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Beliefs about resistance self-efficacy and drug prevalence: do they really affect drug use?

Testing the same structural equation model for eighth-grade users and nonusers, this study examines social influence and cognitive precursors of adolescent drug use among 1138 West Coast students. For the eighth-grade nonusers of alcohol, cigarettes, and marijuana (n = 518), low resistance self-efficacy and prodrug social influences directly predicted generic expectations of using drugs and actual use nine months later. For the users (n = 620), both variables directly affected expectations and indirectly affected actual use. While the latent variable measure of drug use prevalence did not predict either outcome, specific estimates of peer alcohol use directly affected later drinking. Estimates of several other drug-specific relations were required to fit the model, indicating that both general and drug-specific effects are needed to explain adolescent drug use.

Adolescent

Suicidality phenotypes reflect both shared and distinct genetic factors.

Suicidality phenotypes, including suicidal ideation (SI), non-fatal suicide attempt (SA), and suicide death (SD), are heritable and exhibit both shared and phenotype-specific genetic influences. Using genomic structural equation modelling, we estimated the shared genetic architecture across GWAS of SI (176,147 cases, 1,010,300 controls), SA (53,919 cases, 1,063,988 controls), and SD (7,584 cases, 652,070 controls) and conducted a multivariate GWAS of a latent suicidality factor capturing their shared liability. This analysis identified 36 genome-wide significant loci, including seven not previously reported in any suicidality GWAS. Follow-up analyses identified residual genetic variance specific to each phenotype, including three SD-specific genomic risk loci. Conditioning suicidality phenotypes on genetic liability to psychiatric disorders revealed significant residual genetic variance across SI, SA, SD, and the suicidality common factor. Together, these results suggest that suicidality reflects both shared genetic liability and phenotype-specific contributions.

Journal Article

Disentangling adiposity-related and non-adiposity-related genetic pathways for type 2 diabetes.

OBJECTIVE: To identify circulating proteins associated with type 2 diabetes (T2D) risk through pathways not fully explained by body mass index (BMI), and to assess therapeutic actionability. RESEARCH DESIGN AND METHODS: We applied GWAS-by-subtraction within a genomic structural equation model to European ancestry summary statistics for T2D (74,124 cases, 824,006 controls) and BMI (n = 681,275), partitioning T2D liability into BMI-related and BMI-subtracted components. We then performed proteome-wide Mendelian randomization (MR) using cis-protein quantitative trait loci from four plasma proteomics cohorts: ARIC, deCODE, Fenland, and the UK Biobank Pharma Proteomics Project. Prioritized proteins passed sensitivity analyses with alternative MR methods and were supported by colocalization evidence. Tissue-resolution regulatory support was assessed using cis-eQTL colocalization across GTEx and pancreatic islet, subcutaneous adipose, and whole-blood resources. Actionability was evaluated using the druggable genome and Open Targets. RESULTS: GWAS-by-subtraction attenuated the genetic correlation between BMI and BMI-subtracted T2D from 0.54 (SE 0.02) to 0.35 (SE 0.02). Proteome-wide MR prioritized 29 proteins for BMI-subtracted T2D. Thirteen showed eQTL colocalization in at least one tissue, implicating liver and intermediary metabolism (GCDH, NOTCH2), pancreatic islet biology (CTRB2, MANBA), adipose and Wnt signaling (RSPO3, GALNT3), and whole blood regulatory signals (PAM, SNUPN). Sixteen proteins were classified within druggable-genome Tiers 1-3, and five had existing Open Targets compounds. CONCLUSIONS: Integrating GWAS-by-subtraction, proteome-wide MR, and colocalization nominated 29 proteins associated with T2D liability not fully explained by BMI. These findings highlight genetically supported targets for follow-up studies of T2D therapies that complement weight-centered approaches.

Journal Article

Effects of gender and age on the heritability of body mass index.

We estimated genetic and environmental components of variance of body mass index (BMI) among 7245 same-sexed Finnish MZ and DZ twin pairs aged 18-54 years from the nationwide Finnish Twin Cohort. Age accounted for 20 per cent of variance among men and 26 per cent in women. The contributions of additive genetic effects, shared and non-shared environmental effects on BMI-variance were estimated by LISREL structural equation models. Genetic effects accounted for 72 per cent and 68 per cent of total variance in men and non-pregnant women respectively, while 28 per cent of variance among men and 32 per cent among women was due to non-shared environmental effects. This gender difference was statistically significant. Models including shared environmental effects did not improve model fits. The magnitude of the genetic component of BMI was also analysed separately for each 10-year age group. Models with age-specific parameters for genetic and environmental effects fitted significantly better than models with effects constrained to be equal over age. Our results indicate a substantial genetic component in BMI. However, the magnitude of additive genetic effects decreases with age in both genders.

Adult

Self-transcendence and emotional well-being in women with advanced breast cancer.

Self-transcendence has been associated, in previous studies, with stressful life events and emotional well-being. This study examined the relationships among self-transcendence, emotional well-being, and illness-related distress in women with advanced breast cancer. The study employed a cross-sectional correlational design in a convenience sample (n = 107) of women with Stage IIIb and Stage IV breast cancer. Subjects completed a questionnaire that included Reed's Self-Transcendence Scale; Bradburn's Affect Balance Scale (ABS); a Cognitive Well-Being (CWB) Scale based on work by Campbell, Converse, and Rogers; McCorkle and Young's Symptom Distress Scale (SDS); and the Karnofsky Performance Scale (KPS). Data were analyzed using factor analytic structural equations modeling. Self-transcendence decreased illness distress (assessed by the SDS and the KPS) through the mediating effect of emotional well-being (assessed by the ABS and the CWB Scale). Self-transcendence directly affected emotional well-being (beta = 0.69), and emotional well-being had a strong negative effect on illness distress (beta = -0.84). A direct path from self-transcendence to illness distress (beta = -0.31) became nonsignificant (beta = -0.08) when controlling for emotional well-being. Further research using longitudinal data will seek to validate these relationships and to explain how nurses can promote self-transcendence in women with advanced breast cancer, as well as in others with life-threatening illnesses.

Adaptation, Psychological

Cycles in nonlinear age-structured models. I. Renewal equations.

A variety of density-dependent population models can be described by nonlinear renewal equations. This paper develops analytical tools for such models to study the sustained population cycles which arise by bifurcation. The results obtained describe explicitly the direction of bifurcation, and the period, form, and dynamic stability of sustained cycles. The results are illustrated by application to a cohort-controlled model of human populations which has been proposed as a formalization of the Easterlin effect.

Age Factors

An 8-year study of multiple influences on drug use and drug use consequences.

Multiple long-term influences on young adult drug use and abuse were tested within an interactionist perspective using latent-variable causal models. Intrapersonal influences included early drug use and social conformity. Proximal interpersonal influences were captured by perceived peer drug use, perceived adult drug use, and family disruption. More distal influences included perceptions of community approval or disapproval for drug use. Outcome measures included not only use of drugs but also disruptive drug use (getting high at work or school) and self-admitted problems with drugs. Data were obtained from 654 participants at three equally spaced time points during an 8-year longitudinal study that began when the subjects were in junior high school. Confirmatory factor analyses were used to test the adequacy of the hypothesized measurement model. Subsequently, a structural equation, or path model, was used to examine the across-time relations among the latent and manifest variables. Stability effects were found for all repeatedly measured latent variables across the 4-year spans. Social conformity strongly influenced other latent variables across time. Early drug use and perceived adult drug use were prominent predictors of young adult drug use, whereas prior drug use predicted disruptive drug use and a lack of social conformity predicted problems with drug use. Early adult alcohol use predicted later disruptive drug use and problems with drug use. Perceived adult drug use generally influenced later alcohol use, whereas peer drug use influenced later cannabis and hard-drug use. Implications for prevention and treatment using a multicausal interactionist perspective are discussed.

Adult

Sugar-sweetened beverage consumption and incident depression: an exploratory multi-omics analysis of candidate biological mediators.

