Origins of the Tumor Microenvironment: Quantitative Assessment of Adipose-Derived and Bone Marrow–Derived Stroma

To meet the requirements for rapid tumor growth, a complex array of non-neoplastic cells are recruited to the tumor microenvironment. These cells facilitate tumor development by providing matrices, cytokines, growth factors, as well as vascular networks for nutrient and waste exchange, however their precise origins remain unclear. Through multicolored tissue transplant procedures; we have quantitatively determined the contribution of bone marrow-derived and adipose-derived cells to stromal populations within syngeneic ovarian and breast murine tumors. Our results indicate that subpopulations of tumor-associated fibroblasts (TAFs) are recruited from two distinct sources. The majority of fibroblast specific protein (FSP) positive and fibroblast activation protein (FAP) positive TAFs originate from mesenchymal stem/stromal cells (MSC) located in bone marrow sources, whereas most vascular and fibrovascular stroma (pericytes, α-SMA+ myofibroblasts, and endothelial cells) originates from neighboring adipose tissue. These results highlight the capacity for tumors to utilize multiple sources of structural cells in a systematic and discriminative manner

Fixed and random effects models: making an informed choice

This paper assesses the options available to researchers analysing multilevel (including longitudinal) data, with the aim of supporting good methodological decision-making. Given the confusion in the literature about the key properties of fixed and random effects (FE and RE) models, we present these models’ capabilities and limitations. We also discuss the within-between RE model, sometimes misleadingly labelled a ‘hybrid’ model, showing that it is the most general of the three, with all the strengths of the other two. As such, and because it allows for important extensions—notably random slopes—we argue it should be used (as a starting point at least) in all multilevel analyses. We develop the argument through simulations, evaluating how these models cope with some likely mis-specifications. These simulations reveal that (1) failing to include random slopes can generate anti-conservative standard errors, and (2) assuming random intercepts are Normally distributed, when they are not, introduces only modest biases. These results strengthen the case for the use of, and need for, these models

Which Price is Right: Load or Premium?*

This paper uses national time series data for the United States to investigate whether changes in the premium or loading fee offer a better explanation for variations in the percentage of the population with private health insurance from 1960 to 2004. The empirical results suggest that premium provides a better measure of price when estimating the demand for health insurance at the extensive margin. The empirical analysis also indicates that the aggregate short-run price and income elasticities of demand for health insurance are fairly close at −0.19 and 0.27, respectively. One implication is that the percentage of the population with private health insurance in the United States should continue to decline in the future if real premiums persistently grow significantly faster than the overall economy. The Geneva Risk and Insurance Review (2008) 33, 90–105. doi:10.1057/grir.2008.10

Soil recovery across a chronosequence of restored wetlands in the Florida Everglades

The restoration project in the Hole-in-the-Donut of Everglades National Park in Florida, USA is to reestablish native wetlands by complete removal of the invasive plants and the associated soil. However, there is little information available about changes in properties of the newly formed Marl soils in restored wetlands. In this study, we measured soil physicochemical properties, soil enzymatic activities, and stable isotopes of carbon (δ(13)C) in plants and soil organic carbon (SOC) in an undisturbed natural wetland (UNW) and three wetlands restored respectively in 1989, 1996 and 1999 (WR89, WR96 and WR99). The older restored wetlands (WR89 and WR96) are characterized by greater SOC and mineral nitrogen. The values of soil dehydrogenase and phosphatase activities in the four wetlands follow the order: UNW > WR89 > WR96 > WR99, and are consistent with changes in vegetation coverage. The principal component analysis shows that dehydrogenase and phosphatase activities are the vital variables contributing to the soil of UNW. The similar δ(13)C values of SOC and plants in the restored wetlands suggest the formation of SOC during restoration is mainly derived from the associated plants. These results indicate that the newly restored soils develop toward the soil in the UNW with time since restoration