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PubMed2004

Mother-infant bedsharing is associated with an increase in infant heart rate.

OBJECTIVES: We hypothesized that mother-infant bed sharing, compared to solitary sleeping, would be associated with higher infant heart rates. The objective was to compare infant heart rates between the 2 environments and, secondarily, to test for relationships between heart rate and other, previously reported, differences in the same infants. DESIGN: Heart rate was measured in 15 infants over a bed-sharing night and a solitary-sleeping night. Eight of the 15 infants routinely bed shared with the mother at home; the other 7 routinely slept in a room alone. SETTING: The Sleep Disorders Center, University of California, Irvine Medical Center. PARTICIPANTS: Fifteen mother-infant pairs who met criteria for routinely bed sharing or sleeping solitarily. All were healthy, and infants were more than 38 weeks gestation at birth and 11 to 15 weeks old at the time of the study. INTERVENTIONS: None. RESULTS: Analysis of variance indicated that, irrespective of routine sleeping condition, heart rate was lower during solitary sleeping than during bed sharing in all sleep stages. Significant regressions were found with infant temperature. Heart-rate variability was higher during solitary sleeping than during bed sharing (both routine groups) in stages 1 and 2 and rapid eye movement sleep, but only stages 1 and 2 sleep effects were independent of basal heart rate. CONCLUSIONS: Infant heart rate is affected by the mother's presence in the sleep environment. The increase in sympathetic activity in stages 3 and 4 and rapid eye movement sleep might be partly explained by differences in thermoregulation between bed-sharing and solitary-sleeping environments. These results support the notion that sensory differences between bed-sharing and solitary-sleeping environments account for some of the physiologic differences between infant sleep in the 2 sleeping conditions.

Adult↗

PubMed2005

Heart rate variability in dairy cows-influences of breed and milking system.

Heart rate variability parameters in the time, frequency and nonlinear domains were investigated in two breeds of dairy cows (Austrian Simmental and Brown Swiss) milked either in an automatic milking system with partially forced cow traffic or in a herringbone milking parlour. Recordings were made of 24 cows (six of each breed and milking system) during lying, standing idle, and standing being milked, and analysed with linear mixed effects models taking the covariates time of day, live body weight, milk yield, stage of lactation and stage of pregnancy into account. Heart rate and nonlinear deterministic shares were higher, and heart rate variability in the time and frequency domains was lower, later in the day, in cows with higher body weight and in Simmental compared to Brown Swiss cows. Differences in the linear and nonlinear domains during lying indicated an increased level of chronic stress in cows in the automatic milking system with partially forced cow traffic, compared to cows milked in the herringbone milking parlour. No effects of milking system were found during milking, indicating that the stressor in the automatic milking system was not the milking process itself.

Analysis of Variance↗

PubMed1992

Multivariate genetic analysis of blood pressure and body size. The Medical College of Virginia Twin Study.

BACKGROUND: In subjects of all ages, those who weigh the most often have the highest blood pressure. Thus, in epidemiological studies, weight is the most important correlate of blood pressure. Using the data from the Medical College of Virginia Twin Study, we asked these questions: 1) Do the same genetic paths that regulate body size also regulate systolic and diastolic blood pressure? 2) Are there distinct genetic pathways that regulate each of these variables? 3) Does environment play a major regulatory role? 4) Are the correlations among these variables mainly due to genetic or environmental effects? 5) Do genetic paths that regulate body size mediate the correlation between systolic blood pressure and diastolic blood pressure? METHODS AND RESULTS: We ascertained 253 Caucasian twin pairs living in the Commonwealth of Virginia. The average age was 11.2 +/- 0.2 years. We used multivariate path analyses to investigate the genetic relations among systolic blood pressure, diastolic blood pressure, and body size. We found that there was a highly significant genetic relation between systolic blood pressure and body size and between systolic and diastolic blood pressure. There are genetic paths that are shared within these two sets of variables, but in each case, the paths for each pair appear to be separate from one another. CONCLUSIONS: These analyses provide a method to partition correlation coefficients found in epidemiological studies into genetic and environmental components. The correlations found among these three variables are in large part due to these genetic relations. We found no genetic relation between diastolic blood pressure and body size.

