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On a community basis, urban soil contains a potentially large reservoir of accumulated lead. This study was undertaken to explore the temporal relationship between pediatric blood lead (BPb), weather, soil moisture, and dust in Indianapolis, Indiana; Syracuse, New York; and New Orleans, Louisiana. The Indianapolis, Syracuse, and New Orleans pediatric BPb data were obtained from databases of 15,969, 14,467, and 2,295 screenings, respectively, collected between December 1999 and November 2002, January 1994 and March 1998, and January 1998 and May 2003, respectively. These average monthly child BPb levels were regressed against several independent variables: average monthly soil moisture, particulate matter < 10 microm in diameter (PM10), wind speed, and temperature. Of temporal variation in urban children's BPb, 87% in Indianapolis (R2 = 0.87, p = 0.0004), 61% in Syracuse (R2 = 0.61, p = 0.0012), and 59% in New Orleans (R2 = 0.59, p = 0.0000078) are explained by these variables. A conceptual model of urban Pb poisoning is suggested: When temperature is high and evapotranspiration maximized, soil moisture decreases and soil dust is deposited. Under these combined weather conditions, Pb-enriched PM10 dust disperses in the urban environment and causes elevated Pb dust loading. Thus, seasonal variation of children's Pb exposure is probably caused by inhalation and ingestion of Pb brought about by the effect of weather on soils and the resulting fluctuation in Pb loading. [ABSTRACT FROM AUTHOR]

Increasing evidence indicates the role of mitochondrial and vascular dysfunction in aging and aging-associated pathologies; however, the exact mechanisms and chronological processes remain enigmatic. High-energy demand organs, such as the brain, depend on the health of their mitochondria and vasculature for the maintenance of normal functions, therefore representing vulnerable targets for aging. This methodology article describes an analysis pipeline for three-dimensional (3-D) mitochondria-associated signal geometry of two-photon image stacks of brain vasculature. The analysis methods allow the quantification of mitochondria-associated signals obtained in real time in their physiological environment. In addition, signal geometry results will allow the extrapolation of fission and fusion events under normal conditions, during aging, or in the presence of different pathological conditions, therefore contributing to our understanding of the role mitochondria play in a variety of aging-associated diseases with vascular etiology. NEW & NOTEWORTHY Analysis pipeline for 3-D mitochondria-associated signal geometry of two-photon image stacks of brain vasculature.

(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.

Children's ability to monitor subjective feelings of uncertainty (i.e., engage in uncertainty monitoring) is a central metacognitive skill. In the current study, we examined the development of uncertainty monitoring as well as its relations with vocabulary and executive function development in children (N = 137, 52% female) from predominately White and Latinx/Hispanic backgrounds when they were 4-6 years old and enrolled in a Head Start preschool and kindergarten between 2018 and 2019. We found that children's uncertainty monitoring improved during the kindergarten year. Children's executive function and vocabulary in preschool and vocabulary growth from preschool to kindergarten predicted uncertainty monitoring at the end of kindergarten, which sheds new light on potential mechanisms supporting children's metacognitive development., (© 2021 The Authors. Child Development © 2021 Society for Research in Child Development.)

Objectives: The importance of breastfeeding exposure and children's development of self-regulation, independently, are well established. Each of these domains also has been linked to better cognitive development and academic achievement in children. However, little is known about how breastfeeding affects development of early self-regulation skills or whether self-regulation mediates the relationship between breastfeeding and academic achievement, particularly for disadvantaged children. This study examined breastfeeding exposure, self-regulation, and academic achievement in kindergarten among a population of children who previously attended Head Start., Methods: Children were recruited from Head Start classrooms in the Pacific Northwest. Breastfeeding exposure was assessed via parent report. Children's self-regulation (Day Night Stroop, Dimensional Change Card Sort, Head-Knees-Toes-Shoulders-Revised) and academic achievement [Letter-Word Identification and Applied Problems subtests of Woodcock Johnson Tests of Achievement (English) or the Batería III Woodcock-Muñoz (Spanish)] were directly assessed in fall and spring of kindergarten. Regressions were performed using Stata v14.1 and included breastfeeding exposure as the primary independent variable, controlling for child age, sex, and language spoken., Results: Of the 246 children, 56% were reported as White, 34% Latino/a, 4% African American, and 6% other; 83% were ever exposed to breastfeeding. Breastfeeding exposure was predictive of both fall kindergarten academic achievement (emergent math/literacy scores) and self-regulation (p < 0.05) and related to higher math performance in the spring of kindergarten, which was associated with stronger self-regulation in the fall (p = 0.04)., Conclusions: These findings extend our understanding of the positive effects of breastfeeding exposure on children's development and support breastfeeding promotion, particularly for children at risk of academic difficulty., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.

The measurement of self-regulation in young children has been a topic of great interest as researchers and practitioners work to help ensure that children have the skills they need to succeed as they start school. The present study examined how a revised version of a commonly used measure of behavioral self-regulation, the Head-Toes-Knees-Shoulders task (HTKS) called the HTKS-R, and measures of executive function (EF) was related to academic outcomes between preschool and kindergarten (ages 4-6years) in a diverse sample of children from families with low income participating in Head Start in the United States. Participants included 318 children (53% female; 76% White; and 20% Latino/Hispanic) from 64 classrooms in 18 Head Start preschools who were followed over four time points between the fall of preschool and the spring of kindergarten. Results indicated that children with higher HTKS-R scores had significantly higher math and literacy scores at all-time points between preschool and kindergarten. The HTKS-R was also a more consistent predictor of math and literacy than individual EF measures assessing inhibitory control, working memory, and task shifting. Parallel process growth models indicated that children who had high initial scores on the HTKS-R also had relatively higher initial scores on math and literacy. In addition, growth in children's scores on the HTKS-R across the preschool and kindergarten years was related to growth in both children's math and literacy scores over the same period independent of their starting points on either measure. For the HTKS-R and math, children's initial scores were negatively associated with growth over the preschool and kindergarten years indicating that lower skilled children at the start of preschool started to catch up to their more skilled peers by the end of kindergarten., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 McClelland, Gonzales, Cameron, Geldhof, Bowles, Nancarrow, Merculief and Tracy.)

An important part of children's social and cognitive development is their understanding that people are psychological beings with internal, mental states including desire, intention, perception, and belief. A full understanding of people as psychological beings requires a representational theory of mind (ToM), which is an understanding that mental states can faithfully represent reality, or misrepresent reality. For the last 35 years, researchers have relied on false-belief tasks as the gold standard to test children's understanding that beliefs can misrepresent reality. In false-belief tasks, children are asked to reason about the behavior of agents who have false beliefs about situations. Although a large body of evidence indicates that most children pass false-belief tasks by the end of the preschool years, the evidence we present in this monograph suggests that most children do not understand false beliefs or, surprisingly, even true beliefs until middle childhood. We argue that young children pass false-belief tasks without understanding false beliefs by using perceptual access reasoning (PAR). With PAR, children understand that seeing leads to knowing in the moment, but not that knowing also arises from thinking or persists as memory and belief after the situation changes. By the same token, PAR leads children to fail true-belief tasks. PAR theory can account for performance on other traditional tests of representational ToM and related tasks, and can account for the factors that have been found to correlate with or affect both true- and false-belief performance. The theory provides a new laboratory measure which we label the belief understanding scale (BUS). This scale can distinguish between a child who is operating with PAR versus a child who is understanding beliefs. This scale provides a method needed to allow the study of the development of representational ToM. In this monograph, we report the outcome of the tests that we have conducted of predictions generated by PAR theory. The findings demonstrated signature PAR limitations in reasoning about the mind during the ages when children are hypothesized to be using PAR. In Chapter II, secondary analyses of the published true-belief literature revealed that children failed several types of true-belief tasks. Chapters III through IX describe new empirical data collected across multiple studies between 2003 and 2014 from 580 children aged 4-7 years, as well as from a small sample of 14 adults. Participants were recruited from the Phoenix, Arizona metropolitan area. All participants were native English-speakers. Children were recruited from university-sponsored and community preschools and daycare centers, and from hospital maternity wards. Adults were university students who participated to partially fulfill course requirements for research participation. Sociometric data were collected only in Chapter IX, and are fully reported there. In Chapter III, minor alterations in task procedures produced wide variations in children's performance in 3-option false-belief tasks. In Chapter IV, we report findings which show that the developmental lag between children's understanding ignorance and understanding false belief is longer than the lag reported in previous studies. In Chapter V, children did not distinguish between agents who have false beliefs versus agents who have no beliefs. In Chapter VI, findings showed that children found it no easier to reason about true beliefs than to reason about false beliefs. In Chapter VII, when children were asked to justify their correct answers in false-belief tasks, they did not reference agents' false beliefs. Similarly, in Chapter VIII, when children were asked to explain agents' actions in false-belief tasks, they did not reference agents' false beliefs. In Chapter IX, children who were identified as using PAR differed from children who understood beliefs along three dimensions-in levels of social development, inhibitory control, and kindergarten adjustment. Although the findings need replication and additional studies of alternative interpretations, the collection of results reported in this monograph challenges the prevailing view that representational ToM is in place by the end of the preschool years. Furthermore, the pattern of findings is consistent with the proposal that PAR is the developmental precursor of representational ToM. The current findings also raise questions about claims that infants and toddlers demonstrate ToM-related abilities, and that representational ToM is innate., (© 2021 The Authors. Monographs of the Society for Research in Child Development published by Wiley Periodicals LLC on behalf of Society for Research in Child Development.)

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.

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., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Many health professions education institutions exist on land once inhabited by American Indians and Alaska Natives (AI/AN). Land acknowledgment by these academic organizations is helpful, but collaborative support of AI/AN health is also needed. Because tribal-university partnerships in education are fewer than in research but just as important, this article considers health professions schools' responsibilities to offer students clinical rotations on tribal lands and to recruit AI/AN students. Such investment expands student educational opportunity, diversifies clinical workforces, and helps tribes improve health infrastructure and sustainability. This article also offers an adaptable roadmap for building such partnerships., (© 2020 American Medical Association. All Rights Reserved.)

Self-regulation develops rapidly during the years before formal schooling, and it helps lay the foundation for children's later social, academic, and educational outcomes. However, children's self-regulation may be influenced by cultural contexts, sociodemographic factors, and characteristics of the child. The present study investigates whether children's levels of self-regulation, as measured by the Head-Toes-Knees-Shoulders (HTKS) task, are the same in samples from Norway ( M age = 5.79; N = 243, 49.4% girls) and the United States (U.S.) ( M age = 5.65; N = 264, 50.8% girls) and whether the role of mother's education level and child gender on children's self-regulation differ across the two samples. Results showed that Norwegian and U.S. children had similar levels of self-regulation. Mother's education level significantly predicted children's self-regulation in the U.S. sample but not in the Norwegian sample, and this difference across samples was significant. Girls had a significantly higher level of self-regulation than boys in the Norwegian sample, but there were no gender differences in the U.S. sample. However, the effect of child gender on self-regulation did not differ significantly across the two samples. Results highlight the importance of cross-cultural studies of self-regulation., (Copyright © 2020 Lenes, Gonzales, Størksen and McClelland.)

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., Competing Interests: Competing interest statement: H.W.M. is the unremunerated president of Lead Lab, Inc., which obtained private funding to conduct the 2017 survey of New Orleans., (Copyright © 2019 the Author(s). Published by PNAS.)

Considerable research has examined interventions that facilitate school readiness skills in young children. One intervention, Red Light, Purple Light Circle Time Games (RLPL ; Tominey and McClelland, 2011; Schmitt et al., 2015), includes music and movement games that aim to foster self-regulation skills. The present study ( N = 157) focused on children from families with low-income and compared the RLPL intervention (SR) to a revised version of RLPL that included literacy and math content (SR+) and a Business-As-Usual (BAU) control group. In both versions of the intervention, teachers were trained to administer the self-regulation intervention in preschool classrooms with coaching support. Although not statistically significant, children receiving either version of the intervention gained more in self-regulation on the Head-Toes-Knees-Shoulders (HTKS) over the preschool year compared to the BAU group (β = 0.09, p = 0.082, Cohen's d = 0.31). Effect sizes were similar to previous studies (Schmitt et al., 2015; Duncan et al., 2018) and translated to a 21% difference in self-regulation over and above the BAU group at post-test. Furthermore, children participating in either version of the intervention gained significantly more in math across the school year compared to children in the BAU group (β = 0.14; p = 0.003, Cohen's d = 0.38), which translated to a 24% difference in math over and above the BAU group at post-test. Results were somewhat stronger for the SR+ version, although effect sizes across intervention conditions were comparable. There were no statistically significant differences across groups for literacy skills. Results extend previous research and suggest that the RLPL intervention, which includes an explicit focus on self-regulation through music and movement games, may improve children's self-regulation and math scores over the preschool year., (Copyright © 2019 McClelland, Tominey, Schmitt, Hatfield, Purpura, Gonzales and Tracy.)

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.

