Model til belysning af effekten af uddybning af Drogden

Vurdering af effekten af en uddybning af Drogden til 9m, henholdsvis 10 m er gennemført ved at udvikle en simpel trafikmodel for skibstrafikken gennem de danske farvande. Modellen er baseret på en detaljeret analyse af en række forskellige datakilder, kalibrering til observerede godsstrømme og fartøjspassager, samt skønsmæssige vurderinger af den fremtidige udvikling af skibstypers størrelse, dybgang og lasteevne. Konklusionen på analysen er, at der er behov for en vedholdende indsats for at holde trafikken gennem de danske farvande under observation. Kun herigennem opnås en viden om udviklingen i kritiske parametre som dybgang, længde og lasteevne for forskellige skibstyper, der muliggør et bedre grundlag for fremtidige prognoser af trafikken

Plasma organochlorine concentrations and bone ultrasound measurements: a cross-sectional study in peri-and postmenopausal Inuit women from Greenland

BACKGROUND: Inuit women are highly exposed through their traditional seafood based diet to organochlorine compounds, some of them displaying endocrine disrupting properties. We hypothesized that this exposure might be related to bone characteristics that are altered in osteoporosis, because hormone deficiency is a known risk factor for the disease. METHODS: We measured quantitative ultrasound parameters (QUS) at the right calcaneum of 153 peri- and postmenopausal Inuit women (49–64 year old) from Nuuk, Greenland, and investigated the relation between these parameters and plasma organochlorine concentrations. We used high-resolution gas chromatography with electron capture detection to analyze plasma samples for 14 polychlorinated biphenyls (PCB) congeners and 11 chlorinated pesticides and metabolites. We analysed morning urine samples for cadmium, a potential confounder, by atomic absorption spectrometry. We used a validated questionnaire to document dietary and lifestyle habits as well as reproductive and medical histories. RESULTS: Concentrations of PCB 153, a surrogate of exposure to most organochlorines present in plasma samples, were inversely correlated to QUS parameters in univariate analyses (p < 0.001). However, PCB 153 concentrations were not associated with QUS values in multivariate analyses that comprised potential confounding factors such as age, body weight, former oral contraceptive use and current hormone replacement therapy (HRT) use, which were all significant predictors of bone stiffness (total R(2 )= 0.39; p < 0.001). CONCLUSION: Overall we found little evidence that organochlorines exposure is related to osteoporosis in Greenlandic Inuit women, but the hypothesis that exposure to dioxin-like compounds might be linked to decreased bone quality and osteoporosis deserves further attention

Non-disjunction of chromosome 13

We performed a molecular study with 21 microsatellites on a sample of 82 trisomy 13 conceptuses, the largest number of cases studied to date. The parental origin was determined in every case and in 89% the extra chromosome 13 was of maternal origin with an almost equal number of maternal MI and MII errors. The latter finding is unique among human autosomal trisomies, where maternal MI (trisomies 15, 16, 21, 22) or MII (trisomy 18) errors dominate. Of the nine paternally derived cases five were of MII origin but none arose from MI errors. There was some evidence for elevated maternal age in cases with maternal meiotic origin for liveborn infants. Maternal and paternal ages were elevated in cases with paternal meiotic origin. This is in contrast to results from a similar study of non-disjunction of trisomy 21 where paternal but not maternal age was elevated. We find clear evidence for reduced recombination in both maternal MI and MII errors and the former is associated with a significant number of tetrads (33%) that are nullichiasmate, which do not appear to be a feature of normal chromosome 13 meiosis. This study supports the evidence for subtle chromosome-specific influences on the mechanisms that determine non-disjunction of human chromosomes, consistent with the diversity of findings for other trisomie

Low-Density Lipoprotein Cholesterol, Non–High-Density Lipoprotein Cholesterol, Triglycerides, and Apolipoprotein B and Cardiovascular Risk in Patients With Manifest Arterial Disease

