The relationship of thymulin activity, immune parameters of HIV disease progression and substance use in a cohort of HIV seropositive alcohol and drug users

Zinc is essential for the activity of thymulin, a thymic hormone involved in T-lymphocyte differentiation and activation. Zinc deficiency is widespread in populations with HIV infection, and HIV+ drug users are particularly susceptible to zinc deficiency and immune suppression. This dissertation explored the relationship of zinc-bound active thymulin to plasma zinc, CD4+ and CD8+ cell count, the CD4+/CD8+ ratio, and drug use in HIV-infected drug users. Zinc-bound active thymulin was assessed in plasma of HIV+ drug users who were participating in a 30 month zinc supplementation trial. Plasma from 80 participants at the 12 month visit, and 40 of these same participants, randomly selected, at the baseline visit were assessed for zinc-bound active thymulin levels using a modification of the rosette inhibition assay. Thymulin activity was directly associated with CD4+ cell count (β = 0.127, p = 0.002) and inversely associated with cocaine use (β = −0.908, p = 0.026; R2 = 0.188, p = 0.019) independent of HIV viral load, age, gender and antiretroviral use. An increase in thymulin activity was 1.4 times more likely when CD4+ cell count increased (OR = 1.402, 95%CI: 1.006–1.956), independent of change in viral load, antiretroviral use, and age. Participants who used cocaine consistently, were 7.6 times less likely to have an increase in thymulin activity (OR = 0.133, 95%CI: 0.017–1.061). There was a direct correlation between change in plasma zinc and change in zinc-bound active thymulin (r = 0.243, p = 0.13). Analysis of CD4+ cell count decline in 222 participants in the zinc supplementation trial across the 30 months showed that both crack cocaine use and heavy alcohol use accelerated CD4+ cell count decline. Thymulin activity is directly associated with HIV disease progression, measured by CD4+ cell count, and is depressed with cocaine use independent of antiretroviral use and HIV viral load. Cocaine and heavy alcohol accelerate CD4+ cell count decline. The effect of cocaine on thymic output requires further evaluation as a mechanism for the association of cocaine use with faster HIV disease progression.

Maltreatment, psychiatric symptoms and human immunodeficiency virus/sexual transmitted infection risk behavior among youth with alcohol and other drug use problems: A person-centered analysis

Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). ^ LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth. ^

Host and network optimizations for performance enhancement and energy efficiency in data center networks

Modern data centers host hundreds of thousands of servers to achieve economies of scale. Such a huge number of servers create challenges for the data center network (DCN) to provide proportionally large bandwidth. In addition, the deployment of virtual machines (VMs) in data centers raises the requirements for efficient resource allocation and find-grained resource sharing. Further, the large number of servers and switches in the data center consume significant amounts of energy. Even though servers become more energy efficient with various energy saving techniques, DCN still accounts for 20% to 50% of the energy consumed by the entire data center. The objective of this dissertation is to enhance DCN performance as well as its energy efficiency by conducting optimizations on both host and network sides. First, as the DCN demands huge bisection bandwidth to interconnect all the servers, we propose a parallel packet switch (PPS) architecture that directly processes variable length packets without segmentation-and-reassembly (SAR). The proposed PPS achieves large bandwidth by combining switching capacities of multiple fabrics, and it further improves the switch throughput by avoiding padding bits in SAR. Second, since certain resource demands of the VM are bursty and demonstrate stochastic nature, to satisfy both deterministic and stochastic demands in VM placement, we propose the Max-Min Multidimensional Stochastic Bin Packing (M3SBP) algorithm. M3SBP calculates an equivalent deterministic value for the stochastic demands, and maximizes the minimum resource utilization ratio of each server. Third, to provide necessary traffic isolation for VMs that share the same physical network adapter, we propose the Flow-level Bandwidth Provisioning (FBP) algorithm. By reducing the flow scheduling problem to multiple stages of packet queuing problems, FBP guarantees the provisioned bandwidth and delay performance for each flow. Finally, while DCNs are typically provisioned with full bisection bandwidth, DCN traffic demonstrates fluctuating patterns, we propose a joint host-network optimization scheme to enhance the energy efficiency of DCNs during off-peak traffic hours. The proposed scheme utilizes a unified representation method that converts the VM placement problem to a routing problem and employs depth-first and best-fit search to find efficient paths for flows.

