Integrated multiple mediation analysis: A robustness–specificity trade-off in causal structure

Recent methodological developments in causal mediation analysis have addressed several issues regarding multiple mediators. However, these developed methods differ in their definitions of causal parameters, assumptions for identification, and interpretations of causal effects, making it unclear which method ought to be selected when investigating a given causal effect. Thus, in this study, we construct an integrated framework, which unifies all existing methodologies, as a standard for mediation analysis with multiple mediators. To clarify the relationship between existing methods, we propose four strategies for effect decomposition: two-way, partially forward, partially backward, and complete decompositions. This study reveals how the direct and indirect effects of each strategy are explicitly and correctly interpreted as path-specific effects under different causal mediation structures. In the integrated framework, we further verify the utility of the interventional analogues of direct and indirect effects, especially when natural direct and indirect effects cannot be identified or when cross-world exchangeability is invalid. Consequently, this study yields a robustness–specificity trade-off in the choice of strategies. Inverse probability weighting is considered for estimation. The four strategies are further applied to a simulation study for performance evaluation and for analyzing the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer data set from Taiwan to investigate the causal effect of hepatitis C virus infection on mortality

Klebsiella pneumoniae is able to trigger epithelial-mesenchymal transition process in cultured airway epithelial cells

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells

Observation of a ppb mass threshoud enhancement in \psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p}) decay

The decay channel $\psi^\prime\to\pi^+\pi^-J/\psi(J/\psi\to\gamma p\bar{p})$ is studied using a sample of $1.06\times 10^8$ $\psi^\prime$ events collected by the BESIII experiment at BEPCII. A strong enhancement at threshold is observed in the $p\bar{p}$ invariant mass spectrum. The enhancement can be fit with an $S$-wave Breit-Wigner resonance function with a resulting peak mass of $M=1861^{+6}_{-13} {\rm (stat)}^{+7}_{-26} {\rm (syst)} {\rm MeV/}c^2$ and a narrow width that is $\Gamma<38 {\rm MeV/}c^2$ at the 90% confidence level. These results are consistent with published BESII results. These mass and width values do not match with those of any known meson resonance.Comment: 5 pages, 3 figures, submitted to Chinese Physics

Challenges and opportunities for improved understanding of regional climate dynamics

Dynamical processes in the atmosphere and ocean are central to determining the large-scale drivers of regional climate change, yet their predictive understanding is poor. Here, we identify three frontline challenges in climate dynamics where significant progress can be made to inform adaptation: response of storms, blocks and jet streams to external forcing; basin-to-basin and tropical–extratropical teleconnections; and the development of non-linear predictive theory. We highlight opportunities and techniques for making immediate progress in these areas, which critically involve the development of high-resolution coupled model simulations, partial coupling or pacemaker experiments, as well as the development and use of dynamical metrics and exploitation of hierarchies of models

Preferred response of the East Asian summer monsoon to local and non-local anthropogenic sulphur dioxide emissions

In this study, the atmospheric component of a state-of-the-art climate model (HadGEM2-ES) that includes earth system components such as interactive chemistry and eight species of tropospheric aerosols considering aerosol direct, indirect, and semi-direct effects, has been used to investigate the impacts of local and non-local emissions of anthropogenic sulphur dioxide on the East Asian summer monsoon (EASM). The study focuses on the fast responses (including land surface feedbacks, but without sea surface temperature feedbacks) to sudden changes in emissions from Asia and Europe. The initial responses, over days 1–40, to Asian and European emissions show large differences. The response to Asian emissions involves a direct impact on the sulphate burden over Asia, with immediate consequences for the shortwave energy budget through aerosol–radiation and aerosol–cloud interactions. These changes lead to cooling of East Asia and a weakening of the EASM. In contrast, European emissions have no significant impact on the sulphate burden over Asia, but they induce mid-tropospheric cooling and drying over the European sector. Subsequently, however, this cold and dry anomaly is advected into Asia, where it induces atmospheric and surface feedbacks over Asia and the Western North Pacific (WNP), which also weaken the EASM. In spite of very different perturbations to the local aerosol burden in response to Asian and European sulphur dioxide emissions, the large scale pattern of changes in land–sea thermal contrast, atmospheric circulation and local precipitation over East Asia from days 40 onward exhibits similar structures, indicating a preferred response, and suggesting that emissions from both regions likely contributed to the observed weakening of the EASM. Cooling and drying of the troposphere over Asia, together with warming and moistening over the WNP, reduces the land–sea thermal contrast between the Asian continent and surrounding oceans. This leads to high sea level pressure (SLP) anomalies over Asia and low SLP anomalies over the WNP, associated with a weakened EASM. In response to emissions from both regions warming and moistening over the WNP plays an important role and determines the time scale of the response

Determination of the number of J/ψ events with J/ψ → inclusive decays

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Measurement of the matrix element for the decay η′→ηπ +π -

The Dalitz plot of η⊃′→ηπ⊃+π⊃- decay is studied using (225.2±2.8)×106 J/ψ events collected with the BESIII detector at the BEPCII e⊃+e⊃- collider. With the largest sample of η⊃′ decays to date, the parameters of the Dalitz plot are determined in a generalized and a linear representation. Also, the branching fraction of J/ψ→γη⊃′ is determined to be (4.84±0.03±0.24)×10⊃-3, where the first error is statistical and the second systematic. © 2011 American Physical Society.published_or_final_versio

Higher-order multipole amplitude measurement in ψ ′→γχ c2

Using 106×106 ψ ′ events collected with the BESIII detector at the BEPCII storage ring, the higher-order multipole amplitudes in the radiative transition ψ ′→γχ c2→γπ +π -/γK +K - are measured. A fit to the χ c2 production and decay angular distributions yields M2=0.046±0. 010±0.013 and E3=0.015±0.008±0.018, where the first errors are statistical and the second systematic. Here M2 denotes the normalized magnetic quadrupole amplitude and E3 the normalized electric octupole amplitude. This measurement shows evidence for the existence of the M2 signal with 4.4σ statistical significance and is consistent with the charm quark having no anomalous magnetic moment. © 2011 American Physical Society.published_or_final_versio

Regulation of microRNA biogenesis and turnover by animals and their viruses

Item does not contain fulltextMicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes