Simultaneous analysis of the behavioural phenotype, physical factors, and parenting stress in people with Cornelia de Lange syndrome.

BACKGROUND: Studies into the phenotype of rare genetic syndromes largely rely on bivariate analysis. The aim of this study was to describe the phenotype of Cornelia de Lange syndrome (CdLS) in depth by examining a large number of variables with varying measurement levels. Virtually the only suitable multivariate technique for this is categorical principal component analysis. The characteristics of the CdLS phenotype measured were also analysed in relation to parenting stress. METHOD: Data for 37 children and adults with CdLS were collected. The type of gene mutation and relevant medical characteristics were measured. Information on adaptive functioning, behavioural problems, the presence of the autistic disorder and parenting stress were obtained through questionnaires and semi-structured interviews with the parents. Chronological age and gender were also included in the analysis. RESULTS: All characteristics measured, except gender, were highly interrelated and there was much variability in the CdLS phenotype. Parents perceived more stress when their children were older, were lower functioning, had more behavioural problems, and if the autistic disorder was present. A new perspective was acquired on the relation between the gene mutation type and medical and behavioural characteristics. In contrast with earlier research the severity of medical characteristics did not appear a strong prognostic factor for the level of development. CONCLUSION: Categorical principal component analysis proved particularly valuable for the description of this small group of participants given the large number of variables with different measurement levels. The success of the technique in the present study suggests that a similar approach to the characterisation of other rare genetic syndromes could prove extremely valuable. Given the high variability and interrelatedness of characteristics in CdLS persons, parents should be informed about this differentiated perspective.

Consensus molecular alignment based on generalized procrustes analysis.

One of the most serious problems in three-dimensional quantitative structure-activity relationship (3D-QSAR) studies is selection of an alignment rule for molecular super position of the compounds in the data set. In 3D-QSAR analyses of structure-activity data, a reference compound in a defined conformation is chosen, and all structures in the data set are aligned with the reference in a pairwise manner. In subsequent steps, conformation/alignment-dependent descriptors are computed for the compounds and compared to those of the reference. This approach gives much weight to the arbitrarily chosen reference molecule and can introduce a bias in the results. Here an alternative, and more general, approach to molecular alignment is presented that is based on Generalized Procrustes Analysis (GPA). The result is a consensus alignment that uses all molecules in the data set and avoids the bias introduced in the pairwise alignment strategy.

Added value of three-way methods for the analysis of mortality trends illustrated with worldwide female cancer mortality (1968-1985).

Trends in mortality rates are usually presented per tumour site or per country without an overall analysis of the complete data encompassing all three aspects (tumour sites, countries, trends). This paper presents a methodology for such an overall analysis using three-way methods applied to a data set on female mortality rates for 17 tumour sites of 43 countries for the years 1968-1985. Multivariate techniques like biplots and three-mode principal component analysis within an overall three-way analysis-of-variance framework were used. We confirmed the known patterns of comparatively high mortality for women due to cancer of the bladder, intestines, pancreas, rectum, breast, ovary, skin and leukaemia and the relatively low mortality rates for liver cancer in Western and Northern Europe, the USA, Australia and New Zealand. Also, the reverse pattern was observed for Middle and Southern Europe, Hong Kong, Singapore, and in Japan, and in some but not all Latin American countries. The relatively mortality due to cancer was high in the lungs, mouth, larynx and oesophagus in the British Isles, but was much less in other European countries. Mortality due to cancer of the thyroid, uterus, gall bladder and stomach was high in Middle European countries, as was the case in Japan, Chile and Costa Rica. Rates were low for Southern European countries, North America, Australia and New Zealand. Specific deviating patterns in the data were the more rapidly decreasing mortality rates for stomach cancer in Chile and Japan and the more rapidly increasing mortality rates for lung cancer in the USA, Scotland and Denmark. In conclusion, using three-way methods, it was feasible to analyse the cancer mortality data in their entirety. This enabled the simultaneous comparison of trends in relative mortality rates between all countries due to all tumour sites, as well as the identification of specific deviating trends for specific tumour sites in specific countries.

