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AimWe seek a simple and reliable tool to predict malignant behavior of pheochromocytoma and paraganglioma (PPGL).MethodsThis single-center prospective cohort study assessed size of primary PPGLs on preoperative cross-sectional imaging and prospectively scored specimens using the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS). Multiplication of PASS points with maximum lesion diameter (in mm) yielded the SIZEPASS criterion. Local recurrence, metastasis or death from disease were surrogates defining malignancy.Results76 consecutive PPGL patients, whereof 58 with pheochromocytoma and 51 female, were diagnosed at a mean age of 52.0 ± 15.2 years. 11 lesions (14.5%) exhibited malignant features at a median follow-up (FU) of 49 months (range 4-172 mo). Median FU of the remaining cohort was 139 months (range 120-226 mo). SIZEPASS classified malignancy with an area under the curve (AUC) of 0.97 (95%CI 0.93-1.01; p1000 outperformed all known predictors of malignancy, with sensitivity 91%, specificity 94%, and accuracy 93%, and an odds ratio of 72 fold (95%CI 9-571; P90% in cohorts defined by location (adrenal, extra-adrenal) or mutation status.ConclusionsThe SIZEPASS>1000 criterion is a lesion-based, clinically available, simple and effective tool to predict malignant behavior of PPGLs independently of age, sex, location or mutation status.

Résumé Contexte Le testicule représente un lieu où le précurseur de la vitamine D est converti en sa forme active. Il a été suggéré que la perte d’un testicule pouvait induire une réduction des taux sériques de vitamine D. La carence en vitamine D représenterait un problème de santé important à long terme pour les patients présentant des tumeurs testiculaires à cellules germinales (TCG) puisque la plupart d’entre eux survivent. Le but de cette étude était de se tourner vers les taux sériques de 25(OH)-Vitamine D (25OHD) chez les patients présentant des TCG, avant et après orchidectomie. Au total, 177 patients avec TCG ont subi des mesures des taux sériques de 25OHD, dont 83 avec mesures préopératoires et 94 avec des mesures à six points de temps particuliers, de l’immédiat postopératoire jusqu’à plus de 24 mois. Des évaluations longitudinales des taux sériques de 25OHD ont été réalisées individuellement chez les patients avec des mesures répétées. Une seconde analyse a impliqué des cohortes de patients avec des mesures à six points de temps postopératoires. Les taux sériques des patients ont également été comparés à ceux de 2 groupes témoins, l’un composé de 84 patients atteints de maladies testiculaires non néoplasiques, et l’autre de 237 patients atteints de maladies urologiques non néoplasiques. Nous nous sommes également penchés sur les associations des taux de 25OHD avec les taux de testostérone, d’hormone folliculostimulante (FSH), l’âge, l’histologie de la TCG et la saison. Des méthodes statistiques descriptives ont été utilisées pour comparer les groupes et analyser les changements au fil du temps. Résultats Des taux sériques normaux de 25OHD ont été trouvés chez 21,7%, 23,1%, 20,2%, et 21,9% des patients avec GCT, respectivement en préopératoire et après >2 ans, ainsi que chez les patients du groupe témoin 1 et du groupe témoin 2. Les taux ont été significativement plus élevés au printemps et en été, mais aucune association n’a été observée avec d’autres paramètres. Nous avons retrouvé une diminution transitoire significative des taux de 25OHD avec un nadir à 6-12 mois après orchiectomie et un rétablissement par la suite. Conclusion Contrairement aux études précédentes, nous n’avons trouvé aucune réduction permanente des niveaux de sérum 25OHD après orchiectomie, mais une baisse postopératoire transitoire des taux de 25OHD. Il n’y avait pas d’associations entre les taux de 25OHD et l’âge, ni avec les taux de testostérone ou de FSH. Nos résultats peuvent mettre en avant un rôle particulier du testicule dans le métabolisme de la vitamine D et peuvent ainsi améliorer la compréhension des divers rôles physiologiques des testicules.

Adoptive T cell therapy (ACT) has become a treatment option for viral reactivations in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). Animal models have shown that pathogen-specific central memory T cells (TCM) are protective even at low numbers and show long-term survival, extensive proliferation and high plasticity after adoptive transfer. Concomitantly, our own recent clinical data demonstrate that minimal doses of purified (not in-vitro- expanded) human CMV epitope-specific T cells can be sufficient to clear viremia. However, it remains to be determined if human virus-specific TCM show the same promising features for ACT as their murine counterparts. Using a peptide specific proliferation assay (PSPA) we studied the human Adenovirus- (AdV), Cytomegalovirus- (CMV) and Epstein-Barr virus- (EBV) specific TCM repertoires and determined their functional and proliferative capacities in vitro. TCM products were generated from buffy coats, as well as from non-mobilized and mobilized apheresis products either by flow cytometry-based cell sorting or magnetic cell enrichment using reversible Fab-Streptamers. Adjusted to virus serology and human leukocyte antigen (HLA)-typing, donor samples were analyzed with MHC multimer- and intracellular cytokine staining (ICS) before and after PSPA. TCM cultures showed strong proliferation of a plethora of functional virus-specific T cells. Using PSPA, we could unveil tiniest virus epitope-specific TCM populations, which had remained undetectable in conventional ex-vivo-staining. Furthermore, we could confirm these characteristics for mobilized apheresis- and GMP-grade Fab-Streptamer-purified TCM products. Consequently, we conclude that TCM bare high potential for prophylactic low-dose ACT. In addition, use of Fab-Streptamer-purified TCM allows circumventing regulatory restrictions typically found in conventional ACT product generation. These GMP-compatible TCM can now be used as a broad-spectrum antiviral T cell prophylaxis in alloHSCT patients and PSPA is going to be an indispensable tool for advanced TCM characterization during concomitant immune monitoring.

