scholarly journals Inflammatory mediators in the adipo-renal axis: leptin, adiponectin, and soluble ICAM-1

2020 ◽  
Vol 319 (3) ◽  
pp. F469-F475
Author(s):  
Yifan Hua ◽  
Christian Herder ◽  
Hermann Kalhoff ◽  
Anette E. Buyken ◽  
Jonas Esche ◽  
...  
Keyword(s):  
Mediation Analysis ◽  
Inflammatory Cytokine ◽  
Negative Impact ◽  
The Body ◽  
Intercellular Adhesion Molecule ◽  
Acid Excretion ◽  
Intercellular Adhesion Molecule 1 ◽  
Urine Ph ◽  
Causal Mediation ◽  
Causal Mediation Analysis

A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney’s capacity for net acid excretion (NAE). There is increasing evidence, not only for patients with type 2 diabetes but also for healthy individuals, that higher body fatness or waist circumference (WC) has a negative impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules might mediate this relation between adiposity and renal acid excretion function. Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18–25 yr old) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny’s (B&K’s) steps to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24-h pH relationship after strictly controlling for laboratory-measured NAE. In B&K’s mediation analysis, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), and adiponectin significantly associated with the outcome 24-h pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the “natural indirect effects” of WC on 24-h pH via leptin ( P = 0.01) and adiponectin ( P = 0.03) to be significant, with a trend for sICAM-1 ( P = 0.09). The calculated proportions mediated by leptin, adiponectin, and sICAM-1 were 64%, 23%, and 12%, respectively. Both mediation analyses identified an inflammatory cytokine (leptin) and an anti-inflammatory cytokine (adiponectin) along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity.

The Influence of Emotion on Trust

2016 ◽  
Vol 24 (4) ◽  
pp. 492-500 ◽  
Author(s):  
C. Daniel Myers ◽  
Dustin Tingley
Keyword(s):  
Political Behavior ◽  
Mediation Analysis ◽  
Negative Impact ◽  
Negative Emotions ◽  
Trust Game ◽  
Dyadic Trust ◽  
Causal Mediation ◽  
Collateral Effects ◽  
Causal Mediation Analysis ◽  
High Level

Political scientists frequently wish to test hypotheses about the effects of specific emotions on political behavior. However, commonly used experimental manipulations tend to have collateral effects on emotions other than the targeted emotion, making it difficult to ascribe outcomes to any single emotion. In this letter, we propose to address this problem using causal mediation analysis. We illustrate this approach using an experiment examining the effect of emotion on dyadic trust, as measured by the trust game. Our findings suggest that negative emotions can decrease trust, but only if those negative emotions make people feel less certain about their current situation. Our results suggest that only anxiety, a low-certainty emotion, has a negative impact on trust, whereas anger and guilt, two emotions that differ in their control appraisals but induce the same high level of certainty, appear to have no effect on trusting behavior. Importantly, we find that failing to use causal mediation analysis would ascribe apositiveeffect of anxiety on trust, demonstrating the value of this approach.

scholarly journals Exact parametric causal mediation analysis for a binary outcome with a binary mediator

2021 ◽  
Author(s):  
Marco Doretti ◽  
Martina Raggi ◽  
Elena Stanghellini
Keyword(s):  
Logistic Regression ◽  
Direct Effect ◽  
Mediation Analysis ◽  
Delta Method ◽  
Binary Outcome ◽  
Effect Decomposition ◽  
Causal Mediation ◽  
Regression Parameters ◽  
Causal Mediation Analysis ◽  
Parametric Expression

AbstractWith reference to causal mediation analysis, a parametric expression for natural direct and indirect effects is derived for the setting of a binary outcome with a binary mediator, both modelled via a logistic regression. The proposed effect decomposition operates on the odds ratio scale and does not require the outcome to be rare. It generalizes the existing ones, allowing for interactions between both the exposure and the mediator and the confounding covariates. The derived parametric formulae are flexible, in that they readily adapt to the two different natural effect decompositions defined in the mediation literature. In parallel with results derived under the rare outcome assumption, they also outline the relationship between the causal effects and the correspondent pathway-specific logistic regression parameters, isolating the controlled direct effect in the natural direct effect expressions. Formulae for standard errors, obtained via the delta method, are also given. An empirical application to data coming from a microfinance experiment performed in Bosnia and Herzegovina is illustrated.

scholarly journals PLCε1 regulates SDF-1α–induced lymphocyte adhesion and migration to sites of inflammation

2017 ◽  
Vol 114 (10) ◽  
pp. 2693-2698 ◽  
Author(s):  
Marianne Strazza ◽  
Inbar Azoulay-Alfaguter ◽  
Michael Peled ◽  
Alan V. Smrcka ◽  
Edward Y. Skolnik ◽  
...  
Keyword(s):  
T Cell ◽  
Small Gtpase ◽  
The Body ◽  
Delayed Type Hypersensitivity ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Regional Lymph Nodes ◽  
Lymphocyte Adhesion ◽  
Enzymatic Function ◽  
And Migration