Blood Pressure↗

PubMed2004

Haplotype diversity across 100 candidate genes for inflammation, lipid metabolism, and blood pressure regulation in two populations.

Recent studies have suggested that a significant fraction of the human genome is contained in blocks of strong linkage disequilibrium, ranging from ~5 to >100 kb in length, and that within these blocks a few common haplotypes may account for >90% of the observed haplotypes. Furthermore, previous studies have suggested that common haplotypes in candidate genes are generally shared across populations and represent the majority of chromosomes in each population. The conclusions drawn from these preliminary studies, however, are based on an incomplete knowledge of the variation in the regions examined. To bridge this gap in knowledge, we have completely resequenced 100 candidate genes in a population of African descent and one of European descent. Although these genes have been well studied because of their medical importance, we demonstrate that a large amount of sequence variation has not yet been described. We also report that the average number of inferred haplotypes per gene, when complete data is used, is higher than in previous reports and that the number and proportion of all haplotypes represented by common haplotypes per gene is variable. Furthermore, we demonstrate that haplotypes shared between the two populations constitute only a fraction of the total number of haplotypes observed and that these shared haplotypes represent fewer of the African-descent chromosomes than was expected from previous studies. Finally, we show that restricting variation discovery to coding regions does not adequately describe all common haplotypes or the true haplotype block structure observed when all common variation is used to infer haplotypes. These data, derived from complete knowledge of genetic variation in these genes, suggest that the haplotype architecture of candidate genes across the human genome is more complex than previously suggested, with important implications for candidate gene and genomewide association studies.

Africa↗

PubMed2001

[Probable origin of the Robertsonian phenomena in domestic mice in Tunisia].

The Robertsonian phenomenon in house mice (Mus musculus domesticus) from Tunisia consists in the presence of only one 22-chromosome Robertsonian race (22Rb) carrying the maximum number of fusions observed until now. The 22Rb populations exclusively occupy urban centers in the Eastern-Central region of Tunisia where standard population with 40-all acrocentric chromosomes (40Std) occur in surrounding neighborhoods and rural environments. In addition to the habitat partition, allozyme and mitochondrial DNA analyses showed that the 22Rb populations were genetically differentiated from the 40Std ones. This differentiation mostly stemmed from an important decrease in genetic variability in the 22Rb populations from the Sahel towns. The extent of morphological, ecological and genetical divergence observed between these chromosomal races in Tunisia is in agreement with the predictions of the chromosomal speciation model of White which advocates that karyotypic differentiation between taxa can lead to their reproductive isolation and independent evolution. Such a process is verified if the Rb process in Tunisia results from local differentiation which is supported by both the genetic and morphological data. However, the hypothesis of an origin by introduction of these mice from another region of Tunisia or from another country cannot be totally dismissed. In this study, an allozymic analysis of mice (22Rb and 40Std) from the geographically distant city of Kairouan was performed. Results showed that 22Rb and 40Std mice from Kairouan shared the same high degree of variability, and were not genetically differentiated. This contrasts with the results registered in the two chromosomal races in the Sahel towns. Such data argue in favor of a local differentiation of the Robertsonian process in Tunisia and suggest that the decrease in variability of the structural nuclear genes in the Sahel 22Rb populations can be related to an introduction from Kairouan into a Sahel locality resulting in a founder effect or followed by a severe bottleneck prior to its dispersion throughout the Sahel region.

Animals↗

PubMed2002

Does education mediate the relationship between IQ and age of first birth? A behavioural genetic analysis.

This study presents a multivariate behavioural genetic analysis of the relationship between education, intelligence and age of first birth. Analyses investigated the mediational role of education in explaining the relationship between intelligence and age of first birth at both the phenotypic and behavioural genetic level. The data come from the National Longitudinal Survey of Youth (NLSY), a nationally representative survey that included genetically informative full- and half-sibling pairs (n = 1423 pairs). Respondents were aged 14 to 22 when contacted in 1979. Heritability estimates were 0.32, 0.50 and 0.06 for IQ, education and age of first birth, respectively. Shared environment estimates were 0.35, 0.23 and 0.20 respectively. Common genetic and shared environmental factors were substantial in explaining the relationship between intelligence and education, and also education and age of first birth. Education partially mediated the relationship between intelligence and age of first birth only in the phenotypic analyses. After considering the genetic and shared environmental factors that influence all three variables, evidence for mediation was less convincing. This pattern of results suggests that the apparent mediational role of education at the phenotypic level is in fact the result of underlying genetic and shared environmental influences that affect education, IQ and age of first birth in common.

Adolescent↗

PubMed2006

The impact of cost sharing of prescription drug expenditures on health care utilization by the elderly: own- and cross-price elasticities.

PURPOSE: To estimate healthcare demand elasticity and evaluate the impact of deductible/co-payment policy changes for prescription drugs on the use of drugs and physician visits among seniors with rheumatoid arthritis (RA) in British Columbia (BC), Canada. METHODS: According to the BC drug insurance program, prior to 2002, seniors co-paid the dispensing fee of each prescription to an annual maximum of CAN$ 200 (plan A). Starting in 2002, this plan was split into plan A and plan A1 (Premium Assistance) such that the co-payment amount equaled a maximum of CAN$ 25 and CAN$ 10 per prescription to an annual maximum of CAN$ 275 and CAN$ 200, respectively. Because of the endogeneity of the beneficiary price in the presence of a non-linear price schedule resulting from the cost-sharing policy, we implemented the method of instrumental variables to estimate price elasticities. The instrument was based on the price an individual would face under the new cost-sharing policy if their consumption remained at the pre-policy level. RESULTS: A total of 8017 patients were included. The estimated own-price elasticity of demand for prescription drugs and the cross-price elasticity of demand for physician visits were found to be negative and positive, respectively. The implications of our findings were that when cost sharing for prescription drugs increased, the demand for prescription drugs decreased and the demand for physician visits increased. CONCLUSIONS: In a predominantly publicly funded health care system, the selective introduction of market driven cost containment concepts such as patient cost-sharing might have the unintended impact of increasing overall health utilization for seniors with RA.

Aged↗

PubMed1991

Associations of daily mortality and air pollution in Los Angeles County.

We report results of a multiple regression analysis examining associations between aggregate daily mortality counts and environmental variables in Los Angeles County, California for the period 1970 to 1979. Mortality variable included total deaths not due to accidents and violence (M), deaths due to cardiovascular causes (CV), and deaths due to respiratory causes (Resp). The environmental variables included five pollutants averaged over Los Angeles County--total oxidants (Ox), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and KM (a measure of particulate optical reflectance). Also included were three metereological variables measured at the Los Angeles International Airport--temperature (Temp), relative humidity (RH), and extinction coefficient (Bext), the latter estimated from noontime visual range. To reduce the possibility of spurious correlations arising from the shared seasonal cycles of mortality and environmental variables, seasonal cycles were removed from the data by applying a high-pass filter. Cross-correlation functions were examined to determine the lag structure of the data prior to specifying and fitting the multiple regression models relating mortality and the environmental variables. The results demonstrated significant associations of M (or CV) with Ox at lag 1, temperature, and NO2, CO, or KM. Each of the latter three variables were strongly associated with daily mortality but also were highly correlated with one another in the high-frequency band, making it impossible to uniquely estimate their separate relationships to mortality. The results of this study show that small but significant associations exist in Los Angeles County between daily mortality and three separate environmental factors: temperature, primary motor vehicle-related pollutants (e.g., CO, KM, NO2), and photochemical oxidants.

Air Pollutants↗

PubMed2002

Variability within alpha- and beta-adrenoreceptor genes as a predictor of cardiovascular function at rest and in response to mental challenge.

