Insulin-like growth factor-I comparisons in healthy twin children.

Insulin-like growth factor-I (IGF-I) levels in plasma were measured in healthy twin children. The within-pair correlation for 43 monozygotic pairs was r = 0.91 (P < or = 0.0001), an association significantly higher than that for same sex dizygotic pairs (r = 0.40; P < or = 0.06). The high correlation for monozygotic twins indicated a marked genetic influence on IGF-I levels. After correction for age and sex, the correlation between IGF-I level and height was r = 0.38 (P < or = 0.0001). These findings provide clear evidence that IGF-I levels correlate with height, a growth characteristic known to be genetically controlled.

Health consequences of behaviors: injury as a model.

Injury is the third leading cause of death in the United States and the leading cause for children, adolescents, and young adults. Injury results from multiple factors and so may its prevention. The first and simplest approach toward preventing injuries has been to innovatively and aggressively apply a traditional public health model. Strategically, the goal has been to remove harmful agents of injury and to make the environment safer. Tactics such as public information, product regulation, legislative action, and the like have been credited with reductions in mortality and morbidity. To expand our understanding and our prevention strategies across multiple injuries, other scientific knowledge bases and intervention models from fields such as psychology and child development are being used to study childhood injury. These approaches show that in addition to environmental determinants, psychosocial factors involving both the care giver and the child are related to injury. The research programs described here illustrate the advantage of investigating psychosocial factors at both molar and molecular levels. General characteristics of mothers and children related to injury help define families at risk, as well as suggesting vehicles for intervention. Behavioral factors influencing risk perception highlight the etiology of increased risk in adolescence. Injury episodes, even slight, as well as "near injuries" and dangerous and risky behavior can be quantified and analyzed by retrospective ("postmortem") approaches yielding data on commonly occurring consequences (and the lack thereof) for minor injury. Finally, approaches that simulate dangerous situations can identify interaction patterns that result in childhood injury. Based on such research, we are coming to view injuries as the result of patterns of behaviors that develop and persist over time, and as such these patterns can be detected and, one hopes, altered before a serious medical event occurs. The role of the pediatrician after injury occurs is clear. With regard to prevention of injuries, pediatricians' roles are being defined by those individuals who have begun to investigate causes, educate families, and advocate for regulation and prevention. However, like the causes and methods for prevention, the disciplines involved in the study and prevention of injury are multiple. Such a multidisciplinary approach that considers multiple factors, theories, models, and interventions to prevent injury may be the approach that is as simple as possible.

Quantitative genetic analysis of injury liability in infants and toddlers.

A threshold model of latent liability was applied to infant and toddler twin data on total count of injuries sustained during the interval from birth to 36 months of age. A quantitative genetic analysis of estimated twin correlations in injury liability indicated strong genetic dominance effects, but no additive genetic variance was detected. Because interpretations involving overdominance have little research support, the results may be due to low order epistasis or other interaction effects. Boys had more injuries than girls, but this effect was found only for groups whose parents were prompted and questioned in detail about their children's injuries. Activity and impulsivity are two behavioral predictors of childhood injury, and the results are discussed in relation to animal research on infant and adult activity levels, and impulsivity in adult humans. Genetic epidemiological approaches to childhood injury should aid in targeting higher risk children for preventive intervention.

Eye color changes past early childhood. The Louisville Twin Study.

OBJECTIVE: To determine whether eye color changes after 6 years of age. DESIGN: Longitudinal data on eye color were obtained from the Louisville Twin Study, Louisville, Ky. Twins (n = 1513 [individuals]) were assessed at least once and most twins (n = 1386) were examined on 2 or more occasions. Parents of twins were also examined at the study inception, 128 of whom were assessed again from February 1989 to October 1993. MAIN OUTCOME MEASURE: Eye color was assessed at each examination by matching the iridial coloration of the subject to 1 of 15 painted glass eye anterior segments, similar to those in artificial eyes, mounted on a circular disk. The spectrum ranged from light blue (1) to dark brown (15). RESULTS: Among whites (n = 1359), the eye color of 3.8% to 8.6% of the sample twins became 2 U or more darker or 2 U or more lighter during 3- to 9-year intervals between 6 years of age and adulthood (> 18 years, < 24 years). Among identical (monozygotic) twin pairs, there was a high degree of concordance in eye color (r = 0.98 [P < .001]), while in fraternal (dizygotic) twin pairs, the concordance was less pronounced (r = 0.49) and decreased with age (r = 0.07). Among the sample of the mothers of twins, 9% had irides that lightened by 2 U or more during the follow-up period. CONCLUSION: Most individuals achieve stable eye color by 6 years of age. However, a subpopulation of 10% to 15% of white subjects have changes in eye color throughout adolescence and adulthood in the eye color range that can be expected to reflect changes in iridial melanin content or distribution. These data also suggest that such changes in eye color, or the propensity to such changes, may be genetically determined.

Blood glutathione and cysteine concentrations in twin children.

Glutathione and cysteine are major antioxidants in blood that are associated with health and longevity. To ensure their measurement, careful attention to avoid auto-oxidation is necessary to stabilize the samples. Since no report of these compounds has been reported in children, our goal was to determine their levels of reduced and oxidized glutathione (GSH and GSSG) and cysteine (Cys and CSSC), To this end, 140 healthy children, ages 2 to 9 years from the Louisville Twin Study were studied. Blood samples were collected and analyzed for GSH, GSSG, Cys, and CSSC by our HPLC dual electrochemical method. The results showed that GSH and total GSH (GSH + GSSG) levels for monozygotic (MZ) twins were significantly higher (P < 0.001) than levels for dizygotic (DZ) twins. However, the opposite occurred for Cys and total Cys (Cys + CSSC) in that the levels were significantly higher for DZ twins than for MZ twins. (P < 0.005-0.013). In spite of this marked difference in zygosity, the within-pair correlations for twin pairs used for estimating heritability suggested that there was a major environmental influence for total GSH and total Cys. Finally. GSH levels were significantly lower for young (2-9 years) children than adults (P < 0.001).

Evidence for genetic influence on both cross-situation and situation-specific components of behavior.

An assumption often made in the study of personality and in social psychology is that methods variance and situation-specific effects, as key components of measured behavioral variance, are environmental effects. The results of the present research refute that assumption. Nine measures-3 aspects of temperament measured in each of 3 ways-were obtained at age 24 months for twin sibships participating in the Louisville Twin Study. This report describes a new model that captures the unique information potentially available in such data, by combining multitrait-multimethod and twin-family analytic designs. The results indicated significant genetic influence on methods-situations components of variance along with genetic influence on traits. The findings support heuristics that include both situation-specific patterns of behavior and cross-situational consistencies.

Persons, situations, and time: a genetic view of behavioral change in children.

Twin children participating in a longitudinal study were observed at 9, 12, 18, 24, and 30 months of age in two settings: unstructured free play and relatively structured test taking. Behaviors relating to adaptability to the two settings were rated and the scores analyzed for evidence of continuity both across settings and across ages. Age-to-age correlations for the adaptability scores for each setting yielded a simplex pattern of low-moderate order. Correlations of individuals' scores across settings were also of low-moderate order. Within-pair correlations indicated that identical twins were more similar that same-sex fraternal twins in both settings, but correlations were consistently stronger in the playroom setting. Analysis of variance was performed to test for within-pair concordance in the direction and degree of change. Identical pairs remained significantly more similar in adaptability from one setting to another even when change in adaptability occurred. Similar results were found for change across ages; however, these differences were significant only in the playroom setting. Results suggest that situation variables contribute to the low stabilities frequently reported for personality dimensions but that the direction and degree of behavioral change are genetically conditioned.

Assessment of infant mental development: toward a broader perspective.

The limitations on predictions of intelligence provided by single-point neonatal and infant assessments continue to hamper efforts to certify the clinical outcome of children at risk. Although new methods of clinical assessment show promise of offsetting these limitations, each method alone has not markedly improved predictions. From a developmental perspective, a strategy for assessment should include a broad range of measures combined empirically to form a developmental risk registry. The strategy takes into account evolving changes, as well as levels of competencies of the infant, and considers these within the evolving environmental context of the family.

Left ventricular boundary detection from spatio-temporal volumetric computed tomography images.

This paper presents a new automatic technique for left ventricle boundary detection from a set of three-dimensional (3D) computed tomography (CT) volumetric cardiac images. The goals of this paper are to incorporate the temporal information into LV boundary detection, to link the shape modeling and LV boundary detection together, and to provide a compact representation of recovered LV boundaries to cardiac imaging. The proposed technique introduces spatio-temporal boundary detection and iterative model-based boundary refinement to left ventricular boundary extraction. The proposed technique has been applied to two sets of four-dimensional (4D) computed tomography images. Experimental results are compared with the manually edited images.

Classification of chromatic visual evoked potentials with the aid of a neural net.

