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

Identification by proximity labeling of novel lipidic and proteinaceous potential partners of the dopamine transporter

Dopamine (DA) transporters (DATs) are regulated by trafficking and modulatory processes that probably rely on stable and transient interactions with neighboring proteins and lipids. Using proximity-dependent biotin identification (BioID), we found novel potential partners for DAT, including several membrane proteins, such as the transmembrane chaperone 4F2hc, the proteolipid M6a and a potential membrane receptor for progesterone (PGRMC2). We also detected two cytoplasmic proteins: a component of the Cullin1-dependent ubiquitination machinery termed F-box/LRR-repeat protein 2 (FBXL2), and the enzyme inositol 5-phosphatase 2 (SHIP2). Immunoprecipitation (IP) and immunofluorescence studies confirmed either a physical association or a close spatial proximity between these proteins and DAT. M6a, SHIP2 and the Cullin1 system were shown to increase DAT activity in coexpression experiments, suggesting a functional role for their association. Deeper analysis revealed that M6a, which is enriched in neuronal protrusions (filopodia or dendritic spines), colocalized with DAT in these structures. In addition, the product of SHIP2 enzymatic activity (phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2]) was tightly associated with DAT, as shown by co-IP and by colocalization of mCherry-DAT with a specific biosensor for this phospholipid. PI(3,4)P2 strongly stimulated transport activity in electrophysiological recordings, and conversely, inhibition of SHIP2 reduced DA uptake in several experimental systems including striatal synaptosomes and the dopaminergic cell line SH-SY5Y. In summary, here we report several potential new partners for DAT and a novel regulatory lipid, which may represent new pharmacological targets for DAT, a pivotal protein in dopaminergic function of the brainOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This work was supported by grants from the Spanish MINECO (RTI2018-098712-B-100) and the “Fundación Ramón Areces”, the latter also providing an institutional grant to CBMS

A Paraneoplastic Syndrome to Remember: A Case of Disseminated Intravascular Coagulation in Lung Cancer

Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by the widespread activation of coagulation. It can present as an acute life-threatening emergency or as a chronic process. Mortality is highly dependent on the reversibility of the aetiology and degree of coagulation impairment, so treatment of the underlying cause is vital. The authors present the case of a 57-year-old man whose inaugural presentation of lung cancer was chronic DIC, characterized by three thrombotic events, followed by acute DIC, culminating in death. Metastatic lung cancer was diagnosed only after death

Potenciales presas zooplanctónicas (Copepoda y Appendicularia) para Engraulis anchoita en relación con las distribuciones de larvas tempranas y de desove en la región frontal patagónica (océano Atlántico sudoccidental)

We investigated the spatial distribution of the abundance, biomass and size of zooplankton (nauplii, calanoids, cyclopoids and appendicularians) in relation to the distribution of first-feeding larvae and eggs of Engraulis anchoita across the frontal system of Peninsula Valdés. Twelve samples of zooplankton and ichthyoplankton were taken with small Bongo (67 μm) and Pairovet (200 μm) nets during the spring of 2004 along two transects. The total abundance of zooplankton and the chlorophyll a concentration were higher in homogeneous waters, while total biomasses were higher in stratified waters. Temperature was negatively correlated with biological variables and was the main factor affecting the zooplankton distribution. In both transects, abundance peaks of first-feeding larvae were detected at coastal stations along with the smallest fraction of zooplankton ( < 500 μm), while the largest fraction was dominant at the external stations, coinciding with the highest egg abundance. The physical structure of this front generates different levels of food availability for first-feeding larvae. Calanoids (southern transect) and cyclopoids (northern transect) are predominant followed by nauplii and appendicularians. The biomass of zooplankton preys contributes to the carbon transfer to the upper trophic levels and is probably important for the survival and growth of anchovy larvae in this frontal system.Se investigó la distribución espacial de la abundancia, biomasa y las tallas del zooplancton (nauplii, calanoideos, ciclopoideos y apendicularias) en relación con la distribución de las larvas en estadio de primera alimentación y los huevos de Engraulis anchoita en el sistema frontal de Península Valdés. Se tomaron 12 muestras de zooplancton e ictioplancton durante la primavera de 2004 a lo largo de dos transectos, mediante una red Minibongo (67 μm) y una Pairovet (200 μm) respectivamente. La abundancia total del zooplancton y la concentración de clorofila fue mayor en aguas homogéneas, mientras que la biomasa fue mayor en aguas estratificadas. La temperatura se correlacionó negativamente con las variables biológicas siendo ésta el principal factor que afectó la distribución del zooplancton. En las estaciones costeras de ambos transectos, se encontró la mayor abundancia de larvas en coincidencia con la fracción más pequeña de zooplancton ( < 500 μm), mientras que la fracción más grande fue dominante en las estaciones externas, en coincidencia con la mayor abundancia de huevos. La estructura física de este frente genera diferente disponibilidad de alimento para las larvas siendo los calanoideos (transecto sur) y los ciclopoideos (transecto norte) predominantes, seguidos por nauplii y apendicularias. La biomasa de dicho alimento zooplanctónico podría contribuir a la transferencia de carbono a los niveles tróficos superiores y esto sería importante para la supervivencia y crecimiento de la anchoita en este sistema frontal

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

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