A New Full Orifice Disc Valve for Mitral Replacement

Because of dissatisfaction with certain features of the currently available ball and disc valve prostheses when implanted in patients with mitral stenosis and a small volume left ventricle, a full orifice discoid valve has been designed which avoids many of these shortcomings. The valve has been tested mechanically in a pulse duplicator and compared lo existing prostheses. High speed cine studies were used to evaluate turbulence. Implantation was carried out in animals. Evaluation by these various methods indicates that the valve is satisfactory for human implantation and may have significant advantages over other artificial valves when used in patients with mitral stenosis and small left ventricles

Study of Bruner’s Educational Theory (5) : Focusing on After World War Ⅱ

This study examined the formation process of the education theory of Bruner from his autobiography. In this paper, I focus on After World War Ⅱ . After the war, he began again the study of psychology. The main point of view, was the world of psychology called World Three. It is, in psychology with a focus on culture, Bruner was studied this. This paper examined the relationship between Bruner and World Three

Surgical intervention for anomalous origin of the left coronary artery from the pulmonary artery: The Tokyo experience

AbstractBackground: Few studies after surgical repair of the anomalous origin of the left coronary artery have reported the importance of the mitral annuloplasty or the long-term results. Methods: Between January 1982 and March 2000, 29 patients with anomalous origin underwent surgical intervention at our institution (direct aortic reimplantation in 19 and Takeuchi procedure in 10). Age at the time of operation ranged from 2 months to 24 years (median, 29.3 months), and 9 patients were infants. Twenty-four patients had varying degrees of mitral incompetence. Simultaneous mitral annuloplasty at the anterolateral commissure was performed in all 24 patients with incompetence. Results: There were 2 hospital deaths among the infants, and no late deaths. Mean follow-up was 100 ± 57 months, and the actuarial survival was 93.1% at 10 years (70% confidence limits, 87-99). Cardiothoracic ratio at discharge was not decreasing significantly (P =.35); however, this value 5 years after the operation showed the significant decrease (P =.003) versus preoperative value. Preoperative mitral incompetence decreased in all but one of the operative survivors with mitral annuloplasty at the last follow-up. The left ventricular fractional shortening z-score was not normalized at discharge but was normalized in the late period. Conclusion: These data demonstrate that impaired left ventricular function normalized in the long term (even if it was below normal immediately after operation) after 2-coronary repair. We recommend that the simultaneous mitral annuloplasty should be performed at the time of operation for patients who have mitral incompetence with anomalous origin of the left coronary artery. (J Thorac Cardiovasc Surg 2001;121:792-7

Management of Hepatocellular Carcinoma in Japan : JSH Consensus Statements and Recommendations 2021 Update

The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other’s work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC

Genetic Polymorphisms of the Human PNPLA3 Gene Are Strongly Associated with Severity of Non-Alcoholic Fatty Liver Disease in Japanese

Nonalcoholic fatty liver disease (NAFLD) includes a broad range of liver pathologies from simple steatosis to cirrhosis and fibrosis, in which a subtype accompanying hepatocyte degeneration and fibrosis is classified as nonalcoholic steatohepatitis (NASH). NASH accounts for approximately 10-30% of NAFLD and causes a higher frequency of liver-related death, and its progression of NASH has been considered to be complex involving multiple genetic factors interacting with the environment and lifestyle.To identify genetic factors related to NAFLD in the Japanese, we performed a genome-wide association study recruiting 529 histologically diagnosed NAFLD patients and 932 population controls. A significant association was observed for a cluster of SNPs in PNPLA3 on chromosome 22q13 with the strongest p-value of 1.4 × 10(-10) (OR = 1.66, 95%CI: 1.43-1.94) for rs738409. Rs738409 also showed the strongest association (p = 3.6 × 10(-6)) with the histological classifications proposed by Matteoni and colleagues based on the degree of inflammation, ballooning degeneration, fibrosis and Mallory-Denk body. In addition, there were marked differences in rs738409 genotype distributions between type4 subgroup corresponding to NASH and the other three subgroups (p = 4.8 × 10(-6), OR = 1.96, 95%CI: 1.47-2.62). Moreover, a subgroup analysis of NAFLD patients against controls showed a significant association of rs738409 with type4 (p = 1.7 × 10(-16), OR = 2.18, 95%CI: 1.81-2.63) whereas no association was obtained for type1 to type3 (p = 0.41). Rs738409 also showed strong associations with three clinical traits related to the prognosis of NAFLD, namely, levels of hyaluronic acid (p = 4.6 × 10(-4)), HbA1c (p = 0.0011) and iron deposition in the liver (p = 5.6 × 10(-4)).With these results we clearly demonstrated that Matteoni type4 NAFLD is both a genetically and clinically different subset from the other spectrums of the disease and that the PNPLA3 gene is strongly associated with the progression of NASH in Japanese population

Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial

Background Hepatic arterial infusion chemotherapy plus sorafenib in phase 2 trials has shown favourable tumour control and a manageable safety profile in patients with advanced, unresectable hepatocellular carcinoma. However, no randomised phase 3 trial has tested the combination of sorafenib with continuous arterial infusion chemotherapy. We aimed to compare continuous hepatic arterial infusion chemotherapy plus sorafenib with sorafenib alone in patients with advanced, unresectable hepatocellular carcinoma. Methods We did an open-label, randomised, phase 3 trial (SILIUS) at 31 sites in Japan. Eligible patients were aged 20 years or older, with advanced hepatocellular carcinoma not suitable for resection, local ablation, or transarterial chemoembolisation; Eastern Cooperative Oncology Group (ECOG) performance status 0–1; Child-Pugh score 7 or lower; and adequate bone marrow, liver, and renal function. Patients were randomly assigned (1:1) via an interactive web response system with a computer-generated sequence to receive 400 mg sorafenib orally twice daily or 400 mg sorafenib orally twice daily plus hepatic arterial infusion chemotherapy (cisplatin 20 mg/m 2 on days 1 and 8 and fluorouracil 330 mg/m 2 continuously on days 1–5 and 8–12 of every 28-day cycle via an implanted catheter system). The primary endpoint was overall survival. The primary efficacy analysis comprised all randomised patients (the intention-to-treat population), and the safety analysis comprised all randomised patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01214343. Findings Between Nov 4, 2010, and June 10, 2014, 206 patients were randomly assigned (103 to the sorafenib group, 103 to the sorafenib plus hepatic arterial infusion chemotherapy group). One patient in the sorafenib plus hepatic arterial infusion chemotherapy group withdrew after randomisation. Median overall survival was similar in the sorafenib plus hepatic arterial infusion chemotherapy (n=102) and sorafenib monotherapy (n=103) groups (11·8 months [95% CI 9·1–14·5] vs 11·5 months [8·2–14·8]; hazard ratio 1·009 [95% CI 0·743–1·371]; p=0·955). Grade 3–4 adverse events that were more frequent in the sorafenib plus hepatic arterial infusion chemotherapy group than in the sorafenib monotherapy group included anaemia (15 [17%] of 88 vs six [6%] of 102), neutropenia (15 [17%] vs one [1%]), thrombocytopenia (30 [34%] vs 12 [12%]), and anorexia (12 [14%] vs six [6%]). Interpretation Addition of hepatic arterial infusion chemotherapy to sorafenib did not significantly improve overall survival in patients with advanced hepatocellular carcinoma. Funding Japanese Ministry of Health, Labour and Welfare

Management of Hepatocellular Carcinoma in Japan: JSH Consensus Statements and Recommendations 2021 Update

The Clinical Practice Manual for Hepatocellular Carcinoma was published based on evidence confirmed by the Evidence-based Clinical Practice Guidelines for Hepatocellular Carcinoma along with consensus opinion among a Japan Society of Hepatology (JSH) expert panel on hepatocellular carcinoma (HCC). Since the JSH Clinical Practice Guidelines are based on original articles with extremely high levels of evidence, expert opinions on HCC management in clinical practice or consensus on newly developed treatments are not included. However, the practice manual incorporates the literature based on clinical data, expert opinion, and real-world clinical practice currently conducted in Japan to facilitate its use by clinicians. Alongside each revision of the JSH Guidelines, we issued an update to the manual, with the first edition of the manual published in 2007, the second edition in 2010, the third edition in 2015, and the fourth edition in 2020, which includes the 2017 edition of the JSH Guideline. This article is an excerpt from the fourth edition of the HCC Clinical Practice Manual focusing on pathology, diagnosis, and treatment of HCC. It is designed as a practical manual different from the latest version of the JSH Clinical Practice Guidelines. This practice manual was written by an expert panel from the JSH, with emphasis on the consensus statements and recommendations for the management of HCC proposed by the JSH expert panel. In this article, we included newly developed clinical practices that are relatively common among Japanese experts in this field, although all of their statements are not associated with a high level of evidence, but these practices are likely to be incorporated into guidelines in the future. To write this article, coauthors from different institutions drafted the content and then critically reviewed each other’s work. The revised content was then critically reviewed by the Board of Directors and the Planning and Public Relations Committee of JSH before publication to confirm the consensus statements and recommendations. The consensus statements and recommendations presented in this report represent measures actually being conducted at the highest-level HCC treatment centers in Japan. We hope this article provides insight into the actual situation of HCC practice in Japan, thereby affecting the global practice pattern in the management of HCC

A Study of Trend in 1960's about Development of Discipline-Centered-Curriculum in U.S.A : Focus on the music

This paper had two aims to clarify the problem concerning development of the curriculum of Music courses. The first was to illustrate the background of the reform of the curriculums focuses on Music courses in United States and Japan; especially investigate the records of the important symposiums and conferences which influenced on the reforeming of Music courses. The second was to examine the characteristics of developmental aspects of Music course. In the 1960's the structures and constructions of education whose productivity rate were not highly have begun to improve caused by the Sputnik 1957. In the field of natural sciences, the framework of discipline-centered-curriculum was concept which aimed to modernize the course structures of Mathematics, Sciences and Physics. The concept of discipline-centered-currichlum have introduced to Japan as "the reformation of curriculum", which influenced on evolving the construction of the theories of educational methodology, curriculum research and development. However, discipline centered curriculum have researched not only in natural scientific courses but also art courses in the United States

