京都大学 / 0048 / 新制・課程博士 / 博士(社会健康医学) / 甲第19639号 / 社医博第72号 / 新制||社医||9(附属図書館) / 32675 / 京都大学大学院医学研究科社会健康医学系専攻 / (主査)教授 今中 雄一, 教授 佐藤 俊哉, 教授 木原 正博 / 学位規則第4条第1項該当 / Doctor of Public Health / Kyoto University / DFAM

abstract: Automated planning problems classically involve finding a sequence of actions that transform an initial state to some state satisfying a conjunctive set of goals with no temporal constraints. But in many real-world problems, the best plan may involve satisfying only a subset of goals or missing defined goal deadlines. For example, this may be required when goals are logically conflicting, or when there are time or cost constraints such that achieving all goals on time may be too expensive. In this case, goals and deadlines must be declared as soft. I call these partial satisfaction planning (PSP) problems. In this work, I focus on particular types of PSP problems, where goals are given a quantitative value based on whether (or when) they are achieved. The objective is to find a plan with the best quality. A first challenge is in finding adequate goal representations that capture common types of goal achievement rewards and costs. One popular representation is to give a single reward on each goal of a planning problem. I further expand on this approach by allowing users to directly introduce utility dependencies, providing for changes of goal achievement reward directly based on the goals a plan achieves. After, I introduce time-dependent goal costs, where a plan incurs penalty if it will achieve a goal past a specified deadline. To solve PSP problems with goal utility dependencies, I look at using state-of-the-art methodologies currently employed for classical planning problems involving heuristic search. In doing so, one faces the challenge of simultaneously determining the best set of goals and plan to achieve them. This is complicated by utility dependencies defined by a user and cost dependencies within the plan. To address this, I introduce a set of heuristics based on combinations using relaxed plans and integer programming formulations. Further, I explore an approach to improve search through learning techniques by using automatically generated state features to find new states from which to search. Finally, the investigation into handling time-dependent goal costs leads us to an improved search technique derived from observations based on solving discretized approximations of cost functions. / Dissertation/Thesis / Ph.D. Computer Science 2012

The diploma thesis discusses an acquiring a car in a situation when the company has not a sufficient financial amount for its purchase. There are described the main kinds of leasing and credit at the beginning of this thesis. Afterwards is compared accounting as per the Czech regulations and IFRS and the tax impact of each of these types of accounting. The difference in accounting as per the Czech regulations and IFRS is as well illustrated on a leasing contract. The conclusion is focused on a comparison of leasing and credit using a method of net benefit of leasing and method of discounted costs.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / This study pondered what benefits the recycling of municipal solid waste provides for the city of Florianópolis, State of Santa Catarina. To estimate the value of economic, social and environmental benefits of recycling was used the methodology of environmental valuation indicated by Motta (2006 ), which estimates the Social Net Benefit of Reuse (SNBR) obtained with the recycling of key materials in the waste collected, steel, aluminum, paper, plastic and glass. Despite the high cost of selective collection in the city, essential program for waste recycling, it was shown that recycling generates many benefits and economic gains in Florianópolis. The average SNBR estimated for market price is R$ 806,98/t, on the other hand, the average SNBR that reflects the true opportunity cost is equal to R$ 447,92/t. With the estimate of the benefit generated per tonne of each material was possible to verify the potential of recycling in Florianópolis. The potential benefits of recycling of steel, aluminum, paper, plastic and glass in 2012 were estimated at R$ 32 million, demonstrating the gain that the society would have in Florianópolis if all waste liable to recycling sent to the landfill were directed for recycling. However, only 13%, R$ 4,2 million of this amount is currently performed by recycling waste collected by separate collection and sorted by the recyclers associations present in Florianópolis. The study is divided into four chapters dealing, respectively, the theoretical framework, the concept and issues related to municipal solid waste, the methodology used and the information on municipal solid waste in Florianópolis with the results analyzed. / Este trabalho ponderou quais os benefícios que a reciclagem de resíduos sólidos urbanos propicia para o município de Florianópolis, no Estado de Santa Catarina. Para estimar o valor dos benefícios econômicos, sociais e ambientais da reciclagem utilizou-se a metodologia de valoração ambiental indicada por Motta (2006), que estima o Beneficio Líquido Social do Reaproveitamento (BLSR) obtido com a reciclagem dos principais materiais presentes nos resíduos coletados, o aço, o alumínio, o papel, o plástico e o vidro. Apesar do custo elevado da coleta seletiva na cidade, programa essencial para que possa haver a reciclagem de resíduos, comprovou-se que a reciclagem gera diversos benefícios e ganhos econômicos em Florianópolis. O BLSR médio estimado pelo preço de mercado é de R$ 806,98/t e, por outro lado, o BLSR médio que reflete o verdadeiro custo de oportunidade é igual a R$ 447,92/t. Com a estimativa do benefício gerado por tonelada de cada material foi possível verificar o potencial da reciclagem em Florianópolis. Os benefícios potenciais da reciclagem de aço, alumínio, papel, plástico e vidro no ano de 2012 foram estimados em R$ 32 milhões, demonstrando o ganho que a sociedade em Florianópolis teria se todos os resíduos passíveis de reciclagem enviados para o aterro sanitário fossem encaminhados para a reciclagem. Contudo, apenas 13%, R$ 4,2 milhões, desse valor são atualmente realizados, através da reciclagem de resíduos coletados pela coleta seletiva e triados pelas associações de recicladores presentes em Florianópolis. O trabalho está dividido em quatro capítulos tratando, respectivamente, do referencial teórico, do conceito e questões referentes aos resíduos sólidos urbanos, da metodologia utilizada e das informações sobre os resíduos sólidos urbanos em Florianópolis com os resultados analisados.

Indiana University-Purdue University Indianapolis (IUPUI) / Background: The hazard ratio (HR), representing the quantified estimate of treatment effect in survival analysis, measures the instantaneous relative difference of failure risk between two groups. The HR is typically assumed to be independent of time; however, this assumption is usually violated in practice. If the proportionality assumption holds, HR can be validly with the popular Cox proportional hazards model. When not proportional, the Wilcoxon-Gehan has been proposed to test the hypothesis of no difference. These have been recently generalized to evaluate differences in survival time for more than zero survival differences (the “net survival benefit”). Method: In this thesis, an attempt is made to illustrate the properties of generalized Wilcoxon Gehan tests as proposed by Buyse (2009). We use the concept of net survival benefit to re-analyze the trial by the Gastrointestinal Tumor Study Group (1982) by comparing chemotherapy versus combined chemotherapy and radiation in the treatment of locally unresectable gastric cancer. Survival times in days, for the 45 patients were recorded in each treatment arm. In that trial, a delayed treatment effect was observed, thus the HR is non-proportional. To provide a flexible assessment of the treatment effect, the net survival benefit was computed using datasets simulated under typical scenarios of proportional hazards, such as delayed treatment effect. Results: The generalized Wilcoxon statistic U, favored not adding radiation to chemotherapy, but only for survival up to 12 months. At Δ=0, U (0) = 491. In the simulated data sets, the confidence interval under the null hypothesis U (0) is (-152, 388). The test statistic 491 is outside this interval indicating radiation treatment might be beneficial. At U(12) = 219, it is inside the confidence interval of no treatment effect (-154,268) indicating the benefit of Chemo only is gone after 12 months. Conclusions: The net survival benefit measured via Buyse’s generalized Wilcoxon statistic is a measure of treatment effect that is meaningful whether or not hazards are proportional. The associated statistical test is more powerful than the standard log-rank test when a delayed treatment effect is anticipated.

Background: Great strides have been made in combating malaria, however, the indicators in sub Saharan Africa still do not show promise for elimination in the near future as malaria infections still result in high morbidity and mortality among children. The abundance of the malaria-transmitting mosquito vectors in these regions are driven by climate suitability. In order to achieve malaria elimination by 2030, strengthening of surveillance systems have been advocated. Based on malaria surveillance and climate monitoring, forecasting models may be developed for early warnings. Therefore, in this thesis, we strived to illustrate the use malaria surveillance and climate data for policy and decision making by assessing the association between weather variability (from ground and remote sensing sources) and malaria mortality, and by building malaria admission forecasting models. We further propose an economic framework for integrating forecasts into operational surveillance system for evidence based decisionmaking and resource allocation.  Methods: The studies were based in Asembo, Gem and Karemo areas of the KEMRI/CDC Health and Demographic Surveillance System in Western Kenya. Lagged association of rainfall and temperature with malaria mortality was modeled using general additive models, while distributed lag non-linear models were used to explore relationship between remote sensing variables, land surface temperature(LST), normalized difference vegetation index(NDVI) and rainfall on weekly malaria mortality. General additive models, with and without boosting, were used to develop malaria admissions forecasting models for lead times one to three months. We developed a framework for incorporating forecast output into economic evaluation of response strategies at different lead times including uncertainties. The forecast output could either be an alert based on a threshold, or absolute predicted cases. In both situations, interventions at each lead time could be evaluated by the derived net benefit function and uncertainty incorporated by simulation.  Results: We found that the environmental factors correlated with malaria mortality with varying latencies. In the first paper, where we used ground weather data, the effect of mean temperature was significant from lag of 9 weeks, with risks higher for mean temperatures above 250C. The effect of cumulative precipitation was delayed and began from 5 weeks. Weekly total rainfall of more than 120 mm resulted in increased risk for mortality. In the second paper, using remotely sensed data, the effect of precipitation was consistent in the three areas, with increasing effect with weekly total rainfall of over 40 mm, and then declined at 80 mm of weekly rainfall. NDVI below 0.4 increased the risk of malaria mortality, while day LST above 350C increased the risk of malaria mortality with shorter lags for high LST weeks. The lag effect of precipitation was more delayed for precipitation values below 20 mm starting at week 5 while shorter lag effect for higher precipitation weeks. The effect of higher NDVI values above 0.4 were more delayed and protective while shorter lag effect for NDVI below 0.4. For all the lead times, in the malaria admissions forecasting modelling in the third paper, the boosted regression models provided better prediction accuracy. The economic framework in the fourth paper presented a probability function of the net benefit of response measures, where the best response at particular lead time corresponded to the one with the highest probability, and absolute value, of a net benefit surplus.  Conclusion: We have shown that lagged relationship between environmental variables and malaria health outcomes follow the expected biological mechanism, where presentation of cases follow the onset of specific weather conditions and climate variability. This relationship guided the development of predictive models showcased with the malaria admissions model. Further, we developed an economic framework connecting the forecasts to response measures in situations with considerable uncertainties. Thus, the thesis work has contributed to several important components of early warning systems including risk assessment; utilizing surveillance data for prediction; and a method to identifying cost-effective response strategies. We recommend economic evaluation becomes standard in implementation of early warning system to guide long-term sustainability of such health protection programs.

