Quantitative performance assessment of Ultivue multiplex panels in formalin-fixed, paraffin-embedded human and murine tumor specimens.

We present a rigorous validation strategy to evaluate the performance of Ultivue multiplex immunofluorescence panels. We have quantified the accuracy and precision of four different multiplex panels (three human and one mouse) in tumor specimens with varying levels of T cell density. Our results show that Ultivue panels are typically accurate wherein the relative difference in cell proportion between a multiplex image and a 1-plex image is less than 20% for a given biomarker. Ultivue panels exhibited relatively high intra-run precision (CV ≤ 25%) and relatively low inter-run precision (CV >> 25%) which can be remedied by using local intensity thresholding to gate biomarker positivity. We also evaluated the reproducibility of cell-cell distance estimates measured from multiplex images which show high intra- and inter-run precision. We introduce a new metric, multiplex labeling efficiency, which can be used to benchmark the overall fidelity of the multiplex data across multiple batch runs. Taken together our results provide a comprehensive characterization of Ultivue panels and offer practical guidelines for analyzing multiplex images.

Too tired to think: Relationship between post-COVID-19 fatigue and cognition in a veteran sample.

COVID-19 survivors often endorse persistent physical and neuropsychiatric problems following disease recovery, a phenomenon described as "long COVID." Research exploring long-COVID continues to evolve in large-scale studies but remains limited among smaller populations (e.g., veterans). We explored the relationship between persistent post-COVID-19 fatigue and cognition among a sample of 246 veterans who voluntarily enrolled in a COVID-19 Convalescence Programme and completed a mental health evaluation of post-illness mood (depression, anxiety, PTSD), cognition (subjective complaints, Modified Telephone Interview for Cognitive Status [TICS-M] performance), fatigue, pain, and sleep. In concert with our hypotheses, subjective cognitive complaints are not significantly correlated with TICS-M performance, but rather are strongly correlated with long-COVID fatigue. Although cognitive changes are common post-COVID complaints, these are likely better predicted by other factors, (e.g., fatigue, mood, pain, and sleep disruption). Furthermore, comorbid mood, sleep, and pain complaints appeared to mediate the relationship between subjective cognitive complaints and fatigue. Limitations to this study included use of retrospective chart review data, limited access to pre-disease data for comparison, and lack of healthy controls. Clinicians should consider the impact of modifiable conditions associated with cognitive and functional decline, as these conditions may be targets for interdisciplinary treatment in a long-COVID veteran population.

Longitudinal multi-omics study of palbociclib resistance in HR-positive/HER2-negative metastatic breast cancer.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6) therapy plus endocrine therapy (ET) is an effective treatment for patients with hormone receptor-positive/human epidermal receptor 2-negative metastatic breast cancer (HR+/HER2- MBC); however, resistance is common and poorly understood. A comprehensive genomic and transcriptomic analysis of pretreatment and post-treatment tumors from patients receiving palbociclib plus ET was performed to delineate molecular mechanisms of drug resistance. METHODS: Tissue was collected from 89 patients with HR+/HER2- MBC, including those with recurrent and/or metastatic disease, receiving palbociclib plus an aromatase inhibitor or fulvestrant at Samsung Medical Center and Seoul National University Hospital from 2017 to 2020. Tumor biopsy and blood samples obtained at pretreatment, on-treatment (6 weeks and/or 12 weeks), and post-progression underwent RNA sequencing and whole-exome sequencing. Cox regression analysis was performed to identify the clinical and genomic variables associated with progression-free survival. RESULTS: Novel markers associated with poor prognosis, including genomic scar features caused by homologous repair deficiency (HRD), estrogen response signatures, and four prognostic clusters with distinct molecular features were identified. Tumors with TP53 mutations co-occurring with a unique HRD-high cluster responded poorly to palbociclib plus ET. Comparisons of paired pre- and post-treatment samples revealed that tumors became enriched in APOBEC mutation signatures, and many switched to aggressive molecular subtypes with estrogen-independent characteristics. We identified frequent genomic alterations upon disease progression in RB1, ESR1, PTEN, and KMT2C. CONCLUSIONS: We identified novel molecular features associated with poor prognosis and molecular mechanisms that could be targeted to overcome resistance to CKD4/6 plus ET. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03401359. The trial was posted on 18 January 2018 and registered prospectively.

Lead in Air, Soil, and Blood: Pb Poisoning in a Changing World.

(1) Background: Leaded petrol became a worldwide vehicle fuel during the 20th century. While leaded petrol was totally banned on 30 August 2021, its lead (Pb) dust legacy remains in the environment as soil Pb. The health impacts of Pb are well known and risks occur when exposures are above zero. The inextricable links between air Pb, soil Pb, and blood Pb are not widely A. Exposure risks continue even after banning leaded petrol and must be explored. (2) Methods: This article evaluates selected examples of temporal measurements of atmospheric Pb and human Pb exposure and the effect of soil Pb on blood Pb. Several search engines were used to find articles on temporal changes in air Pb and human Pb exposures. New Orleans studies provided empirical data on the association between soil Pb and blood Pb. (3) Results: Vehicle Pb emission trends are closely associated with air Pb and blood Pb. Air Pb deposited in soil becomes a reservoir of Pb dust that is known to be remobilized into the atmosphere. (4) Conclusions: The dust from leaded petrol continues to pose major exposure risks to humans. Exogenous sources of Pb in soil and its remobilization into air along with endogenous bone Pb establish the baseline exposure of children and adults. Reducing human exposure to Pb requires novel policies to decrease exogenous contact from the reservoir of Pb in soil and curtailing remobilization of soil Pb into the atmosphere. Mitigating exposure to soil Pb must therefore play a central role in advancing primary prevention.

Agreement ℜ of Four Analytical Methods Applied to Pb in Soils from the Small City of St. John's, Newfoundland, Canada.

In the small city of St. John's, NL (2020 population ~114,000), 100% of the soils of the pre-1926 properties exceeded the Canadian soil Pb standard, 140 mg/kg. The Pb was traced to high-Pb coal ash used for heating and disposed on the soils outside. Analytical instruments became available in the late 1960s and 1970s and were first used for blood Pb and clinical studies and repurposed for measuring environmental Pb. The environmental research part of this study compared four common soil Pb analysis methods on the same set (N = 96) of St. John's soil samples. The methods: The US EPA method 3050B, portable X-ray fluorescence spectrometry (pXRF), The Chaney-Mielke leachate extraction (1 M nitric acid), and the relative bioaccessibility leaching procedure (US EPA method 1340). Correlation is not the same as agreement ℜ. There is strong agreement (Berry-Mielke's Universal ℜ) among the four soil Pb analytical methods. Accordingly, precaution is normally advisable to protect children from the high-Pb garden soils and play areas. A public health reality check by Health Canada surveillance of St. John's children (N = 257) noted remarkably low blood Pb. The low blood Pb of St. John's' children is contrary to the soil Pb results. Known urban processes causing the rise of environmental Pb and children's Pb exposure includes particle size, aerosol emission by traffic congestion, and quantities of leaded petrol during the 20th century. Smaller cities had minor traffic congestion and limited combustion particles from leaded petrol. From the perspective of the 20th century era of urban Pb pollution, St. John's, NL, children have blood Pb characteristics of a small city.

Pixelwise H-score: A novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images.

Immunohistochemistry (IHC) assays play a central role in evaluating biomarker expression in tissue sections for diagnostic and research applications. Manual scoring of IHC images, which is the current standard of practice, is known to have several shortcomings in terms of reproducibility and scalability to large scale studies. Here, by using a digital image analysis-based approach, we introduce a new metric called the pixelwise H-score (pix H-score) that quantifies biomarker expression from whole-slide scanned IHC images. The pix H-score is an unsupervised algorithm that only requires the specification of intensity thresholds for the biomarker and the nuclear-counterstain channels. We present the detailed implementation of the pix H-score in two different whole-slide image analysis software packages Visiopharm and HALO. We consider three biomarkers P-cadherin, PD-L1, and 5T4, and show how the pix H-score exhibits tight concordance to multiple orthogonal measurements of biomarker abundance such as the biomarker mRNA transcript and the pathologist H-score. We also compare the pix H-score to existing automated image analysis algorithms and demonstrate that the pix H-score provides either comparable or significantly better performance over these methodologies. We also present results of an empirical resampling approach to assess the performance of the pix H-score in estimating biomarker abundance from select regions within the tumor tissue relative to the whole tumor resection. We anticipate that the new metric will be broadly applicable to quantify biomarker expression from a wide variety of IHC images. Moreover, these results underscore the benefit of digital image analysis-based approaches which offer an objective, reproducible, and highly scalable strategy to quantitatively analyze IHC images.

First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody-Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors.

PURPOSE: We investigated safety, tolerability, pharmacokinetics, and antitumor activity of the protein tyrosine kinase 7 (PTK7)-targeted, auristatin-based antibody-drug conjugate (ADC) PF-06647020/cofetuzumab pelidotin (NCT02222922). PATIENTS AND METHODS: Patients received PF-06647020 intravenously every 3 weeks at 0.2-3.7 mg/kg or every 2 weeks at 2.1-3.2 mg/kg, in sequential dose escalation, following a modified toxicity probability interval method. In dose expansion, pretreated patients with advanced, platinum-resistant ovarian cancer, non-small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC) received PF-06647020 2.8 mg/kg every 3 weeks. RESULTS: The most common, treatment-related adverse events for PF-06647020 administered every 3 weeks were nausea, alopecia, fatigue, headache, neutropenia, and vomiting (45%-25%); 25% of patients had grade ≥ 3 neutropenia. Two patients experienced dose-limiting toxicities (grade 3 headache and fatigue) at the highest every 3 weeks dose evaluated. The recommended phase II dose was 2.8 mg/kg every 3 weeks. The overall safety profile observed with PF-06647020 administered every 2 weeks was similar to that of the every 3 weeks regimen. Systemic exposure for the ADC and total antibody generally increased in a dose-proportional manner. Antitumor activity was observed in treated patients with overall objective response rates of 27% in ovarian cancer (n = 63), 19% in NSCLC (n = 31), and 21% in TNBC (n = 29). Responders tended to have moderate or high PTK7 tumor expression by IHC. CONCLUSIONS: This PTK7-targeted ADC demonstrated therapeutic activity in previously treated patients with ovarian cancer, NSCLC, and TNBC at a dose range of 2.1-3.2 mg/kg, supporting further clinical evaluation to refine dose, schedule, and predictive tissue biomarker testing in patients with advanced malignancies.

Soil Lead (Pb) in New Orleans: A Spatiotemporal and Racial Analysis.

Spatialized racial injustices drive morbidity and mortality inequalities. While many factors contribute to environmental injustices, Pb is particularly insidious, and is associated with cardio-vascular, kidney, and immune dysfunctions and is a leading cause of premature death worldwide. Here, we present a revised analysis from the New Orleans dataset of soil lead (SPb) and children's blood Pb (BPb), which was systematically assembled for 2000-2005 and 2011-2016. We show the spatial-temporal inequities in SPb, children's BPb, racial composition, and household income in New Orleans. Comparing medians for the inner city with outlying areas, soil Pb is 7.5 or 9.3 times greater, children's blood Pb is ~2 times higher, and household income is lower. Between 2000-2005 and 2011-2016, a BPb decline occurred. Long-standing environmental and socioeconomic Pb exposure injustices have positioned Black populations at extreme risk of adverse health consequences. Given the overlapping health outcomes of Pb exposure with co-morbidities for conditions such as COVID-19, we suggest that further investigation be conducted on Pb exposure and pandemic-related mortality rates, particularly among Black populations. Mapping and remediating invisible environmental Pb provides a path forward for preventing future populations from developing a myriad of Pb-related health issues.

Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome.

To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.

Spatial-temporal association of soil Pb and children's blood Pb in the Detroit Tri-County Area of Michigan (USA).

Lead is a well-known toxicant associated with numerous chronic diseases. Curtailing industrial emissions, leaded paint, lead in food, and banning highway use of leaded gasoline effectively decreased children's exposure. In New Orleans, irrespective of Hurricane Katrina flooding, lead declined concurrently in topsoil and children's blood. We postulate that topsoil lead and blood lead decreases are associated and common in U.S. cities. This study tests that concept. A small 2002 soil lead survey of 8 Detroit Tri-County Area census tracts was repeated in October 2019. Between 2002 and 2019, Detroit median soil lead decreased from 183 to 92 mg/kg (or 5.4 mg/kg/yr.) and declined in Pontiac from 93 to 68 mg/kg (or 1.4 mg/kg/yr.). Median soil lead remained ~10 mg/kg in outlying communities. Median soil lead (in mg/kg) in communities at < 21 km compared to ≥ 21 km from central Detroit, respectively, decreased from 183 to 33 (P-value 10-12) in 2002 and from 92 to 35 (P-value 10-07) in 2019. Children's lead exposures were highest in Detroit (population 0.7 million in 2010) and lower by more than half in Pontiac (population 60 thousand in 2010). Between 2002 and 2018, children with blood lead ≥4.5 µg/dL in Detroit declined from 44% to 5%, and in Pontiac from 17% to 2%. The most vulnerable children live in the most lead contaminated communities. To meet the goal of primary prevention for children, along with other efforts, this study supports landscaping with low lead soil to reduce exposure in lead contaminated communities.

Author Correction: Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Biallelic mutations in SORD cause a common and potentially treatable hereditary neuropathy with implications for diabetes.

Here we report biallelic mutations in the sorbitol dehydrogenase gene (SORD) as the most frequent recessive form of hereditary neuropathy. We identified 45 individuals from 38 families across multiple ancestries carrying the nonsense c.757delG (p.Ala253GlnfsTer27) variant in SORD, in either a homozygous or compound heterozygous state. SORD is an enzyme that converts sorbitol into fructose in the two-step polyol pathway previously implicated in diabetic neuropathy. In patient-derived fibroblasts, we found a complete loss of SORD protein and increased intracellular sorbitol. Furthermore, the serum fasting sorbitol levels in patients were dramatically increased. In Drosophila, loss of SORD orthologs caused synaptic degeneration and progressive motor impairment. Reducing the polyol influx by treatment with aldose reductase inhibitors normalized intracellular sorbitol levels in patient-derived fibroblasts and in Drosophila, and also dramatically ameliorated motor and eye phenotypes. Together, these findings establish a novel and potentially treatable cause of neuropathy and may contribute to a better understanding of the pathophysiology of diabetes.

The concurrent decline of soil lead and children's blood lead in New Orleans.

Lead (Pb) is extremely toxic and a major cause of chronic diseases worldwide. Pb is associated with health disparities, particularly within low-income populations. In biological systems, Pb mimics calcium and, among other effects, interrupts cell signaling. Furthermore, Pb exposure results in epigenetic changes that affect multigenerational gene expression. Exposure to Pb has decreased through primary prevention, including removal of Pb solder from canned food, regulating lead-based paint, and especially eliminating Pb additives in gasoline. While researchers observe a continuous decline in children's blood lead (BPb), reservoirs of exposure persist in topsoil, which stores the legacy dust from leaded gasoline and other sources. Our surveys of metropolitan New Orleans reveal that median topsoil Pb in communities (n = 274) decreased 44% from 99 mg/kg to 54 mg/kg (P value of 2.09 × 10-08), with a median depletion rate of ∼2.4 mg⋅kg⋅y-1 over 15 y. From 2000 through 2005 to 2011 through 2016, children's BPb declined from 3.6 µg/dL to 1.2 µg/dL or 64% (P value of 2.02 × 10-85), a decrease of ∼0.2 µg⋅dL⋅y-1 during a median of 12 y. Here, we explore the decline of children's BPb by examining a metabolism of cities framework of inputs, transformations, storages, and outputs. Our findings indicate that decreasing Pb in topsoil is an important factor in the continuous decline of children's BPb. Similar reductions are expected in other major US cities. The most contaminated urban communities, usually inhabited by vulnerable populations, require further reductions of topsoil Pb to fulfill primary prevention for the nation's children.

Curtailing Lead Aerosols: Effects of Primary Prevention on Declining Soil Lead and Children's Blood Lead in Metropolitan New Orleans.

After decades of accumulation of lead aerosols in cities from additives in gasoline, in 1975 catalytic converters (which are ruined by lead) became mandatory on all new cars. By 1 January 1986 the rapid phase-down banned most lead additives. The study objective is to review temporal changes of environmental lead and children's blood lead in communities of metropolitan New Orleans. In 2001, a soil lead survey of 287 census tracts of metropolitan New Orleans was completed. In August-September 2005 Hurricanes Katrina and Rita storm surges flooded parts of the city with sediment-loaded water. In April-June 2006, 46/287 (16%) of the original census tracts were selected for resurvey. A third survey of 44/46 (15%) census tracts was completed in 2017. The census tract median soil lead and children's median blood lead decreased across surveys in both flooded and unflooded areas. By curtailing a major urban source of lead aerosols, children's lead exposure diminished, lead loading of soil decreased, and topsoil lead declined. Curtailing lead aerosols is essential for primary prevention. For the sake of children's and ultimately societal health and welfare, the long-term habitability of cities requires terminating all remaining lead aerosols and cleanup of legacy-lead that persists in older inner-city communities.

Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia.

The diagnostic gap for rare neurodegenerative diseases is still considerable, despite continuous advances in gene identification. Many novel Mendelian genes have only been identified in a few families worldwide. Here we report the identification of an autosomal-dominant gene for hereditary spastic paraplegia (HSP) in 10 families that are of diverse geographic origin and whose affected members all carry unique truncating changes in a circumscript region of UBAP1 (ubiquitin-associated protein 1). HSP is a neurodegenerative disease characterized by progressive lower-limb spasticity and weakness, as well as frequent bladder dysfunction. At least 40% of affected persons are currently undiagnosed after exome sequencing. We identified pathological truncating variants in UBAP1 in affected persons from Iran, USA, Germany, Canada, Spain, and Bulgarian Roma. The genetic support ranges from linkage in the largest family (LOD = 8.3) to three confirmed de novo mutations. We show that mRNA in the fibroblasts of affected individuals escapes nonsense-mediated decay and thus leads to the expression of truncated proteins; in addition, concentrations of the full-length protein are reduced in comparison to those in controls. This suggests either a dominant-negative effect or haploinsufficiency. UBAP1 links endosomal trafficking to the ubiquitination machinery pathways that have been previously implicated in HSPs, and UBAP1 provides a bridge toward a more unified pathophysiology.

Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2.

Although mutations in more than 90 genes are known to cause CMT, the underlying genetic cause of CMT remains unknown in more than 50% of affected individuals. The discovery of additional genes that harbor CMT2-causing mutations increasingly depends on sharing sequence data on a global level. In this way-by combining data from seven countries on four continents-we were able to define mutations in ATP1A1, which encodes the alpha1 subunit of the Na+,K+-ATPase, as a cause of autosomal-dominant CMT2. Seven missense changes were identified that segregated within individual pedigrees: c.143T>G (p.Leu48Arg), c.1775T>C (p.Ile592Thr), c.1789G>A (p.Ala597Thr), c.1801_1802delinsTT (p.Asp601Phe), c.1798C>G (p.Pro600Ala), c.1798C>A (p.Pro600Thr), and c.2432A>C (p.Asp811Ala). Immunostaining peripheral nerve axons localized ATP1A1 to the axolemma of myelinated sensory and motor axons and to Schmidt-Lanterman incisures of myelin sheaths. Two-electrode voltage clamp measurements on Xenopus oocytes demonstrated significant reduction in Na+ current activity in some, but not all, ouabain-insensitive ATP1A1 mutants, suggesting a loss-of-function defect of the Na+,K+ pump. Five mutants fall into a remarkably narrow motif within the helical linker region that couples the nucleotide-binding and phosphorylation domains. These findings identify a CMT pathway and a potential target for therapy development in degenerative diseases of peripheral nerve axons.

Detecting expression of 5T4 in CTCs and tumor samples from NSCLC patients.

The fetal oncogene 5T4 is a cell surface protein, with overexpression observed in a variety of cancers as compared to normal adult tissue. The ability to select patients with tumors that express high levels of 5T4 may enrich a clinical trial cohort with patients most likely to respond to 5T4 targeted therapy. To that end, we developed assays to measure 5T4 in both tumors and in circulating tumor cells (CTCs). We identified the presence of 5T4 in both adenocarcinoma and squamous cell carcinoma of lung, in all clinical stages and grades of disease. CTCs were identified in peripheral blood from the majority of patients with NSCLC, and 5T4 was detectable in most samples. Although 5T4 was present in both CTCs and tumors in most patients, there was no concordance between relative amount in either sample type. Clinical response rates of patients treated with the therapies directed against 5T4 in early stage clinical trials, as determined by these assays, may provide important insights into the biology of 5T4 in tumors and the mechanisms of action of 5T4-targeting therapy.

Soil Lead and Children's Blood Lead Disparities in Pre- and Post-Hurricane Katrina New Orleans (USA).

This study appraises New Orleans soil lead and children's lead exposure before and ten years after Hurricane Katrina flooded the city. Introduction: Early childhood exposure to lead is associated with lifelong and multiple health, learning, and behavioral disorders. Lead exposure is an important factor hindering the long-term resilience and sustainability of communities. Lead exposure disproportionately affects low socioeconomic status of communities. No safe lead exposure is known and the common intervention is not effective. An essential responsibility of health practitioners is to develop an effective primary intervention. Methods: Pre- and post-Hurricane soil lead and children's blood lead data were matched by census tract communities. Soil lead and blood lead data were described, mapped, blood lead graphed as a function of soil lead, and Multi-Response Permutation Procedures statistics established disparities. Results: Simultaneous decreases occurred in soil lead accompanied by an especially large decline in children's blood lead 10 years after Hurricane Katrina. Exposure disparities still exist between children living in the interior and outer areas of the city. Conclusions: At the scale of a city, this study demonstrates that decreasing soil lead effectively reduces children's blood lead. Primary prevention of lead exposure can be accomplished by reducing soil lead in the urban environment.

Spatiotemporal exposome dynamics of soil lead and children's blood lead pre- and ten years post-Hurricane Katrina: Lead and other metals on public and private properties in the city of New Orleans, Louisiana, U.S.A.

BACKGROUND: Anthropogenic re-distribution of lead (Pb) principally through its use in gasoline additives and lead-based paints have transformed the urban exposome. This unique study tracks urban-scale soil Pb (SPb) and blood Pb (BPb) responses of children living in public and private communities in New Orleans before and ten years after Hurricane Katrina (29 August 2005). OBJECTIVES: To compare and evaluate associations of pre- and ten years post-Katrina SPb and children's BPb on public and private residential census tracts in the core and outer areas of New Orleans, and to examine correlations between SPb and nine other soil metals. METHODS: The Louisiana Healthy Housing and Childhood Lead Poisoning Prevention Program BPb (µg/dL) data from pre- (2000-2005) and post-Katrina (2010-2015) for ≤6-year-old children. Data from public and adjacent private residential census tracts within core and outer areas are stratified from a database that includes 916 and 922 SPb and 13,379 and 4830 BPb results, respectively, from pre- and post-Katrina New Orleans. Statistical analyses utilize Multi-Response Permutation Procedure and Spearman's Rho Correlation. RESULTS: Pre- to Post-Katrina median SPb decreases in public and private core census tracts were from 285 to 55mg/kg and 710-291mg/kg, respectively. In public and private outer census tracts the median SPb decreased from 109 to 56mg/kg and 88-55mg/kg. Children's BPb percent ≥5µg/dL on public and private core areas pre-Katrina was 63.2% and 67.5%, and declined post-Katrina to 7.6% and 20.2%, respectively. BPb decreases also occurred in outer areas. Soil Pb is strongly correlated with other metals. CONCLUSIONS: Post-Katrina re-building of public housing plus landscaping amends the exposome and reduces children's BPb. Most importantly, Hurricane Katrina revealed that decreasing the toxicants in the soil exposome is an effective intervention for decreasing children's BPb.