Public debt and long-term interest rates: the case of Germany, Italy and the USA

The debate on the sustainability of public finances is closely related to the analysis of the financial and macroeconomic consequences of government debt accumulation. Focusing on the USA, Germany and Italy over the 1983-2003 period, the central issue addressed in this paper is how the accumulation of government debt affects long-term interest rates, both nationally and across borders. The analysis is based on a small, multivariate econometric model, which allows us to disentangle the more permanent and transitory components of interest rate developments. Empirical evidence shows that in all cases a more sustained debt accumulation leads at least temporarily to higher long-term interest rates. This transitory impact also spills-over into other countries, mainly from the US to the two European countries. JEL Classification: E6, H63cointegration, Common Trends, long-term interest rates, public debt

Financial instability and the macroeconomy: measurement, interdependency and the role of monetary policy

The recent crisis brought to the fore the issue of systemic risk, an issue still not sufficiently well understood. The Great Recession put this deficit to the spotlight such that researchers and policy authorities all around the world stepped up efforts to increase our theoretical and empirical understanding of how systemic risk evolves, how it affects the real economy (and vice versa), and which policy tools may address systemic risk both ex ante (crisis prevention) and ex post (crisis management). The three papers of this dissertation shall help closing some of the related knowledge gaps. Chapter 2 tackles systemic risk from a measurement perspective. It presents a financial stress index called the Composite Indicator of Systemic Stress, CISS, with systemic stress understood as materialised systemic risk. Its distinctive design highlights the systemic dimension of financial stress by applying time-varying correlation weights to the aggregation of individual indicators into the composite indicator. I furthermore estimate a threshold VAR model to identify a level of financial stress at which it depresses the real economy and thus becomes fully systemic. Chapter 3 puts the CISS into a broader macro-model perspective to investigate the interrelationships between financial stress, the real economy and monetary policy. Standard and non-standard monetary policy is measured by a short-term interest rate and the growth rate of the ECB balance sheet, respectively. The CISS turns out to be a major and robust driver behind the dynamics of almost all model variables. Chapter 4 adopts a similar VAR setup but allows for independent regime switches in coefficients and error variances, respectively. The CISS impacts particularly strongly on economic activity in the systemic crisis regime that combines the highest shock variances with a stronger transmission of financial shocks to the real economy

Relating Side Chain Organization of PNIPAm with its Conformation in Aqueous Methanol

Combining nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and μs long all-atom simulations with two million particles, we establish a delicate correlation between increased side chain organization of PNIPAm and its collapse in aqueous methanol mixtures. We find that the preferential binding of methanol with PNIPAm side chains, bridging distal monomers along the polymer backbone, results in increased organization. Furthermore, methanol–PNIPAm preferential binding is dominated by hydrogen bonding. Our findings reveal that the collapse of PNIPAm is dominated by enthalpic interactions and that the standard poor solvent (entropic) effects play no major role

Assessment of Local Reaction to Vaccines in Live Piglets with Magnetic Resonance Imaging Compared to Histopathology

The safety of veterinary vaccines is assessed in clinical trials in Europe. The assessment of the local tissue reaction to vaccination by magnetic resonance imaging (MRI) could reduce the number of animals needed because repeated examinations can be performed in the same animal over time. The present study compared the evaluation of local tissue reactions to vaccination using MRI in live pigs with histopathology of porcine tissue, the current gold standard in regulatory safety testing. Eight piglets each were administered one of two commercial vaccines into marked injection sites. All animals were sedated and scanned repeatedly by MRI using a contrast agent up to day 29 after vaccination. On day 29, the animals were euthanized and underwent a pathological examination. The MRI results were compared with the pathomorphological findings at the injection site by regression analysis. The MR images and the pathological examinations yielded matching results concerning the sizes of the affected tissue volumes or areas. The use of MRI for regulatory safety testing can reduce the number of animals needed to 8 per examination group. The volume of a local reaction and its progression over time can be evaluated and documented. If persistent lesions develop a final pathomorphological examination is needed to identify the kind and local distribution of the reaction

Iodination of cyclo-E5-Complexes (E = P, As). Die Iodierung von cyclo‐E5‐Komplexen (E=P, As)

In a high-yield one-pot synthesis, the reactions of [Cp*M(eta(5)-P-5)] (M=Fe (1), Ru (2)) with I(2)resulted in the selective formation of [Cp*MP6I6](+)salts (3,4). The products comprise unprecedented all-cistripodal triphosphino-cyclotriphosphine ligands. The iodination of [Cp*Fe(eta(5)-As-5)] (6) gave, in addition to [Fe(CH3CN)(6)](2+)salts of the rare [As6I8](2-)(in7) and [As4I14](2-)(in8) anions, the first di-cationic Fe-As triple decker complex [(Cp*Fe)(2)(mu,eta(5:5)-As-5)][As6I8] (9). In contrast, the iodination of [Cp*Ru(eta(5)-As-5)] (10) did not result in the full cleavage of the M-As bonds. Instead, a number of dinuclear complexes were obtained: [(Cp*Ru)(2)(mu,eta(5:5)-As-5)][As6I8](0.5)(11) represents the first Ru-As(5)triple decker complex, thus completing the series of monocationic complexes [(Cp(R)M)(2)(mu,eta(5:5)-E-5)](+)(M=Fe, Ru; E=P, As). [(Cp*Ru)(2)As8I6] (12) crystallizes as a racemic mixture of both enantiomers, while [(Cp*Ru)(2)As4I4] (13) crystallizes as a symmetric and an asymmetric isomer and features a unique tetramer of {AsI} arsinidene units as a middle deck

Making sense of big data in health research: Towards an EU action plan.

Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health and healthcare for all Europeans

A Genetic Basis for Mechanosensory Traits in Humans

Hearing and touch are genetically related, and people with excellent hearing are more likely to have a fine sense of touch and vice versa

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes