E-cigarette Use and Respiratory Disorder: An Integrative Review of Converging Evidence from Epidemiological and Laboratory Studies

BackgroundUse of electronic cigarettes (e-cigarettes) is prevalent among adolescents and young adults but there has been limited knowledge about health consequences in human populations. We conduct a systematic review and meta-analysis of results on respiratory disorder from studies of general-population samples and consider the mapping of these results to findings about biological processes linked to e-cigarettes in controlled laboratory studies.MethodWe conduct a literature search and meta-analysis of epidemiological studies on the association of e-cigarette use with asthma and with chronic obstructive pulmonary disease (COPD). We then discuss findings from laboratory studies about effects of e-cigarettes on four biological processes: cytotoxicity, oxidative stress/inflammation, susceptibility to infection, and genetic expression.ResultsEpidemiological studies, both cross-sectional and longitudinal, show a significant association of e-cigarette use with asthma and COPD, controlling for cigarette smoking and other covariates. For asthma (n=15 studies), the pooled adjusted odds ratio (AOR) was 1.39 (CI 1.28–1.51); for COPD (n=9 studies) the AOR was 1.49 (CI 1.36–1.65). Laboratory studies consistently show an effect of e-cigarettes on biological processes related to respiratory harm and susceptibility to illness, with e-cigarette conditions differing significantly from clean-air controls though sometimes less than for cigarettes.ConclusionsThe evidence from epidemiological studies meets established criteria for consistency, strength of effect, temporality, and in some cases a dose-response gradient. Biological plausibility is indicated by evidence from multiple laboratory studies. We conclude that e-cigarette use has consequences for asthma and COPD, which is of significant concern for respirology and public health.

THE CONSISTENCY STRENGTH OF LONG PROJECTIVE DETERMINACY

We determine the consistency strength of determinacy for projective games of length ω2. Our main theorem is that $\Pi _{n + 1}^1 $-determinacy for games of length ω2 implies the existence of a model of set theory with ω + n Woodin cardinals. In a first step, we show that this hypothesis implies that there is a countable set of reals A such that Mn (A), the canonical inner model for n Woodin cardinals constructed over A, satisfies $$A = R$$ and the Axiom of Determinacy. Then we argue how to obtain a model with ω + n Woodin cardinal from this.We also show how the proof can be adapted to investigate the consistency strength of determinacy for games of length ω2 with payoff in $^R R\Pi _1^1 $ or with σ-projective payoff.

WEAKLY REMARKABLE CARDINALS, ERDŐS CARDINALS, AND THE GENERIC VOPĚNKA PRINCIPLE

We consider a weak version of Schindler’s remarkable cardinals that may fail to be ${{\rm{\Sigma }}_2}$-reflecting. We show that the ${{\rm{\Sigma }}_2}$-reflecting weakly remarkable cardinals are exactly the remarkable cardinals, and that the existence of a non-${{\rm{\Sigma }}_2}$-reflecting weakly remarkable cardinal has higher consistency strength: it is equiconsistent with the existence of an ω-Erdős cardinal. We give an application involving gVP, the generic Vopěnka principle defined by Bagaria, Gitman, and Schindler. Namely, we show that gVP + “Ord is not ${{\rm{\Delta }}_2}$-Mahlo” and ${\text{gVP}}(\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle\thicksim}$}}{\Pi } _1 )$ + “there is no proper class of remarkable cardinals” are both equiconsistent with the existence of a proper class of ω-Erdős cardinals, extending results of Bagaria, Gitman, Hamkins, and Schindler.

The consistency strength of hyperstationarity

We introduce the large-cardinal notions of [Formula: see text]-greatly-Mahlo and [Formula: see text]-reflection cardinals and prove (1) in the constructible universe, [Formula: see text], the first [Formula: see text]-reflection cardinal, for [Formula: see text] a successor ordinal, is strictly between the first [Formula: see text]-greatly-Mahlo and the first [Formula: see text]-indescribable cardinals, (2) assuming the existence of a [Formula: see text]-reflection cardinal [Formula: see text] in [Formula: see text], [Formula: see text] a successor ordinal, there exists a forcing notion in [Formula: see text] that preserves cardinals and forces that [Formula: see text] is [Formula: see text]-stationary, which implies that the consistency strength of the existence of a [Formula: see text]-stationary cardinal is strictly below a [Formula: see text]-indescribable cardinal. These results generalize to all successor ordinals [Formula: see text] the original same result of Mekler–Shelah [A. Mekler and S. Shelah, The consistency strength of every stationary set reflects, Israel J. Math. 67(3) (1989) 353–365] about a [Formula: see text]-stationary cardinal, i.e. a cardinal that reflects all its stationary sets.

