Adrenaline-mediated glycogen phosphorylase activation is enhanced in rat soleus muscle with increased glycogen content.

The effect of glycogen content on the activation of glycogen phosphorylase during adrenaline stimulation was investigated in soleus muscles from Wistar rats. Furthermore, adrenergic activation of glycogen phosphorylase in the slow-twitch oxidative soleus muscle was compared to the fast-twitch glycolytic epitrochlearis muscle. The glycogen content was 96.4 +/- 4.4 mmol (kg dw)(-1) in soleus muscles. Three hours of incubation with 10 mU/ml of insulin (and 5.5 mM glucose) increased the glycogen content to 182.2+/-5.9 mmol (kg dw)(-1) which is similar to that of epitrochlearis muscles (175.7+/-6.9 mmol (kg dw)(-1)). Total phosphorylase activity in soleus was independent of glycogen content. Adrenaline (10(-6) M) transformed about 20% and 35% (P < 0.01) of glycogen phosphorylase to the a form in soleus with normal and high glycogen content, respectively. In epitrochlearis, adrenaline stimulation transformed about 80% of glycogen phosphorylase to the a form. Glycogen synthase activation was reduced to low level in soleus muscles with both normal and high glycogen content. In conclusion, adrenaline-mediated glycogen phosphorylase activation is enhanced in rat soleus muscles with increased glycogen content. Glycogen phosphorylase activation during adrenaline stimulation was much higher in epitrochlearis than in soleus muscles with a similar content of glycogen.

Consanguinity and recurrence risk of birth defects: a population-based study.

Recurrence risks give insight into the causes of birth defects and are useful in genetic counseling. There are few population-based studies of recurrence of birth defects for subsequent sibs with consanguineous parents. The aim of this study was to estimate and compare the recurrence risk of birth defects for offspring of first cousins and nonconsanguineous parents. The study population consisted of all single births with a previous sib born in Norway between 1967 and 1995. Altogether 660,398 children had nonconsanguineous parents, and 3,583 had parents who were first cousins. For nonconsanguineous parents the risk of a birth defect for the subsequent sib was 15 per 1,000 births (95% confidence interval: 14.5-15.1) if the previous child did not have a birth defect and 33 (95% confidence interval: 30-37) if the previous child had a birth defect. For parents who were first cousins the risk of a birth defect for the subsequent sib was 36 per 1,000 (95% confidence interval: 30-42) if the previous child did not have a birth defect and 68 (95% confidence interval: 33-122) if the previous child had a birth defect. The risk of recurrence of birth defects is higher for subsequent sibs with first-cousin parents than for those with nonconsanguineous parents. This difference indicates the degree to which the increased homozygosity among offspring of consanguineous parents influences the risk of recurrence of birth defects.

Day care attendance, recurrent respiratory tract infections and asthma.

OBJECTIVE: Our objective was to use a causal model for childhood asthma to determine whether the effect of day care attendance on asthma was mediated by recurrent respiratory tract infections. DESIGN: A cross-sectional survey among 1447 children aged 6-16 years in Oslo. Their parents completed written questionnaires. A recursive logit model was used to estimate direct effects in terms of adjusted odds ratios (aOR). RESULTS: Year of birth, number of siblings and length of maternal education were significantly associated with day care attendance. Attendance at day care increased the risk of early infections, aOR = 1.8 (1.3-2.5), and infections were associated with asthma, aOR = 4.9 (3.4-7.3). The crude association between day care and asthma was cOR = 1.5 (1.0-2.2), whereas the estimated direct effect was small and nonsignificant, aOR = 1.2 (0.8-1.9). The results may be influenced by overreporting of infections among parents of children with asthma. CONCLUSIONS: Our results suggest that children who attend day care have an increased risk of asthma with early infections as a mediator of risk.

Alcohol and sexual victimization: a longitudinal study of Norwegian girls.

In a study of sexual victimization and alcohol consumption, a population sample of Norwegian adolescents from the Oslo area was followed-up through five data collections over a 6-year time span. By means of generalized structural equation modeling, alcohol-related predictors and consequences of sexual assaults were investigated; 17% of the girls reported that they had been sexually assaulted at some time: 7% in childhood, 6% in early adolescence (13-16 years) and 4% in late adolescence (17-19 years). Only 1% of the boys reported having been sexually victimized. Female childhood sex victims reported increased alcohol consumption from their mid-teens, with dramatic increase in alcohol-related problems (using DSM-III-R criteria) at the end of their teens. However, the analyses showed that alcohol consumption was not influenced by childhood sexual abuse when parental use of tobacco and alcohol and normative standards imparted to their children were taken into consideration as confounding variables. There was, on the other hand, a strong effect on alcohol problems. Thus, the victims of childhood sexual abuse seem to be at high risk for alcohol abuse and dependency. Further, early alcohol debut and high alcohol consumption combined with permissive parental norms increased the risk of sexual assault in early adolescence. The girls who were assaulted in early adolescence also reported a high number of sexual partners and early intercourse debut. There was no increase in subsequent alcohol consumption after assaults in this group. Late adolescent victims did not report increased alcohol consumption either prior to or after the assault.

PIP: The association between childhood sexual victimization and alcohol consumption was investigated in a longitudinal study (1987-93) of 465 adolescents (249 girls and 216 boys) from Oslo, Norway. Mean age was 13.7 years at study entry and 19.3 years at study completion. 17.3% of female respondents had a sexual abuse history; 7% were abused in childhood, 6% in early adolescence (13-16 years), and 4% in late adolescence (17-19 years). Only 1% of the boys reported having been sexually victimized. Girls who were victimized in early adolescence had the lowest mean age at first alcohol debut (13.5 years, compared with 15.2 years among nonvictimized girls). Female child sexual abuse victims reported increased alcohol consumption from their mid-teens, with dramatic increases in alcohol-related problems at the end of their teens. The analyses showed that alcohol consumption was not influenced by childhood sexual abuse when parental use of tobacco and alcohol and normative standards imparted to their children were considered as confounding variables. However, the strong effect of victimization on alcohol problems persisted after controls for parental confounding factors. Early alcohol debut and high alcohol consumption, combined with permissive parental norms, increased the risk of sexual assault in early adolescence. Girls who were sexually victimized in early adolescence also reported an early intercourse debut and a high number of sexual partners. Late adolescent victims, on the other hand, did not report increased alcohol consumption either before or after their sexual assault.

Ecstasy and new patterns of drug use: a normal population study.

AIMS: (i) To describe illegal drug use patterns in an adolescent normal population sample with special emphasis on MDMA, ecstasy; (ii) to investigate where ecstasy is introduced in a hypothesized drug use sequence, and (iii) to contrast the predictors of ecstasy use with those of other illegal substances. Special attention was given to the relationship to subcultural music preferences and house-party-going. DESIGN: A school-based survey of the total cohort of adolescents enrolled in the school system in a city. PARTICIPANTS: 10,812 adolescents, age 14-17 years, response rate 94.3%. SETTING: Oslo, the capital and only metropolitan town in Norway. MEASUREMENTS: Social class was measured by the occupation standard ISCO 88, questions were posed as regards frequency of alcohol use and alcohol intoxication, cigarette smoking and use of cannabis, amphetamines, ecstasy and heroin. Alcohol problems were measured by a shortened version of Rutgers Alcohol Problem Index (RAPI), conduct problems were measured according to the four categories of acts forming the basis of the diagnosis conduct disorder in DSM-IV, internalizing mental health problems were measured using items from Hopkins Symptoms Checklist (HCL). A number of questions were asked as regards subcultural music preferences and house-party-going. STATISTICAL MODELS: A hypothesized cumulative sequence in drug use was investigated by means of latent class analysis, and the predictors of the various patterns of drug use were estimated and compared by means of multinominal logistic regression analysis. FINDINGS: The use of ecstasy was often intermingled with the use of cannabis, amphetamines and heroin, in a pattern of polydrug use. The latent class analysis revealed the following drug use sequence: (1) alcohol, (2) cigarettes, (3) cannabis, (4) amphetamines, (5) ecstasy and (6) heroin. There was no significant association between ecstasy use and parental social class or residential area of the town. All patterns of illegal drug use were highly associated with cigarette smoking, alcohol use, alcohol problems and conduct problems, whereas the associations with internalizing mental health problems were of less magnitude. Multinominal logistic regression analysis revealed that the use of ecstasy (E) was significantly more weakly associated with cigarette smoking than were the use of cannabis only (C), amphetamines (A) and the combination of ecstasy and amphetamines (A + E). The association between E and conduct problems (CP) was weaker than the association between CP and A and A + E. Finally, there were associations between E and A + E and House/Techno preferences and house-party-going, which were not found for C and A. CONCLUSIONS: Ecstasy is used by adolescents who use other legal and illegal substances in a polydrug-use pattern. The substance is introduced late in a hypothesized drug use sequence. Even so, ecstasy use seems to differ from the use of, e.g. amphetamines, in that the association with smoking and conduct problems is weaker and that the associations with subcultural music preferences and house-party-going are much stronger.

Paternal contribution to birth weight.

STUDY OBJECTIVE: Understanding causes of variation in birth weight has been limited by lack of sufficient sets of data that include paternal birth weight. The objective was to estimate risks of low birth weight dependent on parental birth weights and to estimate father-mother-offspring correlations for birth weight to explain the variability in birth weight in terms of effects of genes and environmental factors. DESIGN: A family design, using trios of father-mother-firstborn child. SETTING: The complete birth population in Norway 1967-98. PARTICIPANTS: 67 795 families. MAIN RESULTS: The birth weight correlations were 0.226 for mother-child and 0.126 for father-child. The spousal correlation was low, 0.020. The relative risk of low birth weight in the first born child was 8.2 if both parents were low birth weight themselves, with both parents being above 4 kg as the reference. The estimate of heritability is about 0.25 for birth weight, under the assumption that cultural transmission on the paternal side has no effect on offspring prenatal growth. CONCLUSIONS: Paternal birth weight is a significant and independent predictor of low birth weight in offspring. The estimate of the heritability of birth weight in this study is lower than previously estimated from data within one generation in the Norwegian population.

The problem of structural indeterminacy in multidimensional symptom report instruments. The case of SCL-90-R.

The factor structure of SCL-90-R items and scales was analyzed using both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Results of CFA studies at the item-level failed to support the original nine-factor model, as well as several alternative models and EFA suggested very different dimensionality, depending on which criteria were used. Analyses at the scale-level (i.e. the nine original symptom dimensions) suggested that a one- or two-factor model was satisfactory according to descriptive goodness of fit criteria. However, using the likelihood ratio test, specification of four factors was necessary to avoid rejection. According to the likelihood ratio test in a multi-group analysis, a lack of factorial invariance across gender was indicated. Moreover, the factorial structure of the instrument was clearly different across levels of negative affectivity (NA); the dimensionality was substantially higher in the low-NA group as compared to the high-NA group. It is concluded that we are confronted with a profound structural indeterminacy problem and that factor analytic methods and model acceptance criteria alone are insufficient to solve this problem. The indeterminacy problem can be accounted for, at least in part, by the complex logical-semantical structure of SCL-90-R items and scales and the role of the NA trait as a structure generating factor.

Depression during pregnancy and after delivery: a repeated measurement study.

The aim of this study was to examine the risk of depression in the postpartum period (first four months after delivery) as compared to the remaining postnatal year and the pregnancy period. All postpartum women from two municipalities in Norway were included in a questionnaire study of mental health (n = 416). Over 50% of the women (n = 259) answered an identical questionnaire at an additional time either before or after the postpartum period. The level of depression was measured by the Edinburgh Postnatal Depression Scale (EPDS) and the Hopkins Symptom Check List-25 items (SCL-25). The point prevalence of depression (EPDS> or =10) in the first four months postpartum did not differ significantly as compared to other time periods during pregnancy and the postnatal year. This finding remained also after controlling for other risk factors of depression; high score on the life event scale, prior depression and poor partner relationship. There was a non-significant trend of lower prevalence of depression during early pregnancy and after the first eight postnatal months. In conclusion, our findings suggest that the first four months postpartum were not distinguished by higher depression prevalence as compared to other time periods during pregnancy and the first postnatal year.

Alcohol consumption debut: predictors and consequences.

OBJECTIVE: The aim of this study was to investigate the predictors of the timing of alcohol consumption debut and to analyze possible associations between the timing of debut and later alcohol consumption and possible alcohol-related problems. METHOD: A population sample of 465 adolescents (249 girls) from the greater Oslo area was followed up through five data collections over a 6-year span. By means of generalized structural equation modeling--accommodating survival variables--parental and friends' influences on debut age were estimated. Further, the consequences of the age of debut on subsequent alcohol consumption and alcohol problems were studied, taking other influences into consideration. In particular, possible gender differences were investigated. RESULTS: The mean age for alcohol consumption debut was 14.8 years. The age of alcohol debut had an independent effect on both future alcohol consumption and the development of alcohol-related problems, and the effects were invariant across sex. According to the estimated model, a 10% delay in debut age will lead to a 35% decrease in subsequent expected alcohol consumption. CONCLUSIONS: Alcohol debut was an excellent predictor of subsequent alcohol consumption and alcohol problems. The strong preventive implication is that interventions should be implemented in order to postpone alcohol debut age. A weak implication is that preventive measures should be implemented for the early onset drinkers. Further, it seems to be important to give high priority to more thorough studies on the exact nature of the relationships we have investigated here.

The Role of Negative Affectivity in Self assessment of Health: A Structural Equation Approach.

The relationship between negative affectivity (NA, i.e. the Neuroticism trait and transient distress), self-reported medical condition and somatic complaints was assessed in structural equation models also including personality (the Big Five personality domains), socio-demographic, and health behaviour variables. The results indicated that the individual's current distress level and medical condition were by far the strongest predictors of somatic complaints. Compared to the other Big Five domains, Neuroticism was clearly the most important variable in all the models tested; it evidenced substantial direct effects on both distress level and medical condition, and a significant indirect effect on somatic complaints. On the whole, the effects of the sociodemographic and health behaviour variables were of only marginal importance as compared to NA.

Biometrical modeling of twin and family data using standard mixed model software.

Biometrical genetic modeling of twin or other family data can be used to decompose the variance of an observed response or 'phenotype' into genetic and environmental components. Convenient parameterizations requiring few random effects are proposed, which allow such models to be estimated using widely available software for linear mixed models (continuous phenotypes) or generalized linear mixed models (categorical phenotypes). We illustrate the proposed approach by modeling family data on the continuous phenotype birth weight and twin data on the dichotomous phenotype depression. The example data sets and commands for Stata and R/S-PLUS are available at the Biometrics website.

A simple correction for ties when censoring times depend on covariates.

We point out that the conventional methods for ties correction may be seriously biased when censoring times depend on covariates. A simple modification to the Efron correction method is suggested which works remarkably well in simulation studies. The method corresponds closely to breaking ties by random ordering. The modified correction method is easy to implement and computationally no more demanding than the Efron correction.

Day care center characteristics and children's respiratory health.

UNLABELLED: Day care centers provide an important exposure arena with potential harmful health effects for children. This study has linked health effect data from a survey among 942 3-5-year-old Oslo children with information on day care center characteristics collected during inspection of the 175 day care centers these children attended. The aim of the study was to estimate associations between dampness problems and other building characteristics and several respiratory health outcomes. Dampness problems (sign of molds, water leakage, damage to floor/wall) were observed in 51% of the day care centers. In multiple logistic regression analyses none of the studied symptoms and diseases (nightly cough, blocked or runny nose without common cold, wheeze, heavy breathing or chest tightness, the common cold, tonsillitis/pharyngitis, otitis media, bronchitis, pneumonia, asthma, and allergic rhinitis) were systematically associated with dampness problems or type of ventilation in day care centers. None of the studied indicators of day care center exposures were found to have a clear effect on day care children's respiratory health. Even so this study does not rule out negative health effects of day care center exposures. The study demonstrates that population-based studies of these relations are demanding with regard to assessment of exposure and health outcomes. PRACTICAL IMPLICATIONS: Simple and easy-to-register indicators of exposures like dampness problems and type of ventilation assessed in 175 day care centers were not related to respiratory health among 3-5-year-old Norwegian children attending the day care centers. The study does not rule out negative health effects of day care center exposures, but demonstrates methodological challenges needed to be addressed in studies of health effects of the day care environment.

Design and Analysis of Monte Carlo Experiments: Attacking the Conventional Wisdom.

The design and analysis of Monte Carlo experiments, with special reference to structural equation modelling, is discussed in this article. These topics merit consideration, since the validity of the conclusions drawn from a Monte Carlo study clearly hinges on these features. It is argued that comprehensive Monte Carlo experiments can be implemented on a PC if the experiments are adequately designed. This is especially important when investigating modern computer intensive methodologies like resampling and Markov Chain Monte Carlo methods. We are faced with three fundamental challenges in Monte Carlo experimentation. The first problem is statistical precision, which concerns the reliability of the obtained results. External validity, on the other hand, depends on the number of experimental conditions, and is crucial for the prospects of generalising the results beyond the specific experiment. Finally, we face the constraint on available computer resources. The conventional wisdom in designing and analysing Monte Carlo experiments embodies no explicit specification of meta-model for analysing the output of the experiment, the use of case studies or full factorial designs as experimental plans, no use of variance reduction techniques, a large number of replications, and "eyeballing" of the results. A critical examination of the conventional wisdom is presented in this article. We suggest that the following alternative procedures should be considered. First of all, we argue that it is profitable to specify explicit meta-models, relating the chosen performance statistics and experimental conditions. Regarding the experimental plan, we recommend the use of incomplete designs, which will often result in considerable savings. We also consider the use of common random numbers in the simulation phase, since this may enhance the precision in estimating meta-models. The use of fewer replications per trial, enabling us to investigate an increased number of experimental conditions, should also be considered in order to improve the external validity at the cost of the conventionally excessive precision.

Changes in condom use after HIV diagnosis.

We investigated changes in condom use after HIV diagnosis. The study population comprised 78 asymptomatic HIV-infected subjects recruited from a clinic in Oslo, Norway, during 1988-92. In total, 240 follow-up visits were carried out. The response variable was repeated measurements of whether or not condoms were always used during anal/vaginal intercourse at follow-up. The explanatory variables were: time from HIV diagnosis to follow-up, exposure group (heterosexually infected, homosexual men, or infected through injecting drug use), time of HIV diagnosis (before 1987 or later), and history of condom use before HIV diagnosis. Random effects logistic regression analysis was used to study incremental changes in condom use, accommodating an unbalanced repeated measurement design. The use of condoms increased monotonously over time after HIV diagnosis in all exposure groups. Condom use was least likely among injecting drug users, subjects diagnosed before 1987 and subjects without a history of frequent condom use before HIV diagnosis.

[Day care centers, infections and asthma]. / Barnehage, infeksjoner og astma.

BACKGROUND: Our objective was to use a causal model for childhood asthma to determine whether the effect of day care attendance on asthma was mediated by recurrent respiratory tract infections. MATERIAL AND METHODS: The study is based on a cross-sectional survey among 1,447 children aged 6-16 years in Oslo. Their parents completed written questionnaires. A recursive logit model was used to estimate direct effects in terms of adjusted odds ratios (aOR). RESULTS: Year of birth, number of siblings and length of maternal education were significantly associated with after-school care attendance. Attendance increased the risk of early infections, aOR = 1.8 (1.3-2.5), and infections were associated with asthma, aOR = 4.9 (3.4-7.3). The crude association between after-school care and asthma was cOR = 1.5 (1.0-2.2), whereas the estimated direct effect was small and non-significant, aOR = 1.2 (0.8-1.9). The results may be influenced by over-reporting of infections among parents with children with asthma. INTERPRETATION: Our results suggest that children who attend day care have an increased risk of asthma, with early infections as a mediator of risk.

Mortality and temperature in Oslo, Norway, 1990-1995.

The associations between temperature and daily mortality was studied among the citizens of Oslo, Norway, 1990-1995. Data on daily mortality were linked with daily temperatures, relative humidity, wind velocity and air pollution. At temperatures below 10 degrees C, a 1 degrees C fall in the last 7 days average temperature increased the daily mortality from all diseases by 1.4%, respiratory diseases 2.1%, and cardiovascular diseases 1.7%. Above 10 degrees C, there was no statistically significant increase in daily mortality, except for respiratory mortality, which increased by 4.7% per 1 degrees C increase in the last 7 days average temperature. Daily mortality in Oslo increases with temperatures falling below 10 degrees C. The increase starts at lower temperatures than shown in warmer regions of the world, but at higher temperatures than in regions with even colder climates. As well insulated and heated dwellings are standard in Norway today, more adequate clothing during outdoor visits is probably the most important preventive measure for temperature related mortality.

Parameterization of multivariate random effects models for categorical data.

Alternative parameterizations and problems of identification and estimation of multivariate random effects models for categorical responses are investigated. The issues are illustrated in the context of the multivariate binomial logit-normal (BLN) model introduced by Coull and Agresti (2000, Biometrics 56, 73-80). We demonstrate that the BLN model is poorly identified unless proper restrictions are imposed on the parameters. Moreover, estimation of BLN models is unduly computationally complex. In the first application considered by Coull and Agresti, an identification problem results in highly unstable, highly correlated parameter estimates and large standard errors. A probit-normal version of the specified BLN model is demonstrated to be underidentified, whereas the BLN model is empirically underidentified. Identification can be achieved by constraining one of the parameters. We show that a one-factor probit model is equivalent to the probit version of the specified BLN model and that a one-factor logit model is empirically equivalent to the BLN model. Estimation is greatly simplified by using a factor model.

Mental disorder among refugees and the impact of persecution and exile: some findings from an out-patient population.

BACKGROUND: Refugees have long been considered at risk for mental disorder. We sought to characterise this risk in an out-patient refugee sample by analysing the relationship between psychiatric symptoms and dysfunction, and between symptoms and the socio-demographic background and stressors specific to this refugee sample. METHOD: A consecutive sample of 231 refugee patients referred to the psychiatric out-patient unit at the Psychosocial Centre for Refugees, University of Oslo, was examined with a semi-structured interview guide, Brief Psychiatric Rating Scale (BPRS), Hopkins Symptom Check-List (HSCL-25) and a check-list for post-traumatic symptoms (PTSS-10). Global Assessment of Function (GAF) scores were obtained; and the data were analysed using nine predictor variables. RESULTS: It was found that 46.6% of the patients had a post-traumatic stress disorder according to the criteria for DSM-III-R as the main diagnosis, while the mean GAF score for the patients was 57.3. Analysis of the GAF and BPRS data did not reveal any predictor of psychotic behaviour. However, torture emerged as an important predictor of emotional withdrawal/retardation. Also, age, gender and no employment or education predicted for anxiety/depression, while refugee status and no employment or school predicted for hostility/aggression. CONCLUSIONS: The results confirm earlier findings that refugees constitute a population at risk for mental disorder. Past traumatic stressors and current existence in exile constitute independent risk factors. However, stressors other than those discussed here appear to be important also, particularly with regard to psychotic symptoms.

Consanguinity and recurrence risk of stillbirth and infant death.

OBJECTIVES: The aim of this study was to estimate the recurrence risk for stillbirth and infant death and compare results for offspring of first-cousin parents with results for offspring of unrelated parents. METHODS: The study population consisted of all single births with a previous sibling born in Norway between 1967 and 1994. Altogether, 629,888 births were to unrelated parents, and 3466 births were to parents who were first cousins. The risk of stillbirth and infant death was estimated for subsequent siblings contingent on parental consanguinity and survival of the previous sibling. RESULTS: For unrelated parents, the risk of early death (stillbirth plus infant death) for the subsequent sibling was 17 of 1000 if the previous child survived and 67 of 1000 if the previous child died before 1 year of age. For parents who were first cousins, the risk of early death for the subsequent sibling was 29 of 1000 if the previous child survived and 116 of 1000 if the previous child died. CONCLUSIONS: The risk of recurrence of stillbirth and infant death is higher for offspring of first-cousin parents compared with offspring of unrelated parents.