Noget om Agerbruget i en jydsk Hedeegn.

Noget om Agerbruget i en jydsk Hedeegn

Coupled aeroelastic shape and topology optimization of wings

This paper presents a method for simultaneous optimization of the outer shape and internal topology of aircraft wings, with the objective of minimizing drag subject to lift and compliance constraints for multiple load cases. The physics are evaluated by the means of a source-doublet panel method for the aerodynamic response and linear elastic finite elements for the structural response, which are one way coupled. At each design iteration a mapping procedure is applied to map the current wing shape and corresponding pressure loads to the unfitted finite element mesh covering the design domain. Wings of small fixed-wing airplanes both, with and without a stiffening strut, are optimized. The resulting wings show internal topologies with struts and wall-truss combinations, depending on the design freedom of the shape optimization. The lift distributions of the optimized wings show patterns similar to the ones obtained when performing optimization of wing shapes with constraints on the bending moment at the root

Novel model of neuronal bioenergetics: postsynaptic utilization of glucose but not lactate correlates positively with Ca2+ signalling in cultured mouse glutamatergic neurons

We have previously investigated the relative roles of extracellular glucose and lactate as fuels for glutamatergic neurons during synaptic activity. The conclusion from these studies was that cultured glutamatergic neurons utilize glucose rather than lactate during NMDA (N-methyl-d-aspartate)-induced synaptic activity and that lactate alone is not able to support neurotransmitter glutamate homoeostasis. Subsequently, a model was proposed to explain these results at the cellular level. In brief, the intermittent rises in intracellular Ca2+ during activation cause influx of Ca2+ into the mitochondrial matrix thus activating the tricarboxylic acid cycle dehydrogenases. This will lead to a lower activity of the MASH (malate–aspartate shuttle), which in turn will result in anaerobic glycolysis and lactate production rather than lactate utilization. In the present work, we have investigated the effect of an ionomycin-induced increase in intracellular Ca2+ (i.e. independent of synaptic activity) on neuronal energy metabolism employing 13C-labelled glucose and lactate and subsequent mass spectrometric analysis of labelling in glutamate, alanine and lactate. The results demonstrate that glucose utilization is positively correlated with intracellular Ca2+ whereas lactate utilization is not. This result lends further support for a significant role of glucose in neuronal bioenergetics and that Ca2+ signalling may control the switch between glucose and lactate utilization during synaptic activity. Based on the results, we propose a compartmentalized CiMASH (Ca2+-induced limitation of the MASH) model that includes intracellular compartmentation of glucose and lactate metabolism. We define pre- and post-synaptic compartments metabolizing glucose and glucose plus lactate respectively in which the latter displays a positive correlation between oxidative metabolism of glucose and Ca2+ signalling

Prevalence of molecular markers of anti-malarial drug resistance in Plasmodium vivax and Plasmodium falciparum in two districts of Nepal

<p>Abstract</p> <p>Background</p> <p>Sulphadoxine-pyrimethamine (SP) and chloroquine (CQ) have been used in treatment of falciparum and vivax malaria in Nepal. Recently, resistance to both drugs have necessitated a change towards artemisinin combination therapy (ACT) against <it>Plasmodium falciparum </it>in highly endemic areas. However, SP is still used against <it>P. falciparum </it>infections in low endemic areas while CQ is used in suspected cases in areas with lack of diagnostic facilities. This study examines the prevalence of molecular markers of CQ and SP resistance in <it>P. falciparum </it>and <it>Plasmodium vivax </it>to determine if high levels of <it>in vivo </it>resistance are reflected at molecular level as well.</p> <p>Methods</p> <p>Finger prick blood samples (n = 189) were collected from malaria positive patients from two high endemic districts and analysed for single nucleotide polymorphisms (SNPs) in the resistance related genes of <it>P. falciparum </it>and <it>P. vivax </it>for CQ (<it>Pfcrt, Pfmdr1, Pvmdr1</it>) and SP (<it>Pfdhfr, Pfdhps, Pvdhfr</it>), using various PCR-based methods.</p> <p>Results and discussion</p> <p>Positive <it>P. vivax </it>and <it>P. falciparum </it>infections were identified by PCR in 92 and 41 samples respectively. However, some of these were negative in subsequent PCRs. Based on a few <it>P. falciparum </it>samples, the molecular level of CQ resistance in <it>P. falciparum </it>was high since nearly all parasites had the <it>Pfcrt </it>mutant haplotypes CVIET (55%) or SVMNT (42%), though frequency of the <it>Pfmdr1 </it>wild type haplotype was relatively low (35%). Molecular level of SP resistance in <it>P. falciparum </it>was found to be high. The most prevalent <it>Pfdhfr </it>haplotype was double mutant CNRNI (91%), while frequency of <it>Pfdhps </it>double mutant SGEAA and AGEAA were 38% and 33% respectively. Combined, the frequency of quadruple mutations (CNRNI-SGEAA/AGEAA) was 63%. Based on <it>P. vivax </it>samples, low CQ and SP resistance were most likely due to low prevalence of <it>Pvmdr1 </it>Y976F mutation (5%) and absence of triple/quadruple mutations in <it>Pvdhfr</it>.</p> <p>Conclusions</p> <p>Based on the limited number of samples, prevalence of CQ and SP resistance at molecular levels in the population in the study area were determined as high in <it>P. falciparum </it>and low in <it>P. vivax</it>. Therefore, CQ could still be used in the treatment of <it>P. vivax </it>infections, but this remains to be tested <it>in vivo </it>while the change to ACT for <it>P. falciparum </it>seems justified.</p

Bronchopulmonary dysplasia with focus on early prediction and treatment: a narrative review

Background and Objective: Bronchopulmonary dysplasia (BPD) remains a major cause of morbidity and mortality in very preterm infants though early non-invasive ventilation and surfactant treatment and other neonatal therapies have improved the outcome. Therefore, it is necessary to find effective supplemental methods for prediction of BPD. Better understanding of the etiology and molecular mechanisms involved in the pathogenesis of BPD is necessary for development of new effective early treatments. It is generally accepted that BPD is a multifactorial disease often associated with intrauterine infections and placental perfusion disorders. Methods: Recently a new method to predict BPD at birth using artificial intelligence (AI) has been developed. This new method improves the likelihood of developing effective early treatments for BPD. The method combines information on early surfactant treatment, birth weight and gestational age (GA) with analysis of the mid-infrared spectrum of the molecules in gastric aspirate which are produced in the newborn’s lungs. The described methods for early treatment of BPD in this review among others covers inositol, retinol, super oxide dismutase, Clara cell 10 protein, corticosteroids, azithromycin, macrolide and stem cell therapy besides general treatments as nasal continuous positive airway pressure (NCPAP), surfactant, caffeine, oxygen saturation targeting and nutrition. The literature search was performed systemically online via the databases PubMed and Medline between January 1, 2011 and December 31, 2022. Key Content and Findings: A method to predict BPD immediately after birth is now available allowing possibility to develop effective early treatments of BPD. Conclusions: The present review focuses on early prediction and the existing pharmacologic interventions highlighting the potential to improve the outcome of infants with BPD

Analysis of polymorphisms in the merozoite surface protein-3α gene and two microsatellite loci in Sri Lankan Plasmodium vivax: evidence of population substructure in Sri Lanka.

The geographical distribution of genetic variation in Plasmodium vivax samples (N = 386) from nine districts across Sri Lanka is described using three markers; the P. vivax merozoite surface protein-3α (Pvmsp-3α) gene, and the two microsatellites m1501 and m3502. At Pvmsp-3α, 11 alleles were found with an expected heterozygosity (H(e)) of 0.81, whereas at m1501 and m3502, 24 alleles (H(e) = 0.85) and 8 alleles (H(e) = 0.74) were detected, respectively. Overall, 95 unique three locus genotypes were detected among the 279 samples positive at all three loci (H(e) = 0.95). Calculating the pairwise fixation index (F(ST)) revealed statistically significant population structure. The presence of identical 2-loci microsatellite genotypes in a significant proportion of samples revealed local clusters of closely related isolates contributing to strong linkage disequilibrium between marker alleles. The results show evidence of high genetic diversity and possible population substructure of P. vivax populations in Sri Lanka

Distribution, size, shape, growth potential and extent of abdominal aortic calcified deposits predict mortality in postmenopausal women

Background: Aortic calcification is a major risk factor for death from cardiovascular disease. We investigated the relationship between mortality and the composite markers of number, size, morphology and distribution of calcified plaques in the lumbar aorta.Methods: 308 postmenopausal women aged 48-76 were followed for 8.3 ± 0.3 years, with deaths related to cardiovascular disease, cancer, or other causes being recorded. From lumbar X-rays at baseline the number (NCD), size, morphology and distribution of aortic calcification lesions were scored and combined into one Morphological Atherosclerotic Calcification Distribution (MACD) index. The hazard ratio for mortality was calculated for the MACD and for three other commonly used predictors: the EU SCORE card, the Framingham Coronary Heart Disease Risk Score (Framingham score), and the gold standard Aortic Calcification Severity score (AC24) developed from the Framingham Heart Study cohorts.Results: All four scoring systems showed increasing age, smoking, and raised triglyceride levels were the main predictors of mortality after adjustment for all other metabolic and physical parameters. The SCORE card and the Framingham score resulted in a mortality hazard ratio increase per standard deviation (HR/SD) of 1.8 (1.51-2.13) and 2.6 (1.87-3.71), respectively. Of the morphological x-ray based measures, NCD revealed a HR/SD >2 adjusted for SCORE/Framingham. The MACD index scoring the distribution, size, morphology and number of lesions revealed the best predictive power for identification of patients at risk of mortality, with a hazard ratio of 15.6 (p < 0.001) for the 10% at greatest risk of death.Conclusions: This study shows that it is not just the extent of aortic calcification that predicts risk of mortality, but also the distribution, shape and size of calcified lesions. The MACD index may provide a more sensitive predictor of mortality from aortic calcification than the commonly used AC24 and SCORE/Framingham point card systems

Cruciferous vegetable intake is inversely associated with extensive abdominal aortic calcification in elderly women: a cross-sectional study

We have previously shown higher intake of cruciferous vegetables is inversely associated with carotid artery intima-media thickness. To further test the hypothesis that an increased consumption of cruciferous vegetables is associated with reduced indicators of structural vascular disease in other areas of the vascular tree, we aimed to investigate the cross-sectional association between cruciferous vegetable intake and extensive calcification in the abdominal aorta. Dietary intake was assessed, using a food frequency questionnaire, in 684 older women from the Calcium Intake Fracture Outcome Study. Cruciferous vegetables included cabbage, Brussels sprouts, cauliflower and broccoli. Abdominal aortic calcification (AAC) was scored using the Kauppila AAC24 scale on dual energy x-ray absorptiometry (DXA) lateral spine images, and was categorised as “not extensive” (0-5) or “extensive” (≥6). Mean age was 74.9 (SD 2.6) y, median cruciferous vegetable intake was 28.2 (IQR 15.0-44.7) g/d, and 128/684 (18.7%) women had extensive AAC scores. Those with higher intakes of cruciferous vegetables ( \u3e 44.6 g/d) were associated with a 46% lower odds of having extensive AAC in comparison to those with lower intakes ( \u3c 15.0 g/d) after adjustment for lifestyle, dietary and cardiovascular disease risk factors (ORQ4 vs Q1=0.54, 95%CI 0.30, 0.97, P=0.036). Total vegetable intake and each of the other vegetable types were not related to extensive AAC (P \u3e 0.05 for all). This study strengthens the hypothesis that higher intake of cruciferous vegetables may protect against vascular calcification

Anthropometry, carbohydrate and lipid metabolism in the East Flanders Prospective Twin Survey: heritabilities

AIMS/HYPOTHESIS: We determined the genetic contribution of 18 anthropometric and metabolic risk factors of type 2 diabetes using a young healthy twin population. METHODS: Traits were measured in 240 monozygotic (MZ) and 138 dizygotic (DZ) twin pairs aged 18 to 34 years. Twins were recruited from the Belgian population-based East Flanders Prospective Twin Survey, which is characterised by its accurate zygosity determination and extensive collection of perinatal and placental data, including information on chorionicity. Heritability was estimated using structural equation modelling implemented in the Mx software package. RESULTS: Intra-pair correlations of the anthropometric and metabolic characteristics did not differ between MZ monochorionic and MZ dichorionic pairs; consequently heritabilities were estimated using the classical twin approach. For body mass, BMI and fat mass, quantitative sex differences were observed; genetic variance explained 84, 85 and 81% of the total variation in men and 74, 75 and 70% in women, respectively. Heritability estimates of the waist-to-hip ratio, sum of four skinfold thicknesses and lean body mass were 70, 74 and 81%, respectively. The heritability estimates of fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance and beta cell function, as well as insulin-like growth factor binding protein-1 levels were 67, 49, 48, 62 and 47%, in that order. Finally, for total cholesterol, LDL-cholesterol, HDL-cholesterol, total cholesterol:HDL-cholesterol ratio, triacylglycerol, NEFA and leptin levels, genetic factors explained 75, 78, 76, 79, 58, 37 and 53% of the total variation, respectively. CONCLUSIONS/INTERPRETATION: Genetic factors explain the greater part of the variation in traits related to obesity, glucose intolerance/insulin resistance and dyslipidaemia