Tödliche Pneumonitis unter Basistherapie mit Methotrexat

Zusammenfassung: Wir schildern den Fall einer 71-jährigen Schweizerin mit symptomatischer rheumatoider Arthritis, welche vom Rheumatologen mit Methotrexat behandelt worden war. Die Therapie sprach sehr gut an, jedoch starb die Frau unverwartet 2Monate später bei einer kumulativen Dosis von 160mg. In der rechtsmedizinischen Obduktion konnte eine fibrosierende Pneumonitis festgestellt werden. Solch ein fataler Verlauf könnte durch sofortiges Absetzen des Methotrexats bei ersten respiratorischen Symptomen sowie durch Diagnostik mittels Thoraxröntgen und entsprechende Kortisongabe womöglich verhindert werde

Simulating Radiating and Magnetized Flows in Multi-Dimensions with ZEUS-MP

This paper describes ZEUS-MP, a multi-physics, massively parallel, message- passing implementation of the ZEUS code. ZEUS-MP differs significantly from the ZEUS-2D code, the ZEUS-3D code, and an early "version 1" of ZEUS-MP distributed publicly in 1999. ZEUS-MP offers an MHD algorithm better suited for multidimensional flows than the ZEUS-2D module by virtue of modifications to the Method of Characteristics scheme first suggested by Hawley and Stone (1995), and is shown to compare quite favorably to the TVD scheme described by Ryu et. al (1998). ZEUS-MP is the first publicly-available ZEUS code to allow the advection of multiple chemical (or nuclear) species. Radiation hydrodynamic simulations are enabled via an implicit flux-limited radiation diffusion (FLD) module. The hydrodynamic, MHD, and FLD modules may be used in one, two, or three space dimensions. Self gravity may be included either through the assumption of a GM/r potential or a solution of Poisson's equation using one of three linear solver packages (conjugate-gradient, multigrid, and FFT) provided for that purpose. Point-mass potentials are also supported. Because ZEUS-MP is designed for simulations on parallel computing platforms, considerable attention is paid to the parallel performance characteristics of each module. Strong-scaling tests involving pure hydrodynamics (with and without self-gravity), MHD, and RHD are performed in which large problems (256^3 zones) are distributed among as many as 1024 processors of an IBM SP3. Parallel efficiency is a strong function of the amount of communication required between processors in a given algorithm, but all modules are shown to scale well on up to 1024 processors for the chosen fixed problem size.Comment: Accepted for publication in the ApJ Supplement. 42 pages with 29 inlined figures; uses emulateapj.sty. Discussions in sections 2 - 4 improved per referee comments; several figures modified to illustrate grid resolution. ZEUS-MP source code and documentation available from the Laboratory for Computational Astrophysics at http://lca.ucsd.edu/codes/currentcodes/zeusmp2

La Peña de Estebanvela

Pleistocene and Holocene hunter – gatherers in Iberia and the Gibraltar Strait: the current archaeological record, aims to be an updating of the current knowledge on human predatory societies settled in Iberia. The archaeological record of that region is essential for the reconstruction of Human Evolution in Europe in biological, behavioural and cultural domains thus it preserves the earliest and more significant records of the humanization in the continent and because it allows the recovery of the main trends in that process. This is possible thanks to a rich, large and complete record, encompassing all the stages on that development and all the adaptive and cultural modes. Moreover, the discovery of that record is amongst the earliest known archaeological occurrences in the history of our discipline, materialized already during the XIX century. The main aim of that volume is the systematic presentation of the current empirical data written by the same research teams already on work every year on the excavation and analysis of the sites. We have included the current knowledge on the main archaeo-palaeontological sites, those bearing the more significant record. These sites are arranged in eight physiographic and geological regions with the aim of making clear the adaptive ways of human societies to similar environments. Beyond these eight regions it seemed important to us to present the heritage of symbolic behaviour on the caves of the two regions bearing the more extensive record of that cultural trait: the Cantabrian and the Levantine regions. The cave paintings coming from outside these two regions are presented in their own region. Finally, beyond the empirical data, we would like to highlight the main research lines in which the modern Iberian Archaeology is currently engaged in the field of Human Evolution and Palaeoecology.Peer reviewe

Instructional Changes Adopted for an Engineering Course: Cluster Analysis on Academic Failure

