ALBERT

Description: Aerosol composition measurements made in an indoor classroom indicate the uptake of thirdhand smoke (THS) species to indoor particles, a novel exposure route for THS to humans indoors. Chemical speciation of the organic aerosol fraction using mass spectrometric data and factor analysis identified a reduced nitrogen component, predominantly found in the indoor environment, contributing 29% of the indoor submicron aerosol mass. We identify this factor as THS compounds partitioning from interior surfaces to gas phase and then aerosol phase. Partitioning of THS vapors to aerosols requires an aqueous phase for reactive uptake of the reduced nitrogen species (RdNS), leading to seasonal differences in THS concentration indoors. RdNS protonate under the acidic conditions expected for indoor aerosols of outdoor origin. Controlled laboratory measurements performed using cigarette smoke deposited into a Pyrex vessel showed a similar partitioning behavior to aerosol of outdoor origin and mass spectral features comparable to the measured indoor THS factor after 1 week of residence time in the closed vessel. This study reports a new, potentially large THS exposure route from partitioning of surface volatile organic compounds into the aerosol phase and subsequent dispersion in a mechanically ventilated building.

Description: Provenance studies of widely distributed tephras, integrated within a well-defined temporal framework, are important to deduce systematic changes in the source, scale, distribution, and changes in regional explosive volcanism. Here, we establish a robust tephrochronostratigraphy for a total of 157 marine tephra layers collected during IODP Expedition 352. We infer at least three major phases of highly explosive volcanism during Oligocene to Pleistocene time. Provenance analysis based on glass composition assigns 56 of the tephras to a Japan source, including correlations with 12 major and widespread tephra layers resulting from individual eruptions in Kyushu, Central Japan, and North Japan between 115 ka and 3.5 Ma. The remaining 101 tephras are assigned to four source regions along the Izu-Bonin arc. One, exclusively assigned to the Oligocene age, is proximal to the Bonin Ridge islands; two reflect eruptions within the volcanic front and back-arc of the central Izu-Bonin arc, and a fourth region corresponds to the Northern Izu-Bonin arc source. First-order volume estimates imply eruptive magnitudes ranging from 6.3 to 7.6 for Japan-related eruptions and between 5.5 and 6.5 for IBM eruptions. Our results suggest tephras between 30 and 22 Ma reflect a subtly different Izu-Bonin chemical signature compared to the recent arc. After a ∼9 Ma gap in eruption, tephra supply from the Izu-Bonin arc predominated from 15 to 5 Ma, and finally a subequal mixture of tephra sources from the (palaeo)Honshu and Izu-Bonin arcs occured within the last ∼5 Ma. © 2017. The Authors.

Description: Introduction: Sickle cell disease (SCD) is a complex genetic disease with a multifactorial pathophysiology including multi-cell adhesion between red blood cells, white blood cells, platelets and endothelial cells, ultimately resulting in vaso-occlusive crises (VOCs). VOCs are the hallmark of SCD and are the primary cause for hospitalization. These recurrent episodes induce severe pain, decrease quality of life, can cause life-threatening complications, and are associated with increased risk of organ damage and mortality. While the clinical burden of SCD is well-documented, less evidence exists surrounding how the severity of SCD affects patients economically. The number of VOCs and other complications not only affect the likelihood of patients being able to work on a given day, but may also affect their long-term economic prospects. This analysis aims to better understand the association between SCD disease severity and its impact on the likelihood of collecting Supplemental Security Income (SSI) and patient income. Methods: A web-based survey was administered to adult patients (≥18 years) living in the United States with a self-reported diagnosis of SCD. The outcomes of interest for this analysis were Social Security Income (SSI) receipt and self-reported total household annual income. These outcomes were stratified by SCD disease severity. Our first measure of disease severity was the number of self-reported VOCs in the prior year. Our second measure of disease severity was developed through clinical expert opinion and relied on an algorithm for dividing patients into 3 disease severity classes. Severity Class I was defined as having no VOCs requiring treatment by health care providers in the past year; Severity Class II was defined as ≥1 emergency department visit or hospital admission for a VOC, or complication in the past year without any organ damage; and Severity Class III was defined as long-term organ damage (such as stroke or renal disease). Generalized linear models (GLM) with a binomial link function were used to analyze the association between SCD disease severity and SSI collection (one model used VOC frequency; a second model used severity classes). A linear regression model was used to analyze the relationship between VOC frequency and income level, while an ordered logistic regression model was used to analyze the association between SCD disease severity classes and income level. Results: The final sample was comprised of 303 individuals who completed the survey. The average age was 34.4 years (range 18 - 72) and 221 (72.9%) were female. The probability of SSI collection among patients with SCD varied across VOC frequency in the previous year. The probability of collecting SSI for patients having 0 and ≥4 VOCs in the past year, was 12% (95% confidence interval (CI): 4% to 31%) and 47% (39% to 55%), respectively. A chi-squared p-value of 0.002 indicated a statistically significant association between a greater number of VOCs and probability of SSI collection. The probability of SSI collection among SCD patients with Severity Class II and Severity Class III SCD was 16% (7.5% to 32%), and 39% (32.9% to 45%), respectively. A chi-squared p-value of 0.03 indicated a statistically significant association between SCD disease severity class and SSI collection. The predicted mean income for patients with SCD experiencing 0 and ≥4 VOCs in the past year was $47,488 and $34,569, respectively. A linear association test p-value of 0.06 indicated weak evidence of a lower mean income in relation to number of VOCs experienced. The predicted mean income among patients with class II and class III SCD was $42,443 and $36,842, respectively. There was no evidence of association between SCD severity class and mean income (p=0.29). Conclusion: Among patients with SCD, having more VOCs was strongly associated with the probability of collecting SSI and weakly associated with lower income. Disease severity class was strongly associated with the probability of collecting SSI. Disclosures Shafrin: Precision Health Economics, part of Precision Medicine Group: Employment, Equity Ownership. Thom:Bayer AG: Consultancy; Hoffman-La Roche: Consultancy; Pfizer: Consultancy; Novartis Pharma AG: Consultancy. Gaunt:Novartis Pharma AG: Consultancy. Zhao:Precision Health Economics, part of Precision Medicine Group: Employment. Joseph:Cigna: Equity Ownership; Pfizer: Equity Ownership; Amgen: Equity Ownership; Novartis: Employment, Equity Ownership. Bhor:Novartis: Employment, Equity Ownership. Rizio:Optum: Employment. Bronté-Hall:bluebird bio: Research Funding. Shah:GBT: Research Funding; Alexion: Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau.

Description: Introduction: Sickle cell disease (SCD) affects approximately 100,000 people in the United States (US) today. SCD can lead to painful vaso-occlusive crises (VOCs), damage to major organs, increased vulnerability to severe infections, and as such, affects a patient's health-related quality of life (HRQoL). The objective of this study was to quantify how disease severity and the presence of VOCs affects patient quality of life, as measured by the economic metric of patient utilities. While previous studies (Anie et al. 2012) have measured utilities among patients with SCD in the United Kingdom (UK), this is the first US study to evaluate utilities in patients with SCD during and outside the experience of a VOC. Methods: This study was a non-interventional, cross-sectional, online survey of patients with SCD. Individuals were recruited through SCD patient advocacy groups and a market research group. In this analysis, the outcome of interest was health utility values derived from the EuroQoL Five Dimension 5 level (EQ-5D) scale. Utility is a continuous measure of health status, where a utility of 1 represents perfect health, and a utility of 0 represents death. The EQ-5D survey responses were converted to EQ-5D health utilities using the United States EuroQoL value set, and EQ-5D health utility values (mean and 95% confidence intervals [CI]) were estimated. Respondents completed the EQ-5D question twice: once in reference to their health status when they were not experiencing a VOC and once in reference to their health status when experiencing a VOC. We estimated EQ-5D for both these measures. For EQ-5D not during VOC we estimated EQ-5D stratified by three classes of disease severity. These classes were informed by clinical expert severity. Respondents were classified as Severity Class I if they had no history of VOC requiring treatment by health care providers in the past year; Class II if they had ≥1 emergency department (ED) visit or hospital admission in the past year without organ damage; and Class III if they had long term organ damage (such as stroke or renal disease). Results: 326 individuals were screened and 299 individuals were included in the final analytic sample. Among these individuals, the average age was 34.3 years (range 18 - 72); 219 (73.2%) were female and 1 (0.3%) was non-binary. Based on self-report of VOC, as well as presence of complications and organ damage of individuals, 79.6% (238/299) were Severity Class III, 12.0% (36/299) were Class II, and 8.4% (25/299) Class I. The estimated health utility value derived from EQ-5D during VOC was 0.311 (95% CI: 0.286, 0.337). The estimated health utility values not during a VOC derived from EQ-5D was 0.733 (0.713, 0.753) for Severity Class III and 0.775 (0.725, 0.826) for Severity Class II. This result suggests 〉5% worse health status utility in Class III than Class II disease severity, although a Wald t-test for difference in means did not suggest evidence of a statistically significant difference in utility (p-value 0.13). Conclusion: The presence of VOC had a more severe impact on HRQoL for patients with SCD than previously estimated. When not experiencing a crisis, patients with Severity Class III, indicated by presence of organ damage, had 〉5% worse HRQoL than those with Severity Class II. Disclosures Thom: Novartis Pharma AG: Consultancy; Pfizer: Consultancy; Hoffman-La Roche: Consultancy; Bayer AG: Consultancy. Shafrin:Precision Health Economics, part of Precision Medicine Group: Employment, Equity Ownership. Keeney:Novartis Pharma AG: Consultancy; Pfizer: Consultancy. Zhao:Precision Health Economics, part of Precision Medicine Group: Employment. Joseph:Cigna: Equity Ownership; Pfizer: Equity Ownership; Amgen: Equity Ownership; Novartis: Employment, Equity Ownership. Bhor:Novartis: Employment, Equity Ownership. Rizio:Optum: Employment. Bronté-Hall:bluebird bio: Research Funding. Shah:GBT: Research Funding; Alexion: Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau.