Peering In/Overheard.

M.F.A. Thesis. University of Hawaiʻi at Mānoa 2018

Evaluating the Number of Stages in Development of Squamous Cell and Adenocarcinomas across Cancer Sites Using Human Population-Based Cancer Modeling

BACKGROUND: Adenocarcinomas (ACs) and squamous cell carcinomas (SCCs) differ by clinical and molecular characteristics. We evaluated the characteristics of carcinogenesis by modeling the age patterns of incidence rates of ACs and SCCs of various organs to test whether these characteristics differed between cancer subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Histotype-specific incidence rates of 14 ACs and 12 SCCs from the SEER Registry (1973-2003) were analyzed by fitting several biologically motivated models to observed age patterns. A frailty model with the Weibull baseline was applied to each age pattern to provide the best fit for the majority of cancers. For each cancer, model parameters describing the underlying mechanisms of carcinogenesis including the number of stages occurring during an individual's life and leading to cancer (m-stages) were estimated. For sensitivity analysis, the age-period-cohort model was incorporated into the carcinogenesis model to test the stability of the estimates. For the majority of studied cancers, the numbers of m-stages were similar within each group (i.e., AC and SCC). When cancers of the same organs were compared (i.e., lung, esophagus, and cervix uteri), the number of m-stages were more strongly associated with the AC/SCC subtype than with the organ: 9.79±0.09, 9.93±0.19 and 8.80±0.10 for lung, esophagus, and cervical ACs, compared to 11.41±0.10, 12.86±0.34 and 12.01±0.51 for SCCs of the respective organs (p<0.05 between subtypes). Most SCCs had more than ten m-stages while ACs had fewer than ten m-stages. The sensitivity analyses of the model parameters demonstrated the stability of the obtained estimates. CONCLUSIONS/SIGNIFICANCE: A model containing parameters capable of representing the number of stages of cancer development occurring during individual's life was applied to the large population data on incidence of ACs and SCCs. The model revealed that the number of m-stages differed by cancer subtype being more strongly associated with ACs/SCCs histotype than with organ/site

Differences in the GH-IGF-I axis in children of different weight and fitness status

OBJECTIVE: To determine if differences in the GH-IGF-I axis exist between children of high and low aerobic fitness who are obese or of normal weight. DESIGN: 124 children (ages 8–11) divided into four groups based on BMI and VO(2)max (mL O(2)/kg fat free mass(FFM)/min): normal weight — high-fit (NH), normal weight — low-fit (NL), obese — high-fit (OH), and obese — low-fit (OL). Height, weight, skinfolds, body mass index (BMI), body fat percentage and predicted VO(2)max (both ml/kg/min and ml/kg(FFM)/min) were assessed. Resting growth hormone (GH), total insulin-like growth factor 1 (total IGF-I), free insulin-like growth factor 1(free IGF-I), and insulin were measured using morning fasting blood samples. RESULTS: GH was greater in the NH group compared to the OL group only (p<0.01). No group differences existed for either total IGF-I (p=0.53) or free IGF-I (p=0.189). Insulin was greater in the OH and OL groups than the NH and NL groups (p<0.01). With groups combined (or overall), insulin and free IGF-I were related to fitness (insulin — ml/kg/min: r=−0.226, p<0.05 and ml/kg(FFM)/min: r= −0.212, p < 0.05; free IGF-I — ml/kg/min: r=−0.219, p<0.01 and ml/kg(FFM)/min: r= −0.272, p < 0.05). CONCLUSIONS: Fitness may contribute to the obesity related reduction of GH that may be involved with weight gain

The role of meetings in the social practice of strategy

This paper addresses the recent turn in strategy research to practice-based theorizing. Based on a data set of 51 meeting observations, the paper examines how strategy meetings are involved in either stabilizing existing strategic orientations or proposing variations that cumulatively generate change in strategic orientations. Eleven significant structuring characteristics of strategy meetings are identified and examined with regard to their potential for stabilizing or destabilizing existing strategic orientations. Based on a taxonomy of meeting structures, we explain three typical evolutionary paths through which variations emerge, are maintained and developed, and are selected or de-selected. The findings make four main contributions. First, they contribute to the literature on strategy-as-practice by explaining how the practice of meetings is related to consequential strategic outcomes. Second, they contribute to the literature on organizational becoming by demonstrating the role of meetings in shaping stability and change. Third, they extend and elaborate the concept of meetings as strategic episodes. Fourth, they contribute to the literature on garbage can models of strategy-making