Merete Osler

Glostrup Hospital, Glostrup, Capital Region, Denmark

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Publications (259)917.46 Total impact

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    ABSTRACT: Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high-functioning group (-4.6 pg/mL, 95% CI: -7.84, -1.36, P=0.006). The 24-hour mean melatonin concentration (high-functioning group: 4.80±0.70 pg/mL, vs cognitively impaired group: 4.81±0.76 pg/mL; P>0.05) (or the area under the curve, AUC) was not significantly different between the two groups. Cortisol levels were low during the night, and peaked at approximately 8 am. Median cortisol concentrations were similar at all times, as were the 24-hour mean cortisol concentrations and AUC. To the best of our knowledge, ours is the first study to assess circadian measures (ie, melatonin and cortisol) in healthy middle-aged men with different cognitive trajectories in midlife. We found evidence of altered circadian rhythms with a reduced nocturnal melatonin response at 4 am in men with cognitive impairment. The 24-hour concentration and AUC of melatonin and cortisol were similar in the cognitively high-functioning group and in the cognitively impaired.
    Preview · Article · Feb 2016 · Nature and Science of Sleep
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    ABSTRACT: Introduction In the last decade a range of recommendations to increase awareness of depression in acute coronary syndrome patients have been published. To test the impact of those recommendations we examine and compare recent time trends in depression among acute coronary syndrome patients and a reference population. Methods 87 218 patients registered with acute coronary syndrome from 2001-2009 in Denmark and a match reference population were followed through hospital registries and medication prescriptions for early (≤30 days), intermediate (31 days to 6 months) and later (6 months to 2 years) depression in the acute coronary syndrome population and overall depression in the reference population. Cox regression models were used to compare hazard ratios (HRs) for depression over calendar years. Results During the study period, 11.0% and 6.2% were diagnosed with depression in the acute coronary syndrome population and in the reference population, respectively. For the acute coronary syndrome population, the adjusted HRs increased for early (HR (95% CI) 1.04 (1.01-1.06)) and intermediate depression (HR (95% CI) 1.01 (1.00-1.03)), whereas the adjusted HRs did not change for later depression (HR (95% CI) 0.99 (0.98-1.00)). For the reference population the adjusted HRs for depression increased through the study period (HR (95% CI) 1.01 (1.01-1.03)). Conclusion Increase in diagnoses of depressions within 6 months of acute coronary syndrome may be explained by increased focus on depression in this patient group in combination with increased awareness of depression in the general population.
    No preview · Article · Jan 2016 · Nordic journal of psychiatry
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    ABSTRACT: We examined incidence of depression after acute coronary syndrome (ACS) and whether the timing of depression onset influenced survival. All first-time hospitalizations for ACS (n = 97,793) identified in the Danish Patient Registry during 2001-2009 and a reference population were followed for depression and mortality via linkage to patient, prescription, and cause-of-death registries until the end of 2012. Incidence of depression (as defined by hospital discharge or antidepressant medication use) and the relationship between depression and mortality were examined using time-to-event models. In total, 19,520 (20.0%) ACS patients experienced depression within 2 years after the event. The adjusted rate ratio for depression in ACS patients compared with the reference population was 1.28 (95% confidence interval (CI): 1.25, 1.30). During 12 years of follow-up, 39,523 (40.4%) ACS patients and 27,931 (28.6%) of the reference population died. ACS patients with recurrent (hazard ratio (HR) = 1.62, 95% CI: 1.57, 1.67) or new-onset (HR = 1.66, 95% CI: 1.60, 1.72) depression had higher mortality rates than patients with no depression. In the reference population, the corresponding relative estimates for recurrent (HR =1.98, 95% CI: 1.92, 2.05) and new-onset (HR = 2.42, 95% CI: 2.31, 2.54) depression were stronger. Depression is common in ACS patients and is associated with increased mortality independently of time of onset, but here the excess mortality associated with depression seemed to be lower in ACS patients than in the reference population.
    No preview · Article · Jan 2016 · American journal of epidemiology

