Qualitative and Quantitative Detection of Botulinum Neurotoxins from Complex Matrices: Results of the First International Proficiency Test

In the framework of the EU project EQuATox a first international proficiency test (PT) on the detection and quantification of BoNT was conducted. Sample materials included BoNT serotypes A, B and E spiked into buffer, milk, meat extract and serum. A variety of methods was applied by the participants combining different principles of detection, identification and quantification. Based on qualitative assays, 95% of all results reported were correct. Successful strategies for BoNT detection were based on a combination of complementary immunological, MS-based and functional methods or on suitable functional in vivo / in vitro approaches (mouse bioassay, hemidiaphrama assay, Endopep-MS assay). Quantification of BoNT/A, BoNT/B and BoNT/E was performed by 48% of participating laboratories. It turned out that precise quantification of BoNT was difficult resulting in a substantial scatter of quantitative data. This was especially true for results obtained by the mouse bioassay which is currently seen as “gold standard” for BoNT detection. The results clearly demonstrate the urgent need of certified BoNT reference materials and the development of methods replacing animal testing. In this context, the BoNT PT provided the valuable information that both the Endopep-MS assay and the hemidiaphrama assay delivered quantitative results superior to the mouse bioassay.JRC.D.2-Standards for Innovation and sustainable Developmen

Seasonal variation of ozone deposition to a tropical rain forest in southwest Amazonia

International audienceWithin the project EUropean Studies on Trace gases and Atmospheric CHemistry as a contribution to Large-scale Biosphere-atmosphere experiment in Amazonia (LBA-EUSTACH), we performed tower-based eddy covariance measurements of O3 flux above an Amazonian primary rain forest at the end of the wet and dry season. Ozone deposition revealed distinct seasonal differences in the magnitude and diel variation. In the wet season, the rain forest was an effective O3 sink with a mean daytime (midday) maximum deposition velocity of 2.3 cm s?1, and a corresponding O3 flux of ?11 nmol m?2 s?1. At the end of the dry season, the ozone mixing ratio was about four times higher (up to maximum values of 80 ppb) than in the wet season, as a consequence of strong regional biomass burning activity. However, the typical maximum daytime deposition flux was very similar to the wet season. This results from a strong limitation of daytime O3 deposition due to reduced plant stomatal aperture as a response to large values of the specific humidity deficit. As a result, the average midday deposition velocity in the dry burning season was only 0.5 cm s?1. The large diel ozone variation caused large canopy storage effects that masked the true diel variation of ozone deposition mechanisms in the measured eddy covariance flux, and for which corrections had to be made. In general, stomatal aperture was sufficient to explain the largest part of daytime ozone deposition. However, during nighttime, chemical reaction with nitrogen monoxide (NO) was found to contribute substantially to the O3 sink in the rain forest canopy. Further contributions were from non-stomatal plant uptake and other processes that could not be clearly identified. Measurements, made simultaneously on a 22 years old cattle pasture enabled the spatially and temporally direct comparison of O3 dry deposition values from this site with typical vegetation cover of deforested land in southwest Amazonia to the results from the primary rain forest. The mean ozone deposition to the pasture was found to be systematically lower than that to the forest by 30% in the wet and 18% in the dry season

Self-consistent quantal treatment of decay rates within the perturbed static path approximation

The framework of the Perturbed Static Path Approximation (PSPA) is used to calculate the partition function of a finite Fermi system from a Hamiltonian with a separable two body interaction. Therein, the collective degree of freedom is introduced in self-consistent fashion through a Hubbard-Stratonovich transformation. In this way all transport coefficients which dominate the decay of a meta-stable system are defined and calculated microscopically. Otherwise the same formalism is applied as in the Caldeira-Leggett model to deduce the decay rate from the free energy above the so called crossover temperature $T_0$.Comment: 17 pages, LaTex, no figures; final version, accepted for publication in PRE; e-mail: [email protected]

Ancient colonization of marginal habitats. A comparative analysis of case studies from the Ancient World

The present contribution deals with the concepts of marginal habitats in selected regions of the ancient world, ranging from modern Spain to the Jordanian desert and from Turkey to the Ethiopian highlands. Central to this research is the hypothesis that the occupation of areas beyond the ‘normal’ settlement patterns corresponds to colonization processes which reflect specific social strategies and may have stimulated the development of new technological skills. A review of ‘marginality’ research in various disciplines indicates that there is no comprehensive definition of the concept, which can be approached from a multitude of perspectives and with manifold objectives. A survey of the eight case studies and two more in-depth discussions of the sites of Musawwarat (Sudan) and Ayamonte (Spain) highlight the potentials as well as the limits of the archaeological investigation into past marginalities. Patterns of spatial marginalization are the easiest to detect. The studies also show that we must not limit our analysis to the adverse factors connected to different kinds of marginalities. Instead, our analyses suggest that spatially marginal areas were deliberately chosen for settlement – an integration with core-periphery approaches may help us to understand these scenarios, which have received little attention in ‘marginality’ research in archaeology or elsewhere so far

A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours

The aim of the study was to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and the pharmacokinetic profile (Pk) of bendamustine (BM) on a day 1 and 2 every 3 weeks schedule and to recommend a safe phase II dose for further testing. Patients with solid tumours beyond standard therapy were eligible. A 30-min intravenous infusion of BM was administered d1+d2 q 3 weeks. The starting dose was 120 mg m−2 per day and dose increments of 20 mg m−2 were used. Plasma and urine samples were analysed using validated high-performance liquid chromatography/fluorescence assays. Fifteen patients were enrolled. They received a median of two cycles (range 1–8). The MTD was reached at the fourth dose level. Thrombocytopaenia (grade 4) was dose limiting in two of three patients at 180 mg m−2. One patient also experienced febrile neutropaenia. Lymphocytopaenia (grade 4) was present in every patient. Nonhaematologic toxicity including cardiac toxicity was not dose limiting with this schedule. Mean plasma Pk values of BM were tmax 35 min, t1/2 49.1 min, Vd 18.3 l m−2, and clearance 265 ml min−1 m−2. The mean total amount of BM and its metabolites recovered in the first micturition was 8.3% (range 2.7–26%). The MTD of BM in the present dose schedule was 180 mg m−2 on day 1+2. Thrombocytopaenia was dose limiting. The recommended dose for future phase II trials with this schedule is 160 mg m−2 per day

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue

Infrastructure for Detector Research and Development towards the International Linear Collider

The EUDET-project was launched to create an infrastructure for developing and testing new and advanced detector technologies to be used at a future linear collider. The aim was to make possible experimentation and analysis of data for institutes, which otherwise could not be realized due to lack of resources. The infrastructure comprised an analysis and software network, and instrumentation infrastructures for tracking detectors as well as for calorimetry.Comment: 54 pages, 48 picture