Rozprawy doktorskie na temat „Alcohol”

Els enzims presenten una sèrie d’avantatges catalítiques respecte als catalitzadors químics emprats en síntesis química clàssica: especificitat, selectivitat i la possibilitat de treballar en condicions suaus de temperatura i pressió. No obstant, també presenten una sèrie de limitacions com són la baixa estabilitat i les baixes productivitats. En el present treball es combinen dues tècniques per tractar d’optimitzar les reaccions d’interès seleccionades: la immobilització i l’enginyeria de reacció. Les reaccions objectiu d’aquest treball són reaccions d’oxidoreducció centrades en la biosíntesis de molècules, de mitjà i alt valor afegit, d’alt interès industrial. En la primera part de la tesis s’ha utilitzat una alcohol deshidrogenasa (ADH99) per a la oxidació de l’alcohol chlorolactol a chlorolactona i una NAD(P)H oxidasa (NOX) com a sistema de regeneració del cofactor. La chlorolactona és un precursor per a la síntesis d’estatines les quals són fàrmacs utilitzats per a la reducció del LDL-colesterol ja que inhibeixen l’enzim encarregat de la seva biosíntesis. Ambdós enzims van ser immobilitzats eficientment en diferents suports, dels quals es van seleccionar els tres que van mostrar major activitat retinguda. Seguidament es va estudiar l’estabilitat dels derivats immobilitzats en condicions de reacció i es va determinar la càrrega enzimàtica màxim per a cada enzim. Es va descartar l’ús de la NOX immobilitzada ja que no es va millorar l’estabilitat amb cap suport. Posteriorment es van optimitzar les condicions de reacció amb un disseny experimental (DoE) amb l’ADH99 soluble però utilitzant la quantitat màxima d’ADH99 que es pot afegir a la reacció quan es fa servir el l’ADH99 immobilitzada en epoxy-agarosa-UAB M2. Finalment es va estudiar la capacitat de reutilització del derivat immobilitzat, on es va poder millorar 1.5 vegades tant el producte obtingut com el rendiment del biocatalitzador. No obstant, la millor configuració va resultar ser la utilització dels dos enzims en forma soluble. La segona part d’aquesta tesis es va centrar en la reacció d’oxidació de l’alcohol vainillínic a vanil·lina biocatalitzada per l’eugenol oxidasa (EUGO). La vanil·lina és la molècula que dona les propietats organolèptiques a la vainilla, el segon aromatitzant més car del món. La síntesi de vanil·lina via biotecnològica és d’un gran interès industrial ja que pot etiquetar-se com a natural. L’EUGO va ser immobilitzada eficientment en diferents suports dels que es van seleccionar els tres que van retenir més activitat i se’n van estudiar els mateixos paràmetres de l’apartat anterior. En aquest cas els tres derivats immobilitzats van ser utilitzats per a realitzar la reacció de síntesi, amb l’objectiu de seleccionar el més estable operacionalment. Tots els derivats van permetre ser reutilitzats 5 vegades conservant una elevada conversió en l’últim cicle. L’epoxy-agarosa-UAB M2 va ser el suport que millor estabilitat va mostrar. Els bons resultats obtinguts en el segon apartat d’aquest treball van permetre aprofundir en aquesta reacció. Pel que, en el tercer apartat, es va realitzar una optimització de les condicions de reacció des del punt de vista de millorar les mètriques del procés i també amb l’objectiu de fer el procés més sostenible ambientalment. A l’hora d’escollir les noves condicions de reacció es van tenir en compte l’activitat de la EUGO i la seva estabilitat. Ambdues condicions van ser testades en la reacció objectiu amb l’EUGO soluble i immobilitzada. En les noves condicions es va poder millorar la productivitat volumètrica 5.7 i 6.6 vegades respectivament, en comparació a les condicions prèvies. Finalment, en el reciclatge de l’enzim immobilitzat es van poder realitzar 5 cicles de reacció en les primeres condicions i 18 cicles de reacció en les noves condicions on es va poder millorar el rendiment del biocatalitzador 3.9 i 12.4 vegades respectivament.
Las enzimas presentan una serie de ventajas catalíticas respecto a los catalizadores químicos empleados en síntesis química clásica: especificidad, selectividad y la posibilidad de trabajar en condiciones suaves de temperatura y presión. No obstante, también presentan una serie de limitaciones como son la baja estabilidad y las bajas productividades. En el presente trabajo se combinan dos técnicas para tratar de optimizar las reacciones de interés seleccionadas: la inmovilización y la ingeniería de reacción. Las reacciones objetivo de este trabajo son reacciones de oxidoreducción centradas en la biosíntesis de moléculas, de medio y alto valor añadido, de alto interés industrial. En la primera parte de la tesis se ha utilizado una alcohol deshidrogenasa (ADH99) para la oxidación del alcohol chlorolactol a chlorolactona y una NAD(P)H oxidasa (NOX) como sistema de regeneración del cofactor. La chlorolactona es un precursor para la síntesis de estatinas las cuales son fármacos utilizados para la reducción del LDL-colesterol puesto que inhiben la enzima encargada de su biosíntesis. Ambas enzimas fueron inmovilizados eficientemente en diferentes soportes, de los cuales se seleccionaron los tres que mostraron mayor actividad retenida. Seguidamente se estudió la estabilidad de los derivados inmovilizados en condiciones de reacción y se determinó la carga enzimática máximo para cada enzima. Se descartó el uso de la NOX inmovilizada puesto que no se mejoró la estabilidad con ningún apoyo. Posteriormente se optimizaron las condiciones de reacción con un diseño experimental (DoE) con la ADH99 soluble pero utilizando la cantidad máxima de ADH99 que se puede añadir a la reacción cuando se usa la ADH99 inmovilizada en epoxy-agarosa-UAB M2. Finalmente se estudió la capacidad de reutilización del derivado inmovilizado, donde se pudo mejorar 1.5 veces tanto el producto obtenido como el rendimiento del biocatalizador. No obstante, la mejor configuración resultó ser la utilización de las dos enzimas en forma soluble. La segunda parte de esta tesis se centró en la reacción de oxidación del alcohol vanillínico a vanillina biocatalizada por la eugenol oxidasa (EUGO). La vanillina es la molécula que da las propiedades organolépticas a la vainilla, el segundo aromatizante más caro del mundo. La síntesis de vainillina vía biotecnológica es de un gran interés industrial puesto que puede etiquetarse como natural. La EUGO fue inmovilizada eficientemente en diferentes soportes de los que se seleccionaron los tres que retuvieron más actividad y se estudiaron los mismos parámetros que en el apartado anterior. En este caso los tres derivados inmovilizados fueron utilizados para realizar la reacción de síntesis, con el objetivo de seleccionar el más estable operacionalmente. Todos los derivados permitieron ser reutilizados 5 veces conservando una elevada conversión en el último ciclo. La epoxy-agarosa-UAB M2 fue el soporte que mejor estabilidad mostró. Los buenos resultados obtenidos en el segundo apartado de este trabajo permitieron profundizar en esta reacción. Por lo que, en el tercer apartado, se realizó una optimización de las condiciones de reacción desde el punto de vista de mejorar las métricas del proceso y también con el objetivo de hacer el proceso más sostenible ambientalmente. A la hora de escoger las nuevas condiciones de reacción se tuvieron en cuenta la actividad de la EUGO y su estabilidad. Ambas condiciones fueron testadas en la reacción diana con lo EUGO soluble e inmovilizada. En las nuevas condiciones se pudo mejorar la productividad volumétrica 5.7 y 6.6 veces respectivamente, en comparación a las condiciones previas. Finalmente, en el reciclaje de la enzima inmovilizada se pudieron realizar 5 ciclos de reacción en las primeras condiciones y 18 ciclos de reacción en las nuevas condiciones donde se pudo mejorar el rendimiento del biocatalitzador 3.9 y 12.4 veces respectivamente.
Enzymes have some catalytic advantages over chemical catalysts used in classical chemical synthesis: specificity, selectivity and the possibility to work under mild conditions of temperature and pressure. However, they also have some limitations such as low stability and low productivity. This work combines two techniques aiming to optimise the target reactions: immobilisation and reaction engineering. The target reactions of this work are redox reactions focused on the biosynthesis of molecules, of medium-high value, of industrial interest. In the first part of the thesis, an alcohol dehydrogenase (ADH99) was used, with an NAD(P)H oxidase (NOX) as a cofactor regeneration system, to oxidise a chlorolactol to chlorolactone. Chlorolactone is a precursor for the synthesis of statins which are drugs used to lower LDL-cholesterol by inhibiting the enzyme responsible for its biosynthesis. Both enzymes were efficiently immobilised on different supports, selecting the three that showed the highest retained activity. The stability of the immobilised derivatives under reaction conditions was studied and the maximum enzyme load for each enzyme also was determined. The use of immobilised NOX was discarded because no stability improvements were achieved with any support. The reaction conditions were optimised by design of experiments (DoE), using soluble ADH99 added at maximum loading onto an epoxy-agarose support. Finally, the reusability of the immobilised enzyme was studied, where both the total product obtained and the biocatalyst yield could be improved 1.5-fold. However, the best configuration resulted from the use of the two enzymes in soluble form. The second part of this thesis was focused on the oxidation reaction of vanillyl alcohol to vanillin catalysed by eugenol oxidase (EUGO). Vanillin is the molecule that gives vanilla its organoleptic properties. Vanillin biotechnological synthesis is of high interest industrially because it is the second most expensive flavouring in the world and the product can be labelled as natural. Similar to the previous section, EUGO was efficiently immobilised onto different supports, selecting the three that retained most activity. These supports were used to study the stability of the immobilised enzyme and the maximum EUGO load that can be immobilised. In this case, the three immobilised derivatives were used to perform the target reaction, in order to select the most stable operationally. All immobilised derivatives could be reused 5 times maintaining a high conversion in the last cycle. Epoxy-agarose-UAB M2 was the support that showed the best stability, improving the biocatalyst yield 3-fold. The encouraging results obtained in the second section of this work allowed us to deepen the study of this reaction. Therefore, in the third section, an optimisation of the reaction conditions was carried out to improve the process metrics and also aiming to make the process more environmentally sustainable. The EUGO activity and its stability were taken into account to choose the reaction conditions. Both conditions, maximum activity and maximum stability, were tested in the target reaction with soluble and immobilised EUGO. Using the new conditions, it was possible to improve the volumetric productivity 5.7 and 6.6-fold respectively, compared to the previous conditions. Finally, the reusability of the immobilised EUGO allowed us to perform 5 reaction cycles and 18 reaction cycles, with unoptimised and optimised reaction conditions respectively. This resulted in an improvement of the biocatalyst yield of 3.9 and 12.4-fold, respectively, compared to reactions with soluble enzyme under the same conditions.
Universitat Autònoma de Barcelona. Programa de Doctorat en Biotecnologia

An applicable method for the racemic synthesis of 1,2-amino alcohols having tertiary alcohol moiety was developed. This method can be used as a general method for the synthesis of various 1,2-amino alcohols with various tertiary alcohol moieties by changing chloroacetone with different monohalo ketones, and with different aryl halides or alkyl halides. The resultant racemic 1,2-aminoe alcohols were tried to resolve by using various hydrolase type enzymes under different conditions by changing the parameters i.e. solvent, temperature and substrate: enzyme ratios. Finally, poorly resolved amino alcohol 20 with 21 % was used as chiral ligand in diethyl zinc reaction to benzaldhyde and afforded (R)-1-phenylpropan-1-ol almost with 21 % e.e..

The thesis draws on historical and social policy perspectives to examine the factors influencing development and change in alcohol treatment policy between 1950 and 1990. The study uses data from primary and secondary documentation and from taped interviews. Three themes are highlighted as particularly relevant to an examination of policy trends. The first of these is the emergence and evolution of a `policy community'. Spearheaded by psychiatrists in the 1960s, the `policy community' broadened to include other professional groups and the voluntary sector by the 1990s. The second theme concerns the role of research in influencing the nature and direction of treatment policy. The study indicates increasing use of research as the rationale for policy and illustrates the move towards a `contractor' relationship between research workers and policy makers. The final theme deals with the influence on policy of ideological frames and changing conceptualisations of the alcohol problem. Two major shifts were important for treatment, the re-discovery of the disease concept of alcoholism in the 1950s and the emergence of a new public health model of alcohol problems in the 1970s. Within these broad themes, the study includes an examination of tensions - between different professional perspectives, between government departments with differing responsibilities, between different ideologies - and of moves to secure consensus in the formulation and implementation of treatment policy. The final chapter addresses shifts in thinking from the re-emergence of a `disease' model of alcoholism in the 1950s, to a `consumptionist' (population-based) model in the 1970s, towards a `harm reduction' approach to alcohol problems management in the 1990s. The thesis concludes that over the past forty years competing paradigms of the alcohol problem have emerged and gained policy salience within particular historical-social contexts in the search for policy consensus to manage the problematic aspects of alcohol consumption.

Alcohol use (AU) and alcohol use disorder (AUD) are leading causes of morbidity, premature death, and economic burden. They are also associated with high levels of disability and many other negative outcomes. Twin and family studies have consistently shown that AU and AUD are complex traits influenced by both genetic and environmental factors. Although much has been learned about the genetic and environmental etiology of AU and AUD, significant gaps remain. These include the need for a more comprehensive understanding of the roles of risk and protective factors, and the nature of developmental trajectories underpinning the progression from AU to AUD. The aims of this dissertation are: (1) to examine the roles of resilience and personality disorders in the etiology of AU and AUD; (2) to investigate the nature of longitudinal changes in genetic and environmental risk factors responsible for individual differences in AU; and (3) to determine the moderating roles of key environmental risk factors on the impact of aggregate molecular, or polygenic, risk for AU during adolescence. Using both biometrical behavioral genetic and molecular genetic methodologies, five key findings were observed: (1) Resilience is strongly associated with a reduction in risk for AUD, and this relationship appears to be the result of overlapping genetic and shared environmental influences; (2) Borderline and antisocial personality disorders are the strongest and most stable personality pathology predictors of the phenotypic and genotypic liability to AU and AUD across time; (3) Genetic influences on the development of AUD from early adulthood to mid-adulthood are dynamic, whereby two sets of genetic risk factors contribute to AUD risk; (4) The specific genetic influences on AU follow an unfolding pattern of growth over time, whereas unique environmental risk factors are consistent with an accumulation of environmental impacts and risks across time; and (5) High peer group deviance and low parental monitoring are associated with increased AU, while early parental monitoring moderates the polygenic risk for AU at age 20. The implications of these results with regard to prevention and intervention efforts are discussed.

