Scores to predict major bleeding risk during oral anticoagulation therapy: a prospective validation study.

BACKGROUND: Clinical scores may help physicians to better assess the individual risk/benefit of oral anticoagulant therapy. We aimed to externally validate and compare the prognostic performance of 7 clinical prediction scores for major bleeding events during oral anticoagulation therapy. METHODS: We followed 515 adult patients taking oral anticoagulants to measure the first major bleeding event over a 12-month follow-up period. The performance of each score to predict the risk of major bleeding and the physician's subjective assessment of bleeding risk were compared with the C statistic. RESULTS: The cumulative incidence of a first major bleeding event during follow-up was 6.8% (35/515). According to the 7 scoring systems, the proportions of major bleeding ranged from 3.0% to 5.7% for low-risk, 6.7% to 9.9% for intermediate-risk, and 7.4% to 15.4% for high-risk patients. The overall predictive accuracy of the scores was poor, with the C statistic ranging from 0.54 to 0.61 and not significantly different from each other (P=.84). Only the Anticoagulation and Risk Factors in Atrial Fibrillation score performed slightly better than would be expected by chance (C statistic, 0.61; 95% confidence interval, 0.52-0.70). The performance of the scores was not statistically better than physicians' subjective risk assessments (C statistic, 0.55; P=.94). CONCLUSION: The performance of 7 clinical scoring systems in predicting major bleeding events in patients receiving oral anticoagulation therapy was poor and not better than physicians' subjective assessments.

Midgut of Lepidopteran pupae is a major depot of sequestered, mobilizable, ecdysteroids

Extirpation of endocrine organs - a classic maneuver in hormonal research - has been difficult or impossible in the case of the prothoracic glands (PG) of insects. In larval and pupal Lepidoptera the glands are virtually inaccessible unless one sacrifices the insect. Even then, the PG are not easy to remove in their entirety. Consequently, in order to obtain viable preparations lacking PG, one costomarily makes use of abdomens isolated by litigation or surgery.

Association of serum homocysteine with major depressive disorder: results from a large population-based study.

BACKGROUND: Studies on the association between homocysteine levels and depression have shown conflicting results. To examine the association between serum total homocysteine (tHcy) levels and major depressive disorder (MDD) in a large community sample with an extended age range. METHODS: A total of 3392 men and women aged 35-66 years participating in the CoLaus study and its psychiatric arm (PsyCoLaus) were included in the analyses. High tHcy measured from fasting blood samples was defined as a concentration ≥15μmol/L. MDD was assessed using the semi-structured Diagnostic Interview for Genetics Studies. RESULTS: In multivariate analyses, elevated tHcy levels were associated with greater odds of meeting the diagnostic criteria for lifetime MDD among men (OR=1.71; 95% CI, 1.18-2.50). This was particularly the case for remitted MDD. Among women, there was no significant association between tHcy levels and MDD and the association tended to be in the opposite direction (OR=0.61; 95% CI, 0.34-1.08). CONCLUSIONS: In this large population-based study, elevated tHcy concentrations are associated with lifetime MDD and particularly with remitted MDD among men.

MARCKS-related protein (MRP) is a substrate for the Leishmania major surface protease leishmanolysin (gp63).

Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP; MacMARCKS) are protein kinase C substrates in diverse cell types. Activation of murine macrophages by cytokines increases MRP expression, but infection with Leishmania promastigotes during activation results in MRP depletion. We therefore examined the effect of Leishmania major LV39 on recombinant MRP. Both live promastigotes and a soluble fraction of LV39 lysates degraded MRP to yield lower molecular weight fragments. Degradation was independent of MRP myristoylation and was inhibited by protein kinase C-dependent phosphorylation of MRP. MRP was similarly degraded by purified leishmanolysin (gp63), a Leishmania surface metalloprotease. Degradation was evident at low enzyme/substrate ratios, over a broad pH range, and was inhibited by 1,10-phenanthroline and by a hydroxamate dipeptide inhibitor of leishmanolysin. Using mass spectrometric analysis, cleavage was shown to occur within the effector domain of MRP between Ser(92) and Phe(93), in accordance with the substrate specificity of leishmanolysin. Moreover, an MRP construct in which the effector domain had been deleted was resistant to cleavage. Thus, Leishmania infection may result in leishmanolysin-dependent hydrolysis of MRP, a major protein kinase C substrate in macrophages.

Why do UK banks securitize?

The eight years from 2000 to 2008 saw a rapid growth in the use of securitization by UK banks. We aim to identify the reasons that contributed to this rapid growth. The time period (2000 to 2010) covered by our study is noteworthy as it covers the pre- financial crisis credit-boom, the peak of the fi nancial crisis and its aftermath. In the wake of the financial crisis, many governments, regulators and political commentators have pointed an accusing finger at the securitization market - even in the absence of a detailed statistical and economic analysis. We contribute to the extant literature by performing such an analysis on UK banks, focussing principally on whether it is the need for liquidity (i.e. the funding of their balance sheets), or the desire to engage in regulatory capital arbitrage or the need for credit risk transfer that has led to UK banks securitizing their assets. We show that securitization has been signi ficantly driven by liquidity reasons. In addition, we observe a positive link between securitization and banks credit risk. We interpret these latter findings as evidence that UK banks which engaged in securitization did so, in part, to transfer credit risk and that, in comparison to UK banks which did not use securitization, they had more credit risk to transfer in the sense that they originated lower quality loans and held lower quality assets. We show that banks which issued more asset-backed securities before the financial crisis suffered more defaults after the financial crisis.

Central banks and house prices in the run-up to the crisis

The financial crisis and the role played within it by fluctuations in house prices has reopened the debate about whether monetary policy should respond to asset prices. This paper investigates how the central banks of the euro area, the UK and the US considered, understood and responded to the trends in house prices in the six or seven years preceding the crisis, and how they have analysed those developments since the crisis. It suggests that these central banks, particularly the Anglo-Saxon ones, might have been able to take some useful action if they had devoted more intellectual resources to analysing the possible misalignments of house prices and been willing to act on them.

Prevalence of Trypanosoma cruzi infection in blood banks of seven departments of Bolivia

Trypanosoma cruzi infection was studied in 1,298 sera samples of blood banks from 7 capital departments of Bolivia, using the immunofluorescence test (IFI) and Enzyme Linked Immunosorbent Assay (Elisa). The percentages of positivity in these 7 departments have an average of 28% and are distributed as follows: Sta. Cruz 51%, Tarija 45%, Cochabamba 28%, Sucre 39%, La Paz 4.9%, Oruro 6% and Potosi 24%. The prevalence is related with the altitude levels of the different departments. However in Potosi (3,945 m) we found a 24% of prevalence, probably due to the proximity of endemic valleys to the city. The authors suggest a strict control in blood donors since there exists a great risk of infection