Der Einfluss von Tumorgröße, Sauerstoffgehalt und adrenerger Stimulation auf die Expression und Funktion tumorassoziierter Proteine in Kopf-Hals Tumorzelllinien

Diese Dissertation beschäftigt sich mit dem Einfluss von Tumorgröße (in Sphäroiden), Hypoxie, sowie alpha2- und beta2-adrenerger Stimulation auf die Expression der tumorassoziierten Proteine E-, P- und N-Cadherin, MMP2, MMP9 und PD-L1. Außerdem wurde das Migrations-, Invasions- und Proliferationsverhalten nach adrenerger Stimulation untersucht. Gegenstand waren dabei die vier Kopf-Hals-Tumorzelllinien (Plattenepithelkarzinom) PCI 1, PCI 9, PCI 13 und PCI 68

Entwicklung der Altersarmut bis 2036: Trends, Risikogruppen und Politikszenarien

Wie entwickelt sich das Risiko für Altersarmut in der nahen bis mittleren Frist? Welche Gruppen werden besonders von Altersarmut betroffen sein? Welche Auswirkungen haben derzeit diskutierte Rentenreformen auf die Entwicklung der Altersarmut? Es ist das Ziel dieser Simulationsstudie, Antworten auf diese zentralen sozialpolitischen Fragen zu geben. Um das Armutsrisiko zu messen, wird in dieser Analyse das gesamte Einkommen nach Steuern im Haushaltskontext auf Basis von repräsentativen Haushaltsdaten simuliert und geschätzt, wie sich das Armutsrisiko bis zum Jahr 2036 entwickeln wird. In den Simulationen werden die Gesetzliche Rentenversicherung (GRV)/Beamtenversorgung, Betriebliche Altersvorsorge (BAV), Lohneinkommen und private Absicherung (z. B. Riester- und Rürup-Rente, Lebensversicherung und weitere Formen von Geldvermögen) sowie Steuern, Sozialabgaben und Transfers modelliert. [...]How will the risk of old-age poverty develop in the near to mid-term? Which groups will be particularly affected by old-age poverty? What are the effects of pension reforms on the development of old-age poverty? It is the goal of this simulation study to provide answers to these central social policy questions. In order to measure the poverty risk, this analysis simulates the total household income after tax on the basis of representative survey data and estimates how the risk of poverty will develop up to the year 2036. The simulations model the statutory pension insurance, pensions for civil servants, occupational pensions, labor income and private savings (for example subsidized private insurance plans (Riester- and Rürup-Rente), life insurance and other financial assets) as well as taxes, social security contributions and transfers. [...

All-suture anchors for distal biceps tendon repair: a preliminary outcome study

Introduction: The aim of this study was to retrospectively evaluate the clinical outcome of double intramedullary all-suture anchors’ fixation for distal biceps tendon ruptures. Materials and methods: A retrospective case series of patients who underwent primary distal biceps tendon repair with all-suture anchors was conducted. Functional outcome was assessed at a minimum follow-up of at 12 months based on the assessments of the Mayo Elbow Performance Score (MEPS), Andrews–Carson Score (ACS), Quick Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH), and the Visual Analog Scale (VAS) for pain. Maximum isometric strength test for flexion and supination as well as postoperative range of motion (ROM) were determined for both arms. Results: 23 patients treated with all-suture anchors were assessed at follow-up survey (mean age 56.5 ± 11.4 years, 96% male). The follow-up time was 20 months (range Q$_{0.25}$–Q$_{0.75}$, 15–23 months). The following outcome results were obtained: MEPS 100 (range Q$_{0.25}$–Q$_{0.75}$, 100–100); ACS 200 (range Q$_{0.25}$–Q$_{0.75}$, 195–200); QuickDASH 31 (range Q$_{0.25}$–Q$_{0.75}$, 30–31); VAS 0 (range Q$_{0.25}$–Q$_{0.75}$, 0–0). The mean strength compared to the uninjured side was 95.6% (range Q$_{0.25}$–Q$_{0.75}$, 80.9–104%) for flexion and 91.8 ± 11.6% for supination. There was no significant difference in ROM or strength compared to the uninjured side and no complications were observed in any patient. Conclusion: Distal biceps tendon refixation using all-suture anchors provides good-to-excellent results in terms of patient-reported and functional outcome. This repair technique appears to be a viable surgical option, although further long-term results are needed

Submillisievert Computed Tomography of the Chest Using Model-Based Iterative Algorithm: Optimization of Tube Voltage With Regard to Patient Size

Objective: The aim of this study was to define optimal tube potential for soft tissue and vessel visualization in dose-reduced chest CT protocols using model-based iterative algorithm in average and overweight patients. Methods: Thirty-six patients receiving chest CTaccording to 3 protocols (120 kVp/noise index [NI], 60;100 kVp/NI, 65;80 kVp/NI, 70) were included in this prospective study, approved by the ethics committee. Patients' physical parameters and dose descriptors were recorded. Images were reconstructed with model-based algorithm. Two radiologists evaluated image quality and lesion conspicuity;the protocols were intraindividually compared with preceding control CT reconstructed with statistical algorithm (120 kVp/NI, 20). Mean and standard deviation of attenuation of the muscle and fat tissues and signal-to-noise ratio of the aorta were measured. Results: Diagnostic images (lesion conspicuity, 95%-100%) were acquired in average and overweight patients at 1.34, 1.02, and 1.08 mGy and at 3.41, 3.20, and 2.88 mGy at 120, 100, and 80 kVp, respectively. Data are given as CT dose index volume values. Conclusions: Model-based algorithm allows for submillisievert chest CT in average patients;the use of 100 kVp is recommended

Incidence of delayed and missed diagnoses in whole-body multidetector CT in patients with multiple injuries after trauma

Background: Whole-body CT (WBCT) is the imaging modality of choice during the initial diagnostic work-up of multiple injured patients in order to identify serious injuries and initiate adequate treatment immediately. However, delayed diagnosed or even missed injuries have been reported frequently ranging from 1.3% to 47%. Purpose: To highlight commonly missed lesions in WBCT of patients with multiple injuries. Material and Methods: A total of 375 patients (age 42.8 +/- 17.9 years, ISS 26.6 +/- 17.0) with a WBCT (head to symphysis) were included. The final CT report was compared with clinical and operation reports. Discrepant findings were recorded and grouped as relevant and non-relevant to further treatment. In both groups, an experienced trauma radiologist read the CT images retrospectively, whether these lesions were missed or truly not detectable. Results: In 336 patients (89.6%), all injuries in the regions examined were diagnosed correctly in the final reports of the initial CT. Forty-eight patients (12.8%) had injuries in regions of the body that were not included in the CT. Fourteen patients (3.7%) had injuries that did not require further treatment. Twenty-five patients (6.7%) had injuries that required further treatment. With secondary interpretation, 85.4% of all missed lesions could be diagnosed in retrospect from the primary CT data-set. Small pancreatic and bowel contusions were identified as truly non-detectable. Conclusion: In multiple traumas, only a few missed injuries in initial WBCT reading are clinically relevant. However, as the vast majority of these injuries are detectable, the radiologist has to be alert for commonly missed findings to avoid a delayed diagnosis

Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease

Neurodegenerative diseases are a growing burden, and there is an urgent need for better biomarkers for diagnosis, prognosis, and treatment efficacy. Structural and functional brain alterations are reflected in the protein composition of cerebrospinal fluid (CSF). Alzheimer's disease (AD) patients have higher CSF levels of tau, but we lack knowledge of systems-wide changes of CSF protein levels that accompany AD. Here, we present a highly reproducible mass spectrometry (MS)-based proteomics workflow for the in-depth analysis of CSF from minimal sample amounts. From three independent studies (197 individuals), we characterize differences in proteins by AD status (> 1,000 proteins, CV < 20%). Proteins with previous links to neurodegeneration such as tau, SOD1, and PARK7 differed most strongly by AD status, providing strong positive controls for our approach. CSF proteome changes in Alzheimer's disease prove to be widespread and often correlated with tau concentrations. Our unbiased screen also reveals a consistent glycolytic signature across our cohorts and a recent study. Machine learning suggests clinical utility of this proteomic signature

Combining targeted and systematic prostate biopsy improves prostate cancer detection and correlation with the whole mount histopathology in biopsy naïve and previous negative biopsy patients

