Metaanalyse zur genetischen Prädisposition bei Parodontitis unter Verwendung von Polymorphismen

Die Volkskrankheit Parodontitis beschreibt die entzündliche Degeneration des Zahnhalteappa-rates, die auf lange Sicht zur Lockerung einzelner Zähne und sogar zum Verlust der gleichen führen kann. Nach neuesten Zahlen ist in Deutschland jeder zweite jüngere Erwachsene und sogar zwei von drei jüngeren Senioren von dieser Krankheit betroffen.1 Da es sich um eine entzündliche Erkrankung handelt, spielen Entzündungsmediatoren, sog. Zy-tokine, eine entscheidende Rolle bei der Pathogenese der Parodontitis.2 Einige Polymorphismen auf den Genabschnitten einzelner Zytokine wurden in zahlreichen Studien bezüglich ihres Ein-flusses auf das Erkrankungsrisiko für Parodontitis untersucht. Zu den Interleukinen 1 alpha (1α), 1 beta (1β), 4, 6, 8, 10 und 17 sowie zu dem Tumornekrosefaktor alpha (TNF-α) konnten viele Studien mit zum Teil widersprüchlichen Resultaten identifiziert werden. Im Rahmen dieser Dissertation wurde eine Metaanalyse aller bis zum 30.12.2016 auf PubMed publizierten Arbeiten zum IL-1α +4845G/T, IL-1α -889C/T, IL-1β +3954C/T, IL-1β -511C/T, IL-4 -590C/T, IL-6 -174G/C, IL-6 -572G/C, IL-8 +781C/T, IL-8 +396T/G, IL-8 -251A/T, IL-10 -592C/A, IL-10 -819C/T, IL-10 -1082A/G, IL-17 -197G/A, TNF-α -238G/A und TNF-α -308G/A Polymorphismus durchgeführt. Zu allen 16 Polymorphismen wurde jeweils zum do-minanten und rezessiven Modell die Odds Ratio (OR) und das 95%-Konfidenzintervall (95%-CI) berechnet. Die Ergebnisse der Analyse des IL-1β +3954C/T Polymorphismus deuten darauf hin, dass Per-sonen mit dem Genotyp TT sowie Träger des T-Allels ein erhöhtes Risiko besitzen, an Paro-dontitis zu erkranken. Weiterhin lassen die Resultate der Analyse des IL-10 -592C/A Polymor-phismus vermuten, dass wiederum Personen mit dem Genotyp AA sowie Träger des A-Allels häufiger an Parodontitis leiden. Zu den Polymorphismen IL-1α -889C/T, IL-6 -174G/C, IL-8 +781C/T, IL-8 +396T/G und TNF-α -238G/A wurden zum Teil signifikante Werte berechnet, jedoch konnten diese nur in Sensitivitätsanalysen generiert werden oder der Literaturbestand war nicht ausreichend, um ein aussagekräftiges Ergebnis zu erzielen. Bei den restlichen neun Polymorphismen konnte kein statistisch signifikanter Einfluss auf das Parodontitisrisiko nach-gewiesen werden.The periodontal disease describes the inflammatory degeneration of the tooth retaining appa-ratus, which can lead to a long-term relaxation of individual teeth and even to the loss of the same. According to the latest figures, in Germany every second younger adult and even two out of three younger seniors are affected by this disease.1 Since it is an inflammatory disease, inflammatory mediators, so-called cytokines, play a deci-sive role in the pathogenesis of periodontal disease.2 Some polymorphisms on the gene sections of individual cytokines have been investigated in numerous studies regarding their influence on the disease risk for periodontal disease. The interleukins 1 alpha (1α), 1 beta (1β), 4, 6, 8, 10 and 17 as well as the tumor necrosis factor alpha (TNF-α) could be identified in many studies with partly contradictory results. In this thesis, there is shown a meta-analysis of all publications on PubMed until 30.12.2016 about the IL-1α +4845G/T, IL-1α -889C/T, IL-1β +3954C/T, IL-1β -511C/T, IL-4 -590C/T, IL-6 -174G/C, IL-6 -572G/C, IL-8 +781C/T, IL-8 +396T/G, IL-8 -251A/T, IL-10 -592C/A, IL-10 -819C/T, IL-10 -1082A/G, IL-17 -197G/A, TNF-α -238G/A and TNF-α -308G/A polymor-phisms. For all 16 polymorphisms, the Odds Ratio (OR) and the 95% confidence interval (95%-CI) were calculated for the dominant and recessive model. The results of the analysis of the IL-1β + 3954C/T polymorphism indicate that persons with the genotype TT as well as carriers of the T allele are at increased risk of developing periodontal disease. Furthermore, the results of the analysis of the IL-10 -592C/A polymorphism suggest that persons with the genotype AA as well as carriers of the A allele suffer more frequently from periodontitis. Some significant values were calculated for the polymorphisms IL-1α -889C/T, IL-6 -174G/C, IL-8 +781C/T, IL-8 +396T/G and TNF-α -238G/A are generated only in sensitivity analyzes or the literature stock was not sufficient to achieve a meaningful result. In the remaining nine polymorphisms, no statistically significant influence on the risk of peri-odontal disease could be demonstrated

Phase-locked multi-terahertz electric fields exceed 13 MV/cm at 190 kHz repetition rate

We demonstrate a compact source of energetic and phase-locked multi-terahertz pulses at a repetition rate of 190 kHz. Difference frequency mixing of the fundamental output of an Yb:KGW amplifier with the idler of an optical parametric amplifier in GaSe and LiGaS2 crystals yields a passively phase-locked train of waveforms tunable between 12 and 42 THz. The shortest multi-terahertz pulses contain 1.8 oscillation cycles within the intensity full width at half-maximum. Pulse energies of up to 0.16 mu J and peak electric fields of 13 MV/cm are achieved. Electro-optic sampling reveals a phase stability better than 0.1 pi over multiple hours, combined with free carrier-envelope phase tunability. The scalable scheme opens the door to strong-field terahertz optics at unprecedented repetition rates. (C) 2017 Optical Society of Americ

Preoperative fibrinogen/CRP score predicts survival in upper urothelial tract carcinoma patients undergoing radical curative surgery

Purpose Upper tract urothelial carcinoma (UTUC) represents an often aggressive malignancy associated with poor prognosis. Therefore, finding reliable prognostic biomarkers in patients undergoing curative surgery for improved risk stratification is crucial. We evaluated the prognostic value of the Fibrinogen/C-reactive protein (FC)-score in a cohort of surgically treated UTUC patients. Methods 170 patients with radiologically and histologically verified UTUC who underwent radical curative surgery between 1990 and 2020, were included. The FC-score was calculated for each patient, with patients receiving 1 point each if Fibrinogen and/or CRP levels were elevated above the 25th or 75th percentile, respectively. Patients were divided into three subgroups according to their FC-score of 0, 1 or 2 point(s). Kaplan–Meier analysis, uni- and multivariable Cox proportional hazard models were implemented. We determined cancer-specific survival (CSS) as primary endpoint, whereas overall survival (OS) and recurrence-free survival (RFS) were considered secondary endpoints. Results High FC-score (2 points) was significantly associated with adverse histological features such as vascular invasion (OR = 4.08, 95%CI 1.18–14.15, p = .0027) and tumour necrosis (OR = 6.67, 95%CI 1.35–32.96, p = 0.020). Both, uni- and multivariable Cox proportional hazard models showed the FC-score as a significant predictor for CSS (univariable analysis: FC-score = 1: HR = 1.90, 95%CI 0.92–3.93, p = 0.085 | FC-score = 2: HR = 2.86, 95%CI 1.22–6.72, p = 0.016). Furthermore, in univariable analysis, patients with higher FC-score had significantly shorter OS (FC-score = 1: HR = 1.32, 95%CI 0.70–2.49, p = 0.387 | FC-score = 2: HR = 2.19, 95%CI 1.02–4.67, p = 0.043). However, this did not prevail in multivariable analysis. Conclusion The FC-score represents a novel potential biomarker in patients with UTUC undergoing radical curative surgery

First analysis and experiments in aerial manipulation using fully actuated redundant robot arm