O Consórcio Público pode ser uma alternativa viável para atendimento às atuais exigências do cenário de saneamento básico. Assim, o objetivo geral desta pesquisa foi analisar o processo de formação de novos consórcios públicos intermunicipais de resíduos sólidos urbanos, utilizando como estudo de caso o Estado do Paraná. A metodologia baseou-se em pesquisa bibliográfica e de campo. Para a amostra, selecionou-se o grupo de municípios do Consórcio Intermunicipal para Gestão de Resíduos Sólidos Urbanos - CONRESOL e um grupo de municípios não consorciados. Foram aplicados questionários para representantes dos dois grupos. Entre os resultados, pode-se apontar a iniciativa do município como fundamental no processo da formação de novos consórcios; o trâmite jurídico para a implantação do consórcio representando mais segurança jurídica do que um empecilho; e a viabilização da disposição adequada à maior vantagem na formação desse arranjo.

Os sedimentos do rio Belém foram removidos, e a destinação incorreta deles pode provocar impactos ambientais e custos adicionais ao município. O objetivo deste trabalho foi avaliar as alternativas de destinação e uso de sedimentos removidos em desassoreamento do rio Belém em área urbana, com base na legislação ambiental brasileira. As avaliações de destinação, ou de uso ou de ambos, foram feitas a partir de uma avaliação química preliminar de contaminantes inorgânicos (Cd, Pb, Cu, Cr, Ni, Ag e Zn) e hidrocarbonetos aromáticos policíclicos (HAP) relacionada às atividades produtivas da região de contribuição do rio Belém. A avaliação das possíveis destinações e, ou, do uso do sedimento seguiu as normas e legislações ambientais brasileiras para diferentes matrizes, o que revelou ser complexa. Uma quantidade substancial de sedimentos pode ser usada para fins úteis, como solo, material de recuperação de áreas contaminadas, material de preenchimento de obras civis. Padrões ambientais específicos devem ser elaborados para discriminar usos e, ou, destinações de acordo com o desenvolvimento científico. Um protocolo de gerenciamento foi proposto, de forma a ser utilizado em futuras obras de desassoreamento.

The German SAR interferometry mission TanDEM-X performed on two TerraSAR-X satellites flying in close formation will provide a global Digital Elevation Model (DEM). A by-product is so-called the Water Indication Mask (WAM). The purpose of this supplementary information layer is to support the DEM editing process. Water surfaces usually show lower coherence in an interferometric data set due to temporal de-correlation and low backscattering. Consequently the corresponding elevation values derived from the interferogram are random and produce a virtual relief. This paper introduces the operational water body detection workflow that synergistically evaluates amplitude and coherence information. The presented results of two test sites reveal that the methodology is globally applicable, classifications are highly accurate and the algorithm is appropriate for operational image processing. The water body detection consists of two steps: the Water Body Detection (WBD) derived of one single DEM scene and the mosaicking of multiple WBD to a single Water Indication Mask (WAM). The fusion strategy for the final TanDEM-X WAM considers all WBD acquired at different times in two global coverages and bases on a fusion by union containing the results of the amplitude and the coherence.

A general obstacle for clinical cell preparations is limited purity, which causes variability in the quality and potency of cell products and might be responsible for negative side effects due to unwanted contaminants. Highly pure populations can be obtained best using positive selection techniques. However, in many cases target cell populations need to be segregated from other cells by combinations of multiple markers, which is still difficult to achieve--especially for clinical cell products. Therefore, we have generated low-affinity antibody-derived Fab-fragments, which stain like parental antibodies when multimerized via Strep-tag and Strep-Tactin, but can subsequently be removed entirely from the target cell population. Such reagents can be generated for virtually any antigen and can be used for sequential positive enrichment steps via paramagnetic beads. First protocols for multiparameter enrichment of two clinically relevant cell populations, CD4(high)/CD25(high)/CD45RA(high) 'regulatory T cells' and CD8(high)/CD62L(high)/CD45RA(neg) 'central memory T cells', have been established to determine quality and efficacy parameters of this novel technology, which should have broad applicability for clinical cell sorting as well as basic research.

The space tourism industry is growing due to advances in rocket technology. Privatised space travel exposes non-professional astronauts with health profiles comprising underlying conditions to microgravity. Prior research has typically focused on the effects of microgravity on human physiology in healthy astronauts, and little is known how the effects of microgravity may play out in the pathophysiology of underlying medical conditions, such as heart failure. This study used an established, controlled lumped mathematical model of the cardiopulmonary system to simulate the effects of entry into microgravity in the setting of heart failure with both, reduced and preserved ejection fraction. We find that exposure to microgravity eventuates an increased cardiac output, and in patients with heart failure there is an unwanted increase in left atrial pressure, indicating an elevated risk for development of pulmonary oedema. This model gives insight into the risks of space flight for people with heart failure, and the impact this may have on mission success in space tourism. [ABSTRACT FROM AUTHOR]