Robust effect sizes and their confidence intervals for group difference between trajectories in hierarchical linear growth model

Hierarchical linear growth model (HLGM), as a flexible and powerful analytic method, has played an increased important role in psychology, public health and medical sciences in recent decades. Mostly, researchers who conduct HLGM are interested in the treatment effect on individual trajectories, which can be indicated by the cross-level interaction effects. However, the statistical hypothesis test for the effect of cross-level interaction in HLGM only show us whether there is a significant group difference in the average rate of change, rate of acceleration or higher polynomial effect; it fails to convey information about the magnitude of the difference between the group trajectories at specific time point. Thus, reporting and interpreting effect sizes have been increased emphases in HLGM in recent years, due to the limitations and increased criticisms for statistical hypothesis testing. However, most researchers fail to report these model-implied effect sizes for group trajectories comparison and their corresponding confidence intervals in HLGM analysis, since lack of appropriate and standard functions to estimate effect sizes associated with the model-implied difference between grouping trajectories in HLGM, and also lack of computing packages in the popular statistical software to automatically calculate them. ^ The present project is the first to establish the appropriate computing functions to assess the standard difference between grouping trajectories in HLGM. We proposed the two functions to estimate effect sizes on model-based grouping trajectories difference at specific time, we also suggested the robust effect sizes to reduce the bias of estimated effect sizes. Then, we applied the proposed functions to estimate the population effect sizes (d ) and robust effect sizes (du) on the cross-level interaction in HLGM by using the three simulated datasets, and also we compared the three methods of constructing confidence intervals around d and du recommended the best one for application. At the end, we constructed 95% confidence intervals with the suitable method for the effect sizes what we obtained with the three simulated datasets. ^ The effect sizes between grouping trajectories for the three simulated longitudinal datasets indicated that even though the statistical hypothesis test shows no significant difference between grouping trajectories, effect sizes between these grouping trajectories can still be large at some time points. Therefore, effect sizes between grouping trajectories in HLGM analysis provide us additional and meaningful information to assess group effect on individual trajectories. In addition, we also compared the three methods to construct 95% confident intervals around corresponding effect sizes in this project, which handled with the uncertainty of effect sizes to population parameter. We suggested the noncentral t-distribution based method when the assumptions held, and the bootstrap bias-corrected and accelerated method when the assumptions are not met.^

Dynamics of a minimal model of interlocked positive and negative feedback loops of transcriptional regulation by cAMP-response element binding proteins.

cAMP-response element binding (CREB) proteins are involved in transcriptional regulation in a number of cellular processes (e.g., neural plasticity and circadian rhythms). The CREB family contains activators and repressors that may interact through positive and negative feedback loops. These loops can be generated by auto- and cross-regulation of expression of CREB proteins, via CRE elements in or near their genes. Experiments suggest that such feedback loops may operate in several systems (e.g., Aplysia and rat). To understand the functional implications of such feedback loops, which are interlocked via cross-regulation of transcription, a minimal model with a positive and negative loop was developed and investigated using bifurcation analysis. Bifurcation analysis revealed diverse nonlinear dynamics (e.g., bistability and oscillations). The stability of steady states or oscillations could be changed by time delays in the synthesis of the activator (CREB1) or the repressor (CREB2). Investigation of stochastic fluctuations due to small numbers of molecules of CREB1 and CREB2 revealed a bimodal distribution of CREB molecules in the bistability region. The robustness of the stable HIGH and LOW states of CREB expression to stochastic noise differs, and a critical number of molecules was required to sustain the HIGH state for days or longer. Increasing positive feedback or decreasing negative feedback also increased the lifetime of the HIGH state, and persistence of this state may correlate with long-term memory formation. A critical number of molecules was also required to sustain robust oscillations of CREB expression. If a steady state was near a deterministic Hopf bifurcation point, stochastic resonance could induce oscillations. This comparative analysis of deterministic and stochastic dynamics not only provides insights into the possible dynamics of CREB regulatory motifs, but also demonstrates a framework for understanding other regulatory processes with similar network architecture.

Simulation of Drosophila circadian oscillations, mutations, and light responses by a model with VRI, PDP-1, and CLK.

A model of Drosophila circadian rhythm generation was developed to represent feedback loops based on transcriptional regulation of per, Clk (dclock), Pdp-1, and vri (vrille). The model postulates that histone acetylation kinetics make transcriptional activation a nonlinear function of [CLK]. Such a nonlinearity is essential to simulate robust circadian oscillations of transcription in our model and in previous models. Simulations suggest that two positive feedback loops involving Clk are not essential for oscillations, because oscillations of [PER] were preserved when Clk, vri, or Pdp-1 expression was fixed. However, eliminating positive feedback by fixing vri expression altered the oscillation period. Eliminating the negative feedback loop in which PER represses per expression abolished oscillations. Simulations of per or Clk null mutations, of per overexpression, and of vri, Clk, or Pdp-1 heterozygous null mutations altered model behavior in ways similar to experimental data. The model simulated a photic phase-response curve resembling experimental curves, and oscillations entrained to simulated light-dark cycles. Temperature compensation of oscillation period could be simulated if temperature elevation slowed PER nuclear entry or PER phosphorylation. The model makes experimental predictions, some of which could be tested in transgenic Drosophila.

A reduced model clarifies the role of feedback loops and time delays in the Drosophila circadian oscillator.

Although several detailed models of molecular processes essential for circadian oscillations have been developed, their complexity makes intuitive understanding of the oscillation mechanism difficult. The goal of the present study was to reduce a previously developed, detailed model to a minimal representation of the transcriptional regulation essential for circadian rhythmicity in Drosophila. The reduced model contains only two differential equations, each with time delays. A negative feedback loop is included, in which PER protein represses per transcription by binding the dCLOCK transcription factor. A positive feedback loop is also included, in which dCLOCK indirectly enhances its own formation. The model simulated circadian oscillations, light entrainment, and a phase-response curve with qualitative similarities to experiment. Time delays were found to be essential for simulation of circadian oscillations with this model. To examine the robustness of the simplified model to fluctuations in molecule numbers, a stochastic variant was constructed. Robust circadian oscillations and entrainment to light pulses were simulated with fewer than 80 molecules of each gene product present on average. Circadian oscillations persisted when the positive feedback loop was removed. Moreover, elimination of positive feedback did not decrease the robustness of oscillations to stochastic fluctuations or to variations in parameter values. Such reduced models can aid understanding of the oscillation mechanisms in Drosophila and in other organisms in which feedback regulation of transcription may play an important role.

THE INTERACTION BETWEEN INTERNAL AND EXTERNAL INFORMATION ON RELATIONAL DATA SEARCH

People often use tools to search for information. In order to improve the quality of an information search, it is important to understand how internal information, which is stored in user’s mind, and external information, represented by the interface of tools interact with each other. How information is distributed between internal and external representations significantly affects information search performance. However, few studies have examined the relationship between types of interface and types of search task in the context of information search. For a distributed information search task, how data are distributed, represented, and formatted significantly affects the user search performance in terms of response time and accuracy. Guided by UFuRT (User, Function, Representation, Task), a human-centered process, I propose a search model, task taxonomy. The model defines its relationship with other existing information models. The taxonomy clarifies the legitimate operations for each type of search task of relation data. Based on the model and taxonomy, I have also developed prototypes of interface for the search tasks of relational data. These prototypes were used for experiments. The experiments described in this study are of a within-subject design with a sample of 24 participants recruited from the graduate schools located in the Texas Medical Center. Participants performed one-dimensional nominal search tasks over nominal, ordinal, and ratio displays, and searched one-dimensional nominal, ordinal, interval, and ratio tasks over table and graph displays. Participants also performed the same task and display combination for twodimensional searches. Distributed cognition theory has been adopted as a theoretical framework for analyzing and predicting the search performance of relational data. It has been shown that the representation dimensions and data scales, as well as the search task types, are main factors in determining search efficiency and effectiveness. In particular, the more external representations used, the better search task performance, and the results suggest the ideal search performance occurs when the question type and corresponding data scale representation match. The implications of the study lie in contributing to the effective design of search interface for relational data, especially laboratory results, which are often used in healthcare activities.