Many urban areas have elevated soil lead concentrations due to prior large-scale use of lead in products such as paint and automobile gasoline. This presents a potential problem for the growing numbers of wildlife living in urbanized areas as lead exposure is known to affect multiple physiological systems, including the nervous system, in vertebrate species. In humans and laboratory animals, low-level lead exposure is associated with neurological impairment, but less is known about how lead may affect the behavior of urban wildlife. We focused on the Northern Mockingbird Mimus polyglottos, a common, omnivorous North American songbird, to gain insights into how lead may affect the physiology and behavior of urban wildlife. We predicted that birds living in neighborhoods with high soil lead concentrations would (a) exhibit elevated lead concentrations in their blood and feathers, (b) exhibit lower body condition, (c) exhibit less diverse and consistent vocal repertoires, and (d) behave more aggressively during simulated conspecific territorial intrusions compared to birds living in neighborhoods with lower soil lead concentrations. Controlling for other habitat differences, we found that birds from areas of high soil lead had elevated lead concentrations in blood and feathers, but found no differences in body condition or vocal repertoires. However, birds from high lead areas responded more aggressively during simulated intrusions. These findings indicate that sub-lethal lead exposure may be common among wildlife living in urban areas, and that this exposure is associated with increased aggression. Better understanding of the extent of the relationship between lead exposure and aggression and the consequences this could have for survival and reproduction of wild animals are clear priorities for future work in this and other urban ecosystems., (Copyright © 2018. Published by Elsevier B.V.)

This study assessed children's (N = 236) ability to introspect the mental states of seeing and knowing relative to their ability to attribute each state to others. Children could introspect seeing 10 months before they could introspect knowing. Two- and 3-year-olds correctly reported their own seeing states, whereas 3- and 4-year-olds correctly reported their own knowing states. For each mental state, there was a 7-month difference before children could correctly attribute that state to another. These findings indicate that knowing is more difficult to introspect than seeing and that the ability to introspect each mental state emerges prior to the ability to correctly attribute them to others. Theoretical implications for self-other differences in theory-of-mind development are considered., (© 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.)

Background and Objective: This phase 1 study evaluated the safety and tolerability of single intravitreous injections (IVIs) of ICON-1 (Iconic Therapeutics, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD). ICON-1 is a modified factor VIIa protein linked with the Fc portion of a human immunoglobulin G1. The molecule binds tissue factor overexpressed on choroidal neovascularization (CNV) in AMD., Patients and Methods: Open-label, interventional, dose-escalation trial in 18 patients with CNV due to AMD, with six patients per dose cohort. Patients received a single IVI of ICON-1 at baseline in one of three escalating doses: 60 μg, 150 μg, or 300 μg. Standard anti-vascular endothelial growth factor treatment was allowed at the investigator's discretion at least 2 weeks after the ICON-1 injection; patients were followed up to 24 weeks. Dose escalation was based on the absence of significant safety events. At each study visit, best-corrected visual acuity (BCVA), ophthalmic examination (intraocular pressure, slit-lamp, and dilated fundus examination), and ophthalmic imaging (color fundus photography, fluorescein angiography, and optical coherence tomography) assessments were performed. The systemic pharmacokinetics of ICON-1 and presence of anti-ICON-1 antibodies were also assessed., Results: ICON-1 was safe and well-tolerated up to the highest dose administered, which was 300 μg. Commonly reported adverse events were considered related to the IVI procedure or to the underlying nAMD. No significant systemic levels of ICON-1 or anti-ICON-1 antibodies were detected. Preliminary evidence of biological activity (improved BCVA, reduced central retinal thickness, decreased CNV size, and leakage) was most evident with the 300 μg dose at 1 to 2 weeks after the single ICON-1 injection., Conclusion: Intravitreous administration of ICON-1 in single doses up to 300 μg in eyes with neovascular AMD was safe and well-tolerated. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:336-345.]., (Copyright 2018, SLACK Incorporated.)

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., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.

Background: The contribution of lead contaminated soil to blood lead, especially as it is a large reservoir of lead dust, has been underestimated relative to lead-based paint. On 29 August 2005 Hurricane Katrina flooded and disrupted habitation in New Orleans. Soil and blood lead were mapped prior to Katrina. This unique study addresses soil and blood lead conditions pre- and ten years post-Katrina and considers the effectiveness of low lead soil for lead exposure intervention., Objectives: Comparison of soil and blood lead levels pre- and ten years post-Katrina to evaluate and assess the impact of flooding on soil and blood lead at the scale of the city of New Orleans., Methods: Post-Katrina soil and blood lead data were stratified by the same census tracts (n=176) as pre-Katrina data. This unique city scale data-set includes soil lead (n=3314 and 3320, pre- vs. post-Katrina), blood lead (n=39,620 and 17,739, pre- vs. post-Katrina), distance, and changes in percent pre-1940 housing. Statistical analysis entailed permutation procedures and Fisher's Exact Tests., Results: Pre- vs. ten years post-Katrina soil lead median decreased from 280 mg/kg to 132 mg/kg, median blood lead decreased from 5μg/dL to 1.8μg/dL, respectively. Percent pre-1940 housing did not change significantly (P-value=0.674). Soil and blood lead decrease with distance from the center of New Orleans. Except for age-of-housing results, P-values were extremely small (<10(-12))., Conclusions: Ten years after Katrina, profound changes in soil lead and children's blood lead occurred in New Orleans. Decreasing the lead on soil surfaces reduces children's interaction with lead dust, thus underscoring soil as a major of source of exposure., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In Flint; MI; USA; a public health crisis resulted from the switching of the water supply from Lake Huron to a more corrosive source from the Flint River in April 2014; which caused lead to leach from water lines. Between 2010 and 2015; Flint area children's average blood lead patterns display consistent peaks in the third quarter of the year. The third quarter blood lead peaks displayed a declining trend between 2010 and 2013; then rose abruptly between the third quarters of 2013 from 3.6% blood lead levels ≥5 µg/dL to a peak of about 7% in the third quarter of 2014; an increase of approximately 50%. The percentage of blood lead level ≥5 µg/dL in the first quarter of 2015 then dropped to 2.3%; which was the same percentage as the first quarter of 2014 (prior to the Flint River water source change). The Flint quarterly blood lead level peak then rose to about 6% blood lead levels ≥ 5 µg/dL in the third quarter of 2015; and then declined to about 2.5% in the fourth quarter of 2015. Soil lead data collected by Edible Flint food collaborative reveal generally higher soil lead values in the metropolitan center for Flint; with lower values in the outskirts of the city. The questions that are not being asked is why did children's blood lead levels display a seasonal blood lead pattern before the introduction of the new water supply in Flint; and what are the implications of these seasonal blood lead patterns? Based upon previous findings in Detroit and other North American cities we infer that resuspension to the air of lead in the form of dust from lead contaminated soils in Flint appears to be a persistent contribution to lead exposure of Flint children even before the change in the water supply from Lake Huron to the Flint River.

BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD). Therefore, the development of potent and selective inhibitors of BACE1 has been a focus of many drug discovery efforts in academia and industry. Herein, we report the nonclinical and early clinical development of LY2886721, a BACE1 active site inhibitor that reached phase 2 clinical trials in AD. LY2886721 has high selectivity against key off-target proteases, which efficiently translates in vitro activity into robust in vivo amyloid β lowering in nonclinical animal models. Similar potent and persistent amyloid β lowering was observed in plasma and lumbar CSF when single and multiple doses of LY2886721 were administered to healthy human subjects. Collectively, these data add support for BACE1 inhibition as an effective means of amyloid lowering and as an attractive target for potential disease modification therapy in AD., (Copyright © 2015 the authors 0270-6474/15/351199-12$15.00/0.)

Background: Selective kappa opioid receptor antagonism is a promising experimental strategy for the treatment of depression. The kappa opioid receptor antagonist, LY2456302, exhibits ~30-fold higher affinity for kappa opioid receptors over mu opioid receptors, which is the next closest identified pharmacology., Methods: Here, we determined kappa opioid receptor pharmacological selectivity of LY2456302 by assessing mu opioid receptor antagonism using translational pupillometry in rats and humans., Results: In rats, morphine-induced mydriasis was completely blocked by the nonselective opioid receptor antagonist naloxone (3mg/kg, which produced 90% mu opioid receptor occupancy), while 100 and 300 mg/kg LY2456302 (which produced 56% and 87% mu opioid receptor occupancy, respectively) only partially blocked morphine-induced mydriasis. In humans, fentanyl-induced miosis was completely blocked by 50mg naltrexone, and LY2456302 dose-dependently blocked miosis at 25 and 60 mg (minimal-to-no blockade at 4-10mg)., Conclusions: We demonstrate, for the first time, the use of translational pupillometry in the context of receptor occupancy to identify a clinical dose of LY2456302 achieving maximal kappa opioid receptor occupancy without evidence of significant mu receptor antagonism., (© The Author 2015. Published by Oxford University Press on behalf of CINP.)

Accumulating evidence indicates that selective antagonism of kappa opioid receptors may provide therapeutic benefit in the treatment of major depressive disorder, anxiety disorders, and substance use disorders. LY2456302 is a high-affinity, selective kappa opioid antagonist that demonstrates >30-fold functional selectivity over mu and delta opioid receptors. The safety, tolerability, and pharmacokinetics (PK) of LY2456302 were investigated following single oral doses (2-60 mg), multiple oral doses (2, 10, and 35 mg), and when co-administered with ethanol. Plasma concentrations of LY2456302 were measured by liquid chromatography-tandem mass spectrometry method. Safety analyses were conducted on all enrolled subjects. LY2456302 doses were well-tolerated with no clinically significant findings. No safety concerns were seen on co-administration with ethanol. No evidence for an interaction between LY2456302 and ethanol on cognitive-motor performance was detected. LY2456302 displayed rapid oral absorption and a terminal half-life of approximately 30-40 hours. Plasma exposure of LY2456302 increased proportionally with increasing doses and reached steady state after 6-8 days of once-daily dosing. Steady-state PK of LY2456302 were not affected by coadministration of a single dose of ethanol. No clinically important changes in maximum concentration (Cmax ) or AUC of ethanol (in the presence of LY2456302) were observed., (© 2014, The American College of Clinical Pharmacology.)

Urban environments are the major sites for human habitation and this study evaluates soil lead (Pb) and blood Pb at the community scale of a U.S. city. There is no safe level of Pb exposure for humans and novel primary Pb prevention strategies are requisite to mitigate children's Pb exposure and health disparities observed in major cities. We produced a rich source of environmental and Pb exposure data for metropolitan New Orleans by combining a large soil Pb database (n=5467) with blood Pb databases (n=55,551 pre-Katrina and 7384 post-Katrina) from the Louisiana Childhood Lead Poisoning Prevention Program (LACLPPP). Reanalysis of pre- and post-Hurricane Katrina soil samples indicates relatively unchanged soil Pb. The objective was to evaluate the New Orleans soil Pb and blood Pb database for basic information about conditions that may merit innovative ways to pursue primary Pb exposure prevention. The city was divided into high (median census tract soil≥100 mg/kg) and low Pb areas (median census tract soil<100mg/kg). Soil and blood Pb concentrations within the high and low Pb areas of New Orleans were analyzed by permutation statistical methods. The high Pb areas are toward the interior of the city where median soil Pb was 367, 313, 1228, and 103 mg/kg, respectively for samples collected at busy streets, residential streets, house sides, and open space locations; the low Pb areas are in outlying neighborhoods of the city where median soil Pb was 64, 46, 32, and 28 mg/kg, respectively for busy streets, residential streets, house sides, and open spaces (P-values<10(-16)). Pre-Katrina children's blood Pb prevalence of ≥5 μg/dL was 58.5% and 24.8% for the high and low Pb areas, respectively compared to post-Katrina prevalence of 29.6% and 7.5%, for high and low Pb areas, respectively. Elevated soil Pb permeates interior areas of the city and children living there generally lack Pb safe areas for outdoor play. Soil Pb medians in outlying areas were safer by factors ranging from 3 to 38 depending on specific location. Patterns of Pb deposition from many decades of accumulation have not been transformed by hastily conducted renovations during the seven year interval since Hurricane Katrina. Low Pb soils available outside of cities can remedy soil Pb contamination within city interiors. Mapping soil Pb provides an overview of deposition characteristics and assists with planning and conducting primary Pb exposure prevention., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: To describe a patient with macular infarction caused by Staphylococcus epidermidis-induced endophthalmitis., Methods: Case report., Results: An 88-year-old woman was referred to our clinic for endophthalmitis after cataract extraction. She was diagnosed to have an S. epidermidis infection. Her vision dropped from 20/50 to hand motions. During the course of her infection, she developed multiple multifocal branch retinal artery occlusions associated with absolute capillary nonperfusion centrally and was diagnosed with macular infarction., Conclusion: Although most commonly associated with aminoglycoside toxicity, macular infarction can occur after endophthalmitis treatment without the use of aminoglycosides.

In New Orleans a strong inverse association was previously identified between community soil lead and 4th grade school performance. This study extends the association to zinc, cadmium, nickel, manganese, copper, chromium, cobalt, and vanadium in community soil and their comparative effects on 4th grade school performance. Adjusting for poverty, food security, racial composition, and teacher-student ratios, regression results show that soil metals variously reduce and compress student scores. Soil metals account for 22%-24% while food insecurity accounts for 29%-37% of variation in school performance. The impact on grade point averages were Ni > Co > Mn > Cu ~ Cr ~ Cd > Zn > Pb, but metals are mixtures in soils. The quantities of soil metal mixtures vary widely across the city with the largest totals in the inner city and smallest totals in the outer city. School grade point averages are lowest where the soil metal mixtures and food insecurity are highest., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

According to the amyloid cascade hypothesis, cerebral deposition of amyloid-β peptide (Aβ) is critical for Alzheimer's disease (AD) pathogenesis. Aβ generation is initiated when β-secretase (BACE1) cleaves the amyloid precursor protein. For more than a decade, BACE1 has been a prime target for designing drugs to prevent or treat AD. However, development of such agents has turned out to be extremely challenging, with major hurdles in cell penetration, oral bioavailability/metabolic clearance, and brain access. Using a fragment-based chemistry strategy, we have generated LY2811376 [(S)-4-(2,4-difluoro-5-pyrimidin-5-yl-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]thiazin-2-ylamine], the first orally available non-peptidic BACE1 inhibitor that produces profound Aβ-lowering effects in animals. The biomarker changes obtained in preclinical animal models translate into man at doses of LY2811376 that were safe and well tolerated in healthy volunteers. Prominent and long-lasting Aβ reductions in lumbar CSF were measured after oral dosing of 30 or 90 mg of LY2811376. This represents the first translation of BACE1-driven biomarker changes in CNS from preclinical animal models to man. Because of toxicology findings identified in longer-term preclinical studies, this compound is no longer progressing in clinical development. However, BACE1 remains a viable target because the adverse effects reported here were recapitulated in LY2811376-treated BACE1 KO mice and thus are unrelated to BACE1 inhibition. The magnitude and duration of central Aβ reduction obtainable with BACE1 inhibition positions this protease as a tractable small-molecule target through which to test the amyloid hypothesis in man.

Background: Compared with a maximum collective lead (Pb) estimate of ∼1811 metric tons (MT) in exterior paint on 86,000 New Orleans houses, Pb additives in gasoline were estimated at ∼12,000 MT in New Orleans, yielding ∼9100 MT Pb exhausted as aerosols from vehicles; ∼4850 MT were particles>10 μm and ∼4200 MT were particles <0.25 μm., Objectives: To evaluate pre-Hurricane Katrina soil Pb and children's blood Pb at public housing and private residential properties in the inner-city compared with the outer city of New Orleans., Methods: This study includes 224 soil samples from 10 public housing properties and 363 soil samples from residential private properties within an 800 m radius of centroids of public housing census tracts. The Louisiana Childhood Lead Poisoning Prevention Program data from 2000 to 2005 (pre-Hurricane Katrina) was the source for 9807 children's blood Pb (μg/dL) results. Soil and blood Pb data were grouped by public housing census tracts and private residential properties. This study uses Multi-Response Permutation Procedures for statistical analysis., Results: Brick public properties in the city core had significantly more soil Pb contamination and higher prevalence of elevated children's blood Pb than same-aged brick public properties in the outer areas of the city. The pre-Hurricane Katrina New Orleans concentration of Pb dust in the inner-city soil displayed a median of 438 mg/kg or 3.7 times larger than Pb dust in outlying areas where the median soil Pb was 117 mg/kg (p-value=2.9×10(-15)). Also, the pre-Hurricane Katrina prevalence of children's blood Pb≥10 μg/dL was 22.9% within the inner-city compared with 9.1% in the outer areas of New Orleans (p-value=3.4×10(-74))., Conclusions: Comparing the quantities of Pb dust from paint and Pb additives to gasoline, this study supports the later source as a more plausible explanation for the differences in soil Pb and children's blood Pb within public and private housing in the higher traffic congested inner-city core compared with the lower traffic congested outer areas of New Orleans. Similar patterns of environmental Pb dust contamination and childhood Pb exposure are expected in all cities., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The feasibility of reducing children's exposure to lead (Pb) polluted soil in New Orleans is tested. Childcare centers (median = 48 children) are often located in former residences. The extent of soil Pb was determined by selecting centers in both the core and outlying areas. The initial 558 mg/kg median soil Pb (range 14-3692 mg/kg) decreased to median 4.1 mg/kg (range 2.2-26.1 mg/kg) after intervention with geotextile covered by 15 cm of river alluvium. Pb loading decreased from a median of 4887 μg/m(2) (454 μg/ft(2)) range 603-56650 μg/m(2) (56-5263 μg/ft(2)) to a median of 398 μg/m(2) (37 μg/ft(2)) range 86-980 μg/m(2) (8-91 μg/ft(2)). Multi-Response Permutation Procedures indicate similar (P-values = 0.160-0.231) soil Pb at childcare centers compared to soil Pb of nearby residential communities. At ∼$100 per child, soil Pb and surface loading were reduced within hours, advancing an upstream intervention conceptualization about Pb exposure prevention., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Background: Primary pulmonary arterial hypertension is a rare systemic condition that may present with distinct ocular findings., Purpose: To report a patient whose ophthalmic manifestations led to a diagnosis of pulmonary arterial hypertension., Results: A 58-year-old woman presented with bilateral serous detachments, angle closure, dilated episcleral blood vessels, subretinal drusenoid-like deposits, and intraretinal hemorrhages. She was diagnosed with pulmonary arterial hypertension. Her ocular findings resolved once her underlying systemic disorder had been treated., Conclusion: To our knowledge, this is the first reported case in which an ophthalmic evaluation led to the diagnosis of pulmonary arterial hypertension.

Previous studies identified a curvilinear association between aggregated blood lead (BL) and soil lead (SL) data in New Orleans census tracts. In this study we investigate the relationships between SL (mg/kg), age of child, and BL (μg/dL) of 55,551 children in 280 census tracts in metropolitan New Orleans, 2000 to 2005. Analyses include random effects regression models predicting BL levels of children (μg/dL) and random effects logistic regression models predicting the odds of BL in children exceeding 15, 10, 7, 5, and 3 μg/dL as a function of age and SL exposure. Economic benefits of SL reduction scenarios are estimated. A unit raise in median SL⁰·⁵ significantly increases the BL level in children (b=0.214 p= or <0.01), and a unit change in Age⁰·⁵ significantly increases child BL (b=0.401, p= or <0.01). A unit change in Age⁰·⁵ increases the odds of a child BL exceeding 10 μg/dL by a multiplicative factor of 1.23 (95% CI 1.21 to 1.25), and a unit (mg/kg) addition of SL increases the odds of child BL> 10 μg/dL by a factor of 1.13 (95% CI 1.12 to 1.14). Extrapolating from regression results, we find that a shift in SL regulatory standard from 400 to 100 mg/kg provides each child with an economic benefit ranging from $4710 to $12,624 ($US 2000). Children's BL is a curvilinear function of both age and level of exposure to neighborhood SL. Therefore, a change in SL regulatory standard from 400 to 100mg/kg provides children with substantial economic benefit., (Published by Elsevier B.V.)

The subject of this paper is lead (Pb) additives in gasoline and their material and health impact from Pb dust inputs into 90 US urbanized areas (UAs). The mass of Pb additives for 90 UAs as a total of the US Pb additives in 1982 were estimated from vehicle travel, vehicle fuel economy (miles/gallon), ratio of leaded to unleaded fuel, and Pb/gallon. About 500 billion (10⁹) miles of travel in 90 UA's during 1982 account for ~18,000 metric tons (MT), or nearly 30% of the US Pb additives in 1982. Applying the 1982 proportions to the 90 UAs for 1950 through 1982 fuel sales by state accounts for ~1.4 million MT Pb of the US national total of 4.6 million MT during the same years. Fates of Pb additives in engine systems were used to calculate Pb aerosol inputs into the 90 UAs. The inputs range from 100's to more than 100,000 MT of Pb depending on a given UA's traffic flow patterns. Soils are the reservoir of urban Pb dust. The median background soil Pb for the US is 16.5mg/kg (range 10.3 to 30.1mg/kg), and less by an order of magnitude or more than soil Pb within larger UAs. Recognizing the US input of massive gasoline Pb additives into UAs assists with comprehending soil Pb differences between large and small UAs, inner and outer areas of UAs, health disparities, and school achievement issues within UAs. The findings underscore the need for controlling accumulated exterior urban Pb dust from gasoline additives along with paint sources that have accumulated in soil to meet the goal of primary childhood Pb exposure prevention., (Published by Elsevier Ltd.)

Arsenic (As) ranks first on the 2005 and 2007 hazardous substances priority lists compiled for the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). This study describes two New Orleans soil As surveys: (1) a survey of composite soil samples from 286 census tracts and (2) a field survey of soil As at 38 play areas associated with the presence of chromated-copper-arsenate (CCA)-treated wood on residential and public properties. The survey of metropolitan New Orleans soils revealed a median As content of 1.5 mg/kg (range <0.2-16.4) and no distinctive differences between the soils of the city core and outlying areas. Play area accessible soils associated with CCA-treated wood (N = 32) had a median As of 57 mg/kg and 78% of the samples were ≥12 mg/kg, the Louisiana soil As standard. The field survey of play areas for CCA-treated wood (N = 132 samples at 38 sites) was conducted with a portable energy-dispersive X-ray fluorescence (XRF) analyzer. Seventy-five of 132 wood samples (56.8%) were deemed CCA-treated wood. Of the 38 play areas surveyed, 14 (36.8%) had CCA-treated wood. A significant association (Fisher's exact p-value = 0.348 × 10(-6)) was found between CCA-treated wood and soil As (N = 75). At one elementary school CCA-treated woodchips (As range 813-1,654 mg As/kg) covered the playgrounds. The situation in New Orleans probably exists in play areas across the nation. These findings support a precautionary program for testing soils and wood for hazardous substances at all play areas intended for children.

Prior to Hurricanes Katrina and Rita (HKR), significant associations were noted between soil lead (SL) and blood lead (BL) in New Orleans. Engineering failure of New Orleans levees and canal walls after HKR set the stage for a quasi-experiment to evaluate BL responses by 13 306 children to reductions in SL. High density soil surveying conducted in 46 census tracts before HKR was repeated after the flood. Paired t test results show that SL decreased from 328.54 to 203.33 mg/kg post-HKR (t = 3.296, p < or = 0.01). Decreases in SL are associated with declines in children's BL response (r = 0.308, p < or = 0.05). When SL decreased at least 1%, median children's BL declined 1.55 microg/dL. Declines in median BL are largest in census tracts with > or =50% decrease in SL. Also individual BL in children was predicted as a function of SL, adjusting for age, year of observation, and depth of flood waters. At the individual scale, BL decreased significantly in post-HKR as a function of SL, with BL decreases ranging from b = -1.20 to -1.65 microg/dL, depending on the decline of SL and whether children were born in the post-HKR period. Our results support policy to improve soil conditions for children.

The postoperative course of a patient who underwent retinal detachment repair using perfluoro-n-octane (PFO) and perfluoropropane (C(3)F(8)) gas endotamponade is described in which midlenticular optic opacification of a hydrophobic acrylic intraocular lens was noted. Mechanisms for optic opacification are proposed, which include dystrophic calcification and PFO-induced optic degeneration. The case presents a novel case of midlenticular intraocular lens optic opacification in the setting of retained perfluorocarbon liquid following retinal detachment repair., (Copyright 2010, SLACK Incorporated.)

Objectives: Active and passive immunization strategies have been suggested as possible options for the treatment of Alzheimer disease (AD). LY2062430 (solanezumab) is a humanized monoclonal antibody being studied as a putative disease-modifying treatment of AD., Methods: Patients with mild to moderate AD were screened and selected for inclusion. Initial screening was performed for 54 subjects, and 29 of these underwent additional screening; after this second screening, a total of 19 subjects were included. Single doses of solanezumab using 0.5, 1.5, 4.0, and 10.0 mg/kg were administered. Safety assessments included gadolinium-enhanced magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) analyses at baseline and 21 days after dosing. Plasma and CSF concentrations of solanezumab and amyloid beta (Abeta) and cognitive evaluations were obtained., Results: Administration of solanezumab was generally well tolerated except that mild self-limited symptoms consistent with infusion reactions occurred for 2 of 4 subjects given 10 mg/kg. No evidence of meningoencephalitis, microhemorrhage, or vasogenic edema was present based on magnetic resonance image and CSF analyses. A substantial dose-dependent increase in total (bound plus unbound) Abeta was demonstrated in plasma; CSF total Abeta also increased. No changes in cognitive scores occurred., Conclusions: A single dose of solanezumab was generally well tolerated, although infusion reactions similar to those seen with administration of other proteins may occur with higher doses. A dose-dependent change in plasma and CSF Abeta was observed, although changes in cognitive scores were not noted. Further studies of solanezumab for the treatment of AD are warranted.

Purpose: To assess the efficacy and safety of intravitreous pegaptanib sodium (Macugen; EyeTech Pharmaceuticals/Pfizer Inc, New York, New York, USA) for macular edema secondary to branch retinal vein occlusion (BRVO)., Design: Prospective, randomized, dose-finding study., Methods: Twenty subjects from three clinical practices in the United States with BRVO of more than 1 month's and fewer than 6 months' duration; best-corrected visual acuity (BCVA) 70 to 25 Early Treatment Diabetic Retinopathy Study letters inclusive (approximately 20/40 to 20/320 Snellen); and central foveal thickness of 250 microm or more were included. Subjects were randomized 3:1 to intravitreous injections of pegaptanib 0.3 or 1 mg at baseline and at weeks 6 and 12 with subsequent injections at 6-week intervals at investigator discretion until week 48. Principal efficacy outcomes were change from baseline to week 54 in BCVA, center point thickness, central subfield thickness, and macular volume as measured by optical coherence tomography., Results: Fifteen subjects received pegaptanib 0.3 mg and 5 received pegaptanib 1 mg. Eighteen subjects completed the 54-week follow-up. Results were similar in both the 0.3- and 1-mg groups. Overall improvements from baseline to week 54 occurred in mean BCVA (+14 +/- 13 letters), center point thickness (-205 +/- 195 mum), central subfield thickness (-201 +/- 153 mum), and macular volume (-2.2 +/- 1.6 mm(3)). The response was rapid after the first injection, with a mean BCVA improvement of 11 +/- 7 letters at 1 week from the baseline of 56 +/- 12 letters (approximately 20/80 Snellen). One retinal detachment and no cases of endophthalmitis or traumatic cataract were seen., Conclusions: Intravitreous pegaptanib offers a promising alternative as a treatment for macular edema secondary to BRVO., (Copyright 2010 Elsevier Inc. All rights reserved.)

The flooding of New Orleans in late August and September 2005 caused widespread sediment deposition in the flooded areas of the city. Post-flood sampling by US EPA revealed that 37% of sediment samples exceeded Louisiana corrective screening guidelines for arsenic of 12mg/kg, but there was debate over whether this contamination was pre-existing, as almost no pre-flood soil sampling for arsenic had been done in New Orleans. In this study, archived soil samples collected in 1998-1999 were location-matched with 70 residential sites in New Orleans where post-flood arsenic concentrations were elevated. Those same locations were sampled again during the recovery period 18 months later. During the recovery period, sampling for arsenic was also done for the first time at school sites and playgrounds within the flooded zone. Every sample of sediment taken 1-10 months after the flood exceeded the arsenic concentration found in the matched pre-flood soils. The average difference between the two sampling periods was 19.67mg/kg (95% CI 16.63-22.71) with a range of 3.60-74.61mg/kg. At virtually all of these sites (97%), arsenic concentrations decreased substantially by 18 months into the recovery period when the average concentration of matched samples was 3.26mg/kg (95% CI 1.86-4.66). However, 21 (30%) of the samples taken during the recovery period still had higher concentrations of arsenic than the matched sample taken prior to the flooding. In addition, 33% of samples from schoolyards and 13% of samples from playgrounds had elevated arsenic concentrations above the screening guidelines during the recovery period. These findings suggest that the flooding resulted in the deposition of arsenic-contaminated sediments. Diminution of the quantity of sediment at many locations has significantly reduced overall soil arsenic concentrations, but some locations remain of concern for potential long-term soil contamination.

Objective: Recent retrospective analyses have suggested that postoperative endophthalmitis may be more frequent with 25- than 20-gauge pars plana vitrectomy (PPV). Because the infection risk may depend on the suturing status of the sclerotomy, and the perioperative anti-infection protocol, we compared the incidence rate of endophthalmitis after sutureless 25-gauge versus sutured 20-gauge PPV on a large cohort of patients operated with a standardized perioperative anti-infection protocol., Design: Retrospective comparative case series., Participants: Consecutive patients who underwent 20- or 25-gauge PPVs at a single center over a multi-year period., Methods: We analyzed 3597 consecutive PPVs. Patients with a pre-PPV diagnosis of endophthalmitis, PPVs performed for implantation of drug delivery devices, or 25-gauge PPVs with all sclerotomies sutured closed were excluded. Patients with > or =1 week of follow-up were divided into 2 study groups by sclerotomy status at the end of surgery: the 20-gauge group had 3 sutured 20-gauge sclerotomies, and the 25-gauge group had > or =1 unsutured 25-gauge sclerotomy. Endophthalmitis was defined by clinical criteria independent of microbiological results., Main Outcome Measures: The incidence of endophthalmitis was compared between 25- versus 20-gauge groups., Results: Of 3372 PPV surgeries meeting inclusion and exclusion criteria, 1948 and 1424 surgeries were 20- and 25-gauge PPVs, respectively. Average age (+/- standard deviation) of patients was 54.6 (+/- 22.6) and 64.4 (+/- 16.5) years in the 20- and 25-gauge PPV groups, respectively (P<0.0001). Median post-PPV follow-up time was not significantly different between the 2 groups (12.5 vs 13.0 months; P = 0.69). Endophthalmitis was observed in 1 patient (0.07%; 95% confidence interval, 0%-0.21%) from the 25-gauge group and none in the 20-gauge group (P = 0.42; Fisher exact test, 2-tailed). The use of air/gas endotamponade (P<0.0001) and intravitreal triamcinolone (P<0.001) was more common in 25- versus 20-gauge PPV., Conclusions: The incidence of endophthalmitis was low in both groups. We were unable to show a significant difference in the incidence of endophthalmitis between sutureless 25-gauge and sutured 20-gauge PPV, and conclude that a careful perioperative anti-infection protocol may reduce 25-gauge PPV endophthalmitis risk to that of 20-gauge PPV.

Unlabelled: This is a retrospective study of 56 eyes of 49 children undergoing vitrectomy with 25-gauge instrumentation. There were no cases of endophthalmitis, wound leaks or hypotony requiring treatment. A modified approach in which the conjunctiva and sclera is sutured was used for young babies requiring a pars plicata approach., Objective: To evaluate the feasibility and safety of 25-gauge vitrectomy for various vitreoretinal indications in the paediatric population., Methods: Consecutive patients aged 18 years or less undergoing vitrectomy for various vitreoretinal indications over a 5-year period were studied retrospectively. Two different surgical techniques were used: a modified 25-gauge approach in which the sclerotomies and conjunctiva were sutured as described previously for most children under the age of 1 year, and a transconjunctival 25-gauge approach for older children, Results: 56 eyes in 49 children (16 girls and 33 boys) were included. Intraoperative unplanned events or complications included: conversion to 20-gauge vitrectomy (four), conversion of one port to a 20-gauge sclerotomy (two), suspected lens damage (one) and intraoperative bleeding from a vascular ridge (one). Postoperative complications included cataract (five), rhegmatogenous retinal detachment (four) and vitreous haemorrhage (three). The four retinal detachments were either recurrent or occurred in eyes with complex ocular pathology and were not felt to be related to the surgical technique. There were no cases of postoperative hypotony requiring intervention, choroidal detachment, endophthalmitis or sclerotomy-related retinal breaks., Conclusions: 25-gauge vitreoretinal techniques can be used in various paediatric vitreoretinal conditions and facilitate easy access to small spaces in the paediatric eye. To avoid postoperative hypotony, a modified technique is recommended for younger babies in which the conjunctiva and sclera is sutured.

A surgical technique is described combining submacular anti-vascular endothelial growth factor (anti-VEGF) and recombinant tissue plasminogen activator (r-TPA) with pneumatic displacement of massive submacular hemorrhage in age-related macular degeneration. An 84-year-old man with a large, acute submacular hemorrhage secondary to age-related macular degeneration underwent combination vitrectomy, submacular anti-VEGF and r-TPA injection with pneumatic displacement of the hemorrhage. At the last follow-up visit, 7 months after surgery, visual acuity was 20/80 with a small fibrovascular pigment epithelial detachment and atrophic retinal pigment epithelial changes. A 77-year-old woman with known age-related macular degeneration underwent a similar surgical procedure for a similar acute, large submacular hemorrhage related to age-related macular degeneration. Nine months after surgery, the visual acuity was 20/70(-1). Combination submacular anti-VEGF therapy delivered at the time of pars plana vitrectomy and submacular tissue plasminogen activator assisted hemorrhage displacement may be a viable treatment strategy for the management massive submacular hemorrhage.

When Hurricane Katrina struck the U.S. Gulf Coast, levees surrounding New Orleans, Louisiana, USA, were breached, leading to widespread flooding of the city and potential contamination from industrial spills, residential sources, and redistribution of pre-existing pollutants. We chemically characterized sediment samples from five New Orleans locations and used early development and mutagenesis in Japanese medaka (Oryzias latipes) as metrics of the toxic effects of these sediments. Sediment samples were analyzed for organohalogen pesticides, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, and metals. One month after Hurricane Katrina, four of the five sites had unsafe concentrations of arsenic and one or more pesticides, pesticide metabolites, or polycyclic aromatic hydrocarbons. Medaka embryonic mortality and time to hatching both increased during exposure to aqueous extracts of sediments, with the greatest toxicity observed for the most heavily contaminated sediment. Exposure to sediment extracts did not, however, result in significantly elevated rates of mutagenesis. When the most contaminated site was resampled 4.5 months later, the sediment had lower contaminant concentrations and fewer deleterious effects on medaka development. Using the medaka bioassay, therefore, we demonstrate toxic effects of post-Hurricane Katrina sediments immediately following the storm, with some amelioration over time of contaminant concentrations and their negative biological effects.

Purpose: To describe an infant with shaken baby syndrome and a traumatic macular hole treated with pars plana vitrectomy and gas tamponade., Design: Case report., Methods: A 4-month-old infant with suspected shaken baby syndrome presented with intraretinal and premacular hemorrhages. To prevent amblyopia, these hemorrhages were removed by pars plana vitrectomy, during which a full-thickness macular hole was discovered. Completion of a posterior vitreous detachment was not attempted at the time. Six months later, the macular hole remained open and was treated with pars plana vitrectomy, internal limiting membrane peeling, and perfluoropropane tamponade., Results: The procedure was well tolerated, and the macular hole closed without postoperative positioning. The hole remained closed 6 months after surgical repair., Conclusions: Traumatic macular hole may be a complication of shaken baby syndrome. This case demonstrates that pars plana vitrectomy with gas tamponade can be used to successfully treat traumatic macular hole in infants.

Objective: To describe the characteristics of and surgical outcomes for primary pediatric rhegmatogenous retinal detachment (RRD) and to evaluate whether specific characteristics impact anatomical outcomes after surgical intervention., Methods: Data for consecutive patients (18 years of age or younger) with RRD who required surgery over a 5-year period were studied retrospectively. Patients with recurrent retinal detachment or active retinopathy of prematurity were excluded., Results: Forty-six eyes of 45 patients (median age, 9 years) were included. Ninety-eight percent of the patients had at least 1 predisposing factor, including prior surgery (61%), trauma (43%), developmental abnormality (35%), and myopia (17%). Retinal reattachment was attained in 78% of eyes. Younger age (P = 0.019), worse initial vision (P = 0.008), greater extent of retinal detachment (P = 0.007), and presence of proliferative vitreoretinopathy (grade C or worse) (P = 0.008) were associated with worse anatomical outcomes. Vision improved after surgery in 56% of patients, but overall visual results were modest. Thirty-seven percent of patients had vision-threatening lesions in the other eye, and 18% had a history of retinal detachment in the fellow eye., Conclusions: Pediatric RRD is often associated with a predisposing factor. Favorable anatomical and visual outcomes are possible, and lesions in the fellow eye are common.

Purpose: To identify systemic risk factors associated with treatment failure of diode laser photocoagulation for threshold or prethreshold retinopathy of prematurity (ROP)., Methods: Consecutive infants treated with laser at our institution and infants referred from outside centers with progression to stage 4 or 5 ROP after laser treatment were included in this retrospective study. Two groups were identified: those with regression of ROP after laser (LT group; 196 eyes of 98 infants) and those with progression to stage 4 or 5 ROP after laser (ST group; 134 eyes of 80 infants)., Results: Using a multiple logistic regression model, there was a statistically significant association for progression of treated ROP to retinal detachment (RD) with history of sepsis (P < 0.001), oxygen therapy (P = 0.003), mechanical ventilation (P = 0.003), respiratory distress syndrome (RDS; P = 0.005), and patent ductus arteriosus (PDA; P = 0.042). On the other hand, jaundice (P = 0.563), anemia (P = 0.599), thrombocytopenia (P = 0.689), and blood transfusion (P = 0.878) did not show a statistically significant association with failure of laser treatment and progression of ROP to stage 4 or 5 disease., Conclusions: Premature infants with a history sepsis, oxygen therapy, mechanical ventilation, RDS, and PDA may be at a higher risk for progression of ROP despite diode laser treatment.

Metropolitan New Orleans is unique because it has a universal blood lead (BL) screening dataset (n=55,551) from 2000-2005 spatially coupled with a soil lead (SL) dataset (n=5467) completed in 2000. We evaluated empirical associations between measurements of SL and BL exposure responses of children in New Orleans by stratifying the databases by Census Tracts and statistically analyzing them with permutation methods. A consistent curvilinear association occurred annually between SL and BL with robust significance (P-values<10(-23)). The mathematical model of the pooled BL datasets for 2000-2005 is: BL=2.038+0.172 x (SL)(0.5) (agreement (R) of 0.534, an r(2) of 0.528, and a P-value of 1.0 x 10(-211)) indicating that chance alone cannot explain the association. Below 100 mg/kg SL children's BL exposure response is steep (1.4 microg/dL per 100 mg/kg), while above 300 mg/kg SL the BL exposure response is gradual (0.32 microg/dL per 100 mg/kg). In 1995, the BL prevalence was 37%>or=10 microg/dL for the most vulnerable poor and predominantly African-American children. In the era of universal screening the prevalence of elevated BL is 11.8%>or=10 microg/dL for the general population of children. The SL map describes community variations of potential BL exposure. If health effects occur at BL>or=2 microg/dL, then 93.5% of the children in New Orleans are at risk. These results reinforce the proposal that prevention of childhood Pb exposure must include SL remediation as demonstrated by a New Orleans pilot project and a proactive Norwegian government program.