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Description
Research has shown that a developmental process of maturing out of alcohol involvement occurs during young adulthood, and that this process is related to both young adult role transitions (e.g., marriage) and personality developmental (e.g., decreased disinhibition and neuroticism). The current study extended past research by testing whether protective marriage and personality effects on maturing out were stronger among more severe late adolescent drinkers, and whether protective marriage effects were stronger among those who experienced more personality development. Parental alcoholism and gender were tested as moderators of marriage, personality, and late adolescent drinking effects on maturing out; and as distal predictors mediated by these effects. Participants were a subsample (N = 844; 51% children of alcoholics; 53% male, 71% non-Hispanic Caucasian, 27% Hispanic; Chassin, Barrera, Bech, & Kossak-Fuller, 1992) from a larger longitudinal study of familial alcoholism. Hypotheses were tested with latent growth models characterizing alcohol consumption and drinking consequence trajectories from late adolescence to adulthood (age 17-40). Past findings were replicated by showing protective effects of becoming married, sensation-seeking reductions, and neuroticism reductions on the drinking trajectories. Moderation tests showed that protective marriage effects on the drinking trajectories were stronger among those with higher pre-marriage drinking in late adolescence (i.e., higher growth intercepts). This might reflect role socialization mechanisms such that more severe drinking produces more conflict with the demands of new roles (i.e., role incompatibility), thus requiring greater drinking reductions to resolve this conflict. In contrast, little evidence was found for moderation of personality effects by late adolescent drinking or for moderation of marriage effects by personality. Parental alcoholism findings suggested complex moderated mediation pathways. Parental alcoholism predicted less drinking reduction through decreasing the likelihood of marriage (mediation) and muting marriage's effect on the drinking trajectories (moderation), but parental alcoholism also predicted more drinking reduction through increasing initial drinking in late adolescence (mediation). The current study provides new insights into naturally occurring processes of recovery during young adulthood and suggests that developmentally-tailored interventions for young adults could harness these natural recovery processes (e.g., by integrating role incompatibility themes and addressing factors that block role effects among those with familial alcoholism).
ContributorsLee, Matthew R. (Author) / Chassin, Laurie (Thesis advisor) / Corbin, William R. (Committee member) / Mackinnon, David P (Committee member) / Presson, Clark C. (Committee member) / Arizona State University (Publisher)
Created2013
Description
Past literature has indicated that the majority of people with alcohol problems never seek treatment and that this is especially true of women. Relatively few studies have investigated how different types of alcohol-related consequences longitudinally predict men and women's perceived need for treatment and their utilization of treatment services. The current study sought to expand the literature by examining whether gender moderates the links between four frequently endorsed types of consequences and perceived need for or actual utilization of treatment. Two-hundred thirty-seven adults ages 21-36 completed a battery of questionnaires at two time points five years apart. Results indicated that there were four broad types of consequences endorsed by both men and women. Multiple-group models and Wald chi square tests indicated that there were no significant relationships between consequences and treatment outcomes. No gender moderation was found but post-hoc power analyses indicated that the study was underpowered to detect moderation. Researchers need to continue to study factors that predict utilization of alcohol treatment services and the process of recovery so that treatment providers can better address the needs of people with alcohol-related consequences in the areas of referral procedures, clinical assessment, and treatment service provision and planning.
ContributorsBeltran Gonzalez, Iris (Author) / Chassin, Laurie (Thesis advisor) / Tein, Jenn-Yun (Committee member) / Corbin, William (Committee member) / Barrera, Jr., Manuel (Committee member) / Arizona State University (Publisher)
Created2013
Description
Juvenile offenders suffer from substance use disorders at higher rates than adolescents in the general public. Substance use disorders also predict an increased risk for re-offending. Therefore, it is important that these juveniles, in particular, receive the appropriate substance use disorder treatment. The present study used logistic regression to test whether race/ethnicity would moderate the match between substance use disorder diagnosis and the receipt of a substance use disorder related service in a sample of male, serious juvenile offenders. Results showed that among those with a substance use disorder diagnosis, there were no race/ethnicity differences in the receipt of the appropriate service. However, among those without a substance use disorder diagnosis, non-Hispanic Caucasians were more likely to receive substance use service than were Hispanics or African-Americans. Post-hoc analyses revealed that when using a broader definition of substance use problems, significant differences by race/ethnicity in the prediction of service receipt were only observed at low levels of substance use problems. These findings shed light on how race/ethnicity may play a role in the recommendation of substance use disorder services in the juvenile justice system.
ContributorsMansion, Andre (Author) / Chassin, Laurie (Thesis advisor) / Dishion, Thomas (Committee member) / Knight, George (Committee member) / Arizona State University (Publisher)
Created2013
Description
Random peptide microarrays are a powerful tool for both the treatment and diagnostics of infectious diseases. On the treatment side, selected random peptides on the microarray have either binding or lytic potency against certain pathogens cells, thus they can be synthesized into new antimicrobial agents, denoted as synbodies (synthetic antibodies). On the diagnostic side, serum containing specific infection-related antibodies create unique and distinct "pathogen-immunosignatures" on the random peptide microarray distinct from the healthy control serum, and this different mode of binding can be used as a more precise measurement than traditional ELISA tests. My thesis project is separated into these two parts: the first part falls into the treatment side and the second one focuses on the diagnostic side. My first chapter shows that a substitution amino acid peptide library helps to improve the activity of a recently reported synthetic antimicrobial peptide selected by the random peptide microarray. By substituting one or two amino acids of the original lead peptide, the new substitutes show changed hemolytic effects against mouse red blood cells and changed potency against two pathogens: Staphylococcus aureus and Pseudomonas aeruginosa. Two new substitutes are then combined together to form the synbody, which shows a significantly antimicrobial potency against Staphylococcus aureus (<0.5uM). In the second chapter, I explore the possibility of using the 10K Ver.2 random peptide microarray to monitor the humoral immune response of dengue. Over 2.5 billion people (40% of the world's population) live in dengue transmitting areas. However, currently there is no efficient dengue treatment or vaccine. Here, with limited dengue patient serum samples, we show that the immunosignature has the potential to not only distinguish the dengue infection from non-infected people, but also the primary dengue infection from the secondary dengue infections, dengue infection from West Nile Virus (WNV) infection, and even between different dengue serotypes. By further bioinformatic analysis, we demonstrate that the significant peptides selected to distinguish dengue infected and normal samples may indicate the epitopes responsible for the immune response.
ContributorsWang, Xiao (Author) / Johnston, Stephen Albert (Thesis advisor) / Blattman, Joseph (Committee member) / Arntzen, Charles (Committee member) / Arizona State University (Publisher)
Created2013
Description
Levels of heavy episodic drinking peak during emerging adulthood and contribute to the experience of negative consequences. Previous research has identified a number of trait-like personality characteristics that are associated with drinking. Studies of the Acquired Preparedness Model have supported positive expectancies, and to a lesser extent negative expectancies, as mediators of the relation between trait-like characteristics and alcohol outcomes. However, expectancies measured via self-report may reflect differences in learned expectancies in spite of similar alcohol-related responses, or they may reflect true individual differences in subjective responses to alcohol. The current study addressed this gap in the literature by assessing the relative roles of expectancies and subjective response as mediators within the APM in a sample of 236 emerging adults (74.7% male) participating in a placebo-controlled alcohol challenge study. The study tested four mediation models collapsed across beverage condition as well as eight separate mediation models with four models (2 beverage by 2 expectancy/subjective response) for each outcome (alcohol use and alcohol-related problems). Consistent with previous studies, SS was positively associated with alcohol outcomes in models collapsed across beverage condition. SS was also associated with positive subjective response in collapsed models and in the alcohol models. The hypothesized negative relation between SS and sedation was not significant. In contrast to previous studies, neither stimulation nor sedation predicted either weekly drinking or alcohol-related problems. While stimulation and alcohol use appeared to have a positive and significant association, this relation did not hold when controlling for SS, suggesting that SS and stimulation account for shared variability in drinking behavior. Failure to find this association in the placebo group suggests that, while explicit positive expectancies are related to alcohol use after controlling for levels of sensation seeking, implicit expectancies (at least as assessed by a placebo manipulation) are not. That the relation between SS and stimulation held only in the alcohol condition in analyses separate by beverage condition indicates that sensation seeking is a significant predictor of positive subjective response to alcohol (stimulation), potentially above and beyond expectancies.
ContributorsScott, Caitlin (Author) / Corbin, William (Thesis advisor) / Shiota, Michelle (Committee member) / Chassin, Laurie (Committee member) / Arizona State University (Publisher)
Created2012
Description
The hypothalamus pituitary adrenal (HPA) axis and the human genome are important components of the biological etiology of externalizing disorders. By studying the associations between specific genetic variants, diurnal cortisol, and externalizing symptoms we can begin to unpack this complex etiology. It was hypothesized that genetic variants from the corticotropine releasing hormone receptor 1 (CRHR1), FK506 binding protein 51 (FKBP5), catechol-O-methyl transferase (COMT), and dopamine transporter (DAT1) genes and diurnal cortisol intercepts and slopes would separately predict externalizing symptoms. It was also hypothesized that genetic variants would moderate the association between cortisol and externalizing. Participants were 800 twins (51% boys), 88.5% Caucasian, M=7.93 years (SD=0.87) participating in the Wisconsin Twin Project. Hierarchical Linear Modeling (HLM) was used to separate the variance associated with state and trait cortisol measured across three consecutive days and trait cortisol measures were used. There were no main effects of genes on externalizing symptoms. The evening cortisol intercept, the morning cortisol slope and the evening cortisol slope predicted externalizing, but only in boys, such that boys with higher cortisol and flatter slopes across the day also had more externalizing symptoms. The morning cortisol intercept and CRHR1 rs242924 interacted to predict externalizing in both boys and girls, with GG carriers significantly higher compared to TT carriers at one standard deviation below the mean of morning cortisol. For boys only there was a significant interaction between the DAT1 variable number tandem repeat (VNTR) and the afternoon slope and a significant slope for 9/9 carriers and 9/10 carriers such that when the slope was more steep, boys carrying a nine had fewer externalizing symptoms but when the slope was less steep, they had more. Results confirm a link between diurnal trait cortisol and externalizing in boys, as well as moderation of that association by genetic polymorphisms. This is the first study to empirically examine this association and should encourage further research on the biological etiology of externalizing disorder symptoms.
ContributorsSwann, Gregory (Author) / Lemery-Chalfant, Kathryn (Thesis advisor) / Chassin, Laurie (Committee member) / Doane-Sampey, Leah (Committee member) / Arizona State University (Publisher)
Created2012
Description
Although research has documented robust prospective relationships between externalizing symptomatology and subsequent binge drinking among adolescents, the extent to which internalizing symptoms increase risk for drinking remains controversial. In particular, the role of anxiety as a predictor of binge drinking remains unclear. Recent evidence suggests that one possible reason for these mixed findings is that separate dimensions of anxiety may differentially confer risk for alcohol use. The present study tested two dimensions of anxiety - worry and physiological anxiety -- as predictors of binge drinking in a longitudinal study of juvenile delinquents. Overall, results indicate that worry and physiological anxiety showed differential relations with drinking behavior. In general, worry was protective against alcohol use, whereas physiological anxiety conferred risk for binge drinking, but both effects were conditional on levels of offending. Implications for future research examining the role of anxiety in predicting drinking behavior among youth are discussed.
ContributorsNichter, Brandon (Author) / Chassin, Laurie (Thesis advisor) / Barrera, Manuel (Committee member) / Presson, Clark (Committee member) / Arizona State University (Publisher)
Created2014
Description
The majority of non-small cell lung cancer (NSCLC) patients (70%) are diagnosed with adenocarcinoma versus other histological subtypes. These patients often present with advanced, metastatic disease and frequently relapse after treatment. The tumor suppressor, Liver Kinase B1, is frequently inactivated in adenocarcinomas and loss of function is associated with a highly aggressive, metastatic tumor (1). Identification of the mechanisms deregulated with LKB1 inactivation could yield targeted therapeutic options for adenocarcinoma patients. Re-purposing the immune system to support tumor growth and aid in metastasis has been shown to be a feature in cancer progression (2). Tumor associated macrophages (TAMs) differentiate from monocytes, which are recruited to the tumor microenvironment via secretion of chemotaxic factors by cancer cells. We find that NSCLC cells deficient in LKB1 display increased secretion of C-C motif ligand 2 (CCL2), a chemokine involved in monocyte recruitment. To elucidate the molecular pathway regulating CCL2 up-regulation, we investigated inhibitors of substrates downstream of LKB1 signaling in A549, H23, H2030 and H838 cell lines. Noticeably, BAY-11-7082 (NF-κB inhibitor) reduced CCL2 secretion by an average 92%. We further demonstrate that a CCR2 antagonist and neutralizing CCL2 antibody substantially reduce monocyte migration to NSCLC (H23) cell line conditioned media. Using an in vivo model of NSCLC, we find that LKB1 deleted tumors demonstrate a discernible increase in CCL2 levels compared to normal lung. Moreover, tumors display an increase in the M2:M1 macrophage ratio and increase in tumor associated neutrophil (TAN) infiltrate compared to normal lung. This M2 shift was significantly reduced in mice treated with anti-CCL2 or a CCR2 antagonist and the TAN infiltrate was significantly reduced with the CCR2 antagonist. These data suggest that deregulation of the CCL2/CCR2 signaling axis could play a role in cancer progression in LKB1 deficient tumors.
ContributorsFriel, Jacqueline (Author) / Inge, Landon (Thesis advisor) / Lake, Douglas (Thesis advisor) / Blattman, Joseph (Committee member) / Arizona State University (Publisher)
Created2015
Description
The present study tested the factor structure of the externalizing disorders (e.g. attention-deficit hyperactivity disorder (ADHD), conduct disorder (SE), and substance experimentation (SE) ) in adolescence. In addition, this study tested the influence of the GABRA2 gene on the factors of the externalizing spectrum. Confirmatory factor analyses were used to test the factor structure of the externalizing spectrum. Specifically, three competing alternate confirmatory factor analytic models were tested: a one-factor model where all disorders loaded onto a single externalizing factor, a two-factor model where CD and SE loaded onto one factor and ADHD loaded onto another, and a three-factor model, where all three disorders loaded onto separate factors. Structural equation modeling was used to test the effect of a GABRA2 SNP, rs279858, on the factors of the externalizing spectrum. Analyses revealed that a three-factor model of externalizing disorders with correlated factors fit the data best. Additionally, GABRA2 had a significant effect on the SE factor in adolescence, but not on the CD or ADHD factors. These findings demonstrate that the externalizing disorders in adolescence share commonalities but also have separate sources of systematic variance. Furthermore, biological mechanisms may act as a unique etiological factor in the development of adolescent substance experimentation.
ContributorsWang, Frances L (Author) / Chassin, Laurie (Thesis advisor) / Lemery-Chalfant, Kathryn (Committee member) / Geiser, Christian (Committee member) / Arizona State University (Publisher)
Created2012
Description
Research shows that general parenting practices (e.g., support and discipline), influence adolescent substance use. However, socialization theory suggests that parental socialization occurs not only through general parenting practices, but also through parents' attempts to influence specific behaviors and values. A growing literature supports links between substance-specific parenting and adolescent substance use. For adolescent alcohol use, there are considerable limitations and gaps within this literature. To address these limitations, the present study examined the factor structure of alcohol-specific parenting, investigated the determinants of alcohol-specific parenting, and explored its association with nondrinking adolescents' attitudes about alcohol use. Using a high-risk sample of nondrinking adolescents and their parents, the current study found three dimensions of alcohol-specific parenting using both adolescent and parent reports, but also found evidence of non-invariance across reporters. Results also revealed complex roles of parental alcohol use disorder (AUD; including recovered and current AUD), family history of AUD, and current drinking as determinants of the three dimensions of anti-alcohol parenting behaviors. Moreover, the current study showed that the effects of these determinants varied by the reporter of the parenting behavior. Finally, the current study found the dimensions of alcohol-specific parenting to be unique and significant predictors of nondrinking adolescents' attitudes about alcohol, over and above general parenting practices, parent AUD, and parent current drinking. Given its demonstrated distinctness from general parenting practices, its link with adolescent alcohol attitudes, and its potential malleability, alcohol-specific parenting may be an important complement to interventions targeting parents of adolescents.
ContributorsHandley, Elizabeth D (Author) / Chassin, Laurie (Thesis advisor) / MacKinnon, David (Committee member) / Crnic, Keith (Committee member) / Sandler, Irwin (Committee member) / Arizona State University (Publisher)
Created2012