Prenatal metal(loid) mixtures and birth weight for gestational age: A pooled analysis of three cohorts participating in the ECHO program

Background: A growing number of studies have identified both toxic and essential metals which influence fetal growth. However, most studies have conducted single-cohort analyses, which are often limited by narrow exposure ranges, and evaluated metals individually. The objective of the current study was to conduct an environmental mixture analysis of metal impacts on fetal growth, pooling data from three geographically and demographically diverse cohorts in the United States participating in the Environmental Influences on Child Health Outcomes program. Methods: The pooled sample (N = 1,002) included participants from the MADRES, NHBCS, and PROTECT cohorts. Associations between seven metals (antimony, cadmium, cobalt, mercury, molybdenum, nickel, tin) measured in maternal urine samples collected during pregnancy (median: 16.0 weeks gestation) and birth weight for gestational age z-scores (BW for GA) were investigated using Bayesian Kernel Machine Regression (BKMR). Models were also stratified by cohort and infant sex to investigate possible heterogeneity. Chromium and uranium concentrations fell below the limits of detection for most participants and were evaluated separately as binary variables using pooled linear regression models. Results: In the pooled BKMR analysis, antimony, mercury, and tin were inversely and linearly associated with BW for GA, while a positive linear association was identified for nickel. The inverse association between antimony and BW for GA was observed in both males and females and for all three cohorts but was strongest for MADRES, a predominantly low-income Hispanic cohort in Los Angeles. A reverse j-shaped association was identified between cobalt and BW for GA, which was driven by female infants. Pooled associations were null for cadmium, chromium, molybdenum, and uranium, and BKMR did not identify potential interactions between metal pairs. Conclusions: Findings suggest that antimony, an understudied metalloid, may adversely impact fetal growth. Cohort- and/or sex-dependent associations were identified for many of the metals, which merit additional investigation

The Vehicle, Fall 1978

Vol. 2, No. 1 Table of Contents FarewellGregory Manifoldpage 4 Visiting HoursCindy Grocepage 5 The Deer KillerG.L. Bullardpage 6 Identity CrisisCindy Grocepage 9 I ScreamDale Stroheckerpage 11 John RobertLee Martinpage 12 Smiling in WinterNancy Cunninghampage 20 Walt Disney Told Us LiesThomas C. Howellpage 20 LakesideMary McDanielpage 21 Heavy LiteratureTerry Kroenungpage 22 Old FriendsMary McDanielpage 27 A Sunny AfternoonJoan O\u27Connorpage 28 Always TomorrowMary McDanielpage 29 Four SunsetsGregory Manifoldpage 30 Come FreeBob Welshpage 32 Faded PinstripesLee Martinpage 33 WindsongCarolyn Perrypage 38 SilenceSylvia Aldertonpage 39 One More TimeCheri Clousepage 40 Grandfather Was IlliterateCindy Grocepage 41 StonehengeGregory Manifoldpage 43 GabsCheri Clousepage 44 Spindley Bare BranchesJeanne Hansenpage 48 Art CoverLafayette Wilson PhotographBill Cochranpage 3 DrawingLafayette Wilsonpage 10 DrawingLafayette Wilsonpage 19 PhotographBill Cochranpage 21 PhotographBarbara Colemanpage 28 DrawingJoyce Bonwellpage 31 PhotographKathy Sanderspage 39 DrawingKathy Sanderspage 42https://thekeep.eiu.edu/vehicle/1035/thumbnail.jp

Interaction of a dengue virus NS1-derived peptide with the inhibitory receptor KIR3DL1 on natural killer cells

Killer immunoglobulin-like receptors (KIRs) interact with human leucocyte antigen (HLA) class I ligands and play a key role in the regulation and activation of NK cells. The functional importance of KIR-HLA interactions has been demonstrated for a number of chronic viral infections, but to date only a few studies have been performed in the context of acute self-limited viral infections. During our investigation of CD8(+) T cell responses to a conserved HLA-B57-restricted epitope derived from dengue virus (DENV) non-structural protein-1 (NS1), we observed substantial binding of the tetrameric complex to non-T/non-B lymphocytes in peripheral blood mononuclear cells (PBMC) from a long-standing clinical cohort in Thailand. We confirmed binding of the NS1 tetramer to CD56(dim) NK cells, which are known to express KIRs. Using depletion studies and KIR-transfected cell lines, we demonstrated further that the NS1 tetramer bound the inhibitory receptor KIR3DL1. Phenotypical analysis of PBMC from HLA-B57(+) subjects with acute DENV infection revealed marked activation of NS1 tetramer-binding natural killer (NK) cells around the time of defervescence in subjects with severe dengue disease. Collectively, our findings indicate that subsets of NK cells are activated relatively late in the course of acute DENV illness and reveal a possible role for specific KIR-HLA interactions in the modulation of disease outcomes

SAkuraBONSAI: Protocol Design of a Novel, Prospective Study to Explore Clinical, Imaging, and Biomarker Outcomes in Patients With AQP4-IgG-Seropositive Neuromyelitis Optica Spectrum Disorder Receiving Open-Label Satralizumab

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare, autoimmune disease of the central nervous system that produces acute, unpredictable relapses causing cumulative neurological disability. Satralizumab, a humanized, monoclonal recycling antibody that targets the interleukin-6 receptor, reduced NMOSD relapse risk vs. placebo in two Phase 3 trials: SAkuraSky (satralizumab ± immunosuppressive therapy; NCT02028884) and SAkuraStar (satralizumab monotherapy; NCT02073279). Satralizumab is approved to treat aquaporin-4 IgG-seropositive (AQP4-IgG+) NMOSD. SAkuraBONSAI (NCT05269667) will explore fluid and imaging biomarkers to better understand the mechanism of action of satralizumab and the neuronal and immunological changes following treatment in AQP4-IgG+ NMOSD. Objectives: SAkuraBONSAI will evaluate clinical disease activity measures, patient-reported outcomes (PROs), pharmacokinetics, and safety of satralizumab in AQP4-IgG+ NMOSD. Correlations between imaging markers (magnetic resonance imaging [MRI] and optical coherence tomography [OCT]) and blood and cerebrospinal fluid (CSF) biomarkers will be investigated. Study design: SAkuraBONSAI is a prospective, open-label, multicenter, international, Phase 4 study that will enroll approximately 100 adults (18-74 years) with AQP4-IgG+ NMOSD. This study includes two patient cohorts: newly diagnosed, treatment-naïve patients (Cohort 1; n = 60); and inadequate responders to recent (\u3c6 months) rituximab infusion (Cohort 2; n = 40). Satralizumab monotherapy (120 mg) will be administered subcutaneously at Weeks 0, 2, 4, and Q4W thereafter for a total of 92 weeks. Endpoints: Disease activity related to relapses (proportion relapse-free, annualized relapse rate, time to relapse, and relapse severity), disability progression (Expanded Disability Status Scale), cognition (Symbol Digit Modalities Test), and ophthalmological changes (visual acuity; National Eye Institute Visual Function Questionnaire-25) will all be assessed. Peri-papillary retinal nerve fiber layer and ganglion cell complex thickness will be monitored using advanced OCT (retinal nerve fiber layer and ganglion cell plus inner plexiform layer thickness). Lesion activity and atrophy will be monitored by MRI. Pharmacokinetics, PROs, and blood and CSF mechanistic biomarkers will be assessed regularly. Safety outcomes include the incidence and severity of adverse events. Conclusions: SAkuraBONSAI will incorporate comprehensive imaging, fluid biomarker, and clinical assessments in patients with AQP4-IgG+ NMOSD. SAkuraBONSAI will provide new insights into the mechanism of action of satralizumab in NMOSD, while offering the opportunity to identify clinically relevant neurological, immunological, and imaging markers

Associations of Neighborhood Opportunity and Social Vulnerability With Trajectories of Childhood Body Mass Index and Obesity Among US Children

IMPORTANCE: Physical and social neighborhood attributes may have implications for children\u27s growth and development patterns. The extent to which these attributes are associated with body mass index (BMI) trajectories and obesity risk from childhood to adolescence remains understudied. OBJECTIVE: To examine associations of neighborhood-level measures of opportunity and social vulnerability with trajectories of BMI and obesity risk from birth to adolescence. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 54 cohorts (20 677 children) participating in the Environmental Influences on Child Health Outcomes (ECHO) program from January 1, 1995, to January 1, 2022. Participant inclusion required at least 1 geocoded residential address and anthropometric measure (taken at the same time or after the address date) from birth through adolescence. Data were analyzed from February 1 to June 30, 2022. EXPOSURES: Census tract-level Child Opportunity Index (COI) and Social Vulnerability Index (SVI) linked to geocoded residential addresses at birth and in infancy (age range, 0.5-1.5 years), early childhood (age range, 2.0-4.8 years), and mid-childhood (age range, 5.0-9.8 years). MAIN OUTCOMES AND MEASURES: BMI (calculated as weight in kilograms divided by length [if aged \u3c2 \u3eyears] or height in meters squared) and obesity (age- and sex-specific BMI ≥95th percentile). Based on nationwide distributions of the COI and SVI, Census tract rankings were grouped into 5 categories: very low (\u3c20th \u3epercentile), low (20th percentile to \u3c40th \u3epercentile), moderate (40th percentile to \u3c60th \u3epercentile), high (60th percentile to \u3c80th \u3epercentile), or very high (≥80th percentile) opportunity (COI) or vulnerability (SVI). RESULTS: Among 20 677 children, 10 747 (52.0%) were male; 12 463 of 20 105 (62.0%) were White, and 16 036 of 20 333 (78.9%) were non-Hispanic. (Some data for race and ethnicity were missing.) Overall, 29.9% of children in the ECHO program resided in areas with the most advantageous characteristics. For example, at birth, 26.7% of children lived in areas with very high COI, and 25.3% lived in areas with very low SVI; in mid-childhood, 30.6% lived in areas with very high COI and 28.4% lived in areas with very low SVI. Linear mixed-effects models revealed that at every life stage, children who resided in areas with higher COI (vs very low COI) had lower mean BMI trajectories and lower risk of obesity from childhood to adolescence, independent of family sociodemographic and prenatal characteristics. For example, among children with obesity at age 10 years, the risk ratio was 0.21 (95% CI, 0.12-0.34) for very high COI at birth, 0.31 (95% CI, 0.20-0.51) for high COI at birth, 0.46 (95% CI, 0.28-0.74) for moderate COI at birth, and 0.53 (95% CI, 0.32-0.86) for low COI at birth. Similar patterns of findings were observed for children who resided in areas with lower SVI (vs very high SVI). For example, among children with obesity at age 10 years, the risk ratio was 0.17 (95% CI, 0.10-0.30) for very low SVI at birth, 0.20 (95% CI, 0.11-0.35) for low SVI at birth, 0.42 (95% CI, 0.24-0.75) for moderate SVI at birth, and 0.43 (95% CI, 0.24-0.76) for high SVI at birth. For both indices, effect estimates for mean BMI difference and obesity risk were larger at an older age of outcome measurement. In addition, exposure to COI or SVI at birth was associated with the most substantial difference in subsequent mean BMI and risk of obesity compared with exposure at later life stages. CONCLUSIONS AND RELEVANCE: In this cohort study, residing in higher-opportunity and lower-vulnerability neighborhoods in early life, especially at birth, was associated with a lower mean BMI trajectory and a lower risk of obesity from childhood to adolescence. Future research should clarify whether initiatives or policies that alter specific components of neighborhood environment would be beneficial in preventing excess weight in children

The effects of International Equity Cross-Listing on Investor Protection and Firm Value

In this thesis, I examine issues pertaining to equity cross-listing in the United States and the United Kingdom. Specifically, I examine two issues, namely the effects of an international equity cross-listing on domestic investor protection, and firm value. First, in Chapter 3, I examine the effects of listing in the U.S. on the level o f domestic investor protection for non-U.S. firms. Others have examined whether non- U.S. firms can ‘completely’ bond to the U.S. governance regime (like U.S. firms do), as the legal bonding hypothesis predicts. In general these studies conclude that bonding to the U.S. regime is ‘incomplete’. Implicit in this is the belief that domestic/ordinary shareholders are also protected, although this has not been examined. I explicitly examine this issue. My results suggest that the ordinary shareholders of non- U.S. cross-listed firms do enjoy additional protection under the U.S. governance regime. In the remainder o f the thesis, I examine die valuation effects o f listing abroad. I build upon the cross-sectional work of Doidge, Karolyi, and Stulz (2004) and Kristian-Hope, Kang, and Zang (2005), and examine the effects of listing abroad over time for Irish, Emerging, and both Emerging and Developed firms, respectively. My results suggest the following. In Chapter 4 I find that Irish firms that exchange cross-list experience an increase in value after listing abroad. This contrasts notably with the calendar year valuation discount reported by Doidge, Karolyi, and Stulz (2004) for Irish cross-listed firms. In contrast, Level 2/3 exchange-traded Emerging market firms are worth more than non-cross-listed firms in calendar time, but not necessarily in event time. The results outlined in Chapter 5 suggest that listing in the U.S. does not enhance value. After listing in the U.S., these firms are no longer worth more than non-crosslisted firms. Finally, in Chapters 6 and 7, I examine the valuation effects of listing for non-exchange traded issues. I find that trading in the U.S. via a non-exchange issue does not enhance value. The result holds irrespective of how I classify firms. Finally, I extend the later by examining the valuation effects of listing for non-exchange traded firms, on a country-by-country basis. I find that listing does enhance value for firms from certain countries

Quantitative analysis of cocaine in solid mixtures using Raman spectroscopy and chemometric methods

Near-infrared (785 mn) excitation was used to obtain Raman spectra from a series of 33 solid mixtures containing cocaine, caffeine and glucose (9.8-80.6% by weight cocaine), which were then analysed using chemometric methods, Principal component analysis of the data was employed to ascertain what factors influenced the spectral variation across the concentration range. It was found that 98% of the spectral variation was accounted for by three principal components. Analysis of the score and loadings plots for these components showed that the samples can be clearly classified on the basis of cocaine concentration. Discrimination on the basis of caffeine and glucose concentrations was also possible. Quantitative calibration models were generated using partial least-squares algorithms which predicted the concentration of cocaine in the solid mixtures containing caffeine and glucose from the Raman spectrum with a root mean standard error of prediction (RMSEP) of 4.1%, Caffeine and glucose concentrations were estimated with RMSEPs of 5.2 and 6.6%, respectively, These measurements demonstrate the feasibility of using near-IR Raman spectroscopy for rapid quantitative characterization of illegal narcotics. Copyright (C) 2000 John Wiley & Sons, Ltd.Science & Technology Against Drugs Programme (Forbairt