Analysis of recurrent failure times: A time-dependent Yule process approach

Analysis of recurrent events has been widely discussed in medical, health services, insurance, and engineering areas in recent years. This research proposes to use a nonhomogeneous Yule process with the proportional intensity assumption to model the hazard function on recurrent events data and the associated risk factors. This method assumes that repeated events occur for each individual, with given covariates, according to a nonhomogeneous Yule process with intensity function λx(t) = λ 0(t) · exp( x′β). One of the advantages of using a non-homogeneous Yule process for recurrent events is that it assumes that the recurrent rate is proportional to the number of events that occur up to time t. Maximum likelihood estimation is used to provide estimates of the parameters in the model, and a generalized scoring iterative procedure is applied in numerical computation. ^ Model comparisons between the proposed method and other existing recurrent models are addressed by simulation. One example concerning recurrent myocardial infarction events compared between two distinct populations, Mexican-American and Non-Hispanic Whites in the Corpus Christi Heart Project is examined. ^

An analysis of the revenue policy -making process of the Texas Legislature

The purpose of this dissertation was to develop a conceptual framework which can be used to account for policy decisions made by the House Ways and Means Committee (HW&MC) of the Texas House of Representatives. This analysis will examine the actions of the committee over a ten-year period with the goal of explaining and predicting the success of failure of certain efforts to raise revenue.^ The basis framework for modelling the revenue decision-making process includes three major components--the decision alternatives, the external factors and two competing contingency theories. The decision alternatives encompass the particular options available to increase tax revenue. The options were classified as non-innovative or innovative. The non-innovative options included the sales, franchise, property and severance taxes. The innovative options were principally the personal and corporate income taxes.^ The external factors included political and economic constraints that affected the actions of the HW&MC. Several key political constraints on committee decision-making were addressed--including public attitudes, interest groups, political party strength and tradition and precedents. The economic constraints that affected revenue decisions included court mandates, federal mandates and the fiscal condition of the nation and the state.^ The third component of the revenue decision-making framework included two alternative contingency theories. The first alternative theory postulated that the committee structure, including the individual member roles and the overall committee style, resulted in distinctive revenue decisions. This theory will be favored if evidence points to the committee acting autonomously with less concern for the policies of the Speaker of the House. The Speaker assignment theory, postulated that the assignment of committee members shaped or changed the course of committee decision-making. This theory will be favored if there was evidence that the committee was strictly a vehicle for the Speaker to institute his preferred tax policies.^ The ultimate goal of this analysis is to develop an explanation for legislative decision-making about tax policy. This explanation will be based on the linkages across various tax options, political and economic constraints, member roles and committee style and the patterns of committee assignment. ^

Hebbian analysis of the transformation of medial entorhinal grid-cell inputs to hippocampal place fields.

The discovery of grid cells in the medial entorhinal cortex (MEC) permits the characterization of hippocampal computation in much greater detail than previously possible. The present study addresses how an integrate-and-fire unit driven by grid-cell spike trains may transform the multipeaked, spatial firing pattern of grid cells into the single-peaked activity that is typical of hippocampal place cells. Previous studies have shown that in the absence of network interactions, this transformation can succeed only if the place cell receives inputs from grids with overlapping vertices at the location of the place cell's firing field. In our simulations, the selection of these inputs was accomplished by fast Hebbian plasticity alone. The resulting nonlinear process was acutely sensitive to small input variations. Simulations differing only in the exact spike timing of grid cells produced different field locations for the same place cells. Place fields became concentrated in areas that correlated with the initial trajectory of the animal; the introduction of feedback inhibitory cells reduced this bias. These results suggest distinct roles for plasticity of the perforant path synapses and for competition via feedback inhibition in the formation of place fields in a novel environment. Furthermore, they imply that variability in MEC spiking patterns or in the rat's trajectory is sufficient for generating a distinct population code in a novel environment and suggest that recalling this code in a familiar environment involves additional inputs and/or a different mode of operation of the network.

