{e}p)$ = (\Aphys $\pm$ \Deltastat$_{stat}$ $\pm$ \Deltasyst$_{syst}$) $\times$ 10$^{-6}$. The expectation from the Standard Model assuming no strangeness contribution to the vector current is A$_0$ = (\Azero $\pm$ \DeltaAzero) $\times$ 10$^{-6}$. We have improved the statistical accuracy by a factor of 3 as compared to our previous measurements at a higher $Q^2$. We have extracted the strangeness contribution to the electromagnetic form factors from our data to be $G_E^s$ + \FakGMs $G_M^s$ = \GEsGMs $\pm$ \DeltaGEsGMs at $Q^2$ = \Qsquare (GeV/c)$^2$. As in our previous measurement at higher momentum transfer for $G_E^s$ + 0.230 $G_M^s$, we again find the value for $G_E^s$ + \FakGMs $G_M^s$ to be positive, this time at an improved significance level of 2 $\sigma$.Comment: 4 pages, 3 figure

Regulatory T-Cells and Associated Pathways in Metastatic Renal Cell Carcinoma (mRCC) Patients Undergoing DC-Vaccination and Cytokine-Therapy

Purpose: To evaluate CD4+CD25+FOXP3+ T regulatory cells (TREG) and associated immune-regulatory pathways in peripheral blood lymphocytes (PBL) of metastatic renal cell carcinoma (mRCC) patients and healthy volunteers. We subsequently investigated the effects of immunotherapy on circulating TREG combining an extensive phenotype examination, DNA methylation analysis and global transcriptome analysis. Design: Eighteen patients with mRCC and twelve volunteers (controls) were available for analysis. TREG phenotype was examined using flow cytometry (FCM). TREG were also quantified by analyzing the epigenetic status of the FOXP3 locus using methylation specific PCR. As a third approach, RNA of the PBL was hybridized to Affymetrix GeneChip Human Gene 1.0 ST Arrays and the gene signatures were explored using pathway analysis. Results We observed higher numbers of TREG in pre-treatment PBL of mRCC patients compared to controls. A significant increase in TREG was detected in all mRCC patients after the two cycles of immunotherapy. The expansion of TREG was significantly higher in non-responders than in responding patients. Methylation specific PCR confirmed the FCM data and circumvented the variability and subjectivity of the FCM method. Gene Set Enrichment Analysis (GSEA) of the microarray data showed significant enrichment of FOXP3 target genes, CTLA-4 and TGF-ß associated pathways in the patient cohort. Conclusion: Immune monitoring of the peripheral blood and tumor tissue is important for a wide range of diseases and treatment strategies. Adoption of methodology for quantifying TREG with the least variability and subjectivity will enhance the ability to compare and interpret findings across studies

ABCB1 (MDR1) polymorphisms and ovarian cancer progression and survival: A comprehensive analysis from the Ovarian Cancer Association Consortium and The Cancer Genome Atlas

&lt;b&gt;Objective&lt;/b&gt; &lt;i&gt;ABCB1&lt;/i&gt; encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; The best candidates from fine-mapping analysis of 21 &lt;i&gt;ABCB1&lt;/i&gt; SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA). Additionally we analysed 1,562 imputed SNPs around ABCB1 in patients receiving cytoreductive surgery and either ‘standard’ first-line paclitaxel–carboplatin chemotherapy (n = 1158) or any first-line chemotherapy regimen (n = 2867). We also evaluated ABCB1 expression in primary tumours from 143 EOC patients.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Result&lt;/b&gt; Fine-mapping revealed that rs1128503, rs2032582, and rs1045642 were the best candidates in optimally debulked patients. However, we observed no significant association between any SNP and either progression-free survival or overall survival in analysis of data from 14 studies. There was a marginal association between rs1128503 and overall survival in patients with nil residual disease (HR 0.88, 95% CI 0.77–1.01; p = 0.07). In contrast, &lt;i&gt;ABCB1&lt;/i&gt; expression in the primary tumour may confer worse prognosis in patients with sub-optimally debulked tumours.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusion&lt;/b&gt; Our study represents the largest analysis of &lt;i&gt;ABCB1&lt;/i&gt; SNPs and EOC progression and survival to date, but has not identified additional signals, or validated reported associations with progression-free survival for rs1128503, rs2032582, and rs1045642. However, we cannot rule out the possibility of a subtle effect of rs1128503, or other SNPs linked to it, on overall survival.&lt;p&gt;&lt;/p&gt