Gender differences in behavioral and psychosocial correlates of substance abuse among adolescents in residential treatment

This dissertation reports the results of a study that examined differences between genders in a sample of adolescents from a residential substance abuse treatment facility. The sample included 72 males and 65 females, ages 12 through 17. The data were archival, having been originally collected for a study of elopement from treatment. The current study included 23 variables. The variables were from multiple dimensions, including socioeconomic, legal, school, family, substance abuse, psychological, social support, and treatment histories. Collectively, they provided information about problem behaviors and psychosocial problems that are correlates of adolescent substance abuse. The study hypothesized that these problem behaviors and psychosocial problems exist in different patterns and combinations between genders.^ Further, it expected that these patterns and combinations would constitute profiles important for treatment. K-means cluster analysis identified differential profiles between genders in all three areas: problem behaviors, psychosocial problems, and treatment profiles. In the dimension of problem behaviors, the predominantly female group was characterized as suicidal and destructive, while the predominantly male group was identified as aggressive and low achieving. In the dimension of psychosocial problems, the predominantly female group was characterized as abused depressives, while the male group was identified as asocial, low problem severity. A third group, neither predominantly female or male, was characterized as social, high problem severity. When these dimensions were combined to form treatment profiles, the predominantly female group was characterized as abused, self-harmful, and social, and the male group was identified as aggressive, destructive, low achieving, and asocial. Finally, logistic regression and discriminant analysis were used to determine whether a history of sexual and physical abuse impacted problem behavior differentially between genders. Sexual abuse had a substantially greater influence in producing self-mutilating and suicidal behavior among females than among males. Additionally, a model including sexual abuse, physical abuse, low family support, and low support from friends showed a moderate capacity to predict unusual harmful behavior (fire-starting and cruelty to animals) among males. Implications for social work practice, social work research, and systems science are discussed. ^

Mitochondrial inheritance during a parasexual cycle in {\it Fusarium oxysporum\/} forma specialis {\it cubense\/}

Fusarium oxysporum is a diverse, asexual fungal species composed of both saprophytic and pathogenic members. The destructive phytopathogens are classified into formae speciales based on the host species and into vegetative compatibility groups (VCGs) based on the ability of two individuals to form heterokaryons. Parasexuality, a non-sexual mode of genetic exchange unique to some fungi has been demonstrated in the laboratory in Fusarium oxysporum f. sp. cubense (FOC). The goals of this dissertation were threefold: to ascertain whether mitochondrial (mt) markers can distinguish race differences in FOC; to determine genetic relatedness of VCGs in FOC based on a mt marker; and to discover the mode of mt inheritance during a parasexual cycle.^ Band patterns produced by electrophoresis of Hae III digested genomic DNA indicated that VCG differences, not race, could be discerned by mtDNA analysis. Primers were designed to amplify a mt intergenic locus which served as a molecular marker to screen 55 strains of FOC in 16 VCGs using both single strand conformational polymorphism and DNA sequencing. Based on homogeneity of the locus, strains were assigned to seven mitotypes, a classification unit which I introduced and found informative for grouping related VCGs.^ To determine the mode of mt inheritance during a parasexual cycle, strains in different mitotypes were paired. Mitochondrial inheritance in all hybrid progeny was found to be uniparental. I speculated that if a parasexual cycle occurs in nature there would be greater variation in the nuclear genome than the mt. This could produce multiple VCGs within a mitotype, a phenomenon observed in FOC. Based on these data, I concluded that parasexuality in nature may contribute to the diversity observed in Fusarium oxysporum. ^

Life cycle of Deccan trap magma chambers: A crystal scale elemental and strontium isotopic investigation

The Deccan Trap basalts are the remnants of a massive series of lava flows that erupted at the K/T boundary and covered 1-2 million km2 of west-central India. This eruptive event is of global interest because of its possible link to the major mass extinction event, and there is much debate about the duration of this massive volcanic event. In contrast to isotopic or paleomagnetic dating methods, I explore an alternative approach to determine the lifecycle of the magma chambers that supplied the lavas, and extend the concept to obtain a tighter constraint on Deccan’s duration. My method relies on extracting time information from elemental and isotopic diffusion across zone boundaries in individual crystals. I determined elemental and Sr-isotopic variations across abnormally large (2-5 cm) plagioclase crystals from the Thalghat and Kashele “Giant Plagioclase Basalts” from the lowermost Jawhar and Igatpuri Formations respectively in the thickest Western Ghats section near Mumbai. I also obtained bulk rock major, trace and rare earth element chemistry of each lava flow from the two formations. Thalghat flows contain only 12% zoned crystals, with 87 Sr/86Sr ratios of 0.7096 in the core and 0.7106 in the rim, separated by a sharp boundary. In contrast, all Kashele crystals have a wider range of 87Sr/86Sr values, with multiple zones. Geochemical modeling of the data suggests that the two types of crystals grew in distinct magmatic environments. Modeling intracrystalline diffusive equilibration between the core and rim of Thalghat crystals led me to obtain a crystal growth rate of 2.03x10-10 cm/s and a residence time of 780 years for the crystals in the magma chamber(s). Employing some assumptions based on field and geochronologic evidence, I extrapolated this residence time to the entire Western Ghats and obtained an estimate of 25,000–35,000 years for the duration of Western Ghats volcanism. This gave an eruptive rate of 30–40 km3/yr, which is much higher than any presently erupting volcano. This result will remain speculative until a similarly detailed analytical-modeling study is performed for the rest of the Western Ghats formations.

Differences in treatment and intervention needs of girls arrested for status versus criminal offenses

The purpose of this research was to explore the differences in factors associated with girls' status and criminal arrests. This study used data from six juvenile justice programs in multiple states, which was derived from the Juvenile Assessment and Intervention System (JAIS). The sample of 908 adolescent girls (ages 13-19) was ethnically and racially diverse (41% African American, 32% white, 12% Hispanic, 11% Native American and 4% Other). A structural equation model (SEM) was analyzed which tested the potential effects of adolescent substance use, truancy, suicidal ideation/attempt, self-harm, peer legal trouble, parental criminal history and parental and non-parental abuse on type of offense (status and criminal) and whether any of these relationships varied as a function of race/ethnicity. ^ Complex relationships emerged regarding both status and more serious criminal arrests. One of the most important findings was that distinct and different patterns of factors were associated with status arrests compared to criminal arrests. For example, truancy and parental abuse were directly associated with status offenses, whereas parental criminal history was directly related to criminal arrests. However, both status and criminal arrests shared common associations, including substance use, which signifies that certain variables are influential regarding both non-criminal and more serious crimes. In addition, significant meditating influences were observed which help to explain some underlying mechanisms involved in girls' arrest patterns. Finally, race/ethnicity moderated a key relationship, which has serious implications for treatment. ^ In conclusion, the present study is an important contribution to research regarding girls' delinquency in that it overcomes limitations in the existing literature in four primary areas: (1) it utilizes a large, multi-state, ethnically and racially diverse sample of justice system-involved girls, (2) it examines numerous co-occurring factors influencing delinquency from multiple domains (family, school, peers, etc.) simultaneously, (3) it formally examines race/ethnicity as a moderator of these multivariate relationships, and (4) it looks at status and criminal arrests independently in order to highlight possible differences in the patterning of risk factors associated with each. These findings have important implications for prevention, treatment and interventions with girls involved in the juvenile justice system.^

An investigation of multiple pathways of developmental intervention change

Convergence among treatment, prevention, and developmental intervention approaches has led to the recognition of the need for evaluation models and research designs that employ a full range of evaluation information to provide an empirical basis for enhancing the efficiency, efficacy, and effectiveness of prevention and positive development interventions. This study reports an investigation of a positive youth development program using an Outcome Mediation Cascade (OMC) evaluation model, an integrated model for evaluating the empirical intersection between intervention and developmental processes. The Changing Lives Program (CLP) is a community supported positive youth development intervention implemented in a practice setting as a selective/indicated program for multi-ethnic, multi-problem at risk youth in urban alternative high schools. This study used a Relational Data Analysis integration of quantitative and qualitative data analysis strategies, including the use of both fixed and free response measures and a structural equation modeling approach, to construct and evaluate the hypothesized OMC model. Findings indicated that the hypothesized model fit the data (χ2 (7) = 6.991, p = .43; RMSEA = .00; CFI = 1.00; WRMR = .459). Findings also provided preliminary evidence consistent with the hypothesis that in addition to having effects on targeted positive outcomes, PYD interventions are likely to have progressive cascading effects on untargeted problem outcomes that operate through effects on positive outcomes. Furthermore, the general pattern of findings suggested the need to use methods capable of capturing both quantitative and qualitative change in order to increase the likelihood of identifying more complete theory informed empirically supported models of developmental intervention change processes.

Mediational effects in cognitive behavioral treatment for anxiety disorders in children and adolescents

The current study examined whether variables that have been found to influence treatment outcome serve as mediators of a child and adolescent cognitive behavioral treatment (CBT) anxiety program at multiple time points throughout the intervention. The study also examined mediating variables measured at multiple time points during treatment to determine the time lags necessary for changes in the mediator variable to translate into changes on treatment gains. Participants were 168 youth (ages 6 to 16 years; 54% males) and their mothers who presented to the Child Anxiety and Phobia Program (CAPP) at Florida International University (FIU). Overall, results indicate that the mediators at multiple time points influenced youth anxiety in a fluctuating manner, such that a decrease in skills at one given session caused changes in youth anxiety at a later session. This dynamic between the mediator and outcome may be reflective of the process of therapeutic change and suggests that skills gained from session to session took time to exert their effect on youth anxiety. The methodology employed helps to elucidate how variables mediate treatment outcome in youth anxiety disorders.

Thioredoxin and Jab1 control estrogen- and antiestrogen-mediated progression of the cell cycle through p27 interactions

A major problem with breast cancer treatment is the prevalence of antiestrogen resistance, be it de novo or acquired after continued use. Many of the underlying mechanisms of antiestrogen resistance are not clear, although estrogen receptor-mediated actions have been identified as a pathway that is blocked by antiestrogens. Selective estrogen receptor modulators (SERMs), such as tamoxifen, are capable of producing reactive oxygen species (ROS) through metabolic activation, and these ROS, at high levels, can induce irreversible growth arrest that is similar to the growth arrest incurred by SERMs. This suggests that SERM-mediated growth arrest may also be through ROS accumulation. Breast cancer receiving long-term antiestrogen treatment appears to adapt to this increased, persistent level of ROS. This, in turn, leads to the disruption of reversible redox signaling that involves redox-sensitive phosphatases and protein kinases and transcription factors. This has downstream consequences for apoptosis, cell cycle progression, and cell metabolism. For this dissertation, we explored if altering the ROS formed by tamoxifen also alters sensitivity of the drug in resistant cells. We explored an association with a thioredoxin/Jab1/p27 pathway, and a possible role of dysregulation of thioredoxin-mediated redox regulation contributing to the development of antiestrogen resistance in breast cancer. We used standard laboratory techniques to perform proteomic assays that showed cell proliferation, protein concentrations, redox states, and protein-protein interactions. We found that increasing thioredoxin reductase levels, and thus increasing the amount of reduced thioredoxin, increased tamoxifen sensitivity in previously resistant cells, as well as altered estrogen and tamoxifen-induced ROS. We also found that decreasing levels of Jab1 protein also increased tamoxifen sensitivity, and that the downstream effects showed a decrease p27 phosphorylation in both cases. We conclude that the chronic use of tamoxifen can lead to an increase in ROS that alters cell signaling and causing cell growth in the presence of tamoxifen, and that this resistant cell growth can be reversed with an alteration to the thioredoxin/Jab1 pathway.

Treatment moderation and secondary outcomes: Results from a randomized clinical trial

The present study pursued two objectives in the context of a randomized clinical trial of cognitive-behavioral therapy with parent (CBT/P) and group (GCBT) involvement. The first objective was to examine the variability in treatment outcome. There were three specific aims within the first objective, to evaluate: (1) youth characteristics (age, depressive, and externalizing disorders) as moderators of treatment outcome; (2) the differential outcome of the treatment approaches as a function of youth characteristics; and (3) the relative efficacy of the treatment approaches at each level of the moderators. ^ The second objective was to evaluate the efficacy of anxiety treatments along secondary depressive symptoms and externalizing behaviors. There were five specific aims within the second objective, to evaluate: (1) whether anxiety treatment yields reductions in secondary problems, (2) the efficacy of anxiety treatments in reducing secondary problems as a function of approach and youth characteristics, (3) whether reductions in anxiety symptoms significantly mediate changes in secondary problems, (4) the directionality of change in the hypothesized mediated relations, and (5) whether the hypothesized mediated relations are moderated by treatment approach and youth characteristics. The specific aims were pursued using data collected from 183 youth and their mothers. Research questions were tested using multiple regressions and structural equation modeling. ^ Age, depressive, and externalizing disorders were significant moderators. CBT/P relative to GCBT lowered anxiety more for younger than older youth. GCBT relative to CBT/P lowered anxiety more for older than younger youth. GCBT relative to CBT/P lowered anxiety more for depressed youth than non-depressed youth. GCBT relative to CBT/P lowered anxiety less for externalizing youth than non-externalizing youth. Treatment reduced depressive symptoms and externalizing problem behaviors. Reductions in anxiety mediated changes in depressive symptoms and externalizing problem behaviors. Reversed directionality was found in the relation between social anxiety and depressive symptoms. In CBT/P the direction of change was from depressive to social anxiety. The opposite was true in GCBT. Reductions in social anxiety mediated posttreatment changes in depressive symptoms in GCBT but not CBT/P. The reverse was true at follow-up. Reductions in social anxiety mediated changes in depressive symptoms for girls but not boys.^

Group cognitive -behavioral therapy for heterogeneous anxiety disorders in children and adolescents: A multiple baseline study

This study investigated the efficacy of Group Cognitive-Behavioral Therapy (GCBT) in the treatment of heterogeneous anxiety disorders in children. A partially nonconcurrent multiple baseline across groups design was used to assess the effects of the treatment on 12 clinically referred children and adolescents between 6 and 16 years of age who met DSM-IV criteria for an anxiety disorder. Targeted diagnoses included Obsessive Compulsive Disorder, Simple Phobia, Separation Anxiety Disorder, Social Phobia, and Generalized Anxiety Disorder, with three of the children also presenting with school refusal behavior. Duration of baseline for each of the three groups varied and ran for one, two, or three weeks. Dependent measures included diagnostic status, child and parent-completed reports, and daily child and parent ratings of child anxiety severity. Results indicated that GCBT was efficacious in reducing anxious symptoms in children and adolescents treated in diagnostically heterogeneous groups, and that gains were generally maintained at 6 and 12 month follow-ups. Findings are discussed in terms of their theoretical and practical implications for the efficient treatment of children and adolescents with anxiety disorders. ^

Treatment attrition among racial /ethnic minority adolescents participating in a brief motivational intervention for substance use problems: The influence of individual, social, cultural, and treatment factors

