Duty to Protect: Enhancing the Federal Framework to Prevent Childhood Lead Poisoning and Exposure to Environmental Harm

Scientific evidence indisputably demonstrates that lead poisoning causes permanent neurological damage and numerous co-morbidities for children and adults. Exposure to lead hazards irreversibly harms individuals and, left unchecked, can devastate communities into the future. In recognition of these threats, the President\u27s Task Force on Environmental Health Risks and Safety Risks to Children (Task Force) was established by Executive Order in 1997. The original Task Force created the first coordinated federal response to eliminate childhood lead poisoning in the United States and set an ambitious ten-year timeline to achieve its goals of prevention, treatment, research, and progress management. However, the most recent Task Force retreated from these bold goals. Rather than eliminating lead poisoning, in 2018 the Task Force sought merely to reduce it. This Article provides a comprehensive overview of the dangers of lead exposure, details the federal government\u27s evolving response to lead poisoning, and, for the first time, disseminates previously unpublished comments on Drafting a New Federal Strategy to Reduce Childhood Lead Exposures and Impacts, submitted to the Task Force in 2017, ahead of its most recent report. By providing these comments publicly, this Article creates a record of critical recommendations to the Task Force, provides best practices for the federal government\u27s response to lead poisoning, and encourages federal policymakers to take the necessary steps to meet the original goal of eradicating lead hazards and protecting children from lead poisoning

Duty to Protect: Enhancing the Federal Framework to Prevent Childhood Lead Poisoning and Exposure to Environmental Harm

Scientific evidence indisputably demonstrates that lead poisoning causes permanent neurological damage and numerous co-morbidities for children and adults. Exposure to lead hazards irreversibly harms individuals and, left unchecked, can devastate communities into the future. In recognition of these threats, the President\u27s Task Force on Environmental Health Risks and Safety Risks to Children (Task Force) was established by Executive Order in 1997. The original Task Force created the first coordinated federal response to eliminate childhood lead poisoning in the United States and set an ambitious ten-year timeline to achieve its goals of prevention, treatment, research, and progress management

Health Justice Strategies to Eradicate Lead Poisoning: An Urgent Call to Safeguard Future Generations

Despite over a century of evidence that lead is a neurotoxin that causes irreparable harm, today, lead continues to pervade children\u27s environments and remains a constant threat to health and wellbeing. One in three homes across the United States housing children under the age of six has significant lead-based paint hazards that place occupants at risk of permanent neurological harm and lifelong poor health risks. Federal, state, and local governments must use a range of primary prevention strategies in order to fully eradicate the risks and protect children from lead poisoning. This Article provides a comprehensive examination of best practices for addressing lead poisoning and proposes urgent reform measures at the local and state levels. Successful interventions ultimately prioritize health justice strategies and rely on community ownership and cross-sector participation; dedicate significant resources and funding to completely eliminate lead in the environment; and prioritize primary prevention practices that identify lead-based paint hazards before children are exposed

New Particle Formation from the Vapor Phase : From Barrier-Controlled Nucleation to the Collisional Limit

Studies of vapor phase nucleation have largely been restricted to one of two limiting cases—nucleation controlled by a substantial free energy barrier or the collisional limit where the barrier is negligible. For weakly bound systems, exploring the transition between these regimes has been an experimental challenge, and how nucleation evolves in this transition remains an open question. We overcome these limitations by combining complementary Laval expansion experiments, providing new particle formation data for carbon dioxide over a uniquely broad range of conditions. Our experimental data together with a kinetic model using rate constants from high-level quantum chemical calculations provide a comprehensive picture of new particle formation as nucleation transitions from a barrier-dominated process to the collisional limit.Peer reviewe

Application to the Analysis of Germinal Center Reactions In Vivo

Simultaneous detection of multiple cellular and molecular players in their native environment, one of the keys to a full understanding of immune processes, remains challenging for in vivo microscopy. Here, we present a synergistic strategy for spectrally multiplexed in vivo imaging composed of (i) triple two-photon excitation using spatiotemporal synchronization of two femtosecond lasers, (ii) a broad set of fluorophores with emission ranging from blue to near infrared, (iii) an effective spectral unmixing algorithm. Using our approach, we simultaneously excite and detect seven fluorophores expressed in distinct cellular and tissue compartments, plus second harmonics generation from collagen fibers in lymph nodes. This enables us to visualize the dynamic interplay of all the central cellular players during germinal center reactions. While current in vivo imaging typically enables recording the dynamics of 4 tissue components at a time, our strategy allows a more comprehensive analysis of cellular dynamics involving 8 single-labeled compartments. It enables to investigate the orchestration of multiple cellular subsets determining tissue function, thus, opening the way for a mechanistic understanding of complex pathophysiologic processes in vivo. In the future, the design of transgenic mice combining a larger spectrum of fluorescent proteins will reveal the full potential of our method

Identification and validation of potential new biomarkers for prostate cancer diagnosis and prognosis using 2D-DIGE and MS

This study was designed to identify and validate potential new biomarkers for prostate cancer and to distinguish patients with and without biochemical relapse. Prostate tissue samples analyzed by 2D-DIGE (two-dimensional difference in gel electrophoresis) and mass spectrometry (MS) revealed downregulation of secernin-1 (P < 0.044) in prostate cancer, while vinculin showed significant upregulation (P < 0.001). Secernin-1 overexpression in prostate tissue was validated using Western blot and immunohistochemistry while vinculin expression was validated using immunohistochemistry. These findings indicate that secernin-1 and vinculin are potential new tissue biomarkers for prostate cancer diagnosis and prognosis, respectively. For validation, protein levels in urine were also examined by Western blot analysis. Urinary vinculin levels in prostate cancer patients were significantly higher than in urine from nontumor patients (P = 0.006). Using multiple reaction monitoring-MS (MRM-MS) analysis, prostatic acid phosphatase (PAP) showed significant higher levels in the urine of prostate cancer patients compared to controls (P = 0.012), while galectin-3 showed significant lower levels in the urine of prostate cancer patients with biochemical relapse, compared to those without relapse (P = 0.017). Three proteins were successfully differentiated between patients with and without prostate cancer and patients with and without relapse by using MRM. Thus, this technique shows promise for implementation as a noninvasive clinical diagnostic technique

Heterogeneity of cellular inflammatory responses in ageing white matter and relationship to Alzheimer’s and small vessel disease pathologies

Abstract: White matter lesions (WML) are common in the ageing brain, often arising in a field effect of diffuse white matter abnormality. Although WML are associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD), their cause and pathogenesis remain unclear. The current study tested the hypothesis that different patterns of neuroinflammation are associated with SVD compared to AD neuropathology by assessing the immunoreactive profile of the microglial (CD68, IBA1 and MHC‐II) and astrocyte (GFAP) markers in ageing parietal white matter (PARWM) obtained from the Cognitive Function and Ageing Study (CFAS), an ageing population‐representative neuropathology cohort. Glial responses varied extensively across the PARWM with microglial markers significantly higher in the subventricular region compared to either the middle‐zone (CD68 p = 0.028, IBA1 p < 0.001, MHC‐II p < 0.001) or subcortical region (CD68 p = 0.002, IBA1 p < 0.001, MHC‐II p < 0.001). Clasmatodendritic (CD) GFAP+ astrocytes significantly increased from the subcortical to the subventricular region (p < 0.001), whilst GFAP+ stellate astrocytes significantly decreased (p < 0.001). Cellular reactions could be grouped into two distinct patterns: an immune response associated with MHC‐II/IBA1 expression and CD astrocytes; and a more innate response characterised by CD68 expression associated with WML. White matter neuroinflammation showed weak relationships to the measures of SVD, but not to the measures of AD neuropathology. In conclusion, glial responses vary extensively across the PARWM with diverse patterns of white matter neuroinflammation. Although these findings support a role for vascular factors in the pathogenesis of age‐related white matter neuroinflammation, additional factors other than SVD and AD pathology may drive this. Understanding the heterogeneity in white matter neuroinflammation will be important for the therapeutic targeting of age‐associated white matter damage

The Science of Pronominal Usage: He and It in Co-Reference to Inanimate Objects in Late Middle English Texts on Alchemy

This is the author's accepted manuscript. The published version can be found at http://dx.doi.org/10.1177/0075424210384225This article explores the variation between he and it in coreference to inanimate entities (such as mercury, sulfur, and salt). Using alchemical texts from the fifteenth century as material, the article demonstrates that there was much more variation in pronominal reference in this period than has previously been shown. Of the possible explanations suggested by previous research, the earlier grammatical gender system and transference from Latin do not seem to play a role, while pronoun clustering and pronominal reanalysis appear to influence the quantitative distribution. The scale of individuation used by Siemund and Stenroos to explain similar usage is shown not to be a straightforward predictor. Other factors such as personification and perceived similarities between animate and inanimate entities may affect the degree of perceived individuation. The choice of he over she seems to be influenced by pronominal reanalysis and straightforward personification in some cases. In other instances, it is speculated that the he usage reflects (stereotypical) gender conceptions in the Middle Ages

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD