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PubMed2003

Learned associability and associative change in human causal learning.

The Mackintosh (1975) model of associative learning specifies that processing of both the cues presented on a trial and the outcome of that trial will interact to determine the amount of associative change undergone by a given cue. Experiments looking at the distribution of associative change among the elements of a reinforced compound in animal conditioning studies indicate that processing of the outcome of a trial does indeed influence associative change. The work reported here investigates the distribution of associative change among the elements of a reinforced compound in a human causal judgement paradigm, and it indicates that processing of the cues presented on a trial also plays a role in determining associative change (in terms of changes in the associability of cues as a result of experience). Taken in combination, these results provide good support for Mackintosh (1975) and the characterizations of both cue and outcome processing that it offers.

Adult↗

PubMed2002

Causal analysis of exercise and calcium intake behaviors for osteoporosis prevention among young women in Thailand.

The goal of health education is to provide information to affect attitudes, beliefs, and intentions for behavior change. However, little is known about the effects of changes in knowledge on behaviors for osteoporosis prevention. Our objective is to develop and test theoretical models of the effects of knowledge, attitude, and self-efficacy on exercise and calcium intake among young women before and after an intervention program. First, we hypothesized that knowledge would positively predict attitude, self-efficacy, calcium intake, and exercise. Second, attitude would positively predict self-efficacy, calcium intake, and exercise. Third, self-efficacy would positively predict calcium intake and exercise. Fourth, attitude and self-efficacy would mediate the effect of knowledge on calcium intake and exercise. At the beginning and end of the study, participants in the control group and intervention group completed the osteoporosis knowledge test, the osteoporosis health belief scale, the osteoporosis self-efficacy scale, a self-report for food records, and exercise. The causal model was examined as a result of our study. After the intervention program, calcium intake and exercise were predicted by knowledge when mediated by attitudes and self-efficacy. The final model accounted for 30% and 45% of the variance in calcium intake and exercise, respectively. We conclude that interventions to enhance young women's knowledge and self-efficacy may result in increased calcium intake and exercise.

Adolescent↗

PubMed2006

Club drugs as causal risk factors for HIV acquisition among men who have sex with men: a review.

We reviewed medical and psychology databases for articles published between January 1980 and August 2005 demonstrating associations between HIV/Sexually Transmitted Infection risk and club drug use. Seventy-four articles were reviewed, of which 30 provided adjusted risk ratios for associations between HIV/sexually transmitted infection risk and club drug use among men who have sex with men. Definitions and lists of club drugs were broad and inconsistent. We constructed a conceptual framework of biologically plausible pathways for causation. Using Hill's criteria to examine club drugs as causal risk factors for HIV, we found the most evidence for methamphetamine and volatile nitrites; however, more studies are needed.

HIV Infections↗

PubMed2006

Summation in causal learning: elemental processing or configural generalization?

Results from human causal learning tasks that employ multiple cues are often interpreted in terms of the elemental theory of Rescorla and Wagner (1972). However, most results can also be successfully interpreted by the configural model proposed by Pearce (1987, 1994). One method of discriminating between these alternatives is through an investigation of summation and overexpectation. Indeed, demonstrations of these phenomena are fundamental to an elemental approach but are generally incompatible with an account that involves configural processing. Using a procedure in which the magnitude of the outcome varied, evidence for both summation and overexpectation was obtained in two experiments.

Adolescent↗

PubMedDate not supplied

A causal approach to the study of fertility and familism.

This paper tests, within the framework of LISREL, the causal structures of fertility using data from the 1973-74 Growth of Alberta Family Study (GAFS) of women aged 18-44 who are currently married or living common-law. Differential fertility among two groups of women classified by nativity also are examined. The women's background characteristics (e.g., age, religiosity, and education) are viewed as exogenous variables. The endogenous variables are familism and expected family size; familism is designated as an intermediate variable in the model, linking demographic and socioeconomic (including cultural) factors to fertility, The results indicate that familism acts as an important variable explaining fertility, particularly, among foreign-born women. The study confirms and extends earlier research findings that religiosity and education influence couples' fertility, the former positively and the latter negatively.