Commitment language as a predictor of alcohol and marijuana use outcomes among adolescents in school -based group treatment

Despite widespread recognition of the problem of adolescent alcohol and other drug (AOD) abuse, research on its most common treatment modality, group work, is lacking. This research gap is alarming given that outcomes range from positive to potentially iatrogenic. This study sought to identify change mechanisms and/or treatment factors that are observable within group treatment sessions and that may predict AOD use outcomes. This NIH (F31 DA 020233-01A1) study evaluated 108, 10-19 year olds and the 19 school-based treatment groups to which they were previously assigned (R01 AA10246; PI: Wagner). Associations between motivational interviewing (MI) based change talk variables, group leader MI skills, and alcohol and marijuana use outcomes up to 12-months following treatment were evaluated. Treatment session audio recordings and transcripts (1R21AA015679-01; PI: Macgowan) were coded using a new discourse analysis coding scheme for measuring group member change talk (Amrhein, 2003). Therapist MI skills were similarly measured using the Motivational Interviewing Treatment Integrity instrument. Group member responses to commitment predicted group marijuana use at the 1-month follow up. Also, group leader empathy was significantly associated with group commitment for marijuana use at the middle and ending stages of treatment. Both of the above process measures were applied in a group setting for the first time. Building upon MI and social learning theory principles, group commitment and group member responses to commitment are new observable, in-session, process constructs that may predict positive and negative adolescent group treatment outcomes. These constructs, as well as the discourse analysis method and instruments used to measure them, raise many possibilities for future group work process research and practice.

An investigation of the relationship between maltreatment and alcohol and other drug (AOD) problems in African -American and Hispanic adolescent girls

Maltreatment experienced in childhood or adolescence is a known risk factor for later problem alcohol and/or other drug (AOD) use (Bailey & McCloskey, 2005; Shin, Edwards, Heeren, 2009). A growing body of empirical work has found significant associations between adolescent girls’ AOD use and maltreatment experiences. However, questions remain as to how this relation unfolds with African-American and Hispanic adolescent girls. Guided by four relational models that have been proposed in the literature, this study examined the links between maltreatment, trauma symptoms, and alcohol and/or other drug (AOD) problems in a sample of 170 African-American and Hispanic adolescent girls who were participants in a school-based AOD use intervention. Results of this study revealed that maltreatment experiences (physical and emotional abuse) were positively related to trauma symptoms, which were positively related to AOD problem severity, alcohol abuse, alcohol dependency, drug abuse, and drug dependency. Perceived discrimination moderated this relation between sexual abuse and trauma symptoms, such that more perceived discrimination resulted in a stronger effect of sexual abuse on trauma symptoms. Ethnic identity moderated the relation between sexual abuse and AOD problem severity, such that ethnic identity demonstrated protective properties in the relation between sexual abuse and AOD problem severity. My research adds to extant knowledge on the relation between maltreatment and AOD use in adolescent girls and suggests the importance of developing interventions targeting maltreatment and AOD use concurrently.

The influence of neurocognitive impairment, alcohol and other drug (AOD) use, and psychosocial factors on antiretroviral treatment adherence, service utilization and viral load among HIV-seropositive adults

Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) can be affected by problems of neurocognitive (NC) impairment, stress, alcohol and other drug (AOD) abuse, and other barriers. The aims of this research were to: (1) examine factors associated with NC impairment, (2) explore relationships between psychosocial variables with ART adherence and viral load (VL), and (3) evaluate the efficacy of an evidence-based intervention in improving ART adherence, increasing service utilization, and decreasing VL. The first study (n=370) was cross sectional and used structural equation modeling to test whether AOD use, years living with HIV, and time from HIV diagnosis to seeking care were associated with poorer NC functioning. The second study (n=246) used similar methods to test the hypothesis that stress, barriers to adherence, NC impairment, poor social support, and AOD use were related to lower VL mediated by ART adherence. The third study (n=243) evaluated an evidence-based, eight-session program to improve ART adherence, reduce VL, and increase service utilization in a randomized controlled trial. Study participants were PLWH living in South Florida, 18 to 60 years old, with a history of alcohol abuse enrolled from January 2009 through November 2012. Secondary analysis of available data showed: (1) scores on interference with executive functioning increased by 0.32 for each day of marijuana use and 1.18 for each year living with HIV, but no association was found between alcohol use and NC functioning; (2) each barrier to adherence was associated with a 10% decrease in adherence to ART and a 0.42 unit increase in VL (log10) and the relationship between barriers and VL was partially mediated by ART adherence; (3) participants in the evidence-based program were more likely than the comparison group to report an undetectable VL (OR=2.25, p<0.01) at 6 months, but not 3 months, post-intervention. Psychosocial factors affect VL, but ART adherence is essential in achieving an undetectable VL in PLWH.

Maltreatment, Psychiatric Symptoms and Human Immunodeficiency Virus/Sexual Transmitted Infection Risk Behavior Among Youth with Alcohol and Other Drug Use Problems: A Person-Centered Analysis

Multi-problem youth undergoing treatment for substance use problems are at high behavioral risk for exposure to sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Specific risk factors include childhood adversities such as maltreatment experiences and subsequent forms of psychopathology. The current study used a person-centered analytical approach to examine how childhood maltreatment experiences were related to patterns of psychiatric symptoms and HIV/STI risk behaviors in a sample of adolescents (N = 408) receiving treatment services. Data were collected in face-to-face interviews at two community-based facilities. Descriptive statistics and Latent Profile Analysis (LPA) were used to (a) classify adolescents into groups based on past year psychiatric symptoms, and (b) examine relations between class membership and forms of childhood maltreatment experiences, as well as past year sexual risk behavior (SRB). LPA results indicated significant heterogeneity in psychiatric symptoms among the participants. The three classes generated via the optimal LPA solution included: (a) a low psychiatric symptoms class, (b) a high alcohol symptoms class and (c) a high internalizing symptoms class. Class membership was associated significantly with adolescents’ self-reported scores for childhood sexual abuse and emotional neglect. ANOVAs documented significant differences in mean scores for multiple indices of SRB indices by class membership, demonstrating differential risk for HIV/STI exposure across classes. The two classes characterized by elevated psychiatric symptom profiles and more severe maltreatment histories were at increased behavioral risk for HIV/STI exposure, compared to the low psychiatric symptoms class. The high internalizing symptoms class reported the highest scores for most of the indices of SRB assessed. The heterogeneity of psychiatric symptom patterns documented in the current study has important implications for HIV/STI prevention programs implemented with multi-problem youth. The results highlight complex relations between childhood maltreatment experiences, psychopathology and multiple forms of health risk behavior among adolescents. The results underscore the importance of further integration between substance abuse treatment and HIV/STI risk reduction efforts to improve morbidity and mortality among vulnerable youth.

An Investigation of the Relationship Between Maltreatment and Alcohol and Other Drug (AOD) Use Among African-American and Hispanic Adolescent Girls

Maltreatment experienced in childhood or adolescence is a known risk factor for later problem alcohol and/or other drug (AOD) use (Bailey & McCloskey, 2005; Shin, Edwards, Heeren, 2009). A growing body of empirical work has found significant associations between adolescent girls’ AOD use and maltreatment experiences. However, questions remain as to how this relation unfolds with African-American and Hispanic adolescent girls. Guided by four relational models that have been proposed in the literature, this study examined the links between maltreatment, trauma symptoms, and alcohol and/or other drug (AOD) problems in a sample of 170 African-American and Hispanic adolescent girls who were participants in a school-based AOD use intervention. Results of this study revealed that maltreatment experiences (physical and emotional abuse) were positively related to trauma symptoms, which were positively related to AOD problem severity, alcohol abuse, alcohol dependency, drug abuse, and drug dependency. Perceived discrimination moderated this relation between sexual abuse and trauma symptoms, such that more perceived discrimination resulted in a stronger effect of sexual abuse on trauma symptoms. Ethnic identity moderated the relation between sexual abuse and AOD problem severity, such that ethnic identity demonstrated protective properties in the relation between sexual abuse and AOD problem severity. My research adds to extant knowledge on the relation between maltreatment and AOD use in adolescent girls and suggests the importance of developing interventions targeting maltreatment and AOD use concurrently.

Host and Network Optimizations for Performance Enhancement and Energy Efficiency in Data Center Networks

Modern data centers host hundreds of thousands of servers to achieve economies of scale. Such a huge number of servers create challenges for the data center network (DCN) to provide proportionally large bandwidth. In addition, the deployment of virtual machines (VMs) in data centers raises the requirements for efficient resource allocation and find-grained resource sharing. Further, the large number of servers and switches in the data center consume significant amounts of energy. Even though servers become more energy efficient with various energy saving techniques, DCN still accounts for 20% to 50% of the energy consumed by the entire data center. The objective of this dissertation is to enhance DCN performance as well as its energy efficiency by conducting optimizations on both host and network sides. First, as the DCN demands huge bisection bandwidth to interconnect all the servers, we propose a parallel packet switch (PPS) architecture that directly processes variable length packets without segmentation-and-reassembly (SAR). The proposed PPS achieves large bandwidth by combining switching capacities of multiple fabrics, and it further improves the switch throughput by avoiding padding bits in SAR. Second, since certain resource demands of the VM are bursty and demonstrate stochastic nature, to satisfy both deterministic and stochastic demands in VM placement, we propose the Max-Min Multidimensional Stochastic Bin Packing (M3SBP) algorithm. M3SBP calculates an equivalent deterministic value for the stochastic demands, and maximizes the minimum resource utilization ratio of each server. Third, to provide necessary traffic isolation for VMs that share the same physical network adapter, we propose the Flow-level Bandwidth Provisioning (FBP) algorithm. By reducing the flow scheduling problem to multiple stages of packet queuing problems, FBP guarantees the provisioned bandwidth and delay performance for each flow. Finally, while DCNs are typically provisioned with full bisection bandwidth, DCN traffic demonstrates fluctuating patterns, we propose a joint host-network optimization scheme to enhance the energy efficiency of DCNs during off-peak traffic hours. The proposed scheme utilizes a unified representation method that converts the VM placement problem to a routing problem and employs depth-first and best-fit search to find efficient paths for flows.

The Influence of Neurocognitive Impairment, Alcohol and other Drug (AOD) Use, and Psychosocial Factors on Antiretroviral Treatment Adherence, Service Utilization and Viral Load Among HIV-Seropositive Adults

Among people living with HIV (PLWH), adherence to antiretroviral therapy (ART) can be affected by problems of neurocognitive (NC) impairment, stress, alcohol and other drug (AOD) abuse, and other barriers. The aims of this research were to: (1) examine factors associated with NC impairment, (2) explore relationships between psychosocial variables with ART adherence and viral load (VL), and (3) evaluate the efficacy of an evidence-based intervention in improving ART adherence, increasing service utilization, and decreasing VL. The first study (n=370) was cross sectional and used structural equation modeling to test whether AOD use, years living with HIV, and time from HIV diagnosis to seeking care were associated with poorer NC functioning. The second study (n=246) used similar methods to test the hypothesis that stress, barriers to adherence, NC impairment, poor social support, and AOD use were related to lower VL mediated by ART adherence. The third study (n=243) evaluated an evidence-based, eight-session program to improve ART adherence, reduce VL, and increase service utilization in a randomized controlled trial. Study participants were PLWH living in South Florida, 18 to 60 years old, with a history of alcohol abuse enrolled from January 2009 through November 2012. Secondary analysis of available data showed: (1) scores on interference with executive functioning increased by 0.32 for each day of marijuana use and 1.18 for each year living with HIV, but no association was found between alcohol use and NC functioning; (2) each barrier to adherence was associated with a 10% decrease in adherence to ART and a 0.42 unit increase in VL (log10) and the relationship between barriers and VL was partially mediated by ART adherence; (3) participants in the evidence-based program were more likely than the comparison group to report an undetectable VL (OR=2.25, p Psychosocial factors affect VL, but ART adherence is essential in achieving an undetectable VL in PLWH.