The negative individual and social impacts of alcohol consumption raise a considerable policy interest surrounding alcohol treatment. Economic evaluations help on the allocation of scarce health care resources, but these have been inadequately conducted in the alcohol field. This thesis builds up a taxonomy of alcohol-related consequences that should be included in economic evaluations of alcohol treatment and uses this taxonomy to critically review the published evidence around the cost effectiveness of alcohol treatments. The review provides a set of recommendations and most of them are pursued throughout the thesis. An economic model for the cost effectiveness of alcohol treatments is developed. The framework provides the means to conduct economic evaluation while bearing the complexity and challenges of decision making in the field of human behaviour. A link between drinking patterns, health consequences and alcohol treatment effectiveness and cost effectiveness is created. This is a probabilistic lifetime model that uses the cohort simulation approach. The model can be applied to any setting and this is exemplified for a UK-scenario. The methods and data for the generation of UK-specific model inputs are described and used in two model applications. A first application of the model extrapolates the results of a short term randomized controlled trial and provides the expected lifetime costs and outcomes of the treatments compared, by age and gender. A second application compares two alcohol treatments delivered in different countries and to populations very different at baseline. Both case-studies show the importance of time and that only a long-term analysis can capture both short-term alcohol consequences, such as injuries, and long-term consequences, such as most forms of alcohol-related chronic diseases. Assumptions and implications of the methods and analyses are discussed and recommendations for future research are presented.

Prenatal alcohol exposure (PAE) can lead to fetal alcohol spectrum disorder (FASD). FASD refers to a range of lifelong conditions caused by PAE, characterised by a distinctive facial phenotype, growth deficiencies and/or neurobehavioural impairments. This thesis presents four studies that I conducted to address knowledge gaps relevant to the epidemiology of PAE and FASD. First, objective measures of PAE are essential for identifying children at risk of adverse outcomes. Biomarkers have been advocated for use in universal PAE screening programs but their validity had not been comprehensively evaluated. I conducted a systematic review and found that biomarker test performance varied widely across studies. The quality of published studies was low, resulting in insufficient evidence to support the use of objective measures of PAE in practice. Second, the prevalence of FASD in the UK was unknown. Active case ascertainment studies have not been possible due to funding and ethical issues. To overcome these issues, I developed an algorithm to estimate FASD prevalence using existing data from a population-based birth cohort in England (ALSPAC). Up to 17% of children met criteria for FASD, indicating that it is a significant public health concern. Third, although PAE is the sole necessary cause of FASD, it is not always sufficient. Understanding risk factors for FASD is important for informing prevention strategies. However, existing studies have mostly been limited to discussion of association, rather than causation. I produced a causal diagram to depict hypothesised causal pathways to FASD. I used this diagram to guide analyses in a FASD risk factor study, reported below. Finally, I investigated FASD risk factors using multivariable logistic regression within the ALSPAC cohort. Prenatal stress, smoking and mental health problems increased the odds of FASD. Social support and folic acid supplementation were protective. These results indicate novel potential targets for FASD intervention.

The liquid-liquid equilibrium (LLE) data for water with active, racemic and nonracemic alcohol systems were measured by analytical, calorimetric and synthetic techniques. A new method for purification of alcohols and a semiautomated apparatus for the precise determination of LLE data by the synthetic procedure were developed. Liquid-liquid mutual solubilities of water + organic mixtures were also obtained analytically using both isopiestic vapour exchange and direct two-liquid equilibration techniques. The molar heats of mixing of water + alcohol mixtures and molar integral solution enthalpies were measured with a modified 1KB calorimeter. The differences between the present solubility data and those reported previously have been discussed in terms of impurity effects. 2-Butanol contaminated with n-octane dissolved less water but the presence of cosolvent impurities in 2-butanol resulted in the system being bound by a solubility loop. In general alcohol rich phase solubilities are sensitive to impurities while those in the aqueous phase appear to be largely unaffected. The unusual solubility behaviour of water with (±) 2-butanol at low temperatures was confirmed. The region of liquid-liquid immiscibility of the system lies within the temperature range of 268 K and 387 K. The calorimetric heats of mixing data for this system below 278 K suggested that the molar heat capacity of the system at constant E pressure, CEp,m, was negative. Both active 2-butanol and (±) 2-butanol exhibited identical solubility behaviour with water. The unusual solubility behaviour of water + alcohol systems have been discussed in terms of changes in extent of hydrate formations and racemic compound formations. Both racemic alcohols and tertiary alcohols with water exhibited unusual solubility behaviour in their respective alcohol rich phases.

Altering alcohol expectancies has reduced alcohol use among college students and may lead to successful prevention of alcohol use among high school students. We randomly assigned 379 12th-grade students to an expectancy challenge, traditional alcohol information, or control condition, and used Individual Differences Scaling to map expectancies into memory network format with Preference Mapping to model likely paths of association. After expectancy and traditional alcohol interventions, higher drinking male participants exhibited a greater likelihood to associate alcohol use with negative and sedating consequences and a decreased likelihood to associate alcohol with positive and arousing consequences. Drinking decreases paralleled the magnitude of changes in their likely path of expectancy activation. Children and adults who emphasize negative and sedating effects have been found to be less likely to use alcohol. Therefore, expectancy challenge interventions that have been successful at modifying expectancies and subsequently decreasing alcohol consumption among heavy drinking college students may be useful in the development of prevention curricula for high school students.
Ph.D.
Department of Psychology
Sciences
Psychology

This paper tries to find out whether a short ban on sales of liquors reduced the harmful use of alcohol with respect to motor vehicle accidents. I make use of short (two weeks) alcohol prohibition which was imposed by the Ministry of Health Care in the Czech Republic in September 2012 aiming to stop the deadly wave of methanol poisoning. To estimate the effect of prohibition on the number of road traffic accidents, I exploit the methodology of differences-in-differences. I use daily data about traffic accidents from the Czech Republic (treatment group) and from neighboring countries such as Austria, Germany and Poland (control group). The result suggests that there is no significant drop in term of road traffic accidents.

Thesis (M. A. (Social Work)) --University of Limpopo, 2019.
The study was aimed at exploring the family member‟s experiences of living with people who consume home brewed alcohol (spayoni) in Oakley. Oakley is a village based in Ehlanzeni district, Mpumalanga province. The researcher looked into the financial management, balancing of the work-family nexus and the manner in which people that consume spayoni deal with and conduct themselves in violent situations. A qualitative research approach was used by the researcher through an exploratory design. A total number of nine (9) respondents took part in the study. They were identified by the use of a purposive and snowball sampling method. Furthermore, the researcher used a semi-structured interview to collect data which was analysed by a thematic analysis structure. Data obtained from the study reveals that people that consume spayoni spend less time with family members as they are either out at work or drinking spayoni throughout the day. They leave home very early in the morning and come back late at night. Family roles and relationships are negatively affected by their routines. The people that consume spayoni mostly rely in piece jobs hence they don‟t have stable income. Nonetheless, the little money that they get is spent solely on the purchase of spayoni. They do not prioritise financial contribution towards household needs. The study also identified that people that consume spayoni are generally disrespectful when drunk but refrain from violent situations. In order to combat the challenges faced by the family members, internal and external measures should be put in place. The use of community awareness campaigns is one method which can help in reducing the demand of spayoni in Oakley village. Involvement of monitoring bodies such as the Liquor control boards and the local traditional authorities will assist the community to have regulations governing the supply of home brewed alcohol. Family members should also develop platforms of open communication between each other to avoid misunderstandings and build a more positive family environment.

Alcohol is one of the most widely used recreational drugs in the United States today, despite being associated with a myriad of negative effects. Alcohol consumption occurs most frequently within social contexts, and seems to be strongly related to many social factors. It is known that an individual's expectations of the effects of alcohol influences his/her drinking behavior, and that social alcohol expectancies are some of the most frequently reported expectancies. In this study, we explored the relationship between alcohol expectancies and social influences by examining whether exposure to a social context would differentially activate alcohol expectancies. 115 young-adult male participants were exposed to either a social context or a control condition. Subsequently, participants' alcohol expectancies were assessed using both explicit and implicit measurements. Differences between conditions were found on the implicit expectancy measure (a free association task) but not on the explicit expectancy measures. Results from the free association task indicated that participants who were exposed to a social context were more likely to report positive and arousing words in response to the prompt "alcohol makes me _______". These differences suggest that exposure to a social context may not overtly change individuals' alcohol expectancies, but may increase the availability of positive and arousing alcohol expectancies. This increase in availability of positive and arousing expectancies may explain one of the mechanisms involved in deciding to engage in social drinking.

Many studies have explored the relationship of one's alcohol use both to family environment and to the drinking behavior of the parents. However, most of these studies have used clinical samples. The participants in this study were from a non-clinical, college undergraduate sample (N = 206). The sample included 69% females and 31% males who were primarily Caucasian.A causal path model was used to assess the relationships between familial alcohol use, the perceptions of family environment, propensity for substance use, and actual alcohol use. Participants completed the Michigan Alcoholism Screening Test (MAST) for themselves, their parents, and one sibling. Family environment measures completed by participants included: the Children of Alcoholics Screening Test (CAST) to measure the "experience" of family alcohol use; the Family of Origin Scale (FOS) as a measure of the family affectional environment; and the Family Adaptability and Cohesion Scales (FACES Ill) as a measure of family structural and relational factors. The MacAndrew Scale (MAC) was completed to assess the propensity for substance use.A path analysis of the proposed model indicated that family alcohol use did not exert a significant direct effect on propensity for or actual use of alcohol, nor did it exert any significant effect on the family affectional environment. Each of these is a rather surprising result and contrary to results of previous studies. However, family alcohol use significantly affected the "experience" of living in such a family environment, especially when alcohol use became more problematic. Family alcohol use, mediated by this "experience," had significant effects on family structural components of leadership and control, as measured by FACES III. The "experience" of family alcohol use was significantly and negatively related to the affectional environment of the family. The indirect effects of this "experience" were significant only through the control component of family structure and direct effects this "experience" were significant only for actual use of alcohol. Propensity for use and actual use were also significantly related as was expected.Nearly 50% of the sample indicated a propensity for use (MAC > 24), actual problematic use of alcohol (MAST > 5), or both, when using the standard cutoff scores of these instruments. It appears that further analysis of family influences on these behaviors, especially those behaviors that create difficulties in life, is warranted. Treatment approaches have typically maintained that improved family affective and relational environments are primary treatment goals. That the affectional environment of the family was not significantly affected by familial use of alcohol was another unexpected outcome and also warrants further study.
Department of Counseling Psychology and Guidance Services

The aim of the study was to develop a culturally sensitive Grounded Theory of Navajo parenting for families who are living with Fetal Alcohol Syndrome (FAS)/Fetal Alcohol Effects (FAE). The research question was: What are the social and cultural factors and processes that Navajo families use to mange care for a child with FAS/FAE? The philosophical perspectives that guided the study were: the Navajo philosophy, or view of life; resilience (middle range theory); the Family Stress Theory; and the Resiliency Mode of Family Stress, Adjustment, and Adaptation. Resilience was used as the over arching conceptual perspective for the study. A Grounded Theory of Navajo Parenting emerged from the data. Key categories to support the emerging theory were identified. The core category was Versatility through Transcendence. The supporting categories were: Strategies for Managing Challenges; Transcendence in Parenting; Intergenerational Alcohol Abuse, Violence and Suffering; and Knowledge/Acquisition of Needs. The families described their stories of transcendence through substance abuse, suffering, and violence to be able to parent their children who were living with the primary and secondary challenges of prenatal alcohol exposures. Further research is needed to test and expand this emerging theory of Navajo parenting of children with FAS/FAE. The challenges that were related to FAS/FAE were more easily managed with patterns of resilience within the families. Factors that influenced family's abilities to parent will be disseminated to assist other families who are managing the problems associated with FAS/FAE.

This thesis pertains to the pathogenesis of alcoholic pancreatitis, a considerable burden in terms of morbidity, mortality and health related costs. It has long been known that only a minority of alcoholics develop clinically evident pancreatitis, suggesting that (an) additional trigger factor(s) is required to elicit overt disease. Endotoxin (lipopolysaccharide LPS), from gut-derived gram negative bacteria may be one such trigger factor, since alcoholics exhibit increased levels of serum endotoxin. In addition, the degree of endotoxinaemia has been reported to correlate with the severity of pancreatitis. Studies described in this thesis report, i) the development of a novel rodent model of alcoholic pancreatitis produced by challenging alcohol-fed animals with single or repeated doses of LPS. The animals exhibit features of both acute (acinar vacuolisation, necrosis, pancreatic oedema, haemorrhage and inflammatory infiltration) and chronic (acinar atrophy and pancreatic fibrosis) pancreatitis; ii) the reversion of pancreatic injury (including fibrosis) upon withdrawal of alcohol in the model and the persistence of pancreatic damage with continuation of alcohol feeding; iii) activation of pancreatic stellate cells (PSCs, known to play a central role in fibrogenesis) in vivo and in vitro by alcohol and LPS; iv) the inhibition of PSC apoptosis in vivo and in vitro upon exposure to alcohol and LPS and the induction of PSC apoptosis in vivo upon withdrawal of alcohol from the diet and v) the presence of LPS receptors TLR4 and CD14 on PSCs, which would explain the responsiveness of PSCs to LPS. Thus the work in this thesis provides strong evidence in support of endotoxin as a clinically relevant trigger factor for the initiation of alcoholic pancreatitis and as a factor that promotes disease progression. The thesis also provides the first experimental evidence to support the clinical reports of a beneficial effect of abstinence on chronic pancreatitis. Delineation of the mechanisms mediating the induction, progression and reversibility of alcoholic pancreatitis has the potential to direct the development of new therapeutic interventions for alcohol-related pancreatic injury.

Context: There are two ways that digital media may influence alcohol use. The first is commercial alcohol marketing. The second is user-created alcohol promotion, defined as content distributed through new media that promotes consumption, but independent of commercial marketing. This thesis explores how both types of content promote alcohol, what association there is between exposure and alcohol-related attitudes and behaviour, and the differences between marketing and user-created promotion. Method: A mixed method design was employed, divided into two studies. The first was a content analysis of the design features, topical references, and messages suggested about alcohol in digital marketing and user-created promotion on Facebook, Twitter, and YouTube. The second was a cross-sectional survey with young adults (n = 405). This measured awareness of, and participation with, digital marketing and user-created promotion, and the association with consumption, higher-risk drinking, brand recall, expectancies, and drinking motives. Results: The content analysis found that digital marketing had personalised designs which contained subtle and positive messages about consumption, whereas user-created promotion had simpler designs, displayed little ethical practice, and contained overt messages about higher-risk drinking. The cross-sectional survey found that young adults were aware of, and participating with, both digital marketing and user-created promotion, with exposure greater for the latter. Exposure to both types of content was positively associated with alcohol use, higher-risk consumption, and drinking intentions. User-created promotion had a stronger association with all outcomes than marketing. The association between exposure and consumption, for both types of content, was mediated through drinking motives and expectancies. Conclusion: Young adults are aware of, and participating with, a range of digital marketing and user-created promotion. That such exposure is associated with alcohol-related attitudes and behaviour highlights the potential of new media to influence alcohol consumption. Further research is required to better understand young people’s experience with digital media and the challenges of addressing online health risk messages.

Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2006.
Title from electronic title page (viewed Oct. 10, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Epidemiology, School of Public Health." Discipline: Epidemiology; Department/School: Public Health.

