Semiparametric Mixed Models for Medical Monitoring Data: An Overview.

The potential to characterize nonlinear progression over time is now possible in many health conditions due to advancements in medical monitoring and more frequent data collection. It is often of interest to investigate differences between experimental groups in a study or identify the onset of rapid changes in the response of interest using medical monitoring data; however, analytic challenges emerge. We review semiparametric mixed-modeling extensions that accommodate medical monitoring data. Throughout the review, we illustrate these extensions to the semiparametric mixed-model framework with an application to prospective clinical data obtained from 24-hour ambulatory blood pressure monitoring, where it is of interest to compare blood pressure patterns from children with obstructive sleep apnea to those arising from healthy controls.

Endometrial thickness for invasive investigations in women with postmenopausal bleeding.

OBJECTIVE: To determine the prevalence of endometrial hyperplasia and endometrial cancer in postmenopausal women with endometrial thickness of 4.1-8 mm on transvaginal ultrasound scan. DESIGN: Prospective observational study carried out in the Heart of England NHS Trust Teaching Hospital in the West Midlands, UK, in a population of 58 women with postmenopausal bleeding. METHOD: Prospective analysis of all women referred to the Rapid Access Clinic in the Heart of England Hospital with a history of postmenopausal bleeding over a 12-month period (April 2007-April 2008). Endometrial histology was taken as the final diagnosis. The main outcome measure was endometrial histology in women with postmenopausal bleeding with endometrial thickness of 4.1-8 mm. RESULTS: All women (n = 58) diagnosed with endometrial thickness of 4.1-8 mm on transvaginal sonography were included in the analysis. Pipelle endometrial biopsy could only be performed in 22 women (37.9%). Hysteroscopy was performed in 45 women (77.5%). Out of these, a histological diagnosis was available in 28 women (62.2%). In the remaining 17 women, the endometrium was observed as atrophic on hysteroscopy. In these 17 cases, either no or insufficient endometrial sample was obtained. In total, two (3.4%) women were diagnosed with complex endometrial hyperplasia and two (3.4%) women were diagnosed with endometrial carcinoma. CONCLUSION: There was a significant prevalence of endometrial hyperplasia and endometrial cancer in postmenopausal women with a history of postmenopausal bleeding and who had endometrial thickness of 4.1-8 mm. Therefore, the current recommendation of histological assessment on all women with endometrial thickness >4 mm should remain unchanged.

Physiological effects on demography: a long-term experimental study of testosterone's effects on fitness.

Understanding physiological and behavioral mechanisms underlying the diversity of observed life-history strategies is challenging because of difficulties in obtaining long-term measures of fitness and in relating fitness to these mechanisms. We evaluated effects of experimentally elevated testosterone on male fitness in a population of dark-eyed juncos studied over nine breeding seasons using a demographic modeling approach. Elevated levels of testosterone decreased survival rates but increased success of producing extra-pair offspring. Higher overall fitness for testosterone-treated males was unexpected and led us to consider indirect effects of testosterone on offspring and females. Nest success was similar for testosterone-treated and control males, but testosterone-treated males produced smaller offspring, and smaller offspring had lower postfledging survival. Older, more experienced females preferred to mate with older males and realized higher reproductive success when they did so. Treatment of young males increased their ability to attract older females yet resulted in poor reproductive performance. The higher fitness of testosterone-treated males in the absence of a comparable natural phenotype suggests that the natural phenotype may be constrained. If this phenotype were to arise, the negative social effects on offspring and mates suggest that these effects might prevent high-testosterone phenotypes from spreading in the population.