Semiparametric Estimation of Models for Natural Direct and Indirect Effects

In recent years, researchers in the health and social sciences have become increasingly interested in mediation analysis. Specifically, upon establishing a non-null total effect of an exposure, investigators routinely wish to make inferences about the direct (indirect) pathway of the effect of the exposure not through (through) a mediator variable that occurs subsequently to the exposure and prior to the outcome. Natural direct and indirect effects are of particular interest as they generally combine to produce the total effect of the exposure and therefore provide insight on the mechanism by which it operates to produce the outcome. A semiparametric theory has recently been proposed to make inferences about marginal mean natural direct and indirect effects in observational studies (Tchetgen Tchetgen and Shpitser, 2011), which delivers multiply robust locally efficient estimators of the marginal direct and indirect effects, and thus generalizes previous results for total effects to the mediation setting. In this paper we extend the new theory to handle a setting in which a parametric model for the natural direct (indirect) effect within levels of pre-exposure variables is specified and the model for the observed data likelihood is otherwise unrestricted. We show that estimation is generally not feasible in this model because of the curse of dimensionality associated with the required estimation of auxiliary conditional densities or expectations, given high-dimensional covariates. We thus consider multiply robust estimation and propose a more general model which assumes a subset but not all of several working models holds.

Direct and indirect effects of screening for Chlamydia trachomatis on the prevention of pelvic inflammatory disease: a mathematical modeling study

BACKGROUND Pelvic inflammatory disease (PID) results from the ascending spread of microorganisms, including Chlamydia trachomatis, to the upper genital tract. Screening could improve outcomes by identifying and treating chlamydial infections before they progress to PID (direct effect) or by reducing chlamydia transmission (indirect effect). METHODS We developed a compartmental model that represents a hypothetical heterosexual population and explicitly incorporates progression from chlamydia to clinical PID. Chlamydia screening was introduced, with coverage increasing each year for 10 years. We estimated the separate contributions of the direct and indirect effects of screening on PID cases prevented per 100,000 women. We explored the influence of varying the time point at which clinical PID could occur and of increasing the risk of PID after repeated chlamydial infections. RESULTS The probability of PID at baseline was 3.1% by age 25 years. After 5 years, the intervention scenario had prevented 187 PID cases per 100,000 women and after 10 years 956 PID cases per 100,000 women. At the start of screening, most PID cases were prevented by the direct effect. The indirect effect produced a small net increase in PID cases, which was outweighed by the effect of reduced chlamydia transmission after 2.2 years. The later that progression to PID occurs, the greater the contribution of the direct effect. Increasing the risk of PID with repeated chlamydial infection increases the number of PID cases prevented by screening. CONCLUSIONS This study shows the separate roles of direct and indirect PID prevention and potential harms, which cannot be demonstrated in observational studies.

Why do adaptable people feel less insecure? Indirect effects of career adaptability on job and career insecurity via two types of perceived marketability

The aim of the present study was to analyze if and how career adaptability reduces different types of insecurity. More specifically, we argue in a theoretical model at the intersection of career and organizational research that perceived internal and external marketability serve as connecting variables in the link between career adaptability and job and career insecurity. We tested our assumptions by means of multiple indirect effects path analyses across two measurement points (6 month timespan) with data from 142 university researchers working in the STEM fields. The results showed that career adaptability was positively related to perceived internal and external marketability, which both subsequently were negatively associated with job and career insecurity. We draw theoretical implications for career research in intra- and extraorganizational settings and discuss practical implications for fostering secure employment.

Social Support at the Workplace, Motivation to Transfer, and Training Transfer: A Multi-Level Indirect Effects Model

Supervisor support, peer support and transfer motivation have been identified as important predictors for training transfer. Transfer motivation is supposed to mediate the support–training transfer relationship. Especially after team training interventions that include all team members (i.e., intact-team training), individual perception of these factors might be shared among team members. However, an integration of the team level in the training transfer process is rare, yet still needed. Analyzing 194 employees from 34 teams in the context of intact-team training interventions, we found similar relationships and processes at both levels of analysis: Social support enhances transfer motivation at the individual and team levels. Furthermore, motivation to transfer increases training transfer and serves as a connecting mechanism in the social support–training transfer link. The results underline the importance of (1) considering multiple levels in theories and research about the training transfer process and (2) ensuring the practice of individual-directed support and a shared, supportive climate within teams.

Interplay between the prostaglandin transporter OATP2A1 and prostaglandin E2-mediated cellular effects.

Prostaglandins such as prostaglandin E2 (PGE2) play a pivotal role in physiological and pathophysiological pathways in gastric mucosa. Little is known about the interrelation of the prostaglandin E (EP) receptors with the prostaglandin transporter OATP2A1 in the gastric mucosa and gastric carcinoma. Therefore, we first investigated the expression of OATP2A1 and EP4 in normal and carcinoma gastric mucosa. Different PGE2-mediated cellular pathways and mechanisms were investigated using human embryonic kidney cells (HEK293) and the human gastric carcinoma cell line AGS stably transfected with OATP2A1. Colocalization and expression of OATP2A1 and EP4 were detected in mucosa of normal gastric tissue and of gastric carcinomas. OATP2A1 reduced the PGE2-mediated cAMP production in HEK293 and AGS cells overexpressing EP4 and OATP2A1. The expression of OATP2A1 in AGS cells resulted in a reduction of [(3)H]-thymidine incorporation which was in line with a higher accumulation of AGS-OATP2A1 cells in S-phase of the cell cycle compared to control cells. In contrast, the expression of OATP2A1 in HEK293 cells had no influence on the distribution in the S-phase compared to control cells. OATP2A1 also diminished the PGE2-mediated expression of interleukin-8 mRNA (IL-8) and hypoxia-inducible-factor 1α (HIF1α) protein in AGS-OATP2A1 cells. The expression of OATP2A1 increased the sensitivity of AGS cells against irinotecan which led to reduced cell viability. Taken together, these data show that OATP2A1 influences PGE2-mediated cellular pathways. Therefore, OATP2A1 needs to be considered as a key determinant for the understanding of the physiology and pathophysiology of prostaglandins in healthy and tumorous gastric mucosa.

Recognition of diverse sequences by class I zinc fingers: asymmetries and indirect effects on specificity in the interaction between CF2II and A+T-rich elements.

The Drosophila CF2II protein, which contains zinc fingers of the Cys2His2 type and recognizes an A+T-rich sequence, behaves in cell culture as an activator of a reporter chloramphenicol acetyltransferase gene. This activity depends on C-terminal but not N-terminal zinc fingers, as does in vitro DNA binding. By site-specific mutagenesis and binding site selection, we define the critical amino acid-base interactions. Mutations of single amino acid residues at the leading edge of the recognition helix are rarely neutral: many result in a slight change in affinity for the ideal DNA target site; some cause major loss of affinity; and others change specificity for as many as two bases in the target site. Compared to zinc fingers that recognize G+C-rich DNA, CF2II fingers appear to bind to A+T-rich DNA in a generally similar manner, but with additional flexibility and amino acid-base interactions. The results illustrate how zinc fingers may be evolving to recognize an unusually diverse set of DNA sequences.

Market orientation of service networks:direct and indirect effects on sustained competitive advantage

Market orientation is an organization-wide concept that helps explain sustained competitive advantage (SCA). Since networks become ever more important, especially in the service sector, there is need to expand the concept of MO to a network setting. In line with Narver and Slater (1990), the concept of Market Orientation of Networks (MONW) is developed. This study indicates how MONW relates to the resource-based view (RBV) of the firm and the industrial organization (IO) view in explaining SCA. It is argued that MONW has direct and indirect effects on SCA. More precisely, the antecedent effect of MONW to resources and industry structure is considered.

