BackgroundCannabinoids represent unique compounds for treating tumors, including astrocytomas. Whether CB1 and CB2 receptors mediate this therapeutic effect is unclear.Principal FindingsWe generated astrocytoma subclones that express set levels of CB1 and CB2, and found that cannabinoids induce apoptosis only in cells expressing low levels of receptors that couple to ERK1/2. In contrast, cannabinoids do not induce apoptosis in cells expressing high levels of receptors because these now also couple to the prosurvival signal AKT. Remarkably, cannabinoids applied at high concentration induce apoptosis in all subclones independently of CB1, CB2 and AKT, but still through a mechanism involving ERK1/2.SignificanceThe high expression level of CB1 and CB2 receptors commonly found in malignant astrocytomas precludes the use of cannabinoids as therapeutics, unless AKT is concomitantly inhibited, or cannabinoids are applied at concentrations that bypass CB1 and CB2 receptors, yet still activate ERK1/2.

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Abstract. The interactions between climate, vegetation and fire can strongly influence the future trajectories of vegetation in Earth system models. We evaluate the relationships between tropical climate, vegetation and fire in the global vegetation model JSBACH, using a simple fire scheme and the complex fire model SPITFIRE with the aim to identify potential for model improvement. We use two remote-sensing products (based on MODIS and Landsat) in different resolutions to assess the robustness of the obtained observed relationships. We evaluate the model using a multivariate comparison that allows us to focus on the interactions between climate, vegetation and fire and test the influence of land use change on the modelled patterns. Climate–vegetation–fire relationships are known to differ between continents; we therefore perform the analysis for each continent separately. The observed relationships are similar in the two satellite data sets, but maximum tree cover is reached at higher precipitation values for coarser resolution. This shows that the spatial scale of models and data needs to be consistent for meaningful comparisons. The model captures the broad spatial patterns with regional differences, which are partly due to the climate forcing derived from an Earth system model. Compared to the simple fire scheme, SPITFIRE strongly improves the spatial pattern of burned area and the distribution of burned area along increasing precipitation. The correlation between precipitation and tree cover is higher in the observations than in the largely climate-driven vegetation model, with both fire models. The multivariate comparison identifies excessive tree cover in low-precipitation areas and a too-strong relationship between high fire occurrence and low tree cover for the complex fire model. We therefore suggest that drought effects on tree cover and the impact of burned area on tree cover or the adaptation of trees to fire can be improved. The observed variation in the relationship between precipitation and maximum tree cover between continents is higher than the simulated one. Land use contributes to the intercontinental differences in fire regimes with SPITFIRE and strongly overprints the modelled multimodality of tree cover with SPITFIRE. The multivariate model–data comparison used here has several advantages: it improves the attribution of model–data mismatches to model processes, it reduces the impact of biases in the meteorological forcing on the evaluation and it allows us to evaluate not only a specific target variable but also the interactions.

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The structural dynamics of short-pulse laser irradiated surfaces and nano-structures has been studied with nm spatial and ultrafast temporal resolution by means of single-shot coherent XUV-scattering techniques. The experiments allowed us to time-resolve the formation of laser-induced periodic surface structures, and to follow the expansion and disintegration of nano-objects during laser ablation.

The Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) demonstrated the efficacy of hydroxyurea in reducing the rate of painful crises compared to placebo. We used resource utilization data collected in the MSH to determine the cost-effectiveness of hydroxyurea. The MSH was a randomized, placebo-controlled double-blind clinical trial involving 299 patients at 21 sites. The primary outcome, visit to a medical facility, was one of the criteria to define occurrence of painful crisis. Cost estimates were applied to all outpatient and emergency department visits and inpatient hospital stays that were classified as a crisis. Other resources for which cost estimates were applied included hospitalization for chest syndrome, analgesics received, hydroxyurea dosing, laboratory testing, and clinic visits for management of patient care. Annualized differential costs were calculated between hydroxyurea- and placebo-receiving patients. Hospitalization for painful crisis accounted for the majority of costs in both arms of the study, with an annual mean of $12,160 (95% CI: $9,440, $14,880) for hydroxyurea and $17,290 (95% CI: $13,010, $21,570) for placebo. The difference in means was $5,130 (95% CI: $60, $10,200; P = 0.048). Chest syndrome was the next largest cost with a mean difference of $830 (95% CI: $-340, $2,000; P = 0.16). The hydroxyurea arm was also associated with lower costs for emergency department visits, transfusion, and use of opiate analgesics. In total, the annual average cost per patient receiving hydroxyurea was $16,810 (95% CI: $13,350, $20,270) and the annual average costs per patient receiving placebo was $22,020 (95% CI: $17,340, $26,710). The difference in means was $5,210 (95% CI: $-610, $11,030; P = 0.21). The cost of hydroxyurea with the more intensive monitoring required when using this drug appears to be more than offset by decreased costs for medical care of painful crisis and analgesic use. Although the total cost difference was not significant statistically, these results suggest that hydroxyurea therapy is cost-effective compared to placebo in the management of adult patients with sickle cell anemia. If hydroxyurea can prevent development of chronic organ damage, long-term savings may be even greater.

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Yield. -The title core-shell nanoparticles are prepared from a MeOH solution of CePO4:Tb nanoparticles, H3PO4 in dihexyl ether, and LaCl3·7H2O (200°C, yield given in g). Growth of the LaPO4 shell around the core particles increases the quantum yield of the Tb emission to 70% and the total quantum yield to 80%. These reproducible values are not far from the quantum yield of the bulk material, which is 86% for the Tb emission and 93% for the total emission. The quantum yield of these nanoparticles can probably be further increased by optimizing the thickness of the shell and by employing metal salts of very high purity. -(KOEMPE, K.; BORCHERT, H.; STORZ, J.; LOBO, A.; ADAM, S.; MOELLER, T.; HAASE*, M.; Angew.