Preformed and regenerated phosphate in ocean general circulation models: can right total concentrations be wrong?

Phosphate distributions simulated by seven state-of-the-art biogeochemical ocean circulation models are evaluated against observations of global ocean nutrient distributions. The biogeochemical models exhibit different structural complexities, ranging from simple nutrient-restoring to multi-nutrient NPZD type models. We evaluate the simulations using the observed volume distribution of phosphate. The errors in these simulated volume class distributions are significantly larger when preformed phosphate (or regenerated phosphate) rather than total phosphate is considered. Our analysis reveals that models can achieve similarly good fits to observed total phosphate distributions for a very different partitioning into preformed and regenerated nutrient components. This has implications for the strength and potential climate sensitivity of the simulated biological carbon pump. We suggest complementing the use of total nutrient distributions for assessing model skill by an evaluation of the respective preformed and regenerated nutrient components

In Vivo Methods for the Assessment of Topical Drug Bioavailability

This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described

MRI of Arterial Flow Reserve in Patients with Intermittent Claudication: Feasibility and Initial Experience

Objectives: The aim of this work was to develop a MRI method to determine arterial flow reserve in patients with intermittent claudication and to investigate whether this method can discriminate between patients and healthy control subjects. Methods: Ten consecutive patients with intermittent claudication and 10 healthy control subjects were included. All subjects underwent vector cardiography triggered quantitative 2D cine MR phase-contrast imaging to obtain flow waveforms of the popliteal artery at rest and during reactive hyperemia. Resting flow, maximum hyperemic flow and absolute flow reserve were determined and compared between the two groups by two independent MRI readers. Also, interreader reproducibility of flow measures was reported. Results: Resting flow was lower in patients compared to controls (4.961.6 and 11.163.2 mL/s in patients and controls, respectively (p,0.01)). Maximum hyperemic flow was 7.362.9 and 16.463.2 mL/s (p,0.01) and the absolute flow reserve was 2.461.6 and 5.361.3 mL/s (p,0.01), respectively in patients and controls. The interreader coefficient of variation was below 10 % for all measures in both patients and controls. Conclusions: Quantitative 2D MR cine phase-contrast imaging is a promising method to determine flow reserve measures in patients with peripheral arterial disease and can be helpful to discriminate patients with intermittent claudication fro

Preformed and regenerated phosphate in ocean general circulation models: can right total concentrations be wrong?

Phosphate distributions simulated by seven state-of-the-art biogeochemical ocean circulation models are evaluated against observations of global ocean nutrient distributions. The biogeochemical models exhibit different structural complexities, ranging from simple nutrient-restoring to multi-nutrient NPZD type models. We evaluate the simulations using the observed volume distribution of phosphate. The errors in these simulated volume class distributions are significantly larger when preformed phosphate (or regenerated phosphate) rather than total phosphate is considered. Our analysis reveals that models can achieve similarly good fits to observed total phosphate distributions for a~very different partitioning into preformed and regenerated nutrient components. This has implications for the strength and potential climate sensitivity of the simulated biological carbon pump. We suggest complementing the use of total nutrient distributions for assessing model skill by an evaluation of the respective preformed and regenerated nutrient components