Fulminant Lung Fibrosis in Non-Resolvable Covid-19 Requiring Transplantation

BACKGROUND: Coronavirus Disease 2019 (COVID-19) can lead to the development of acute respiratory distress syndrome (ARDS). In some patients with non-resolvable (NR) COVID-19, lung injury can progress rapidly to the point that lung transplantation is the only viable option for survival. This fatal progression of lung injury involves a rapid fibroproliferative response and takes on average 15 weeks from initial symptom presentation. Little is known about the mechanisms that lead to this fulminant lung fibrosis (FLF) in NR-COVID-19. METHODS: Using a pre-designed unbiased PCR array for fibrotic markers, we analyzed the fibrotic signature in a subset of NR-COVID-19 lungs. We compared the expression profile against control lungs (donor lungs discarded for transplantation), and explanted tissue from patients with idiopathic pulmonary fibrosis (IPF). Subsequently, RT-qPCR, Western blots and immunohistochemistry were conducted to validate and localize selected pro-fibrotic targets. A total of 23 NR-COVID-19 lungs were used for RT-qPCR validation. FINDINGS: We revealed a unique fibrotic gene signature in NR-COVID-19 that is dominated by a hyper-expression of pro-fibrotic genes, including collagens and periostin. Our results also show a significantly increased expression of Collagen Triple Helix Repeat Containing 1(CTHRC1) which co-localized in areas rich in alpha smooth muscle expression, denoting myofibroblasts. We also show a significant increase in cytokeratin (KRT) 5 and 8 expressing cells adjacent to fibroblastic areas and in areas of apparent epithelial bronchiolization. INTERPRETATION: Our studies may provide insights into potential cellular mechanisms that lead to a fulminant presentation of lung fibrosis in NR-COVID-19. FUNDING: National Institute of Health (NIH) Grants R01HL154720, R01DK122796, R01DK109574, R01HL133900, and Department of Defense (DoD) Grant W81XWH2110032 to H.K.E. NIH Grants: R01HL138510 and R01HL157100, DoD Grant W81XWH-19-1-0007, and American Heart Association Grant: 18IPA34170220 to H.K.-Q. American Heart Association: 19CDA34660279, American Lung Association: CA-622265, Parker B. Francis Fellowship, 1UL1TR003167-01 and The Center for Clinical and Translational Sciences, McGovern Medical School to X.Y

Corporate pension plans and investment choices: bargaining or conforming?

This paper investigates the impacts of defined-benefit (DB) pension plans on the corporate investment choices between diversifying and non-diversifying investments. We find a firm’s DB plan coverage is negatively associated with its propensity of making a major investment. Subject to a major investment decision, however, the firms with higher DB plan coverage is more likely to diversify, i.e. acquire firms abroad or in other industries, rather than invest in fixed assets or make non-diversifying (i.e. domestic horizontal) acquisitions. Moreover, in diversifying acquisitions, they are more likely to invest in countries or industries with strongly unionized workforce. Further analysis on post-investment performance shows that firms with higher DB plan coverage experience a greater improvement in operating profitability after a diversifying acquisition, and the improvement mainly comes from a higher asset turnover rather than cost reduction. On the other hand, DB plan sponsoring firms experience a decline in profitability after a large capital expenditure or a non-diversifying acquisition. We propose both bargaining motive and conforming motive can explain these results

Sources of macroeconomic fluctuations : case of Asian NIEs.

In this research, we examine the impacts of both international and country-specific shocks on the behavior of key macroeconomic variables using two common-trends models.Doctor of Philosophy (NBS

Prédiction de second ordre et résidu par quantification vectorielle pour la compression vidéo

Video compression has become a mandatory step in a wide range of digital video applications. Since the development of the block-based hybrid coding approach in the H.261/MPEG-2 standard, new coding standard was ratified every ten years and each new standard achieved approximately 50% bit rate reduction compared to its predecessor without sacrificing the picture quality. However, due to the ever-increasing bit rate required for the transmission of HD and Beyond-HD formats within a limited bandwidth, there is always a requirement to develop new video compression technologies which provide higher coding efficiency than the current HEVC video coding standard. In this thesis, we proposed three approaches to improve the intra coding efficiency of the HEVC standard by exploiting the correlation of intra prediction residue. A first approach based on the use of previously decoded residue shows that even though gains are theoretically possible, the extra cost of signaling could negate the benefit of residual prediction. A second approach based on Mode Dependent Vector Quantization (MDVQ) prior to the conventional transformed scalar quantization step provides significant coding gains. We show that this approach is realistic because the dictionaries are independent of QP and of a reasonable size. Finally, a third approach is developed to modify dictionaries gradually to adapt to the intra prediction residue. A substantial gain is provided by the adaptivity, especially when the video content is atypical, without increasing the decoding complexity. In the end we get a compromise of complexity and gain for a submission in standardization.La compression vidéo est une étape cruciale pour une grande partie des applications de télécommunication. Depuis l'avènement de la norme H.261/MPEG-2, un nouveau standard de compression vidéo est produit tous les 10 ans environ, avec un gain en compression de 50% par rapport à la précédente. L'objectif de la thèse est d'obtenir des gains en compression par rapport à la dernière norme de codage vidéo HEVC. Dans cette thèse, nous proposons trois approches pour améliorer la compression vidéo en exploitant les corrélations du résidu de prédiction intra. Une première approche basée sur l'utilisation de résidus précédemment décodés montre que, si des gains sont théoriquement possibles, le surcoût de la signalisation les réduit pratiquement à néant. Une deuxième approche basée sur la quantification vectorielle mode-dépendent (MDVQ) du résidu préalablement à l'étape classique transformée-quantification scalaire, permet d'obtenir des gains substantiels. Nous montrons que cette approche est réaliste, car les dictionnaires sont indépendants du QP et de petite taille. Enfin, une troisième approche propose de rendre adaptatif les dictionnaires utilisés en MDVQ. Un gain substantiel est apporté par l'adaptivité, surtout lorsque le contenu vidéo est atypique, tandis que la complexité de décodage reste bien contenue. Au final on obtient un compromis gain-complexité compatible avec une soumission en normalisation