A multi-scale imaging approach to understand osteoarthritis development

X-ray phase-contrast imaging is an innovative and advanced imaging method. Contrary to conventional radiology, where the image contrast is primarily determined by X-ray attenuation, phase-contrast images contain additional information generated by the phase shifts or refraction of the X-rays passing through matter. The refractive effect on tissue samples is orders of magnitude higher than the absorption effect in the X-ray energy range used in biomedical imaging. This technique makes it possible to produce excellent and enhanced image contrast, particularly when examining soft biological tissues or features with similar X-ray attenuation properties. In combination with high spatial resolution detector technology and computer tomography, X-ray phase-contrast imaging has been proved to be a powerful method to examine tissue morphology and the evolution of pathologies three-dimensionally, with great detail and without the need of contrast agents. This Thesis work has focused on developing an accurate, multi-scale X-ray-based methodology for imaging and characterizing the early stages of osteoarthritis. X-ray phase-contrast images acquired at different spatial resolutions provide unprecedented insights into cartilage and the development of its degeneration, i.e., osteoarthritis. Other types of X-ray phase-contrast imaging techniques and setups using spatial resolutions ranging from micrometer down to nanometer were applied. Lower spatial resolutions allow large sample coverage and comprehensive representations, while the nanoscale analysis provides a precise depiction of anatomical details and pathological signs. X-ray phase-contrast results are correlated to data obtained, on the same specimens, by standard laboratory methods, such as histology and transmission electron microscopy. Furthermore, X-ray phase-contrast images of cartilage were acquired using different X-ray sources and results were compared in terms of image quality. It was shown that with the use of synchrotron radiation, more detailed images and much faster data acquisitions could be achieved. A second focus in this Thesis work has been the investigation of the reaction of healthy and degenerated cartilage under different physical pressures, simulating the different levels of stress to which the tissue is subject during daily movements. A specifically designed setup was used to dynamically study cartilage response to varying pressures with X-ray phase-contrast micro-computed tomography, and a fully volumetric and quantitative methodology to accurately describe the tissue morphological variations. This study revealed changes in the behavior of the cartilage cell structure, which differ between normal and osteoarthritic cartilage tissues. The third focus of this Thesis is the realization of an automated evaluation procedure for the discrimination of healthy and cartilage images with osteoarthritis. In recent years, developments in neural networks have shown that they are excellently suited for image classification tasks. The transfer learning method was applied, in which a pre-trained neural network with cartilage images is further trained and then used for classification. This enables a fast, robust and automated grouping of images with pathological findings. A neural network constructed in this way could be used as a supporting instrument in pathology. X-ray phase-contrast imaging computed tomography can provide a powerful tool for a fully 3D, highly accurate and quantitative depiction and characterization of healthy and early stage-osteoarthritic cartilage, supporting the understanding of the development of osteoarthritis.Röntgen-Phasenkontrast-Bildgebung ist eine innovative und weiterführende Bildgebungsmethode. Im Gegensatz zu herkömlichen Absorptions-Röntgenaufnahmen, wie sie in der Radiologie verwendet werden, wird der Kontrast bei dieser Methode aus dem Effekt der Phasenverschiebung oder auch Brechung der Röngtenstrahlen gebildet. Der Brechungseffekt bei Gewebeproben ist um ein Vielfaches höher als der Absorptionseffekt des elektromagnetischen Spektrums der Röntgenstrahlen. Diese Methode ermöglicht die Darstellung von großen Kontraste im Gewebe. Unter Verwendung eines hochauflösenden Detektors und in Kombination mit der Computer-Tomographie, ist Phasenkontrast-Bildgebung eine sehr gute Methode um Knorpelgewebe und Arthrose im Knorpel zu untersuchen. Diese Arbeit beschreibt primär ein Verfahren zur Darstellung arthrotischen Knorpels im Anfangsstadium. Die mit verschiedenen Auflösungen und 3D-Phasen-Kontrast-Methoden produzierten Aufnahmen ermöglichen einen noch nie dagewesenen Einblick in den Knorpel und die Entwicklung von Arthrose im Anfangsstadium. Hierbei kam die propagationsbasierte Phasenkontrastmethode mit einer Auflösung im mikrometer Bereich und die (Nano)-Holotomographie-Methode mit einer Auflösung im Submicrometer Bereich zum Einsatz. Durch Auflösung im mikrometer Bereich kann ein großes Volumen im Knorpel gescannt werden, während die Nano-Holotomographie Methode eine sehr große Detailauflösung aufweißt. Die Phasenkontrast-Aufnahmen werden mit zwei anderen wissenschaftlichen Methoden verglichen: mikroskopische Abbildungen histologisch aufgearbeiteter Knorpelproben und Aufnahmen eines Transmissionselektroskop zeigen sehr große Übereinstimmungen zur Röntgen-Phasenkontrast-Bildgebung. Desweiteren wurden Phasenkontrast-Aufnahmen von Knorpel aus unterschiedlichen Röntgenquellen verglichen. Hierbei zeigte sich, dass mit Hilfe des Teilchenbeschleunigers (Synchrotron) detailreichere und schnellere Aufnahmen erzielt werden können. Bilder aus Flüssig-Metall-Quellen zeigen sich durchaus von guter Qualität, erfordern jedoch sehr lange Aufnahmezeiten. In dieser Arbeit wird zudem das Verhalten von Knorpelgewebe, welches ein Anfangsstadium von Arthrose aufweist, unter physikalischem Druck untersucht. Hierfür wurden 3D-Computertomographie-Aufnahmen von komprimiertem Knorpelgewebe angefertig und mit Aufnahmen ohne Komprimierung verglichen. Ein quantitativer Vergleich machte Veränderungen des Verhaltens der Knorpelzellstruktur (Chondronen) sichtbar. Es konnte gezeigt werden, dass Chondrone bei arthrotischem Knorpel ein verändertes Kompressionsverhalten haben. Der dritte Fokus dieser Arbeit liegt auf der automatisierten Auswertung von Aufnahmen gesunden und arthrotischen Knorpelgewebes. Die Entwicklungen im Bereich der Neuronale Netze zeigten in den letzten Jahren, dass diese sich hervoragend für Bildklassifizierungsaufgaben eignen. Es wurde die Methode des transferierenden Lernens angewandt, bei der ein vortrainiertes Neuronales Netz mit Knorpelbildern weitertrainiert und anschließend zur Klassifizierung eingesetzt wird. Dadurch ist eine schnelle, robuste und automatisierte Gruppierung von Bildern mit pathologischen Befunden möglich. Ein derart konstruiertes Neuronales Netz könnte als unterstützendes Instrument in der Pathologie angewandt werden. Röntgen-Phasenkontrast-CT kann ein leistungsstarkes Werkzeug für eine umfassende, hochpräzise und quantitative 3D-Darstellung und Charakterisierung von gesundem Knorpel und athrotischem Knorpel im Frühstadium bieten, um das Verständnis der Entwicklung von Osteoarthritis zu erweitern

