The cost of treating relapsed indolent non-Hodgkin's lymphoma in an international setting: retrospective analysis of resource use

Background and Objectives. Few economic data exist on the treatment of indolent non-Hodgkin´s lymphoma (NHL) and there are none in the published literature concerning relapsed disease. This international analysis (Canada, Germany, Italy) was established to estimate the overall direct cost of treating patients with relapsed indolent NHL and determine the main cost components of treatment. Design and Methods. Telephone interviews were used to identify the most commonly used treatment regimens in each country. CHOP, CVP and fludarabine were chosen for economic analysis, which was based on retrospective data from 424 patients. Results. Overall treatment costs for a course of six cycles varied more than 5-fold, from EURO3,445 to 17,940 between regimens and countries. The treatment setting had a major impact on costs, with in-patient costs being up to three times greater than the equivalent out-patient values. Drug administration costs comprised 46-60% of the overall treatment costs in the in-patient setting. Adverse event management was the major cost component for out-patient CHOP and CVP therapy (52-75%), and a significant proportion (24-40%) of in-patient costs for these regimens. Drug acquisition accounted for less than half of treatment costs for most of the regimens analyzed. Interpretation and Conclusions. This study shows that not simply drug acquisition costs, but the costs of drug administration, particularly in the in-patient setting, and adverse event management are major contributors to the overall treatment costs for relapsed indolent NHL

Holocene forest and land-use history of the Erzgebirge, central Europe: a review of palynological data

The ongoing ecological conversion of mountain forests in central Europe from widespread Picea monocultures to mixed stands conceptually also requires a historical perspective on the very long-term, i.e. Holocene, vegetation and land-use dynamics. Detailed sources of information for this are palynological data. The Erzgebirge in focus here, with a maximum height of 1244 m a.s.l., represents an extreme case of extensive historical deforestation since the Middle Ages due to mining, metallurgy, and other industrial activities, as well as rural and urban colonisation. For this regional review we collected and evaluated 121 pollen diagrams of different stratigraphic, taxonomic, and chronological resolution. This number makes this region an upland area in central Europe with an exceptionally high density of palynological data. Using well-dated diagrams going back to the early Holocene, main regional vegetation phases were derived: the Betula–Pinus phase (ca. 11 600–10 200 cal yr BP), the Corylus phase (ca. 10 200–9000 cal yr BP), the Picea phase (ca. 9000–6000 cal yr BP), the Fagus–Picea phase (ca. 6000–4500 cal yr BP), the Abies–Fagus–Picea phase (ca. 4000–1000 cal yr BP), and the anthropogenic vegetation phase (ca. 1000–0 cal yr BP). Some diagrams show the presence or even continuous curves of potential pasture and meadow indicators from around 2000 cal BCE at the earliest. Even cereal pollen grains occur sporadically already before the High Medieval. These palynological indications of a local prehistoric human impact also in the higher altitudes find parallels in the (geo-)archaeologically proven Bronze Age tin placer mining and in the geochemically proven Iron Age metallurgy in the Erzgebirge. The pollen data show that immediately before the medieval clearing, i.e. beginning at the end of the 12th century CE, forests were mainly dominated by Fagus and Abies and complemented by Picea with increasing share towards the highest altitudes. According to historical data, the minimum of the regional forest cover was reached during the 17th–18th centuries CE. The dominance of Picea in modern pollen spectra is caused by anthropogenic afforestation in the form of monocultures since that time. Future palynological investigations, preferably within the framework of altitudinal transect studies, should aim for chronologically and taxonomically high-resolution and radiometrically well-dated pollen diagrams from the larger peatlands.</p

Strong Influence of Coadsorbate Interaction on CO Desorption Dynamics on Ru(0001) Probed by Ultrafast X-Ray Spectroscopy and \u3cem\u3eAb Initio\u3c/em\u3e Simulations

We show that coadsorbed oxygen atoms have a dramatic influence on the CO desorption dynamics from Ru(0001). In contrast to the precursor-mediated desorption mechanism on Ru(0001), the presence of surface oxygen modifies the electronic structure of Ru atoms such that CO desorption occurs predominantly via the direct pathway. This phenomenon is directly observed in an ultrafast pump-probe experiment using a soft x-ray free-electron laser to monitor the dynamic evolution of the valence electronic structure of the surface species. This is supported with the potential of mean force along the CO desorption path obtained from density-functional theory calculations. Charge density distribution and frozen-orbital analysis suggest that the oxygen-induced reduction of the Pauli repulsion, and consequent increase of the dative interaction between the CO 5σ and the charged Ru atom, is the electronic origin of the distinct desorption dynamics. Ab initio molecular dynamics simulations of CO desorption from Ru(0001) and oxygen-coadsorbed Ru(0001) provide further insights into the surface bond-breaking process

Room-Temperature Ballistic Transport in III-Nitride Heterostructures

Room-temperature (RT) ballistic transport of electrons is experimentally observed and theoretically investigated in III-nitrides. This has been largely investigated at low temperatures in low band gap III–V materials due to their high electron mobilities. However, their application to RT ballistic devices is limited by their low optical phonon energies, close to KT at 300 K. In addition, the short electron mean-free-path at RT requires nanoscale devices for which surface effects are a limitation in these materials. We explore the unique properties of wide band-gap III-nitride semiconductors to demonstrate RT ballistic devices. A theoretical model is proposed to corroborate experimentally their optical phonon energy of 92 meV, which is ∼4× larger than in other III–V semiconductors. This allows RT ballistic devices operating at larger voltages and currents. An additional model is described to determine experimentally a characteristic dimension for ballistic transport of 188 nm. Another remarkable property is their short carrier depletion at device sidewalls, down to 13 nm, which allows top-down nanofabrication of very narrow ballistic devices. These results open a wealth of new systems and basic transport studies possible at RT.United States. Defense Advanced Research Projects Agency. Nitride Electronic NeXt-Generation Technology (NEXT) ProgramUnited States. Office of Naval Research. Young Investigator Progra

DOGS: Reaction-Driven de novo Design of Bioactive Compounds

We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design of Genuine Structures) features a ligand-based strategy for automated ‘in silico’ assembly of potentially novel bioactive compounds. The quality of the designed compounds is assessed by a graph kernel method measuring their similarity to known bioactive reference ligands in terms of structural and pharmacophoric features. We implemented a deterministic compound construction procedure that explicitly considers compound synthesizability, based on a compilation of 25'144 readily available synthetic building blocks and 58 established reaction principles. This enables the software to suggest a synthesis route for each designed compound. Two prospective case studies are presented together with details on the algorithm and its implementation. De novo designed ligand candidates for the human histamine H4 receptor and γ-secretase were synthesized as suggested by the software. The computational approach proved to be suitable for scaffold-hopping from known ligands to novel chemotypes, and for generating bioactive molecules with drug-like properties