Poly(vinyl alcohol) (PVA) is a polymer used in numerous applications, principally those in which its high water solubility is a desirable asset. However there are also areas where PVA is limited by its inherent solubility (for example some specific environments in the biomedical field). This work has sought to overcome such limits by manipulating the surface of PVA in order to propose various means by which the surface solvent resistance might be increased while maintaining the bulk properties of the polymer. Both chemical and physical modifications have been tried and in each case progress has been made towards insolubilizing a single surface of the polymer when in film form. Grafting various species onto the surface of PVA was successfully performed. It is believed that such species bonded to the PVA via attachment to the hydroxyl groups (though this has not been proven conclusively). The data contained herein has led to the conclusion that the primary factor in reducing solubility this way is the removal of the hydroxyl groups, and not the attachment of specifically highly hydrophobic molecules. Introducing permanent cross-links into the surface region has been attempted via various routes. The data recorded shows promise however the system is far from optimised. The biggest challenge remaining is to optimise the depth of material cross-linked. Some steps have been made towards understanding and controlling this parameter though there is much scope for further investigation. The methods used have built on those used for bulk cross-linking and as such are new for the case of surface specific treatment. An interesting phenomenon in some semi-crystalline polymers reported in recent years is that of surface specific crystallization. This effect has been successfully induced and observed in PVA to produce what is believed to be a highly crystalline surface layer, and crystalline regions of PVA are generally accepted to be more water resistant than amorphous ones. In summary, in this work several surface-specific treatments for PVA have been trialled, providing options for post-film forming modification to reduce the surface water sensitivity whilst retaining the bulk properties of the polymer.

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Bachelors
Sciences
Psychology

This thesis is an analysis of a curriculum development process used to train youth workers to raise and respond to alcohol issues. Within an interpretivist framework, a seven-stage model of curriculum planning was developed. Stage 1 involved examination of the literature on youth work and alcohol and youth work training, an empirical needs assessment study (via a national survey and in-depth consultation in one youth service) and examination of the results in relation to the literature on young people and alcohol. Stage 2 used the stage 1 data to define the rationale, which in turn informed stages 3-5, formulation of aims and learning outcomes, learning activities and teaching resources. Stage 6, delivery, involved pilot courses in in- service and initial-training contexts. Illuminative evaluation was used to assess the training process (Stage 7) and its impact on youth worker practice. The staged model was found to be a practical curriculum development framework, particularly combined with an action-research approach. The study confirmed the importance of thorough training needs assessment, including the needs of service users. Youth workers were found to typically adopt a reactive approach to alcohol issues, which focused on individual young drinkers rather than structural determinants of alcohol-related harm. The pilot courses were successful in stimulating planned alcohol education initiatives. Features of training that enabled youth workers to tackle alcohol issues included: a clear rationale based on youth work principles, harm-reduction goals, understanding the place and meaning of alcohol in young people's lives, a practice focus and managerial support. The study discusses the implications of the findings for youth work training and informal education practice and suggests a strategy for fixture development of the alcohol training materials.

The thesis aims: - to analyse the extent of alcohol-related problems in Hungary, - to assess available policy options to reduce the incidence of alcohol-related problems - to understand Hungarian policy making in the alcohol field - to prepare recommendations for alcohol policy that are relevant to the Hungarian situation It consists of eight chapters. Chapters follow the aims by first introducing the target and the place of the study (Chapter 1), second providing evidence about the extent of alcohol related problems in Hungary and in comparison to other countries (Chapter 2), third summarising policy means to influence the incidence of alcohol related problems based on experiences of other countries and locate alcohol policy in the broader policy context (Chapter 3), then presenting the framework and the methods used for the analysis (Chapter 4), analysing the policy environment by looking at the legislative background (Chapter 5), the organisational structure and major alcohol policy movements of the past decades (Chapter 6), characteristics of public policy making in general and public health and alcohol policy making in particular (Chapter 7), and the current situation of alcohol policy through actors - their understanding, interests, influence, relation to each other and to specific alcohol policy instruments - (Chapter 8), finally summarising the findings and preparing feasible policy recommendations for Hungary (Chapter 9).

Dissertação de Mestrado em Nutrição Clínica apresentada à Faculdade de Ciências da Nutrição e Alimentação da Universidade do Porto
Resumo da tese: Enquadramento: O facto de o álcool ser o segundo componente alimentar com maior densidade energética sustenta a ideia de que consumos elevados ou mesmo moderados, a longo prazo, possam contribuir para o aumento da ingestão energética, e consequentemente conduzir a um aumento do índice de massa corporal dos indivíduos. A variabilidade da ingestão de álcool existente na população Portuguesa permite observar amplitudes de exposição suficientes para melhor estudar esta relação. Objectivo: Quantificação da associação entre a prevalência de obesidade e a ingestão de etanol, numa amostra urbana de adultos portugueses. Métodos: A amostra seleccionada aleatoriamente, era constituída por 2372 indivíduos adultos (mulheres e homens), na avaliação de obesidade total e por 2383 (mulheres e homens), na avaliação de obesidade central. Estes indivíduos faziam parte da coorte do estudo EPIPorto. Inquiridores treinados procederam à aplicação de um questionário estruturado e avaliação de parâmetros sócio-demográficos e antropométricos. Foi definida obesidade total como o Indice de massa corporal (IMC) peso (kg) /altura (m)2) igual ou superior a 30 kg.m2 e central valores de perímetro da cintura (PC) superior a 88 cm ou 102 cm, para mulheres e homens, respectivamente. A ingestão de etanol foi estimada através de um questionário semi-quantitativo de frequência de alimentos, previamente validado, referente ao ano anterior à entrevista, e ao longo da vida. Os indivíduos foram classificados em 4 classes de ingestão de etanol (g/dia): 0; 0, 1-15,0; 15,0; 30,0 nas mulheres e 0; 0,1-30,0; 30,1-60,0; 60,0 nos homens.
Thesis abstract: Background: The high alcohol consumption in Portugal, and the high energy content of alcoholic beverages, makes alcohol a potential contributor to the obesity. Objective: To evaluate the association between ethanol consumption and overall and central obesity in adults of an urban Portuguese population. Methods: This cross-sectional analysis included 2372 for evaluate overall obesity and 2383 for central obesity. The participants were randomly selected from Porto in-habitants (age: 18 years) enrolled in EPIPorto Study (1999-2003). Trained interviewers applied a questionnaire comprising information on social, demographic, behavioural characteristics, and anthropometrical measures were recorded. Data on ethanol intake were obtained by using a validated semi- quantitative food frequency questionnaire. Subjects were classified in to 4 classes of ethanol intake (g/day):0; 0.1-15.0; 15.1-30.0 ;: 30.0 in women and 0; 0.1-30.0; 30.1-60.0 ;: 60.0 in men. Overall obesity was considered when the body mass index (BMI) was: 30.0 kg/m2 , central obesity, if Waist Circumference (WC) was higher than 88 cm or 102 cm, for women and men respectively. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression with separate models fitted for sex. Results: Prevalence of ethanol intake higher than 30g/day for women and 60g/day for men, was 5.3% in obese women vs. 3.3% in non obese, and 28.4% in obese men vs. 15.8% in non obese. After adjustment for age, education, BMI, smoking, energy intake and sports practice, men who consumed more than 60g/day were more frequently obese (overall) comparing with non drinkers (OR=1.64, 95% CI: 1.33-5.22).

This thesis represents an attempt to study the effects of alcohol intoxication on emotional behaviour in normal individuals. The pharmacology of ethanol was reviewed briefly and a framework for the study of emotion and the effects of drinking on it was delineated within the general information processing paradigm. The experimental research carried out in this thesis concentrated on two aspects of emotional behaviour that have particularly attracted the interest of those investigating the effects of alcohol: sexual response and anxiety. In an experiment that used the Balanced Placebo Design alcohol was found to reduce the ability to voluntarily inhibit sexual response to erotic stimulation. The most likely explanation of this effect is an impairment of the cognitive processes necessary to suppress the physiological sexual reaction. A review of the literature reveals that a relatively high dose of alcohol (more than 0.8 g/kg) consistently reduces cardiac response to social stress. The effect of a lower dose was investigated. A repeated measures design was used in order to minimize the error variance due to the inter-individual variability in the effects of alcohol that it was thought had obscured the effect of low doses in previous studies. Despite the fact that the response to the social stress task habituated from the first to the second session, which complicated the results, this study provided some support to the thesis of the anxiety reducing effects of moderate doses of alcohol. In order to investigate the effects of alcohol on the primary response to stressing environmental stimuli, the psychophysiological response to high-intensity auditory stimulation was examined. Alcohol seemed to make subjects react to the stimuli in a more defensive, less receptive manner. This effect might have been caused by the blood alcohol concentration still increasing at the moment of the test.

