Hierarchical Archimedean copula models for the analysis of binary familial data.

Archimedean copulas are commonly used in a wide range of statistical models due to their simplicity, manageable analytical expressions, rich choices of generator functions, and other workable properties. However, the exchangeable dependence structure inherent to Archimedean copulas limits its application to familial data, where the dependence among family members is often different. When response variables are binary, modeling the familial associations becomes more challenging due to the stringent constraints imposed on the dependence parameters. This paper proposes hierarchical Archimedean copulas to account for the natural hierarchical dependence structure in familial data and addresses the details in the modeling of binary familial data and the inference based on maximum likelihood estimate. An example showing the flexibility of this powerful tool is also presented with possible extension to other similar studies.

Weighted scores method for regression models with dependent data.

There are copula-based statistical models in the literature for regression with dependent data such as clustered and longitudinal overdispersed counts, for which parameter estimation and inference are straightforward. For situations where the main interest is in the regression and other univariate parameters and not the dependence, we propose a "weighted scores method", which is based on weighting score functions of the univariate margins. The weight matrices are obtained initially fitting a discretized multivariate normal distribution, which admits a wide range of dependence. The general methodology is applied to negative binomial regression models. Asymptotic and small-sample efficiency calculations show that our method is robust and nearly as efficient as maximum likelihood for fully specified copula models. An illustrative example is given to show the use of our weighted scores method to analyze utilization of health care based on family characteristics.

Computer modeling technology to assess extracapsular tissue coverage of whole mount sections after retropubic and laparoscopic radical prostatectomy.

PURPOSE: The introduction of new surgical approaches to radical prostatectomy requires methodologies that permit valid comparison that are more expedient than long-term outcomes of biochemical local and distant failure and survival. We used a computer modeling program to assess the percent of extracapsular tissue coverage of prostate glands removed by the open retropubic and laparoscopic approaches. MATERIALS AND METHODS: Specimens were available for 15 and 17 patients who underwent open and laparoscopic radical prostatectomy, respectively. Serial whole mount sections were taken at 5 mm intervals. A genitourinary pathologist drew the contours of the prostate capsule on each tissue section. The whole mount was scanned to produce digital images. A software program was used to create a file with capsule information and a file with extraprostatic fibroadipose tissue information. Two separate point cloud files were generated to represent the capsule and extraprostatic models, and software algorithms were used to generate differences in the point clouds to quantify the extent of extracapsular tissue coverage. RESULTS: When separated into sides dissected by a nerve or nonnerve sparing technique, the overall percent of gland surface coverage by extracapsular fibroadipose tissue was statistically greater with laparoscopic dissection than with the open approach. When a segmental analysis of gland coverage was evaluated, a statistically greater percent of fibroadipose coverage was associated with laparoscopic dissection in the apical and inferolateral segments with nonnerve sparing, and in the apical segment with nerve sparing. CONCLUSIONS: This small radical prostatectomy series, analyzed by computer reconstruction as described, provides information suggesting that overall extracapsular tissue coverage is at least equal if not superior using the laparoscopic vs the open approach. This was specifically the case in areas of inferolateral and apical dissection with nonnerve sparing procedures and in areas of the apical dissection with nerve sparing procedures.

Aging is associated with a rapid decline in frequency, alterations in subset composition, and enhanced Th2 response in CD1d-restricted NKT cells from human peripheral blood.

NKT cells are important for initiating and regulating immune responses. We investigated the age-related changes in the CD1d-restricted semi-invariant NKT (iNKT) cells in peripheral blood of healthy adults. The iNKT cell frequency was 2.5- to 10.7-fold less in healthy elderly subjects (61 years and over) compared to the healthy young subjects (20-40 years, p<0.001). This age-related decline in iNKT cells was observed both in freshly isolated PBMC and in cultures where iNKT cells were enriched by alpha-GalCer stimulation using either the Valpha24/Vbeta11 TCR antibody pair or the CD1d-tetramer as the iNKT cell marker. The decline in frequency was associated with an alteration in the iNKT cell subset compositions: an increase in the proportion of CD4+ subset and a decrease in the proportion of CD4/CD8 double-negative (DN) subset. The age-related decline in iNKT cells and changes in subset composition were independent from the age-related changes of conventional T cells/T cell subsets. Additionally, there was a Th1 to Th2 shift in the cytokine response profile from iNKT cells with aging. We conclude that aging is associated with a significant decline in iNKT cell frequency in peripheral blood, accompanied with alterations in subset composition and cytokine response profile.