A cladistic analysis of apolipoprotein B gene variation and plasma lipid and apolipoprotein B levels, using familial data

Any functionally important mutation is embedded in an evolutionary matrix of other mutations. Cladistic analysis, based on this, is a method of investigating gene effects using a haplotype phylogeny to define a set of tests which localize causal mutations to branches of the phylogeny. Previous implementations of cladistic analysis have not addressed the issue of analyzing data from related individuals, though in human studies, family data are usually needed to obtain unambiguous haplotypes. In this study, a method of cladistic analysis is described in which haplotype effects are parameterized in a linear model which accounts for familial correlations. The method was used to study the effect of apolipoprotein (Apo) B gene variation on total-, LDL-, and HDL-cholesterol, triglyceride, and Apo B levels in 121 French families. Five polymorphisms defined Apo B haplotypes: the signal peptide Insertion/deletion, Bsp 1286I, XbaI, MspI, and EcoRI. Eleven haplotypes were found, and a haplotype phylogeny was constructed and used to define a set of tests of haplotype effects on lipid and apo B levels.^ This new method of cladistic analysis, the parametric method, found significant effects for single haplotypes for all variables. For HDL-cholesterol, 3 clusters of evolutionarily-related haplotypes affecting levels were found. Haplotype effects accounted for about 10% of the genetic variance of triglyceride and HDL-cholesterol levels. The results of the parametric method were compared to those of a method of cladistic analysis based on permutational testing. The permutational method detected fewer haplotype effects, even when modified to account for correlations within families. Simulation studies exploring these differences found evidence of systematic errors in the permutational method due to the process by which haplotype groups were selected for testing.^ The applicability of cladistic analysis to human data was shown. The parametric method is suggested as an improvement over the permutational method. This study has identified candidate haplotypes for sequence comparisons in order to locate the functional mutations in the Apo B gene which may influence plasma lipid levels. ^

Implementation analysis of the Texas Vendor Drug Program

An agency is accountable to a legislative body in the implementation of public policy. It has a responsibility to ensure that the implementation of that policy is consistent with its statutory objectives.^ The analysis of the effectiveness of implementation of the Vendor Drug Program proceeded in the following manner. The federal and state roles and statutes pursuant to the formulation of the Vendor Drug Program were reviewed to determine statutory intent and formal provisions. The translation of these into programmatic details was examined focusing on the factors impacting the implementation process. Lastly, the six conditions outlined by Mazmanian and Sabatier as criteria for effective implementation, were applied to the implementation of the Vendor Drug Program to determine if the implementation was effective in relation to consistency with statutory objectives.^ The implementation of the statutes clearly met four of the six conditions for effective implementation: (1) clear and consistent objectives; (2) a valid causal theory; (3) structured the process to maximize agency and target compliance with the objectives; and (4) had continued support of constituency groups and sovereigns.^ The implementation was basically consistent with the statutory objectives, although the determination of vendor reimbursement has had and continues to have problems. ^

Genetic analysis of tumor progression susceptibility in the mouse skin model

In the field of chemical carcinogenesis the use of animal models has proved to be a useful tool in dissecting the multistage process of tumor formation. In this regard the outbred SENCAR mouse has been the strain of choice in the analysis of skin carcinogenesis given its high sensitivity to the chemically induced acquisition of premalignant lesions, papillomas, and the later progression of these lesions into squamous cell carcinomas (SCC).^ The derivation of an inbred strain from the SENCAR stock called SSIN, that in spite of a high sensitivity to the development of papillomas lack the ability to transform these premalignant lesions into SCC, suggested that tumor promotion and progression were under the genetic control of different sets of genes.^ In the present study the nature of susceptibility to tumor progression was investigated. Analysis of F1 hybrids between the outbred SENCAR and SSIN mice suggested that there is at least one dominant gene responsible for susceptibility to tumor progression.^ Later development of another inbred strain from the outbred SENCAR stock, that had sensitivity to both tumor promotion and progression, allowed the formulation of a more accurate genetic model. Using this newly derived line, SENCAR B/Pt. and SSIN it was determined that there is one dominant tumor progression susceptibility gene. Linkage analysis showed that this gene maps to mouse chromosome 14 and it was possible to narrow the region to a 16 cM interval.^ In order to better characterize the nature of the progression susceptibility differences between these two strains, their proliferative pattern was investigated. It was found that SENCAR B/Pt, have an enlarged proliferative compartment with overexpression of cyclin D1, p16 and p21. Further studies showed an aberrant overexpression of TGF-$\beta$ in the susceptible strain, an increase in apoptosis, p53 protein accumulation and early loss of connexin 26. These results taken together suggest that papillomas in the SENCAR B/Pt. mice have higher proliferation and may have an increase in genomic instability, these two factors would contribute to a higher sensitivity to tumor progression. ^

Transcriptional regulation and functional analysis of the human Wilms' tumor 1 gene

The Wilms' tumor 1 gene (WT1) encodes a zinc-finger transcription factor and is expressed in urogenital, hematopoietic and other tissues. It is expressed in a temporal and spatial manner in both embryonic and adult stages. To obtain a better understanding of the biological function of WT1, we studied two aspects of WT1 regulation: one is the identification of tissue-specific cis-regulatory elements that regulate its expression, the other is the downstream genes which are modulated by WT1.^ My studies indicate that in addition to the promoter, other regulatory elements are required for the tissue specific expression of this gene. A 259-bp hematopoietic specific enhancer in intron 3 of the WT1 gene increased the transcriptional activity of the WT1 promoter by 8- to 10-fold in K562 and HL60 cells. Sequence analysis revealed both GATA and c-Myb motifs in the enhancer fragment. Mutation of the GATA motif decreased the enhancer activity by 60% in K562 cells. Electrophoretic mobility shift assays showed that both GATA-1 and GATA-2 proteins in K562 nuclear extracts bind to this motif. Cotransfection of the enhancer containing reporter construct with a GATA-1 or GATA-2 expression vector showed that both GATA-1 and GATA-2 transactivated this enhancer, increasing the CAT reporter activity 10-15 fold and 5-fold respectively. Similar analysis of the c-Myb motif by cotransfection with the enhancer CAT reporter construct and a c-Myb expression vector showed that c-Myb transactivated the enhancer by 5-fold. A DNase I-hypersensitive site has been identified in the 258 bp enhancer region. These data suggest that GATA-1 and c-Myb are responsible for the activity of this enhancer in hematopoietic cells and may bind to the enhancer in vivo. In the process of searching for cis-regulatory elements in transgenic mice, we have identified a 1.0 kb fragment that is 50 kb downstream from the promoter and is required for the central nervous system expression of WT1.^ In the search for downstream target genes of WT1, we noted that the proto-oncogene N-myc is coexpressed with the tumor suppressor gene WT1 in the developing kidney and is overexpressed in many Wilms' tumors. Sequence analysis revealed eleven consensus WT1 binding sites located in the 1 kb mouse N-myc promoter. We further showed that the N-myc promoter was down-regulated by WT1 in transient transfection assays. Electrophoretic mobility shift assays showed that oligonucleotides containing the WT1 motifs could bind WT1 protein. Furthermore, a Denys-Drash syndrome mutant of WT1, R394W, that has a mutation in the DNA binding domain, failed to repress the N-myc promoter. This suggests that the repression of the N-myc promoter is mediated by DNA binding of WT1. This finding helps to elucidate the relationship of WT1 and N-myc in tumorigenesis and renal development. ^

ANALYSIS OF THE CORYNEBACTERIUM PARVUM-INDUCED DECLINE OF MURINE NATURAL KILLER CELL-MEDIATED CYTOTOXICITY

Treatment of mice with the immunomodulating agent, Corynebacterium parvum (C. parvum), was shown to result in a severe and long-lasting depression of splenic natural killer (NK) cell-mediated cytotoxicity 5-21 days post-inoculation. Because NK cells have been implicated in immunosurveillance against malignancy (due to their spontaneous occurrence and rapid reactivity to a variety of histological types of tumors), as well as in resistance to established tumors, this decreased activity was of particular concern, since this effect is contrary to that which would be considered therapeutically desirable in cancer treatment (i.e. a potentiation of antitumor effector functions, including NK cell activity, would be expected to lead to a more effective destruction of malignant cells). Therefore, an analysis of the mechanism of this decline of splenic NK cell activity in C.parvum treated mice was undertaken.^ From in vitro co-culturing experiments, it was found that low NK-responsive C. parvum splenocytes were capable of reducing the normally high-reactivity of cells from untreated syngeneic mice to YAC-1 lymphoma, suggesting the presence of NK-directed suppressor cells in C. parvum treated animals. This was further supported by the demonstration of normal levels of cytotoxicity in C. parvum splenocyte preparations following Ficoll-Hypaque separation, which coincided with removal of the NK-suppressive capabilities of these cells. The T cell nature of these regulatory cells was indicated by (1) the failure of C. parvum to cause a reduction of NK cell activity, or the generation of NK-directed suppressor cells in T cell-deficient athymic mice, (2) the removal of C. parvum-induced suppression by T cell-depleting fractionation procedures or treatments, and (3) demonstration of suppression of NK cell activity by T cell-enriched C. parvum splenocytes. These studies suggest, therefore, that the eventual reduction of suppression by T cell elimination and/or inhibition, may result in a promotion of the antitumor effectiveness of C. parvum due to the contribution of "freed" NK effector cell activity.^ However, the temporary suppression of NK cell activity induced by C. parvum (reactivity of treated mice returns to normal levels within 28 days after C. parvum injection), may in fact be favorable in some situations, e.g. in bone marrow transplantation cases, since NK cells have been suggested to play a role also in the process of bone marrow graft rejection.^ Therefore, the discriminate use of agents such as C. parvum may allow for the controlled regulation of NK cell activity suggested to be necessary for the optimalization of therapeutic regimens. ^

