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BACKGROUND/OBJECTIVES: The aim was to examine the causal effect of vitamin D on serum adiponectin using a multiple instrument Mendelian randomization approach. SUBJECTS/METHODS: Serum 25-hydroxy vitamin D (25(OH)D) and serum total or high molecular weight (HMW) adiponectin were measured in two Danish population-based studies: the Inter99 study (6405 adults, 30-60 years) conducted in 1999-2001, and the MONICA10 study (2656 adults, 41-71 years) conducted in 1993-1994. RESULTS: In the Inter99 study, serum 25(OH)D was positively associated with total adiponectin (the effect estimate in % per doubling of 25(OH)D was 4.78, 95% CI: 1.96, 7.68, P CONCLUSIONS: The results indicate a possible causal association between serum 25(OH)D and total adiponectin. However, the association was not replicated for HMW adiponectin. Thus, further studies are needed to confirm a causal relationship. European Journal of Clinical Nutrition (2014) 68, 189-195; doi: 10.1038/ejcn.2013.233; published online 13 November 2013 Keywords: causation; filaggrin; instrumental variables; rs2282679; 25-hydroxy vitamin D; adipokines, INTRODUCTION It is suggested that circulating 25-hydroxyvitamin D (25(OH)D) is inversely associated with insulin resistance and development of type 2 diabetes. (1,2) The mechanism by which vitamin D may affect [...]

On-line partial discharge (PD) testing has become a powerful tool to plan the maintenance of stator windings of high voltage motors and generators. Interpretation of PD data is best done by monitoring the trend in PD over time. Unfortunately the trend in PD is sometimes difficult to ascertain, especially if the humidity within the stator is variable over time. This paper shows several examples of how PD is affected by humidity in operating machines. Laboratory experiments were also performed to duplicate this phenomenon. In most practical situations, it appears that the PD activity decreases as the humidity increases.

Objective: Mechanical restraint (MR) is used to prevent patients from harming themselves or others during inpatient treatment. The objective of this study was to investigate whether incident MR occurring in the first 3 days following admission could be predicted based on analysis of electronic health data available after the first hour of admission. Methods: The dataset consisted of clinical notes from electronic health records from the Central Denmark Region and data from the Danish Health Registers from patients admitted to a psychiatric department in the period from 2011 to 2015. Supervised machine learning algorithms were trained on a randomly selected subset of the data and validated using an independent test dataset. Results: A total of 5050 patients with 8869 admissions were included in the study. One hundred patients were mechanically restrained in the period between one hour and 3 days after the admission. A Random Forest algorithm predicted MR with an area under the curve of 0.87 (95% CI 0.79–0.93). At 94% specificity, the sensitivity was 56%. Among the ten strongest predictors, nine were derived from the clinical notes. Conclusions: These findings open for the development of an early warning system that may guide interventions to reduce the use of MR. [ABSTRACT FROM AUTHOR]

This article focuses on the role of local municipalities in detecting and sanctioning benefit fraud, specifically fraud with social assistance benefits. Since the early 2000's, the government's attention for benefit fraud has been increased, resulting in the strengthening of the tasks and responsibilities of local municipalities in combatting and detecting fraud. There are indications that this has been successful: there is an increase in detection and the number of people that claims to offend the rules is decreasing. However, there is a significant amount of variety between municipalities in their performance with this regard. The authors argue that these differences are related to the design and implementation of local policies concerning the detection of benefit fraud. They offer several recommendations for more effective policies at the local level. These recommendations include a better use of available data and knowledge about the background of offenders and social assistance recipients. [ABSTRACT FROM AUTHOR]