Adolescent↗

PubMed2004

The relationship between public causal beliefs and social distance toward mentally ill people.

OBJECTIVE: The aim of this study is to investigate the nature of the relationship between public causal beliefs and social distance toward people with mental disorders, particularly schizophrenia and depression. METHOD: In total, three representative surveys were carried out in Germany, Russia and Mongolia using personal, fully structured interviews. RESULTS: Despite the subjects' different cultural backgrounds, their responses show similar trends with regard to attributing depression and schizophrenia to psychosocial causes: 'acute stress' (life event) was most frequently endorsed as the cause for these two disorders. The biological causes ('brain disease' and 'heredity') were less frequently selected for depression than for schizophrenia. Irrespective of place and type of mental disorder, endorsing biological factors as the cause of schizophrenia was associated with a greater desire for social distance, the same relationship applies to depression in half the instances. CONCLUSIONS: It would be premature to draw conclusions with regard to interventions aimed at reducing discrimination based on stigma. However, our study provides stimulus for re-considering the assumptions underlying antistigma interventions: that promulgating biological concepts among the public might not contribute to a desired reduction in social distance toward people with mental disorders.

Adolescent↗

PubMed1976

Causal relations among cell cycle processes in Tetrahymena pyriformis. An analysis employing temperature-sensitive mutants.

Utilization of temperature-sensitive mutants of Tetrahymena pyriformis affected in cell division or developmental pathway selection has permitted elucidation of causal dependencies interrelating micronuclear and macronuclear replication and division, oral development, and cytokinesis. In those mutants in which cell division is specifically blocked at restrictive temperatures, micronuclear division proceeds with somewhat accelerated periodicity but maintains normal coupling to predivision oral development. Macronuclear division is almost totally suppressed in an early acting mutant (mola) that prevents formation of the fission zone, and is variably affected in other mutants (such as mo3) that allow the fission zone to form but arrest constriction. However, macronuclear DNA synthesis can proceed for about four cycles in the nondividing mutant cells. A second class of mutants (psm) undergoes a switch of developmental pathway such that cells fail to enter division but instead repeatedly carry out an unusual type of oral replacement while growing in nutrient medium at the restrictive temperature. Under these circumstances no nuclei divide, yet macronuclear DNA accumulation continues. These results suggest that (a) macronuclear division is stringently affected by restriction of cell division, (b) micronuclear division and replication can continue in cells that are undergoing the type of oral development that is characteristic of division cycles, and (c) macronuclear DNA synthesis can continue in growing cells regardless of their developmental status. The observed relationships among events are consistent with the further suggestion that the cell cycle in this organism may consist of separate clusters of events. with a varying degree of coupling among clusters. A minimal model of the Tetrahymena cell cycle that takes these phenomena into account is suggested.

Animals↗

PubMed1998

Missense mutations in disease genes: a Bayesian approach to evaluate causality.

The problem of interpreting missense mutations of disease-causing genes is an increasingly important one. Because these point mutations result in alteration of only a single amino acid of the protein product, it is often unclear whether this change alone is sufficient to cause disease. We propose a Bayesian approach that utilizes genetic information on affected relatives in families ascertained through known missense-mutation carriers. This method is useful in evaluating known disease genes for common disease phenotypes, such as breast cancer or colorectal cancer. The posterior probability that a missense mutation is disease causing is conditioned on the relationship of the relatives to the proband, the population frequency of the mutation, and the phenocopy rate of the disease. The approach is demonstrated in two cancer data sets: BRCA1 R841W and APC I1307K. In both examples, this method helps establish that these mutations are likely to be disease causing, with Bayes factors in favor of causality of 5.09 and 66.97, respectively, and posterior probabilities of .836 and .985. We also develop a simple approximation for rare alleles and consider the case of unknown penetrance and allele frequency.