Abstract-In this paper we describe a system for aerial manipulation composed of a helicopter platform and a fully actuated seven Degree of Freedom (DoF) redundant industrial robotic arm. We present the first analysis of such kind of systems and show that the dynamic coupling between helicopter and arm can generate diverging oscillations with very slow frequency which we called phase circles. Based on the presented analysis, we propose a control approach for the whole system. The partial decoupling between helicopter and arm -which eliminates the phase circles -is achieved by means of special movement of robotic arm utilizing its redundant DoF. For the underlying arm control a specially designed impedance controller was proposed. In different flight experiments we showcase that the proposed kind of system type might be used in the future for practically relevant tasks. In an integrated experiment we demonstrate a basic manipulation task -impedance based grasping of an object from the environment underlaying a visual object tracking control loop

EDGAR: An Autonomous Driving Research Platform -- From Feature Development to Real-World Application

While current research and development of autonomous driving primarily focuses on developing new features and algorithms, the transfer from isolated software components into an entire software stack has been covered sparsely. Besides that, due to the complexity of autonomous software stacks and public road traffic, the optimal validation of entire stacks is an open research problem. Our paper targets these two aspects. We present our autonomous research vehicle EDGAR and its digital twin, a detailed virtual duplication of the vehicle. While the vehicle's setup is closely related to the state of the art, its virtual duplication is a valuable contribution as it is crucial for a consistent validation process from simulation to real-world tests. In addition, different development teams can work with the same model, making integration and testing of the software stacks much easier, significantly accelerating the development process. The real and virtual vehicles are embedded in a comprehensive development environment, which is also introduced. All parameters of the digital twin are provided open-source at https://github.com/TUMFTM/edgar_digital_twin

Galactic Core-Collapse Supernovae at IceCube: “Fire Drill” Data Challenges and follow-up

The next Galactic core-collapse supernova (CCSN) presents a once-in-a-lifetime opportunity to make astrophysical measurements using neutrinos, gravitational waves, and electromagnetic radiation. CCSNe local to the Milky Way are extremely rare, so it is paramount that detectors are prepared to observe the signal when it arrives. The IceCube Neutrino Observatory, a gigaton water Cherenkov detector below the South Pole, is sensitive to the burst of neutrinos released by a Galactic CCSN at a level >10σ. This burst of neutrinos precedes optical emission by hours to days, enabling neutrinos to serve as an early warning for follow-up observation. IceCube\u27s detection capabilities make it a cornerstone of the global network of neutrino detectors monitoring for Galactic CCSNe, the SuperNova Early Warning System (SNEWS 2.0). In this contribution, we describe IceCube\u27s sensitivity to Galactic CCSNe and strategies for operational readiness, including "fire drill" data challenges. We also discuss coordination with SNEWS 2.0

All-Energy Search for Solar Atmospheric Neutrinos with IceCube

The interaction of cosmic rays with the solar atmosphere generates a secondary flux of mesons that decay into photons and neutrinos – the so-called solar atmospheric flux. Although the gamma-ray component of this flux has been observed in Fermi-LAT and HAWC Observatory data, the neutrino component remains undetected. The energy distribution of those neutrinos follows a soft spectrum that extends from the GeV to the multi-TeV range, making large Cherenkov neutrino telescopes a suitable for probing this flux. In this contribution, we will discuss current progress of a search for the solar neutrino flux by the IceCube Neutrino Observatory using all available data since 2011. Compared to the previous analysis which considered only high-energy muon neutrino tracks, we will additionally consider events produced by all flavors of neutrinos down to GeV-scale energies. These new events should improve our analysis sensitivity since the flux falls quickly with energy. Determining the magnitude of the neutrino flux is essential, since it is an irreducible background to indirect solar dark matter searches

TXS 0506+056 with Updated IceCube Data

Past results from the IceCube Collaboration have suggested that the blazar TXS 0506+056 is a potential source of astrophysical neutrinos. However, in the years since there have been numerous updates to event processing and reconstruction, as well as improvements to the statistical methods used to search for astrophysical neutrino sources. These improvements in combination with additional years of data have resulted in the identification of NGC 1068 as a second neutrino source candidate. This talk will re-examine time-dependent neutrino emission from TXS 0506+056 using the most recent northern-sky data sample that was used in the analysis of NGC 1068. The results of using this updated data sample to obtain a significance and flux fit for the 2014 TXS 0506+056 "untriggered" neutrino flare are reported