Ib Skovgaard

Maternal fish oil supplementation in lactation: Effect on visual acuity and n−3 fatty acid content of infant erythrocytes

Studies on formula-fed infants indicate a beneficial effect of dietary DHA on visual acuity. Cross-sectional studies have shown an association between breast-milk DHA levels and visual acuity in breast-fed infants. The objective in this study was to evaluate the biochemical and functional effects of fish oil (FO) supplements in lactating mothers. In this double-blinded randomized trial, Danish mothers with habitual fish intake below the 50th percentile of the Danish National Birth Cohort were randomized to microencapsulated FO [1.3 g/d long-chain n−3 FA (n−3 LCPUFA)] or olive oil (OO). The intervention started within a week after delivery and lasted 4 mon. Mothers with habitual high fish intake and their infants were included as a reference group. Ninety-seven infants completed the trial (44 OO-group, 53 FO-group) and 47 reference infants were followed up. The primary outcome measures were: DHA content of milk samples (0, 2, and 4 mon postnatal) and of infant red blood cell (RBC) membranes (4 mon postnatal), and infant visual acuity (measured by swept visual evoked potential at 2 and 4 mon of age). FO supplementation gave rise to a threefold increase in the DHA content of the 4-mon milk samples (P<0.001). DHA in infant RBC reflected milk contents (r=0.564, P<0.001) and was increased by almost 50% (P<0.001). Infant visual acuity was not significantly different in the randomized groups but was positively associated at 4 mon with infant RBC-DHA (P=0.004, multiple regression). We concluded that maternal FO supplementation during lactation did not enhance visual acuity of the infants who completed the intervention. However, the results showed that infants with higher RBC levels of n−3 LCPUFA had a better visual acuity at 4 mon of age, suggesting that n−3 LCPUFA may influence visual maturation.

Efficient Estimation of Fixed and Time‐varying Covariate Effects in Multiplicative Intensity Models

The proportional hazards assumption of the Cox model does sometimes not hold in practise. An example is a treatment effect that decreases with time. We study a general multiplicative intensity model allowing the influence of each covariate to vary non-parametrically with time. An efficient estimation procedure for the cumulative parameter functions is developed. Its properties are studied using the martingale structure of the problem. Furthermore, we introduce a partly parametric version of the general non-parametric model in which the influence of some of the covariates varies with time while the effects of the remaining covariates are constant. This semiparametric model has not been studied in detail before. An efficient procedure for estimating the parametric as well as the non-parametric components of this model is developed. Again the martingale structure of the model allows us to describe the asymptotic properties of the suggested estimators. The approach is applied to two different data sets, and a Monte Carlo simulation is presented.

An isobole-based statistical model and test for synergism/antagonism in binary mixture toxicity experiments

Synergism and antagonism are often defined in relation to the model of Concentration Addition (CA). Hence, it is vital for the conclusion of mixture toxicity studies to be able to test whether an observed deviation from CA reflects a true deviation or whether it is simply due to random variation. In this paper we consider a non-linear regression model for the classical ray designs for binary mixture experiments. The model combines dose–response curves for each mixture in the experiment with an isobole model, describing possible deviations from CA. The method allows us to test whether the chosen isobole model is reasonable for the data and to test the hypothesis of CA. Furthermore, it provides us with a measure of the degree of synergism/antagonism. The method is flexible since both the dose–response relationships and the isobole model can be chosen arbitrarily. We demonstrate the use of the method on datasets where combinations of pesticides are tested on a floating plant, Lemna minor, and an algae, Pseudokirchneriella subcapitata. Furthermore, we conduct a simulation study in order to explore the power with which a specific deviation from CA can be distinguished in different test-systems.

Design of the OPUS School Meal Study: a randomised controlled trial assessing the impact of serving school meals based on the New Nordic Diet.

Introduction: Danish children consume too much sugar and not enough whole grain, fish, fruit, and vegetables. The Nordic region is rich in such foods with a strong health-promoting potential. We lack randomised controlled trials that investigate the developmental and health impact of serving school meals based on Nordic foods. Aim: This paper describes the rationale, design, study population, and potential implications of the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. Methods: In a cluster-randomised cross-over design, 1021 children from 3rd and 4th grades (8–11 years old) at nine Danish municipal schools were invited to participate. Classes were assigned to two 3-month periods with free school meals based on the New Nordic Diet (NND) or their usual packed lunch (control). Dietary intake, nutrient status, physical activity, cardiorespiratory fitness, sleep, growth, body composition, early metabolic and cardiovascular risk markers, illness, absence from school, wellbeing, cognitive function, social and cultural features, food acceptance, waste, and cost were assessed. Results: In total, 834 children (82% of those invited) participated. Although their parents were slightly better educated than the background population, children from various socioeconomic backgrounds were included. The proportion of overweight and obese children (14%) resembled that of earlier examinations of Danish school children. Drop out was 8.3%. Conclusions: A high inclusion rate and low drop out rate was achieved. This study will be the first to determine whether school meals based on the NND improve children’s diet, health, growth, cognitive performance, and early disease risk markers.

Early programming of the IGF-I axis: negative association between IGF-I in infancy and late adolescence in a 17-year longitudinal follow-up study of healthy subjects.

BACKGROUND IGF-I is a major regulator of growth, influenced primarily by diet in infancy and primarily by GH in childhood. Breastfed infants have lower IGF-I levels compared to formula fed and tend to be shorter. The higher protein content of infant formula has a stimulatory effect on IGF-I production. Conversely, studies suggest that later in childhood, those breastfed are taller and have higher IGF-I levels. Therefore, it has been suggested that the IGF-I axis may be programmed by diet during infancy. The association between IGF-I in infancy and later life is not known. OBJECTIVE To examine the association between IGF-I in infancy and adolescence. DESIGN Infants (109) from the observational Copenhagen cohort study. METHODS Serum-IGF-I was measured during infancy (2, 6, and 9 months) and at follow-up at 17 years. Associations were examined by correlation tests and linear regression controlling for gender, breastfeeding, and other covariates. Likelihood ratio test based on residual log likelihood was applied for analysis including all measurements during infancy. RESULTS There was an inverse association between IGF-I at 9 months and 17 years (r=-0.39, P=0.014, and n=40). A 1 ng/ml higher IGF-I concentration at 9 months corresponded to 0.95 ng/ml lower IGF-I concentration at 17 years. IGF-I levels at 2 and 6 months were not significantly associated with IGF-I at 17 years, but the estimated directions were negative. These associations were not changed when adjusted for breastfeeding and other covariates except IGF-I at 2 months which was significantly negatively associated with IGF-I at 17 years (P=0.030) corresponding to a 0.96 ng/ml lower IGF-I concentration at 17 years per ng/ml IGF-I at 2 months. Inclusion of all measurements during infancy showed a negative association with 17-year values (r=-0.26, P=0.043, and n=109). CONCLUSION The results support the hypothesis that the IGF-I axis can be programmed early in life.

Effects of inter-varietal diversity, biotic stresses and environmental productivity on grain yield of spring barley variety mixtures

Varietal seed mixtures tend to increase and stabilize crop yields, yet their application is sparse. Large-scale cultivation of variety mixtures may require a better understanding of how inter-varietal interactions and their interaction with the environment may influence the grain yield of variety mixtures relative to their component varieties. For this purpose, six variety mixtures of spring barley and 14 component varieties were grown in each of 17 trial environments. A total of 28 observed and a priori plant characteristics, including grain yield, disease severity and weed competitiveness, were derived for each component variety in each trial. The relationship between inter-varietal diversity of each characteristic and the mixing effect on grain yield was analysed. Additionally, various types of yield stability were estimated and compared among mixtures and component varieties. One mixture out-yielded all of its component varieties in almost half of the trial environments. Inter-varietal diversity in grain yield potential correlated significantly with mixing effect, as did straw length diversity when weighted with weed pressure. The grain yields of most mixtures were more stable across environments than their component varieties when accounting also for the general response to environmental productivity. Hence, most mixtures adapted slightly better to environmental productivity and were less sensitive to environmental stress than their component varieties. We conclude that the efficacy of variety mixtures may be enhanced by mixing relatively high-yielding varieties differing in responsiveness to environmental productivity.

