Implied correlations of iTraxx tranches during the financial crisis

Implied Base Correlations of Single-tranche CDOs on standardized Credit Indices such as the iTraxx Europe have been used in the credit derivatives market for price communication. During the financial crisis, implied correlations have been quite volatile indicating the growing fraction of systematic credit risk of STCDOs. This paper analyses the determinants of tranche implied base correlations for the period September 2006 until April 2009. It will be shown that realized asset correlations between iTraxx Europe corporates are not able to explain the extreme movements of tranche implied correlations during the financial crisis. Additionally, it will be seen that the worsening creditworthiness of market participants in the interbank market as well as growing pressure on their refinancing conditions correlated significantly with the development of implied base correlations of iTraxx tranches. --Implied Correlation,Asset Correlation,Systematic Credit Risk,Market Liquidity,Funding Liquity

Implied correlations of iTraxx tranches during the financial crisis

Implied Base Correlations of Single-tranche CDOs on standardized Credit Indices such as the iTraxx Europe have been used in the credit derivatives market for price communication. During the financial crisis, implied correlations have been quite volatile indicating the growing fraction of systematic credit risk of STCDOs. This paper analyses the determinants of tranche implied base correlations for the period September 2006 until April 2009. It will be shown that realized asset correlations between iTraxx Europe corporates are not able to explain the extreme movements of tranche implied correlations during the financial crisis. Additionally, it will be seen that the worsening creditworthiness of market participants in the interbank market as well as growing pressure on their refinancing conditions correlated significantly with the development of implied base correlations of iTraxx tranches

Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Gene Regulation of Intestinal Porcine Epithelial Cells IPEC-J2 Is Dependent on the Site of Deoxynivalenol Toxicological Action

The intestinal epithelial cell layer represents the border between the luminal and systemic side of the gut. The decision between absorption and exclusion of substances is the quintessential function of the gut and varies along the gut axis. Consequently, potentially toxic substances may reach the basolateral domain of the epithelial cell layer via blood stream. The mycotoxin deoxynivalenol (DON) is a Fusarium derived secondary metabolite known to enter the blood stream and displaying a striking toxicity on the basolateral side of polarised epithelial cell layers in vitro. Here we analysed potential mechanisms of apical and basolateral DON toxicity reflected in the gene expression. We used the jejunum-derived, polarised intestinal porcine epithelial cell line IPEC-J2 as an in vitro cell culture model. Luminal and systemic DON challenge of the epithelial cell layer was mimicked by a DON application from the apical or basolateral compartment of membrane inserts for 72 h. We compared the genome-wide gene expression of untreated and DON-treated IPEC-J2 cells with the GeneChip® Porcine Genome Array of Affymetrix. Low basolateral DON (200 ng/mL) application triggered 10 times more gene transcripts in comparison to the corresponding apical application (2539 versus 267) despite the intactness of the challenged cell layer as measured by transepithelial electrical resistance. Analysis of the regulated genes by bioinformatic resource DAVID identified several groups of biochemical pathways modulated by concentration and orientation of DON application. Selected genes representing pathways of the cellular metabolism, information processing and structural design were analysed in detail by quantitative PCR. Our findings clearly show that apical and basolateral challenge of epithelial cell layers trigger different gene response profiles paralleled with a higher susceptibility towards basolateral challenge. The evaluation of toxicological potentials of mycotoxins should take this difference in gene regulation dependent on route of application into account

Gothic Revival Architecture Before Horace Walpole's Strawberry Hill

The Gothic Revival is generally considered to have begun in eighteenth-century Britain with the construction of Horace Walpole’s villa, Strawberry Hill, Twickenham, in the late 1740s. As this chapter demonstrates, however, Strawberry Hill is in no way the first building, domestic or otherwise, to have recreated, even superficially, some aspect of the form and ornamental style of medieval architecture. Earlier architects who, albeit often combining it with Classicism, worked in the Gothic style include Sir Christopher Wren, Nicholas Hawksmoor, William Kent and Batty Langley, aspects of whose works are explored here. While not an exhaustive survey of pre-1750 Gothic Revival design, the examples considered in this chapter reveal how seventeenth- and eighteenth-century Gothic emerged and evolved over the course of different architects’ careers, and how, by the time that Walpole came to create his own Gothic ‘castle’, there was already in existence in Britain a sustained Gothic Revivalist tradition

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Datoranvändandets betydelse för vuxna personer med utvecklingsstörning

Fem vuxna personer med svår utvecklingsstörning och flerfunktionshinder i en daglig verksamhet valdes ut att delta i ett datorprojekt. Personer med utvecklingsstörning kan själva ha svårt att ge uttryck för sina behov av stimulans och aktivitet. Därför är det mycket angeläget att personal i den dagliga verksamheten kan finna meningsfulla aktiviteter för målgruppen som kan stödja deras aktivitetsförmåga och självbestämmande. Projektets huvudsakliga syfte var att bidra till att skapa kunskap om datoranvändande i daglig verksamhet för vuxna personer med olika grad av svår utvecklingsstörning och flerfunktionshinder. Ett delsyfte var att belysa betydelsen av datorn som aktivitet samt att studera om personerna som aktiva verktygsanvändare i samspel med personal kunde utveckla olika förmågor. Det var viktigt att aktiviteten utformades så att varje person efter sin förmåga, kunde prova på och använda olika kommunikations- och styrsätt i interaktion med sin omgivning. För att kunna använda dator som aktivitet för målgruppen krävdes utbildning i datorkunskap, för den personal som deltog i projektet. I projektet ingick fem personal, fyra som hade sin fasta tjänst i verksamheten och en projektledare. I projektet ingick även en utomstående forskare som också var handledare till personalen. Insamling av data för målgruppen gjordes på flera sätt som exempelvis genom dagboksanteckningar och videoinspelningar av aktivitetstillfällen med dator. Intervjuer med personal gjordes före och efter projektslut. Resultaten av projektet visade att samtliga deltagande personer ökade sin aktivitetsförmåga och sitt dator- och verktygsanvändande. Det blev tydligt att den pedagogik och det förhållningssätt personal använde i samspelet med personerna hade stor betydelse för deras utveckling och bemästringsstrategier. Att personerna utvecklade alternativa bemästringsstrategier i datoranvändandet berodde sannolikt på att personalen tillät och uppmuntrade detta. Resultatet av datoranvändandet bidrog även till en ökad dator- och teknikmognad hos personalen.Godkänd; 2008; 20081212 (asga