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Analysis of mediating variables in prevention and intervention research.

Mediational analysis is one way to test specific hypotheses derived from theory. Although this analysis has been suggested in the prevention literature, mediation analysis rarely is conducted. As the field of prevention matures, more questions about how prevention programs work (or fail to work) will emerge. Studies of mediation can address these questions, thereby reducing the cost and enhancing the impact of prevention programs. The methods outlined here can be applied in the evaluation of primary, secondary, and tertiary prevention programs. Since most prevention studies include measurement of some mediating constructs, mediation effects can be assessed on many existing data sets. Mediation analysis can be used to test ideas about prevention.

Data Interpretation, Statistical↗

Self-efficacy and psychosocial functioning in schizophrenia: a mediational analysis.

The construct of self-efficacy has been hypothesized to mediate the relationship between efforts at coping with psychiatric illness and functional outcome. This study examined whether self-efficacy mediated the relationships between psychosocial functioning and important predictors of functioning: premorbid functioning, negative symptoms, and cognitive functioning. Although self-efficacy was positively associated with psychosocial functioning, it did not mediate the relationships between functioning and the other established predictors. Rather, negative symptoms were the strongest predictor of functioning and mediated the relationship between self-efficacy and functioning. The findings suggest that negative symptoms, and not self-efficacy, are the most critical determinants of psychosocial functioning in schizophrenia, and that psychosocial treatment should focus on the amelioration of these symptoms.

Adult↗

Controlled ribonucleotide tailing of cDNA ends (CRTC) by terminal deoxynucleotidyl transferase: a new approach in PCR-mediated analysis of mRNA sequences.

Controlled ribonucleotide tailing of cDNA ends (CRTC) by terminal deoxynucleotidyl transferase is a polymerase chain reaction (PCR)-mediated technique that was developed to facilitate cloning and direct sequence analysis of complete 5'-terminal unknown coding regions of rare RNA molecules. In contrast with standard tailing protocols using dNTPs as the substrate, ribo-tailing of cDNA ends is easily controllable, self-limited (from two to four rNMP incorporations) and highly efficient (>98%). By virtue of the homopolymeric ribo-tail, the modified cDNA is anchored to the 3' overhang of a double-stranded DNA-adaptor in a T4 DNA ligase-dependent ligation. PCR amplification, mediated by two sequence-specific primers, yields the desired unique product suitable for cloning and dideoxy-sequencing.

Base Sequence↗

Mediation analysis of a school-based drug prevention program: effects of Project ALERT.

This study used mediation analyses, implemented in a longitudinal structural equation modeling framework, to examine the mechanisms by which a social-influence-based school drug use prevention program (Project ALERT) achieved its effects on past month cigarette use and alcohol misuse. Participants were 4277 South Dakotan middle-school students (2554 treatment and 1723 control) measured at baseline and 1 year later on past month cigarette use and alcohol misuse, as well as cigarette- and alcohol-related mediating variables targeted by the Project ALERT curriculum (i.e., resistance self-efficacy, positive and negative beliefs about use, and peer influence). Results for cigarettes showed that all hypothesized mediating variables were significant mediators of ALERT's effect on intentions to smoke and past month cigarette use, with peer influence being the strongest. Results for alcohol point to positive beliefs about the consequences of drinking as an important mediator for alcohol misuse. Taken together, the findings highlight an avenue for program improvement through increased impact on peer influence to use alcohol and drugs.

Adolescent↗

Early-adulthood body mass index, mammographic density and post-menopausal breast cancer risk: a mediation analysis.

BACKGROUND: To explore potential mechanistic pathways and inform prevention strategies, this study examined whether mammographic density (MD) mediates the inverse association between higher early-adulthood body mass index (BMI) and lower post-menopausal breast cancer risk. METHODS: We analysed data from 33,816 post-menopausal women in the UK PROCAS cohort, with self-reported BMI at age 20. MD was measured using full-field digital mammography and assessed using the visual analogue scale (VAS) percentage density and Volpara®-derived fibroglandular volume (FGV). Counterfactual mediation modelling estimated natural direct and indirect effects. RESULTS: Over a median follow-up of 10.44 years, there were 1261 new post-menopausal breast cancers. Higher VAS and FGV were associated with increased breast cancer risk. BMI at age 20 was associated with lower VAS density and reduced breast cancer risk [Hazard Ratio per 5 kg/m²: 0.849 (0.771-0.938)]. The calculated proportion mediated by VAS density was 59.9% (32.6-150), after accounting for intermediate confounding by BMI in later adulthood. FGV was positively associated with higher BMI at cohort entry but not at age 20. CONCLUSIONS: Lower VAS density may partially explain the inverse association between early-adulthood BMI and post-menopausal breast cancer risk. The link between FGV and breast cancer risk may represent a different biological pathway.

