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Search Results: 1 - 10 of 208 matches for " Mogens Fenger "
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Analysis of heterogeneity and epistasis in physiological mixed populations by combined structural equation modelling and latent class analysis
Mogens Fenger, Allan Linneberg, Thomas Werge, Torben J?rgensen
BMC Genetics , 2008, DOI: 10.1186/1471-2156-9-43
Abstract: 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.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.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.Despite tremendous progress in our understanding of the human genome and the rapidly advancing ability to probe genetic variation, investigation of the human genome has yielded onl
Predictors of Serum Total IgE in a Random Sample of 7–17 Year Old Children
Sofie Strømgaard,Simon Francis Thomsen,Mogens Fenger,Vibeke Backer
ISRN Allergy , 2011, DOI: 10.5402/2011/169859
Abstract:
Genetic Variant SCL2A2 Is Associated with Risk of Cardiovascular Disease – Assessing the Individual and Cumulative Effect of 46 Type 2 Diabetes Related Genetic Variants
Anders Borglykke, Niels Grarup, Thomas Spars?, Allan Linneberg, Mogens Fenger, J?rgen Jeppesen, Torben Hansen, Oluf Pedersen, Torben J?rgensen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0050418
Abstract: Aim To assess the individual and combined effect of 46 type 2 diabetes related risk alleles on incidence of a composite CVD endpoint. Methods Data from the first Danish MONICA study (N = 3523) and the Inter99 study (N = 6049) was used. Using Cox proportional hazard regression the individual effect of each risk allele on incident CVD was analyzed. Risk was presented as hazard ratios (HR) per risk allele. Results During 80,859 person years 1441 incident cases of CVD (fatal and non-fatal) occurred in the MONICA study. In Inter99 942 incident cases were observed during 61,239 person years. In the Danish MONICA study four gene variants were significantly associated with incident CVD independently of known diabetes status at baseline; SLC2A2 rs11920090 (HR 1.147, 95% CI 1.027–1.283 , P = 0.0154), C2CD4A rs7172432 (1.112, 1.027–1.205 , P = 0.0089), GCKR rs780094 (1.094, 1.007–1.188 , P = 0.0335) and C2CD4B rs11071657 (1.092, 1.007–1.183 , P = 0.0323). The genetic score was significantly associated with increased risk of CVD (1.025, 1.010–1.041, P = 0.0016). In Inter99 two gene variants were associated with risk of CVD independently of diabetes; SLC2A2 (HR 1.180, 95% CI 1.038–1.341 P = 0.0116) and FTO (0.909, 0.827–0.998, P = 0.0463). Analysing the two populations together we found SLC2A2 rs11920090 (HR 1.164, 95% CI 1.070–1.267, P = 0.0004) meeting the Bonferroni corrected threshold for significance. GCKR rs780094 (1.076, 1.010–1.146, P = 0.0229), C2CD4B rs11071657 (1.067, 1.003–1.135, P = 0.0385) and NOTCH2 rs10923931 (1.104 (1.001 ; 1.217 , P = 0.0481) were found associated with CVD without meeting the corrected threshold. The genetic score was significantly associated with increased risk of CVD (1.018, 1.006–1.031, P = 0.0043). Conclusions This study showed that out of the 46 genetic variants examined only the minor risk allele of SLC2A2 rs11920090 was significantly (P = 0.0005) associated with a composite endpoint of incident CVD below the threshold for statistical significance corrected for multiple testing. This potential pathway needs further exploration.