Estimating direct and indirect effects of foreign direct investment on firm productivity in the presence of interactions between firms

We implement a method to estimate the direct effects of foreign-ownership on foreign firms' productivity and the indirect effects (or spillovers) from the presence of foreign-owned firms on other foreign and domestic firms' productivity in a unifying framework, taking interactions between firms into account. To do so, we relax a fundamental assumption made in empirical studies examining a direct causal effect of foreign ownership on firm productivity, namely that of no interactions between firms. Based on our approach, we are able to combine direct and indirect effects of foreign ownership and calculate the total effect of foreign firms on local productivity. Our results show that all these effects vary with the level of foreign presence within a cluster, an important finding for the academic literature and policy debate on the benefits of attracting foreign owned firms.

Plant-mediated ‘apparent effects’ between mycorrhiza and insect herbivores

Peer reviewed

A Recursive Income Model for Canadians : The Direct and Indirect Effects of Family Background (Working Paper 28)

This paper presents the results of a multi-equation income model which has been estimated for Canadian men and women which incorporates the effects of a number of important family background variables, including mother’s and father’s education, parents’ immigration status, their age at immigration, place of birth, language development, and learning background. Not only education, but also the individual’s tested literacy and numeracy levels are treated as intermediate outcomes which are affected by background and which, in turn, affect income. Many of the background variables are found to have important indirect effects on income which would be missed by more conventional approaches. We also find some interesting gender aspects with respect to the influences of parents’ educations on their children’s outcomes. Various policy implications of the findings are discussed.

Indirect Effects of Parental Coping on Children’s Psychosocial Adjustment in the Context of Pediatric Cancer

Thesis (Ph.D.)--University of Washington, 2016-08

Using Causal Models for the Calculation of Direct and Indirect Effects: An Example From Occupational Health

International audience

Predator diversity enhances secondary production and decreases the likelihood of trophic cascades

We manipulated the diversity of top predators in a three trophic level marine food web. The food web included four top benthic marine fish predators (black goby, rock goby, sea scorpion and shore rockling), an intermediate trophic level of small fish, and a lower trophic level of benthic invertebrates. We kept predator density constant and monitored the response of the lower trophic levels. As top predator diversity increased, secondary production increased. We also observed that in the presence of the manipulated fish predators, the density of small gobiid fish (intermediate consumers) was suppressed, releasing certain groups of benthic invertebrates (caprellid amphipods, copepods, nematodes and spirorbid worms) from heavy intermediate predation pressure. We attribute the mechanism responsible for this trophic cascade to a trait-mediated indirect interaction, with the small gobiid fish changing their use of space in response to altered predator diversity. In the absence of top fish predators, a full-blown trophic cascade occurs. Therefore the diversity of predators reduces the likelihood of trophic cascades occurring and hence provides insurance against the loss of an important ecosystem function (i.e. secondary production).

Proactive motivation and engagement in career behaviors: Investigating direct, mediated, and moderated effects

Proactive career behaviors become increasingly important in today's career environment, but little is known about how and when motivational patterns affect individual differences. In a six-month longitudinal study among German university students (Study 1; N = 289) it was demonstrated that motivation in terms of “can do” (self-efficacy and context beliefs), “reason to” (autonomous career goals), and “energized to” (positive affect) significantly predicted career behaviors. Contrary to expectation, negative context beliefs had a positive effect when combined with other motivational states. Study 2 replicated and extended those results by investigating whether “can do” motivation mediates the effect of proactive personality and whether those effects are conditional upon the degree of career choice decidedness. We tested a moderated multiple mediation model with a unique sample of 134 German students, assessed three times, each interval being 6 weeks apart. The results showed that effects of proactivity were partially carried through higher self-efficacy beliefs but not context beliefs. Supporting a moderation model, indirect effects through self-efficacy beliefs were not present for students with very low decidedness.