Diffusion-driven transport in clayrock formations

Clay mineral-rich sedimentary formations are currently under investigation to evaluate their potential use as host formations for installation of deep underground disposal facilities for radioactive waste (e.g. Boom Clay (BE), Opalinus Clay (CH), Callovo-Oxfordian argillite (FR)). The ultimate safety of the corresponding repository concepts depends largely on the capacity of the host formation to limit the flux towards the biosphere of radionuclides (RN) contained in the waste to acceptably low levels. Data for diffusion-driven transfer in these formations shows extreme differences in the measured or modelled behaviour for various radionuclides, e. g. between halogen RN (Cl-36, I-129) and actinides (U-238,U-235, Np-237, Th-232, etc.), which result from major differences between RN of the effects on transport of two phenomena: diffusion and sorption. This paper describes recent research aimed at improving understanding of these two phenomena, focusing on the results of studies carried out during the EC Funmig IP on clayrocks from the above three formations and from the Boda formation (HU). Project results regarding phenomena governing water, cation and anion distribution and mobility in the pore volumes influenced by the negatively-charged surfaces of clay minerals show a convergence of the modelling results for behaviour at the molecular scale and descriptions based on electrical double layer models. Transport models exist which couple ion distribution relative to the clay-solution interface and differentiated diffusive characteristics. These codes are able to reproduce the main trends in behaviour observed experimentally, e.g. D-e(anion) < D-e(HTO) < D-e(cation) and D-e(anion) variations as a function of ionic strength and material density. These trends are also well-explained by models of transport through ideal porous matrices made up of a charged surface material. Experimental validation of these models is good as regards monovalent alkaline cations, in progress for divalent electrostatically-interacting cations (e.g. Sr2+) and still relatively poor for 'strongly sorbing', high K-d cations. Funmig results have clarified understanding of how clayrock mineral composition, and the corresponding organisation of mineral grain assemblages and their associated porosity, can affect mobile solute (anions, HTO) diffusion at different scales (mm to geological formation). In particular, advances made in the capacity to map clayrock mineral grain-porosity organisation at high resolution provide additional elements for understanding diffusion anisotropy and for relating diffusion characteristics measured at different scales. On the other hand, the results of studies focusing on evaluating the potential effects of heterogeneity on mobile species diffusion at the formation scale tend to show that there is a minimal effect when compared to a homogeneous property model. Finally, the results of a natural tracer-based study carried out on the Opalinus Clay formation increase confidence in the use of diffusion parameters measured on laboratory scale samples for predicting diffusion over geological time-space scales. Much effort was placed on improving understanding of coupled sorption-diffusion phenomena for sorbing cations in clayrocks. Results regarding sorption equilibrium in dispersed and compacted materials for weakly to moderately sorbing cations (Sr2+, Cs+, Co2+) tend to show that the same sorption model probably holds in both systems. It was not possible to demonstrate this for highly sorbing elements such as Eu(III) because of the extremely long times needed to reach equilibrium conditions, but there does not seem to be any clear reason why such elements should not have similar behaviour. Diffusion experiments carried out with Sr2+, Cs+ and Eu(III) on all of the clayrocks gave mixed results and tend to show that coupled diffusion-sorption migration is much more complex than expected, leading generally to greater mobility than that predicted by coupling a batch-determined K-d and Ficks law based on the diffusion behaviour of HTO. If the K-d measured on equivalent dispersed systems holds as was shown to be the case for Sr, Cs (and probably Co) for Opalinus Clay, these results indicate that these cations have a D-e value higher than HTO (up to a factor of 10 for Cs+). Results are as yet very limited for very moderate to strongly sorbing species (e.g. Co(II), Eu(III), Cu(II)) because of their very slow transfer characteristics. (C) 2011 Elsevier Ltd. All rights reserved.

Epidermal growth factor receptor inhibitors plus chemotherapy in non-small-cell lung cancer: biologic rationale for combination strategies

Chemotherapy continues to play an essential role in the treatment of most stages of non-small-cell lung cancer (NSCLC). In fact, within the past 5 years, this role has greatly expanded into adjuvant therapy for early-stage resected disease. Likewise, agents targeting the epidermal growth factor receptor (EGFR), particularly the tyrosine kinase inhibitors gefitinib and erlotinib, have proven to be clinically active in patients with advanced-stage NSCLC. Because of these findings, it is logical to expect that combinations of these 2 classes of antineoplastic agents would prove more efficacious than either one alone. Yet 4 large randomized phase III trials of chemotherapy with or without an EGFR tyrosine kinase inhibitor in unselected patients with advanced-stage NSCLC, altogether totaling > 4000 patients, did not demonstrate improvement in clinical outcomes with the combination. Whether these negative results will be reproduced in ongoing combination studies of chemotherapy plus monoclonal antibodies directed against EGFR remain to be determined. Herein, we review recent preclinical and clinical data addressing this topic and explore the biologic rationale for developing new combination strategies based on patient selection by molecular and clinical factors, or by pharmacodynamic parameters.