Dynamics of a minimal model of interlocked positive and negative feedback loops of transcriptional regulation by cAMP-response element binding proteins.

cAMP-response element binding (CREB) proteins are involved in transcriptional regulation in a number of cellular processes (e.g., neural plasticity and circadian rhythms). The CREB family contains activators and repressors that may interact through positive and negative feedback loops. These loops can be generated by auto- and cross-regulation of expression of CREB proteins, via CRE elements in or near their genes. Experiments suggest that such feedback loops may operate in several systems (e.g., Aplysia and rat). To understand the functional implications of such feedback loops, which are interlocked via cross-regulation of transcription, a minimal model with a positive and negative loop was developed and investigated using bifurcation analysis. Bifurcation analysis revealed diverse nonlinear dynamics (e.g., bistability and oscillations). The stability of steady states or oscillations could be changed by time delays in the synthesis of the activator (CREB1) or the repressor (CREB2). Investigation of stochastic fluctuations due to small numbers of molecules of CREB1 and CREB2 revealed a bimodal distribution of CREB molecules in the bistability region. The robustness of the stable HIGH and LOW states of CREB expression to stochastic noise differs, and a critical number of molecules was required to sustain the HIGH state for days or longer. Increasing positive feedback or decreasing negative feedback also increased the lifetime of the HIGH state, and persistence of this state may correlate with long-term memory formation. A critical number of molecules was also required to sustain robust oscillations of CREB expression. If a steady state was near a deterministic Hopf bifurcation point, stochastic resonance could induce oscillations. This comparative analysis of deterministic and stochastic dynamics not only provides insights into the possible dynamics of CREB regulatory motifs, but also demonstrates a framework for understanding other regulatory processes with similar network architecture.

A model of late long-term potentiation simulates aspects of memory maintenance.

Late long-term potentiation (L-LTP) denotes long-lasting strengthening of synapses between neurons. L-LTP appears essential for the formation of long-term memory, with memories at least partly encoded by patterns of strengthened synapses. How memories are preserved for months or years, despite molecular turnover, is not well understood. Ongoing recurrent neuronal activity, during memory recall or during sleep, has been hypothesized to preferentially potentiate strong synapses, preserving memories. This hypothesis has not been evaluated in the context of a mathematical model representing ongoing activity and biochemical pathways important for L-LTP. In this study, ongoing activity was incorporated into two such models - a reduced model that represents some of the essential biochemical processes, and a more detailed published model. The reduced model represents synaptic tagging and gene induction simply and intuitively, and the detailed model adds activation of essential kinases by Ca(2+). Ongoing activity was modeled as continual brief elevations of Ca(2+). In each model, two stable states of synaptic strength/weight resulted. Positive feedback between synaptic weight and the amplitude of ongoing Ca(2+) transients underlies this bistability. A tetanic or theta-burst stimulus switches a model synapse from a low basal weight to a high weight that is stabilized by ongoing activity. Bistability was robust to parameter variations in both models. Simulations illustrated that prolonged periods of decreased activity reset synaptic strengths to low values, suggesting a plausible forgetting mechanism. However, episodic activity with shorter inactive intervals maintained strong synapses. Both models support experimental predictions. Tests of these predictions are expected to further understanding of how neuronal activity is coupled to maintenance of synaptic strength. Further investigations that examine the dynamics of activity and synaptic maintenance can be expected to help in understanding how memories are preserved for up to a lifetime in animals including humans.

Behavioral and psychosocial factors associated with sexual risk in a population of crack cocaine users

The purpose of this dissertation was to examine the relationship between key psychosocial and behavioral components of the Transtheoretical Model and the Theory of Reasoned Action for sexual risk reduction in a population of crack cocaine smokers and sex workers, not in drug treatment. ^ The first study examined the results of an analysis of the association between two principal constructs in the Transtheoretical Model, the processes of change and the stages of change for condom use, in a high risk population. In the analysis of variance for all respondents, the overall F-test revealed that people in different stages have different levels of experiential process use, F(3,317) = 17.79, p = 0.0001 and different levels of behavioral process use, F(3,317) = 28.59, p = .0001. For the experiential processes, there was a significant difference between the precontemplation/contemplation stage, and both the action, and maintenance, stages.^ The second study explored the relationship between the Theory of Reasoned Action “beliefs” and the stages-of-change in the same population. In the analysis of variance for all participants, the results indicate that people in different stages did value the positive beliefs differently, F(3,502) = 15.38, p = .0001 but did not value the negative beliefs differently, F(3,502) = 2.08, p = .10. ^ The third study explored differences in stage-of-change by gender, partner type drug use, and HIV status. Three discriminant functions emerged, with a combined χ2(12) = 139.57, p = <.0001. The loading matrix of correlations between predictors and discriminant functions demonstrate that the strongest predictor for distinguishing between the precontemplation/contemplation stage and the preparation, action, and maintenance stages (first function) is partner type (.962). The loadings on the second discriminant function suggest that once partner type has been accounted for, ever having HIV/AIDS (.935) was the best predictor for distinguishing between the first three stages and the maintenance stage. ^ These studies demonstrate that behavioral change theories can contribute important insight to researchers and program planners attempting to alter HIV risk behavior in high-risk populations. ^

Survival analysis of longevity in siblings

Do siblings of centenarians tend to have longer life spans? To answer this question, life spans of 184 siblings for 42 centenarians have been evaluated. Two important questions have been addressed in analyzing the sibling data. First, a standard needs to be established, to which the life spans of 184 siblings are compared. In this report, an external reference population is constructed from the U.S. life tables. Its estimated mortality rates are treated as baseline hazards from which the relative mortality of the siblings are estimated. Second, the standard survival models which assume independent observations are invalid when correlation within family exists, underestimating the true variance. Methods that allow correlations are illustrated by three different methods. First, the cumulative relative excess mortality between siblings and their comparison group is calculated and used as an effective graphic tool, along with the Product Limit estimator of the survival function. The variance estimator of the cumulative relative excess mortality is adjusted for the potential within family correlation using Taylor linearization approach. Second, approaches that adjust for the inflated variance are examined. They are adjusted one-sample log-rank test using design effect originally proposed by Rao and Scott in the correlated binomial or Poisson distribution setting and the robust variance estimator derived from the log-likelihood function of a multiplicative model. Nether of these two approaches provide correlation estimate within families, but the comparison with the comparison with the standard remains valid under dependence. Last, using the frailty model concept, the multiplicative model, where the baseline hazards are known, is extended by adding a random frailty term that is based on the positive stable or the gamma distribution. Comparisons between the two frailty distributions are performed by simulation. Based on the results from various approaches, it is concluded that the siblings of centenarians had significant lower mortality rates as compared to their cohorts. The frailty models also indicate significant correlations between the life spans of the siblings. ^

A survey of the implementation status of environmental management systems in U.S. colleges and universities, and, An environmental management system implementation model for U.S. colleges and universities

A census of 925 U.S. colleges and universities offering masters and doctorate degrees was conducted in order to study the number of elements of an environmental management system as defined by ISO 14001 possessed by small, medium and large institutions. A 30% response rate was received with 273 responses included in the final data analysis. Overall, the number of ISO 14001 elements implemented among the 273 institutions ranged from 0 to 16, with a median of 12. There was no significant association between the number of elements implemented among institutions and the size of the institution (p = 0.18; Kruskal-Wallis test) or among USEPA regions (p = 0.12; Kruskal-Wallis test). The proportion of U.S. colleges and universities that reported having implemented a structured, comprehensive environmental management system, defined by answering yes to all 16 elements, was 10% (95% C.I. 6.6%–14.1%); however 38% (95% C.I. 32.0%–43.8%) reported that they had implemented a structured, comprehensive environmental management system, while 30.0% (95% C.I. 24.7%–35.9%) are planning to implement a comprehensive environmental management system within the next five years. Stratified analyses were performed by institution size, Carnegie Classification and job title. ^ The Osnabruck model, and another under development by the South Carolina Sustainable Universities Initiative, are the only two environmental management system models that have been proposed specifically for colleges and universities, although several guides are now available. The Environmental Management System Implementation Model for U.S. Colleges and Universities developed is an adaptation of the ISO 14001 standard and USEPA recommendations and has been tailored to U.S. colleges and universities for use in streamlining the implementation process. In using this implementation model created for the U.S. research and academic setting, it is hoped that these highly specialized institutions will be provided with a clearer and more cost-effective path towards the implementation of an EMS and greater compliance with local, state and federal environmental legislation. ^

Sexual orientation and sexual behavior patterns: Evaluation of agreement and variation in a cohort of male, African American drug users in Houston, TX

Background. Sexual orientation and sexual behavior among men have shown disagreement in past studies. The term "on the down low" has been adopted by many to describe "straight" identifying men who have sex with men but do not inform their primary female partner. Methods. This secondary analysis of data collected from the "DASH Project---A Hepatitis B Vaccine Model for HIV Vaccine Trial in Drug Users," assessed sexual behavior patterns among African American drug-using men over time. Using a screener questionnaire to determine sexual orientation and sexual behavior of the men, the study specifically evaluated "straight" identified men who have sex with women only (MSW) to determine what factors were associated with sexual behavior variation to include men during follow-up. The Fisher's Exact Test was used to evaluate the factors. Results. Variation of sexual behavior was highest among "bisexual" identified men followed by "gay" identified men. Fifteen of the original 593 "straight" and MSW men had sexual behavior variation to include men. In the analysis of "straight" and MSW men with variation in sexual behavior compared to those who did not, living on the streets, greater number of sexual partners, trading sex for drugs, and trading sex for money were associated with sexual behavior variation (all p-values <0.01). Conclusions. The factors were only associated when considering the interview when the variation occurred. The same factors at screening were not predictive of sexual behavior variation in the future. Environmental factors, such as living situation, appear to play a role in sexual behavior variations in "straight" and MSW men. ^ Keywords. sexual behavior, sexual orientation, Fisher's Exact Test^

Predictors of HIV testing among injection drug users

The current analysis examined the association of several demographic and behavioral variables with prior HIV testing within a population of injection drug users (IDUs) living in Harris County, Texas in 2005 (n=563). After completing the initial univariate analyses of all potential predictors, a multivariable model was created. This model was designed to guide future intervention efforts. Data used in this analysis were collected by the University of Texas School of Public Health in association with the Houston Department of Health and Human Services for the first IDU cycle of the National HIV Behavioral Surveillance System. About 76% of the IDUs reported previously being tested for HIV. Demographic variables that displayed a significant association with prior testing during the univariate analyses include age, race/ethnicity, birth outside the United States, education level, recent arrest, and current health insurance coverage. Several drug-related and sexual behaviors also demonstrated significant associations with prior testing, including age of first injection drug use, heroin use, methamphetamine use, source of needles or syringes, consistent use of new needles, recent visits to a shooting gallery or similar location, previous alcohol or drug treatment, condom use during their most recent sexual encounter, and having sexual partners who also used injection drugs. Additionally, the univariate analyses revealed that recent use of health or HIV prevention services was associated with previously testing for HIV. The final multivariable model included age, race/ethnicity, recent arrest, previous alcohol or drug treatment, and heroin use. ^

A cross sectional examination of risky sexual behaviors among a population of drug users

This study is a secondary data analysis that assesses the relationship between risky sexual behaviors and sexually transmitted infections (STIs) among drug users. This study analyzes data collected from drug users in the Houston Metropolitan area during 2004 and through August 2005, by researchers with the DASH (Drugs, AIDS, STDs and Hepatitis) project at The University of Texas at Houston School of Public Health. Specifically, the sexually transmitted infections that will be of interest in this proposed study are Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV). Risky sexual behaviors that will be examined include lack of condom use, sexual orientation, trading sex for drugs, trading sex for money, and number of male and female sexual partners in the last 4 weeks. ^ Unadjusted, gender, sexual orientation, number of recent male and female sex partners, and a history of injection drug use were all found to be significant independent variables that increased the odds of STI status. When included in an overall model, these variables significantly increased the odds of STI status, including HBV infection, HIV infection, and HBV/HIV co-infection. History of injection drug use was significant for both HBV and HBV/HIV co-infection, whereas a gay sexual orientation was significant for both HIV and HBV/HIV co-infection. Additionally, having excessive female sex partners was significant for HIV infection. This significant association increases the need for implementation of stronger intervention programs tailored to suit this population's needs such as a combination of drug and sexually transmitted disease (STD) treatment. ^ The importance of these findings is that they establish the strength of associations between the previously mentioned risky sexual behaviors and STI status among drug users. This is crucial for assessing future risk of infection as well as for serving as a necessary component in intervention and treatment programs both for drug use and STIs. ^

Prevalence and risk factors for human immunodefiency virus and hepatitis C virus co-infection among drug users in innercity neighborhoods in Houston, Texas

Background. There are 200,000 HIV/HCV co-infected people in the US and IDUs are at highest risk of exposure. Between 52-92% of HIV infected IDUs are chronically infected with HCV. African Americans and Hispanics bear the largest burden of co-infections. Furthermore HIV/HCV co-infection is associated with high morbidity and mortality if not treated. The present study investigates the demographic, sexual and drug related risk factors for HIV/HCV co-infection among predominantly African American injecting and non-injecting drug users living in two innercity neighborhoods in Houston, Texas. ^ Methods. This secondary analysis used data collected between February 2004 and June 2005 from 1,889 drug users. Three case-comparison analyses were conducted to investigate the risk factors for HIV/HCV co-infection. HIV mono-infection, HCV mono-infection and non-infection were compared to HIV/HCV co-infection to build multivariate logistic regression models. Race/ethnicity and age were forced into each model regardless of significance in the univariate analysis. ^ Results. The overall prevalence of HIV/HCV co-infection was 3.9% while 39.8% of HIV infected drug users were co-infected with HCV and 10.7% of HCV infected drug users were co-infected with HIV. Among HIV infected IDUs the prevalence of HCV was 71.7% and among HIV infected NIDUs the prevalence of HCV was 24%. In the multivariate analysis, HIV/HCV co-infection was associated with injecting drug use when compared to HIV mono-infection, with MSM when compared to HCV mono-infection and with injecting drug use as well as MSM when compared to non-infection. ^ Conclusion. HIV/HCV co-infection was associated with a combination of sexual and risky injecting practices. More data on the prevalence and risk factors for co-infection among minority populations is urgently needed to support the development of targeted interventions and treatment options. Additionally there should be a focus on promoting safer sex and injecting practices among drug users as well as the expansion of routine testing for HIV and HCV infections in this high risk population.^

Factors associated with needle sharing among Black male injection drug users in Harris County, Texas

Background. Injection drug users (IDUs) are at increased risk for HIV transmission due to unique risk behaviors, such as sharing needles. In Houston, IDUs account for 18% of all HIV/AIDS cases among Black males. ^ Objectives. This analysis compared demographic, behavioral, and psychosocial characteristics of needle sharing and non-sharing IDUs in a population of Black males in Harris County, Texas. ^ Methods. Data used for this analysis were from the second IDU cycle of the National HIV Behavioral Surveillance System. This dataset included a sample of 288 Black male IDUs. Univariate and multivariate statistical analysis were performed to determine statistically significant associations of needle sharing in this population and to create a functional model to inform local HIV prevention programs. ^ Results. Half of the participants in this analysis shared needles in the past 12 months. Compared to non-sharers, sharers were more likely to be homeless (OR=3.70, p<0.01) or arrested in the past year (OR=2.31, p<0.01), inject cocaine (OR=2.07, p<0.01), report male-to-male sex in the past year (OR=6.97, p<0.01), and to exchange sex for money or drugs. Sharers were less likely than non-sharers to graduate high school (OR=0.36, p<0.01), earn $5,000 or more a year (OR=1.15, p=0.05), get needles from a medical source (OR=0.59, p=0.03), and ever test for HIV (OR=0.17, p<0.01). Sharers were more likely to report depressive symptoms (OR=3.49, p<0.01), lower scores on the family support scale (mean difference 0.41, p=0.01) and decision-making confidence scale (mean difference 0.38, p<0.01), and greater risk-taking (mean difference -0.49, p<0.01) than non-sharers. In a multivariable logistic regression, sharers were less likely to have graduated high school (OR=0.33, p<0.01) and have been tested for HIV (OR=0.12, p<0.01) and were more likely to have been arrested in the past year (OR=2.3, p<0.01), get needles from a street source (OR=3.87, p<0.01), report male-to-male sex (OR=7.01, p<0.01), and have depressive symptoms (OR=2.36, p=0.02) and increased risk-taking (OR=1.78, p=0.01). ^ Conclusions. IDUs that shared needles are different from those that did not, reporting lower socioeconomic status, increased sexual and risk behaviors, increased depressive symptoms and increased risk-taking. These findings suggest that intervention programs that also address these demographic, behavioral, and psychosocial factors may be more successful in decreasing needle sharing among this population.^