The effects of an early stressful life event on sensorimotor gating in adult rats.

There is increasing evidence that patients suffering from schizophrenia have disturbances in the brain and other parts of the body indicative of a disturbed development. These findings have led to the so-called neurodevelopmental hypotheses of schizophrenia, which state that schizophrenia (or a predisposition for this disease) results from perinatal disturbances which affect the normal development of the central nervous system. In order to study such a possible relationship we have used early short-lasting (24 h) maternal deprivation, and studied the influence of this life event on prepulse inhibition of the acoustic startle at adult age in rats, since it has been shown that schizophrenic patients show a disruption of prepulse inhibition. The results show that early maternal deprivation significantly reduced prepulse inhibition when the animals were tested at postnatal day (pnd) 69 (birth being pnd 0). The effects were qualitatively similar when deprivation took place on pnd 3, 6 or 9, although at the later days the effects were stronger. There was little influence on baseline startle response (except for a small reduction seen after deprivation on pnd 6). In separate experiments it was shown that the effect of maternal deprivation on prepulse inhibition was not seen before puberty and was similar for male and female offspring. Moreover, the effects could be reversed by treatment with the classical antipsychotic, haloperidol, or the putative atypical antipsychotic, quetiapine (both given 15 min before the prepulse inhibition experiment). In summary, the results show that an early stressful life event can have a delayed influence on prepulse inhibition in rats, qualitatively similar to the disturbances seen in schizophrenic patients. These data suggest that maternal deprivation (i.e., a 24 h separation of rat pups from their mother early in life) may represent an interesting animal model for investigating the influence of early life events on the information processing and general functioning of an individual at adult age.

Dynamics of behaviour in the Strange Situation: a structural equation approach.

In this paper, we present a structural equation approach to modelling infant behaviour in the Strange Situation. A model was developed on a Dutch data set, and was subsequently cross-validated for an American data set containing the original Ainsworth data. Model building is reported in some detail as no previous similar analyses of the Strange Situation exist in the literature. The latent variables in the preferred model are stranger wariness, minimization or deactivation of attachment concerns, and maximization or hyperactivation of attachment concerns. Stranger wariness influences only the subsequent behaviour towards the mother, and behaviour in the second reunion episode is dependent on the same mother behaviour in the first reunion episode, and not on other mother behaviours. Structural equation modelling behaviour in the Strange Situation is shown to provide further insight into the dynamics of the procedure.

Classifying infants in the Strange Situation with three-way mixture method of clustering.

The quality of the attachment relationship between mother and infant is typically determined in the Strange Situation. The assignments of infants to the A (avoidant), B (secure), and C (resistant) attachment classes are largely but not exclusively based on measurements during the reunion episodes. In this paper, the measurements in the reunion episodes are used to derive a clustering of the infants via three-way mixture method of clustering, a technique especially designed for clustering three-way mixture method of clustering, a technique especially designed for clustering three-way data (here: infants, variables and episodes). The results are compared with the A-B-C classification, and the relevance of the outcomes for attachment research are discussed. At the same time, the paper aims to demonstrate the use and usefulness of the three-way clustering procedure for data from the social and behavioural sciences.

The relative effects of maternal and child problems on the quality of attachment: a meta-analysis of attachment in clinical samples.

In this meta-analysis of 34 clinical studies on attachment the hypothesis is tested that maternal problems such as mental illness lead to more deviating attachment classification distributions than child problems such as deafness. A correspondence analysis on 21 North American studies with normal subjects produced a baseline against which the clinical samples could be evaluated. Separate analyses were carried out on studies containing the traditional A, B, C classifications and on studies that also included the recently discovered D or A/C category. Results show that groups with a primary identification of maternal problems show attachment classification distributions highly divergent from the normal distributions, whereas groups with a primary identification of child problems show distributions that are similar to the distributions of normal samples. The introduction of the D or A/C classifications (about 15% in normal samples) reveals an overrepresentation of D or A/C in the child problem groups, but the resulting distribution still is much closer to the normal distributions compared to the samples with maternal problems. In clinical samples, the mother appears to play a more important role than the child in shaping the quality of the infant-mother attachment relationship.

Multiattribute evaluation of regional cotton variety trials.

The Australian Cotton Cultivar Trials (ACCT) are designed to investigate various cotton [Gossypium hirsutum (L.)] lines in several locations in New South Wales and Queensland each year. If these lines are to be assessed by the simultaneous use of yield and lint quality data, then a multivariate technique applicable to three-way data is desirable. Two such techniques, the mixture maximum likelihood method of clustering and three-mode principal component analysis, are described and used to analyze these data. Applied together, the methods enhance each other's usefulness in interpreting the information on the line response patterns across the locations. The methods provide a good integration of the responses across environments of the entries for the different attributes in the trials. For instance, using yield as the sole criterion, the excellence of the namcala and coker group for quality is overlooked. The analyses point to a decision in favor of either high yields of moderate to good quality lint or moderate yield but superior lint quality. The decisions indicated by the methods confirmed the selections made by the plant breeders. The procedures provide a less subjective, relatively easy to apply and interpret analytical method of describing the patterns of performance and associations in complex multiattribute and multilocation trials. This should lead to more efficient selection among lines in such trials.

Individual Differences in Assimilation Resistance and Affective Responses in Problem Solving.

Data on problem solving collected within the framework of Eckblad's (198lb) cognitive theory of affect are analyzed with three-mode principal component analysis. Eckblad's theory contends that affect is mediated by cognitive schemes. When schemes are inadequate for input assimilation, the resistances call forth affects with respect to the events. In this study, the task information load was varied to provide different levels of resistance. Data comprised 6 judgment scales (Pleasant-Unpleasant, Interesting-Boring, Comfortable-Uncomfortable, ComplexSimple, Varied-Monotone, and Confused-Clear) by 8 problem solving tasks (ordered a priori by information load) by 32 thirteen-year-old boys. The general results were consistent with the hypotheses of curvex scale relationships and joint scale-task fan-shaped vector configurations, but the fit was modest and vulnerable to other interpretations. Although many of the problems were accommodated by Eckblad's general scheme theory, it is suggested that assimilation resistance must be more rigorously operationalized to afford greater insight into the correspondence between cognition and affect. In general, this study illustrates the effectiveness of the threemode principal component analysis (TUCKALS) method for the assessment of the nomothetic validity of a theoretical framework as it pertains to within and across person variation.

Changes over time in the relationship between hand preference and writing hand among left-handers.

In a cross-sectional Dutch sample the percentage of left-handers writing with their left hand increased from 0% for people of 40 yr and over, to 100% for 14 yr olds and younger. The implications of this result for the use of writing hand as an index for handedness are discussed, and causes for this phenomenon are briefly explored.

Implicit Theories of Personality: Further Evidence of Extreme Response Style.

Five groups of 19 subjects made ratings on 11 personality trait scales of overlapping subsets of 59 artificial stimulus persons who were described by one to five personality trait adjectives. The data were analyzed per group of subjects (blockwise) and per type of stimulus person (questionnaire-wise) by means of three-mode principal component analyses. This yielded highly similar structures for the scales, and in the blockwise analyses, for the stimulus persons. This similarity was substantiated by external three-mode analyses, which showed that all stimulus persons can be mapped into one overall configuration. In all analyses it was found that differences between subjects consisted of differences in extremity of judgment, which suggests the operation of response style.

Group And Individual Implicit Theories Of Personality: An Application Of Three-Mode Principal Component Analysis.

Data produced by 60 subjects rating 31 artificial persons on 11 personality trait scales were analyzed by three-mode principal component analysis. The subjects shared a circular configuration of stimuli and scales. Individuals tended to depart from this pattern in extremity of judgement rather than configuration, suggesting the operation of a response style. The advantages of including "artificial subjects," and of partitioning the residual sums of squares are discussed.