Regulation of integrins is critical for lymphocyte adhesion to endothelium and migration throughout the body. Inside-out signaling to integrins is mediated by the small GTPase Ras-proximate-1 (Rap1). Using an RNA-mediated interference screen, we identified phospholipase Cε 1 (PLCε1) as a crucial regulator of stromal cell-derived factor 1 alpha (SDF-1α)-induced Rap1 activation. We have shown that SDF-1α-induced activation of Rap1 is transient in comparison with the sustained level following cross-linking of the antigen receptor. We identified that PLCε1 was necessary for SDF-1α-induced adhesion using shear stress, cell morphology alterations, and crawling on intercellular adhesion molecule 1 (ICAM-1)–expressing cells. Structure–function experiments to separate the dual-enzymatic function of PLCε1 uncover necessary contributions of the CDC25, Pleckstrin homology, and Ras-associating domains, but not phospholipase activity, to this pathway. In the mouse model of delayed type hypersensitivity, we have shown an essential role for PLCε1 in T-cell migration to inflamed skin, but not for cytokine secretion and proliferation in regional lymph nodes. Our results reveal a signaling pathway where SDF-1α induces T-cell adhesion through activation of PLCε1, suggesting that PLCε1 is a specific potential target in treating conditions involving migration of T cells to inflamed organs.

Factors explaining socio-economic inequalities in survival from colon cancer: a causal mediation analysis

2021 ◽  
pp. cebp.0222.2021
Author(s):  
Nina Afshar ◽  
S. Ghazaleh Dashti ◽  
Luc te Marvelde ◽  
Tony Blakely ◽  
Andrew Haydon ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Mediation Analysis ◽  
Causal Mediation ◽  
Causal Mediation Analysis ◽  
Economic Inequalities

Bayesian sensitivity analysis for unmeasured confounding in causal mediation analysis

2017 ◽  
Vol 28 (2) ◽  
pp. 515-531 ◽  
Author(s):  
Lawrence C McCandless ◽  
Julian M Somers
Keyword(s):  
Sensitivity Analysis ◽  
Mediation Analysis ◽  
Indirect Effects ◽  
Direct And Indirect Effects ◽  
Unmeasured Confounding ◽  
Intermediate Variable ◽  
Causal Mediation ◽  
Important Concern ◽  
Analysis Technique ◽  
Causal Mediation Analysis

Causal mediation analysis techniques enable investigators to examine whether the effect of the exposure on an outcome is mediated by some intermediate variable. Motivated by a data example from epidemiology, we consider estimation of natural direct and indirect effects on a survival outcome. An important concern is bias from confounders that may be unmeasured. Estimating natural direct and indirect effects requires an elaborate series of assumptions in order to identify the target quantities. The analyst must carefully measure and adjust for important predictors of the exposure, mediator and outcome. Omitting important confounders may bias the results in a way that is difficult to predict. In recent years, several methods have been proposed to explore sensitivity to unmeasured confounding in mediation analysis. However, many of these methods limit complexity by relying on a handful of sensitivity parameters that are difficult to interpret, or alternatively, by assuming that specific patterns of unmeasured confounding are absent. Instead, we propose a simple Bayesian sensitivity analysis technique that is indexed by four bias parameters. Our method has the unique advantage that it is able to simultaneously assess unmeasured confounding in the mediator–outcome, exposure–outcome and exposure–mediator relationships. It is a natural Bayesian extension of the sensitivity analysis methodologies of VanderWeele, which have been widely used in the epidemiology literature. We present simulation findings, and additionally, we illustrate the method in an epidemiological study of mortality rates in criminal offenders from British Columbia.

scholarly journals Prying Open the Black Box of Causality - A Causal Mediation Analysis Test of Procedural Justice Policing

2017 ◽  
Author(s):  
Krisztián Pósch
Keyword(s):  
Procedural Justice ◽  
Treatment Effect ◽  
Mediation Analysis ◽  
Black Box ◽  
Mediation Effects ◽  
Causal Mediation ◽  
Treatment Implementation ◽  
Causal Mediation Analysis ◽  
The Impact ◽  
Sense Of Power

Objectives: Review causal mediation analysis as a method for estimating and assessing direct and indirect effects in experimental criminology. Test procedural justice theory by examining the extent to which procedural justice mediates the impact of contact with the police on various outcomes. Apply causal mediation analysis to better interpret data from a field experiment that had suffered from a particular type of implementation failure.Methods: Data from a block-randomised controlled trial of procedural justice policing (the Scottish Community Engagement Trial) were analysed. All constructs were measured using surveys distributed during roadside police checks. The treatment implementation was assessed by analysing the treatment effect consistency and heterogeneity. Causal mediation analysis and sensitivity analysis were used to assess the mediating role of procedural justice.Results: First, the treatment effect was consistent and fairly homogeneous, indicating that the systematic variation in the study is attributable to the design. Second, procedural justice acts as a mediator channelling the treatment’s effect towards normative alignment (NIE=-0.207), duty to obey (NIE=-0.153), sense of power (NIE=-0.078), and social identity (NIE=-0.052), all of which are moderately robust to unmeasured confounding. The NIEs for risk of sanction and personal morality were highly sensitive, while for coerced obligation and sense of power they were non-significant. Conclusions: Causal mediation analysis is a versatile tool that can salvage experiments with systematic yet ambiguous treatment effects by allowing researchers to “pry open” the black box of causality. Most of the theoretical propositions of procedural justice policing were supported. Future studies are needed with more discernible causal mediation effects.

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