エネルギー輸出国の脆弱性とエネルギーセキュリティの評価フレームワーク：現在の化石燃料依存社会と将来の水素社会の事例

京都大学新制・課程博士博士(エネルギー科学)甲第24924号エネ博第466号京都大学大学院エネルギー科学研究科エネルギー社会・環境科学専攻(主査)教授 MCLELLAN Benjamin, 教授 宇根﨑 博信, 教授 河本 晴雄学位規則第4条第1項該当Doctor of Energy ScienceKyoto UniversityDFA

Competing risk bias in prognostic models predicting hepatocellular carcinoma occurrence: impact on clinical decision making

Existing models predicting hepatocellular carcinoma (HCC) occurrence do not account for competing risk events and, thus, may overestimate the probability of HCC. Our goal was to quantify this bias for patients with cirrhosis and cured hepatitis C. We analyzed a nationwide cohort of patients with cirrhosis and cured hepatitis C infection from Scotland. Two HCC prognostic models were developed: (1) a Cox regression model ignoring competing risk events and (2) a Fine-Gray regression model accounting for non-HCC mortality as a competing risk. Both models included the same set of prognostic factors used by previously developed HCC prognostic models. Two predictions were calculated for each patient: first, the 3-year probability of HCC predicted by model 1 and second, the 3-year probability of HCC predicted by model 2. The study population comprised 1629 patients with cirrhosis and cured HCV, followed for 3.8 years on average. A total of 82 incident HCC events and 159 competing risk events (ie, non-HCC deaths) were observed. The mean predicted 3-year probability of HCC was 3.37% for model 1 (Cox) and 3.24% for model 2 (Fine-Gray). For most patients (76%), the difference in the 3-year probability of HCC predicted by model 1 and model 2 was minimal (ie, within 0 to ±0.3%). A total of 2.6% of patients had a large discrepancy exceeding 2%; however, these were all patients with a 3-year probability exceeding >5% in both models. Prognostic models that ignore competing risks do overestimate the future probability of developing HCC. However, the degree of overestimation—and the way it is patterned—means that the impact on HCC screening decisions is likely to be modest

The risk of hepatocellular carcinoma in cirrhotic patients with hepatitis C and sustained viral response:role of the treatment regimen

Background & Aims: Previous studies have reported a high frequency of hepatocellular carcinoma (HCC) occurrence in patients with advanced liver disease, after receipt of interferon (IFN)-free therapy for hepatitis C virus (HCV) infection. Our objective was to verify and account for this phenomenon using data from the Scottish HCV clinical database. Methods: We identified HCC-naïve individuals with liver cirrhosis receiving a course of antiviral therapy in Scotland from 1997–2016 resulting in a sustained virologic response. Patients were followed-up from their treatment start date to the earliest of: date of death, date of HCC occurrence, or 31 January 2017. We used Cox regression to compare the risk of HCC occurrence according to treatment regimen after adjusting for relevant co-factors (including: demographic factors; baseline liver disease stage; comorbidities/health behaviours, virology, and previous treatment experience). HCC occurrence was ascertained through both the HCV clinical database and medical chart review. For our main analysis, treatment regimen was defined as IFN-free vs. IFN-containing. Results: A total of 857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free therapy was associated with a significantly increased risk of HCC (HR: 2.48; p = 0.021). However, after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, p = 0.744). Conclusion: These findings suggest that the higher incidence of HCC following sustained virologic response with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se. Lay summary: We examined the risk of liver cancer in 857 patients with cirrhosis in Scotland who received hepatitis C antiviral therapy and achieved a cure. We compared the risk of first-time liver cancer in patients treated with the newest interferon-free regimens, to patients treated with interferon. After accounting for the different characteristics of these two treatment groups, we found no evidence that interferon-free therapy is associated with a higher risk of liver cancer

Synthesis of fluorescent analogs of relaxin family peptides and their preliminary in vitro and in vivo characterization

