Spatial Variability in Relationships between Early Childhood Lead Exposure and Standardized Test Scores in Fourth Grade North Carolina Public School Students (2013-2016).

BACKGROUND: Exposure to lead during childhood is detrimental to children's health. The extent to which the association between lead exposure and elementary school academic outcomes varies across geography is not known. OBJECTIVE: Estimate associations between blood lead levels (BLLs) and fourth grade standardized test scores in reading and mathematics in North Carolina using models that allow associations between BLL and test scores to vary spatially across communities. METHODS: We link geocoded, individual-level, standardized test score data for North Carolina public school students in fourth grade (2013-2016) with detailed birth records and blood lead testing data retrieved from the North Carolina childhood blood lead state registry on samples typically collected at 1-6 y of age. BLLs were categorized as: 1µg/dL (reference), 2µg/dL, 3-4µg/dL and ≥5µg/dL. We then fit spatially varying coefficient models that incorporate information sharing (smoothness), across neighboring communities via a Gaussian Markov random field to provide a global estimate of the association between BLL and test scores, as well as census tract-specific estimates (i.e., spatial coefficients). Models adjusted for maternal- and child-level covariates and were fit separately for reading and math. RESULTS: The average BLL across the 91,706 individuals in the analysis dataset was 2.84µg/dL. Individuals were distributed across 2,002 (out of 2,195) census tracts in North Carolina. In models adjusting for child sex, birth weight percentile for gestational age, and Medicaid participation as well as maternal race/ethnicity, educational attainment, marital status, and tobacco use, BLLs of 2µg/dL, 3-4µg/dL and ≥5µg/dL were associated with overall lower reading test scores of -0.28 [95% confidence interval (CI): -0.43, -0.12], -0.53 (-0.69, -0.38), and -0.79 (-0.99, -0.604), respectively. For BLLs of 1µg/dL, 2µg/dL, 3-4µg/dL and ≥5µg/dL, spatial coefficients-that is, tract-specific adjustments in reading test score relative to the "global" coefficient-ranged from -9.70 to 2.52, -3.19 to 3.90, -11.14 to 7.85, and -4.73 to 4.33, respectively. Results for mathematics were similar to those for reading. CONCLUSION: The association between lead exposure and reading and mathematics test scores exhibits considerable heterogeneity across North Carolina communities. These results emphasize the need for prevention and mitigation efforts with respect to lead exposures everywhere, with special attention to locations where the cognitive impact is elevated. https://doi.org/10.1289/EHP13898.

Probing the biophysical properties of primary breast tumor-derived fibroblasts.

As cancer progresses, cells must adapt to a new and stiffer environment, which can ultimately alter how normal cells within the tumor behave. In turn, these cells are known to further aid tumor progression. Therefore, there is potentially a unique avenue to better understand metastatic potential through single-cell biophysical assays performed on patient-derived cells. Here, we perform biophysical characterization of primary human fibroblastic cells obtained from mammary carcinoma and normal contralateral tissue. Through a series of tissue dissociation, differential centrifugation and trypsinization steps, we isolate an adherent fibroblastic population viable for biomechanical testing. 2D TFM and 3D migration measurements in a collagen matrix show that fibroblasts obtained from patient tumors generate more traction forces and display improved migration potential than their counterparts from normal tissue. Moreover, through the use of an embedded spheroid model, we confirmed the extracellular matrix (ECM) remodeling behavior of primary cells isolated from carcinoma. Overall, correlating biophysical characterization of normal- and carcinoma-derived samples from individual patient along with patient outcome may become a powerful approach to further our comprehension of metastasis and ultimately design drug targets on a patient-specific basis.