SEARCH · PubMed Health

Results for “causality”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,207 records · Page 67Linked to original sources

PubMed1991

Geschwind's theory of cerebral lateralization: developing a formal, causal model.

Geschwind and Galaburda (1987) have proposed a complex and influential model of cerebral lateralization that is based on the argument that increased fetal testosterone levels modify neural development, immune development, and neural crest development. The theory can explain many aspects of cerebral lateralization and its relation to learning disorders, giftedness, and immune deficits. This article clarifies the structure of the theory by presenting it as a causal-path model. The internal coherence of the model is then evaluated by assessing the central concept of anomalous dominance, the role of timing in the articulation of the model, and the invocation of nonlinear processes. Finally, the article considers the problems implicit in testing a "grand" theoretical model and derives some principles for assessing the testability of various predictions, given the practical constraints of sample size and the problems of measurement error.

Autoimmune Diseases↗

PubMed1992

Externalizing behavior problems and academic underachievement in childhood and adolescence: causal relationships and underlying mechanisms.

Conceptual and measurement issues surrounding externalizing behavior problems and academic underachievement, the strength and specificity of the covariation between these domains, and the viability of explanatory models that link these areas are reviewed. In childhood, inattention and hyperactivity are stronger correlates of academic problems than is aggression; by adolescence, however, antisocial behavior and delinquency are clearly associated with underachievement. Whereas investigations with designs that allow accurate causal inference are scarce, unidirectional paths from 1 domain to the other have received little support. Indeed, the overlap of externalizing problems with cognitive and readiness deficits early in development suggests the influence of antecedent variables. Low socioeconomic status, family adversity, subaverage IQ, language deficits, and neurodevelopmental delay are explored as possible underlying factors.

Adolescent↗

PubMed2003

Context change as the mechanism of reinstatement in causal learning.

Four experiments were conducted to explore the mechanism of reinstatement in human causal learning. After a retroactive interference treatment in which a stimulus was first followed by an outcome (A+) and then followed by a different outcome (A*), simple exposure to the original outcome (+) in the interference-test context produced partial reinstatement of the first-learned information (A+). When exposure to the outcome took place in a context different from the interference-test context, reinstatement was not observed (Experiment 1). Equivalent results appeared when the outcome presented during reinstatement was different from the one originally related to the stimulus affected by interference, independent of whether the interfering outcome (Experiments 2, 3, and 4) or a new outcome (Experiments 3 and 4) was presented before the test. These results suggest an interpretation of reinstatement in terms of a context change between interference and testing.

Adolescent↗

PubMed2005

Outcome additivity and outcome maximality influence cue competition in human causal learning.

Recent research suggests that outcome additivity pretraining modulates blocking in human causal learning. However, the existing evidence confounds outcome additivity and outcome maximality. Here the authors present evidence for the influence of presenting information about outcome maximality (Experiment 1) and outcome additivity (Experiment 2) on subsequent forward blocking. The results of Experiment 3 confirm that, with outcome maximality controlled, outcome additivity affects backward blocking but not release from overshadowing. Finally, the results of Experiment 4 demonstrate that information about outcome additivity has a similar effect on forward blocking if presented after the blocking training instead of before. The results are compatible with the idea that blocking results from inferential processes at the time of testing and not from a failure to acquire associative strength during training.

Adolescent↗

PubMed2004

Propensity score estimation with boosted regression for evaluating causal effects in observational studies.

Causal effect modeling with naturalistic rather than experimental data is challenging. In observational studies participants in different treatment conditions may also differ on pretreatment characteristics that influence outcomes. Propensity score methods can theoretically eliminate these confounds for all observed covariates, but accurate estimation of propensity scores is impeded by large numbers of covariates, uncertain functional forms for their associations with treatment selection, and other problems. This article demonstrates that boosting, a modern statistical technique, can overcome many of these obstacles. The authors illustrate this approach with a study of adolescent probationers in substance abuse treatment programs. Propensity score weights estimated using boosting eliminate most pretreatment group differences and substantially alter the apparent relative effects of adolescent substance abuse treatment.

Evaluation Studies as Topic↗

PubMed1975

Reactions to male and female success and failure in sex-linked occupations: impressions of personality, causal attributions, and perceived likelihood of different consequences.

Female subjects responded to three short verbal cues in which either a male or female character succeeded or failed in an examination qualifying the male (or female) for entry into an occupation. Three occupations were involved varying in masculine dominance (medicine, teaching, and nursing). In responding to each cue, subjects first rated the character in the cue on semantic differential scales to provide impressions of personality, then rated the importance of different possible causes of the outcome (causal attribution), and finally rated the likelihood that each of a set of possible consequences might follow the outcome. Results indicated a fairly pervasive tendency for the female subjects to upgrade successful males in relation to unsuccessful males but to downgrade successful females in relation to unsuccessful females. Results were discussed in relation to sex roles in society as they relate to permissible achievements for males and females.

