Ischemic heart disease is currently the leading cause of death globally. Coronary artery bypass grafting (CABG) is considered the best treatment for many patients and its success depends on the long-term patency of the conduits. Greater use of arterial grafts has been advocated because of their higher long-term patency compared to saphenous vein grafts (SVGs). Despite this, SVGs account for up to 80% of all grafts used in CABG. Consequently, the long-term patency of the saphenous vein (SV) is one of the most crucial challenges in cardiovascular surgery. The no-touch (NT) SV in CABG has shown a superior patency rate, slower progression of atherosclerosis, and better clinical outcome compared to conventional veins up to 8.5 years postoperatively. The aim of this thesis was to study the long-term angiographic, echocardiographic, and clinical aspects of CABG patients receiving either NT or conventional vein grafts and to investigate the health-related quality of life (HRQoL) in this patient group. Studies I-II report a randomized trial between NT and conventional veins where 74 patients were followed-up at a mean of 16 years postoperatively. Study III is a prospective cohort trial in which 97 patients with NT vein grafts anastomosed to the left anterior descending artery (LAD) were included and followed-up at a mean of 6 years postoperatively. Study IV included 257 patients in whom HRQoL and graft patency were studied during the same follow-up visit. Overall, NT vein grafts showed a higher patency compared to conventional veins at a mean of 16 years, 83% vs. 64% (p=0.03), which was similar to the patency of the left internal thoracic artery, 88%. The NT group had a better left ventricular ejection fraction compared to the conventional group, 57.9% vs. 49.4% (p=0.011). After a mean of 6 years, the patency rate of NT SVs to the LAD was 95.6% and to non-LAD targets, 93.9%. Graft patency was an independent predictor of HRQoL in CABG patients. These patients reported a function and wellbeing similar to that of the Swedish population and clearly higher health status than those in the same disease group in the general population.

L’influence du genre épique se manifeste à travers plusieurs biais dans l’œuvre, apparemment hétérogène, de Claudien. Le poète se présente clairement comme uates, héritier d’Homère, d’Ennius et de Virgile – mais revendique une matière historique et non plus mythologique. La langue témoigne également d’une forte influence du genre épique, que ce soit dans le lexique ou l’emploi de la comparaison homérique. La reprise de motifs, parfois déformés ou renouvelés, confirme cette influence : thème guerrier, songes, présages, prodiges, prophéties, jeux… Si la morale héroïque est plus malmenée, concurrencée par les valeurs chrétiennes, l’univers épique se trouve encore actualisé à travers les figures divines et mythologiques qu’on peut appréhender au moyen d’une lecture typologique. La somme de ces éléments formels est au service d’un propos épique, poétique et politique, célébrant Roma aeterna et Natura. Il apparaît ainsi que l’écriture épique est le dénominateur commun à l’ensemble du corpus, et que les carmina maiora méritent d’être considérés comme une épopée politique. / There is a clear epic vein in Claudian's apparently heterogeneous work, and it appears in a variety of ways. The poet clearly considers himself to be a uates, an heir to Homer, Ennius and Virgil, even though his subject matter is historical, not mythological. The language he uses is also strongly influenced by that of the epic genre, as exemplified by the use of a specifically epic lexicon and the resort to homeric similes. The way he builds on and renews traditional epic motifs (battle scenes, dreams, omens, miracles, prophecies, games ...) reveals the influence of the epic genre on his writings as well. Even though the ethics of heroism are undercut by the rise of Christian values, the divine and mythological figures that can be broached trough a typological reading are proof enough that the world of the epic is still very much present. All these elements contribute to a work that celebrates Roma Aeterna and Natura and is all at once epic – poetic and political. It thus appears that the epic vein is what unifies the corpus, and that the carmina maiora should be read as a political epic.