The knowledge of climate effects of atmospheric aerosols is associated with large uncertainty, and a better understanding of their physical and chemical properties is needed, especially in the Arctic environment. The objective of the present study is to improve our understanding of the processes affecting the composition of aerosols in the high Arctic. Therefore size-segregated aerosols were sampled at a high Arctic site, Station Nord (Northeast Greenland), in March 2009 using a Micro Orifice Uniform Deposit Impactor. The aerosol samples were extracted in order to analyse three water-soluble anions: chloride, nitrate and sulphate. The results are discussed based on possible chemical and physical transformations as well as transport patterns. The total concentrations of the ions at Station Nord were 53-507 ng m-3, 2-298 ng m-3 and 535-1087 ng m-3 for chloride (Cl-), nitrate (NO-3 ) and sulphate (SO2-4 ), respectively. The aerosols in late winter/early spring, after polar sunrise, are found to be a mixture of long-range transported and regional to local originating aerosols. Fine particles, smaller than 1 μm, containing SO2-4 , Cl- and NO-3 , are hypothesized to originate from long-range transport, where SO2-4 is by far the dominating anion accounting for 50-85% of the analyzed mass. The analysis suggests that Cl- and NO-3 in coarser particles (> 1.5 μm) originate from local/regional sources. Under conditions where the air mass is transported over sea ice at high wind speeds, very coarse particles (> 18 μm) are observed, and it is hypothesized that frost flowers on the sea ice are a source of the very coarse nitrate particles. [ABSTRACT FROM AUTHOR]

OBJECTIVE This study aimed to examine vitamin D status as a determinant for development of type 2 diabetes and deterioration of glucose homeostasis. RESEARCH DESIGN AND METHODS A random sample of the general population of Copenhagen, Denmark, was taken as part of the Inter99 study. Included were 6,405 men and women aged 30-65 years at baseline (1999-2001), with 4,296 participating in the follow-up examination 5 years later (2004-2006). Vitamin D was determined at baseline as serum 25-hydroxyvitamin D [25(OH)D]. Diabetes was defined based on an oral glucose tolerance test and a glycosylated hemoglobin (HbA(1c)) test. Secondary outcomes included continuous markers of glucose homeostasis. RESULTS The risk of incident diabetes associated with a 10 nmol/L increase in 25(OH)D was odds ratio (OR) 0.91 (95% CI 0.84-0.97) in crude analyses. The association became statistically nonsignificant after adjustment for confounders, with an OR per 10 nmol/L of 0.94 (0.86-1.03). Low 25(OH)D status was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis after adjustment for confounders. Fasting and 2-h glucose and insulin as well as the degree of insulin resistance increased significantly more during follow-up among those with low 25(OH)D levels compared with those with higher levels. CONCLUSIONS Low 25(OH)D status was not significantly associated with incident diabetes after adjustment for confounders. However, it was significantly associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis, indicating that low vitamin D status could be related to deterioration of glucose homeostasis. [ABSTRACT FROM AUTHOR]

The knowledge of climate effects of atmospheric aerosols is associated with large uncertainty, and a better understanding of their physical and chemical properties is needed, especially in the Arctic environment. The objective of the present study is to improve our understanding of the processes affecting the composition of the aerosols in the high Arctic. Therefore size-segregated aerosols were sampled at a high Arctic site, Station Nord (Northeast Greenland), in March 2009 using a Micro Orifice Uniform Deposit Impactor. The aerosol samples were extracted in order to analyze the three water-soluble anions: chloride, nitrate and sulphate. The results are discussed based on possible chemical and physical transformations as well as transport patterns. The total concentrations of the ions at Station Nord were 53-507 ngm-3, 2- 298 ngm-3 and 535-1087 ngm-3 for chloride (Cl-), nitrate (NO- 3 ) and sulphate (SO2- 4 ), respectively. The aerosols in late winter/early spring, after polar sunrise, are found to be a mixture of long-range transported and regional to local originating aerosols. Fine particles, smaller than 1 μm, containing SO2- 4 , Cl- and NO- 3 , are hypothesized to originate from long-range transport, where SO2- 4 is by far the dominating anion accounting for 50-85%of the analyzed mass. The analysis suggests that Cl- and NO- 3 in coarser particles (>1.5 μm) originate from local/regional sources. Under conditions where the air mass is transported over sea-ice at high wind speeds, very coarse particles (>18 μm) are observed and it is hypothesized that frost flowers on the sea ice is a source of very coarse chloride particles in the Arctic. [ABSTRACT FROM AUTHOR]

