The aim of the dissertation was to detect rubber inflatables carrying migrants and refugees using remote sensing data. The research follows the vision of providing civilian rescue teams on the ground with situational images to support their search for boats in distress. We utilised synthetic aperture radar (SAR) to provide a search infrastructure for maritime rescue operations that is independent of the time of day and weather conditions. We carried out two measurement campaigns lasting around six months with a 12m-long inflatable boat to collect SAR images from various satellites and analysed the results. In this way, we gained a comprehensive understanding of the radar patterns of inflatable boats in SAR data and were able to show that automated detection is possible. As part of the work, existing ship detectors were systematically analysed and new detectors specially adapted to the test object were developed.
Ziel der Dissertation war es, mit MigrantInnen und Geflüchteten besetzte Schlauchboote mittels Fernerkundungsdaten zu detektieren. Die Forschung folgt der Vision, zivilen Rettungskräfte vor Ort Lagebilder zu liefern um deren Suche nach Booten in Seenot zu unterstützen. Um eine tageszeit- und witterungsunabhängige Suchinfrastruktur für die maritime Seenotrettung zu ermöglichen, nutzten wir „Synthetic Aperture Radar“ (SAR). Wir führten zwei ca. sechsmonatige Messkampagnen mit einem 12m langen Fluchtschlauchboot durch, um SAR-Bilder verschiedener Satelliten zu sammeln und werteten die Ergebnisse aus. Damit schufen wir ein umfassendes Verständnis der Radarmustern von Schlauchbooten in SAR-Daten und konnten zeigen, dass eine Detektion möglich ist. Im Rahmen der Arbeit wurden systematisch existierende Schiffsdetektoren untersucht und daraus neue, speziell auf das Testobjekt abgestimmte Detektoren entwickelt.
In dieser Arbeit wurde der prognostische Einfluss von Immunzellsubpopulationen der B- und T-Lymphozyten in der direkten Tumorumgebung sowie von Treibermutationen in Abhängigkeit von Checkpointproteinen und dem klinischen Tumorstadium untersucht. Hierfür erfolgte die immunhistochemische Untersuchung von 156 Adenokarzinomen der Lunge sowie die NGS Sequenzierung von 17 therapierelevanten Genen der Tumor-DNA. Bei 100 dieser Fälle war der Vitalstatus bekannt. In der Korrelationsanalyse konnte u.a. ein signifikant geringeres Auftreten von CD8+ TILs, CD20+ B-TILs im Stadium IV nachgewiesen werden. Einen signifikanten Einfluss auf die Immunzellen der direkten Tumorumgebung wies ebenfalls ein Expressionsstatus von >50% PD-L1+ Tumorzellen sowie das Vorhandensein bestimmter Treibermutationen auf. Als prognostisch günstig für das Überleben der Patienten wurden hierbei hohe Anzahlen von CD3+ und CD20+ TILs sowie CD19+ B-Follikel identifiziert.
In this study we investigated the prognostic value of the immune cell subpopulations of B- and T-cells in the tumormicroenvironment as well as drivermutations and checkpointproteins in different clinical tumor stages. We performed immunhistochemical investigations of 156 adenocarcinomas of the Lung and NGS-sequencing of 17 therapeutic significant gene-sequences in the tumor-DNA. Survival outcome was known in 100 of these cases. Statistical analysis displayed a significant decrease in cell numbers of CD8+, CD20+ TILs as well as CD19+ B-follicles in stage IV disease. Other significant influences on the immune cells in the direct tumorenvironment were a PD-L1 expression status of >50% tumor cells and a decrease in numbers of CD19+ B-follicles and CD20+ B-TILS in the direct tumor microenvironment in case of positive mutationstatus for drivermutations. Prognostic significance could be shown for high numbers of CD3+ and CD20+ Tils as well as CD19+ B-follicles.
von Navid Farassat ; Daniel Böhringer ; Sebastian Küchlin ; Fanni E. Molnár ; Anne Schwietering ; Dorina Seger ; Martin J. Hug ; Anja-Birte Knöbel ; Sabine Schneider-Fuchs ; Gabriele Ihorst ; Bettina Kathrin Wabbels ; Christina Beisse ; Focke Ziemssen ; Frank Schüttauf ; Andrea Martina Hedergott ; Theresia Ring-Mangold ; Claudia Schuart ; Armin Wolf ; Stefanie Schmickler ; Julia Biermann ; Philipp Eberwein ; Karsten Hufendiek ; Anja Eckstein ; Gabriele Gusek-Schneider ; Michael Peter Schittkowski ; Thomas Lischka ; Wolf A. Lagrèze
Clinical trials; Medical ophthalmology; OPHTHALMOLOGY; Paediatric ophthalmology
Introduction Myopia is a major cause of degenerative eye disease and increases the risk of secondary visual impairment. Mitigating its progression therefore has great potential of clinically relevant benefit as shown by using highly diluted atropine eye drops in children of Asian origin. However, limited evidence is available regarding the efficacy and safety of low-dose atropine therapy in non-Asian populations. Hence, the Low-dose AtropIne for Myopia Control in Children (AIM) study will test the efficacy and safety of 0.02% atropine vs placebo in a German population. - Methods and analysis AIM is a national, multicentre, prospective, randomised, placebo-controlled, double-blind trial with two parallel arms. The primary objective is to assess the efficacy of atropine 0.02% eyedrops for myopia control in children of Caucasian origin. The primary outcome is the change in cycloplegic refraction after 1 year of treatment (D/year). Secondary and tertiary outcome measures comprise the change in axial length (mm/year) in children treated with 0.02% atropine compared with placebo, the myopic progression of participants treated with 0.01% compared with 0.02% atropine (D/year and mm/year), and the safety profile of both 0.02% and 0.01% atropine. Furthermore, the myopic progression 1 year after cessation of therapy with 0.02% atropine will be evaluated. Inclusion criteria are an age of 8-12 years and myopia of −1 D to −6 D with an estimated annual myopia progression of ≥0.5 D. After randomisation, patients will receive either atropine 0.02% (arm A) or placebo eye drops (arm B) in the first year of treatment. In the second year, they will continue to receive atropine 0.02% (arm A) or switch to atropine 0.01% (arm B). In the third year, they will switch to placebo (arm A) or continue with atropine 0.01% (arm B). To achieve a statistical power of 80%, the calculated sample size is 300. The trial has started in October 2021 with a planned recruitment period of 18 months. - Ethics and dissemination AIM has been approved by the Central Ethics Committee of the University Medical Center Freiburg (21-1106), local ethics committees of each participating centre and the German Federal Institute for Drugs and Medical Devices (61-3910-4044659). It complies with the Declaration of Helsinki, local laws and ICH-GCP. Results and underlying data from this trial will be disseminated through peer-reviewed publications and conference presentations. - Trial registration number NCT03865160.
BMJ open London : BMJ Publishing Group, 2011 13(2023), 4, Artikel-ID e068822, Seite 1-11 Online-Ressource
Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium’s possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response — defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10−12, R2 = 1.9%) and continuous (P = 6.4 × 10−9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10−4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