As first-year students come from diverse backgrounds, basic skills should be accessible to everyone as soon as possible. Transferring such skills to these students is challenging, especially in highly technical courses. Ensuring that essential knowledge is acquired quickly promotes the student’s self-esteem and may positively influence failure rates. Metaphors can help do this. Metaphors are used to understand the unknown. This paper shows how we made a turn in student learning at the University of Almeria. Our hypothesis assumed that metaphors accelerate the acquisition of basic knowledge so that other skills built on that foundation are easily learned. With these goals in mind, we changed the way we teach by using metaphors and abstract concepts in a computer organisation course, a technical course in the first year of an information technology engineering degree. Cluster analysis of the data on collective student performance after this methodological change clearly identified two distinct groups. These two groups perfectly matched the before and after scenarios of the use of metaphors. The study was conducted during 11 academic years (2002/2003 to 2012/2013). The 475 observations made during this period illustrate the usefulness of this change in teaching and learning, shifting from a propositional teaching/learning model to a more dynamic model based on metaphors and abstractions. Data covering the whole period showed favourable evolution of student achievement and reduced failure rates, not only in this course, but also in many of the following more advanced courses.The paper is structured in five sections. The first gives an introduction, the second describes the methodology. The third section describes the sample and the study carried out. The fourth section presents the results and, finally, the fifth section discusses the main conclusions

Statistical Mechanics of Soft Margin Classifiers

We study the typical learning properties of the recently introduced Soft Margin Classifiers (SMCs), learning realizable and unrealizable tasks, with the tools of Statistical Mechanics. We derive analytically the behaviour of the learning curves in the regime of very large training sets. We obtain exponential and power laws for the decay of the generalization error towards the asymptotic value, depending on the task and on general characteristics of the distribution of stabilities of the patterns to be learned. The optimal learning curves of the SMCs, which give the minimal generalization error, are obtained by tuning the coefficient controlling the trade-off between the error and the regularization terms in the cost function. If the task is realizable by the SMC, the optimal performance is better than that of a hard margin Support Vector Machine and is very close to that of a Bayesian classifier.Comment: 26 pages, 12 figures, submitted to Physical Review

Local maximum points of explicitly quasiconvex functions

This work concerns generalized convex real-valued functions defined on a nonempty convex subset of a real topological linear space. Its aim is twofold: first, to show that any local maximum point of an explicitly quasiconvex function is a global minimum point whenever it belongs to the intrinsic core of the function’s domain and second, to characterize strictly convex normed spaces by applying this property for a particular class of convex functions

ColoLipidGene: Signature of lipid metabolism-related genes to predict prognosis in stage-II colon cancer patients

Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolismrelated genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk groupThis work was supported by Ministerio de Ciencia e Innovación del Gobierno de España (Plan Nacional I + D + i AGL2013–48943-C2–2-R and IPT-2011–1248-060000), Comunidad de Madrid (P2013/ABI-2728. ALIBIRDCM) and European Union Structural Funds. CIBEREHD is funded by the Instituto de Salud Carlos III. This is a collaborative study between the Molecular Oncology Unit of The Institute of Advanced Studies of Madrid IMDEA Food and the Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD

Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach

Citation: Lin, Z. M., Cuneo, M., Rowe, J. D., Li, M. J., Tell, L. A., Allison, S., . . . Gehring, R. (2016). Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach. Bmc Veterinary Research, 12, 10. https://doi.org/10.1186/s12917-016-0884-4Background: Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i.e., the marker residue CP-60,300), respectively, using liquid chromatography mass spectrometry. Based on these new data and related literature data, a NLME-PK compartmental model with first-order absorption and elimination was used to model plasma concentrations and cumulative excreted amount in milk. Monte Carlo simulations with 100 replicates were performed to predict the time when the upper limit of the 95% confidence interval of milk concentrations was below the tolerance. Results: All animals were healthy throughout the study with normal appetite and milk production levels, and with mild-moderate injection-site reactions that diminished by the end of the study. The measured data showed that milk concentrations of the marker residue of tulathromycin were below the limit of detection (LOD = 1.8 ng/ml) 39 days after the second injection. A 2-compartment model with milk as an excretory compartment best described tulathromycin plasma and CP-60,300 milk pharmacokinetic data. The model-predicted data correlated with the measured data very well. The NLME-PK model estimated that tulathromycin plasma concentrations were below LOD (1.2 ng/ml) 43 days after a single injection, and 62 days after the second injection with a 95% confidence. These estimated times are much longer than the current meat withdrawal time recommendation of 18 days for tulathromycin in non-lactating cattle. Conclusions: The results suggest that twice subcutaneous injections of 2.5 mg/kg tulathromycin are a clinically safe extra-label alternative approach for treating pulmonary infections in lactating goats, but a prolonged withdrawal time of at least 39 days after the second injection should be considered to prevent violative residues in milk and any dairy goat being used for meat should have an extended meat withdrawal time