Genetics of the ceramide/sphingosine-1-phosphate rheostat in blood pressure regulation and hypertension
Mogens Fenger, Allan Linneberg, Torben, J?rgensen, Sten Madsbad, Karen S?bye, Jesper Eugen-Olsen, J?rgen Jeppesen
BMC Genetics , 2011, DOI: 10.1186/1471-2156-12-44
Abstract: 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.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.Hypertension, defined as office blood pressure (BP) measurements of 140/90 mm Hg or greater, affects 30% of the adult population, and is a major risk factor for stroke, heart disease, and end-stage renal disease [1]. Hypertension arises as a consequence of altered activity in signal transduction pathways and interactions of complex intra- and intercellular processes [2,3]. However, the exact mechanism and causes of hypertension are unknown in 95% of the cases (essential hypertension). In the remaining 5% of cases, the cause of hypertension is secondary to various conditions including endocrine disorders as well as drug-induced hypertension [4]. Although several clinical and biochemical variables are correlated to hypertension [5-7] the causes of essential hyperten
Vitamin D Status and Cause-Specific Mortality: A General Population Study
Tea Skaaby, Lise Lotte Nystrup Husemoen, Charlotta Pisinger, Torben J?rgensen, Betina Heinsb?k Thuesen, Mogens Fenger, Allan Linneberg
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0052423
Abstract: Background Vitamin D deficiency is associated with an increased risk of all-cause mortality in observational studies. The specific causes of death underlying this association lack clarity. We investigated the association between vitamin D status and cause-specific mortality. Methods We included a total of 9,146 individuals from the two population-based studies, Monica10 and Inter99, conducted in 1993–94 and 1999–2001, respectively. Vitamin D status was assessed as serum 25-hydroxyvitamin D. Information on causes of death was obtained from The Danish Register of Causes of Death until 31 December 2009. There were a total of 832 deaths (median follow-up 10.3 years). Results Multivariable Cox regression analyses with age as underlying time axis and vitamin D quartiles showed significant associations between vitamin D status and death caused by diseases of the respiratory system, the digestive system, and endocrine, nutritional and metabolic diseases with hazard ratios (HRs) 0.26 (ptrend = 0.0042), 0.28 (ptrend = 0.0040), and 0.21 (ptrend = 0.035), respectively, for the fourth vitamin D quartile compared to the first. We found non-significantly lower HRs for death caused by mental and behavioural diseases and diseases of the nervous system, but no association between vitamin D status and death caused by neoplasms or diseases of the circulatory system. Conclusion The associations of vitamin D status and cause-specific mortality suggest that we also look elsewhere (than to cardiovascular disease and cancer) to explain the inverse association between vitamin D status and mortality.
Governance Dynamics in European Employment Policy
Menno Fenger
Central European Journal of Public Policy , 2008,
Abstract: In the last decade, modern welfare states were confronted with major economic, technological, and demographic challenges. Extensive research has been done on the ways in which modern welfare states respond to these challenges (e.g., Starke et al. 2008, Scharpf and Schmidt 2000). However, in this research usually the contents of the policies take a central place. This article focuses on the extent to which changes in the governance mechanisms in social security and employment policy might be observed. Three types of governance mechanisms are distinguished in this article: hierarchical governance, market governance, and societal governance. This article explores the differences in changes in governance mechanisms that can be observed in six European countries. Moreover, it assesses three potential explanations for these differences. The first explanation assumes a global trend towards market-based mechanisms of governance. The second explanation focuses on the concept of policy learning in the European Union. In the third explanation, historical differences and path dependencies stand central. The article concludes that, despite some converging tendencies, historical differences, to a large extent, account for remaining differences in the use of governance mechanisms in employment policies.
Vitamin D Status, Filaggrin Genotype, and Cardiovascular Risk Factors: A Mendelian Randomization Approach
Tea Skaaby, Lise Lotte Nystrup Husemoen, Torben Martinussen, Jacob P. Thyssen, Michael Melgaard, Betina Heinsb?k Thuesen, Charlotta Pisinger, Torben J?rgensen, Jeanne D. Johansen, Torkil Menné, Berit Carlsen, Pal B. Szecsi, Steen Stender, Runa Vavia Fenger, Mogens Fenger, Allan Linneberg
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057647
Abstract: Background Vitamin D deficiency is associated with increased cardiovascular disease risk in observational studies. Whether these associations are causal is not clear. Loss-of-function mutations in the filaggrin gene result in up to 10% higher serum vitamin D concentrations, supposedly due to a decreased UV-protection of the keratinocytes. We used a Mendelian randomization approach to estimate the causal effect of vitamin D status on serum lipids, blood pressure, body mass index, waist circumference, and the metabolic syndrome. Methods Three population based studies were included, Monica10 (2,656 individuals aged 40–71 years), Inter99 (6,784 individuals aged 30–60 years), and Health2006 (3,471 individuals aged 18–69 years) conducted in 1993–94, 1999–2001, and 2006–2008, respectively. Participants were genotyped for the two most common filaggrin gene mutations in European descendants R501X and 2282del4, in all three studies and further for the R2447X mutation in the Inter99 and Health2006 studies. Filaggrin genotype was used as instrumental variable for vitamin D status. Baseline measurements of serum 25-hydroxyvitamin D were performed in all three studies. Results Instrumental variable analyses showed a 23.8% (95% confidence interval, CI 3.0, 48.6) higher HDL cholesterol level and a 30.5% (95% CI: 0.8, 51.3) lower serum level of triglycerides per doubling of vitamin D. These associations were, however, not statistically significant when applying the Bonferroni adjusted significance level. The remaining lipids showed non-significant changes in a favorable direction. Doubling of vitamin D gave a non-significantly lower odds ratio = 0.26 (95% CI: 0.06, 1.17) of the metabolic syndrome. There were no statistically significant causal effects of vitamin D status on blood pressure, body mass index, or waist circumference. Conclusion Our results support a causal effect of higher vitamin D status on a more favorable lipid profile, although more studies in other populations are needed to confirm our results.
Welfare Regimes in Central and Eastern Europe: Incorporating Post-Communist Countries in a Welfare Regime Typology
H J M Fenger
Contemporary Issues and Ideas in Social Sciences , 2007,
Abstract: This article uses hierarchical cluster analysis to empirically assess if the post-communist welfare states of Central and Eastern Europe can be classified according to any of Esping-Andersen's well-known welfare types, or if they form a distinct group of their own. It shows that at the start of the twenty-first century, there are clear differences in the governmental programmes and the social situation between traditional Western welfare states and post-communist welfare states. The article argues that the welfare states in post-communist countries might be subdivided into three groups: (1) a group of former-USSR countries, including Russia and Belarus; (2) a group of rather successful Central and Eastern European countries including Poland and the Czech Republic, and (3) a group of developing welfare states, consisting of Romania, Moldova and Georgia.
On-demand sedation with propofol for colonoscopy—A prospective pilot study of the influence on short-term memory, psychomotor function and postural stability*  [PDF]
Mogens R?rb?k Madsen
Open Journal of Clinical Diagnostics (OJCD) , 2013, DOI: 10.4236/ojcd.2013.33023
Abstract: Background: After sedated colonoscopy, patients are discharged on the basis of their subjective judgment that they have recovered, corroborated by the nursing staff. The aim of this study was to assess objectively whether patients were in fact fully recovered at the time of discharge, and to demonstrate whether the methods of testing applied could detect any influence of sedation on short-term memory, psychomotor function and postural stability. Methods: Twenty-two patients were investigated. At the beginning of the procedure, a defined bolus of propofol/alfentanil was given intravenously. During the procedure, an additional bolus was injected one or more times as requested by the patient. After colonoscopy, the patients stayed in the recovery room until the patients judged that they had recovered completely, which was also the judgement of the nursing staff at that time. Before colonoscopy and again before discharge, tests were performed of short-term memory, psychomotor function and postural stability (balance). Results: A positive correlation was found between the duration of colonoscopy and the amount of sedative given (p < 0.03). No differences in short-term memory or postural control were found when measurements obtained before and after colonoscopy were compared. Reaction time was prolonged significantly after colonoscopy (p < 0.01), which was mainly due to prolongation of perception time (p < 0.003). No correlation was found between the observed reduction in psychomotor function and the amount of sedative given. Conclusions: The introduction of ultrashort-acting sedative and hypnotic agents has facilitated out-patient colonoscopy. However, although they feel that they have recovered fully, some patients are still affected by the sedative at the time of discharge, as demonstrated by tests of short-term memory, reaction time and postural stability.
Fri ter. Om de italienske lokalradioer
Mogens Schmidt
Massekultur & Medier , 1981,
Abstract: Fri ter. Om de italienske lokalradioer
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