Achievement↗

PubMed1978

Epidemiological evidence for causal relationship between Epstein-Barr virus and Burkitt's lymphoma from Ugandan prospective study.

Results from a prospective sero-epidemiological study initiated in Uganda in 1971 indicate that children with high antibody titres to Epstein-Barr virus structural antigens are at high risk of developing Burkitt's lymphoma. These findings strongly support a causal relationship between the Epstein-Barr virus and Burkitt's lymphoma but suggest that the oncogenic potential of the virus is realised only in exceptional circumstances.

Age Factors↗

PubMed2006

Reactive oxygen species have a causal role in multiple forms of insulin resistance.

Insulin resistance is a cardinal feature of type 2 diabetes and is characteristic of a wide range of other clinical and experimental settings. Little is known about why insulin resistance occurs in so many contexts. Do the various insults that trigger insulin resistance act through a common mechanism? Or, as has been suggested, do they use distinct cellular pathways? Here we report a genomic analysis of two cellular models of insulin resistance, one induced by treatment with the cytokine tumour-necrosis factor-alpha and the other with the glucocorticoid dexamethasone. Gene expression analysis suggests that reactive oxygen species (ROS) levels are increased in both models, and we confirmed this through measures of cellular redox state. ROS have previously been proposed to be involved in insulin resistance, although evidence for a causal role has been scant. We tested this hypothesis in cell culture using six treatments designed to alter ROS levels, including two small molecules and four transgenes; all ameliorated insulin resistance to varying degrees. One of these treatments was tested in obese, insulin-resistant mice and was shown to improve insulin sensitivity and glucose homeostasis. Together, our findings suggest that increased ROS levels are an important trigger for insulin resistance in numerous settings.

3T3-L1 Cells↗

PubMed2005

Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome.

The increasing incidence of obesity and the metabolic syndrome over the past two decades has coincided with a marked increase in total fructose intake. Fructose--unlike other sugars--causes serum uric acid levels to rise rapidly. We recently reported that uric acid reduces levels of endothelial nitric oxide (NO), a key mediator of insulin action. NO increases blood flow to skeletal muscle and enhances glucose uptake. Animals deficient in endothelial NO develop insulin resistance and other features of the metabolic syndrome. As such, we propose that the epidemic of the metabolic syndrome is due in part to fructose-induced hyperuricemia that reduces endothelial NO levels and induces insulin resistance. Consistent with this hypothesis is the observation that changes in mean uric acid levels correlate with the increasing prevalence of metabolic syndrome in the US and developing countries. In addition, we observed that a serum uric acid level above 5.5 mg/dl independently predicted the development of hyperinsulinemia at both 6 and 12 months in nondiabetic patients with first-time myocardial infarction. Fructose-induced hyperuricemia results in endothelial dysfunction and insulin resistance, and might be a novel causal mechanism of the metabolic syndrome. Studies in humans should be performed to address whether lowering uric acid levels will help to prevent this condition.

Fructose↗

PubMed1994

A null mutation in the human CNTF gene is not causally related to neurological diseases.

We report a null mutation in the human ciliary neurotrophic factor gene (CNTF). The mutated allele shows a G to A transition producing a new splice acceptor site and the resulting mRNA species codes for an aberrant protein. Analysis of tissue samples and transfection of CNTF minigenes into cultured cells demonstrates that the mutated allele expresses only the mutated mRNA species. In 391 Japanese people tested, 61.9% were normal homozygotes, 35.8% heterozygotes and 2.3% mutant homozygotes. The distribution of the three genotypes is similar in healthy and neurological disease subjects, indicating that human CNTF deficiency is not causally related to neurological diseases.

Alleles↗

PubMed2002

Topological and causal structure of the yeast transcriptional regulatory network.

Interpretation of high-throughput biological data requires a knowledge of the design principles underlying the networks that sustain cellular functions. Of particular importance is the genetic network, a set of genes that interact through directed transcriptional regulation. Genes that exert a regulatory role encode dedicated transcription factors (hereafter referred to as regulating proteins) that can bind to specific DNA control regions of regulated genes to activate or inhibit their transcription. Regulated genes may themselves act in a regulatory manner, in which case they participate in a causal pathway. Looping pathways form feedback circuits. Because a gene can have several connections, circuits and pathways may crosslink and thus represent connected components. We have created a graph of 909 genetically or biochemically established interactions among 491 yeast genes. The number of regulating proteins per regulated gene has a narrow distribution with an exponential decay. The number of regulated genes per regulating protein has a broader distribution with a decay resembling a power law. Assuming in computer-generated graphs that gene connections fulfill these distributions but are otherwise random, the local clustering of connections and the number of short feedback circuits are largely underestimated. This deviation from randomness probably reflects functional constraints that include biosynthetic cost, response delay and differentiative and homeostatic regulation.

Gene Expression Regulation, Fungal↗

PubMed2025

Towards improved fine-mapping of candidate causal variants.

Fine-mapping in genome-wide association studies aims to identify potentially causal genetic variants among a set of candidate variants that are often highly correlated with each other owing to linkage disequilibrium. A variety of statistical approaches are used in fine-mapping, almost all of which are based on a multiple regression framework to model the relationship between genotype and phenotype, while accommodating specific assumptions about the distribution of variant effect sizes and using different inference algorithms. Owing to their modelling flexibility and the ease of making inferential statements, these approaches are predominantly Bayesian in nature. Recently, these approaches have been improved by refining modelling assumptions, integrating additional information, accommodating summary statistics, and developing scalable computational algorithms that improve computation efficiency and fine-mapping resolution.

Humans↗

PubMed2004

Body mass index and parent-reported self-esteem in elementary school children: evidence for a causal relationship.

OBJECTIVE: To clarify relationships between body mass index (BMI) and self-esteem in young children at a population level. To assess whether low self-esteem precedes or follows development of overweight/obesity in children. DESIGN: Prospective cohort study in elementary schools throughout Victoria, Australia. Child BMI and self-esteem were measured in 1997 and 2000. SUBJECTS: Random sample of 1,157 children who were in the first 4 y of elementary school (aged 5-10 y) at baseline. MEASURES: BMI was calculated from measured height and weight, then transformed to z-scores. Children were classified as nonoverweight, overweight or obese based on international cut-points. Low child self-esteem was defined as a score below the 15th percentile on the self-esteem subscale of the parent-reported Child Health Questionnaire. RESULTS: Overweight/obese children had lower median self-esteem scores than nonoverweight children at both timepoints, especially at follow-up. After accounting for baseline self-esteem, higher baseline BMI z-score predicted poorer self-esteem at follow-up (P=0.008). After accounting for baseline BMI z-score, poorer baseline self-esteem did not predict higher BMI z-score at follow-up. While nonoverweight children with low baseline self-esteem were more likely to develop overweight/obesity (OR=2.1, 95% CI=1.2, 3.6), this accounted for only a small proportion of the incidence of overweight. CONCLUSIONS: Our data show an increasingly strong association between lower self-esteem and higher body mass across the elementary school years. Overweight/obesity precedes low self-esteem in many children, suggesting a causal relationship. This indicates that prevention and management strategies for childhood overweight/obesity need to begin early to minimise the impact on self-esteem.

Body Mass Index↗

PubMed2001

Hypothesis: phenol and hydroquinone derived mainly from diet and gastrointestinal flora activity are causal factors in leukemia.

High background levels of phenol and hydroquinone are present in the blood and urine of virtually all individuals, but vary widely. Phenol and hydroquinone have been strongly implicated in producing leukemia associated with benzene exposure, because they reproduce the hematotoxicity of benzene, cause DNA and chromosomal damage found in leukemia, inhibit topoisomerase II, and alter hematopoiesis and clonal selection. The widely varying background levels of phenol and hydroquinone in control individuals stem mainly from direct dietary ingestion, catabolism of tyrosine and other substrates by gut bacteria, ingestion of arbutin-containing foods, cigarette smoking, and the use of some over-the-counter medicines. We hypothesize that these background sources of phenol and hydroquinone and associated adducts play a causal role in producing some forms of de novo leukemia in the general population. This hypothesis is consistent with recent epidemiological findings associating leukemia with diets rich in meat and protein, the use of antibiotics (which change gastrointestinal flora make-up), lack of breastfeeding, and low activity of NAD(P)H quinone oxidoreductase which detoxifies quinones derived from phenol and hydroquinone and protects against benzene hematotoxicity. An attractive feature of our hypothesis is that it may explain why many people who have no known occupational exposures or significant smoking history develop leukemia. The hypothesis predicts that susceptibility to the disease would be related to diet, medicinal intake, genetics and gut-flora composition. The latter two of these are largely beyond our control, and thus dietary modification and reduced use of medicines that elevate phenol levels may be the best intervention strategies for lowering leukemia risk.

Diet↗

PubMed2006

Fine mapping of the MAPT locus using quantitative trait analysis identifies possible causal variants in Alzheimer's disease.

In addition to senile plaques, neurofibrillary tangles are characteristic of Alzheimer's disease (AD) pathology, suggesting a clear involvement of the microtubule-associated protein tau (MAPT) in AD. Recent findings, suggesting that the H1c haplotype is associated with increased risk, now also implicate MAPT genetically. In this study, we aim to clarify this association by a fine mapping approach using both a traditional phenotypic association analysis and a quantitative trait (QT) analysis using cerebrospinal fluid (CSF) tau protein levels in the German population. Here, we report that both methodologies identify that the H1c haplotype may play important role in AD (AD risk, P=0.007, uncorrected; CSF tau levels, P=0.027, uncorrected). Further, the use of a sliding window approach in the QT analysis allowed for the narrowing down of the region where a probable causal variant may be located. The data suggest that this may lie at or within close proximity to the rs242557 single nucleotide polymorphism as association with CSF tau levels seems to be primarily driven by rs242557 in a gene dosage-dependent manner (trend model: P=0.002, uncorrected). These findings provide functional evidence to support the genetic association of MAPT with AD.

Aged↗

PubMed1999

The expression of P-glycoprotein is causally related to a less aggressive phenotype in human osteosarcoma cells.

The relationship between P-glycoprotein expression and malignancy is controversial. We have recently found that, in osteosarcoma, multidrug resistance (MDR) is associated with a less aggressive behavior, both in vitro and in clinical settings. In this study, we evaluated whether P-glycoprotein overexpression has a cause-effect relationship with the reduced metastatic potential of MDR cells, or rather reflects a more complex phenotype. MDR1 gene-transfected osteosarcoma cell clones, showing different levels of P-glycoprotein expression, were analysed for their in vitro characteristics and their tumorigenic and metastatic ability in athymic mice. Apart from the different levels of P-glycoprotein, no significant change in the expression of surface antigens or in the differentiative features were observed in the MDR1 gene transfectants compared to the parental cell lines or control clones, obtained by transfection with neo gene alone. In contrast to controls, however, MDR1 transfectants showed a significantly lower ability to grow in semi-solid medium and were completely unable to grow and give lung metastases in athymic mice. These findings indicate that P-glycoprotein overexpression is causally associated with a low malignant potential of osteosarcoma cells, and open new insights on the role and functions of P-glycoprotein activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2002

Downregulation of Betaig-h3 gene is causally linked to tumorigenic phenotype in asbestos treated immortalized human bronchial epithelial cells.

Although Betaig-h3 gene has been suggested to modulate cell adhesion and tumor formation, its physiological functions are not well understood. Using human papillomavirus immortalized human bronchial epithelial (BEP2D) cells, we found that Betaig-h3 expression was markedly decreased in asbestos-induced tumorigenic cells. Fusion of tumorigenic and control BEP2D cells resulted in the recovery of Betaig-h3 gene expression to control level and the loss of tumorigenic phenotype. Furthermore, ectopic expression of Betaig-h3 gene in asbestos-induced tumorigenic cells inhibited cell growth in vitro, anchorage independent phenotype, as well as tumorigenicity in nude mice. Betaig-h3 gene is ubiquitously expressed in various normal human tissues, with the exception of the brain, where there is little or no expression. In contrast, there was a decrease or absence in expression of the Betaig-h3 gene in 14 human tumor cell lines of diverse histological types examined, when compared with normal human cells or tissues. The result strongly suggests that loss of Betaig-h3 expression is a frequent event in human cancer and causally related to acquisition of tumorigenic phenotype in asbestos-treated BEP2D cells.

Asbestos↗

PubMed1980

Urine concentration of 3-ethyl-5-hydroxy-4,5-dimethyl-delta 3-pyrrolin-2-one ('mauve factor') is not causally related to schizophrenia or to acute intermittent porphyria.

1. 3-Ethyl-5-hydroxy-4,5-dimethyl-delta 3-pyrrolin-2-one (HPL, 'mauve factor') was determined quantitatively in the urine of schizophrenic, general medical and porphyric subjects by a sensitive gas/liquid-chromatographic method using a nitrogen-specific detector. 2. A comparative evaluation with previously used methods for HPL was made and some problems of specificity are discussed. 3. The concentration of HPL in early morning and spot smaples of urine from 146 subjects with schizophrenia was not greater than that in 42 general medical patients, contrary to previous reports. 4. Of the three patients with acute intermittent porphyria, two excreted HPL. One subject, studied over a 2 year period, did so intermittently in a manner unrelated to her attacks of porphyria. 5. It is concluded that the urine content of HPL is unlikely to be causally related to schizophrenia or to the clinical manifestations of acute intermittent porphyria.

Acute Disease↗