Several mechanisms have been proposed to explain the process of vein pattern formation in plant tissues. The most widely accepted amongst biologists is the canalization hypothesis, derived from pea root and stem experiments. According to this hypothesis, a signal, thought to be the phytohormone auxin, is transported polarly from cell to cell from the shoot to the root and is canalized progressively into narrow channels of high auxin fluxes that later differentiate to become vascular tissue. In this project, we set out to test whether auxin canalization drives vein pattern formation, using Arabidopsis thaliana mutants with increased auxin transport (max4-1, max3-9, max2-1 and max1-1). We predicted that the mutants would have distinct vein patterns and especially different angles between the primary and secondary veins, compared to the wild type. First rosette leaves of 15 plants per genotype were harvested for analysis each day from 7 to 17 days after sowing, giving a total of eight hundred twenty-five leaf samples to analyze. Venation patterns were extracted and analyzed using custom-made software written with Matlab. Overall, compared with the wild type, mutants with the highest auxin transport (max4-1 and max3-9) had different vein patterns at early developmental stages, confirming a role for auxin transport in vein patterning. However, veins of mutants and wild type connected at similar angles, which is not consistent with the auxin canalization hypothesis, as originally formulated.

PURPOSE: Retinal and choroidal ischemic retinopathies such as retinal-vein occlusion (RVO), diabetic retinopathy (DR), and age-related macular degeneration (AMD) are ocular diseases caused by abnormal changes in the microvasculature. The ischemia can lead to macular edema or neovascularization, which can affect vision. Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) can help to reduce macular edema and improve visual acuity. Lost to follow-up (LTFU) after anti-VEGF injections increases the risk of vision loss in patients with RVO, DR, and AMD. METHODS: Patients scheduled for an IVI of anti-VEGF between September 2009 and September 2019 with either RVO, DR, or AMD were included in the analysis. LTFU was defined as missing an appointment without another evaluation for at least one interval exceeding 180 days. All patients were seen by a single provider at an urban, hospital-based, single-site retina practice in Boston, MA. RESULTS: Among the 698 patients (mean [SD] age, 70.23 [14.2] years; 373 [53.4%] female) identified as receiving an IVI, 121 (17.3%) were LTFU. Age was not found to be statistically different between the LTFU and not LTFU groups (mean difference, -1.67; 95% CI, -4.66¬–1.32; P=.27). Odds of LTFU was lower among patients with AMD (odds ratio [OR], 0.57; 95% CI, 0.36-0.92; P=.02). Odds of LTFU was greater among patients with Medicaid insurance (OR, 2.31; 95% CI, 1.22-4.33; P=.01), compared with patients with Medicare insurance. A trend towards higher risk of LTFU was seen in patients with DR (OR, 1.42; 95% CI, 0.94-2.15; P=.09) and a toward lower risk in patients with two or more eye diseases (OR, 0.53; 95% CI, 0.24-1.15; P=.10). Medicaid insurance was the only significant (P=.02) independent risk factor of LTFU in the multivariate regression. CONCLUSION: We found a high rate of LTFU after anti-VEGF injections among patients with RVO, DR, AMD, and identified risk and protective factors associated with LTFU among this population. Although our results may not be generalizable, data on LTFU in a clinical practice setting are needed to understand the scope of the problem so that interventions may be designed to improve outcomes.

Le foie possède une capacité de régénération importante qui lui permet de reconstituer son volume suite à une agression. L’induction d’une régénération hépatique est réalisée en pratique courante en chirurgie hépatique afin de préparer le foie à une hépatectomie majeure. Elle est également utilisée dans de nombreux modèles animaux afin de favoriser la prise de greffe hépatocytaire au cours de la transplantation d’hépatocytes pour le traitement de maladies métaboliques héréditaires hépatiques. Les principaux objectifs de ce travail ont été d’étudier une méthode peu invasive pour induire une importante régénération hépatique : d’une part pour élargir les possibilités de prise en charge des patients nécessitant une hépatectomie, et d’autre part pour favoriser la prise de greffe des hépatocytes transplantés pour le traitement des maladies métaboliques héréditaires hépatiques.Dans un premier temps, nous avons mis au point chez le rat une technique d’embolisation portale partielle résorbable répétée (EPPRR) visant à entrainer un stimulus additionnel de régénération hépatique. Ces travaux ont validé le concept de la méthode d’EPPRR en montrant une augmentation de la prolifération hépatocytaire et une hypertrophie dans la partie du foie non embolisée.Ce protocole d’EPPRR a ensuite été appliqué dans un modèle préclinique de gros animal. Nous avons étudié chez le porc les conséquences de l’EPPRR et montré que cette technique était reproductible, bien tolérée, et qu’elle permettait une hypertrophie de la partie du foie non embolisée.Parallèlement, nous avons appliqué l’EPPRR avant transplantation d’hépatocytes chez le rat. A partir du foie de rats transgéniques exprimant la GFP (green fluorescent protein), nous avons pu isoler des hépatocytes GFP+. Ces cellules ont été transplantées dans le foie de rats receveurs GFP- en association avec une EPPRR. Nous avons montré que le stimulus de régénération répété provoqué par l’EPPRR permettait une augmentation de la prise de greffe.En conclusion, l’EPPRR est une technique peu invasive capable d’induire une régénérative hépatique efficace. Cette approche pourrait jouer un rôle dans la prise en charge des tumeurs hépatique et l’optimisation de la transplantation d’hépatocytes pour le traitement des maladies métaboliques héréditaires hépatiques. / The liver has an important regenerative capacity allowing reconstitution of the hepatic volume after an aggression. The induction of liver regeneration is used in routine clinical practice before liver surgery in order to prepare the liver for major hepatectomy. It is also used in numerous animal models in order to increase hepatocyte engraftment during hepatocyte transplantation for the treatment of inherited metabolic liver diseases. The main objective of this work was to evaluate a minimally invasive approach to induce substantial liver regeneration: firstly, to expand the therapeutic options for patients requiring an hepatectomy, and secondly to increase the engraftment of transplanted hepatocytes for the treatment of inherited metabolic liver diseases.In a first study, we developed in the rat model a technique of repeated reversible portal vein embolization (RRPVE) to induce an additional stimulus of liver regeneration. This study established the proof of concept of the RRPVE method, showing an increase in hepatocyte proliferation and hypertrophy in the non-embolized liver.This RRPVE protocol was then used in a preclinical model of large animal. We studied in swine the consequences of the RRPVE and showed that the procedure was reproducible, well tolerated, and allowed hypertrophy of the non-embolized liver.In parallel, we applied RRPVE before hepatocyte transplantation in the rat model. From the liver of transgenic rats expressing GFP (green fluorescent protein), we were able to isolate GFP+ hepatocytes. These cells were transplanted in the liver of recipient GFP- rats in association with RRPVE. We demonstrated that the repetition of the regeneration stimulus induced by RRPVE allowed increased hepatocyte engraftment.In conclusion, RRPVE is a minimally invasive technique able to induce efficient liver regeneration. This approach could play a part in the management of hepatic malignancies and the optimization of hepatocyte transplantation in the treatment of inherited metabolic liver diseases.

Im Rahmen von UPNS4D+ wird von mir der Teilbereich der automatisierten untertägigen Detektion von Gangerzlagerstätten und seltenen Erden bearbeitet. Dies erfolgt mittels eines Multisensoransatzes, der aus einer Hyperspektralkamera, einer RGB-Kamera und einem Laserscanner besteht. Die Grundlagen für die Kombination von hyperspektraler Bildverarbeitung und einer RGB-Kamera sind in der Industrie im Bereich von automatisierten Sortieranlagen zu finden. Im Bereich der Fernerkundung ist der Einsatz hyperspektraler Bilder für die Detektion geologischer Merkmale seit einigen Jahrzehnten üblich. Hier kann im Rahmen meiner Forschung gezeigt werden, dass mittels hyperspektraler Bilder Pyrit unter Tage detektiert werden kann. / In my research I work on a system which detects automatically the ore and rare earth element in a mine. This is part of UPNS4D+. For the detection I use a multi sensor system which consists of a hyperspectral camera, a RGB camera and a Laser scanner. Basics of this combination can be found in the industry. The combination of a RGB camera and a hyperspectral camera enables an automatic sorting of for example waste materials. Landsat satellites in the 1970 uses spectral information in order to detect the geology of the surface. I have tested the hyperspectral imaging in the Reiche Zeche and I can now show that Pyrite can be detected.

Background: Guidelines recommend the use of multiple pharmacologic agents and/or mechanical compressive devices for prevention of venous thromboembolism, but preference for any specific agent is no longer given in regard to safety or efficacy. Objective: To compare postoperative bleeding rates in patients receiving enoxaparin, rivaroxaban, or aspirin for thromboprophylaxis after undergoing elective total hip arthroplasty or total knee arthroplasty. Methods: This retrospective cohort analysis evaluated patients who received thromboprophylaxis with either enoxaparin, rivaroxaban, or aspirin. All data were collected from the electronic medical record. The primary outcome was any postoperative bleeding. Results: A total of 1244 patients were included with 366 in the aspirin, 438 in the enoxaparin, and 440 in the rivaroxaban arms. Those who received aspirin or enoxaparin were less likely to experience any bleeding compared to those patients who received rivaroxaban (P <.05). There was also a lower rate of major bleeding in these groups, but the differences were not significant. Conclusions: Aspirin and enoxaparin conferred similar bleeding risks, and both exhibited less bleeding than patients who received rivaroxaban.

Background: The Regulation of Coagulation in Orthopedic Surgery to Prevent Deep Venous Thrombosis and Pulmonary Embolism (RECORD) 1 to 4 trials compared rivaroxaban 10 mg daily with commonly used doses of enoxaparin and demonstrated similar rates of VTE and bleeding. Objective: To evaluate bleeding events between patients who received enoxaparin or rivaroxaban for prevention of venous thromboembolism (VTE) following total hip arthroplasty (THA) or total knee arthroplasty (TKA). Methods: Retrospective cohort that compared patients undergoing THA and TKA who received enoxaparin (enoxaparin) with those who received rivaroxaban (rivaroxaban) and also with those who received enoxaparin in the RECORD 1 to 4 trials (enoxaparin RECORD). The primary outcome was any postoperative bleeding, defined as a composite of major and clinically relevant nonmajor bleeding based on the definitions in the RECORD 1 to 4 trials. Results: There was a lower rate of any postoperative bleeding (2.2% vs 6.8%, P = 0.004) in patients who received enoxaparin compared with rivaroxaban, and bleeding rates between the enoxaparin group and the enoxaparin RECORD groups were similar (2.2% vs 2.5%, P = 0.085). Major bleeding in the enoxaparin group (0.2%) was not significantly different from that in the rivaroxaban group (1.4%, P = 0.12) or the RECORD group (0.2%, P = 0.93). Clinically relevant nonmajor bleeding was also lower in the enoxaparin group compared with the rivaroxaban group (2.0% vs 5.5%, P = 0.012). Conclusions: The use of enoxaparin for VTE prophylaxis following THA and TKA was associated with a lower rate of the primary outcome (any postoperative bleeding) compared with the use of rivaroxaban in a similar cohort of patients.

Background: Drug eluting stents (DES) are preferred over bare metal stents (BMS) for native coronary artery revascularization unless contraindicated. However, the preferred stent choice for saphenous venous graft (SVG) percutaneous coronary interventions (PCI) is unclear due to conflicting results. Methods: PubMed, Clinical trials registry and the Cochrane Center Register of Controlled Trials were searched through June 2018. Seven studies (n = 1639) comparing DES versus BMS in SVG-PCI were included. Endpoints were major adverse cardiac events (MACE), cardiovascular mortality, all-cause mortality, myocardial infarction (MI), target vessel revascularization (TVR), target lesion revascularization (TLR), in-stent thrombosis, binary in-stent restenosis, and late lumen loss (LLL). Results: Overall, during a mean follow up of 32.1 months, there was no significant difference in the risk of MACE, cardiovascular mortality, all-cause mortality, MI, stent thrombosis, TVR and TLR between DES and BMS. However, short-term follow up (mean 11 months) showed lower rate of MACE (OR 0.66 [0.51, 0.85]; p = 0.002), TVR (OR 0.47 [0.23, 0.97]; p = 0.04) and binary in-stent restenosis (OR 0.14 [0.06, 0.37]; p < 0.0001) in DES as compared with BMS. This benefit was lost on long-term follow up with a mean follow up 35.5 months. Conclusion: In this meta-analysis of SVG-PCI, DES use was associated with similar MACE, cardiovascular mortality, all-cause mortality, MI, in-stent thrombosis, TVR and TLR compared with BMS during long-term follow up. There was high incidence of MACE noted in both DES and BMS suggesting a need for exploring novel strategies to treat SVG disease to improve clinical outcomes.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20986号 / 医博第4332号 / 新制||医||1027(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 富樫 かおり, 教授 羽賀 博典, 教授 別所 和久 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM