Norge från stark unionspartner till underlydande rike

I anledning af 200-året for freden i Kiel i januar 1814, hvor Danmark- Norge under Frederik VI måtte afstå Norge til Sverige, hvorved unionen imellem de to lande fra 1380 sprængtes, afholdt Det Kongelige Bibliotek en foredragsrække om “Danmark-Norge før og efter 1814”. Disse foredrag bringes i let redigeret udgave i dette og kommende numre af Magasin. Denne artikel om Kalmarunionen indleder temaet.I anledning af 200-året for freden i Kiel i januar 1814, hvor Danmark- Norge under Frederik VI måtte afstå Norge til Sverige, hvorved unionen imellem de to lande fra 1380 sprængtes, afholdt Det Kongelige Bibliotek en foredragsrække om “Danmark-Norge før og efter 1814”. Disse foredrag bringes i let redigeret udgave i dette og kommende numre af Magasin. Denne artikel om Kalmarunionen indleder temaet

Urinary proteomics pilot study for biomarker discovery and diagnosis in heart failure with reduced ejection fraction

Background Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF) may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF. Methods and Results Urine samples were analyzed by on-line capillary electrophoresis coupled to electrospray ionization micro time-of-flight mass spectrometry (CE-MS) to generate individual urinary proteome profiles. In an initial biomarker discovery cohort, analysis of urinary proteome profiles from 33 HFrEF patients and 29 age- and sex-matched individuals without HFrEF resulted in identification of 103 peptides that were significantly differentially excreted in HFrEF. These 103 peptides were used to establish the support vector machine-based HFrEF classifier HFrEF103. In a subsequent validation cohort, HFrEF103 very accurately (area under the curve, AUC = 0.972) discriminated between HFrEF patients (N = 94, sensitivity = 93.6%) and control individuals with and without impaired renal function and hypertension (N = 552, specificity = 92.9%). Interestingly, HFrEF103 showed low sensitivity (12.6%) in individuals with diastolic left ventricular dysfunction (N = 176). The HFrEF-related peptide biomarkers mainly included fragments of fibrillar type I and III collagen but also, e.g., of fibrinogen beta and alpha-1-antitrypsin. Conclusion CE-MS based urine proteome analysis served as a sensitive tool to determine a vast array of HFrEF-related urinary peptide biomarkers which might help improving our understanding and diagnosis of heart failure

Usefulness of the Athlete Burnout Questionnaire (ABQ) as a screening tool for the detection of clinically relevant burnout symptoms among young elite athletes

Objectives: Having psychometrically sound instruments is essential to the understanding of the determinants and consequences of athlete burnout. Therefore, this study examines the psychometric properties of a German version of the Athlete Burnout Questionnaire (ABQ) and its usefulness as a screening tool for the detection of clinically relevant burnout symptoms. Design: Prospective study. Method: 257 young elite athletes were recruited from Swiss Olympic Sport Classes (37% females; M = 16.8 years, SD = 1.4). 197 students were assessed a second time after six months. All students filled in a standardized questionnaire about domain-specific and domain-unspecific burnout symptoms, depressive symptoms, stress, and life satisfaction. Results: Confirmatory factor analysis supported the three-factor structure of the ABQ. Moreover, all subscales had acceptable internal consistency. Support was also found for the convergent validity of the ABQ; all subscales were positively correlated with perceived stress, burnout and depression, whereas negative correlations existed with life satisfaction. By contrast, some ABQ subscales shared only limited variance, the three ABQ subscales did not predict each other across time, and none of the ABQ subscales was suitable for the screening of clinically relevant burnout symptoms. Conclusions: While the factor structure and internal consistency of the ABQ was supported, our study corroborates previous concerns about the psychometric properties and validity of the ABQ. While the ABQ has advanced research on athlete burnout, we hold that further debates about the most suitable way to assess burnout among elite athletes are urgently needed

Policies to Enhance Prescribing Efficiency in Europe: Findings and Future Implications

Introduction: European countries need to learn from each other to address unsustainable increases in pharmaceutical expenditures. Objective: To assess the influence of the many supply and demand-side initiatives introduced across Europe to enhance prescribing efficiency in ambulatory care. As a result provide future guidance to countries. Methods: Cross national retrospective observational study of utilization (DDDs – defined daily doses) and expenditure (Euros and local currency) of proton pump inhibitors (PPIs) and statins among 19 European countries and regions principally from 2001 to 2007. Demand-side measures categorized under the “4Es” – education engineering, economics, and enforcement. Results: Instigating supply side initiatives to lower the price of generics combined with demand-side measures to enhance their prescribing is important to maximize prescribing efficiency. Just addressing one component will limit potential efficiency gains. The influence of demand-side reforms appears additive, with multiple initiatives typically having a greater influence on increasing prescribing efficiency than single measures apart from potentially “enforcement.” There are also appreciable differences in expenditure (€/1000 inhabitants/year) between countries. Countries that have not introduced multiple demand side measures to counteract commercial pressures to enhance the prescribing of generics have seen considerably higher expenditures than those that have instigated a range of measures. Conclusions: There are considerable opportunities for European countries to enhance their prescribing efficiency, with countries already learning from each other. The 4E methodology allows European countries to concisely capture the range of current demand-side measures and plan for the future knowing that initiatives can be additive to further enhance their prescribing efficiency

In Vivo Mapping of Vascular Inflammation Using Multimodal Imaging

Plaque vulnerability to rupture has emerged as a critical correlate to risk of adverse coronary events but there is as yet no clinical method to assess plaque stability in vivo. In the search to identify biomarkers of vulnerable plaques an association has been found between macrophages and plaque stability--the density and pattern of macrophage localization in lesions is indicative of probability to rupture. In very unstable plaques, macrophages are found in high densities and concentrated in the plaque shoulders. Therefore, the ability to map macrophages in plaques could allow noninvasive assessment of plaque stability. We use a multimodality imaging approach to noninvasively map the distribution of macrophages in vivo. The use of multiple modalities allows us to combine the complementary strengths of each modality to better visualize features of interest. Our combined use of Positron Emission Tomography and Magnetic Resonance Imaging (PET/MRI) allows high sensitivity PET screening to identify putative lesions in a whole body view, and high resolution MRI for detailed mapping of biomarker expression in the lesions.Macromolecular and nanoparticle contrast agents targeted to macrophages were developed and tested in three different mouse and rat models of atherosclerosis in which inflamed vascular plaques form spontaneously and/or are induced by injury. For multimodal detection, the probes were designed to contain gadolinium (T1 MRI) or iron oxide (T2 MRI), and Cu-64 (PET). PET imaging was utilized to identify regions of macrophage accumulation; these regions were further probed by MRI to visualize macrophage distribution at high resolution. In both PET and MR images the probes enhanced contrast at sites of vascular inflammation, but not in normal vessel walls. MRI was able to identify discrete sites of inflammation that were blurred together at the low resolution of PET. Macrophage content in the lesions was confirmed by histology.The multimodal imaging approach allowed high-sensitivity and high-resolution mapping of biomarker distribution and may lead to a clinical method to predict plaque probability to rupture

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants