Regionalisatie van terreinbeheer

De maatschappelijke context waarbinnen de terreinbeheerders hun rol dienen te realiseren is sterk veranderd. Zo decentraliseerde en regionaliseerde het natuurbeleid, zoals de Ecologische Hoofdstructuur nu onder de provinciale bevoegdheid valt. Daarnaast kijken terreinbeheerders zelf steeds meer over de grenzen van hun eigen terreinen heen en verbreden ze hun doelen. Daarbij zijn er bij regionalisatie twee ontwikkelrichtingen: nadruk op de eigen organisatie, ook wel ‘organisatiebranding’, of focus op de regio onder het motto ‘regiobranding’

Segmentation-driven optimization for iterative reconstruction in optical projection tomography: an exploration

Three-dimensional reconstruction of tomograms from optical projection microscopy is confronted with several drawbacks. In this paper we employ iterative reconstruction algorithms to avoid streak artefacts in the reconstruction and explore possible ways to optimize two parameters of the algorithms, i.e., iteration number and initialization, in order to improve the reconstruction performance. As benchmarks for direct reconstruction evaluation in optical projection tomography are absent, we consider the assessment through the performance of the segmentation on the 3D reconstruction. In our explorative experiments we use the zebrafish model system which is a typical specimen for use in optical projection tomography system; and as such frequently used. In this manner data can be easily obtained from which a benchmark set can be built. For the segmentation approach we apply a two-dimensional U-net convolutional neural network because it is recognized to have a good performance in biomedical image segmentation. In order to prevent the training from getting stuck in local minima, a novel learning rate schema is proposed. This optimization achieves a lower training loss during the training process, as compared to an optimal constant learning rate. Our experiments demonstrate that the approach to the benchmarking of iterative reconstruction via results of segmentation is very useful. It contributes an important tool to the development of computational tools for optical projection tomography.Computer Systems, Imagery and Medi

Marketing channel choice and marketing timing of peri-urban vegetable growers in Vietnam

Agriculture is an important sector in the peri-urban area of Hanoi. It supplies 62 to 80% of vegetable consumption, of which 28% comes from Dong Anh district, which borders Hanoi City. Growing vegetables is an important income source for the farmers in Dong Anh as it contributes about 30% to their family earnings. Marketing channel choice and marketing timing affects farmers¿ profit by the obtained output price and the necessary (transaction) costs. This study focuses mainly on these factors¿ impact on output price. The influence of marketing channel choice and marketing timing on the output price has been analysed by performing One Way ANOVA and Post Hoc Bonferroni Tests with data of 63 households in Dong Anh collected in 2003 and 2004 by the VEGSYS project. The three most important vegetables in the area were selected: kohlrabi (Brassica oleracea), wrapped heart mustard (Brassica juncea var. rugosa), and wax gourd (Cucurbita hispida). To analyse which household characteristics influence the choice of marketing channel and marketing timing, T-tests and logistical regressions have been performed, next to qualitative interviews with farmers and traders. Output prices are significantly different between marketing channels. Farmers receive significantly higher kohlrabi and wrapped heart mustard prices from the farm gate collector than when they sell it at the local market. Farmers receive the highest wax gourd price at the Hanoi wholesale market, which requires good quality contrary to the local market. Farmers with high opportunity costs sell to the collector or at the local market. Farmers with large quantities will sell to the collector or at the Hanoi wholesale market. Timing of marketing also influences output price. Vegetables sold in the early season receive significantly higher prices than in the rest of the year. The profit however, is often not higher in the early season due to higher labour and capital costs. Farmers selling in the early season have a significantly higher education level than those selling in regular seaso

Systems pharmacology of hepatic metabolism in zebrafish larvae

Interspecies translation of pharmacological processes needs to improve to reduce attrition in drug development. Systems pharmacology integrates systems biology and pharmacometrics to characterise and quantify system-specific behaviour upon exposure to drugs in different species. The zebrafish is a suitable vertebrate model organism for systems pharmacology, combining high-throughput potential with high genetic homology to higher vertebrates. Zebrafish larvae have been increasingly used for drug screens, but the influence of internal drug and metabolite exposure is hardly studied. Quantifying this internal exposure is essential for establishing both exposure-response and dose-exposure relationships, needed for translation. The zebrafish may also serve as a suitable model species for translational studies on the occurrence of hepatotoxicity and the influence of hepatic dysfunction on drug metabolism. Pharmacolog

Development of a population pharmacokinetic model to predict brain distribution and dopamine D2 receptor occupancy of raclopride in nonanesthetized rat

BACKGROUND: Raclopride is a selective antagonist of the dopamine D2 receptor. It is one of the most frequently used in vivo D2 tracers (at low doses) for assessing drug-induced receptor occupancy (RO) in animals and humans. It is also commonly used as a pharmacological blocker (at high doses) to occupy the available D2 receptors and antagonize the action of dopamine or drugs on D2 in preclinical studies. The aims of this study were to comprehensively evaluate its pharmacokinetic (PK) profiles in different brain compartments and to establish a PK-RO model that could predict the brain distribution and RO of raclopride in the freely moving rat using a LC-MS based approach.METHODS: Rats (n=24) received a 10-min IV infusion of non-radiolabeled raclopride (1.61μmol/kg, i.e. 0.56mg/kg). Plasma and the brain tissues of striatum (with high density of D2 receptors) and cerebellum (with negligible amount of D2 receptors) were collected. Additional microdialysis experiments were performed in some rats (n=7) to measure the free drug concentration in the extracellular fluid of the striatum and cerebellum. Raclopride concentrations in all samples were analyzed by LC-MS. A population PK-RO model was constructed in NONMEM to describe the concentration-time profiles in the unbound plasma, brain extracellular fluid and brain tissue compartments and to estimate the RO based on raclopride-D2 receptor binding kinetics.RESULTS: In plasma raclopride showed a rapid distribution phase followed by a slower elimination phase. The striatum tissue concentrations were consistently higher than that of cerebellum tissue throughout the whole experimental period (10-h) due to higher non-specific tissue binding and D2 receptor binding in the striatum. Model-based simulations accurately predicted the literature data on rat plasma PK, brain tissue PK and D2 RO at different time points after intravenous or subcutaneous administration of raclopride at tracer dose (RO 30%).CONCLUSION: For the first time a predictive model that could describe the quantitative in vivo relationship between dose, PK and D2 RO of raclopride in non-anesthetized rat was established. The PK-RO model could facilitate the selection of optimal dose and dosing time when raclopride is used as tracer or as pharmacological blocker in various rat studies. The LC-MS based approach, which doses and quantifies a non-radiolabeled tracer, could be useful in evaluating the systemic disposition and brain kinetics of tracers.Pharmacolog

Outside-in systems pharmacology combines innovative computational methods with high-throughput whole vertebrate studies

To advance the systems approach in pharmacology, experimental models and computational methods need to be integrated from early drug discovery onward. Here, we propose outside‐in model development, a model identification technique to understand and predict the dynamics of a system without requiring prior biological and/or pharmacological knowledge. The advanced data required could be obtained by whole vertebrate, high‐throughput, low‐resource dose‐exposure‐effect experimentation with the zebrafish larva. Combinations of these innovative techniques could improve early drug discovery.Pharmacolog

Multi-modal 3D reconstruction and measurements of zebrafish larvae and its organs using axial-view microscopy

Computer Systems, Imagery and MediaAnimal sciencesPharmacolog

Meerwaarde door gebiedsgerichte samenwerking in natuurbeheer?

Dit rapport is een verslag van de aanzetten tot en gerealiseerde gebiedsgerichte samenwerking tussen reguliere natuurterreinbeheerders en particuliere terreinbeheerders zoals agrarische natuurverenigingen en landgoedeigenaren. In het verslag wordt aangegeven of en hoe gebiedsgerichte samenwerking tot meerwaarde kan leiden in ecologische, financiele, bestuurlijke en maatschappelijke zin. Verder wordt aangegeven waarom gebiedsgerichte samenwerking al dan niet van de grond komt en wat overheden kunnen doen om gebiedsgerichte samenwerking te versterken. Trefwoorden: agrarisch natuurbeheer, beheersplan, bestuurlijk draagvlak, Drentsche Aa, ecologisch, financiën, maatschappelijk draagvlak, meerwaarde, natuurbeheer, gebiedsplan, particulier natuurbeheer, Roode beek, samenwerking, Soerel, westelijke Langstraat

Evaluation of impermeable covers for bedding in patients with allergic rhinitis

BACKGROUND: Encasing bedding in impermeable covers reduces exposure to house-dust mites, but the clinical benefit of this intervention as part of mite-avoidance measures for patients with allergic rhinitis is not known. We performed a multicenter, randomized, placebo-controlled trial of one year of use of impermeable bedding covers in the bedrooms of patients with rhinitis who were sensitized to house-dust mites to determine the effects on the signs and symptoms of disease. METHODS: Three participating university medical centers enrolled 279 patients with allergic rhinitis who were randomly assigned to receive impermeable or non-impermeable (control) covers for their mattress, pillow, and duvet or blanket. At the start of the study, all participants received information on general allergen-avoidance measures. The severity of rhinitis was measured on a rhinitis-specific visual-analogue scale and by means of a daily symptom score and nasal allergen provocation testing. We also measured the concentrations of Dermatophagoides pteronyssinus (Der p1) and D. farinae (Der f1) in dust from patients' mattresses, bedroom floors, and living-room floors at base line and after 12 months as a measure of the efficacy of the intervention. RESULTS: A total

Impact of post-hatching maturation on the pharmacokinetics of paracetamol in zebrafish larvae

Zebrafish larvae are increasingly used in pharmacological and toxicological studies, but it is often overlooked that internal exposure to exogenous compounds, rather than the incubation medium concentration, is driving observed effects. Moreover, as the zebrafish larva is a developing organism, continuous physiological changes impact pharmacokinetic or toxicokinetic processes like the absorption and elimination of exogenous compounds, influencing the interpretation of observations and conclusions drawn from experiments at different larval ages. Here, using paracetamol as paradigm compound, mathematical modelling is used to quantify absorption and elimination rates from internal exposure over time profiles after waterborne treatment, as well as changes in these parameters in post-hatching larvae of 3, 4, and 5 days post fertilisation (dpf). An increase of 106% in absorption rate was observed between 3 and 4 dpf, but no further increase at 5 dpf, and an increase of 17.5% in elimination rate for each dpf. Paracetamol clearance, determined from elimination rate constants and reported total larval volumes of 253, 263, and 300 nL at 3, 4, and 5 dpf respectively, correlates best with higher vertebrates at 5 dpf. This suggests that when studying direct effects of exogenous compounds, experiments with zebrafish larvae are best performed at 5 dpf.PharmacologyAnalytical BioScience