  • No preview · Article · Jan 2016 · Journal of the American Geriatrics Society
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    ABSTRACT: Objective: The aim was to estimate the effects of ponderal index at birth and body mass index (BMI) in early adulthood on C-reactive protein (CRP) and interleukin-6 (IL-6) and to quantify the effects through subsequent measures of body size. In a subanalysis, the contributions of maternal BMI to the inflammatory status of offspring were investigated. Methods: The study was based on 2,986 Danish males from the Copenhagen Aging and Midlife Biobank. Path analysis was employed to estimate direct and indirect effects. Results: A 10% higher maternal BMI was associated with 7% higher CRP and 3% higher IL-6 among offspring. A 10% higher ponderal index at birth was associated with 4% lower CRP in late midlife; this effect was only partially mediated by later growth. A 10% higher BMI in early adulthood was associated with 8% higher CRP and 4% higher IL-6 in late midlife. The findings suggest that weight gain in adulthood is associated with low-grade inflammation in late midlife. Conclusions: Ponderal index at birth is associated with CRP in later life independently of adult BMI. The findings additionally suggest that preventing weight gain in early adulthood would be beneficial for inflammatory status in later life.
    No preview · Article · Dec 2015 · Obesity
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    ABSTRACT: Cognitive impairment in patients with Alzheimer's disease (AD) is associated with reduction in hippocampal volume in magnetic resonance imaging (MRI). However, it is unknown whether hippocampal texture changes in persons with mild cognitive impairment (MCI) that does not have a change in hippocampal volume. We tested the hypothesis that hippocampal texture has association to early cognitive loss beyond that of volumetric changes. The texture marker was trained and evaluated using T1-weighted MRI scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and subsequently applied to score independent data sets from the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) and the Metropolit 1953 Danish Male Birth Cohort (Metropolit). Hippocampal texture was superior to volume reduction as predictor of MCI-to-AD conversion in ADNI (area under the receiver operating characteristic curve [AUC] 0.74 vs 0.67; DeLong test, p = 0.005), and provided even better prognostic results in AIBL (AUC 0.83). Hippocampal texture, but not volume, correlated with Addenbrooke's cognitive examination score (Pearson correlation, r = -0.25, p < 0.001) in the Metropolit cohort. The hippocampal texture marker correlated with hippocampal glucose metabolism as indicated by fluorodeoxyglucose-positron emission tomography (Pearson correlation, r = -0.57, p < 0.001). Texture statistics remained significant after adjustment for volume in all cases, and the combination of texture and volume did not improve diagnostic or prognostic AUCs significantly. Our study highlights the presence of hippocampal texture abnormalities in MCI, and the possibility that texture may serve as a prognostic neuroimaging biomarker of early cognitive impairment. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Dec 2015 · Human Brain Mapping
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    ABSTRACT: Background: Patients with low socioeconomic position have higher rates of mortality after diagnosis of acute coronary syndrome (ACS), but little is known about the mechanisms behind this social inequality. The aim of the present study was to examine whether any educational inequality in survival after ACS was influenced by comorbid conditions including depression. Methods: From 2001 to 2009 all first-time ACS patients were identified in the Danish National Patient Registry. This cohort of 83 062 ACS patients and a matched reference population were followed for incident depression and mortality until December 2012 by linkage to person, patients and prescription registries. Educational status was defined at study entry and the impact of potential confounders and mediators (age, gender, cohabitation status, somatic comorbidity and depression) on the relation between education and mortality were identified by drawing a directed acyclic graph and analysed using multiple Cox regression analyses. Findings: During follow-up, 29 583(35.6%) of ACS patients and 19 105(22.9%) of the reference population died. Cox regression analyses showed an increased mortality in the lowest educated compared to those with high education in both ACS patients and the reference population. Adjustment for previous and incident depression or other covariables only attenuated the relations slightly. This pattern of associations was seen for mortality after 30 days, 1 year and during total follow-up. Conclusion: In this study the relative excess mortality rate in lower educated ACS patients was comparable with the excess risk associated with low education in the background population. This educational inequality in survival remained after adjustment for somatic comorbidity and depression.
    Full-text · Article · Oct 2015 · PLoS ONE

  • No preview · Article · Oct 2015 · Acta Paediatrica

  • No preview · Article · Sep 2015 · World psychiatry: official journal of the World Psychiatric Association (WPA)
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    ABSTRACT: Mitochondrial bioenergetics, mitochondrial reactive oxygen species (ROS) and cellular levels of nucleotides have been hypothesized as early indicators of Alzheimer's disease (AD). Utilizing relative decline of cognitive ability as a predictor of AD risk, we evaluated the correlation between change of cognitive ability and mitochondrial bioenergetics, ROS and cellular levels of deoxyribonucleotides. Change of cognitive abilities, scored at ages of approximately 20 and 57 was determined for a cohort of 1985 male participants. Mitochondrial bioenergetics, mitochondrial ROS and whole-cell levels of deoxyribonucleotide triphosphates were measured in peripheral blood mononuclear cells (PBMCs) from a total of 103 selected participants displaying the most pronounced relative cognitive decline and relative cognitive improvement. We show that relative cognitive decline is associated with higher PBMC content of deoxythymidine-triphosphate (dTTP) (20%), but not mitochondrial bioenergetics parameters measured in this study or mitochondrial ROS. Levels of dTTP in PBMCs are indicators of relative cognitive change suggesting a role of deoxyribonucleotides in the etiology of AD.
    Full-text · Article · Sep 2015 · Mitochondrion
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    ABSTRACT: Lower case fatality and increased use of evidence-based invasive management incl. coronary angiography (CAG) have been reported for patients admitted with acute myocardial infarction (AMI) in the last 25 years. This article seeks to investigate whether these advances have benefitted patients in all socio-economic groups and how this has impacted on inequality in case fatality. Forty three thousand eight hundred and forty three patients admitted with AMI in the period from 2001 to 2009 were included. Socio-economic position was measured using individual information on education. Age-standardized cumulative incidence of CAG within 1, 3 and 30 days along with age-standardized case fatality within 30 and 365 days were estimated. Cox regression models were used to model the relative inequality over time. Use of CAG within 1, 3 and 30 days increased for all educational groups over time and the inequality in CAG within 1 and 3 days seen in the beginning of the time frame was eliminated. Case fatality decreased in all educational groups and the relative inequality in 30 days case fatality decreased for women but not 365 days case fatality. No change was seen for inequality in case fatality for men. Increased use of CAG within the evidence based time frame was observed along with a decrease in inequality. However, a reduction in inequality was only observed for short term case fatality, and only for women. These results suggest that inequality in case fatality is not primarily driven by inequality in invasive management of AMI. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
    No preview · Article · Sep 2015 · The European Journal of Public Health
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    ABSTRACT: Little is known about the influence of lifetime socio-economic position (SEP) on adult depression. We examined the association of SEP during the life course with depressive mood in late midlife and explored whether cognitive function at age 20, health-related behaviour and inflammatory biomarkers explained any associations. A cohort of 2482 Danish men born in 1953 with information from birth, and conscript board examinations was followed-up with assessment of depressive mood and blood sampling in 2010. Simple and multiple linear regression were used to investigate associations among variables. Social circumstances during the life course were associated with depressive mood. Further, low lifetime SEP was associated with lower cognitive score, smoking, alcohol use, high body mass index (BMI) and increased level of high sensitive ProReactive Protein and Interleukin-6. These covariables were also associated with depressive mood and when they were included into the regression model together with life time SEP, the β-estimates for the latter attenuated, when smoking, alcohol and BMI were entered, while the inclusion of cognitive function and the inflammatory biomarkers had limited effect on the relation between lifetime SEP and depressive mood. Lifetime SEP was associated with depressive mood and health-related behaviour explained a part of the relation. © The Author 2015. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.
    No preview · Article · Jul 2015 · The European Journal of Public Health

  • No preview · Article · Jul 2015 · International Journal of Epidemiology
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    ABSTRACT: Insights into the causes of variances in physical performance are important to prevent mobility limitations in old age. We examined associations between intelligence in early adulthood and midlife physical performance. Data from the Copenhagen Aging and Midlife Biobank were analyzed using linear regression. In total, 2,848 male cohort members had intelligence scores from conscription and physical performance measures from midlife. In adjusted models, a 1 SD increase in intelligence resulted in 1.10 more chair-rises (p < .001), a 1.03 cm higher jump (p < .001), a 3.69% smaller balance area (p < .001), a 0.71 kg increase in handgrip strength (p < .001), and a 5.03 N increase in back force (p < .001). Results for flexibility and abdominal force were not significant. Public health interventions should focus on addressing people with different cognitive abilities and bear in mind that prevention of mobility limitations might need to start early in life. © The Author(s) 2015.
    No preview · Article · Jul 2015 · Journal of Aging and Health
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    ABSTRACT: In order to reduce social inequality in cancer survival, knowledge is needed about where in the cancer trajectory disparities occur, and how social and health-related aspects may interact. We aimed to determine whether socioeconomic factors are related to cancer diagnosis stage, and whether socioeconomic disparities in survival after ovarian cancer can be explained by socioeconomic differences in cancer stage, comorbidity, treatment or lifestyle factors. In the Danish Gynaecological Cancer Database we identified 2873 cases of ovarian cancer diagnosed between 2005 and 2010. From this data we retrieved information on prognostic factors, treatment information and lifestyle factors. Age, vital status, comorbidity, education, income and cohabitation status were ascertained from nationwide administrative registers. Associations were analyzed with logistic regression and Cox regression models. Educational level was weakly associated with cancer stage. Short education, lower income and living without a partner were related to poorer survival after ovarian cancer. Among women with early cancer stage, HR (95% CI) for death was 1.75 (1.20-2.54) in shorter compared to longer educated women. After adjustment for comorbid conditions, cancer stage, tumour histology, operation status and lifestyle factors, socioeconomic differences in survival persisted. Socioeconomic disparities in survival after ovarian cancer were to some extent, but not fully explained by differences in important prognostic factors, suggesting further investigations into this problem, however implying that socially less advantaged ovarian cancer patients should receive attention during cancer treatment and rehabilitation. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Apr 2015
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    ABSTRACT: Background An association between education and preterm delivery has been observed in populations across Europe, but differences in methodology limit comparability. We performed a direct cross-cohort comparison of educational disparities in preterm delivery based on individual-level birth cohort data.Methods The study included data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal, and Spain. The cohorts included between 2434 and 99 655 pregnancies. The association between maternal education and preterm delivery (22–36 completed weeks of gestation) was reported as risk ratios, risk differences, and slope indexes of inequality with 95% confidence intervals (CIs).ResultsSingleton preterm live delivery proportion varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and maternal characteristics. Nevertheless, there were similar educational differences in risk of preterm delivery in 8 of the 12 cohorts with slope index of inequality varying between 2.2 [95% CI 1.1, 3.3] and 4.0 [95% CI 1.4, 6.6] excess preterm deliveries per 100 singleton deliveries among the educationally most disadvantaged, and risk ratio between the lowest and highest education category varying from 1.4 [95% CI 1.1, 1.8] to 1.9 [95% CI 1.2, 3.1]. No associations were found in the last four cohorts.Conclusions Educational disparities in preterm delivery were found all over Europe. Despite differences in the distributions of education and preterm delivery, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics did not explain the differences.
    Full-text · Article · Apr 2015 · Paediatric and Perinatal Epidemiology
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    ABSTRACT: PurposeThe aim of this Cohort study of 10 527 Danish men was to investigate the extent to which the association between hypnotics and mortality is confounded by several markers of disease and living conditions.Methods Exposure was purchases of hypnotics 1995–1999 (“low users” (150 or less defined daily dose (DDD)) or “high users” (151 or more DDD)). Follow-up for all-cause mortality was from 1 Jan 2000 to 19 June 2010. Cox proportional hazard models were used to study the association. Covariates were entered one at a time and simultaneously. Results were reported using hazard ratio (HR) and 95% confidence intervals (CI).ResultsWhen covariates were entered one at a time, the changes in HR estimates showed that psychiatric disease, socioeconomic position and substance abuse reduced the excess risk by 17–36% in the low user group and by 45–52% in the high user group. Somatic disease, intelligence score and cohabitation reduced the excess risk by 2–11% in the low user group and 8–24% in the high user group. When adjusting for all covariates, the HR was reduced to 1.22 95% CI (0.97–1.54) in the low user group and 1.43 95% CI (1.11–1.85) in the high user group.Conclusions The results of this study point at psychiatric disease, substance abuse and socioeconomic position as potential confounding factors partly explaining the association between use of hypnotics and all-cause mortality. Copyright © 2015 John Wiley & Sons, Ltd.
    Full-text · Article · Feb 2015 · Pharmacoepidemiology and Drug Safety
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    ABSTRACT: To estimate the association between educational status and alcohol-related somatic and non-somatic morbidity and mortality among full siblings in comparison with non-related individuals. Cohort study. Denmark. Approximately 1.4 million full siblings born in Denmark between 1950 and 1979 were followed from age 28 until age 58 or censoring due to alcohol-related hospitalization and mortality. Cox-regression analyses were used to estimate associations of educational status with alcohol-related outcomes. Results from cohort analyses based on non-related individuals and inter-sibling analyses were compared. A lower educational status was associated with a higher rate of alcohol-related outcomes, especially among the youngest (28-37 years of age) and individuals born 1970-1979. Compared with the cohort analyses, the associations attenuated slightly in the inter-sibling analysis. For example in the cohort analysis, females with a basic school education born 1970-1979 had an increased rate of alcohol-related non-somatic morbidity and mortality (Hazard rate ratio (HR) =4.05, CI 95% 3.27-5.02) compared to those with a vocational education. In the inter-sibling analysis, the HR attenuated (HR = 2.66, CI 95% 1.95-3.63). For alcohol-related somatic outcomes the corresponding figures were HR = 3.47 (CI 95% 2.63-4.58) and HR = 3.36 (CI 95% 2.10-5.38), respectively. In general, the associations were stronger among females than males (aged 28-37) in the analyses on alcohol-related non-somatic outcomes. Health conditions earlier in life explained only a minor part of the associations. The association between educational status and alcohol-related somatic and non-somatic morbidity and mortality is only to a small degree driven by familial factors. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2014 · Addiction
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    ABSTRACT: Background An educational gradient in preterm birth has been observed in many countries. The distribution of education and other characteristics of women giving birth are the end result of complex processes that play out over the life course. If these processes play out differently in different contexts, cross-cohort comparisons may be helpful in understanding the educational gradient in preterm birth. We performed a cross-cohort comparison of educational disparities in preterm birth based on European birth cohort data. Methods The study included individual-level data from 12 European cohorts from Denmark, England, France, Lithuania, the Netherlands, Norway, Italy, Portugal and Spain. The studies covered the period 1990 to 2012 and included between 2434 and 99,655 pregnancies each. The association between maternal education and preterm birth for singleton live births was examined separately in each cohort by linear and logistic regression and reported as risk ratios, risk differences and slope indexes of inequality. Results The percentage of singleton preterm live births varied between 3.7% and 7.5%. There were large variations between the cohorts in the distribution of education and other maternal characteristics. In spite of this, there were similar educational differences in risk of preterm birth in 8 of the 12 cohorts. In these cohorts, the slope index of inequality varied between 2.2 and 3.2 per 100 singleton live births, and relative risk between the lowest and highest education group varied from 1.4 to 1.9. In the remaining 4 cohorts from England, France, Italy and Portugal, one showed a weaker gradient (Slope Index of Inequality =1.5 (-1.0, 3.9)), two showed no educational differences (SII=-0.3 (-2.0, 1.5) and SII=0.9 (-1.3, 3.1)), and the gradient was reversed in the last cohort (SII=-1.2 (-4.6, 2.3)). Conclusion Educational disparities in risk of preterm birth were found in birth cohorts from all over Europe. Despite differences in the distribution of education and level of preterm birth, the results were remarkably similar across the cohorts. For those few cohorts that did not follow the pattern, study and country characteristics were unable to explain the differences.
    No preview · Article · Sep 2014 · Journal of Epidemiology & Community Health
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    ABSTRACT: Cognitive abilities decline with age, but with considerable individual variation. The neurobiological correlate of this variation is not well described. Functional brain imaging studies have demonstrated reduced task-induced deactivation (TID) of the brain's default mode network (DMN) in a wide range of neurodegenerative diseases involving cognitive symptoms, in conditions with increased risk of Alzheimer's disease, and even in advanced but healthy aging. Here, we investigated brain activation and deactivation during a visual-motor task in 185 clinically healthy males from a Danish birth cohort, whose cognitive function was assessed in youth and midlife. Using each individual as his own control, we defined a group with a large degree of cognitive decline, and a control group. When correcting for effects of total cerebral blood flow and hemoglobin level, we found reduced TID in the posterior region of the DMN in the cognitive decline group compared to the control group. Furthermore, increased visual activation response was found in the cognitive decline group, indicating that the TID reduction was not exclusively due to overall impaired vascular reactivity. These results suggest a neurobiological basis for subclinical cognitive decline in late midlife, which includes TID alterations similar to the pattern seen in patients with AD and mild cognitive impairment. Hence, TID reduction might be suggested as an early marker for subtle cognitive decline in aging. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    No preview · Article · Sep 2014 · Human Brain Mapping

Publication Stats

7k Citations
917.46 Total Impact Points


  • 1995-2015
    • Glostrup Hospital
      • • Research Centre for Prevention and Health
      • • Centre for Preventive Medicine
      • • Medical Department C
      Glostrup, Capital Region, Denmark
  • 1993-2015
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 1992-2015
    • Aarhus University
      • • Danish Pain Research Center
      • • Department of Clinical Epidemiology
      Aarhus, Central Jutland, Denmark
  • 2006-2014
    • University of Southern Denmark
      • • Aging Research Center
      • • Institute of Public Health
      Odense, South Denmark, Denmark
  • 2013
    • Odense Zoo
      Odense, South Denmark, Denmark
  • 2012
    • Danish Cancer Society
      København, Capital Region, Denmark
  • 2008
    • National Institute of Public Health
      København, Capital Region, Denmark
  • 1997-2003
    • Copenhagen University Hospital Hvidovre
      • Department of Cardiology
      Hvidovre, Capital Region, Denmark
  • 2002
    • National Institute of Public Health, Denmark
      København, Capital Region, Denmark
  • 1998-2002
    • Copenhagen University Hospital
      København, Capital Region, Denmark
  • 1999
    • Statens Serum Institut
      København, Capital Region, Denmark
  • 1996
    • University of Copenhagen
      København, Capital Region, Denmark