To cite this article: Thuesen BH, Husemoen LLN, Ovesen L, Jørgensen T, Fenger M, Gilderson G, Linneberg A. Atopy, asthma, and lung function in relation to folate and vitamin B12 in adults. Allergy 2010; 65: 1446-1454. Background: Recent studies suggested low serum folate and impaired folate metabolism as potential risk factors for development of asthma and atopic disease, but the results are inconsistent. The aim of this study was to investigate the relations of markers of folate and vitamin B12 (B12) deficiency with different phenotypes of asthma and atopy. Methods: A random sample of 6784 persons from a general population aged 30-60 years participated in a health examination in 1999-2001, and 4516 (66.6%) of those also participated in a follow-up examination 5 years later. The examinations included spirometry, measurements of serum folate and B12, specific IgE to inhalant allergens, total IgE, and genotyping of the MTHFR-C677T polymorphism - a genetic marker of impaired folate metabolism. Information about dietary intake of folate and B12, asthma diagnosis, and airway symptoms was obtained by questionnaires. Results: Low serum folate levels and the TT genotype of the MTHFR-C677T polymorphism were associated with increased prevalence of self-reported doctor-diagnosed asthma [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.05-1.79 and OR 1.52; 95% CI 1.12-2.06, respectively] and attacks of shortness of breath (OR 1.43, 95% CI 1.14-1.79 and OR 1.47; 95% CI: 1.14-1.91, respectively). We found no significant associations with lung function or atopic outcomes. Serum levels of B12 and dietary intake of folate and B12 were not associated with asthma or atopy. Conclusions: We found that two objective markers of folate deficiency were associated with self-reported doctor-diagnosed asthma and attacks of shortness of breath, but not with lung function or atopy. [ABSTRACT FROM AUTHOR]

The cluster of obesity, insulin resistance, dyslipidaemia and hypertension, called the metabolic syndrome, has been suggested as a risk factor for cardiovascular disease and type 2 diabetes. The aim of the present study was to evaluate whether there are common genetic and environmental factors influencing this cluster in a general population of twin pairs. A multivariate genetic analysis was performed on nine endophenotypes associated with the metabolic syndrome from 625 adult twin pairs of the GEMINAKAR study of the Danish Twin Registry. All endophenotypes showed moderate to high heritability (0.31–0.69) and small common environmental variance (0.05–0.21). In general, genetic and phenotypic correlations between the endophenotypes were strong only within sets of physiologically similar endophenotypes, but weak to moderate for other pairs of endophenotypes. However, moderate correlations between insulin resistance indices and either obesity-related endophenotypes or triacylglycerol levels indicated that some common genetic backgrounds are shared between those components. We demonstrated that, in a general population, the endophenotypes associated with the metabolic syndrome apparently do not share a substantial common genetic or familial environmental background. [ABSTRACT FROM AUTHOR]

SUMMARY Aims To establish the impact on the insulin resistance syndrome of the intron 14 Xba1-polymorphism in human muscle glycogen synthase (GYS1). Methods Parameters related to the insulin resistance syndrome were measured in 244 monozygotic twins and 322 dizygotic twins with or without impaired glucose tolerance. In addition a standard oral glucose tolerance test (OGTT) was performed. The twins were genotyped for Xba1-polymorphism in GYS1 intron 14. Results The allele frequency of Xba1 non-cutters (A1) was 0.95 and of cutters (A2) was 0.05. Of the 566 twins examined, 90.0% had the genotype A1A1 and the remainder had the genotype A1A2. No A2A2-genotypes were detected. In 11 genotypic discordant dizygotic twin pairs the insulin resistance was significantly increased in the twins carrying the A1A2 genotype regardless of sex (HOMA index 1.81 (A1A1) vs. 2.57 (A1A2), P < 0.05). Diastolic blood pressure was increased in female carriers of the A2-allele with impaired glucose tolerance or Type 2 diabetes mellitus (79 ± 1 vs. 94 ± 4 mmHg, P < 0,01). Apart from a marginal increased waist-to-hip ratio, no other elements of the insulin resistance syndrome were associated with the polymorphism. Conclusions The Xba1-polymorphism of the human muscle glycogen synthase gene is correlated to insulin resistance and to diastolic blood pressure. The polymorphism does not involve any known transcription factor or any structural change in GYS1, and these correlations are therefore most probably caused by linkage to other functional polymorphisms in GYS1 or other gene polymorphisms on chromosome 19. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor regarding a study on the pathogenesis of the insulin resistance syndrome previously published in "Diabetologia."