Resource Extraction Contracts Under Threat of Expropriation: Theory and Evidence

We use fiscal data on 2,468 oil extraction agreements in 38 countries to study tax contracts between resource-rich countries and independent oil companies. We analyze why expropriations occur and what determines the degree of oil price exposure of host countries. With asymmetric information about a country\u27s expropriation cost, even optimal contracts feature expropriations. Near linearity in the oil price of real-world hydrocarbon contracts also helps to explain expropriations. We show theoretically and verify empirically that oil price insurance provided by tax contracts is increasing in a country\u27s cost of expropriation and decreasing in its production expertise. The timing of actual expropriations is consistent with our model

Estimated Impact of the Fed’s Mortgage-Backed Securities Purchase Program

We examine the quantitative impact of the Federal Reserve’s mortgage-backed securities (MBS) purchase program. We focus on how much of the recent decline in mortgage interest rate spreads can be attributed to these purchases. The question is more difficult than frequently perceived because of simultaneous changes in prepayment and default risks. When we control for these risks, we find evidence of statistically insignificant or small effects of the program. For specifications where the existence or announcement of the program appears to have lowered spreads, we find no separate effect of the size of the stock of MBS purchased by the Fed.

Inside the Mind of a Stock Market Crash

We analyze how investor expectations about economic growth and stock returns changed during the February-March 2020 stock market crash induced by the COVID-19 pandemic, as well as during the subsequent partial stock market recovery. We surveyed retail investors who are clients of Vanguard at three points in time: (i) on February 11-12, around the all-time stock market high, (ii) on March 11-12, after the stock market had collapsed by over 20\%, and (iii) on April 16-17, after the market had rallied 25\% from its lowest point. Following the crash, the average investor turned more pessimistic about the short-run performance of both the stock market and the real economy. Investors also perceived higher probabilities of both further extreme stock market declines and large declines in short-run real economic activity. In contrast, investor expectations about long-run (10-year) economic and stock market outcomes remained largely unchanged, and, if anything, improved. Disagreement among investors about economic and stock market outcomes also increased substantially following the stock market crash, with the disagreement persisting through the partial market recovery. Those respondents who were the most optimistic in February saw the largest decline in expectations, and sold the most equity. Those respondents who were the most pessimistic in February largely left their portfolios unchanged during and after the crash.Comment: 13 page

Social Capital and Economic Mobility

In recent years, social scientists have identified many factors that facilitateupward income mobility, from early childhood health interventions toelementary school improvements to sectoral job training programs. Inaddition to these approaches, many have argued that social capital – thestrength of an individual's social network and community – may be animportant factor in upward mobility. But social capital has proven to bechallenging to measure, making it difficult to study whether it matters,and, if it does, how it can be increased.To address this challenge, we use privacy-protected data on 21 billionfriendships from Facebook to measure three types of social capital incommunities across America

Estimated Impact of the Federal Reserve\u27s Mortgage-Backed Securities Purchase Program

Examines the quantitative impact of mortgage-backed securities (MBS) purchase program on mortgage interest rate spreads

Convolutional neuronal networks combined with X-ray phase-contrast imaging for a fast and observer-independent discrimination of cartilage and liver diseases stages

We applied transfer learning using Convolutional Neuronal Networks to high resolution X-ray phase contrast computed tomography datasets and tested the potential of the systems to accurately classify Computed Tomography images of different stages of two diseases, i.e. osteoarthritis and liver fibrosis. The purpose is to identify a time-effective and observer-independent methodology to identify pathological conditions. Propagation-based X-ray phase contrast imaging WAS used with polychromatic X-rays to obtain a 3D visualization of 4 human cartilage plugs and 6 rat liver samples with a voxel size of 0.7x0.7x0.7 mu m(3) and 2.2x2.2x2.2 mu m(3), respectively. Images with a size of 224x224 pixels are used to train three pre-trained convolutional neuronal networks for data classification, which are the VGG16, the Inception V3, and the Xception networks. We evaluated the performance of the three systems in terms of classification accuracy and studied the effect of the variation of the number of inputs, training images and of iterations. The VGG16 network provides the highest classification accuracy when the training and the validation-test of the network are performed using data from the same samples for both the cartilage (99.8%) and the liver (95.5%) datasets. The Inception V3 and Xception networks achieve an accuracy of 84.7% (43.1%) and of 72.6% (53.7%), respectively, for the cartilage (liver) images. By using data from different samples for the training and validation-test processes, the Xception network provided the highest test accuracy for the cartilage dataset (75.7%), while for the liver dataset the VGG16 network gave the best results (75.4%). By using convolutional neuronal networks we show that it is possible to classify large datasets of biomedical images in less than 25 min on a 8 CPU processor machine providing a precise, robust, fast and observer-independent method for the discrimination/classification of different stages of osteoarthritis and liver diseases