275 research outputs found

    Adjustment for time-invariant and time-varying confounders in ‘unexplained residuals’ models for longitudinal data within a causal framework and associated challenges

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    ‘Unexplained residuals’ models have been used within lifecourse epidemiology to model an exposure measured longitudinally at several time points in relation to a distal outcome. It has been claimed that these models have several advantages, including: the ability to estimate multiple total causal effects in a single model, and additional insight into the effect on the outcome of greater-than-expected increases in the exposure compared to traditional regression methods. We evaluate these properties and prove mathematically how adjustment for confounding variables must be made within this modelling framework. Importantly, we explicitly place unexplained residual models in a causal framework using directed acyclic graphs. This allows for theoretical justification of appropriate confounder adjustment and provides a framework for extending our results to more complex scenarios than those examined in this paper. We also discuss several interpretational issues relating to unexplained residual models within a causal framework. We argue that unexplained residual models offer no additional insights compared to traditional regression methods, and, in fact, are more challenging to implement; moreover, they artificially reduce estimated standard errors. Consequently, we conclude that unexplained residual models, if used, must be implemented with great care

    Ozone Quantification by Selected Ion Flow Tube Mass Spectrometry: Influence of Humidity and Manufacturing Gas of Ozone Generator

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    The quantification of ozone by SIFT-MS was investigated in conditions suitable with an industrial emission context (high ozone demand, dry air/oxygen as the manufacturing gas of the ozone generator, and high humidity levels beyond saturation at room conditions). Ozone reacts with four negative precursor ions available in the SIFT-MS device (NO2–, O2–, HO–, and O–), each precursor ion having its specific domain of linearity. For a high ozone concentration range, only NO2– and O2– have resulted in a linear behavior (between 1 and 100 ppmv of O3 for NO2–, between 1 and 50 ppmv of O3 for O2–). No water interference was identified during ozone measurements by SIFT-MS using NO2– and O2– precursor ions, even with extreme humidity levels. The presence of nitrogen oxide contaminants (due to the use of dry air as the manufacturing gas of the ozone generator) affected the ozone quantification by SIFT-MS. It is critical for NO2– precursor ions, whose rate constant varied as a function of NO2 concentrations. With O2– precursor ion, ozone was successfully measured in the presence of nitrogen oxides; however, the secondary chemistry must be taken into account

    Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR

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    Erratum in : Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR. [Cell. 2019]International audienceInnate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-likereceptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatorysignals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect theimmune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DC)are exacerbated by a high fatty acid (FA) metabolic environment. FA suppress the TLR-inducedhexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changesenhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded proteinresponse (UPR) leading to a distinct transcriptomic signature, with IL-23 as hallmark. Interestingly,chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response.Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innateimmunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR

    Effects of chromatic light interventions and wavelengths on ocular biometry in human myopia: A systematic review and meta-analysis

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    Studies highlight the use of different wavelengths of light as emerging interventions to slow myopia progression in children. This review evaluates the effects of different wavelengths of chromatic light interventions on ocular biometry in humans. A literature search of MEDLINE, CINAHL, Scopus, ProQuest Central, Web of Science, and trial registries identified thirty-seven studies examining the effects of either long-term (4 weeks- 24 months) or short-term (between 10–120 min and ≤ 4 weeks) monochromatic light exposure. A random-effects model was used to calculate the weighted mean difference (WMD) and 95 % confidence intervals (CI) in spherical equivalent refraction (SER), axial length (AL) and subfoveal choroidal thickness (ChT). In studies examining long-term exposure to both long- and short-wavelength light, significant changes in AL, SER, and ChT were observed primarily with long-wavelength red light used in repeated low-level red light (RLRL) therapy. RLRL resulted in a significant reduction in AL and SER, and an increase in subfoveal ChT compared to a control group wearing single vision spectacles (SVS) at both 6 and 12 months (WMD at 6 and 12 months, AL:0.24 and –0.36 mm; SER: 0.31 and 0.77 D; ChT: +32.12 and +31.78 µm). Exposure to short-wavelength (blue and/or violet light) resulted in only a modest change in AL and myopia progression in children [mean change (95 % CI) at 12 months, AL:0.04 mm (–0.15 to 0.07); SER: 0.04 D (–0.16 to 0.24)]. Short-term exposure to both long- and short-wavelengths on ocular biometry in young adults showed equivocal results. LED-based blue light (454–456 nm) induced choroidal thickening and a reduction in AL, whereas red light produced the opposite effects. In conclusion, longer-term exposure to RLRL and violet light can slow myopia progression in children, with RLRL showing a stronger effect. Short-term exposure to different wavelengths offers insights for developing newer light-based myopia therapies
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