OBJECTIVES The goal was to develop a scoring system to predict the 30-day mortality rate for patients undergoing surgery for acute type A aortic dissection on the basis of the German Registry for Acute Type A Aortic Dissection (GERAADA) data set and to provide a Web-based application for standard use. METHODS A total of 2537 patients enrolled in GERAADA who underwent surgery between 2006 and 2015 were analysed. Variable selection was performed using the R-package FAMoS. The robustness of the results was confirmed via the bootstrap procedure. The coefficients of the final model were used to calculate the risk score in a Web-based application. RESULTS Age [odds ratio (OR) 1.018, 95% confidence interval (CI) 1.009–1.026; P < 0.001; 5-year OR: 1.093], need for catecholamines at referral (OR 1.732, 95% CI 1.340–2.232; P < 0.001), preoperative resuscitation (OR 3.051, 95% CI 2.099–4.441; P < 0.001), need for intubation before surgery (OR 1.949, 95% CI 1.465–2.585; P < 0.001), preoperative hemiparesis (OR 1.442, 95% CI 0.996–2.065; P = 0.049), coronary malperfusion (OR 1.870, 95% CI 1.386–2.509; P < 0.001), visceral malperfusion (OR 1.748, 95% CI 1.198–2.530; P = 0.003), dissection extension to the descending aorta (OR 1.443, 95% CI 1.120–1.864; P = 0.005) and previous cardiac surgery (OR 1.772, 95% CI 1.048–2.903; P = 0.027) were independent predictors of the 30-day mortality rate. The Web application based on the final model can be found at https://www.dgthg.de/de/GERAADA_Score. CONCLUSIONS The GERAADA score is a simple, effective tool to predict the 30-day mortality rate for patients undergoing surgery for acute type A aortic dissection. We recommend the widespread use of this Web-based application for standard use.

Different studies on the position of the non-indigenous species Neogobius melanostomus within the coastal food web of the Pomeranian Bay (western Baltic) were performed, resulting in a quantitative and qualitative species list of prey organisms found in the stomachs of the invader and an estimation concerning the importance of round goby as prey for different resident predators. It seems that the colonization process is not fully completed yet, but the results reveal that the species is already established in the food web 16 years after the first observation within the study area. The results show that N. melanostomus feed upon a wide range of different resident organisms. While a direct predation effect on native fish species appears rather unlikely, indirect effects such as competition cannot yet be excluded. In addition, our results reveal an ontogenetic diet shift and that the round goby itself already serves as an important prey for piscivorous fish and seabirds. Finally, we formulate different hypotheses based on our results which will require further research. ARTICLE HISTORY

The present data demonstrate that the level of regional 201Tl activity in redistribution and, in particular, reinjection images is significantly related to the mass of preserved viable myocytes in poststenotic left ventricular myocardium. Therefore, the residual 201Tl activity provides information about viability within irreversible perfusion defects and may itself serve as marker of myocardial viability.

Infection by Cytomegalovirus (CMV) is characterized by the massive expansion and continued maintenance of CMV-specific CD8 + T cells for certain CMV-derived peptides. This phenomenon called “memory inflation" has made CMV a primary target for the generation of T cell based vaccine vectors against various diseases. However, many aspects concerning the generation and maintenance of the inflationary CD8 + T cell response still remain to be resolved. In this study, we combined experimental data and mathematical models to analyze the dynamics of circulatory inflationary CD8 + T cells within individual mice infected by MCMV. Obtaining frequent measurements on the number and frequency of CMV-specific CD8 + T cells up to 70 days post infection, we find that mathematical models assuming differing viral stimuli during acute infection and the inflationary phase provide a better description for the observed dynamics than models relying on similar viral stimuli during both phases. In addition, our analysis allowed a detailed quantification of the different phases of memory inflation within individual mice (1 st -expansion - contraction - 2 nd expansion/maintenance) indicating remarkable consistency of the timing of these phases across mice, but considerable variation in the size of the individual responses between mice. Our analysis provides a first step toward generating a mechanistic framework for analyzing the generation and maintenance of inflationary CD8 + T cells while accounting for individual heterogeneity. Extending these analyses by incorporating measurements from additional compartments and more prolonged sampling will help to obtain a systematic and quantitative understanding of the factors regulating the process of memory inflation.