Adenomatous Polyposis Coli↗

PubMed2000

Causal relationships between HIV-1 coreceptor utilization, tropism, and pathogenesis in human thymus.

The pathogenic differences between CXCR4 (X4)- and CCR5 (R5)-utilizing strains of HIV-1 may be predominantly due to differences in viral tropism, which in turn may be due to differential coreceptor utilization. We tested this hypothesis in the human thymus organ of the SCID-hu Thy/Liv mouse, using recombinants of NL4-3 that were isogenic except for Env coreceptor-binding determinants of the V1-V3 loops. Conversion of NL4-3 from an X4 to an R5 isolate was associated with altered tropism for cell subpopulations within the Thy/Liv organ (with a higher frequency of infection of thymic stromal cells, including macrophages), a slower rate of replication, and a lower level of cytopathicity. These observations underscore the causal relationships between tropism, coreceptor use, and cytopathicity in the human thymus in vivo.

Animals↗

PubMed2005

The effect of Gencydo injections on hayfever symptoms: a therapeutic causality report.

OBJECTIVES: The aim of this study was to study the effect of Gencydo (Weleda AG, Arlesheim, Switzerland) injections on hayfever symptoms. DESIGN: This is a therapeutic causality report based on the practices of 13 Dutch general practitioners. SUBJECTS: Thirteen (13) patients with a mean history of hayfever with grass pollen allergy of 9 years duration, who in previous years used conventional hayfever medication because of the severity of symptoms during the pollen season. INTERVENTIONS: Gencydo injections were given in 12 patients before the onset of and during the grass pollen season, and in one patient during the grass pollen season only. OUTCOME MEASURES: Nasal and non-nasal hayfever symptom severity, use of rescue medication (antihistamines or corticosteroids), and subjective experiences of patients were used as outcome measures. RESULTS: Nine (9) of 13 patients showed no increase of symptom severity during the so-called pollen season. Both the mean maximal total nasal symptom score per patient and the mean total nasal symptom score for the entire study group during the days with a grass pollen count >100 were mild. Percentages of individual "strong" or "severe" nasal symptom scores were low. There was no statistically significant difference in mean total nasal symptom score between the period when the pollen count was <100 and the period when it was >100. Conventional rescue medication for hayfever was used only eight times, all by one person. Nine (9) patients (69%) reported an improvement of symptoms (eight patients cited strong improvement and one patient noted slight improvement). CONCLUSIONS: There are clear indications that Gencydo treatment was effective in a large subgroup of the research population.

Administration, Intranasal↗

PubMed1989

Causal association of interferon-gamma with tumor regression.

Mouse interferon-gamma (MuIFN-gamma) can cause the rejection of malignant cells in vivo. The evidence presented here in support of this claim includes, first, that spontaneous regression of MSC sarcomas was associated with high intratumoral concentrations of endogenously-produced MuIFN-gamma. By contrast, progressively growing, lethal neoplasms of the same kind invariably contained very little IFN-gamma. Second, spontaneously regressing MSC sarcomas were converted into progressively growing, lethal neoplasms by injecting mice with a monoclonal antibody that neutralized the biological effects of endogenous IFN-gamma. Another monoclonal antibody that bound to, but did not neutralize, mouse IFN-gamma had no effect on the course of tumor regression. Together, these data causally relate MuIFN-gamma to the successful rejection of malignant cells in vivo. They also suggest that findings of poor therapeutic efficacy for IFN-gamma are probably attributable to problems other than an intrinsic lack in the biological activity of the lymphokine.

Animals↗

PubMed1994

A multicenter study using causal readings, self-recordings, and ambulatory blood pressure monitoring to assess isradipine effects. AMICUS Study Group.