BACKGROUND: Depression is a leading cause of mental and physical disability globally, with its onset and progression influenced by a complex interplay of dietary, psychological, and biological factors. Recent research suggests a link between sugar-sweetened beverage (SSB) consumption and depression risk, although the potential biological pathways underlying this association remain poorly understood. METHODS: This study utilized data from 192,045 participants in the UK Biobank to examine the prospective association between SSB consumption and incident depression using Cox proportional hazards models. SSBs were defined as the sum of five beverage categories assessed via the Oxford WebQ 24-hour dietary recall. Directional consistency of the association was further examined across three external supporting datasets encompassing diverse populations: NHANES, YRBSS, and the Lianyungang Municipal School Health and Risk Factor Surveillance Study Dataset. We further investigated whether proteins, metabolites, inflammatory markers, and brain imaging phenotypes may serve as candidate mediators statistically consistent with mediation of the SSB-depression association. RESULTS: High SSB consumption was associated with an 18% higher risk of incident depression compared with non-consumers (HR = 1.18; 95% CI: 1.11-1.25), with consistent directional associations observed across external supporting datasets. A plasma proteomic signature comprising 229 proteins was constructed using elastic net regularization and was associated with an increased risk of incident depression. Exploratory mediation analyses identified 72 proteins, 36 metabolites, and 5 inflammatory markers as candidate mediators, with IL1RN showing the strongest protein-level candidate mediating effect (9.6%), and Unsaturation and neutrophil count showing the strongest metabolite- and inflammatory marker-level effects, respectively. CONCLUSIONS: This study provides preliminary evidence that proteins, metabolites, and inflammatory markers may serve as candidate mediators statistically consistent with mediation of the association between SSB consumption and incident depression. These findings are exploratory and hypothesis-generating, and future experimental studies are needed to validate these candidate pathways and assess their potential as targets for dietary interventions in depression prevention.

Humans

Coping: a genetic epidemiological investigation.

This study examines data on self-report coping behaviour, life events and symptoms of anxiety and depression in a general population sample of 827 female twin pairs. Factor analysis identified three almost uncorrelated coping factors: turning to others; problem solving; and denial. Turning to others and problem solving were negatively and denial was positively related to levels of anxiety and depression. Turning to others and problem solving buffered the depressogenic and anxiogenic effects of stressful life events, while denial exacerbated the anxiogenic effects of life events. Structural equation model-fitting indicated that twin resemblance in turning to others and problem solving could be explained entirely by genetic factors with an estimated heritability of 30 and 31%, respectively. For denial, twin resemblance could be best explained by familial-environmental factors accounting for 19% of the total variation. Genes may affect the vulnerability to psychiatric disorders in part by influencing coping behaviour.

Adaptation, Psychological

Age structure in predator-prey systems: intraspecific carnivore interaction, passive diffusion, and the paradox of enrichment.

An existing arthropod predator-prey model incorporating age structure in the carnivore through the use of the von Foerster equation is extended to include the effects of intraspecific carnivore interaction and passive diffusion or migration. A linear stability analysis of the community equilibrium point of that differential-integral equation system is performed and the resulting secular equation analyzed by the method of D-partitions. These stability results are then compared to those obtained by employing an analogous differential equation model without age structure, in particular as they relate to the so-called paradox of enrichment. In the absence of passive diffusion, it is shown that, unlike for a differential equation model, the paradox of enrichment can occur even with a carnivore which exhibits intraspecific competition. This destabilizing effect of age structure is seen to occur most dramatically when interspecific interactions are large, while the effect of passive diffusion is to offset that tendency and restabilize the system. These predictions are in accordance with relevant experimental evidence involving mites.

Aging

Structural equation analysis of an exercise/sleep health practices model on quality of life of elderly persons.

An exercise/sleep model from past research was tested for relationships with a quality of life measure of the health status of 126 elderly persons. Past statistical analyses of this relationship used canonical correlation statistical analyses. In the following study, when structural equation analysis (LISREL VII) was applied to the same data, an altered model resulted: an exercise-only model. To examine this relationship further, researchers should employ a longitudinal design with a more comprehensive model and larger sample of elderly persons.

Activities of Daily Living

A QSAR model for the estimation of carcinogenicity: example application to an azo-dye.

Since carcinogenicity bioassays are time-consuming, costly, and use animal resources, structure-activity relationship equations which model toxicological end-points have been developed to make available alternative methods which approximate the results that could be obtained from bioassays but which are less expensive and time-consuming and use fewer, if any, animals. These equations are based on sets of bioassay results and explain the end-point under consideration in terms of substructural and other parameters which describe the chemical entities. The resulting equations--or models--can then be used to estimate--or predict--the end-point for new structures. The estimation is followed by validation procedures.

Animals

A quantitative analysis of metabolite fluxes along some of the pathways of intermediary metabolism in Tetrahymena pyriformis.

A detailed model of intermediary metabolism has been constructed which is consistent with all known information on the compartmental structure of metabolism in Tetrahymena, on the enzyme complement of this cell, and on the localization of the enzymes. The model allows computation of the specific activity of every carbon atom of all metabolites and thus of the flux of carbon along the major pathways of metabolism under steady state conditions. To test the model, data were required from cells grown under standard conditions and then suspended in a dilute salt solution and incubated for 1 hour in a mixture of acetate, pyruvate, hexanoate, bicarbonate, and glutamate labeled in a total of 10 positions, but with only one substrate labeled in any given flask. Twenty-seven measurements of label incorporation into CO2, lipids, glycogen, glutamate, and alanine were made, plus measurements of label distribution into fatty acid and glycerol moieties for 4 of the substrates and of oxygen consumption and of glycogenolysis, yielding 33 independent measurements. These, plus about 18 "limit" measurements which also constrain any possible solutions, were in sufficient excess of the 23 independent parameters to permit a stringent assessment of the model. Equations derived directly from the structure of the model and from the known stereochemistry of the reactions were programmed on a PDP-15 computer and values of the Qo2 and of label expected to be incorporated into the various products actually measured were computed for any given set of flux rates. A set of flux rates was found which yielded an excellent fit to the observed data. The ability to achieve a fit to the data for an overdetermined system constitutes strong support for this structural model of intermediary metabolism and the computed flux rates therefore provide a quantitative description of metabolite flow in the intact cell. Despite the redundancy of measurements relative to parameters to be determined, it was not possible to define a unique set of values for the flux through phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase, although the relationship between these fluxes is specified by the model. The analysis allows estimation of the recycling of phosphoenopyruvate through pyruvate kinase under conditions of net glyconeogenesis and an apparently futile exchange of acetyl-CoA between the inner and outer mitochondrial compartments. Carbon flow through the glyoxylate bypass under these conditions is about one-third of that through the Krebs cycle. The analysis also shows a net transport of malate from the peroxisomes to the mitochondria, consistent with the anaplerotic role of the peroxisomal glyoxylate bypass in Tetrahymena.

Acetates

[Determinants and educational approaches to AIDS anxiety in adolescents].

On the basis of a questionnaire filled out by 480 adolescents determinants of fear of AIDS were evaluated with a model of linear structural equations. The main factors that appeared were knowledge about AIDS (those who know more report less fear), personal involvement (those who are confronted more with the problem of AIDS report more fear) and sexual experience (those who are sexually more experienced report less fear). The last finding is interpreted to the effect that mainly sexually inexperienced adolescents, who are usually also the younger ones, shift their sexual fears to the AIDS-complex.

Acquired Immunodeficiency Syndrome

Mutagenicity (Ames): a structure-activity model.

A statistical structure-activity model of the Salmonella typhimurium (Ames) test has been devised based on 472 chemicals for which this endpoint has been measured. The model uses substructural fragments as the independent parameters to explain the difference in mutagenicity of the different chemicals. The model is able to classify 86% of the chemicals into their correct categories; the false-positive rate is 4.7%, and the false-negative rate 5.3%. Approximately 10% of the chemicals cannot be classified by the existing equation. This structure-activity model can be used as a preliminary screen prior to other testing as well as for setting priorities for more detailed investigations.

False Negative Reactions

Carcinogenesis: a predictive structure-activity model.

A statistical structure-activity equation has been developed for the estimation of carcinogenic potential for chemicals that have not been subjected to carcinogenesis assays. This discriminant equation is based on substructural fragments and molecular weight obtained for 343 compounds. The data base used for the design of the equation was obtained from the monographs of the International Agency for Research on Cancer. The accuracy of classification for the carcinogens in the model is between 87 and 91%, and for noncarcinogens between 78 and 80% in the presence of between 5.5 and 10.2% of the compounds not being classifiable. The false negative rate ranges between 4 and 5%; the false positive rate is near 11%.

Carcinogens

[Model building in pharmacokinetics/Part II: Generalized theoretical presentation of complete integration of linear compartment models of optional structure (author's transl)].

The method of Laplace transformation is used to obtain the integral of linear differential equations for pharmacokinetic models. A general solution uniform in structure for all types of models (mammillary, catenary, mixed) was established. Choice of one more application compartments, of kinetics describing the input procedure and of elimination pathways is free.

Kinetics

A predator prey model with age structure.

A general predator-prey model is considered in which the predator population is assumed to have an age structure which significantly affects it fecundity. The model equations are derived from the general McKendrick equations for age structured populations. The existence, stability and de-stabilization of equilibria are studied as they depend on the prey's natural carrying capacity and the maturation period m of the predator. The main result of the paper is that for a broad class of maturation functions positive equilibria are either unstable for small m or are destabilized as m decreases to zero. This is in contrast to the usual rule of thumb that increasing (not decreasing) delays in growth rate responses cause instabilities.

Aging