PET kinetics of radiolabeled antidepressant, [N-methyl-11C]mirtazapine, in the human brain

BACKGROUND: We compared six kinetic models with and without the requirement of arterial cannulation for estimating the binding potential of [N-methyl-(11)C]mirtazapine in the living human brain. METHODS: Distribution volumes of [N-methyl-(11)C]mirtazapine in brain regions were estimated using single- and two-tissue compartment models as well as a graphical plasma input model. The two-tissue compartment model provided a direct estimate of the binding potentials of [N-methyl-(11)C]mirtazapine in brain regions, while binding potentials of the single-tissue compartment model and the graphical plasma input model were estimated indirectly from ratios of distribution volumes in brain regions. We obtained also direct estimates of binding potentials using a graphical reference tissue model and two nonlinear reference tissue models. RESULTS: The two-tissue compartment model required several fits with different initial guesses for avoiding negative values of parameters. Despite the extra fits, estimates of distribution volumes and binding potentials of [N-methyl-(11)C]mirtazapine obtained by the two-tissue compartment model were far more variable than those produced by the other methods. The graphical plasma input method and the graphical reference tissue method provided estimates of the binding potential that correlated closely, but differed in magnitude. The single-tissue compartment model provided relatively low estimates of binding potentials with curves that failed to fit the data as well as the three other methods that used the entire series of positron emission tomography data. The reference tissue method and the simplified reference tissue method provided similar, consistent estimates of binding potentials. However, certain assumptions of the simplified reference tissue method may not be fulfilled by the radioligand. CONCLUSION: The reference tissue method is appropriate for estimating the binding potential of [N-methyl-(11)C]mirtazapine in regions of the human brain so that the binding potential of [N-methyl-(11)C]mirtazapine can be estimated without arterial cannulation

Estudo dos líquenes dos Açores. Parte 2 - Líquenes das encostas de altitude da montanha do Pico. Comparação entre as floras de líquenes de altitude das ilhas dos Açores, Madeira e Canárias

Descreve-se a flora de líquenes das encostas alas do Pico, a maior montanha dos Açores, entre 1200-2300 m de altitude. Reconhecem-se duas zonas florísticas distintas: uma elevada, 1500-2300 m, acima da camada de inversão, pobre em espécies, e uma zona baixa, entre 1200-1500 m com maior diversidade específica, dependente da persistência da faixa de nuvens. Registaram-se 49 espécies de líquenes, 14 das quais são novas ocorrências para os Açores, incluindo duas que se descrevem de novo: Ochrolechia azorica e Stereocaulon macaronesicum. Compara-se a comunidade de líquenes acima de faixa de nuvens do Pico, dominada principalmente por Stereocaulon e Placopsis gelida, com as floras documentadas de altitude de outras ilhas da Macaronésia. Considera-se que a escassez de espécies de líquenes nas encostas de altitude do Pico é, em primeiro lugar, o resultado do isolamento recente dos Açores, mas também da natureza recente do substracto e das severas condições climatéricas.ABSTRACT: The lichen flora of the upper slopes of Pico, the major mountain in the Azores, is described between altitudes 1200-2300 m. Two distinct floristic zones are recognised: an upper, species poor, zone from 1500-2300 m above the inversion layer and a lower, more species diverse, zone from 1200-1500 m dependent on the persistence of the cloud layer, 49 species are reported, 14 of which are new records for the Azores, including two which are newly described: Ochrolechia azorica and Stereocaulon macaronesicum. The lichen communities above the cloud layer, dominated principally by species of Stereocaulon and Placopsis gelida are compared with those of other documented floras of Macaronesian islands al high elevations. The paucity of species on the upper slopes of Pico is considered to be primarily the result of the isolation of the Azores, the recent nature of the substrate and severity of the climatic conditions

Effect of Hyperbaric Oxygen Therapy on whole blood cyanide concentrations in carbon monoxide intoxicated patients from fire accidents

<p>Abstract</p> <p>Background</p> <p>Hydrogen cyanide (HCN) and carbon monoxide (CO) may be important components of smoke from fire accidents. Accordingly, patients admitted to hospital from fire accidents may have been exposed to both HCN and CO. Cyanide (CN) intoxication results in cytotoxic hypoxia leading to organ dysfunction and possibly death. While several reports support the use of hyperbaric oxygen therapy (HBO) for the treatment of severe CO poisoning, limited data exist on the effect of HBO during CN poisoning. HBO increases the elimination rate of CO haemoglobin in proportion to the increased oxygen partial pressure and animal experiments have shown that in rats exposed to CN intoxication, HBO can increase the concentration of CN in whole blood.</p> <p>Objective</p> <p>The purpose of the present study was to determine whole blood CN concentrations in fire victims before and after HBO treatment.</p> <p>Materials and methods</p> <p>The patients included were those admitted to the hospital because of CO intoxication, either as fire victims with smoke inhalation injuries or from other exposures to CO. In thirty-seven of these patients we measured CN concentrations in blood samples, using a Conway/microdiffusion technique, before and after HBO. The blood samples consisted of the remaining 2 mL from the arterial blood gas analysis. CN concentration in blood from fire victims was compared to 12 patients from non-fire accidents but otherwise also exposed to CO intoxication.</p> <p>Results</p> <p>The mean WB-CN concentration before patients received HBO did not differ significantly between the two groups of patients (p = 0.42). The difference between WB-CN before and after HBO did not differ significantly between the two groups of patients (p = 0.7). Lactate in plasma before and after did not differ significantly between the two groups of patients. Twelve of the 25 fire patients and one of the non-fire patients had been given a dose of hydroxycobalamin before HBO.</p> <p>Discussion and Conclusion</p> <p>CN concentrations in blood from patients admitted to hospital with CO intoxication and smoke inhalation exposure did not differ significantly from controls. Accordingly, we were not able to detect any changes in CN concentrations in blood after treatment with HBO.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: NCT00280579</p

Nearshore wave forecasting and hindcasting by dynamical and statistical downscaling

A high-resolution nested WAM/SWAN wave model suite aimed at rapidly establishing nearshore wave forecasts as well as a climatology and return values of the local wave conditions with Rapid Enviromental Assessment (REA) in mind is described. The system is targeted at regions where local wave growth and partial exposure to complex open-ocean wave conditions makes diagnostic wave modelling difficult. SWAN is set up on 500 m resolution and is nested in a 10 km version of WAM. A model integration of more than one year is carried out to map the spatial distribution of the wave field. The model correlates well with wave buoy observations (0.96) but overestimates the wave height somewhat (18%, bias 0.29 m). To estimate wave height return values a much longer time series is required and running SWAN for such a period is unrealistic in a REA setting. Instead we establish a direction-dependent transfer function between an already existing coarse open-ocean hindcast dataset and the high-resolution nested SWAN model. Return values are estimated using ensemble estimates of two different extreme-value distributions based on the full 52 years of statistically downscaled hindcast data. We find good agreement between downscaled wave height and wave buoy observations. The cost of generating the statistically downscaled hindcast time series is negligible and can be redone for arbitrary locations within the SWAN domain, although the sectors must be carefully chosen for each new location. The method is found to be well suited to rapidly providing detailed wave forecasts as well as hindcasts and return values estimates of partly sheltered coastal regions.Comment: 20 pages, 7 figures and 2 tables, MREA07 special issue on Marine rapid environmental assessmen

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

Digital Technology and design processes II: Follow-up report on FabLab@School survey among Danish youth

This report is part of the [email protected] research program, which investigates the use of digital fabrication technologies and design activities among students aged 11-15 years in Danish schools. In order to measure the effects of the [email protected] educational program from 2014 to late 2016, this follow-up survey was administered to two groups: first, schools in which FabLab and design activities had been carried out in the [email protected] project throughout a 2-year period (FabLab schools), and second, a control group of schools that were not part of the [email protected] project (control schools). The survey reported here, is a follow-up to a similar survey conducted in the fall of 2014

Galaxy cluster strong lensing: image deflections from density fluctuations along the line of sight

A standard method to study the mass distribution in galaxy clusters is through strong lensing of background galaxies in which the positions of multiple images of the same source constrain the surface mass distribution of the cluster. However, current parametrized mass models can often only reproduce the observed positions to within one or a few arcsec which is worse than the positional measurement uncertainty. One suggested explanation for this discrepancy is the additional perturbations of the path of the light ray caused by matter density fluctuations along the line of sight. We investigate this by calculating the statistical expectation value for the angular deflections caused by density fluctuations, which can be done given the matter power spectrum. We find that density fluctuations can, indeed, produce deflections of a few arcsec. We also find that the deflection angle of a particular image is expected to increase with source redshift and with the angular distance on the sky to the lens. Since the light rays of neighbouring images pass through much the same density fluctuations, it turns out that the images' expected deflection angles can be highly correlated. This implies that line-of-sight density fluctuations are a significant and possibly dominant systematic for strong lensing mass modeling and set a lower limit to how well a cluster mass model can be expected to replicate the observed image positions. We discuss how the deflections and correlations should explicitly be taken into account in the mass model fitting procedure.Comment: 5 pages, 3 figures, MNL accepted. Matches accepted versio

Exercise training reverses myocardial dysfunction induced by CaMKIIδC overexpression by restoring Ca2+-homeostasis

Several conditions of heart disease, including heart failure and diabetic cardiomyopathy, are associated with upregulation of cytosolic Ca2+/calmodulin-dependent protein kinase II (CaMKIIδC) activity. In the heart, CaMKIIδC isoform targets several proteins involved in intracellular Ca2+ homeostasis. We hypothesized that high-intensity endurance training activates mechanisms that enable a rescue of dysfunctional cardiomyocyte Ca2+ handling and thereby ameliorate cardiac dysfunction despite continuous and chronic elevated levels of CaMKIIδC. CaMKIIδC transgenic (TG) and wild-type (WT) mice performed aerobic interval exercise training over 6 wk. Cardiac function was measured by echocardiography in vivo, and cardiomyocyte shortening and intracellular Ca2+ handling were measured in vitro. TG mice had reduced global cardiac function, cardiomyocyte shortening (47% reduced compared with WT, P &#60; 0.01), and impaired Ca2+ homeostasis. Despite no change in the chronic elevated levels of CaMKIIδC, exercise improved global cardiac function, restored cardiomyocyte shortening, and reestablished Ca2+ homeostasis to values not different from WT. The key features to explain restored Ca2+ homeostasis after exercise training were increased L-type Ca2+ current density and flux by 79 and 85%, respectively (P &#60; 0.01), increased sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) function by 50% (P &#60; 0.01), and reduced diastolic SR Ca2+ leak by 73% (P &#60; 0.01), compared with sedentary TG mice. In conclusion, exercise training improves global cardiac function as well as cardiomyocyte function in the presence of a maintained high CaMKII activity. The main mechanisms of exercise-induced improvements in TG CaMKIIδC mice are mediated via increased L-type Ca2+ channel currents and improved SR Ca2+ handling by restoration of SERCA2a function in addition to reduced diastolic SR Ca2+ leak

Digital Technology and design processes: Report on a FabLab@School survey among Danish youth

This report contains findings from a survey on Danish adolescents aged 11-15 years conducted in the fall of 2014 among 1236 students. It is a part of the [email protected] research program, which investigates the use of digital fabrication technologies in Danish schools