Journal Article↗

Mediator analysis of Moms on the move.

This study examined whether improvements in physical activity discovered in a test of Moms on the Move were mediated by the behavioral constructs from which the intervention was derived. Identifying mediator variables is vital for intervention planning. The intervention was derived from the Transtheoretical Model (TTM) of behavior change and promoted moderately intense activities like walking. Sedentary mothers with children enrolled in the Women, Infants, and Children program (N = 44) were randomly assigned to the experimental intervention or attention control. Large effect sizes were reported for improvements in physical activity and changes in TTM constructs. This study examined whether the physical activity improvements were mediated by the behavioral constructs. Statistical analyses used bivariate correlation coefficients and two-stage multiple linear regression. These exploratory findings did not support the hypothesis that increased physical activity, which was associated with the experimental intervention, was mediated by the TTM constructs.

Adolescent↗

Candidate gene studies in the 21st century: meta-analysis, mediation, moderation.

The results of a large body of candidate gene studies of behavioural and psychiatric phenotypes have been largely inconclusive, with most findings failing to replicate reliably. A variety of approaches that augment the 'traditional' candidate gene approach are discussed, including the use of meta-analysis to combine findings from existing published reports, the investigation of mediating variables (including the use of intermediate phenotypes or endophenotypes) and the awareness of possible moderating influences (such as sex or ethnicity) and gene-environment interactions on genetic associations, possibly via epigenetic mechanisms. Advances in genotyping technology will also allow the routine use of haplotype analysis and linkage disequilibrium mapping. Examples of how these approaches may improve our understanding of how genetic associations with behavioural and psychiatric phenotypes obtain are given.

Behavior↗

HIV-related knowledge, stigma, and willingness to disclose: A mediation analysis.

Increasing HIV knowledge is a focus of many HIV education and prevention efforts. While the bivariate relationship of HIV serostatus disclosure with HIV-related knowledge and stigma has been reported in the literature, little is known about the mediation effect of stigma on the relationship of HIV knowledge with HIV serostatus disclosure. Data from 4,208 rural-to-urban migrants in China were analyzed to explore this issue. Overall, 70% of respondents reported willingness to disclose their HIV status if they were HIV-positive. Willingness to disclose was negatively associated with misconceptions about HIV transmission and stigma. Stigma mediated the relationship between misconceptions and willingness to disclose among women but not men. The mediation effect of stigma suggests that stigmatization reduction would be an important component of HIV prevention approaches. Gender inequality needs to be addressed in stigmatization reduction efforts.

Adolescent↗

Handgrip strength and risk of common infections and sepsis: Two prospective cohorts with proteomic mediation analysis.

BACKGROUND: Recent evidence links adiposity with the risk of severe infections, but whether muscle strength may also be an independent risk factor is less studied. We investigated the association between handgrip strength and risk of common infections and sepsis and explored potential mediation by plasma proteomic biomarkers. METHODS: We analyzed data from 405,451 UK Biobank participants and replicated the main findings in 4474 Chinese adults from the Hong Kong Osteoporosis Study (HKOS). Baseline handgrip strength was measured by a dynamometer. Cox models were used to estimate its association with incidence of pneumonia, urinary tract infection (UTI), skin infection, and sepsis, adjusting for sociodemographic, lifestyle, and health-related factors. Mediation analyses were performed using 2912 plasma proteins in a UK Biobank subsample (n = 42,414) to identify biological pathways. RESULTS: In UK Biobank (median follow-up 13.6-15.3 years), lower handgrip strength was associated with significantly increased risk of pneumonia (hazard ratio per 5-kg decrement=1.10; 95% CI=1.09-1.11), UTI (1.10; 1.09-1.11), skin infection (1.05; 1.04-1.05), and sepsis (1.08; 1.07-1.10). Associations were largely consistent in HKOS, and the relative risks associated with low grip strength were generally most pronounced in underweight individuals. GDF15 and PLAUR were identified as the most important proteins which mediated 12-14% of these associations. CONCLUSION: Low handgrip strength is associated with increased risks of common infections and sepsis, particularly in underweight individuals, with partial mediation by proteins related to inflammation and immune-related pathways. Handgrip strength assessment may provide prognostic value beyond body mass index for clinical risk stratification.

Humans↗

Understanding a link between sexual harassment and eating disorder symptoms: a mediational analysis.

Using data from 3 samples of working women and men, the present study examines the association between sexual harassment and eating disorder symptoms by studying the processes that may underlie this relationship. The results of structural equation modeling suggest a link between sexual harassment and eating disorder symptoms among women and indicate that this relationship is mediated by psychological distress, self-esteem, and self-blame. Further, sexual harassment was found to predict eating disorder symptoms among women even when experiences of sexual assault were included in the model. No relationship was found between sexual harassment and eating disorder symptoms among men. The theoretical and clinical implications of these results are discussed.

Adolescent↗

The trichotomous model and investment in learning to prepare for a sport test: a mediational analysis.

BACKGROUND: Contemporary views on motivation suggest that the approach-avoidance achievement goals conceptualization--namely the trichotomous model--can shed light on the important issue of student motivation. AIMS: To test the predictive value of the trichotomous model on the investment in learning a sport task for test preparation, and to validate a model which included a set of psychological processes (i.e., state anxiety and competence valuation) which mediate the relationship between the three goals (i.e., performance-approach, performance-avoidance, and mastery goals) and test preparation. The study was designed to investigate the direct and mediational effects of three experimental goal conditions on the time in which pupils prepared for a sport test. SAMPLE: French male school pupils (N = 75). Pupils were aged 13-15 years and attended schools in southern France. METHOD: Pupils prepared themselves for a sport task with a 5-minute period of training, and performed in one of three experimental conditions to which they were randomly assigned: a performance goal with a positive outcome focus (performance-approach), a performance goal with a negative outcome focus (performance-avoidance), or a mastery goal. RESULTS: Pupils in the performance-avoidance group reported higher state anxiety and lower competence valuation than those in the performance-approach and mastery groups, and this psychological state was associated with less time taken to prepare for the test. CONCLUSION: School pupils placed in an examination preparation context that elicits a performance goal with a negative outcome focus (performance-avoidance) show motivational deficits which manifest themselves in less time spent practising. The trichotomous model appears to be valid for the study of motivational processes in school physical education.

Adolescent↗

Personal goals and depression among Vietnamese American and European American young adults: a mediational analysis.

The authors report preliminary findings supporting the utility of the self-concordance model (K. M. Sheldon & A. J. Elliot, 1999) as an alternative approach to studying depression among Vietnamese American (N = 121) and European American (N = 155) college students. The participants completed measures of personal goals, goal self-concordance, and depression. Compared with the European American participants, the Vietnamese American participants reported higher levels of depression and lower levels of goal self-concordance. According to mediational analyses, ethnicity no longer accounted for significant variance in depression after the authors statistically controlled for goal self-concordance.

Adult↗

Perceived smoking norms, socioenvironmental factors, personal attitudes and adolescent smoking in China: a mediation analysis with longitudinal data.

PURPOSE: To gather information on inter-relationships among risk factors affecting adolescent smoking for tobacco control in China, the world's largest tobacco producer and consumer. METHOD: Longitudinal data were collected six months apart in 2003 from 813 students in grades 7, 8, 10, and 11 from two schools in Beijing, China. Linear regression was used to assess both the direct effect from predictor variables (smoking among influential others, pro-tobacco media, and attitudes toward smoking) on cigarette use and the indirect effect mediated through the perceived smoking norms (percentage of smokers among peers). RESULTS: Among the 803 subjects (mean age of 15.5 years, SD = 1.7; 52.1% female), 18.3% of males and 1.7% of females smoked in the past 30 days. Smoking among influential others (best friends, father, mother, male teachers, female teachers, and adults in general) and perceived positive psychological and social rewards from smoking at baseline were associated with number of cigarettes smoked at follow-up, whereas exposure to pro-tobacco media was not significantly associated with smoking. The mediated effect was greater for adult smoking (70% to 90%) than for best friend smoking (11% to 16%). CONCLUSION: Smoking among influential others and attitudes toward smoking influence adolescent smoking both directly and indirectly. The finding of the indirect effect mediated through perceived smoking norms expands our knowledge on smoking etiology. Effective adolescent smoking intervention programs in China need to include a component targeting adult smoking to reduce perceived smoking norms.

Adolescent↗

Goal setting, achievement orientation, and intrinsic motivation: a mediational analysis.

This study investigated the interactive effects of achievement orientation and evaluative focus of assigned, task-specific goals on intrinsic motivation for an enjoyable pinball game. Regression analyses revealed that the effect of performance or mastery-focused goals on intrinsic motivation varied as a function of achievement orientation. Specifically, the provision of task-specific standards with a performance focus enhanced intrinsic motivation for achievement-oriented individuals, whereas the assignment of such goals proved deleterious to the intrinsic motivation of those low in achievement orientation. Individuals low in achievement orientation displayed the highest levels of intrinsic motivation when provided with mastery-focused goals. A similar pattern of effects was obtained on competence valuation and task involvement, both of which were additionally validated as mediators of the direct effects on intrinsic motivation.

Achievement↗

Vectors containing infrequently cleaved restriction sites for use in BAL 31 nuclease-assisted and end-label-mediated analysis of cloned DNA fragments.

Cloning vectors derived from plasmids pUC8 and pUC18 and phage M13mp10 were constructed so as to have multiple cloning sites (MCS) flanked by the recognition/cleavage sites for the Sfi I and Not I restriction nucleases. Cleavage of vectors containing cloned DNA fragments with either of the infrequently cleaving Sfi I or Not I endonucleases will usually yield linear DNAs cleaved only at the corresponding site in the MCS, so that the cloned insert can be degraded unidirectionally by the duplex exonuclease activity of the BAL 31 nucleases until an amount equal to the length of the vector has been degraded. The ends of the above constructs resulting from cleavage with Not I or Sfi I can readily be labeled, with labeling at only the terminus of the cloned DNA available for the Sfi I site. The BAL 31 nuclease-mediated procedures enhance a previous technique for mapping of restriction enzyme fragments, allow for localization of sequences in cloned segments for which a probe is available, and improve a method for sequencing cloned inserts through the production of sets of nested unidirectional deletions from either end of the parent cloned fragment. The advantages of end-label-mediated restriction site mapping using the above vectors over existing such procedures are also demonstrated.

Bacteriophages↗

Dual-color detection of DNA sequence variants by ligase-mediated analysis.

Genetic screening for sequence variants associated with disease is assuming increasing importance in clinical medicine as well as in research. We describe an efficient method for such analyses, comprising a combination of practical features: (1) Amplified DNA samples are analyzed for their ability to serve as templates in standardized allele-specific ligation reactions between oligonucleotide probes; (2) Two allele-specific probes, differentially labeled with either of two lanthanide labels, compete for ligation to a third oligonucleotide (the signal from the two labeled probes can thus be directly compared in a sensitive time-resolved fluorescence detection reaction); and (3) Large sets of analyses are processed in parallel using a 96-pin capture manifold, serving to reduce pipetting steps and the risk of contamination. We present here the basis of the technique and its application to the screening for two common mutations causing cystic fibrosis and alpha 1-antiytrypsin deficiency.

Base Sequence↗

Fluorescence-mediated analysis of mitochondrial preprotein import in vitro.

Mitochondrial biogenesis is a crucial element of the functional maintenance of a eukaryotic cell. The organelle must import the majority of its proteins from the cytosol where they are synthesized as precursors. In vitro import assays have been developed in which isolated mitochondria are incubated with precursor proteins, that are generated either by in vitro translation systems or by expression and purification as recombinant proteins. The detection of imported proteins is performed by autoradiography or by Western blot. We have now established a novel detection system for imported precursor proteins that is based on fluorescent labeling. We constructed a mitochondrial preprotein containing a C-terminal SNAP-tag that can label itself with a single fluorescein molecule in an enzymatic reaction. The fluorescent preproteins were efficiently imported into isolated mitochondria and showed kinetic behavior similar to that of standard preproteins. The fluorescence detection was sensitive and significantly faster than other comparable procedures. We also showed that precursor proteins containing a SNAP-tag domain could be successfully labeled in a postimport reaction in intact mitochondria. In summary, the use of a reporter domain modified with a fluorescent dye provides a novel, sensitive, and fast detection method to analyze the properties of the mitochondrial import reaction in vitro.

Cell Adhesion Molecules, Neuronal↗

Mediator analysis: an overview of recent research on carers supporting people with intellectual disability and challenging behavior.

Families and front-line care staff are often key agents in helping deliver behavioural interventions to people with intellectual disability and challenging behaviour. The present paper reviews factors which may impact on the effectiveness of such interventions. Both PsychLit and MedLine were used to conduct an automated literature search which included the terms 'learning disability', 'mental handicap', 'mental retardation', 'intellectual disability', 'challenging behaviour', 'families' and 'staff. This search was substantially augmented by additional citations obtained from books and journal articles. The impact of attitudes, beliefs and emotional states as setting conditions for interventions was highlighted. A variety of more general setting conditions related to intervention effectiveness were also identified. Implications for both clinical practice and future research were discussed.

Adaptation, Psychological↗