The present study has the primary aim of examining the predictors of treatment attrition among racial/ethnic minority adolescents with substance use problems. This study explores the potential differential influence of specific individual, social, cultural, and treatment factors on treatment attrition within three racial/ethnic subgroups of adolescents. Participants: A unique feature of the study is the use of a racial/ethnic minority sample (N=453), [U.S.-born Hispanics (n = 262), Foreign-born Hispanics (n = 117), and African-Americans (n = 74)]. Multivariate logit analyses were used to examine the influence of specific factors on treatment attrition among the full sample of adolescents, as well as within each racial/ethnic subgroup. Consistent with expectations, multivariate logit analyses reveal that, the specific factors associated with attrition varied across the three racial/ethnic subgroups. Having parents with problem substance use, being on the waitlist, and being court mandated to treatment emerged as predictors of attrition among the US-born Hispanics, while only Conduct Disorder was significantly associated with greater attrition among foreign-born Hispanics. Finally, among African-Americans, parental crack/cocaine use, parental abstinence from alcohol, and being on the waitlist were predictive of attrition. Multiple factors were associated with treatment attrition among racial/ethnic minority adolescents with specific factors differentially predicting attrition within each racial/ethnic subgroup. African-American youth were more than twice as likely as their Hispanic counterparts to leave treatment prematurely. It is critically important to understand the predictors of attrition among racial/ethnic minority youth in order to better meet the needs of youth most at risk of dropping out. ^

Alterations in Glutathione Levels and Apoptotic Regulators Are Associated with Acquisition of Arsenic Trioxide Resistance in Multiple Myeloma

Arsenic trioxide (ATO) has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2–3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH) levels. At low, clinically achievable concentrations, resistance was primarily associated with an increase in expression of the anti-apoptotic protein Bfl-1 and a decrease in expression of the pro-apoptotic protein Noxa. However, as the concentration of ATO increased, elevated levels of intracellular GSH in 8226/S-ATOR05 became the primary mechanism of ATO resistance. Removal of arsenic selection resulted in a loss of the resistance phenotype, with cells becoming sensitive to high concentrations of ATO within 7 days following drug removal, indicating changes associated with high level resistance (elevated GSH) are dependent upon the presence of arsenic. Conversely, not until 50 days without arsenic did cells once again become sensitive to clinically relevant doses of ATO, coinciding with a decrease in the expression of Bfl-1. In addition we found cross-resistance to melphalan and doxorubicin in 8226/S-ATOR05, suggesting ATO-resistance pathways may also be involved in resistance to other chemotherapeutic agents used in the treatment of multiple myeloma.

Treatment attrition among racial/ethnic minority adolescents participating in a brief motivational intervention for substance use problems : the influence of individual, social, cultural, and treatment factors

The present study has the primary aim of examining the predictors of treatment attrition among racial/ethnic minority adolescents with substance use problems. This study explores the potential differential influence of specific individual, social, cultural, and treatment factors on treatment attrition within three racial/ethnic subgroups of adolescents. Participants: A unique feature of the study is the use of a racial/ethnic minority sample (N=453), [U.S.-born Hispanics (n = 262), Foreign-born Hispanics (n = 117), and African- Americans (n = 74)]. Multivariate logit analyses were used to examine the influence of specific factors on treatment attrition among the full sample of adolescents, as well as within each racial/ethnic subgroup. Consistent with expectations, multivariate logit analyses reveal that, the specific factors associated with attrition varied across the three racial/ethnic subgroups. Having parents with problem substance use, being on the waitlist, and being court mandated to treatment emerged as predictors of attrition among the US-born Hispanics, while only Conduct Disorder was significantly associated with greater attrition among foreign-born Hispanics. Finally, among African-Americans, parental crack/cocaine use, parental abstinence from alcohol, and being on the waitlist were predictive of attrition. Multiple factors were associated with treatment attrition among racial/ethnic minority adolescents with specific factors differentially predicting attrition within each racial/ethnic subgroup. African-American youth were more than twice as likely as their Hispanic counterparts to leave treatment prematurely. It is critically important to understand the predictors of attrition among racial/ethnic minority youth in order to better meet the needs of youth most at risk of dropping out.

Time, Cost, and Environmental Impact Analysis for Sustainable Design at Multiple Building Levels

Construction projects are complex endeavors that require the involvement of different professional disciplines in order to meet various project objectives that are often conflicting. The level of complexity and the multi-objective nature of construction projects lend themselves to collaborative design and construction such as integrated project delivery (IPD), in which relevant disciplines work together during project conception, design and construction. Traditionally, the main objectives of construction projects have been to build in the least amount of time with the lowest cost possible, thus the inherent and well-established relationship between cost and time has been the focus of many studies. The importance of being able to effectively model relationships among multiple objectives in building construction has been emphasized in a wide range of research. In general, the trade-off relationship between time and cost is well understood and there is ample research on the subject. However, despite sustainable building designs, relationships between time and environmental impact, as well as cost and environmental impact, have not been fully investigated. The objectives of this research were mainly to analyze and identify relationships of time, cost, and environmental impact, in terms of CO2 emissions, at different levels of a building: material level, component level, and building level, at the pre-use phase, including manufacturing and construction, and the relationships of life cycle cost and life cycle CO2 emissions at the usage phase. Additionally, this research aimed to develop a robust simulation-based multi-objective decision-support tool, called SimulEICon, which took construction data uncertainty into account, and was capable of incorporating life cycle assessment information to the decision-making process. The findings of this research supported the trade-off relationship between time and cost at different building levels. Moreover, the time and CO2 emissions relationship presented trade-off behavior at the pre-use phase. The results of the relationship between cost and CO2 emissions were interestingly proportional at the pre-use phase. The same pattern continually presented after the construction to the usage phase. Understanding the relationships between those objectives is a key in successfully planning and designing environmentally sustainable construction projects.

Life Cycle of Deccan Trap Magma Chambers: A Crystal Scale Elemental and Strontium Isotopic Investigation

The Deccan Trap basalts are the remnants of a massive series of lava flows that erupted at the K/T boundary and covered 1-2 million km2 of west-central India. This eruptive event is of global interest because of its possible link to the major mass extinction event, and there is much debate about the duration of this massive volcanic event. In contrast to isotopic or paleomagnetic dating methods, I explore an alternative approach to determine the lifecycle of the magma chambers that supplied the lavas, and extend the concept to obtain a tighter constraint on Deccan’s duration. My method relies on extracting time information from elemental and isotopic diffusion across zone boundary in an individual crystal. I determined elemental and Sr-isotopic variations across abnormally large (2-5 cm) plagioclase crystals from the Thalghat and Kashele “Giant Plagioclase Basalts” from the lowermost Jawhar and Igatpuri Formations respectively in the thickest Western Ghats section near Mumbai. I also obtained bulk rock major, trace and rare earth element chemistry of each lava flow from the two formations. Thalghat flows contain only 12% zoned crystals, with 87Sr/86Sr ratios of 0.7096 in the core and 0.7106 in the rim, separated by a sharp boundary. In contrast, all Kashele crystals have a wider range of 87Sr/86Sr values, with multiple zones. Geochemical modeling of the data suggests that the two types of crystals grew in distinct magmatic environments. Modeling intracrystalline diffusive equilibration between the core and rim of Thalghat crystals led me to obtain a crystal growth rate of 2.03x10-10 cm/s and a residence time of 780 years for the crystals in the magma chamber(s). Employing some assumptions based on field and geochronologic evidence, I extrapolated this residence time to the entire Western Ghats and obtained an estimate of 25,000 – 35,000 years for the duration of Western Ghats volcanism. This gave an eruptive rate of 30 – 40 km3/yr, which is much higher than any presently erupting volcano. This result will remain speculative until a similarly detailed analytical-modeling study is performed for the rest of the Western Ghats formations.