The antihypertensive efficacy of isradipine has been widely studied. In most studies, however, blood pressure values were assessed by causal readings (CR) only. Furthermore, whether or not such blood pressure readings are sufficient proof of efficacy is still under discussion. Thus, a multicenter study was devised wherein blood pressure were recorded by CR, self-recordings, and noninvasive ambulatory monitoring (ABM). A total of 595 patients with mild-to-moderate hypertension were treated for 6 months starting with 1.25 mg of isradipine twice daily. If, after 4 weeks of treatment, CR-determined diastolic blood pressure (DBP) was still > 90 mm Hg, this dosage was doubled (n = 327) and, at week 8, pindolol at 5 mg or spirapril at 3 mg daily was added if necessary for blood pressure control. On the basis of CR, the results confirmed that low dosages of isradipine twice daily are safe and effective in the treatment of mild-to-moderate hypertension. The mean decrease in CR-determined blood pressure was 28.5/19.0 mm Hg at week 24, and the normalization rate (DBP < or = 90 mm Hg) for all patients treated was 78.2%. However, SR-determined blood pressure reduction was 20.0/13.0 mm Hg, with a normalization rate of 42%, whereas ABM-determined blood pressure reduction was 7.0/4.2 mm Hg. On the basis of ABM recordings, 66% of the patients had a DBP < 90 mm Hg on entry into the study and their blood pressures did not decrease with treatment. Thus, it appears that CR-determined blood pressures bias study results by including normotensives and thereby overestimating efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2004

Advances to Bayesian network inference for generating causal networks from observational biological data.

MOTIVATION: Network inference algorithms are powerful computational tools for identifying putative causal interactions among variables from observational data. Bayesian network inference algorithms hold particular promise in that they can capture linear, non-linear, combinatorial, stochastic and other types of relationships among variables across multiple levels of biological organization. However, challenges remain when applying these algorithms to limited quantities of experimental data collected from biological systems. Here, we use a simulation approach to make advances in our dynamic Bayesian network (DBN) inference algorithm, especially in the context of limited quantities of biological data. RESULTS: We test a range of scoring metrics and search heuristics to find an effective algorithm configuration for evaluating our methodological advances. We also identify sampling intervals and levels of data discretization that allow the best recovery of the simulated networks. We develop a novel influence score for DBNs that attempts to estimate both the sign (activation or repression) and relative magnitude of interactions among variables. When faced with limited quantities of observational data, combining our influence score with moderate data interpolation reduces a significant portion of false positive interactions in the recovered networks. Together, our advances allow DBN inference algorithms to be more effective in recovering biological networks from experimentally collected data. AVAILABILITY: Source code and simulated data are available upon request. SUPPLEMENTARY INFORMATION: http://www.jarvislab.net/Bioinformatics/BNAdvances/

Algorithms↗

PubMed2007

Human allergy and geohelminth infections: a review of the literature and a proposed conceptual model to guide the investigation of possible causal associations.

Geohelminth infections and allergic disease are major public health problems and there is evidence in developing countries that they are associated. Although there is an extensive literature of the relationship between geohelminth infections and allergy, there is little consensus on whether the association is causal and if so, whether geohelminth infections may increase or decrease the risk of allergy. An explanation for the conflicting findings of epidemiological studies is that geohelminths decrease the risk of allergy in areas of high infection prevalence and increase the risk of allergy in areas of low prevalence. Chronic geohelminth infections are inversely associated with allergy and anthelmintic treatment may increase the prevalence of allergy. In this paper, we review studies that have investigated the relationship between geohelminths and allergy; discuss the relevance of prevalence and timing of geohelminth infections and propose a conceptual model to define relevant scientific questions in future human and animal studies.

Anthelmintics↗

PubMed2000

Children's Difficulties in Text Comprehension: Assessing Causal Issues.

In this article we consider the difficulties of children who have a specific reading comprehension problem. Our earlier work has shown that good and poor comprehenders differ, in particular, in their ability to make inferences, integrate information in text, understand story structure, and monitor their understanding. We outline some studies that illustrate the poor comprehenders' problems and present two studies that use a comprehension-age match design to explore the direction of causality between comprehension skill and other abilities. We also present data from the first and second stages of a longitudinal study, when the children were 7 to 8 and 8 to 9 years old. Multiple regression analyses show that a number of factors predict significant variance in comprehension skill even after "general ability" factors such as IQ and vocabulary have been taken into account. These findings suggest that, not only can children have comprehension problems in the absence of word recognition problems, but that distinctly different skills predict variance in word recognition and variance in comprehension. The data support the view that single-word reading skills and the ability to build integrated text representations make independent contributions to overall reading ability. We discuss the implications of these findings for our understanding of children's problems in text comprehension, for deaf readers, and for remediation.

Journal Article↗

PubMed2026

Genomes of the ex-type strains of Elsinoë mangiferae and E. perseae, the causal agents of scab on mango and avocado.

Elsinoë species are slow-growing, hemibiotrophic to necrotrophic fungi that cause scab diseases on economically important fruit crops. Genome resources for many host-specific species remain limited. We report high-quality draft genome assemblies for the ex-type strains of Elsinoë mangiferae (CBS 226.50) and E. perseae (CBS 406.34), causal agents of mango and avocado scab, respectively. Among 5 approaches tested, a Nanopore-only NextDenovo assembly produced the most contiguous genomes, yielding 24.5 Mb (E. mangiferae) and 25.1 Mb (E. perseae) assemblies with 13 and 18 contigs, respectively, BUSCO completeness scores of ∼94%, and multiple putative telomere-to-telomere chromosomes. Gene prediction identified 9,134 and 9,243 genes, respectively. Functional annotation revealed enrichment of metabolic and regulatory pathways, including those involved in posttranslational modification, protein transport, and secondary metabolism. Carbohydrate-active enzyme repertoires were small but conserved, consistent with stealth pathogenicity strategies and low plant cell wall degradation. Both genomes encoded large secretomes (>850 proteins), diverse protease repertoires (>300 proteins), Ecp2-like effector proteins, and multiple biosynthetic gene clusters, including clusters with similarity to those associated with elsinochrome and ACT-toxin II biosynthesis, some of which may contribute to host-pathogen interactions and disease development. A large fraction of genes lacked functional characterization, suggesting incomplete databases and/or the presence of lineage-specific genes potentially involved in virulence or host adaptation. These genome resources fill critical gaps for underrepresented Elsinoë species and provide taxonomically anchored references essential for diagnostics, comparative genomics, and research into the molecular basis of host specificity and pathogenicity in scab-causing fungi.

Persea↗

PubMed2003

Mosaicism of Solid Gold supports the causality of a noncoding A-to-G transition in the determinism of the callipyge phenotype.

To identify the callipyge mutation, we have resequenced 184 kb spanning the DLK1-, GTL2-, PEG11-, and MEG8-imprinted domain and have identified an A-to-G transition in a highly conserved dodecamer motif between DLK1 and GTL2. This was the only difference found between the callipyge (CLPG) allele and a phylogenetically closely related wild-type allele. We report that this SNP is in perfect association with the callipyge genotype. The demonstration that Solid Gold-the alleged founder ram of the callipyge flock-is mosaic for this SNP virtually proves the causality of this SNP in the determinism of the callipyge phenotype.

Animals↗

PubMed1990

Mental and physical health of caregiving spouses: development of a causal model.

This study modeled the causal relationship between physical health and depression among a sample of 315 people providing home care for a spouse who had been diagnosed as having Alzheimer's disease. In addition to significant stability paths and correlations among variables at any one point in time, significant lagged paths were found in which depression (1) predicted physical health (2), depression (2) predicted physical health (3), and depression (1) predicted burden (2). Contrasting the overall model for husband and wife caregivers over a 6-month period indicated that the model was significant for wives but not for husbands.

Aged↗