The current thesis aimed to explore the relationship between disinhibition and alcohol consumption in non-dependent drinkers. Specifically, whether (dis)inhibition can be considered a ‘state’ variable, which is responsive to motivational biases, cues and training. It was examined whether any fluctuations in (dis)inhibition could influence subsequent ad-libitum alcohol consumption, in sober individuals (de Wit, 2009). Furthermore, the effects of beliefs about disinhibition, exclusively in relation to alcohol-seeking, were also examined with respect to possible effects on alcohol-seeking. These general research questions were examined in a heavy drinking, student population. Chapter One discussed in detail the relationship between disinhibition and alcohol consumption by examining evidence from relevant models of addiction. Chapter Two described the general methods used in the experimental chapters of the thesis. In the first experimental chapter (Chapter Three) individuals were primed with different motivational biases on how to respond on a stop-signal task, before ad-libitum consumption was measured. Different motivational biases led to group differences in inhibition performance, it was demonstrated that a restrained mental set led to a reduction in alcohol consumption in the laboratory. Expanding this finding, Chapter Four examined the effect of these motivational biases on neuropsychophysiological measures (Event Related Potentials and Source dipole analyses) of inhibitory control; associations between inhibition indices and ad-libitum consumption were discussed. Chapter Five set out to examine whether inhibitory control could be trained specifically to alcohol cues, and whether this training could serve to reduce alcohol consumption in the laboratory (Experiment One and Two) and outside the laboratory (Experiment One) in response to emerging research (Houben et al 2011a). Two different types of inhibition training, motor and oculomotor, were compared in this chapter. Results demonstrated some success for motor, but not oculomotor inhibition, in both training behaviour and reductions in alcohol consumption, highlighting the fundamental differences in these constructs. Chapter Six examined whether alcohol cues could cause disinhibition in heavy social drinkers, but found no evidence for cue-related disinhibition. However, some evidence for disinhibition and cue-reactivity was established and possible methodological issues discussed. In the final experimental chapter (Chapter Seven) restraint beliefs were examined in relation to ad-libitum alcohol consumption. It was found that beliefs could influence ad-libitum alcohol-seeking, however results were at first glance paradoxical to behavioural research. The overall results of this thesis offer some of the first experimental support for the causal relationship between state disinhibition and alcohol consumption in sober, non-dependent individuals. Support was offered for the theories of addiction that postulate the association between disinhibition and alcohol consumption, specifically recent models that suggest disinhibition is a state which can influence drinking behaviour. Finally, support for recent theories that suggest targeting controlled processes may serve to reduce alcohol consumption in populations at high risk for alcohol abuse.

Diss. Ph. D.--Geography--Berkeley--University of California, 1940. Titre de soutenance : Aboriginal drink areas in New Spain.
Bibliogr. p. 136-144. Bibliogr. des oeuvres de l'auteur p. 147-148. Index.

Alcohol dependence damages the brain through a multiplicity of factors including thiamine deficiency, liver disease, head injuries, and repeated episodes of alcohol withdrawal. Alcohol withdrawal is a potential opportunity for reducing damage as it is an intensive time of contact between doctors and patients. Pre-clinical models of alcohol dependence have demonstrated activation of microglia, resident tissue macrophages, and expression of cytokines and other inflammatory mediators both in the brain and peripheral blood during alcohol withdrawal. These changes were associated with neuronal death, and learning deficits. Similar processes may occur in man as increased microglial numbers, increased chemokine expression and raised circulating pro-inflammatory cytokines have been reported in alcohol dependence. The aim of the thesis was to characterise the peripheral cytokine profile during alcohol detoxification, to investigate whether there are relationships between peripheral cytokines and clinical features of alcohol withdrawal, to investigate neuroinflammation in alcohol dependence by using [11C]PBR28 Positron Emission Tomography to assess microglial activation in recently abstinent alcohol dependent patients in vivo and to investigate how these processes relate to elevated cortisol and elevated cerebral glutamate reported in alcohol withdrawal respectively. The longitudinal study undertaken in 51 alcohol dependent patients during detoxification demonstrated that both pro- and anti-inflammatory cytokines, and chemokines, decreased significantly during detoxification while T cell cytokines increase. IL-6 was positively associated with withdrawal severity and depressive symptoms during withdrawal. The chemokine CCL-2 was positively associated with performance on cognitive tasks. Serum cortisol was in the high normal range and decreased during detoxification. The salivary Cortisol Awakening Response (CAR) was also in the normal range at all time points. Both serum cortisol and the CAR were positively correlated with IL-6 concentrations suggesting hyperfunction of the HPA axis during alcohol detoxification may relate in part to inflammatory stimulation. The PET study comparing alcohol dependent men in early abstinence and healthy controls was undertaken using the ligand, [11C]PBR28 that binds to the Translocator Protein 18 kDa (TSPO) richly expressed in microglia. Alcohol dependent patients had lower TSPO binding in the hippocampi than healthy controls. TSPO binding in the hippocampus was also positively correlated with performance on tests of verbal memory. This suggests that hippocampal microglial loss or dysfunction may be related to memory problems in alcohol dependence. Given that benzodiazepines are used to treat alcohol withdrawal, an in vitro binding study was conducted to investigate whether benzodiazepines would significantly block [11C]PBR28 binding and found that benzodiazepines do not block a significant proportion of TSPO at all but the highest clinical doses. The relationship between brain glutamate, as measured with Magnetic Resonance Spectroscopy, and microglial activation was investigated. Alcohol dependent patients had significantly lower glutamate + glutamine (Glx) concentrations in the occipital cortex with no difference in glutamate concentrations in the anterior cingulate cortex (ACC). In summary, there are changes in both peripheral and brain inflammatory processes in early abstinence from alcohol dependence that are related to clinical symptoms. Peripheral pro-inflammatory cytokines are raised early in detoxification relative to late detoxification and are related to withdrawal and affective symptoms. Surprisingly, evidence of decreased microglial function in the hippocampus was found and this related to poorer cognitive function, suggesting a positive role for immune cells in the brain in alcohol dependence. Inflammatory processes were related to HPA axis function during detoxification but not to changes in brain glutamate concentrations. In conclusion, characterisation of inflammation through multiple approaches in this series of studies demonstrates the likely importance of such processes and provides novel approaches for treatment to reduce brain damage due to alcoholism.

Dissertação de Mestrado em Nutrição Clínica apresentada à Faculdade de Ciências da Nutrição e Alimentação da Universidade do Porto
Resumo da tese: Enquadramento: O facto de o álcool ser o segundo componente alimentar com maior densidade energética sustenta a ideia de que consumos elevados ou mesmo moderados, a longo prazo, possam contribuir para o aumento da ingestão energética, e consequentemente conduzir a um aumento do índice de massa corporal dos indivíduos. A variabilidade da ingestão de álcool existente na população Portuguesa permite observar amplitudes de exposição suficientes para melhor estudar esta relação. Objectivo: Quantificação da associação entre a prevalência de obesidade e a ingestão de etanol, numa amostra urbana de adultos portugueses. Métodos: A amostra seleccionada aleatoriamente, era constituída por 2372 indivíduos adultos (mulheres e homens), na avaliação de obesidade total e por 2383 (mulheres e homens), na avaliação de obesidade central. Estes indivíduos faziam parte da coorte do estudo EPIPorto. Inquiridores treinados procederam à aplicação de um questionário estruturado e avaliação de parâmetros sócio-demográficos e antropométricos. Foi definida obesidade total como o Indice de massa corporal (IMC) peso (kg) /altura (m)2) igual ou superior a 30 kg.m2 e central valores de perímetro da cintura (PC) superior a 88 cm ou 102 cm, para mulheres e homens, respectivamente. A ingestão de etanol foi estimada através de um questionário semi-quantitativo de frequência de alimentos, previamente validado, referente ao ano anterior à entrevista, e ao longo da vida. Os indivíduos foram classificados em 4 classes de ingestão de etanol (g/dia): 0; 0, 1-15,0; 15,0; 30,0 nas mulheres e 0; 0,1-30,0; 30,1-60,0; 60,0 nos homens.
Thesis abstract: Background: The high alcohol consumption in Portugal, and the high energy content of alcoholic beverages, makes alcohol a potential contributor to the obesity. Objective: To evaluate the association between ethanol consumption and overall and central obesity in adults of an urban Portuguese population. Methods: This cross-sectional analysis included 2372 for evaluate overall obesity and 2383 for central obesity. The participants were randomly selected from Porto in-habitants (age: 18 years) enrolled in EPIPorto Study (1999-2003). Trained interviewers applied a questionnaire comprising information on social, demographic, behavioural characteristics, and anthropometrical measures were recorded. Data on ethanol intake were obtained by using a validated semi- quantitative food frequency questionnaire. Subjects were classified in to 4 classes of ethanol intake (g/day):0; 0.1-15.0; 15.1-30.0 ;: 30.0 in women and 0; 0.1-30.0; 30.1-60.0 ;: 60.0 in men. Overall obesity was considered when the body mass index (BMI) was: 30.0 kg/m2 , central obesity, if Waist Circumference (WC) was higher than 88 cm or 102 cm, for women and men respectively. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression with separate models fitted for sex. Results: Prevalence of ethanol intake higher than 30g/day for women and 60g/day for men, was 5.3% in obese women vs. 3.3% in non obese, and 28.4% in obese men vs. 15.8% in non obese. After adjustment for age, education, BMI, smoking, energy intake and sports practice, men who consumed more than 60g/day were more frequently obese (overall) comparing with non drinkers (OR=1.64, 95% CI: 1.33-5.22).

Die These fasst die ersten Untersuchungen zum Pawlowsch`-Instrumentellen Transfer in alkoholabhängigen (AA) Patienten zusammen. Es ist bekannt, dass kontextuelle Umgebungsreize Verhalten beeinflussen. Tier- und Humanstudien haben gezeigt, dass positive Pawlowsche Reize instrumentelles Antwortverhalten verstärken und negative Pawlowsche Reize dieses reduzieren (PIT-Effekt). Bei Abhängigkeit wird angenommen, dass dieser Mechanismus relevant für Rückfall ist, da z.B. drogenassoziierte Reize bei Patienten im Vergleich zu Kontrollen erhöhtes Verlagen und funktionelle Aktivität in Belohnungsarealen auslösen. In Tier- und Humanstudien wurden stärkere PIT-Effekte vor allem mit funktioneller Aktivierung im Nucleus Accumbens (NAcc) beobachtet. Weiterhin zeigten sich bei Probanden mit stärkerem PIT-Effekt und bei AA Patienten erhöhte Impulsivitätswerte. Die PIT-Aufgabe besteht aus 3 Hauptteilen: i) Instrumentelle Konditionierung, ii) Pawlowsche Konditionierung, iii) Transfer mit Pawlowschen oder alkoholassoziierten Kontextstimuli. Impulsives Auswahlverhalten wurde durch die delay discounting Aufgabe erhoben. Es zeigten sich signifikant stärkere PIT-Effekte mit Pawlowschen Kontextreizen in AA Patienten im Vergleich zu Kontrollen mit funktioneller Aktivierung im NAcc, die zur Rückfallvorhersage beitrug. Der Transfer mit alkoholassoziierten Kontextreizen bewirkte eine signifikante Reduktion des instrumentellen Antwortverhaltens mit neuronalem Korrelat im NAcc nur bei abstinenten Patienten. Impulsives Auswahlverhalten und PIT hingen nur bei Patienten positiv zusammen. Die Studien lassen darauf schließen, dass PIT ein für Rückfall wichtiger Mechanismus ist mit funktionellem Korrelat im NAcc, der sich für motivationale Prozesse als auch als Salienzsignal relevant gezeigt hat. Die Subgruppe von hoch impulsiven Patienten ist im Besonderen durch Kontextreize im instrumentellen Antwortverhalten beeinflussbar, daher sollte ihr besondere Aufmerksamkeit bei Interventionen zukommen.
This thesis summarizes the first Pavlovian-to-instrumental transfer (PIT) studies in alcohol-dependent (AD) patients. Contextual stimuli are known to influence our behavior. Animal and human studies showed that positive Pavlovian stimuli enhance and negative Pavlovian stimuli reduce instrumental behavior (PIT effect). This mechanism might be relevant for relapse risk, as drug-associated stimuli have shown to enhance e.g. craving and functional activation in reward-related brain areas in patients compared to controls. In animal and human studies enhanced PIT effects were associated with activation particularly in the nucleus accumbens (NAcc). Moreover, control subjects with stronger PIT effects and AD patients were more impulsive on different facets of impulsivity. The PIT task consists of three main parts: i) instrumental conditioning, ii) Pavlovian conditioning, iii) transfer with Pavlovian background stimuli and instrumental task in the foreground (nondrug-related PIT: Pavlovian contextual cues; drug-related PIT: alcohol-related contextual cues). Choice impulsivity was measured by delay discounting task. We observed significantly enhanced nondrug-related PIT effects in AD patients compared to controls with a functional activation in the NAcc being predictive for relapse. Regarding drug-related PIT effects, we observed significantly reduced instrumental behavior during alcohol-related backgrounds with neural correlates in the NAcc in abstainers only. Choice impulsivity was positively related to PIT in AD patients only. Our data suggest that PIT is a mechanism contributing to relapse in AD patients with functional correlations within the NAcc, which based on our data is involved in motivation and attribution of salience. The subgroup of high impulsive patients is particularly susceptible for PIT effects, thus should be main target for intervention programs.

Thesis (M.A.)--University of Missouri-Columbia, 2007.
The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on November 5, 2007) Includes bibliographical references.

