Heidelberg University

About: Heidelberg University is a education organization based out in Heidelberg, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 62066 authors who have published 119109 publications receiving 4678423 citations. The organization is also known as: Ruprecht-Karls-Universität Heidelberg & University of Heidelberg.

The evolutionary history of 2,658 cancers

Abstract: Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.

Intracellular compartmentation of cardiac troponin T and its release kinetics in patients with reperfused and nonreperfused myocardial infarction.

Abstract: In a previous study on the diagnostic efficiency of troponin T measurements in patients with suspected acute myocardial infarction (AMI), the authors found a high variability of troponin T serum concentration changes on day 1 in patients with AMI who underwent thrombolytic treatment. Therefore, the aims of the present study were to investigate the intracellular compartmentation of troponin T and to analyze the effects of AMI reperfusion on the appearance kinetics of cardiac troponin T in serum. Cardiac troponin T was measured with a newly developed bideterminant sandwich assay using cardiospecific, affinity-purified polyclonal antibodies and peroxidase-labeled monoclonal antibody. An unbound cytosolic troponin T pool was found in ultracentrifuged homogenates of myocardial tissue of different species ranging from 0.013 to 0.036 mg/g wet weight. The soluble troponin T molecule had electrophoretic properties identical to troponin T compartmented in the myofibrils. The clinical study group comprised 57 patients with AMI undergoing thrombolytic treatment. Blood flow to the infarct zone and point of time of reperfusion were tested by immediate and late angiography. The appearance of troponin T in serum on day 1 after the onset of AMI depended strongly on reperfusion and on duration of ischemia before reperfusion. Thus, in patients with early reperfused AMI, a marked peak in troponin T serum concentrations was found at 14 hours after the onset of pain. This early troponin T peak was absent in patients with AMI reperfusion occurring greater than 5.5 hours after the onset of pain and in patients with nonreperfused AMI. By contrast, the kinetics of troponin T release after the first day after AMI were unaffected by reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Multi-scale initial conditions for cosmological simulations

Abstract: We discuss a new algorithm to generate multi-scale initial conditions with multiple levels of refinements for cosmological 'zoom-in' simulations. The method uses an adaptive convolution of Gaussian white noise with a real-space transfer function kernel together with an adaptive multi-grid Poisson solver to generate displacements and velocities following first- (1LPT) or second-order Lagrangian perturbation theory (2LPT). The new algorithm achieves rms relative errors of the order of 10{sup -4} for displacements and velocities in the refinement region and thus improves in terms of errors by about two orders of magnitude over previous approaches. In addition, errors are localized at coarse-fine boundaries and do not suffer from Fourier-space-induced interference ringing. An optional hybrid multi-grid and Fast Fourier Transform (FFT) based scheme is introduced which has identical Fourier-space behaviour as traditional approaches. Using a suite of re-simulations of a galaxy cluster halo our real-space-based approach is found to reproduce correlation functions, density profiles, key halo properties and subhalo abundances with per cent level accuracy. Finally, we generalize our approach for two-component baryon and dark-matter simulations and demonstrate that the power spectrum evolution is in excellent agreement with linear perturbation theory. For initial baryon density fields, it is suggested to use the local Lagrangian approximation in order to generate a density field for mesh-based codes that is consistent with the Lagrangian perturbation theory instead of the current practice of using the Eulerian linearly scaled densities.

The Short FES-I: a shortened version of the falls efficacy scale-international to assess fear of falling

Abstract: BACKGROUND: the 16-item Falls Efficacy Scale-International (FES-I) has been shown to have excellent reliability and construct validity. However, for practical and clinical purposes, a shortened version of the FES-I would be useful. OBJECTIVE: to develop and validate a shortened version of FES-I while preserving good psychometric properties. DESIGN: initial development of a shortened version using data from a UK survey (Short FES-I; n = 704), test of reliability and validity of the Short FES-I using data from a Dutch survey (n = 300). SETTING: community samples. METHODS: comparison of reliability and validity of the Short FES-I and the FES-I in a random sample of 193 people aged between 70 and 92. RESULTS: the internal and 4-week test-retest reliability of the Short FES-I is excellent (Cronbach's alpha 0.92, intra-class coefficient 0.83) and comparable to the FES-I. The correlation between the Short FES-I and the FES-I is 0.97. Patterns in differences with respect to mean scores according to age, sex, falls history, and overall fear of falling are similar for the Short FES-I and the FES-I. The FES-I had slightly better power to discriminate between groups differentiated by age, sex, falls history, and fear falling, but differences are small. CONCLUSIONS: the Short FES-I is a good and feasible measure to assess fear of falling in older persons. However, if researchers or clinicians are particularly interested in the distributions of specific fear of falling-related activities not included in the Short FES-I, the use of the full FES-I is recommended. Language: en