Exhaled breath analysis using electronic nose in cystic fibrosis and primary ciliary dyskinesia patients with chronic pulmonary infections.

The current diagnostic work-up and monitoring of pulmonary infections may be perceived as invasive, is time consuming and expensive. In this explorative study, we investigated whether or not a non-invasive exhaled breath analysis using an electronic nose would discriminate between cystic fibrosis (CF) and primary ciliary dyskinesia (PCD) with or without various well characterized chronic pulmonary infections. We recruited 64 patients with CF and 21 with PCD based on known chronic infection status. 21 healthy volunteers served as controls. An electronic nose was employed to analyze exhaled breath samples. Principal component reduction and discriminant analysis were used to construct internally cross-validated receiver operator characteristic (ROC) curves. Breath profiles of CF and PCD patients differed significantly from healthy controls p = 0.001 and p = 0.005, respectively. Profiles of CF patients having a chronic P. aeruginosa infection differed significantly from to non-chronically infected CF patients p = 0.044. We confirmed the previously established discriminative power of exhaled breath analysis in separation between healthy subjects and patients with CF or PCD. Furthermore, this method significantly discriminates CF patients suffering from a chronic pulmonary P. aeruginosa (PA) infection from CF patients without a chronic pulmonary infection. Further studies are needed for verification and to investigate the role of electronic nose technology in the very early diagnostic workup of pulmonary infections before the establishment of a chronic infection.

Evaluation of reproductive barriers contributes to the development of novel interspecific hybrids in the Kalanchoë genus

BackgroundInterspecific hybridization is a useful tool in ornamental breeding to increase genetic variability and introduce new valuable traits into existing cultivars. The successful formation of interspecific hybrids is frequently limited by the presence of pre- and post-fertilization barriers. In the present study, we investigated the nature of hybridization barriers occurring in crosses between Kalanchoë species and evaluated possibilities of obtaining interspecific hybrids.ResultsThe qualitative and quantitative analyses of pollen tube growth in situ were performed following intra- and interspecific pollinations. They revealed occurrence of pre-fertilization barriers associated with inhibition of pollen germination on the stigma and abnormal growth of pollen tubes. Unilateral incongruity related to differences in pistil length was also observed. The pollen quality was identified as a strong factor influencing the number of pollen tubes germinating in the stigma. In relation to post-fertilization barriers, endosperm degeneration was a probable barrier hampering production of interspecific hybrids. Moreover, our results demonstrate the relation of genetic distance estimated by AFLP marker analysis of hybridization partners with cross-compatibility of Kalanchoë species. At the same time, differences in ploidy did not influence the success of interspecific crosses.ConclusionsOur study presents the first comprehensive analysis of hybridization barriers occurring within Kalanchoë genus. Reproductive barriers were detected on both, pre- and post-fertilization levels. This new knowledge will contribute to further understanding of reproductive isolation of Kalanchoë species and facilitate breeding of new cultivars. For the first time, interspecific hybrids between K. nyikae as maternal plant and K. blossfeldiana as well as K. blossfeldiana and K. marnieriana were generated.

Nonparametric maximum likelihood estimation of randomly time-transformed curves

Alignment of curves by nonparametric maximum likelihood estimation can be done when the individual transformations of the time axis is assumed to be of a parametric form, known up to some individual unobserved random parameters. We suggest a fast algorithm, based on a Laplace approximation, to find the nonparametric maximum likelihood estimator (NPMLE) for the shape function. We find smooth estimates for the shape functions without choosing any smoothing parameters or kernel function and we estimate realizations of the unobserved transformation parameters that align the curves to satisfy the eye. The method is applied to two data examples of electrophoretic spectra on feta cheese samples and on wheat samples, respectively. A small simulation study indicates reasonable robustness against assumptions regarding the error covariance function.