Low-density lipoprotein cholesterol (LDL-C) only partly represents the atherogenic lipid burden, and a growing body of evidence suggests that non–high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and apolipoprotein B (apoB) are more accurate in estimating lipid-related cardiovascular disease risk. Our objective was to compare the relation among LDL-C, non-HDL-C, triglycerides, and apoB and the occurrence of future vascular events and mortality in patients with manifest arterial disease. This is a prospective cohort study of 7,216 patients with clinically manifest arterial disease in the Secondary Manifestations of Arterial Disease Study. Cox proportional hazard models were used to quantify the risk of major cardiovascular events (MACE; i.e., stroke, myocardial infarction, and vascular mortality) and all-cause mortality. Interaction was tested for type of vascular disease at inclusion. MACE occurred in 1,185 subjects during a median follow-up of 6.5 years (interquartile range 3.4 to 9.9 years). Adjusted hazard ratios (HRs) of MACE per 1 SD higher were for LDL-C (HR 1.15, 95% confidence interval [CI] 1.09 to 1.22), for non-HDL-C (HR 1.17, 95% CI 1.11 to 1.23), for log(triglycerides) (HR 1.12, 95% CI 1.06 to 1.19), and for apoB HR (1.12, 95% CI 0.99 to 1.28). The relation among LDL-C, non-HDL-C, and cardiovascular events was comparable in patients with cerebrovascular disease, coronary artery disease, or polyvascular disease and absent in those with aneurysm of abdominal aorta or peripheral artery disease. In conclusion, in patients with a history of cerebrovascular, coronary artery, or polyvascular disease, but not aneurysm of abdominal aorta or peripheral artery disease, higher levels of LDL-C and non-HDL-C are related to increased risk of future MACE and of comparable magnitude

Microsphere-Based Rapamycin Delivery, Systemic Versus Local Administration in a Rat Model of Renal Ischemia/Reperfusion Injury

The increasing prevalence and treatment costs of kidney diseases call for innovative therapeutic strategies that prevent disease progression at an early stage. We studied a novel method of subcapsular injection of monodisperse microspheres, to use as a local delivery system of drugs to the kidney. We generated placebo- and rapamycin monodisperse microspheres to investigate subcapsular delivery of drugs. Using a rat model of acute kidney injury, subcapsular injection of placebo and rapamycin monodisperse microspheres (monospheres) was compared to subcutaneous injection, mimicking systemic administration. We did not find any adverse effects related to the delivery method. Irrespective of the injection site, a similar low dose of rapamycin was present in the circulation. However, only local intrarenal delivery of rapamycin from monospheres led to decreased macrophage infiltration and a significantly lower amount of myofibroblasts in the kidney, where systemic administration did not. Local delivery of rapamycin did cause a transient increase in the deposition of collagen I, but not of collagen III. We conclude that therapeutic effects can be increased when rapamycin is delivered subcapsularly by monospheres, which, combined with low systemic concentrations, may lead to an effective intrarenal delivery method

Life-long impairment of glucose homeostasis upon prenatal exposure to psychostimulants

Maternal drug abuse during pregnancy is a rapidly escalating societal problem. Psychostimulants, including amphetamine, cocaine, and methamphetamine, are amongst the illicit drugs most commonly consumed by pregnant women. Neuropharmacology concepts posit that psychostimulants affect monoamine signaling in the nervous system by their affinities to neurotransmitter reuptake and vesicular transporters to heighten neurotransmitter availability extracellularly. Exacerbated dopamine signaling is particularly considered as a key determinant of psychostimulant action. Much less is known about possible adverse effects of these drugs on peripheral organs, and if in utero exposure induces lifelong pathologies. Here, we addressed this question by combining human RNA-seq data with cellular and mouse models of neuroendocrine development. We show that episodic maternal exposure to psychostimulants during pregnancy coincident with the intrauterine specification of pancreatic beta cells permanently impairs their ability of insulin production, leading to glucose intolerance in adult female but not male offspring. We link psychostimulant action specifically to serotonin signaling and implicate the sex-specific epigenetic reprogramming of serotonin-related gene regulatory networks upstream from the transcription factor Pet1/Fev as determinants of reduced insulin production.Peer reviewe

Study of Spin and Decay-Plane Correlations of W Bosons in the e+e- -> W+W- Process at LEP

Data collected at LEP at centre-of-mass energies \sqrt(s) = 189 - 209 GeV are used to study correlations of the spin of W bosons using e+e- -> W+W- -> lnqq~ events. Spin correlations are favoured by data, and found to agree with the Standard Model predictions. In addition, correlations between the W-boson decay planes are studied in e+e- -> W+W- -> lnqq~ and e+e- -> W+W- -> qq~qq~ events. Decay-plane correlations, consistent with zero and with the Standard Model predictions, are measured