Innovative chemotherapeutical treatment options for alveolar and cystic echinococcosis

Echinococcus granulosus and Echinococcus multilocularis are cestode parasites, of which the metacestode (larval) stages cause the diseases cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. Albendazole and mebendazole are presently used for chemotherapeutical treatment. However, these benzimidazoles do not appear to be parasiticidal in vivo against AE. In addition, failures in drug treatments as well as the occurrence of side-effects have been reported. New drugs are needed to cure AE and CE, which are considered to be neglected diseases. Strategies currently being implemented to identify novel chemotherapeutical treatment options include (i) conventional primary in vitro testing of broad-spectrum anti-infective drugs, either in parallel with, or followed by, animal experimentation; (ii) studies of drugs which interfere with the proliferation of cancer cells and of Echinococcus metacestodes; (iii) exploitation of the similarities between the parasite and mammalian signalling machineries, with a special focus on targeting specific signalling receptors; (iv) in silico approaches, employing the current Echinococcus genomic database information to search for suitable targets for compounds with known modes of action. In the present article, we review the efforts toward obtaining better anti-parasitic compounds which have been undertaken to improve chemotherapeutical treatment of echinococcosis, and summarize the achievements in the field of host-parasite interactions which may also lead to new immuno-therapeutical options.

Ligament origins are preserved in distal radial intraarticular two-part fractures: a computed tomography-based study

Background Operative fixation of intraarticular distal radius fractures is increasingly common. A greater understanding of fracture patterns will aid surgical fixation strategy. Previous studies have suggested that ligamentous insertions may less commonly be involved, but these have included heterogeneous groups of fractures and have not addressed Lister's tubercle. Purpose We hypothesize that fracture lines of distal radial intraarticular 2-part fractures have reproducible patterns. They propagate through the cortical bone between ligament origins and do not involve Lister's tubercle. Methods Axial CT scans of two-part intraarticular distal radius fractures were assessed independently by two examiners. The fractures were mapped onto a grid and the cortical breaches expressed as a percentile of the total radial width or length. The cortical breaches were compared with the ligamentous insertions on the distal and Lister's tubercle. Associated injuries were also documented. Results The cortical breaches occurred between the ligamentous insertions in 85%. Lister's tubercle was not involved in 95% of the fractures. Three major fracture patterns emerged: radial styloid, dorsal, and volar. Each major pattern had two subtypes. Associated injuries were common. Scapholunate dissociation was associated with all types, not just the radial styloid fracture pattern. Conclusions The fracture patterns of two-part intraarticular fractures mostly involved the interligamentous zones. Three major groups were identified: dorsal, volar, and radial styloid. Lister's tubercle was preserved with fractures tending to propagate radial or ulnar to this structure. We suggest conceptualizing fracture fragments as osseo-ligamentous units to aid prediction of fracture patterns and associated injury. Study Design Diagnostic III Level of Evidence 3.

Adapting agricultural land management to climate change: a regional multi-objective optimization approach

In several regions of the world, climate change is expected to have severe impacts on agricultural systems. Changes in land management are one way to adapt to future climatic conditions, including land-use changes and local adjustments of agricultural practices. In previous studies, options for adaptation have mostly been explored by testing alternative scenarios. Systematic explorations of land management possibilities using optimization approaches were so far mainly restricted to studies of land and resource management under constant climatic conditions. In this study, we bridge this gap and exploit the benefits of multi-objective regional optimization for identifying optimum land management adaptations to climate change. We design a multi-objective optimization routine that integrates a generic crop model and considers two climate scenarios for 2050 in a meso-scale catchment on the Swiss Central Plateau with already limited water resources. The results indicate that adaptation will be necessary in the study area to cope with a decrease in productivity by 0–10 %, an increase in soil loss by 25–35 %, and an increase in N-leaching by 30–45 %. Adaptation options identified here exhibit conflicts between productivity and environmental goals, but compromises are possible. Necessary management changes include (i) adjustments of crop shares, i.e. increasing the proportion of early harvested winter cereals at the expense of irrigated spring crops, (ii) widespread use of reduced tillage, (iii) allocation of irrigated areas to soils with low water-retention capacity at lower elevations, and (iv) conversion of some pre-alpine grasslands to croplands.

Upconverter materials and upconversion solar-cell devices: simulation and characterization with broad solar spectrum illumination

Upconverter materials and upconverter solar devices were recently investigated with broad-band excitation revealing the great potential of upconversion to enhance the efficiency of solar cell at comparatively low solar concentration factors. In this work first attempts are made to simulate the behavior of the upconverter β-NaYF4 doped with Er3+ under broad-band excitation. An existing model was adapted to account for the lower absorption of broader excitation spectra. While the same trends as observed for the experiments were found in the simulation, the absolute values are fairly different. This makes an upconversion model that specifically considers the line shape function of the ground state absorption indispensable to achieve accurate simulations of upconverter materials and upconverter solar cell devices with broadband excitations, such as the solar radiation.

MRD's approach: Ideally suited to support Future Earth research agenda in mountains

Both Future Earth and Mountain Research and Development (MRD) aim to support production and dissemination of knowledge for sustainable development. As shown in Future Earth’s Strategic Research Agenda 2014, the global research community has begun to acknowledge its societal role and the need for a new type of research in which scientists link disciplines and coproduce transformation knowledge with stakeholders. Future Earth has defined three research themes that conceptualize the issues to be dealt with at the same time as the way in which this should be done. In many ways, MRD’s policy has made the journal a forerunner of Future Earth’s stipulated “step-change in research”. Indeed, MRD’s section policies aim to support similar contents and ways of producing these forms of knowledge. MRD publishes “systems knowledge” in its MountainResearch section, “target knowledge” in its MountainAgenda section, and “transformation knowledge” in its MountainDevelopment section. Each of these sections has dedicated review criteria to assess and enhance the quality of the knowledge presented in the papers. In this poster, we provide examples from each of the three sections of what the knowledge types look like, how they are assessed, and how they contribute to the three Future Earth themes.