Background: This study explores the application of CardioSecur ® (CS-ECG), a hand-held 4-electrode/22-lead ECG-device, in comparison with conventional 12-lead electrocardiogram (c12L-ECG) in patients with acute chest pain in the prehospital emergency setting. Methods: CS-ECG systems were provided for two physician-staffed emergency ambulances and parallel recordings of c12L-ECG and CS-ECG were obtained from all patients with acute chest pain. Treating emergency physicians were asked to evaluate the CS-ECG system with a standardized questionnaire. Following study completion, acquired ECGs were analyzed separately by two independent cardiologists blinded to all other medical records. Results: Over a period of 20 months a total of 203 patients were included in our study. According to a standardized questionnaire, 79% of emergency medical professionals preferred application of CS-ECG, with 87% of teams judging CS-ECG to be beneficial for patients. Morover, 79% of physicians reported a reduction in time to definitive diagnosis with implementation of CS-ECG. The majority of professional users attested user-friendliness and feasibility of CS-ECG in terms of easy general handling (94%), application (93%), and placement of electrodes (98%). During prehospital triage, both c12L-ECG and CS-ECG correctly identified 31 (91%) patients with ST-elevation myocardial infarction (STEMI). Conclusion: In this first pilot study, implementation of the CardioSecur ®-ECG system in the prehospital emergency setting demonstrated feasibility and user-friendliness so that emergency teams generally preferred CS-ECG to c12L-ECG. Diagnostic yield of CS-ECG was similar to c12L-ECG recordings.

SUMMARY1. The effects of neuropeptide-Y (NPY) on the membrane potential of vascular smooth muscle cells were studied in renal arterioles of hydronephrotic mouse kidneys.2. Kidney vessels are only weakly coupled with length constants of less than 10 /tsm and are most probably 'multiunit' vessels.3. The vasoconstrictor peptide NPY reversibly depolarizes only smooth muscle cells in arterioles at distances > 200,um from the glomerulus, whereas no changes of the membrane potential can be evoked close to the glomerulus (distance < 50 ,m).4. The depolarizations, when present, are dose dependent. 5. Regardless of distance from the glomerulus cells respond uniformly to application of the vasoconstrictor angiotensin II.

Most biological systems are difficult to analyse due to a multitude of interacting components and the concomitant lack of information about the essential dynamics. Finding appropriate models that provide a systematic description of such biological systems and that help to identify their relevant factors and processes can be challenging given the sheer number of possibilities. Model selection algorithms that evaluate the performance of a multitude of different models against experimental data provide a useful tool to identify appropriate model structures. However, many algorithms addressing the analysis of complex dynamical systems, as they are often used in biology, compare a preselected number of models or rely on exhaustive searches of the total model space which might be unfeasible dependent on the number of possibilities. Therefore, we developed an algorithm that is able to perform model selection on complex systems and searches large model spaces in a dynamical way. Our algorithm includes local and newly developed non-local search methods that can prevent the algorithm from ending up in local minima of the model space by accounting for structurally similar processes. We tested and validated the algorithm based on simulated data and showed its flexibility for handling different model structures. We also used the algorithm to analyse experimental data on the cell proliferation dynamics of CD4 + and CD8 + T cells that were cultured under different conditions. Our analyses indicated dynamical changes within the proliferation potential of cells that was reduced within tissue-like 3D ex vivo cultures compared to suspension. Due to the flexibility in handling various model structures, the algorithm is applicable to a large variety of different biological problems and represents a useful tool for the data-oriented evaluation of complex model spaces.

Whole sporozoite vaccines represent one of the most promising strategies to induce protection against malaria. However, the development of efficient vaccination protocols still remains a major challenge. To understand how the generation of immunity is affected by variations in vaccination dosage and frequency, we systematically analyzed intrasplenic and intrahepatic CD8+ T cell responses following varied immunizations of mice with radiation-attenuated sporozoites. By combining experimental data and mathematical modeling, our analysis indicates a reversing role of spleen and liver in the generation of protective liver-resident CD8+ T cells during priming and booster injections: While the spleen acts as a critical source compartment during priming, the increase in vaccine-induced hepatic T cell levels is likely due to local reactivation in the liver in response to subsequent booster injections. Higher dosing accelerates the efficient generation of liver-resident CD8+ T cells by especially affecting their local reactivation. In addition, we determine the differentiation and migration pathway from splenic precursors toward hepatic memory cells thereby presenting a mechanistic framework for the impact of various vaccination protocols on these dynamics. Thus, our work provides important insights into organ-specific CD8+ T cell dynamics and their role and interplay in the formation of protective immunity against malaria.