Twelve normal subjects, and six color blind (three protanopes and three deuteranopes) individuals were used in this study. Visual evoked potentials (50-150 msec post-stimulus) were recorded in response to three stimuli: (a) three horizontal, achromatic bars alternating in luminosity between bright and dim, (b) bars alternating between blue and red, and (c) bars alternating between green and red. The resulting waveforms were normalized in amplitude and submitted to a commercial neural net program for classification. The network correctly identified 24 of the 36 normal responses. (2) The network was also asked to distinguish between the responses of normal and color blind individuals. Based upon the blue/red response, the network correctly classed 12 of 18 responses, and based upon the green/red response correctly classified 14 of 18 (including all 6 color blinds). (3) These results are statistically highly significant and suggest that the VEP elicited by chromatic stimulation is substantially different from that elicited by achromatic stimuli.

Twins with academic learning problems: antecedent characteristics.

Developmental histories of 46 children experiencing academic difficulties, all of whom had participated since birth in a longitudinal study of twins, were compared with a matched control group of twins. Genetic influences on the liability for academic difficulties are suggested, since identical pairs were more likely than fraternal pairs to be concordant both for academic difficulties and for preschool behavioral characteristics specific to the index group.

Twins: within-pair similarity on Bayley's Infant Behavior Record.

Summary scores for behaviors rated on Bayley's Infant Behavior Record were obtained by summing sequential ratings for same-sex twins participating in a longitudinal study. The first year scores were based on visits made at 3, 6, 9, and 12 months, by 55 identical and 27 fraternal pairs; the second year scores were based on visits at 18, 24, and 30 months, by 47 identical and 27 fraternal pairs. During the first year, within-pair correlations for almost all behaviors were stronger for identical than for fraternal pairs; in the second year, within-pair correlations for identical twins were similar to those of fraternal twins except for the more cognitive behaviors. Composite scores were calculated for two behavioral clusters--one composed of behaviors related to Primary Cognition, and the other composed of behaviors related to Extraversion. Within-pair correlations were higher for identical than for fraternal twins in both the first and second years, indicating stronger and more consistent genetic influences on the more cognitive behaviors.

Hereditary determinants of manual torque.

Data from a longitudinal study of twin children and siblings, 155 girls and 134 boys (aged 4 to 9 yr.), on a torque test confirmed that during this age period manually produced circling patterns change from clockwise to counterclockwise orientation. A genetic influence is suggested.

Cognitive and personality factors associated with the double trapezium illusion.

76 pairs of 9- to 11-yr.-old twins (41 female, 35 male) who were discordant on the magnitude of error for the double trapezium illusion were given the Children's Personality Questionnaire and the Wechsler Intelligence Scale for Children (WISC). The Wilcoxon matched-pair signed-ranks test was used to determine whether the twins with relatively smaller magnitudes of error than their co-twins also manifested systematic differences on the personality factor scores and the WISC subtest scores. Among the female pairs, twins with smaller magnitudes of the illusion were relatively more stable (Factor C), more shrewd (Factor N), obtained higher scores on Similarities and Digit Span, and had longer reaction times before responding to the figures. Among the male pairs, similar trends were found but the differences were not as pronounced. The results are discussed in terms of Piaget's theory concerning children's deployment of attention and Kagan's reflective-impulsive dimension in children's cognitive judgments.

Antiplasmodial activity and cytotoxicity of 10ß-aminoquinolinylethylethers of artemisinin.

Each year roughly 800 000 people die of malaria, with 95% being African children. The shortcomings of the current drugs and the emergence of P. falciparum resistance to the artemisinin class of compounds warrant the search for new classes or derivatives. In search for such compounds, a series of 10ß-amino-quinolinylethylethers of artemisinin, previously synthesized from this laboratory were screened for antimalarial activity against both the chloroquine-susceptible 3D7 and -resistant K1 strains of P. falciparum. Their cytotoxicity was also assessed against HEK 293 and HepG2 cell lines.The parasitic and mammalian cells were incubated with compounds at various concentrations for 72 h. The antimalarial activity was determined using SYBR Green I-based fluorescence. For cytotoxicity determination, cells were grown to confluence and CellTiter-Glo luminescent cell viability assay was used.All derivatives proved to be active against both strains with good selectivity towards the parasitic cells. The derivative 11 featuring 2 artemisinin moieties and an aminoethylpiperazine linker was the most active of all. It possessed 17- and 166-fold more potency than artemether against 3D7 (EC50: 9.5 vs. 166 nM) and K1 (10.9 vs. 1723.3 nM), respectively, while was found to be as potent as artesunate against both strains.Derivative 11 stands as a good candidate to be further investigated primarily in vitro in comparison with an equimolar combination of chloroquine (CQ) and artemisinin to ascertain its advantages, if any, over the combination.