Discussion: “Comparison of Statistical Methods for Assessing Spatial Correlations Between Maps of Different Arterial Properties” (Rowland, E. M., Mohamied, Y., Chooi, K. Y., Bailey, E. L., and Weinberg, P. D., 2015, ASME J. Biomech. Eng., 137(10), p. 101003): An Alternative Approach Using Segmentation Based on Local Hemodynamics

The biological response of living arteries to mechanical forces is an important component of the atherosclerotic process and is responsible, at least in part, for the well-recognized spatial variation in atherosusceptibility in man. Experiments to elucidate this response often generate maps of force and response variables over the arterial surface, from which the force–response relationship is sought. Rowland et al. discussed several statistical approaches to the spatial autocorrelation that confounds the analysis of such maps and applied them to maps of hemodynamic stress and vascular response obtained by averaging these variables in multiple animals. Here, we point out an alternative approach, in which discrete surface regions are defined by the hemodynamic stress levels they experience, and the stress and response in each animal are treated separately. This approach, applied properly, is insensitive to autocorrelation and less sensitive to the effect of confounding hemodynamic variables. The analysis suggests an inverse relation between permeability and shear that differs from that in Rowland et al. Possible sources of this difference are suggested

Obesity Indicators and C - reactive Protein in African and Haitian Americans with and without Type 2 Diabetes

Purpose: High sensitivity C-reactive protein (CRP) is a risk factor for cardiovascular disease based on finding in primarily non-Hispanic White populations. Obesity, another risk factor for cardiovascular disease, is higher in Blacks as compared to non-Hispanic Whites. The objective of this study was to assess the relationship between CRP, a marker of systemic inflammation, and obesity indicators by ethnicity, diabetes status and gender for two Black ethnicities. Methods: Anthropometrics and venous blood were collected for African and Haitian Americans with and without type 2 diabetes in a cross-sectional study. A total of 434 participants; 190 African Americans, 244 Haitian Americans, met the inclusion criteria of CRP ≤10 mg/L. Main effects and interactions of ethnicity, diabetes status, gender, and each obesity indicator (waist circumference, waist-to-height ratio, and body mass index) were performed using General Linear Models. Results: African Americans were more likely to be obese, have higher CRP, and smoke as compared to Haitian Americans. Haitian Americans has a lower rate of health care coverage than African American. Having a higher education level than Haitian Americans was a protective health factor for African Americans; whereas, Haitian Americans were protected by a higher percent married as compared to African Americans. All obesity indicators were associated with CRP. All differences in CRP by ethnicity and diabetes status were negated by obesity indicators. Being female was associated with higher CRP for waist circumference and BMI models. Adjusting for health insurance, smoking, marital status and education negated the relationship of gender and CRP for waist-to- height ratio. Conclusion: Being African American as opposed to Haitian American was a greater risk factor for obesity and inflammation. Obesity was associated with elevated CRP levels in African and Haitian Americans regardless of diabetes status. Inflammation constitutes a serious health problem for minorities with high rates of obesity

Gene Expression Signatures of Radiation Response Are Specific, Durable and Accurate in Mice and Humans

Background: Previous work has demonstrated the potential for peripheral blood (PB) gene expression profiling for the detection of disease or environmental exposures. Methods and Findings: We have sought to determine the impact of several variables on the PB gene expression profile of an environmental exposure, ionizing radiation, and to determine the specificity of the PB signature of radiation versus other genotoxic stresses. Neither genotype differences nor the time of PB sampling caused any lessening of the accuracy of PB signatures to predict radiation exposure, but sex difference did influence the accuracy of the prediction of radiation exposure at the lowest level (50 cGy). A PB signature of sepsis was also generated and both the PB signature of radiation and the PB signature of sepsis were found to be 100 % specific at distinguishing irradiated from septic animals. We also identified human PB signatures of radiation exposure and chemotherapy treatment which distinguished irradiated patients and chemotherapy-treated individuals within a heterogeneous population with accuracies of 90 % and 81%, respectively. Conclusions: We conclude that PB gene expression profiles can be identified in mice and humans that are accurate i

Serum after Autologous Transplantation Stimulates Proliferation and Expansion of Human Hematopoietic Progenitor Cells

Regeneration after hematopoietic stem cell transplantation (HSCT) depends on enormous activation of the stem cell pool. So far, it is hardly understood how these cells are recruited into proliferation and self-renewal. In this study, we have addressed the question if systemically released factors are involved in activation of hematopoietic stem and progenitor cells (HPC) after autologous HSCT. Serum was taken from patients before chemotherapy, during neutropenia and after hematopoietic recovery. Subsequently, it was used as supplement for in vitro culture of CD34+ cord blood HPC. Serum taken under hematopoietic stress (4 to 11 days after HSCT) significantly enhanced proliferation, maintained primitive immunophenotype (CD34+, CD133+, CD45−) for more cell divisions and increased colony forming units (CFU) as well as the number of cobblestone area-forming cells (CAFC). The stimulatory effect decays to normal levels after hematopoietic recovery (more than 2 weeks after HSCT). Chemokine profiling revealed a decline of several growth-factors during neutropenia, including platelet-derived growth factors PDGF-AA, PDGF-AB and PDGF-BB, whereas expression of monocyte chemotactic protein-1 (MCP-1) increased. These results demonstrate that systemically released factors play an important role for stimulation of hematopoietic regeneration after autologous HSCT. This feedback mechanism opens new perspectives for in vivo stimulation of the stem cell pool

MODEL-BASED SHEAR STRESS GRADIENT IN REALISTIC VASCULAR FLOWS AND ITS RELATION TO ARTERIAL MACROMOLECULAR PERMEABILITY

ABSTRACT Evans blue dye (EBD) was injected into the carotid arteries of three anesthetized pigs and allowed to circulate for 90 minutes. At the conclusion of the 90-minute period, the animals were sacrificed and injection casts of the infrarenal aorta and iliac-femoral arteries were prepared. The casts with their surrounding arteries were removed and immersed in fixative. After fixation, the EBD-stained vessels were separated from the casts, which were used to construct computational meshes for simulation of the flow fields and wall shear stress distributions that had existed in the casted regions during the experiments. The inlet flow waves and flow partitions were based on flow measurements performed during each experiment. Based on a conceptual model of the relation between shear stress nonuniformity and permeability increase, the spatial and angular variation of the gradient of the time-average shear stress at the walls of the external iliac arteries was found from the computational fluid dynamic simulations for each experiment. Using affine transformations, the gradient and time-average shear stress results, and the EBD optical density distributions, were mapped to a common template, allowing pixel-by-pixel correlations of the hemodynamic stress parameters and local permeability. The results suggest that both shear stress gradient and time-average shear play a role in determining vascular permeability to macromolecules