Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (5 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2016)

In epidemiologic studies, researchers are commonly interested in quantifying geospatial effects on the incidence of disease to illustrate health disparities potentially attributable to environmental, demographic, and/or socioeconomic factors. The current research we focus on the development of advanced statistical modeling methods to determine how the pattern of disease outcome changes over geographical location.

We first extend and illustrate the utility of MapGAM, a user-friendly R package that provides a unified framework for estimating, predicting and drawing inference on covariate-adjusted spatial effects using individual-level data. The package also facilitates visualization of spatial effects via automated mapping procedures. MapGAM estimates covariate-adjusted spatial associations with a univariate outcome using generalized additive models that include a non-parametric bivariate smooth term of geolocation parameters. Estimation and mapping methods are implemented for continuous, discrete, and right-censored survival data.

Next, we note that smoothing approaches commonly implemented in generalized additive models and used in spatial analyses assume the amount of smoothing to be equal across geographical regions. The result is that some regions tend to be under-smoothed, while others are over-smoothed. We extend the work of Yue, etc. (2010) in the context of brain imaging analysis and propose a hierarchical Bayesian adaptive thin-plate spline that allows for spatial smoothing of continuous, binary and count outcomes along with the ability to adjust for potential confounding factors. The proposed method allows for the amount of smoothing to flexibly vary depending on the local extent of spatial effect by using nonstationary spatial Gaussian Markov random fields. Performance of the approach is evaluated via simulation and the proposed methodology is applied to an epidemiologic study investigating spatial heterogeneity in the risk of preterm birth among Massachusetts residents.

Finally, we further extend the proposed adaptive smoothing techniques to the case of right-censored survival outcome data. Simulation is used to compare the performance of the proposed method to commonly used non-adaptive smoothing method, and the approach is applied to data from an epidemiology study seeking to quantify spatial variability in the survival times of advanced-stage ovarian cancer patients in California.

    Cover page: Statistical Methods for Quantifying Spatial Effects on Disease Incidence Using Individual-Level Data
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2020)
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2016)
      The striatum is an important subcortical structure with extensive connections to other regions of the brain. These connections are believed to play important roles in behaviors such as reward-related processes and impulse control, which show significant sex differences. However, little is known about sex differences in the striatum-projected fiber connectivity. The current study examined sex differences between 50 Chinese males and 79 Chinese females in their fiber connections between the striatum and nine selected cortical and subcortical regions. Despite overall similarities, males showed stronger fiber connections between the left caudate and rostral cingulate cortex, between the right putamen and the lateral orbitofrontal cortex, between the bilateral putamen and the ventro-lateral prefrontal cortex, and between the right caudate and the ventro-lateral prefrontal cortex, whereas females showed stronger fiber connections between the right putamen and the dorsolateral prefrontal cortex, between bilateral caudate and hippocampus, and between the left putamen and hippocampus. These findings help us to understand sex differences in the striatum-projected fiber connections and their implications for sex differences in behaviors.
        Cover page: Sex Differences in Fiber Connection between the Striatum and Subcortical and Cortical Regions
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2015)

        Objective

        We sought to determine the impact of geographic location on advanced-stage ovarian cancer mortality in relation to adherence to National Comprehensive Cancer Network (NCCN) treatment guidelines and hospital case volume.

        Study design

        This was a retrospective observational cohort study of patients diagnosed with stage IIIC/IV epithelial ovarian cancer (Jan. 1, 1996, through Dec. 31, 2006) identified from the California Cancer Registry. Generalized additive models were created to assess the effect of spatial distributions of geographic location, demographic characteristics, disease-related variables, adherence to NCCN guidelines, and hospital case volume, with simultaneous smoothing of geographic location and adjustment for confounding variables.

        Results

        A total of 11,765 patients were identified. Twelve of the 378 hospitals (3.2%) were high-volume hospitals (HVH) (≥20 cases/y) and cared for 2112 patients (17.9%). For all patients, the median distance to an HVH was 22.7 km/14.1 miles and 80% were located within 79.6 km/49.5 miles of an HVH. Overall, 45.4% of patients were treated according to NCCN guidelines. The global test for location revealed that geographic position within the state was significantly correlated with ovarian cancer mortality after adjusting for other variables (P < .001). Distance to receive care ≥32 km/20 miles was protective against mortality (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.79-0.93), while distance from an HVH ≥80 km/50 miles was associated with an increased risk of death (HR, 1.13; 95% CI, 1.03-1.23). The effects of geographic predictors were attenuated when nonadherence to NCCN guidelines (HR, 1.25; 95% CI, 1.18-1.32) and care at an HVH (HR, 0.87; 95% CI, 0.81-0.93) were introduced into the model.

        Conclusion

        Geographic location is a significant predictor of advanced-stage ovarian cancer mortality and the effect is primarily related to the likelihood of receiving NCCN guideline adherent care and treatment at an HVH.
          Cover page: Spatial analysis of advanced-stage ovarian cancer mortality in California
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2024)

          Background

          Pulmonary ischaemia-reperfusion injury (IRI) is a major contributor to poor lung transplant outcomes. We recently demonstrated a central role of airway-centred natural killer (NK) cells in mediating IRI; however, there are no existing effective therapies for directly targeting NK cells in humans.

          Methods

          We hypothesised that a depleting anti-CD94 monoclonal antibody (mAb) would provide therapeutic benefit in mouse and human models of IRI based on high levels of KLRD1 (CD94) transcripts in bronchoalveolar lavage samples from lung transplant patients.

          Results

          We found that CD94 is highly expressed on mouse and human NK cells, with increased expression during IRI. Anti-mouse and anti-human mAbs against CD94 showed effective NK cell depletion in mouse and human models and blunted lung damage and airway epithelial killing, respectively. In two different allogeneic orthotopic lung transplant mouse models, anti-CD94 treatment during induction reduced early lung injury and chronic inflammation relative to control therapies. Anti-CD94 did not increase donor antigen-presenting cells that could alter long-term graft acceptance.

          Conclusions

          Lung transplant induction regimens incorporating anti-CD94 treatment may safely improve early clinical outcomes.
            Cover page: CD94+ Natural Killer cells potentiate pulmonary ischemia-reperfusion injury.
            Top