OBJECTIVE: Guidelines for previous negative biopsy (PNB) cohorts with a suspicion of prostate cancer (PCa) after positive multiparametric (mp) magnetic-resonance-imaging (MRI) often favour the fusion-guided targeted prostate-biopsy (TB) only approach for Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions. However, recommendations lack direct biopsy performance comparison within biopsy naïve (BN) vs. PNB patients and its prognostication of the whole mount pathology report (WMPR), respectively. We suppose, that the combination of TB and concomitant TRUS-systematic biopsy (SB) improves the PCa detection rate of PI-RADS 2, 3, 4 or 5 lesions and the International Society of Urological Pathology (ISUP)-grade predictability of the WMPR in BN- and PNB patients. METHODS: Patients with suspicious mpMRI, elevated prostate-specific-antigen and/or abnormal digital rectal examination were included. All PI-RADS reports were intramurally reviewed for biopsy planning. We compared the PI-RADS score substratified TB, SB or combined approach (TB/SB) associated BN- and PNB-PCa detection rate. Furthermore, we assessed the ISUP-grade variability between biopsy cores and the WMPR. RESULTS: According to BN (n = 499) vs. PNB (n = 314) patients, clinically significant (cs) PCa was detected more frequently by the TB/SB approach (62 vs. 43%) than with the TB (54 vs. 34%) or SB (57 vs. 34%) (all p < 0.0001) alone. Furthermore, we observed that the TB/SB strategy detects a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports, both in BN and PNB men. In contrast, applied biopsy techniques were equally effective to detect csPCa within PI-RADS 2 lesions. In case of csPCa diagnosis the TB approach was more often false-negative in PNB patients (BN 11% vs. PNB 19%; p = 0.02). The TB/SB technique showed in general significantly less upgrading, whereas a higher agreement was only observed for the total and BN patient cohort. CONCLUSION: Despite csPCa is more frequently found in BN patients, the TB/SB method always detected a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports of our BN and PNB group. The TB/SB strategy predicts the ISUP-grade best in the total and BN cohort and in general shows the lowest upgrading rates, emphasizing its value not only in BN but also PNB patients

A joint numerical study of multi-regime turbulent combustion

This article presents a joint numerical study on the Multi Regime Burner configuration. The burner design consists of three concentric inlet streams, which can be operated independently with different equivalence ratios, allowing the operation of stratified flames characterized by different combustion regimes, including premixed, non-premixed, and multi-regime flame zones. Simulations were performed on three LES solvers based on different numerical methods. Combustion kinetics were simplified by using tabulated or reduced chemistry methods. Finally, different turbulent combustion modeling strategies were employed, covering geometrical, statistical, and reactor based approaches. Due to this significant scattering of simulation parameters, a conclusion on specific combustion model performance is impossible. However, with ten numerical groups involved in the numerical simulations, a rough statistical analysis is conducted: the average and the standard deviation of the numerical simulation are computed and compared against experiments. This joint numerical study is therefore a partial illustration of the community's ability to model turbulent combustion. This exercise gives the average performance of current simulations and identifies physical phenomena not well captured today by most modeling strategies. Detailed comparisons between experimental and numerical data along radial profiles taken at different axial positions showed that the temperature field is fairly well captured up to 60 mm from the burner exit. The comparison reveals, however, significant discrepancies regarding CO mass fraction prediction. Three causes may explain this phenomenon. The first reason is the higher sensitivity of carbon monoxide to the simplification of detailed chemistry, especially when multiple combustion regimes are encountered. The second is the bias introduced by artificial thickening, which overestimates the species’ mass production rate. This behavior has been illustrated by manufacturing mean thickened turbulent flame brush from a random displacement of 1-D laminar flame solutions. The last one is the influence of the subgrid-scale flame wrinkling on the filtered chemical flame structure, which may be challenging to model.</p

A joint numerical study of multi-regime turbulent combustion

This article presents a joint numerical study on the Multi Regime Burner configuration. The burner design consists of three concentric inlet streams, which can be operated independently with different equivalence ratios, allowing the operation of stratified flames characterized by different combustion regimes, including premixed, non-premixed, and multi-regime flame zones. Simulations were performed on three LES solvers based on different numerical methods. Combustion kinetics were simplified by using tabulated or reduced chemistry methods. Finally, different turbulent combustion modeling strategies were employed, covering geometrical, statistical, and reactor based approaches. Due to this significant scattering of simulation parameters, a conclusion on specific combustion model performance is impossible. However, with ten numerical groups involved in the numerical simulations, a rough statistical analysis is conducted: the average and the standard deviation of the numerical simulation are computed and compared against experiments. This joint numerical study is therefore a partial illustration of the community's ability to model turbulent combustion. This exercise gives the average performance of current simulations and identifies physical phenomena not well captured today by most modeling strategies. Detailed comparisons between experimental and numerical data along radial profiles taken at different axial positions showed that the temperature field is fairly well captured up to 60 mm from the burner exit. The comparison reveals, however, significant discrepancies regarding CO mass fraction prediction. Three causes may explain this phenomenon. The first reason is the higher sensitivity of carbon monoxide to the simplification of detailed chemistry, especially when multiple combustion regimes are encountered. The second is the bias introduced by artificial thickening, which overestimates the species’ mass production rate. This behavior has been illustrated by manufacturing mean thickened turbulent flame brush from a random displacement of 1-D laminar flame solutions. The last one is the influence of the subgrid-scale flame wrinkling on the filtered chemical flame structure, which may be challenging to model.</p