OBJECTIVES: To investigate the association between polymorphic variation in alpha- and beta-adrenoreceptor genes and cardiovascular activity at rest and in response to psychological challenge in a sample in which the heritability of these cardiovascular phenotypes may be established. METHODS: Several common polymorphisms were characterized within ADRA1B (alpha1B), ADRA2A (alpha2A), ADRB1 (beta1) and ADRB2 (beta2) and examined in relation to heart rate (HR) and systolic (SBP) and diastolic (DBP) blood pressure, both at rest and in response to stress. Participants were 309 European-American, young adult men and women (including 101 monozygotic and 44 dizygotic twin pairs). RESULTS: In the full sample, participants carrying any G allele at base pair (bp) 1165 in ADRB1 exhibited elevated resting SBP and DBP and a larger DBP response to mental challenge compared to homozygotes for the C allele (P < 0.04). An AA genotype at bp 145 in ADRB1 was also associated with higher resting SBP and DBP than AG or GG genotypes (P < 0.03). At bp 46 in ADRB2, GG homozygotes had higher resting DBP than subjects possessing any A allele (P < 0.05). For the same polymorphism, however, AG heterozygotes showed lower SBP than both AA and GG homozygotes (P < 0.05). In a subsample of genetically unrelated individuals, ADRB1 (1165) continued to predict resting SBP, DBP and DBP response to stress (P < 0.03), while ADRB2 (46) was associated with resting SBP (P < 0.04) but not DBP. Finally, the degree of allele sharing at ADRB1 (1165) also predicted variability in SBP and DBP at rest among dizygotic twin pairs (P < 0.04). CONCLUSIONS: These results indicate that some polymorphic variation within adrenoreceptor genes contributes to interindividual variability in resting SBP and DBP and in DBP response to mental challenge.

Adult↗

PubMed1990

Regression modelling of HLA haplotype sharing in affected siblings.

A link between the HLA system and disease susceptibility can be assessed through the observation of families containing two or more affected siblings. Departures from Mendelian inheritance of the parental haplotypes among the affected siblings are an indication of such a relationship. Other variables, such as environmental factors, may also be related to disease susceptibility. An approach to examining the degree of haplotype sharing and the effect of other variables of interest on observed sharing is presented and two examples analyzed.

Biometry↗

PubMed1986

Twin study methodology and variability in xenobiotic placental metabolism.

The present study assesses the contribution of genetic and environmental factors to variability in placental aryl hydrocarbon hydroxylase and glutathione transferase activities using twin study methodology. Twin placentas were collected at the time of delivery. The placenta, except for a single layer of maternal decidua, consists of fetal tissue exhibiting fetal genotype. Microsomal and cytosolic fractions were prepared under stringent protocols to prevent enzyme activity loss. There were two monozygotic-monochorionic pairs, five monozygotic-dichorionic pairs, and 21 dizygotic-dichorionic pairs that showed measurable aryl hydrocarbon hydroxylase activity using the direct fluorometric assay. Most of the mothers were smokers. Aryl hydrocarbon hydroxylase activity was measured with two different substrates, benzo(a)pyrene and 7-ethoxyresorufin. Glutathione transferase activity was measured using glutathione and 1-chloro-2,4-dinitrobenzene as substrates for a spectrophotometric assay that follows the conversion of the aromatic substrate. Twin pair similarity was calculated with intraclass correlation coefficients. There is a high correlation between the activities of the two aryl hydrocarbon hydroxylase substrates (r = .814), but no correlation between aryl hydrocarbon hydroxylase and glutathione transferase activity levels. There is little evidence of genetic variability underlying the variation in the enzyme activities because monozygotic-dichorionic twins are no more similar to each other for the three substrate activities than are the dizygotic twins. To delineate the prenatal environmental influences on placental enzyme variability, dichorionic placentation was subdivided further into contiguous and noncontiguous placental position. Lower intraclass correlation coefficients are obtained for the dizygotic twins whose placentas were noncontiguous compared with dizygotic twins with contiguous placentas. The results suggest that most of the variability seen in these placental enzyme systems is due to environmental differences within uteri, rather than genetic variability in the population. This does not negate the possibility that between-pair, or population, variability may have a genetic component, because even dizygotic twins share a large proportion of their genes. This study points out that a significantly variable environment exists within the human uterus.

Aryl Hydrocarbon Hydroxylases↗

PubMed2003

Shared, not unique, components of personality and psychosocial functioning predict depression severity after acute-phase cognitive therapy.

In a sample of 100 patients with recurrent major depression, we collected depression severity data early and late in acute-phase cognitive therapy, plus a wide range of psychosocial variables that have been studied extensively in depression research, including measures of interpersonal, cognitive, and social functioning, and personality traits using an inventory that is linked with the Big-Three tradition in personality assessment theory. By assessing this broad range of variables in a single study, we could examine the extent to which relations of these variables with depression were due to (a) a common factor shared across this diverse set of constructs, (b) factors shared among each type of construct (personality vs. psychosocial measures), or (c) specific aspects of the individual measures. Only the most general factor shared across the personality and psychosocial variables predicted later depression.

