Introduction: Cigarette preference increases as a function of nicotine content, but preference can be shifted by manipulating cigarette cost. The aim of the present study is to model whether the behavioral-economic metric of unit price (cigarette cost/nicotine content) accounts for cigarette preference shifts and whether preference changes to very low nicotine content cigarettes (VLNCs) are associated with corresponding changes in smoking rate. Methods: 169 daily smokers from populations vulnerable to smoking completed sessions in which choices between smoking normal nicotine content (NNC) (15.8mg/g) and VLNC (0.4mg/g) cigarettes were concurrently available. In Condition 1, choices for both products were available ad-lib at an equal cost of 10 responses/choice. In Condition 2, VLNCs were again available ad-lib at 10 responses/choice, but NNCs were available on a progressive-ratio (PR) schedule wherein response cost (and unit price) increased following each NNC choice (10,160,320…8400 responses/choice). Results were analyzed using ANOVAs and a binomial test (p<.05). Results: Participants preferred NNCs over VLNCs in Condition 1, but shifted preference to VLNCs in Condition 2 (p<.001) immediately before the point in the PR progression where unit price for NNCs exceeded unit price for VLNCs (p<.001). Additionally, this preference shift corresponded with reduced total cigarette consumption compared to Condition 1 levels (p<.001). Conclusions: These results suggest that unit price of nicotine underpins cigarette preference and may provide a metric by which regulators can predict product preference and potentially impact it through policy. These results also demonstrate that VLNCs sustain lower smoking rates than NNCs even under acute laboratory conditions.

abstract: In the fifteen years between the discovery of fetal alcohol syndrome (FAS) in 1973 and the passage of alcohol beverage warning labels in 1988, FAS transformed from a medical diagnosis between practitioner and pregnant women to a broader societal risk imbued with political and cultural meaning. I examine how scientific, social, moral, and political narratives dynamically interacted to construct the risk of drinking during pregnancy and the public health response of health warning labels on alcohol. To situate such phenomena I first observe the closest regulatory precedents, the public health responses to thalidomide and cigarettes, which established a federal response to fetal risk. I then examine the history of how the US defined and responded to the social problem of alcoholism, paying particular attention to the role of women in that process. Those chapters inform my discussion of how the US reengaged with alcohol control at the federal level in the last quarter of the twentieth century. In the 1970s, FAS allowed federal agencies to carve out disciplinary authority, but robust public health measures were tempered by uncertainty surrounding issues of bureaucratic authority over labeling, and the mechanism and extent of alcohol’s impact on development. A socially conservative presidency, dramatic budgetary cuts, and increased industry funding reshaped the public health approach to alcoholism in the 1980s. The passage of labeling in 1988 required several conditions: a groundswell of other labeling initiatives that normalized the practice; the classification of other high profile, socially unacceptable alcohol-related behaviors such as drunk driving and youth drinking; and the creation of a dual public health population that faced increased medical, social, and political scrutiny, the pregnant woman and her developing fetus. / Dissertation/Thesis / Doctoral Dissertation Biology 2016

付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 新制・課程博士 / 博士(医学) / 甲第23092号 / 医博第4719号 / 新制||医||1050(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 黒田 知宏, 教授 上杉 志成, 教授 藤渕 航 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Rationale: Nicotine is the addictive component in cigarettes which maintains cigarette smoking that subsequently leads to morbidity and mortality. There are growing regulatory efforts to lower the nicotine content in cigarettes so that they are minimally addictive. Valid methods for assessing the abuse liability of cigarettes are essential to these efforts. While subjective effect measures and hypothetical purchase tasks are appealing because they are far easier to administer, it is unclear whether these methods can be used to evaluate acute relative reinforcing, a critical component of abuse liability. This secondary analysis sought to evaluate the utility of one subjective effects measure, the modified Cigarette Evaluation Questionnaire (mCEQ), and one hypothetical purchase task, the Cigarette Purchase Task (CPT), for predicting acute relative reinforcing efficacy as measured by concurrent choice Self-Administration (SA) Method: Current smokers (N=169) belonging to one of three vulnerable populations (socioeconomically disadvantaged women of childbearing age, opioid-maintained individuals, or individuals with affective disorders) participated in a multi-site, double blind study evaluating research cigarettes with varying levels of nicotine content (0.4, 2.4, 5.2, 15.8 mg/g). In Phase 1 (4 sessions, 1 research cigarette per session) participants completed the mCEQ and CPT following ad-lib smoking of the research cigarette. In Phase II (6 sessions) cigarette preference was assessed using two-dose concurrent choice tests. Difference scores were calculated for each of the five mCEQ subscales and five CPT indices for all six possible dose comparisons evaluated in Phase II. We evaluated the utility of the mCEQ subscale and CPT index difference scores for predicting preference for the higher dose in a given dose comparison using a mixed-model of repeated measures analysis of variance. Finally, we used stepwise regressions to determine which subscales and indices served as independent predictors of concurrent choice SA. Results: Among mCEQ subscales, higher Satisfaction and Enjoyment of Respiratory Tract Sensation were independently predictive of higher dose preference in the choice testing regardless of dose comparison. There was a significant Satisfaction X Vulnerable Population interaction where increases in Satisfaction difference scores corresponded to greater changes in higher dose preference among socioeconomically disadvantaged women of childbearing age compared to other Vulnerable Populations. Among CPT indices, Elasticity was the only independent predictor of choice. However, there was a significant Elasticity X Dose Comparison X Vulnerable Population interaction associated with its predictive utility where the relationship between elasticity and choice differed by dose among opioid-maintained individuals. In a final model, including all subscales and indices, Satisfaction and Enjoyment of Respiratory Tract Sensations remained the only significant predictors of choice. Discussion: Concurrent choice testing, subjective effects and hypothetical purchase tasks capture some common features of abuse liability. Concurrent choice testing and the Satisfaction subscale were the most concordant measures. The observation that CPT indices are not robust predictors of choice in a concurrent arrangement suggests this measure may have greater utility for capturing individual differences as opposed to isolating the acute relative reinforcing effects of nicotine. Nevertheless, all three measures can contribute to efforts to assess the abuse liability of cigarettes varying in nicotine dose and important work aimed at regulating these products to improve human health.

運用科學知識在當代環境管制政策幾乎已屬常態。然而，科學卻不一定能有效解決環境污染問題。本研究探討雲林六輕石化廠區的揮發性有機物（VOCs）空氣污染問題，發現運作二十多年的六輕，其排放之VOCs數值，至今尚未釐清，但企業仍不斷擴廠，引發當地健康風險問題；同時，國光石化的環評中，PM2.5（細懸浮微粒）引發重大政治爭議，民間提出對抗性科學論述影響決策方向，後續，更促成相關管制法規通過。 在上述管制科學爭議中，本文採用新政治科學社會學所提供的制度、網絡與權力，與環境決策知識建構的途徑觀點，探討雲林石化廠區所排放的揮發性有機物（VOCs）、懸浮微粒（PM2.5）相關之管制科學爭議。運用次級資料分析法、田野調查以及深入訪談法，嘗試分析強調科學循證作為基礎的管制政策，何以仍落入管制失靈的窘境？本文探討兩個個案，其不同調的科學數字如何依循管制制度生產、傳遞及運用？其中，VOCs排放數字如何被各個政治行動者賦予政治性意涵，進而延宕政府管制的能力？甚而導致府際間嚴重衝突？而PM2.5的對抗性科學論述是如何被生產、傳遞乃至公共化？相關之政策網絡如何有效地將PM2.5的管制政策推入政治議程中，成為正式法規的一環？ 本研究發現，在VOCs個案中，基於污染物的特性、石化廠區的龐大營運複雜度、以及企業為管制資訊之主要來源等因素，使VOCs排放具有相當大的科學不確定性。不過，現行制度將這些科學不確定性切割成一場又一場對於企業資訊的審查，對於掌握確切污染狀況極其有限。在PM2.5個案中，在幾個重大政策窗事件出現之前，民間社會已有一定的知識建構基礎。而重大政策窗事件如六輕工安大火、國光石化興建以及2011年總統選舉等，促成不同社會網絡連結，協助、生產出對抗性論述，並結合公眾媒體的廣泛傳播特性，將相關科技風險知識公共化，終使得PM2.5管制法案成為正式規範之一。 / Scientific knowledge has been commonly employed for making environmental regulatory policies. This thesis aims at analyzing the contamination problems resulted from Volatile Organic Compounds (VOCs) released by the Six Naphtha Cracking Complex; it is discovered that the emission of VOCs remains a mystery after two decades of operation. However, the industrial expansion plan continues and has done a severe environmental and health destruction to the local community. Meanwhile, PM2.5, Fine Particulate Matters also triggered political controversies in the Environmental Impact Assessment process of Kuokuang Petrochemical Plant, the Eighth Naphtha Cracking Project(8th naphtha). The civil society has raised the opposing argument on the PM2.5 matter in terms of health impact, thereby influencing the direction of policy making and passing the regulations. In light of the controversies of regulatory science, this thesis adopts the perspective of New Political sociology of Science (NPSS), which substantiates the approach of institution, network and power, and other aspects of knowledge construction to analyze the emission of VOCs and PM2.5 in the petrochemical field. Moreover, secondary data, field research, and in-depth interviews are utilized to analyze these regulatory predicaments. It is discovered in the cases of VOCs, the scientific uncertainty is composed of the characteristics of VOCs, the complexity of petrochemical plant’s operations and the main regulatory information is generated by industries. Nevertheless, the regulatory institution just divided the scientific uncertainty into the tremendous conferences which peer-reviewed the information from industries. Furthermore, this regulatory institution hinders the true conditions of pollution from being known. In the meantime, in terms of PM2.5, the general public has had a solid knowledge pertaining to the critical national matters, such as several fire disasters of 6th naphtha, the policy of 8th naphtha, and the presidential election in 2011. Moreover, these policy windows promote the connection of social network and assistance, and accordingly generate the opposing discourse. The technology risk-related knowledge has also been conveyed by the mass media, thus ultimately enacting the PM2.5.