SQUARES, ASCENT PATHS, AND CHAIN CONDITIONS

With the help of various square principles, we obtain results concerning the consistency strength of several statements about trees containing ascent paths, special trees, and strong chain conditions. Building on a result that shows that Todorčević’s principle $\square \left( {\kappa ,\lambda } \right)$ implies an indexed version of $\square \left( {\kappa ,\lambda } \right)$, we show that for all infinite, regular cardinals $\lambda < \kappa$, the principle $\square \left( \kappa \right)$ implies the existence of a κ-Aronszajn tree containing a λ-ascent path. We then provide a complete picture of the consistency strengths of statements relating the interactions of trees with ascent paths and special trees. As a part of this analysis, we construct a model of set theory in which ${\aleph _2}$-Aronszajn trees exist and all such trees contain ${\aleph _0}$-ascent paths. Finally, we use our techniques to show that the assumption that the κ-Knaster property is countably productive and the assumption that every κ-Knaster partial order is κ-stationarily layered both imply the failure of $\square \left( \kappa \right)$.

Causal Inference in Cancer Epidemiology

Judgments about causality are central to the development of interventions intended to reduce exposure to risk factors that cause cancer. Because causation is not directly observable in medicine, scientists and philosophers have had to develop sets of constructs and heuristics that define “cause” operationally. The criteria in this framework, often attributed to the British medical statistician Sir Austin Bradford Hill or to the 1964 Report of the US Surgeon General on tobacco, include consistency, strength of association, specificity, temporality, coherence/plausibility/analogy, biological gradient, and experiment. This chapter reviews these criteria in depth and considers the challenges of applying them to population research on cancer. It discusses the concepts of causation in the context of the multistage nature of cancer, the “counterfactual” notion of causation, the component cause model for understanding diseases with multiple causes, and the “weight of the evidence” approach for integrating information from multiple lines of research.

UNIVERSALLY BAIRE SETS AND GENERIC ABSOLUTENESS

We prove several equivalences and relative consistency results regarding generic absoluteness beyond Woodin’s ${\left( {{\bf{\Sigma }}_1^2} \right)^{{\rm{u}}{{\rm{B}}_\lambda }}}$ generic absoluteness result for a limit of Woodin cardinals λ. In particular, we prove that two-step $\exists ^&#x211D; \left( {{\rm{\Pi }}_1^2 } \right)^{{\rm{uB}}_\lambda } $ generic absoluteness below a measurable limit of Woodin cardinals has high consistency strength and is equivalent, modulo small forcing, to the existence of trees for ${\left( {{\bf{\Pi }}_1^2} \right)^{{\rm{u}}{{\rm{B}}_\lambda }}}$ formulas. The construction of these trees uses a general method for building an absolute complement for a given tree T assuming many “failures of covering” for the models $L\left( {T,{V_\alpha }} \right)$ for α below a measurable cardinal.

Absoluteness via resurrection

The resurrection axioms are forcing axioms introduced recently by Hamkins and Johnstone, developing on ideas of Chalons and Veličković. We introduce a stronger form of resurrection axioms (the iterated resurrection axioms [Formula: see text] for a class of forcings [Formula: see text] and a given ordinal [Formula: see text]), and show that [Formula: see text] implies generic absoluteness for the first-order theory of [Formula: see text] with respect to forcings in [Formula: see text] preserving the axiom, where [Formula: see text] is a cardinal which depends on [Formula: see text] ([Formula: see text] if [Formula: see text] is any among the classes of countably closed, proper, semiproper, stationary set preserving forcings). We also prove that the consistency strength of these axioms is below that of a Mahlo cardinal for most forcing classes, and below that of a stationary limit of supercompact cardinals for the class of stationary set preserving posets. Moreover, we outline that simultaneous generic absoluteness for [Formula: see text] with respect to [Formula: see text] and for [Formula: see text] with respect to [Formula: see text] with [Formula: see text] is in principle possible, and we present several natural models of the Morse–Kelley set theory where this phenomenon occurs (even for all [Formula: see text] simultaneously). Finally, we compare the iterated resurrection axioms (and the generic absoluteness results we can draw from them) with a variety of other forcing axioms, and also with the generic absoluteness results by Woodin and the second author.

CALIBRATING DETERMINACY STRENGTH IN LEVELS OF THE BOREL HIERARCHY

We analyze the set-theoretic strength of determinacy for levels of the Borel hierarchy of the form$\Sigma _{1 + \alpha + 3}^0 $, forα<ω1. Well-known results of H. Friedman and D.A. Martin have shown this determinacy to requireα+ 1 iterations of the Power Set Axiom, but we ask what additional ambient set theory is strictly necessary. To this end, we isolate a family of weak reflection principles, Π1-RAPα, whose consistency strength corresponds exactly to the logical strength of${\rm{\Sigma }}_{1 + \alpha + 3}^0 $determinacy, for$\alpha < \omega _1^{CK} $. This yields a characterization of the levels ofLby or at which winning strategies in these games must be constructed. Whenα= 0, we have the following concise result: The leastθso that all winning strategies in${\rm{\Sigma }}_4^0 $games belong toLθ+1is the least so that$L_\theta \models {\rm{``}}{\cal P}\left( \omega \right)$exists, and all wellfounded trees are ranked”.