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Legacies of Lead Paint Contamination in the Mineral Soils Adjacent to Historic Buildings
No full textFor hundreds of years, compounds containing the element lead (Pb) have been added to paint in order to improve the texture and weather resistance. Across the United States, millions of homes and buildings were painted with lead-based paints up through the 1970s, when lead paint was phased out following medical research confirming the link between lead and a variety of neurological and developmental disorders. Over 170 million Americans are estimated to have been exposed to lead levels above safe concentrations, many of whom were likely exposed to soil lead while playing in yards as children. Although the phase-out of lead in paint began over 50 years ago, the legacies of contamination from lead paint are still present in the soil in a meaningful way. This is largely due to the immobile nature of lead in the soil, tightly binding to clays and other particles, preventing it from being leached out of the soil. Previous soil lead studies have attempted to characterize spatial patterns of contamination at various scales, but this study is unique in the highly fine-scale sampling design around each structure. Up to 190 samples were taken around each structure, at a point density of 1 sample every 4-12 square meters, prioritizing areas closer to the base of the structure. Nine study sites were chosen in the vicinity of Durham, North Carolina, including 2 buildings that continue to be well-maintained, 5 dilapidated structures, and 2 footprints of buildings burned to the ground. For our study, we surveyed the top inch of the mineral soil using an Olympus Vanta portable X-ray Fluorescence Machine to get lead concentration in parts per million. At all nine of our study sites, we found evidence of elevated lead levels in the mineral soil that can reasonably be attributed to legacies of paint contamination. Sites varied in the intensity of lead contamination, ranging from maximum values below 300ppm to multiple samples above 5000ppm, and each had its own unique footprint of soil lead. Interpolations of lead concentration were created in ArcGIS from the point data. Despite the variation, we were able to draw a variety of conclusions about the state of soil lead around historic structures: • Concentrations are typically highest adjacent to the base of the structure, and often decline rapidly with distance. • Concentrations often decline back down to the geologic background within 4-12 meters of the structure, related to the maximum concentration. • The corners of buildings are often hotspots for lead contamination, likely due to weathering patterns of paint. • Topography and erosion of soil can affect concentrations and directionality of elevated lead plumes. • We did not find any direct pattern between lead levels and a building’s height, age, location, or level of maintenance. • Destroyed/burned structures can show very high hotspots even within the footprint of the former structure. • Mulch and other ground covers may either protect the soil from contamination or insulate the soil lead from loss. Statistical and geospatial analysis was used to help characterize the spatial patterns of the contamination at each site. For each structure, data of lead concentration versus distance from the building was used to generate a logarithmic regression that can be used to predict concentration at any given distance. For two structures, interpolations were georeferenced to estimate the area of spatial contamination at different thresholds. Other analyses were done on a site-specific basis, such as comparing concentrations at the different cardinal directions from one structure. All of our results were communicated and interpreted to the landowners to help inform their knowledge of their properties. This is especially important considering most of our sites are open to the public, and multiple have outdoor programs for children. For each site, we estimated a total health risk, based on the levels of lead contamination and the potential for human exposure. Considering the levels still present in soils even after 50+ years, more research is needed into soil remediation methods, as the high values we found in soils demonstrate that lead still poses a considerable risk to humans
Reporting the Shots: Exploring Barriers and Facilitators in Pediatric Vaccine Reporting
No full textFor 30 years, the Vaccines for Children (VFC) Program has ensured low-income children have access to vaccines, leading to millions of illnesses averted, hundreds of thousands of deaths avoided and billions of dollars in health savings. Yet policy, technology and personnel gaps allow many VFC vaccines to remain unreported to a jurisdiction’s immunization information system (IIS). This study identified potential barriers and facilitators to IIS reporting among VFC providers through in-depth, qualitative interviews with pediatric healthcare workers across four reporting-mandated, but historically under-reporting states: Colorado, Connecticut, Maryland, and Massachusetts. The study also highlighted COVID-19 influences on provider IIS reporting
Discovery and Characterization of Novel Thanatin Orthologs Against Escherichia coli LptA and Pseudomonas aeruginosa LptH
No full textMultidrug resistance (MDR) in bacteria is ever growing and complicates treatment of infections, especially in patients who are critically ill and immunocompromised. Treatment often utilizes a regiment of small molecule drugs, however resistance against them develops after prolonged usage. An alternative class of molecules, antimicrobial peptides (AMPs), have remained of interest due to its vast potential of becoming pharmacological agents. AMPs, or host defense peptides, are naturally expressed in many organisms, including microbes, plants, and humans. AMPs are expressed to control the population of bacteria, fungi, and viruses as a defense mechanism. Mining host genomes for AMPs will prove to be a valuable source of novel alternative drug molecules. Characterization of AMPs will lead to be a better understanding of their mechanism of action and allow for applications to novel targets. Here in this dissertation, we apply these methods to thanatin, an AMP identified from the spined soldier bug (Podisus maculiventris) that was reported to regulate the gut microbiome population by targeting Gram-positive bacteria, Gram-negative bacteria, and fungi.First, we mined genomic databases to discover novel thanatin orthologs. We generated these orthologs and characterized their binding against Escherichia coli LptA, a known target of thanatin, via bio-layer interferometry (BLI) and their antimicrobial activity against several E. coli strains via minimum inhibition concentration (MIC) assays. We found a subset of thanatin sequences that target E. coli better than P. maculiventris thanatin, as shown with increased binding affinity, cell permeability, and overall potency. We crystallized and determined the structures of Chinavia ubica thanatin and Murgantia histrionica thanatin, the two most improved thanatin orthologs, in complex with E. coli LptA to better understand the interaction. We performed mutagenesis studies to show that thanatin residues A10 and M21 interacts with the hydrophobic core of LptA and improves binding and synergistically improves cell permeability to increase antimicrobial activity against E. coli. We redesigned M. histrionica thanatin to truncate the sequence and remove the need for a disulfide bond. Our stapled peptide retained binding affinity to LptA, however potency was hampered. Despite seeing no improvement in antimicrobial activity, we present a novel scaffold for the next generation of thanatin-based AMPs.
Next, we characterized thanatin against Pseudomonas aeruginosa, a known but weaker target of thanatin. We confirmed binding of P. maculiventris thanatin to LptH, the P. aeruginosa homolog of E. coli LptA, via BLI and isothermal titration calorimetry (ITC) and showed inhibition of P. aeruginosa strain RP73 via MIC assays. We used homology modeling and an E. coli model system to identify the resistance factor of thanatin to be LptH Y51 at the predicted binding interface. We attempted to overcome the hinderance of LptH Y51 by modeling thanatin to accommodate it. Our designs cooperated in the E. coli model system, however they did not translate to improve binding with LptH. Interestingly, we discovered that thanatin Y10 is essential to binding LptH. We applied the small library of thanatin orthologs to LptH and P. aeruginosa and did not discover any sequences with improved binding or antimicrobial activity. Our small library screening highlighted the necessity of thanatin Y10 and the resistance factor LptH Y51 again. We investigated the role of improved potency of thanatin with P. aeruginosa through c-amidation. Our E. coli model system shows a key rescued interaction between the c-amidated terminus of thanatin and LptA R76Q that mimics LptH. We crystallized and determined the structure of c-amidated truncated thanatin and LptA R76Q to gain insight on the interaction. However, we did not observe the hypothesized rescued interaction. When translating our findings to LptH, we did not observe improved binding due to c-amidation via BLI, but we did via ITC. Conflicting data about how thanatin interacts with LptH could be clarified with a high-resolution protein:peptide complex structure, however attempts to experimentally obtain one has been difficult. Overall, we provide some insight on the mechanism of how thanatin targets LptH in P. aeruginosa, but further studies will be needed to fully elucidate its mechanism of action.
Collectively, this dissertation provides an example of how natural sources can be mined to uncover novel AMPs to target bacteria with MDR on the rise. We present various insights gained on the mechanism of action of thanatin by characterizing thanatin and its novel orthologs against E. coli LptA and P. aeruginosa LptH. The characterization of thanatin will allow for improved AMPs to be designed in the next generation of thanatin peptides to target pathogens.
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Investigating the Origin and Role of Catecholamines in the Visual Cortex of the Macaque Monkey
No full textThe catecholamines - norepinephrine and dopamine- are released into cortex from subcortical nuclei. It is classically assumed, for example, that dopamine receptors in cortex bind molecules released by dopaminergic axons. In the case of cortex, those axons would be the ascending fibers of the ventral tegmental area (VTA). Interestingly, dopamine receptors are found in all layers of primary visual cortex (V1), but the innervation from the VTA is mostly restricted to layers 1 and 6. This anatomical mismatch raises the question as to whether or not dopamine from the VTA is the primary ligand for dopamine receptors in V1. An alternative possibility is that the locus coeruleus (LC) co-releases dopamine and norepinephrine into V1. LC axons innervate all layers of V1 and are thus anatomically positioned to provide a ligand to activate dopamine receptors. Another possibility is that dopamine from VTA axons passively diffuses to the middle layers of V1 from layers 1 and 6, and a third possibility is that norepinephrine is binding to these middle layer dopamine receptors. I will present results from a series of studies that address these three possibilities in which I find that activation of the LC can elicit release of both catecholamines into V1 in a manner that depends on experimental parameters such as the intensity and frequency of electrical stimulation of the LC. The data suggests that the LC co-releases dopamine with norepinephrine in a state-dependent manner.</p
Reliability of a Novel Classification System for Thoracic Disc Herniations.
No full textStudy designCross-sectional survey.ObjectiveTo assess the reliability of a proposed novel classification system for thoracic disc herniations (TDHs).Summary of background dataTDHs are complex entities varying substantially in many factors, including size, location, and calcification. To date, no comprehensive system exists to categorize these lesions.MethodsOur proposed system classifies 5 types of TDHs using anatomical and clinical characteristics, with subtypes for calcification. Type 0 herniations are small (≤40% of spinal canal) TDHs without significant spinal cord or nerve root effacement; type 1 are small and paracentral; type 2 are small and central; type 3 are giant (>40% of spinal canal) and paracentral; and type 4 are giant and central. Patients with types 1-4 TDHs have correlative clinical and radiographic evidence of spinal cord compression. Twenty-one US spine surgeons with substantial TDH experience rated 10 illustrative cases to determine the system's reliability. Interobserver and intraobserver reliability were determined using the Fleiss kappa coefficient. Surgeons were also surveyed to obtain consensus on surgical approaches for the various TDH types.ResultsHigh agreement was found for the classification system, with 80% (range 62-95%) overall agreement and high interrater and intrarater reliability (kappa 0.604 [moderate to substantial agreement] and kappa 0.630 [substantial agreement], respectively). All surgeons reported nonoperative management of type 0 TDHs. For type 1 TDHs, most respondents (71%) preferred posterior approaches. For type 2 TDHs, responses were roughly equivalent for anterolateral and posterior options. For types 3 and 4 TDHs, most respondents (72% and 68%, respectively) preferred anterolateral approaches.ConclusionsThis novel classification system can be used to reliably categorize TDHs, standardize description, and potentially guide the selection of surgical approach. Validation of this system with regard to treatment and clinical outcomes represent lines of future study
Age-related differences in frontoparietal activation for target and distractor singletons during visual search.
No full textAge-related decline in visual search performance has been associated with different patterns of activation in frontoparietal regions using functional magnetic resonance imaging (fMRI), but whether these age-related effects represent specific influences of target and distractor processing is unclear. Therefore, we acquired event-related fMRI data from 68 healthy, community-dwelling adults ages 18-78 years, during both conjunction (T/F target among rotated Ts and Fs) and feature (T/F target among Os) search. Some displays contained a color singleton that could correspond to either the target or a distractor. A diffusion decision analysis indicated age-related increases in sensorimotor response time across all task conditions, but an age-related decrease in the rate of evidence accumulation (drift rate) was specific to conjunction search. Moreover, the color singleton facilitated search performance when occurring as a target and disrupted performance when occurring as a distractor, but only during conjunction search, and these effects were independent of age. The fMRI data indicated that decreased search efficiency for conjunction relative to feature search was evident as widespread frontoparietal activation. Activation within the left insula mediated the age-related decrease in drift rate for conjunction search, whereas this relation in the FEF and parietal cortex was significant only for individuals younger than 30 or 44 years, respectively. Finally, distractor singletons were associated with significant parietal activation, whereas target singletons were associated with significant frontoparietal deactivation, and this latter effect increased with adult age. Age-related differences in frontoparietal activation therefore reflect both the overall efficiency of search and the enhancement from salient targets
Reoperation rates in minimally invasive, hybrid and open surgical treatment for adult spinal deformity with minimum 2-year follow-up.
No full textIntroductionMinimally invasive surgical (MIS) techniques are gaining popularity in the treatment of adult spinal deformity (ASD). The premise is that MIS techniques will lead to equivalent outcomes and a reduction in perioperative complications when compared with open techniques. Potential issues with MIS techniques are a limited capacity to correct lumbar lordosis, unknown long-term efficacy, and the potential need for revision surgery. This study compares reoperation rates and reasons for reoperation following MIS, hybrid, and open surgery for ASD through multicenter database analysis.MethodsWe retrospectively analyzed a prospective multicenter ASD database comparing open and MIS correction techniques. Inclusion criteria were: age > 18 years with minimum 20° coronal lumbar Cobb angle, a minimum of three levels fused, and minimum 2-year follow-up. Patients were propensity matched for preoperative sagittal vertebral axis (SVA), pelvic incidence-lumbar lordosis (PI-LL), and number of levels fused. We included 189 patients from three propensity-matched subgroups of 63 patients each: (1) MIS: lateral or transforaminal lumbar interbody fusion (LIF) and percutaneous pedicle instrumentation, (2) Hybrid: MIS LIF with open posterior segmental fixation (PSF), and (3) OPEN: open posterior fixation ± osteotomies.ResultsWith propensity matching, there were significant differences between groups in pre-op SVA or PI-LL (p > 0.05). The MIS group had significantly fewer levels fused (5.4) (0-14) than the OPEN group (7.4) (p = 0.002) (0-17). The rate of revision surgery was significantly different between the groups with a higher rate of revision (27 %) amongst the HYB group versus MIS = 11.1 %, and OPEN = 12.0 %. The most common reason for reoperation in the OPEN and HYB groups was a postoperative neurological deficit (7.9 and 11.1 %), respectively. The most common reason for reoperation in the MIS group was pseudoarthrosis (7.9 %).ConclusionsReoperation rates were not statistically different among the MIS, and OPEN surgical groups, but differed significantly on multivariate analysis with HYB group. The incidence of reoperations was twice as high in the Hybrid group compared to OPEN and MIS
A Unified Framework for Evidence-Based Diagnostic Criteria Programs in Movement Disorders.
No full textSophie Seita. <i>Provisional Avant-Gardes: Little Magazine Communities from Dada to Digital</i>. Stanford, Calif.: Stanford University Press, 2019. 272 pp.
No full textImpact of bundle type, price framing and familiarity on purchase intention for the bundle
No full textBundling of products is very prevalent in the marketplace. For example, travel packages include airfare, lodging, and a rental car. Considerable economic research has focused on the change in profits and consumer surplus that ensues if bundles are offered. There is relatively little research in marketing that deals with bundling, however. In this article we concentrate on some tactical issues of bundling, such as which types of products should be bundled, what price one can charge for the bundle, and how the price of the bundle should be presented to consumers to improve purchase intent. For example, we hypothesize that bundles composed of complements or equally priced goods will result in higher purchase intention. We also hypothesize that price increases will result in larger purchase intention changes than price decreases. Further, we expect that the presentation format for describing the price of the bundle will influence purchase intention in general, and, depending on the price level of the bundle, different presentation formats will result in higher purchase intention. Finally, we hypothesize that purchase intention changes associated with different price levels will be higher for subjects who are familiar with the products than for subjects who are less familiar with the products. We used an interactive computer experiment conducted among 83 Master of Business Administration (MBA) students to test our hypotheses. Our findings suggest that: (1) bundles composed of complements have a higher purchase intent than bundles of similar or unrelated products, (2) consumers are more sensitive to a bundle price increase than to a bundle price decrease of equal amounts, (3) different presentation formats for describing the price of the bundle influence purchase intention, and (4) more familiar subjects respond to different presentations of equivalent bundles in different ways than less familiar subjects. We did not find any support for the hypothesis that bundles composed of similarly priced items have higher purchase intent than bundles composed of unequally priced products. © 1995