Maternal tobacco smoking and offspring autism spectrum disorder or traits in ECHO cohorts

Given inconsistent evidence on preconception or prenatal tobacco use and offspring autism spectrum disorder (ASD), this study assessed associations of maternal smoking with ASD and ASD-related traits. Among 72 cohorts in the Environmental Influences on Child Health Outcomes consortium, 11 had ASD diagnosis and prenatal tobaccosmoking (n = 8648). and 7 had Social Responsiveness Scale (SRS) scores of ASD traits (n = 2399). Cohorts had diagnoses alone (6), traits alone (2), or both (5). Diagnoses drew from parent/caregiver report, review of records, or standardized instruments. Regression models estimated smoking-related odds ratios (ORs) for diagnoses and standardized mean differences for SRS scores. Cohort-specific ORs were meta-analyzed. Overall, maternal smoking was unassociated with child ASD (adjusted OR, 1.08; 95% confidence interval [CI], 0.72–1.61). However, heterogeneity across studies was strong: preterm cohorts showed reduced ASD risk for exposed children. After excluding preterm cohorts (biased by restrictions on causal intermediate and exposure opportunity) and small cohorts (very few ASD cases in either smoking category), the adjusted OR for ASD from maternal smoking was 1.44 (95% CI, 1.02–2.03). Children of smoking (versus non-smoking) mothers had more ASD traits (SRS T-score + 2.37 points, 95% CI, 0.73–4.01 points), with results homogeneous across cohorts. Maternal preconception/prenatal smoking was consistently associated with quantitative ASD traits and modestly associated with ASD diagnosis among sufficiently powered United States cohorts of non-preterm children. Limitations resulting from self-reported smoking and unmeasured confounders preclude definitive conclusions. Nevertheless, counseling on potential and known risks to the child from maternal smoking is warranted for pregnant women and pregnancy planners. Lay Summary: Evidence on the association between maternal prenatal smoking and the child's risk for autism spectrum disorder has been conflicting, with some studies reporting harmful effects, and others finding reduced risks. Our analysis of children in the ECHO consortium found that maternal prenatal tobacco smoking is consistently associated with an increase in autism-related symptoms in the general population and modestly associated with elevated risk for a diagnosis of autism spectrum disorder when looking at a combined analysis from multiple studies that each included both pre- and full-term births. However, this study is not proof of a causal connection. Future studies to clarify the role of smoking in autism-like behaviors or autism diagnoses should collect more reliable data on smoking and measure other exposures or lifestyle factors that might have confounded our results

Complexity and algorithms for monomial and clausal predicate abstraction

In this paper, we investigate the asymptotic complexity of various predicate abstraction problems relative to the asymptotic complexity of checking an annotated program in a given assertion logic. Unlike previous approaches, we pose the predicate abstraction problem as a decision problem, instead of the traditional inference problem. For assertion logics closed under weakest (liberal) precondition and Boolean connectives, we show two restrictions of the predicate abstraction problem where the two complexities match. The restrictions correspond to the case of monomial and clausal abstraction. For these restrictions, we show a symbolic encoding that reduces the predicate abstraction problem to checking the satisfiability of a single formula whose size is polynomial in the size of the program and the set of predicates. We also provide a new iterative algorithm for solving the clausal abstraction problem that can be seen as the dual of the Houdini algorithm for solving the monomial abstraction problem

Cumulative exposure to environmental pollutants during early pregnancy and reduced fetal growth: The Project Viva cohort

Background: Reduced fetal growth is associated with perinatal and later morbidity. Prenatal exposure to environmental pollutants is linked to reduced fetal growth at birth, but the impact of concomitant exposure to multiple pollutants is unclear. The purpose of this study was to examine interactions between early pregnancy exposure to cigarette smoke, traffic pollution, and select perfluoroalkyl substances (PFASs) on birth weight-for-gestational age (BW/GA). Methods: Among 1597 Project Viva mother-infant pairs, we assessed maternal cigarette smoking by questionnaire, traffic pollution at residential address by black carbon land use regression model, and plasma concentration of select PFASs in early pregnancy. We calculated sex-specific BW/GA z-scores, an index of fetal growth, from national reference data. We fit covariate-adjusted multi-pollutant linear regression models and examined interactions between exposures, using a likelihood-ratio test to identify a best-fit model. Results: Two hundred six (13%) mothers smoked during pregnancy. Mean [standard deviation (SD)] for black carbon was 0.8 (0.3) μg/m3, perfluorooctane sulfonate (PFOS) was 29.1 (16.5) ng/mL, and BW/GA z-score was 0.19 (0.96). In the best-fit model, BW/GA z-score was lower in infants of mothers exposed to greater black carbon [- 0.08 (95% CI: -0.15, - 0.01) per interquartile range (IQR)]. BW/GA z-score (95% CI) was also lower in infants of mothers who smoked [- 0.09 (- 0.23, 0.06)] or were exposed to greater PFOS [- 0.03 (- 0.07, 0.02) per IQR], although confidence intervals crossed the null. There were no interactions between exposures. In secondary analyses, instead of PFOS, we examined perfluorononanoate (PFNA) [mean (SD): 0.7 (0.4) ng/mL], a PFAS more closely linked to lower BW/GA in our cohort. The best-fit multi-pollutant model included positive two-way interactions between PFNA and both black carbon and smoking (p-interactions = 0.03). Conclusions: Concurrent prenatal exposures to maternal smoking, black carbon, and PFOS are additively associated with lower fetal growth, whereas PFNA may attenuate associations of smoking and black carbon with lower fetal growth. It is important to examine interactions between multiple exposures in relation to health outcomes, as effects may not always be additive and may shed light on biological pathways. © 2018 The Author(s)

Long-term exposure to traffic-related air pollution and non-accidental mortality: A systematic review and meta-analysis

Background: The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest across the globe. Following its 2010 review, the Health Effects Institute appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected health outcomes. This paper describes the main findings of the systematic review on non-accidental mortality. Methods: The Panel used a systematic approach to conduct the review. An extensive search was conducted of literature published between 1980 and 2019. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP, which included studies beyond the near-roadway environment. We performed random-effects meta-analysis when at least three estimates were available of an association between a specific exposure and outcome. We evaluated confidence in the evidence using a modified Office of Health Assessment and Translation (OHAT) approach, supplemented with a broader narrative synthesis. Results: Thirty-six cohort studies were included. Virtually all studies adjusted for a large number of individual and area-level covariates—including smoking, body mass index, and individual and area-level socioeconomic status—and were judged at a low or moderate risk for bias. Most studies were conducted in North America and Europe, and a few were based in Asia and Australia. The meta-analytic summary estimates for nitrogen dioxide, elemental carbon and fine particulate matter—pollutants with more than 10 studies—were 1.04 (95% CI 1.01, 1.06), 1.02 (1.00, 1.04) and 1.03 (1.01, 1.05) per 10, 1 and 5 µg/m3, respectively. Effect estimates are interpreted as the relative risk of mortality when the exposure differs with the selected increment. The confidence in the evidence for these pollutants was judged as high, because of upgrades for monotonic exposure–response and consistency across populations. The consistent findings across geographical regions, exposure assessment methods and confounder adjustment resulted in a high confidence rating using a narrative approach as well. Conclusions: The overall confidence in the evidence for a positive association between long-term exposure to TRAP and non-accidental mortality was high

Zap: Automated Theorem Proving for Software Analysis

Automated theorem provers (ATPs) are a key component that many software verification and program analysis tools rely on. However, the basic interface provided by ATPs (validity/satisfiability checking of formulas) has changed little over the years. We believe that program analysis clients would benefit greatly if theorem provers were to provide a richer set of operations. We describe our desiderata for such an interface to an ATP, the logics (theories) that an ATP for program analysis should support, and present how we have incorporated many of these ideas in Zap, an ATP built at Microsoft Research

Long-term exposure to traffic-related air pollution and selected health outcomes: A systematic review and meta-analysis

The health effects of traffic-related air pollution (TRAP) continue to be of important public health interest. Following its well-cited 2010 critical review, the Health Effects Institute (HEI) appointed a new expert Panel to systematically evaluate the epidemiological evidence regarding the associations between long-term exposure to TRAP and selected adverse health outcomes. Health outcomes were selected based on evidence of causality for general air pollution (broader than TRAP) cited in authoritative reviews, relevance for public health and policy, and resources available. The Panel used a systematic approach to search the literature, select studies for inclusion in the review, assess study quality, summarize results, and reach conclusions about the confidence in the evidence. An extensive search was conducted of literature published between January 1980 and July 2019 on selected health outcomes. A new exposure framework was developed to determine whether a study was sufficiently specific to TRAP. In total, 353 studies were included in the review. Respiratory effects in children (118 studies) and birth outcomes (86 studies) were the most commonly studied outcomes. Fewer studies investigated cardiometabolic effects (57 studies), respiratory effects in adults (50 studies), and mortality (48 studies). The findings from the systematic review, meta-analyses, and evaluation of the quality of the studies and potential biases provided an overall high or moderate-to-high level of confidence in an association between long-term exposure to TRAP and the adverse health outcomes all-cause, circulatory, ischemic heart disease and lung cancer mortality, asthma onsetin chilldren and adults, and acute lower respiratory infections in children. The evidence was considered moderate, low or very low for the other selected outcomes. In light of the large number of people exposed to TRAP – both in and beyond the near-road environment - the Panel concluded that the overall high or moderate-to-high confidence in the evidence for an association between long-term exposure to TRAP and several adverse health outcomes indicates that exposures to TRAP remain an important public health concern and deserve greater attention from the public and from policymakers. © 2022 The Author(s

Author manuscript, published in "Verification, Model Checking, and Abstract Interpretation, Madrid: Spain (2010)" DOI: 10.1007/978-3-642-11319-2_21 An analysis of permutations in arrays ⋆

Abstract. This paper is concerned with the synthesis of invariants in programs with arrays. More specifically, we consider properties concerning array contents up to a permutation. For instance, to prove a sorting procedure, one has to show that the result is sorted, but also that it is a permutation of the initial array. In order to analyze this kind of properties, we define an abstract interpretation working on multisets of values, and able to discover invariant equations about such multisets.

Illuminating a cross-cultural leadership challenge: When identity groups collide

When societal conflicts between social identity groups spill over into organizations, leaders face the formidable challenge of attempting to bridge differences and manage the conflict in order to accomplish work. After reviewing the literature on intergroup conflict, workplace diversity and social identity theory, we examine four potential leadership strategies for managing identity-based conflicts. The four leadership strategies are decategorization, recategorization, subcategorization and crosscutting. Examples drawn from an interview-based study are used to illustrate theoretical constructs found in the literature. We then consider each of these strategies in cross-cultural contexts and generate propositions to reflect differences in the effectiveness of the strategies in collectivist versus individualist cultures