'Trust is good, control is better': the 1974 Herstatt-Bank crisis and its implications for international regulatory reform

With its international supervisory and regulatory implications, the failure of Bankhaus Herstatt is one of the landmarks of post-war financial history. This article offers the first comprehensive historical account of the Herstatt crisis, and contributes to the wider discussions on international supervisory and regulatory reform since the mid-1970s, including regulatory capture, markets' self-regulation and resolution of failed banks. In doing so, it first argues that contrary to a widely held view, the German authorities received early and repeated warnings about Herstatt's dealings but this involved only limited and ineffective regulatory/supervisory responses, then it turns to the actual collapse of the bank in June 1974, and finally explores the wider regulatory issues raised by the Herstatt case

Importance of Fuel Cell Tests for Stability Assessment - Suitability of Titanium Diboride as an Alternative Support Material

Carbon corrosion is a severe issue limiting the long-term stability of carbon- supported catalysts, in particular in the highly dynamic conditions of automotive applications. (Doped) oxides have been discussed as suitable alternatives to replace carbon, but often suffer from poor electron conductivity. That is why non-oxide ceramics, such as tungsten carbide and titanium nitride, have been discussed recently. Titanium diboride has also been proposed, due to its promising activity and stability in an aqueous electrochemical cell. In this work, Pt nanoparticles were deposited onto μm- sized TiB2 particles with improved grain size, manufactured into porous gas diffusion electrodes and tested in a realistic polymer electrolyte membrane (PEM) fuel cell environment. In contrast to the model studies in an aqueous electrochemical cell, in the presence of oxygen and high potentials at the cathode side of a real fuel cell, TiB2 becomes rapidly oxidized as indicated by intensely colored regions in the membrane-electrode assembly (MEA). Moreover, already the electrode manufacturing process led to the formation of titanium oxides, as shown by X-ray diffraction measurements. This demonstrates that Cyclic Voltammetry (CV) measurements in an aqueous electrochemical cell are not sufficient to prove stability of novel materials for fuel cell applications

Calcitonin concentrations in patients with chronic kidney disease and medullary thyroid carcinoma or c-cell hyperplasia

It is currently not known which level of pentagastrin-stimulated calcitonin serum concentration indicates medullary thyroid carcinoma in patients with chronic kidney disease (CKD). We examined CKD stage 3–5 patients who had total thyroidectomy because of a pentagastrin-stimulated calcitonin concentration greater than 100pg/ml, and tested the diagnostic performance of basal and pentagastrin-stimulated calcitonin levels for differentiating medullary thyroid carcinoma and C-cell hyperplasia in this patient population. A total of 180 CKD patients presented with an elevated calcitonin level and had a pentagastrin stimulation test. Forty patients showed a maximum pentagastrin-stimulated calcitonin concentration greater than 100pg/ml, and 22 patients had a total thyroidectomy. Seven of these 22 patients presented with a medullary thyroid carcinoma, all other patients showed C-cell hyperplasia. Patients with medullary thyroid carcinoma showed higher unstimulated (212pg/ml (36–577) vs 42pg/ml (17–150); P<0.001) and higher maximum pentagastrin-stimulated calcitonin concentrations (862pg/ml (431–2423) vs 141pg/ml (102–471); P<0.001) as compared to patients with C-cell hyperplasia. The sensitivity (100%) and specificity (93%) estimates suggested that a maximum pentagastrin-stimulated calcitonin concentration greater than 400pg/ml indicates the presence of medullary thyroid carcinoma in patients with CKD. Receiver-operating characteristic (ROC) analysis revealed an area under the ROC plot of 0.99 for maximum pentagastrin-stimulated calcitonin concentrations. A maximum pentagastrin-stimulated calcitonin concentration greater than 400pg/ml appears to be a clinically meaningful threshold for thyroidectomy

The Performance of Private Equity Funds: Does Diversification Matter?

This paper is the first systematic analysis of the impact of diversification on the performance of private equity funds. A unique data set allows the exact evaluation of diversification across the dimensions financing stages, industries, and countries. Very different levels of diversification can be observed across sample funds. While some funds are highly specialized others are highly diversified. The empirical results show that the rate of return of private equity funds declines with diversification across financing stages, but increases with diversification across industries. Accordingly, the fraction of portfolio companies which have a negative return or return nothing at all, increase with diversification across financing stages. Diversification across countries has no systematic effect on the performance of private equity funds

Predictors associated with mortality of extracorporeal life support therapy for acute heart failure: single-center experience with 679 patients

Background: Extracorporeal life support (ECLS) therapy is increasingly used for cardiac and respiratory support postcardiotomy, refractory cardiogenic shock and cardiopulmonary resuscitation. This study aims to describe in-hospital mortality of patients requiring ECLS, identify independent predictors associated with mortality and analyze changes of mortality over time. Methods: This retrospective study includes all adult ECLS cases at the University Hospital Zurich, a designated ECLS center in Switzerland, in the period 2007 to 2019. Results: ECLS therapy was required in 679 patients (median age 60 years, 27.5% female). In-hospital mortality was 55.5%. Cubic spline interpolation did not detect evidence for a change in mortality over the whole period of 13 years. In-hospital mortality significantly varied between ECLS indications: 70.7% (152/215) for postcardiotomy, 67.9% (108/159) for cardiopulmonary resuscitation, 47.0% (110/234) for refractory cardiogenic shock, and 9.9% (7/71) for lung transplantation and expansive thoracic surgery (P<0.001). Logistic regression modelling showed excellent discrimination in the receiver operating characteristic (ROC) area under the curve (AUC) of 0.89 [95% confidence interval (CI): 0.87-0.92] and identified significant mortality predictors: age, simplified acute physiology score (SAPS) II, as well as new liver failure and each allogenic blood transfusion unit given per day. ECLS after cardiopulmonary resuscitation was associated with significantly higher mortality compared to ECLS for refractory cardiogenic shock. Conclusions: In-hospital mortality of patients treated with ECLS therapy is high. Outcomes have not changed significantly in the observed period. We identified age, SAPS II, new liver failure and each allogenic blood transfusion unit given per day as independent mortality predictors. Knowledge of predictors strongly associated with in-hospital mortality may affect future decisions about ECLS indications and the respective management to use this elaborate therapy more effectively. Keywords: Extracorporeal circulation; extracorporeal life support (ECLS)/extracorporeal membrane oxygenation (ECMO); mortality; outcome; predictor

F-Fluorodeoxyglucose (FDG)-PET features of focal nodular hyperplasia (FNH) of the liver

PET imaging. The lesions were found incidentally. The 18F-FDG PET of Vienna, Vienna, Austria imaging was performed with a dedicated PET tomograph after intravenous injection of 300-370 MBq 18F-FDG. The 18F-FDG accumulation in the lesions was (semi)quantified by calculating the standardized uptake value (SUV) and SUV has been corrected for the lean body mass (LBM). Eight patients with liver metastases spread from melanoma (nΩ2) and colorectal carcinoma (nΩ6) served as controls. The size of the FNH lesions and of the control group ranged from 2.0 to 8.5 cm (mean 4.83 cm∫2.37) and from 1.5 to 6 cm (mean 3.28∫1.52), respectively. Results: While in malignant liver lesions the accumulation of 18F-FDG was significantly increased, all FNH lesions showed normal or even decreased accumulation of 18F-FDG. In FNH lesions, SUV ranged between 1.5 and 2.6 (mean 2.12∫0.38), whereas all liver metastases showed an increased SUV rang- PET is a new imaging method that has been successfully applied to image malignant tumors. While a large number of studies has been published in the last years about the usefulness of 18F-FDG PET in a variety of malignant diseases, the glucose metabolism of FNH in vivo has not bee

Evaluation of APOBEC3B Recognition Motifs by NMR Reveals Preferred Substrates.

APOBEC3B (A3B) deamination activity on ssDNA is considered a contributing factor to tumor heterogeneity and drug resistance in a number of human cancers. Despite its clinical impact, little is known about A3B ssDNA substrate preference. We have used nuclear magnetic resonance to monitor the catalytic turnover of A3B substrates in real-time. This study reports preferred nucleotide sequences for A3B substrates, including optimized 4-mer oligonucleotides, and reveals a breadth of substrate recognition that includes DNA sequences known to be mutated in drug-resistant cancer clones. Our results are consistent with available clinical and structural data and may inform the design of substrate-based A3B inhibitors

Identification of SERPINA1 as single marker for papillary thyroid carcinoma through microarray meta analysis and quantification of its discriminatory power in independent validation

<p>Abstract</p> <p>Background</p> <p>Several DNA microarray based expression signatures for the different clinically relevant thyroid tumor entities have been described over the past few years. However, reproducibility of these signatures is generally low, mainly due to study biases, small sample sizes and the highly multivariate nature of microarrays. While there are new technologies available for a more accurate high throughput expression analysis, we show that there is still a lot of information to be gained from data deposited in public microarray databases. In this study we were aiming (1) to identify potential markers for papillary thyroid carcinomas through meta analysis of public microarray data and (2) to confirm these markers in an independent dataset using an independent technology.</p> <p>Methods</p> <p>We adopted a meta analysis approach for four publicly available microarray datasets on papillary thyroid carcinoma (PTC) nodules versus nodular goitre (NG) from N2-frozen tissue. The methodology included merging of datasets, bias removal using distance weighted discrimination (DWD), feature selection/inference statistics, classification/crossvalidation and gene set enrichment analysis (GSEA). External Validation was performed on an independent dataset using an independent technology, quantitative RT-PCR (RT-qPCR) in our laboratory.</p> <p>Results</p> <p>From meta analysis we identified one gene (SERPINA1) which identifies papillary thyroid carcinoma against benign nodules with 99% accuracy (n = 99, sensitivity = 0.98, specificity = 1, PPV = 1, NPV = 0.98). In the independent validation data, which included not only PTC and NG, but all major histological thyroid entities plus a few variants, SERPINA1 was again markedly up regulated (36-fold, p = 1:3*10^-10) in PTC and identification of papillary carcinoma was possible with 93% accuracy (n = 82, sensitivity = 1, specificity = 0.90, PPV = 0.76, NPV = 1). We also show that the extracellular matrix pathway is strongly activated in the meta analysis data, suggesting an important role of tumor-stroma interaction in the carcinogenesis of papillary thyroid carcinoma.</p> <p>Conclusions</p> <p>We show that valuable new information can be gained from meta analysis of existing microarray data deposited in public repositories. While single microarray studies rarely exhibit a sample number which allows robust feature selection, this can be achieved by combining published data using DWD. This approach is not only efficient, but also very cost-effective. Independent validation shows the validity of the results from this meta analysis and confirms SERPINA1 as a potent mRNA marker for PTC in a total (meta analysis plus validation) of 181 samples.</p

Olanzapine: A potent agonist at the hM4D(Gi) DREADD amenable to clinical translation of chemogenetics

Designer receptors exclusively activated by designer drugs (DREADDs) derived from muscarinic receptors not only are a powerful tool to test causality in basic neuroscience but also are potentially amenable to clinical translation. A major obstacle, however, is that the widely used agonist clozapine N-oxide undergoes conversion to clozapine, which penetrates the blood-brain barrier but has an unfavorable side effect profile. Perlapine has been reported to activate DREADDs at nanomolar concentrations but is not approved for use in humans by the Food and Drug Administration or the European Medicines Agency, limiting its translational potential. Here, we report that the atypical antipsychotic drug olanzapine, widely available in various formulations, is a potent agonist of the human M4 muscarinic receptor-based DREADD, facilitating clinical translation of chemogenetics to treat central nervous system diseases