This dissertation consists of six essays in health economics.The first essay, “Economic evaluations in health care: Basic principles and special topics”, serves as an introduction to economic evaluations in health care, including estimations of costs, health effects, and the discount rate. Special topics of interest for the rest of the studies are also discussed, e.g. the role of modelling in cost-effectiveness analysis, and methods for dealing with incomplete observations in clinical trial data. The main theme of the second essay, “Consumption and production by age in Sweden: Basic facts and health economic implications”, is a fairly detailed compilation of consumption and production figures by age in Sweden. The purpose of this is to use the difference between consumption and production in each age group as a measure of the average costs of added years of life in the general population. In economic evaluations of health care interventions, only future costs for related ill­nesses have typically been included in the analysis. However, the health economist David Meltzer has argued that future costs for un­related illnesses and general consumption should also be in­cluded in eco­nomic evaluations. Otherwise, the analysis will not be consistent with expected utility maximiza­tion. The third essay is entitled “The possibility of predicting health care costs in the future from predicted changes in age structure and age specific mortality: The case of Sweden”. Changes in the age structure, especially the growing number of elderly people, have raised concerns about increasing costs for health and elderly care in the future. However, the number of elderly per se is not the main problem, since the growing number of elderly people is a result of better health and hence lower morta­lity. The main purpose of the study is to investigate if future health care costs can be predicted based on forecasts of future changes in age structure and mortality rates. It is shown here that at least in Sweden and in the U.S., there is a linear relationship between age-specific mortality and age-specific health care costs. When these relationships are applied retrospectively to old data, however, the predictions are underestimates of the actual costs. These results are in line with earlier studies, which show that the future age structure is not likely to have a great impact on the future health care costs. The fourth essay is called “Cost effectiveness of bisoprolol in the treatment of chronic congestive heart failure in Sweden: Analysis using data from the Cardiac Insufficiency Bisoprolol Study II” (with Niklas Zethraeus and Bengt Jönsson). Treatment of heart failure with beta blockers was introduced in Sweden already in the 1970s, but it was not until the 1990s that large-scale clinical trials established the efficacy of beta blockers in reducing heart failure mortality. The study consists of an economic evaluation of the beta blocker bisoprolol added to standard treatment of chronic heart failure, compared with placebo added to the same standard treatment. The study raises a number of methodological issues. At the forefront are the inclusion of costs of added years of life, and the question of how to model health effects that extend beyond the clinical trial on which the economic evaluation is based. The results indi­cate that treatment with bisoprolol is cost-effective. A drawback of the analysis in the fourth study was that the expected survival after the end of follow-up was modelled deterministically. This makes it impossible to assess the uncertainty of the cost-effectiveness estimate in a realistic way. The fifth essay is entitled “Assessing uncertainty in cost-effectiveness analysis by combining resampling of clinical trial data with stochastic modelling: The economic evaluation of bisoprolol for heart failure revisited”. Here, the drawback with the fourth study that was mentioned above is addressed by using resamp­ling of the clinical trial data in combination with stochastic modelling of the expected survival after the end of follow-up in the clinical trial. The methodology is inspired by the bootstrap method, which is a simulation technique whereby various statistics, like the mean and variance, can be estimated through repeated resampling from the original sample. The difference from the traditional boot­strap method is that resampling of observations from the clinical trial data is combined with stochastic modelling of the expected remaining lifetime of the patients who were alive at the end of the clinical trial. Cost-effectiveness acceptability curves for treatment of heart failure with bisoprolol were obtained as a result of the analysis. The sixth essay, “Survival analysis techniques for estimating the costs attributable to head and neck cancer in Sweden”, concerns the estimation of average treatment cost attri­butable to a disease when the data contain censored, i.e. incomplete, observations. For various reasons, censored observations are common in medical and epidemiological studies. As a result, the length of the survival time or the size of the costs for those who are alive at the end of follow-up are not exactly known. This is of course problematic if we want to estimate the average survival time or the average cost for all patients, both survivors and non-survivors included. In this study, the Kaplan-Meier sample-average estimator is used for overcoming the problem with censored observations. It is a method that has been proposed specifically for handling censored cost data. / Diss. Stockholm: Handelshögsk., 2002

Diss. Stockholm: Handelshögsk., 2002.