We live in an environment in which alcohol is easily available and widely marketed. Alcohol advertising has been shown to increase long-term and short-term alcohol consumption. On the other hand, governments and industry use warning labels and public health campaigns to inform the public of the harmful effects of alcohol in an attempt reduce alcohol-related harm. There is not much evidence that labels and campaigns affect drinking behaviour, but evidence from other domains suggests that individual differences in attentional processing might moderate effects on behaviour. In this thesis, I tested the general hypothesis that individual differences in visual attention to alcohol cues and responsible drinking statements would underlie the effect of alcohol-related mass persuasion attempts (i.e., alcohol advertisements, warning labels and public health campaigns) on drinking behaviour and its antecedents, in young adult alcohol consumers. The secondary aim of this thesis was to examine the direct effect of alcohol-related mass persuasion attempts on drinking intentions and alcohol consumption shortly after exposure. To study this, I first conducted a cross-sectional study and a between-subjects experimental study to investigate attention to warning labels on alcohol packaging and examine whether priming participants to direct their attention to warning labels would prompt them to intend to drink less alcohol. Findings suggested that existing UK warning labels did not attract substantial attention and the amount of attention that participants directed to them did not affect their drinking intentions (Chapter 2). I subsequently conducted three experimental studies to examine to what extent novel warning labels would capture attention and affect willingness to pay for alcohol. Findings showed that novel warning labels did not attract more attention than existing warning labels, nor did they significantly influence willingness to pay for alcohol (Chapter 3). With regard to televised alcohol advertisements, I conducted a between-subjects experiment in a semi-naturalistic environment to investigate whether alcohol advertising affected proximal alcohol consumption in a brand-specific or general manner. Results suggested that alcohol advertising did not affect drinking behaviour, however methodological limitations mean that these findings should be interpreted with caution (Chapter 4). Next, I conducted two experimental studies to examine how individual differences in visual attention to alcohol cues and responsible drinking statements in alcohol-related television adverts predicted drinking intentions and proximal alcohol consumption. Findings showed that attention to responsible drinking statements did not predict drinking intentions or immediate alcohol consumption, but visual attention to alcohol portrayal (an actor sipping alcohol) in alcohol advertising predicted increased alcohol consumption in the laboratory (Chapter 5). Overall, these findings demonstrate that responsible drinking statements/labels attract limited attention and that increased attention to these labels does not prompt alcohol consumers to intend to reduce their drinking. I found no evidence that alcohol-related persuasion affected immediate alcohol consumption or drinking intentions, but attentional processing of alcohol portrayal in alcohol advertising was associated with increased alcohol consumption shortly after exposure to the adverts. Finally, I conducted a focus group study to explore subjective evaluations of current warning labels and responsible drinking adverts Findings showed that participants did not consider warning labels/adverts to be personally relevant and that they mistrusted the message source. Instead, participants suggested that warning messages focussing on alcohol-related harm (to themselves or others) might be more persuasive. Combined with the findings from the laboratory studies, these findings suggest responsible drinking statements could attract more attention if their content and format were changed. The findings reported in this thesis further our understanding of the role of attention in alcohol-related persuasion. In line with recently published evaluations of public health campaigns and warning labels, these studies suggest that warnings in alcohol advertising and on packaging in their current form have little scope for changing drinking behaviour. Instead, it might be more fruitful to increase the noticeability of warning labels and impose restrictions on alcohol marketing and/or the visual content used within alcohol marketing.

L'auteur n'a pas fourni de résumé en français
Key to alleviating the terrible costs of human violence and aggression are identifying and understanding key pharmacological moderators of human aggression. Two primary pharmacological candidates known to influence aggression are alcohol, the intoxicating ingredient of many popular beverages, and serotonin, a class of neurotransmitters important in behavioral regulation. I present four complementary investigations into these two pharmacological targets, examining respectively: (1) the interaction between aggressive personality features and alcohol intoxication, (2) alcohol’s influence on moral reasoning in the face of moral dilemmas involving the use of aggression, (3) the size and strength of the relationship between central serotonin activity and various measures of human aggression, and finally, (4) the ability of Omega-3 supplementation to attenuate aggression via its impact on serotonergic functioning

L'alcool est la première cause de maladie hépatique en France, et la maladie alcoolique du foie est responsable de près de 7000 décès par an. La surcharge graisseuse est la troisième cause de maladie hépatique, et s'inscrit dans le cadre plus large du syndrome métabolique. La physiopathologie de ces deux types de maladies hépatiques est très similaire. La stéatose, définie par l'accumulation excessive de triglycérides dans le foie, est la première lésion retrouvée chez les patients. La stéatose peut évoluer vers la stéato‐hépatite lorsqu'elle est associée à une inflammation, une mort hépatocytaire, et à l'initiation d'une réponse fibrogénique. La stéato‐hépatite évolue parfois vers la cirrhose, stade ultime avant le carcinome hépatocellulaire. Il n'existe à ce jour aucun traitement efficace de ces maladies hormis le sevrage alcoolique dans le cadre de la maladie alcoolique du foie et un régime associé à de l'exercice dans le cadre de la maladie hépatique d'origine non‐alcoolique. Il est donc urgent d'identifier de nouvelles stratégies thérapeutiques pour lutter contre la progression de ces maladies.L'activation des cellules de Küpffer, les macrophages résidents du foie, joue un rôle déterminant dans le processus inflammatoire qui initie l'atteinte hépatique. Comme tous les macrophages, les cellules de Küpffer peuvent adopter tout un spectre de phénotypes parmi lesquels on distingue deux extrêmes : le phénotype M1 ou pro‐inflammatoire et le phénotype M2 ou anti‐inflammatoire. Les données de la littérature ainsi que celles préalablement obtenues par le laboratoire d'accueil ont établi les effets délétères d'une polarisation pro‐inflammatoire M1 des cellules de Küpffer sur l'évolution de la maladie hépatique d'origine alcoolique ou non alcoolique. Cependant, aucune étude n'avait examiné l'impact d'une polarisation anti‐inflammatoire (M2) des cellules de Küpffer sur ces maladies.L'objectif de ce travail a été d'évaluer si favoriser la polarisation des cellules de Küpffer vers un phénotype M2 anti‐inflammatoire pouvait limiter la progression des maladies hépatiques d'origine alcoolique ou non alcoolique.Afin de mener à bien ce projet, nous avons combiné l'utilisation de modèles murins de maladie hépatique d'origine alcoolique ou non alcoolique, des approches pharmacologiques et des expériences sur cellules isolées. Ces études ont été complétées par des données obtenues sur des biopsies humaines.Ce travail a permis de démontrer que favoriser la polarisation M2 des cellules de Küpffer protège le foie de la stéatose, de la mort hépatocytaire et de l'inflammation. Ces résultats identifient un nouveau mécanisme anti‐inflammatoire déclenché par les cellules de Küpffer polarisées M2 : l'induction sélective de l'apoptose des cellules de Küpffer polarisées M1. Ce travail ouvre de nouvelles perspectives à l'identification de stratégies pour limiter la progression des maladies hépatiques et pourrait également avoir des retombées plus larges dans le cadre d'autres maladies chroniques inflammatoires ciblant d'autres tissus que le foie
Summary not transmitted

Diss. (sammanfattning) Stockholm : Stockholms universitet, 2010.
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: In press. Paper 2: Submitted. Paper 3: Submitted. Härtill 4 uppsatser.

Earlier ages of alcohol initiation have been associated with an increased vulnerability for Alcohol Use Disorder and general risk taking behaviors beyond genetic influence. Reward processes, including reward anticipation (pleasure before receiving alcohol/general reward), reward learning (how quickly one pairs a stimulus with alcohol/general reward), and reward consummation (pleasure when receiving alcohol/general reward), have been implicated as potential mechanisms accounting for this vulnerability. However, no careful bio-behavioral research has been conducted on the effect of age of alcohol initiation on general and alcohol-related reward processes. Using Event Related Potentials (ERPs), the current study addressed this gap in a sample of 123 current alcohol drinkers. The Monetary Incentive Delay-General task and Monetary Incentive Delay-Alcohol task were administered to participants, in which reward learning (quickness of pairing the neutral cue or alcohol cue with monetary feedback), reward anticipation (activity to neutral cue or alcohol cue), and reward consummation (activity to monetary feedback) were examined. Electroencephalography was used to collect ERPs that index reward anticipation (P3) and reward consummation (P3 and Late Positive Potential) during these tasks. Earlier ages of alcohol initiation were associated with increased alcohol-related reward learning and decreased alcohol-related reward consummation (P3 and Late Positive Potential) beyond genetic and environmental covariates. There were no other significant relationships. These findings support and extend alcohol theories by showing that earlier ages of alcohol initiation may foster a greater sensitization in alcohol-specific reward-learning and more pronounced decreases in alcohol-related consummation. Although in need of direct testing, this might explain why earlier ages of alcohol initiation are associated with an increased vulnerability to Alcohol Use Disorder.