Authentic Discourse and Model Exemplars in Japanese Language Textbooks: A Case Study of Apologies and Requests

In recent years, the communicative approach has prevailed in second language teaching, such that model dialogues are presented in textbooks for language learners. However, there has been little research on the extent to which such exemplars reflect authentic discourse in Japanese. This thesis, therefore, explores the speech acts of Japanese language native speakers (NSs), non-native speakers who are learning Japanese (NNSs), and discourse model examples presented in Japanese language textbooks (TXs) in order to investigate their similarities and differences, and thereby enhance the contents of textbooks. In particular, this thesis focuses on the discourse structure and expressions. The study takes a quantitative approach to the data analysis, using two different scenarios in settings of apology and requests. NSs pairs and NNSs pairs were requested to perform role-plays of two different scenarios in Japanese. The conversational data of the role-plays were transcribed, and the model exemplars of apology and request presented in the selected Japanese language textbooks were also analysed. The analysis employs the framework of cross-cultural speech act realisation patterns (CCSARP) of Blum-Kulka et al. (1989) to categorise utterances based on the intentions of the speakers into two parts, namely: Head Acts (HAs) and Supportive Moves (SMs). Once the data were classified by the CCSARP, individual HAs and SMs were sorted according to Brown and Levinson’s politeness theory (1987), which divides politeness strategies into four types: bald on record, positive politeness, negative politeness, and off record. By adopting both CCSARP and politeness theory, the characteristics of the discourse strategies and expressions of the three groups analysed in this thesis can be grasped. The analysis produces several new findings by identifying various ways in which the model dialogues in Japanese language textbooks fail to reflect the natural discourse of Japanese native speakers. The thesis presents suggestions for improvement for the benefit of textbook authors in future

Attenuation of Responsiveness to Interferon-α Treatment by Preceded Overactivation of Interferon-mediated Pathway in Patients Chronically Infected by Hepatitis C Virus

The Interferon (IFN) receptor-mediated signal transduction pathways involve the two novel DNA-binding factors, interferon regulatory factor-1 (IRF-1) and IRF-2. Both recognize the same DNA sequence, in which the expression ratio of IRF-1 to IRF-2 is relevant to induction of IFN-inducible genes, because IRF-1 acts as a transcriptional activator and IRF-2 as a counterpart. In the present study, 54 patients with chronic hepatitis C and the age-and sex-matched 7 subjects with fatty liver as a control were subjected to analysis of the expression ratio of IRF-1 to IRF-2 mRNA in the liver tissue obtained at the time of livert biopsy by reverse transcription-polymerase chain reaction in combination with a restriction fragment length polymorphism assay. The expression ratio of IRF-1 to IRF-2 mRNA in the liver tissue in patients chronically infected by hepatitis C virus (HCV) was significantly higher than that in control, although the values did not correlate with the serum levels of HCV-RNA. Of 54 patients, 28 received IFN treatment, resulting in complete response in 8 patients. With respect to responsiveness to IFN treatment, patients who had complete response had the relatively lower ratios of IRF-1 to IRF-2 mRNA in the liver tissue, compared with those who did not. These results indicate that the IFN-mediated pathway is spontaneously activated in patients with chronic hepatitis C, and that its preceded overactivation counteracts on the efficacy of IFN treatment in these patients

Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants

遺伝性乳癌の遺伝学的・臨床学的特徴を解明 --BRCA1/2 変異乳癌は両アレルの不活化の有無により異なった特徴を持つ--. 京都大学プレスリリース. 2020-10-26.The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1, 995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants

Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1, 995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction

A retrospective comparative study of recombinant human thrombomodulin and gabexate mesilate in sepsis-induced disseminated intravascular coagulation patients

The novel biological agent recombinant human thrombomodulin (rhTM) has been used clinically in Japan to treat disseminated intravascular coagulation (DIC) since 2008. Previous studies have shown the efficacy of rhTM versus heparin therapy or non-rhTM therapy. We retrospectively evaluated and compared the efficacies of rhTM and gabexate mesilate (GM) in patients diagnosed with sepsis-induced DIC. From September 2010 to October 2012, patients with sepsis-induced DIC who were treated with rhTM (n = 13) or GM (n = 10) at Nagasaki Municipal Hospital were extracted. Patients receiving other anticoagulants in combination were excluded. Clinical information, laboratory data, Sequential Organ Failure Assessment (SOFA) scores, and DIC scores were obtained from the medical records. Mortality at days 7 and 30 after DIC diagnosis and changes in laboratory data and SOFA scores from days 1-7 were evaluated. The groups\u27 clinical characteristics did not differ, except for the relatively higher C-reactive protein (CRP) levels in the rhTM group (P = 0.0508). The survival rates of the rhTM and GM groups on days 7 and 30 were 92.3%, 69.2% and 80%, 70%, respectively, both group indicated similar mortality. However, on day 7, the platelet counts, SOFA scores, and CRP levels significantly improved in the rhTM group; the platelet counts and SOFA scores did not improve significantly in the GM group. The platelet counts of the rhTM group significantly improved compared to the GM group (P = 0.004). Recombinant human thrombomodulin might be more effective for sepsis-induced DIC than GM

A Critique of Natural Discourse in Intermediate Level Textbooks for Learners of Japanese as a Second or Other Language

The number of learners of Japanese as a second or other language has increased rapidly worldwide over the past several decades. The objectives of their study have largely changed from pursuing purely academic research interests to acquiring the communicative skills needed for business or leisure purposes. There are five language competency skills needed to master foreign languages: reading, writing, listening, speaking and intercultural competence. Students, particularly those studying outside Japan, depend more on textbooks for learning how to speak than their peers in Japan; and speaking is studied formally through analysis of model discourses in selected textbooks. In particular, if the learner’s first language is very different from Japanese, which in fact almost all other languages are, the complexity of the spoken language, including gender difference and respect forms, presents most learners with certain challenges that require adequate explanation to be comprehended. Likewise, the larger the cultural gap between learner and target language, the greater are the challenges for acquiring intercultural competence, which is closely interrelated with the production of ‘natural speech’. It is, therefore, crucial for learners from other cultures who have little opportunity to speak in Japanese to learn from a textbook of good quality which provides appropriate explanation of the social and cultural context of the model dialogues they employ as exemplars. The present study aims to analyse and evaluate the appropriateness of model dialogues contained in intermediate level textbooks for learners of Japanese as a second or other language. The findings suggest that none of the selected textbooks included satisfactory explanation about the model discourses, so there seems to be much room for improvement in this regard. It is anticipated that the results of this study will contribute to the design concept of foreign language textbooks in future