Relaxin, a heterodimeric polypeptide hormone, is a key regulator of collagen metabolism and multiple vascular control pathways in humans and rodents. Its actions are mediated via its cognate G-protein-coupled receptor, RXFP1 although it also "pharmacologically" activates RXFP2, the receptor for the related, insulin-like peptide 3 (INSL3), which has specific actions on reproduction and bone metabolism. Therefore, experimental tools to facilitate insights into the distinct biological actions of relaxin and INSL3 are required, particularly for studies of tissues containing both RXFP1 and RXFP2. Here, we chemically functionalized human (H2) relaxin, the RXFP1-selective relaxin analog H2:A(4-24)(F23A), and INSL3 to accommodate a fluorophore without marked reduction in binding or activation propensity. Chemical synthesis of the two chains for each peptide was followed by sequential regioselective formation of their three disulfide bonds. Click chemistry conjugation of Cy5.5 at the B-chain N-terminus, with conservation of the disulfide bonds, yielded analogs displaying appropriate selective binding affinity and ability to activate RXFP1 and/or RXFP2 in vitro. The in vivo biological activity of Cy5.5-H2 relaxin and Cy5.5-H2:A(4-24)(F23A) was confirmed in mice, as acute intracerebroventricular (icv) infusion of these peptides (but not Cy5.5-INSL3) stimulated water drinking, an established behavioral response elicited by central RXFP1 activation. The central distribution of Cy5.5-conjugated peptides was examined in mice killed 30 min after infusion, revealing higher fluorescence within brain tissue near-adjacent to the cerebral ventricle walls relative to deeper brain areas. Production of fluorophore-conjugated relaxin family peptides will facilitate future pharmacological studies to probe the function of H2 relaxin/RXFP1 and INSL3/RXFP2 signaling in vivo while tracking their distribution following central or peripheral administration

Performance of models to predict hepatocellular carcinoma risk among UK patients with cirrhosis and cured HCV infection

Background & aimsHepatocellular carcinoma (HCC) prediction models can inform clinical decisions about HCC screening provided their predictions are robust. We conducted an external validation of 6 HCC prediction models for UK patients with cirrhosis and a HCV virological cure.MethodsPatients with cirrhosis and cured HCV were identified from the Scotland HCV clinical database (N = 2,139) and the STratified medicine to Optimise Treatment of Hepatitis C Virus (STOP-HCV) study (N = 606). We calculated patient values for 4 competing non-genetic HCC prediction models, plus 2 genetic models (for the STOP-HCV cohort only). Follow-up began at the date of sustained virological response (SVR) achievement. HCC diagnoses were identified through linkage to nation-wide cancer, hospitalisation, and mortality registries. We compared discrimination and calibration measures between prediction models.ResultsMean follow-up was 3.4-3.9 years, with 118 (Scotland) and 40 (STOP-HCV) incident HCCs observed. The age-male sex-ALBI-platelet count score (aMAP) model showed the best discrimination; for example, the Concordance index (C-index) in the Scottish cohort was 0.77 (95% CI 0.73-0.81). However, for all models, discrimination varied by cohort (being better for the Scottish cohort) and by age (being better for younger patients). In addition, genetic models performed better in patients with HCV genotype 3. The observed 3-year HCC risk was 3.3% (95% CI 2.6-4.2) and 5.1% (3.5-7.0%) in the Scottish and STOP-HCV cohorts, respectively. These were most closely matched by aMAP, in which the mean predicted 3-year risk was 3.6% and 5.0% in the Scottish and STOP-HCV cohorts, respectively.ConclusionsaMAP was the best-performing model in terms of both discrimination and calibration and, therefore, should be used as a benchmark for rival models to surpass. This study underlines the opportunity for 'real-world' risk stratification in patients with cirrhosis and cured HCV. However, auxiliary research is needed to help translate an HCC risk prediction into an HCC-screening decision.Lay summaryPatients with cirrhosis and cured HCV are at high risk of developing liver cancer, although the risk varies substantially from one patient to the next. Risk calculator tools can alert clinicians to patients at high risk and thereby influence decision-making. In this study, we tested the performance of 6 risk calculators in more than 2,500 patients with cirrhosis and cured HCV. We show that some risk calculators are considerably better than others. Overall, we found that the 'aMAP' calculator worked the best, but more work is needed to convert predictions into clinical decisions

Crop Updates 2009 - Cereals

This session covers twenty seven papers from different authors: PLENARY 1. Building soil carbon for productivity and implications for carbon accounting, Jeff Baldock, CSIRO Land and Water, Adelaide, SA 2. Fact or Fiction: Who is telling the truth and how to tell the difference, Doug Edmeades, agKnowledge Ltd, Hamilton 3. Four decades of crop sequence trials in Western Australia, Mark Seymour,Department of Agriculture and Food BREAK CROPS 4. 2008 Break Crops survey Report, Paul Carmody,Development Officer, Department of Agriculture and Food 5. Attitudes of Western Australian wheatbelt growers to ‘Break Crops’, Paul Carmody and Ian Pritchard, Development Officers, Department of Agriculture and Food 6. The value of organic nitrogen from lupins, Alan Meldrum, Pulse Australia 7.The area of break crops on farm: What farmers are doing compared to estimates based on maximising profit, Michael Robertson and Roger Lawes,CSIRO Floreat, Rob Sands,FARMANCO Farm Consultants, Peter White,Department of Agriculture and Food, Western Australia, Felicity Byrne and Andrew Bathgate,Farming Systems Analysis CROP SPECIFIC Breeding 8. Identification of WALAB2014 as a potential albus lupin variety for northern agricultural region of Western Australia, Kedar Adhikari, Department of Agriculture and Food 9. Enhancement of black spot resistance in field pea, Kedar Adhikari, Tanveer Khan, Stuart Morgan and Alan Harris, Department of Agriculture and Food 10. Desi chickpea breeding: Evaluation of advanced line, Khan, TN1, Harris, A1, Gaur, P2, Siddique, KHM3, Clarke, H4, Turner, NC4, MacLeod, W1, Morgan, S1 1Department of Agriculture and Food, Western Australia, 2International Crop Research Institute for the Semi Arid Tropics (ICRISAT), 3The University of Western Australia, 4Centre for Legumes in Mediterranean Agriculture 11. Pulse Breeding Australia-Australian Field Pea Improvement Program (AFPIP), Ian Pritchard1, Chris Veitch1, Stuart Morgan1, Alan Harris1 and Tony Leonforte 2 1 Department of Agriculture and Food, Western Australia, 2 Department off Primary Industries, Victoria Disease 12. Interaction between wheat varieties and fungicides to control stripe rust for grain and quality, Kith Jayasena, Geoff Thomas, Rob Loughman, Kazue Tanaka and Bill MacLeod, Department of Agriculture and Food 13. Findings of canola disease survey 2008 and its implications for better disease management in 2009, Ravjit Khangura, WJ MacLeod, P White, P Carmody and M Amjad, Department of Agriculture and Food 14. Combating wheat leaf diseases using genome sequencing and functional genomics, Richard Oliver, Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University 15. Distribution and survival of wheat curl mite (Aceria tosichella), vector of Wheat Streak Mosaic Virus, in the WA grainbelt during 2008, Dusty Severtson, Peter Mangano, John Botha and Brenda Coutts, Department of Agriculture and Food 16. Partial resistance to Stagonspora (Septoria) Partial resistance to Stagonospora (Septoria) nodorum blotch and response to fungicide in a severe epidemic scenario, Manisha Shankar1, Richard Oliver2, Kasia Rybak2and Rob Loughman1 1Department of Agriculture and Food, Western Australia, 2Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University, Western Australia 17. Black pod syndrome in lupins can be reduced by regular insecticide sprays, Peter White and Michael Baker,Department of Agriculture and Food Variety performance 18. Incorporating new herbicide tolerant juncea canola into low rainfall cropping systems in Western Australia, Mohammad Amjad, Department of Agriculture and Food 19. Varietal differences in germ end staining of barley, Andrea Hills,Department of Agriculture and Food 20. Wheat variety performance in the Central Agricultural Region in 2008, Shahajahan Miyan, Department of Agriculture and Food 21. Barley variety identification using DNA fingerprinting, Peter Portmann, Agriconnect, Perth WA Dr Nicole Rice, Southern Cross University, Lismore NSW Prof Robert Henry, Southern Cross University, Lismore NSW 22. Forecast disease resistance profile for the Western Australian barley crop over the next three years, Jeff J. Russell, Department of Agriculture and Food 23. Malting barley varieties differ in their flowering date and their response to changes in sowing date, BH Paynter and Jeff J. Russell,Department of Agriculture and Food 24. Market development for new barley varieties, Linda Price,Barley Australia 25. Response of wheat varieties to sowing time at Mt Barker, Katanning and Newdegate in 2008, Brenda Shackley and Vicki Scanlan,Department of Agriculture and Food 26. Flowering dates of wheat varieties in 2008 at three locations in Western Australia, Darshan Sharma, Brenda Shackley and Christine Zaicou-Kunesch, Department of Agriculture and Food 27. Agronomic responses of new wheat varieties in the norther agricultural region in 2008, Christine Zaicou-Kunesch, Department of Agriculture and Foo

Stereological analysis of liver biopsy histology sections as a reference standard for validating non-invasive liver fat fraction measurements by MRI

© 2016 St. Pierre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background and Aims: Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods: VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results: Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7-8.8)% and 2.4 (95% CI 2.2-2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69-0.93) and 0.990 (95% CI 0.985-0.994) respectively. Small biases (=3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using Hepa-Fat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions: Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF