Measuring the Effects of Mouse Allergen and Black Carbon Exposure on Children Living in New York City with Allergic Diseases

Measuring the Effects of Mouse Allergen and Black Carbon Exposure on Children Living in New York City with Allergic Diseases Medina Samira Jackson-Browne Background: Exposure to allergens and combustion by-products are risk factors for allergic health outcomes in children. The connection between exposure to allergens and allergic diseases such as asthma, in some children, is through the development of a biological condition known as allergic sensitization. In susceptible children, sensitization may occur when early-life exposure to an allergen causes the production of immunoglobulin E (IgE) antibodies. In asthmatic children, repeated exposures to this allergen may lead to clinical manifestations including airway inflammation, airway mucous production, bronchospasms, and bronchial hyper-responsiveness. Sensitization and repeated exposure to allergens may, therefore, be important risk factors for asthma morbidity in children. Findings from a cross-sectional asthma study of children living in NYC published previously by our group found a positive association between cockroach and dust-mite allergens measured in bed dust and sensitization risk to these allergens consistent with other studies. However, contrary to previously published research, no association was observed between mouse allergen measured in bed dust and mouse sensitization risk in our study. In urban areas such as New York City (NYC), exposure to combustion by-products, including black carbon (BC), has been shown to be associated with both asthma development and asthma morbidity. BC has been proposed to exacerbate asthma symptoms directly through airway irritation or by behaving as an adjuvant, enhancing the production of IgE antibodies following exposure to an allergen in sensitized individuals. Our group previously observed an association between indoor measured BC concentrations and airway inflammation, however no association was found between BC and asthma symptoms for children living in NYC. In the present study, we sought to address some of the limitations of the previous work. These limitations included a singular measurement of mouse allergen exposure, a shorter-term BC exposure measurement, and a cross-sectional study design for asthma symptom risks. My overarching hypothesis for this dissertation is that exposures to mouse allergen and BC are significant risk factors for allergic sensitization and asthma morbidity, respectively, for children living in NYC. I tested these hypotheses in three separate manuscripts by assessing multiple mouse exposure measurements with the risk for mouse sensitization (Chapter 2), testing the correlation between 7-day measured indoor BC and particulate matter smaller than 2.5 microns (PM2.5) concentrations with annual modeled outdoor BC and PM2.5 concentrations (Chapter 3), and determining whether annual modeled outdoor BC concentration is associated with persistent asthma symptoms, over a three-year period, for asthmatic children in NYC (Chapter 4). Methods: For all manuscripts, data from an asthma case-control cohort of children (age 7-8 years) previously established by our group, the NYC Neighborhood Asthma and Allergy Study (NAAS), was utilized for analysis (n=350). Kitchen floor and bed settled dust samples were collected from the children’s home during the initial home visit. Mouse allergen concentrations were quantified from both kitchen floor and bed dust samples using an enzyme-linked immunosorbent assay (ELISA). Blood samples were also collected during this visit. IgE antibodies to mouse allergens were measured by ImmunoCAP (Phadia, Uppsala, Sweden) from these blood samples. Information on the frequency of mouse sightings in the previous 12 months was extracted from a questionnaire administered to parents of NAAS children. Neighborhood and school mouse sightings were collected from reports from the NYC Department of Health and Mental Hygiene (DOHMH). Indoor PM2.5 and BC samples were collected from air samplers placed in NAAS children’s home for an average of 7 days. In collaboration with the NYC DOHMH, we were given access to 2-year averaged modeled outdoor PM2.5 and BC concentrations collected from air monitors at 124 street-level locations throughout NYC from 2008-2010. After the initial home visit, asthmatic NAAS children were followed-up annually for asthma symptoms. The questionnaire data collected from the asthmatics followed were used to evaluate the persistence or remittance of asthma symptoms over the 3-years following the initial home visit. Results: In our mouse study we found that increasing mouse allergen measured from kitchen floor dust and children whose parents reported greater than weekly mouse sightings in the previous 12 months has an increased risk of mouse sensitization (prevalence risk (PR) = 1.09 [1.02-1.17], p=0.04 and PR= 3.84 [1.95-6.97], p=0.001 respectively). Neither mouse allergen measured from settled bed dust (PR = 1.06 [0.95-1.19], p=0.46) nor neighborhood rodent reports (PR = 1.25 [0.94-1.68], p=0.16) were significantly associated with an increased risk of sensitization to mouse. Exposure to mouse at school was also not associated with an increased risk of mouse sensitization (PR=0.66 [0.35-1.26], p=0.30). Results from the correlation study indicated both annual modeled outdoor PM2.5 and BC concentrations were weakly correlated with 7-day measured indoor PM2.5 and BC concentrations (r = 0.21 and 0.39, respectively, p < 0.01). However, annual modeled outdoor BC concentrations predicted almost 20% of the variability of 7-day measured indoor BC (R2=0.19, p<0.001) compared to only 4% of the variability of 7-day indoor PM2.5 explained by annual modeled outdoor PM2.5, which predicted measured indoor PM2.5 (R2 = 0.04, p < 0.001). Our regression analysis of the asthma morbidity study found no significant association between longer-term neighborhood modeled BC concentrations at study participant’s home (PR = 0.87 [0.58-1.29, p=0.49] and school addresses (PR =1.09 [0.77-1.56], p=0.60) and persistent asthma symptoms. Conclusions: My findings suggest that mouse allergen measured from kitchen floor dust and parent reported mouse sightings are important risk factors of mouse sensitization for children living in urban areas such as NYC. The results of the BC analysis indicate a moderate correlation between annual modeled outdoor BC concentrations and 7-day measured indoor BC concentrations. The annual modeled outdoor BC also predicted 20% of the variability in 7-day measured indoor BC. Conversely, PM2.5 analysis indicate that annual modeled outdoor PM2.5 is not correlated with 7-day measured indoor PM2.5 concentrations. Finally, regression analysis of BC exposure and asthma morbidity indicate that annual modeled outdoor BC is not predictive of persistent asthma symptoms in our cohort

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation. the GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores &gt;2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores &gt;2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score &gt;2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores &gt;2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores &gt;2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Alcohol and marijuana use trajectories in a diverse longitudinal sample of adolescents: examining use patterns from age 11 to 17 years

AimsWe tested race/ethnic differences in alcohol and marijuana (AM) trajectories (comprising an intercept term, reflecting overall probability of use, and a slope term, reflecting change in probability of use) during adolescence, whether AM use trajectories predicted high school outcomes, and whether outcomes differed by race/ethnicity after controlling for trajectory of AM use.DesignThis longitudinal study involved 6509 youth from 16 middle schools in Southern California surveyed from age 11.5 (2008) to age 17 (2015) years; all surveys assessed AM use, and the final survey also examined high school outcomes.SettingYouth completed five surveys in middle school and two on-line surveys in high school.ParticipantsThe sample was 50% male and 80% non-white.MeasurementsIntercept (at 2.75 years post-baseline) and slope of AM use were examined as outcomes for race/ethnic differences. AM use trajectories were examined as predictors of academic performance and unpreparedness, social functioning, mental and physical health and delinquency.FindingsWe found differences in trajectories of use by race/ethnicity, with white youth reporting a higher overall intercept of alcohol use compared to all other groups (versus Asian P &lt; 0.001, black P = 0.001, multi-ethnic P = 0.008). Overall, examination of trajectories of use showed that adolescents with a higher alcohol use intercept term reported greater academic unpreparedness (P &lt; 0.001) and delinquency (P &lt; 0.001) at wave 7 in high school. In addition, youth with a higher intercept for marijuana use reported greater academic unpreparedness (P &lt; 0.001) and delinquency (P &lt; 0.001), and poorer academic performance (P = 0.032) and mental health (P = 0.002) in high school. At wave 7, compared to white youth, Hispanic and multi-ethnic youth reported poorer academic performance (P &lt; 0.001 and P = 0.034, respectively); Asian, black and Hispanic youth reported higher academic unpreparedness (P &lt; 0.001, P = 0.019, and P = 0.001); and Asian youth and multi-ethnic youth reported poorer physical health (P = 0.012 and P = 0.018) controlling for AM use.ConclusionsGreater AM use was associated with worse functioning in high school for all youth. After controlling for AM use, non-white youth reported worse outcomes in high school for academics and health