L’évaluation financière des choix stratégiques entrepreneuriaux

The objective of this dissertation is to develop the quantitative models that adopt the real options analysis for financially evaluating the entrepreneurial strategic choices. However, it does not only focus on the technical aspects (or its mathematical methodologies). The models proposed in the dissertation aim to provide the practically useful information in order for both entrepreneurs and investors to make decisions in the contractual negotiation of financing and investing in the start-ups and ventures.This dissertation consists of two parts. The first part gives the definitions of the essential concepts that shall be incorporated into the research question. Adopting the perspectives that are provided in entrepreneurial finance leads us to focus on the fair negotiations among participants in the process of decision-making, while the traditional corporate finance emphasises the principal-agent problem. Actually, the common methods, such as Discounted Cash-Flows and Internal Rate of Return, are not always suitable for implementing financial valuations in the context of entrepreneurial finance. Therefore, the research question of this dissertation can be set as follows: How should strategic choices in contract negotiation be financially evaluated?In order to deal with this problem, three particular issues are introduced in the second part. The real options analysis is utilised in all of the three issues, which is quite suitable for analysing them.The first article deals with the issue of licensing contract with bio-pharma venture. In summary, when closing a licensing contract negotiation, those in charge of the negotiation must consider many factors, such as the phases of R&D, the investment costs and the market volatility. In addition to those, the interaction of the participants of the contractual negotiation should be taken into account. For modelling this relationship, the assumption of dynamic interaction between licensor and licensee is introduced.The second article focuses on the dilution problem in the second financing round under the existence of convertible note holders. According to the simulation results, “discount” and “valuation cap” have a great impact on the equity decision-making cost. The results also show that the costs increase when the degree of discount becomes greater and the valuation cap becomes smaller. This may jeopardize the success of negotiation. Entrepreneurs should take these factors into consideration in the second financing round.The third article analyses the exit choice (acquisition or IPO), especially the “IPO valuation premium puzzle” proposed by Bayar et Chemmanur (2011). While entrepreneurs and venture capitalists prefer an IPO, acquisition can be chosen. Utilising the game theory, this contradictory phenomenon can be explained as the two Nash equilibria. In addition to financial market risks, entrepreneurs should pay attention to the relationship with venture capitalists, when they choose the exit strategy.L’objectif de cette thèse est de développer des modèles quantitatifs utilisant les options réelles pour une évaluation financière des choix stratégiques entrepreneuriaux. Cependant, il ne s’agit pas seulement de développer des aspects techniques (ou manipulations mathématiques). Les modèles proposés dans la thèse visent également à fournir des informations pratiques utiles à la fois aux entrepreneurs et aux investisseurs, afin de faciliter la prise de décision dans les négociations contractuelles pour le financement et l'investissement dans les start-ups et les firmes entrepreneuriales.Cette thèse se compose de deux parties. La première partie définit les concepts utilisés afférents à la question de recherche. L’adoption de la perspective proposée par la finance entrepreneuriale nous permet de centrer notre approche sur la négociation et une relation d'égalité entre les participants dans le processus de prise de décision, alors que la finance d’entreprise traditionnelle s’intéresse à la relation principal-agent. En effet, les méthodes généralement utilisées comme les cash-flows actualisés (DCF) ou le Taux de Rendement Interne (TRI) ne sont pas adéquates pour effectuer une évaluation financière dans un contexte entrepreneurial. Ainsi, la problématique de cette thèse peut être formulée de la manière suivante : Comment les choix stratégiques des start-ups et firmes entrepreneuriales devraient-ils être évalués dans le cadre des négociations contractuelles ?Afin de traiter cette problématique, trois problèmes particuliers seront exposés dans la deuxième partie. Nous proposerons de les étudier à partir de l’approche par les options réelles qui convient parfaitement à l'analyse des choix stratégiques dans un contexte de finance entrepreneuriale.Le premier article analyse l’évaluation d’un contrat de licence dans le secteur biopharmaceutique. En résumé, lors de la conclusion d’un contrat de licence, les dirigeants et les responsables de la négociation doivent prendre en compte de nombreux facteurs tels que la phase de développement, la prévision des coûts d'investissement et la volatilité des marchés. De plus, la prise en compte des interactions comportementales des deux parties lors de la négociation du contrat de licence est essentielle pour la construction d'un modèle de simulation, notamment en ce qui concerne l’interaction dynamique entre le donneur de licence et le preneur de licence.Le deuxième article s’intéresse à la question de la dilution pour les nouveaux actionnaires lors du deuxième tour de financement en présence de détenteurs d’obligations convertibles. Selon les résultats de la simulation, il est possible de vérifier que le taux de « discount » et le « valuation cap » ont un impact important sur le coût de la prise de décision en matière d’investissement en actions. Les résultats montrent également que plus le taux de discount est élevé et moins le valuation cap est important, plus les coûts sont élevés, et la probabilité de succès de la négociation devient donc faible. Par conséquent, l’entrepreneur doit en tenir compte lorsqu’il entre en négociation lors du deuxième tour de financement.Le troisième article aborde le choix d’une stratégie de sortie pour un entrepreneur (acquisition ou introduction en bourse) notamment « The IPO valuation premium puzzle » proposé par Bayar et Chemmanur (2011). Bien qu'il soit normal que l’entrepreneur et les investisseurs en capital-risque envisagent l’introduction en bourse, il est également possible qu'ils choisissent l'acquisition comme stratégie de sortie. En utilisant la théorie des jeux, ce phénomène contradictoire peut être expliqué par l’existence de deux équilibres de Nash. En complément de la gestion des risques afférents au marché, l’entrepreneur doit prêter attention à la relation avec le capital-risqueur lorsqu’il choisit la stratégie de sortie