Abstract Background Several attempts to decipher the genetics of hypertension of unknown causes have been made including large-scale genome-wide association analysis (GWA), but only a few genes have been identified. Unsolved heterogeneity of the regulation of blood pressure and the shortcomings of the prevailing monogenic approach to capture genetic effects in a polygenic condition are the main reasons for the modest results. The level of the blood pressure is the consequence of the genotypic state of the presumably vast network of genes involved in regulating the vascular tonus and hence the blood pressure. Recently it has been suggested that components of the sphingolipid metabolism pathways may be of importance in vascular physiology. The basic metabolic network of sphingolipids has been established, but the influence of genetic variations on the blood pressure is not known. In the approach presented here the impact of genetic variations in the sphingolipid metabolism is elucidated by a two-step procedure. First, the physiological heterogeneity of the blood pressure is resolved by a latent class/structural equation modelling to obtain homogenous subpopulations. Second, the genetic effects of the sphingolipid metabolism with focus on de novo synthesis of ceramide are analysed. The model does not assume a particular genetic model, but assumes that genes operate in networks. Results The stratification of the study population revealed that (at least) 14 distinct subpopulations are present with different propensity to develop hypertension. Main effects of genes in the de novo synthesis of ceramides were rare (0.14% of all possible). However, epistasis was highly significant and prevalent amounting to approximately 70% of all possible two-gene interactions. The phenotypic variance explained by the ceramide synthesis network were substantial in 4 of the subpopulations amounting to more than 50% in the subpopulation in which all subjects were hypertensive. Construction of the network using the epistatic values revealed that only 17% of the interactions detected were in the direct metabolic pathway, the remaining jumping one or more intermediates. Conclusions This study established the components of the ceramide/sphingosine-1-phosphate rheostat as central to blood pressure regulation. The results in addition confirm that epistasis is of paramount importance and is most conspicuous in the regulation of the rheostat network. Finally, it is shown that applying a simple case-control approach with single gene association analysis is bound to fail, short of identifying a few potential genes with small effects.

Abstract Background Biological systems are interacting, molecular networks in which genetic variation contributes to phenotypic heterogeneity. This heterogeneity is traditionally modelled as a dichotomous trait (e.g. affected vs. non-affected). This is far too simplistic considering the complexity and genetic variations of such networks. Methods In this study on type 2 diabetes mellitus, heterogeneity was resolved in a latent class framework combined with structural equation modelling using phenotypic indicators of distinct physiological processes. We modelled the clinical condition "the metabolic syndrome", which is known to be a heterogeneous and polygenic condition with a clinical endpoint (type 2 diabetes mellitus). In the model presented here, genetic factors were not included and no genetic model is assumed except that genes operate in networks. The impact of stratification of the study population on genetic interaction was demonstrated by analysis of several genes previously associated with the metabolic syndrome and type 2 diabetes mellitus. Results The analysis revealed the existence of 19 distinct subpopulations with a different propensity to develop diabetes mellitus within a large healthy study population. The allocation of subjects into subpopulations was highly accurate with an entropy measure of nearly 0.9. Although very few gene variants were directly associated with metabolic syndrome in the total study sample, almost one third of all possible epistatic interactions were highly significant. In particular, the number of interactions increased after stratifying the study population, suggesting that interactions are masked in heterogenous populations. In addition, the genetic variance increased by an average of 35-fold when analysed in the subpopulations. Conclusion The major conclusions from this study are that the likelihood of detecting true association between genetic variants and complex traits increases tremendously when studied in physiological homogenous subpopulations and on inclusion of epistasis in the analysis, whereas epistasis (i.e. genetic networks) is ubiquitous and should be the basis in modelling any biological process.