Functional analysis of BLAP75, a BLM-associated protein

Bloom syndrome (BS) is an autosomal recessive disorder characterized by dwarfism, immunodeficiency, impaired fertility, and most importantly, early development of a broad range of cancers. The hallmark of BS cells is hyper-recombination, characterized by a drastically elevated frequency of sister chromatid exchange (SCE). BLM, the gene mutated in BS, encodes a DNA helicase of the RecQ protein family. BLM is thought to participate in several DNA transactions and to interact with many proteins involved in DNA replication, recombination, and repair. However, the precise function of BLM and the BLM-dependent anti-tumor mechanism remain obscure. ^ A novel protein, BLAP75 (BLM-associated polypeptide, 75KD), was identified to form an evolutionarily conserved complex with BLM and DNA topoisomerase IIIα (Topo IIIα). Our work demonstrates that loss of BLAP75 destabilized BLM and Topo IIIα proteins. BLAP75 colocalized with BLM in subnuclear foci in response to DNA damage and the recruitment of BLM to these foci was BLAP75-dependent. Moreover, depletion of BLAP75 by siRNA resulted in an elevated SCE rate similar to cells depleted of BLM by siRNA. In addition, RNAi-mediated silencing of BLAP75 greatly diminished cell viability. This cellular deficiency was rescued by expression of wild type BLAP75 but not BLAP75 with mutated conserved domain III, which abrogated the interaction between BLAP75, BLM and Topo IIIα, suggesting that the integrity of BLM-Topo IIIα-BLAP75 complex might be critical for cell survival. Finally, I found that BLAP75 was phosphorylated during mitosis and upon various DNA-damaging agents, implying that BLAP75 might also function in mitosis and DNA damage response. ^ Taken together, this study has defined BLAP75 as an integral component of the BLM complex to maintain genome stability. Our findings provide insights into the molecular mechanisms of the BLM helicase pathway and tumorigenesis process associated with these mechanisms. ^

Analysis of prognostic factors for the development of metastases and survival in renal cell carcinoma patients

Introduction and objective. A number of prognostic factors have been reported for predicting survival in patients with renal cell carcinoma. Yet few studies have analyzed the effects of those factors at different stages of the disease process. In this study, different stages of disease progression starting from nephrectomy to metastasis, from metastasis to death, and from evaluation to death were evaluated. ^ Methods. In this retrospective follow-up study, records of 97 deceased renal cell carcinoma (RCC) patients were reviewed between September 2006 to October 2006. Patients with TNM Stage IV disease before nephrectomy or with cancer diagnoses other than RCC were excluded leaving 64 records for analysis. Patient TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were analyzed in relation to time to metastases. Time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from metastases to death. Finally, analysis of laboratory values at time of evaluation, Eastern Cooperative Oncology Group performance status (ECOG), UCLA Integrated Staging System (UISS), time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from evaluation to death. Linear regression and Cox Proportional Hazard (univariate and multivariate) was used for testing significance. Kaplan-Meier Log-Rank test was used to detect any significance between groups at various endpoints. ^ Results. Compared to negative lymph nodes at time of nephrectomy, a single positive lymph node had significantly shorter time to metastasis (p<0.0001). Compared to other histological types, clear cell histology had significant metastasis free survival (p=0.003). Clear cell histology compared to other types (p=0.0002 univariate, p=0.038 multivariate) and time to metastasis with log conversion (p=0.028) significantly affected time from metastasis to death. A greater than one year and greater than two year metastasis free interval, compared to patients that had metastasis before one and two years, had statistically significant survival benefit (p=0.004 and p=0.0318). Time from evaluation to death was affected by greater than one year metastasis free interval (p=0.0459), alcohol consumption (p=0.044), LDH (p=0.006), ECOG performance status (p<0.001), and hemoglobin level (p=0.0092). The UISS risk stratified the patient population in a statistically significant manner for survival (p=0.001). No other factors were found to be significant. ^ Conclusion. Clear cell histology is predictive for both time to metastasis and metastasis to death. Nodal status at time of nephrectomy may predict risk of metastasis. The time interval to metastasis significantly predicts time from metastasis to death and time from evaluation to death. ECOG performance status, and hemoglobin levels predicts survival outcome at evaluation. Finally, UISS appropriately stratifies risk in our population. ^

Racial disparities in CD4 counts at initial HIV-1 diagnosis: Analysis of the Adult Spectrum of HIV disease dataset and public health implications

Introduction. The HIV/AIDS disease burden disproportionately affects minority populations, specifically African Americans. While sexual risk behaviors play a role in the observed HIV burden, other factors including gender, age, socioeconomics, and barriers to healthcare access may also be contributory. The goal of this study was to determine how far down the HIV/AIDS disease process people of different ethnicities first present for healthcare. The study specifically analyzed the differences in CD4 cell counts at the initial HIV-1 diagnosis with respect to ethnicity. The study also analyzed racial differences in HIV/AIDS risk factors. ^ Methods. This is a retrospective study using data from the Adult Spectrum of HIV Disease (ASD), collected by the City of Houston Department of Health. The ASD database contains information on newly reported HIV cases in the Harris County District Hospitals between 1989 and 2000. Each patient had an initial and a follow-up report. The extracted variables of interest from the ASD data set were CD4 counts at the initial HIV diagnosis, race, gender, age at HIV diagnosis and behavioral risk factors. One-way ANOVA was used to examine differences in baseline CD4 counts at HIV diagnosis between racial/ethnic groups. Chi square was used to analyze racial differences in risk factors. ^ Results. The analyzed study sample was 4767. The study population was 47% Black, 37% White and 16% Hispanic [p<0.05]. The mean and median CD4 counts at diagnosis were 254 and 193 cells per ml, respectively. At the initial HIV diagnosis Blacks had the highest average CD4 counts (285), followed by Whites (233) and Hispanics (212) [p<0.001 ]. These statistical differences, however, were only observed with CD4 counts above 350 [p<0.001], even when adjusted for age at diagnosis and gender [p<0.05]. Looking at risk factors, Blacks were mostly affected by intravenous drug use (IVDU) and heterosexuality, whereas Whites and Hispanics were more affected by male homosexuality [ p<0.05]. ^ Conclusion. (1) There were statistical differences in CD4 counts with respect to ethnicity, but these differences only existed for CD4 counts above 350. These differences however do not appear to have clinical significance. Antithetically, Blacks had the highest CD4 counts followed by Whites and Hispanics. (2) 50% of this study group clinically had AIDS at their initial HIV diagnosis (median=193), irrespective of ethnicity. It was not clear from data analysis if these observations were due to failure of early HIV surveillance, HIV testing policies or healthcare access. More studies need to be done to address this question. (3) Homosexuality and bisexuality were the biggest risk factors for Whites and Hispanics, whereas for Blacks were mostly affected by heterosexuality and IVDU, implying a need for different public health intervention strategies for these racial groups. ^

Health care policy analysis of Medicaid's early and periodic screening, diagnosis, and treatment (EPSDT) benefit in Colorado

The purpose of this thesis is to identify "best practice" recommendations for successful implementation of the EPSDT outreach program at Memorial Health System's Hospital for Children in Colorado Springs through a policy analysis of Medicaid EPSDT services in Colorado. A successful program at Memorial will increase education and awareness of EPSDT services, enrollment, and access to and utilization of health care services for eligible children. Methodology utilized in this study included questionnaires designed for the EPSDT contract administrator and outreach coordinators/workers; analysis of current federal and state policies; and studies conducted at the federal and state level, and by various advocacy groups. The need for this analysis of EPSDT came about in part through an awareness of increasingly high numbers of children in poverty and who are uninsured. Though the percentage of children living in poverty in Colorado is slightly below the national average (see Table 2), according to data analyzed by The Annie E. Casey Foundation, the percentage of children (0-18) living in poverty in Colorado increased from 10% in 2000 to 16% in 2006, a dramatic increase of 60% surpassed by only one other state in the nation (The Annie E. Casey Foundation, 2008). By comparison, the U.S. percentage of children in poverty during the same time frame rose from 17% to 18% (The Annie E. Casey Foundation, 2008). What kind of health care services are available to this vulnerable and growing group of Coloradans, and what are the barriers that affect their enrollment in, access to and utilization of these health care services? Barriers identified included difficulty with the application process; system and process issues; a lack of providers; and a lack of awareness and knowledge of EPSDT. Fiscal restraints and legislation at the federal and state level are also barriers to increasing enrollment and access to services. Outreach services are a critical component of providing EPSDT services, and there were several recommendations regarding outreach and case management that will benefit the program in the future. Through this analysis and identification of a broad range of barriers, a clearer picture emerged of current challenges within the EPSDT program as well as a broad range of strategies and recommendations to address these challenges. Through increased education and advocacy for EPSDT and the services it encompasses; stronger collaboration and cooperation between all groups involved, including providing a Medical Home for all eligible children; and new legislation putting more money and focus on comprehensive health care for low-income uninsured children; enrollment, access to and utilization of developmentally appropriate and quality health care services can be achieved. ^

Analysis of the E1-ubiquitin activating enzyme, Uba1, in cell death and tissue growth in Drosophila

Ubiquitination is an essential process involved in basic biological processes such as the cell cycle and cell death. Ubiquitination is initiated by ubiquitin-activating enzymes (E1), which activate and transfer ubiquitin to ubiquitin-conjugating enzymes (E2). Subsequently, ubiquitin is transferred to target proteins via ubiquitin ligases (E3). Defects in ubiquitin conjugation have been implicated in several forms of malignancy, the pathogenesis of several genetic diseases, immune surveillance/viral pathogenesis, and the pathology of muscle wasting. However, the consequences of partial or complete loss of ubiquitin conjugation in multi-cellular organisms are not well understood. Here, we report the characterization of nba1, the sole E1 in Drosophila. We have determined that weak and strong nba1 alleluias behave genetically different and sometimes in opposing phenotypes. For example, weak uba1 alleluias protect cells from cell death whereas cells containing strong loss-of-function alleluias are highly apoptotic. These opposing phenotypes are due to differing sensitivities of cell death pathway components to ubiquitination level alterations. In addition, strong uba1 alleluias induce cell cycle arrest due to defects in the protein degradation of Cyclins. Surprisingly, clones of strong uba1 mutant alleluias stimulate neighboring wild-type tissue to undergo cell division in a non-autonomous manner resulting in severe overgrowth phenotypes in the mosaic fly. I have determined that the observed overgrowth phenotypes were due to a failure to downregulate the Notch signaling pathway in nba1 mutant cells. Aberrant Notch signaling results in the secretion of a local cytokine and activation of JAK/STAT pathway in neighboring cells. In addition, we elucidated a model describing the regulation of the caspase Dronc in surviving cells. Binding of Dronc by its inhibitor Diap1 is necessary but not sufficient to inhibit Dronc function. Ubiquitin conjugation and Uba1 function is necessary for the negative regulation of Dronc. ^

A qualitative analysis of leadership styles and the selection of quality improvement in primary care practice

In the Practice Change Model, physicians act as key stakeholders, people who have both an investment in the practice and the capacity to influence how the practice performs. This leadership role is critical to the development and change of the practice. Leadership roles and effectiveness are an important factor in quality improvement in primary care practices.^ The study conducted involved a comparative case study analysis to identify leadership roles and the relationship between leadership roles and the number and type of quality improvement strategies adopted during a Practice Change Model-based intervention study. The research utilized secondary data from four primary care practices with various leadership styles. The practices are located in the San Antonio region and serve a large Hispanic population. The data was collected by two ABC Project Facilitators from each practice during a 12-month period including Key Informant Interviews (all staff members), MAP (Multi-method Assessment Process), and Practice Facilitation field notes. This data was used to evaluate leadership styles, management within the practice, and intervention tools that were implemented. The chief steps will be (1) to analyze if the leader-member relations contribute to the type of quality improvement strategy or strategies selected (2) to investigate if leader-position power contributes to the number of strategies selected and the type of strategy selected (3) and to explore whether the task structure varies across the four primary care practices.^ The research found that involving more members of the clinic staff in decision-making, building bridges between organizational staff and clinical staff, and task structure are all associated with the direct influence on the number and type of quality improvement strategies implemented in primary care practice.^ Although this research only investigated leadership styles of four different practices, it will offer future guidance on how to establish the priorities and implementation of quality improvement strategies that will have the greatest impact on patient care improvement. ^