Acute Disease↗

PubMed1985

Segmental homology between T-cell receptors and immunoglobulin variable regions: evidence that antisera to synthetic JH1 peptide react with murine and human T-cell products.

To determine precisely the nature of serological determinants shared between T-cell surface molecules and immunoglobulin variable regions, the capacity of antisera directed against a synthetic peptide corresponding to the entire JH 1 region of classical immunoglobulin plus five residues of the D region were tested for their capacity to bind to T-cell membranes and isolated T-cell products. The anti-JH 1 antisera reacted with normal and monoclonal in vitro grown T-cell lines as judged by microhemagglutination and binding in enzyme-linked immunosorbent assays. Immunologically cross-reactive membrane components disclosed by immunoblot transfer analysis ("Western blots") consisted of major components in the molecular weight range 30-35,000 and minor components in the range 65-70,000. The major product of the human T-cell leukemia line MOLT-3 had an approximate mass of 34,000 Da, a value consistent with the predicted size of the molecule specified by the recently described putative T-cell receptor gene YT35. The 65 to 70,000-Da components are most probably tightly associated dimers of the 30 to 35,000-Da forms. It was possible to align the JH sequences of molecules reactive with the anti-JH 1 antisera and other characterized VH sequences of molecules known to be cross-reactive with T-cell products. This facilitated a comparison disclosing clear segmental homology between the protein sequence derived from the YT35 gene and immunoglobulin VH framework regions sharing approximately 50% of sequence identity. The identification of VH-related T-cell products (termed VT-bearing molecules) with products of putative T-cell receptor genes gained further support by N-terminal sequence of the 68,000-Da product of the 70-N2 T-cell line which showed homology to the predicted N-terminal region of the YT35 product. These serological and protein chemical data, coupled with the comparison to gene sequence, show that T-cell components that bear serological determinants cross-reactive with VH show segmental homology with products of putative T-cell receptor genes and immunoglobulin VH.

Animals↗

PubMed2006

Rate of acquisition, adult age, and basic cognitive abilities predict forgetting: new views on a classic problem.

Rate of forgetting is putatively invariant across individuals, sharing few associations with individual-differences variables known to influence encoding and retrieval. This classic topic in learning and memory was revisited using a novel statistical application, multilevel modeling, to examine whether (a) slopes of forgetting varied across individuals and (b) observed individual differences in forgetting shared systematic relations with adult age, learning speed, and cognitive ability. Participants (N = 136) received mnemonic training prior to memorizing 4-digit numbers to perfection, and retention was tested immediately after training and after 30 min, 24 hr, 7 weeks, and 8 months. Slower rate of learning to criterion, older age, and poorer cognitive performance predicted accelerated forgetting with associations most pronounced within 24 hr from baseline. Observed correlates of differential forgetting slopes are similar to those previously found to affect encoding, suggesting continuity rather than asymmetry of prediction for these memory processes.

Adult↗

PubMed2005

The US twin study of age-related macular degeneration: relative roles of genetic and environmental influences.

CONTEXT: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among older individuals in many parts of the world. The relative importance of genes and environment in the etiology of this major public health problem is not well understood. OBJECTIVE: To investigate the impact of genetic and environmental factors. PARTICIPANTS: Living twins in the National Academy of Sciences-National Research Council World War II Veteran Twin Registry born between 1917 and 1927. METHODS: Twins were surveyed for the known presence of macular degeneration. Enrolled twins underwent a standardized examination and fundus photography. Age-related macular degeneration evaluation was completed for 840 elderly male twins, 210 monozygotic and 181 dizygotic complete twin pairs, both concordant and discordant for presence or absence of AMD, and 58 singletons. A bivariate twin model incorporating initial screening ascertainment and age effects was employed to partition variation in liability to AMD and signs of maculopathy into additive genetic, common environment, and unique environment components. MAIN OUTCOME MEASURE: Heritability of AMD grade and signs of maculopathy based on clinical examination and fundus photographs. RESULTS: Of the 840 twins, 331 had no signs of maculopathy and 241 had early signs, while 162 had intermediate AMD and 106 had advanced AMD. Heritability (additive genetic) estimates were significant for overall AMD grade (0.46) and for intermediate (0.67) and advanced (0.71) AMD. Significant unique environmental proportions of variance were also observed for these AMD variables (0.37, 0.19, and 0.24, respectively). Shared or common environmental contributions were not significant (0.05-0.17). For specific macular drusen and retinal pigment epithelial characteristics, significant genetic (0.26-0.71) and unique environmental (0.28-0.64) proportions of variance were detected. CONCLUSIONS: Genetic factors play a substantial role in the etiology of AMD and associated macular characteristics, explaining 46% to 71% of the variation in the overall severity of the disease. Environmental factors unique to each twin also contribute to the occurrence of this disease. This quantification of relative genetic and environmental contributions to the development of AMD should guide future research on this important cause of blindness.

Aged↗

PubMed1999

Associations between daily physical activity and physical fitness in Flemish males: A cross-sectional analysis.

The relationship of physical activity to several components of physical fitness was investigated in a sample of 166 males 40 years of age. In addition to Pearson correlations, multivariate canonical correlations were calculated. Physical activity during work (work index), sport (sport index), and leisure time (leisure time index) was assessed by the Baecke questionnaire. Physical fitness included cardiorespiratory fitness measures, the body mass index (BMI), the sum of seven skinfold thicknesses (SKI), percentage body fat (PFAT), balance, and several tests of muscle strength and endurance, flexibility, and speed of limb movement. More than 86% of the variance was shared by the two first canonical variables. The first canonical variable can be interpreted as a health-related fitness function. Carciorespiratory fitness, balance, speed of limb movement, explosive strength, and trunk muscle strength are clearly related to this function. From the physical activity measures, the Baecke sport index correlated significantly with this health-related fitness function. The second canonical variable can be explained as a fatness function, since body weight, BMI, SKI, and PFAT showed the highest correlations with the variable. The Baecke work index was inversely related to this canonical variable. The sample was also divided into physical activity groups in order to look for differences in physical fitness. The data indicate that physical activity during work was modestly, but inversely related to adiposity. Sport activity was beneficially associated to several fitness components, including cardiorespiratory fitness, trunk muscle strength, and upper body muscular endurance. Am. J. Hum. Biol. 11:587-597, 1999. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗

PubMed1999

Design of artificial neural network and its applications to the analysis of alcoholism data.

Artificial neural networks were applied to the alcoholism data to reveal nonlinear relationships between intermediate phenotypes, marker identity-by-descent sharing, and the affection status. A variable number of hidden units were considered to achieve a balance between the minimal mean-squared error and over-fitting of the data. The predictability of the affection status based on intermediate phenotype information (event-related potential 300, monoamine oxidase, and gender) was 65% to 75%, and sensitivity/specificity ranged around 50% to 80%. The IBD approach succeeded in identifying the same marker as previous studies, but also found additional peaks.

Alcoholism↗

PubMed1995

Site-specific recombination in the replication terminus region of Escherichia coli: functional replacement of dif.

The replication terminus region of the Escherichia coli chromosome encodes a locus, dif, that is required for normal chromosome segregation at cell division. dif is a substrate for site-specific recombination catalysed by the related chromosomally encoded recombinases XerC and XerD. It has been proposed that this recombination converts chromosome multimers formed by homologous recombination back to monomers in order that they can be segregated prior to cell division. Strains mutant in dif, xerC or xerD share a characteristic phenotype, containing a variable fraction of filamentous cells with aberrantly positioned and sized nucleoids. We show that the only DNA sequences required for wild-type dif function in the terminus region of the chromosome are contained within 33 bp known to bind XerC and XerD and that putative active site residues of the Xer recombinases are required for normal chromosome segregation. We have also shown that recombination by the loxP/Cre system of bacteriophage P1 will suppress the phenotype of a dif deletion strain when loxP is inserted in the terminus region. Suppression of the dif deletion phenotype did not occur when either dif/Xer or loxP/Cre recombination acted at other positions in the chromosome close to oriC or within lacZ, indicating that site-specific recombination must occur within the replication terminus region in order to allow normal chromosome segregation.

Base Sequence↗