Epidemiology and pathophysiology of cancer-associated thrombosis

Venous thromboembolism (VTE) is a common complication in patients with malignant disease. First recognised by Bouillard in 1823 and later described by Trousseau in 1844, multiple studies have since provided considerable evidence for a clinical association between VTE and cancer. Across all cancers, the risk for VTE is elevated 7-fold; in certain malignancies, the risk for VTE may be increased up to 28-fold. Venous thromboembolism is the second leading cause of death in patients with cancer; among survivors, complications commonly include recurrent VTE and post-thrombotic syndrome, and (more rarely) chronic thromboembolic pulmonary hypertension, which are costly, and have a profound impact on the patient's quality of life. Tumour cells can activate blood coagulation through multiple mechanisms, including production of procoagulant, fibrinolytic, and proaggregating activities, release of proinflammatory and proangiogenic cytokines, and interacting directly with host vascular and blood cells (e.g., endothelial cells, leukocytes, and platelets) through adhesion molecules. Increasing evidence suggests that elements of the haemostatic system also have a direct role in eliciting or enhancing angiogenesis, cell survival, and metastasis. Despite the problem posed by VTE in the setting of cancer, it is evident that a significant number of oncologists do not recognise the link between cancer, its treatment, and thrombogenesis. On 22 May 2009, a group of UK-based physicians met in London, UK, to evaluate recent data on cancer thrombosis. This article (1 of 4) briefly reviews key data on the epidemiology and pathophysiology of VTE as a context for a discussion and consensus statement developed by meeting attendees, on the implications of this information for UK clinical practice

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

publishersversionPeer reviewe

CALIFA, the Calar Alto Legacy Integral Field Area survey III. Second public data release

CALIFA is the first legacy survey being performed at Calar Alto. The CALIFA collaboration would like to thank the IAA-CSIC and MPIA-MPG as major partners of the observatory, and CAHA itself, for the unique access to telescope time and support in manpower and infrastructures. The CALIFA collaboration thanks also the CAHA staff for the dedication to this project. R.G.B., R.G.D., and E.P. are supported by the Spanish Ministerio de Ciencia e Innovacion under grant AYA2010-15081. S.Z. is supported by the EU Marie Curie Integration Grant "SteMaGE" Nr. PCIG12-GA-2012-326466 (Call Identifier: FP7-PEOPLE-2012 CIG). J.F.B. acknowledges support from grants AYA2010-21322-C03-02 and AIB-2010-DE-00227 from the Spanish Ministry of Economy and Competitiveness (MINECO), as well as from the FP7 Marie Curie Actions of the European Commission, via the Initial Training Network DAGAL under REA grant agreement number 289313. Support for L.G. is provided by the Ministry of Economy, Development, and Tourism's Millennium Science Initiative through grant IC12009, awarded to The Millennium Institute of Astrophysics, M.A.S.L.G. also acknowledges support by CONICYT through FONDECYT grant 3140566. A.G. acknowledges support from the FP7/2007-2013 under grant agreement n. 267251 (AstroFIt). J.M.G. acknowledges support from the Fundacao para a Ciencia e a Tecnologia (FCT) through the Fellowship SFRH/BPD/66958/2009 from FCT (Portugal) and research grant PTDC/FIS-AST/3214/2012. RAM was funded by the Spanish programme of International Campus of Excellence Moncloa (CEI). J.M.A. acknowledges support from the European Research Council Starting Grant (SEDmorph; P.I. V. Wild). I.M., J.M. and A.d.O. acknowledge the support by the projects AYA2010-15196 from the Spanish Ministerio de Ciencia e Innovacion and TIC 114 and PO08-TIC-3531 from Junta de Andalucia. AMI acknowledges support from Agence Nationale de la Recherche through the STILISM project (ANR-12-BS05-0016-02). M.M. acknowledges financial support from AYA2010-21887-C04-02 from the Ministerio de Economia y Competitividad. P.P. is supported by an FCT Investigador 2013 Contract, funded by FCT/MCTES (Portugal) and POPH/FSE (EC). P.P. acknowledges support by FCT under project FCOMP-01-0124-FEDER-029170 (Reference FCT PTDC/FIS-AST/3214/2012), funded by FCT-MEC (PIDDAC) and FEDER (COMPETE). T.R.L. thanks the support of the Spanish Ministerio de Educacion, Cultura y Deporte by means of the FPU fellowship. PSB acknowledges support from the Ramon y Cajal program, grant ATA2010-21322-C03-02 from the Spanish Ministry of Economy and Competitiveness (MINECO). C.J.W. acknowledges support through the Marie Curie Career Integration Grant 303912. V.W. acknowledges support from the European Research Council Starting Grant (SEDMorph P.I. V. Wild) and European Career Re-integration Grant (Phiz-Ev P.I.V. Wild). Y.A. acknowledges financial support from the Ramon y Cajal programme (RyC-2011-09461) and project AYA2013-47742-C4-3-P, both managed by the Ministerio de Economia y Competitividad, as well as the "Study of Emission-Line Galaxies with Integral-Field Spectroscopy" (SELGIFS) programme, funded by the EU (FP7-PEOPLE-2013-IRSES-612701) within the Marie-Sklodowska-Curie Actions scheme. We thank the referee David Wilman for very useful comments that improved the presentation of the paper.This paper describes the Second Public Data Release (DR2) of the Calar Alto Legacy Integral Field Area (CALIFA) survey. The data for 200 objects are made public, including the 100 galaxies of the First Public Data Release (DR1). Data were obtained with the integral-field spectrograph PMAS/PPak mounted on the 3.5 m telescope at the Calar Alto observatory. Two different spectral setups are available for each galaxy, (i) a lowresolution V500 setup covering the wavelength range 3745–7500 Å with a spectral resolution of 6.0 Å (FWHM); and (ii) a medium-resolution V1200 setup covering the wavelength range 3650–4840 Å with a spectral resolution of 2.3 Å (FWHM). The sample covers a redshift range between 0.005 and 0.03, with a wide range of properties in the color–magnitude diagram, stellar mass, ionization conditions, and morphological types. All the cubes in the data release were reduced with the latest pipeline, which includes improved spectrophotometric calibration, spatial registration, and spatial resolution. The spectrophotometric calibration is better than 6% and the median spatial resolution is 200 : 4. In total, the second data release contains over 1.5 million spectra.Instituto de Salud Carlos III Spanish Government AYA2010-15081 AYA2010-15196European Union (EU) PCIG12-GA-2012-326466Spanish Ministry of Economy and Competitiveness (MINECO) AYA2010-21322-C03-02 AIB-2010-DE-00227FP7 Marie Curie Actions of the European Commission, via the Initial Training Network DAGAL under REA 289313Ministry of Economy, Development, and Tourism's Millennium Science Initiative IC12009Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 3140566Fundacao para a Ciencia e a Tecnologia (FCT) from FCT (Portugal) SFRH/BPD/66958/2009Spanish programme of International Campus of Excellence Moncloa (CEI)European Research Council (ERC)Junta de Andalucia TIC 114 PO08-TIC-3531French National Research Agency (ANR) ANR-12-BS05-0016-02Spanish Government AYA2010-21887-C04-02FCT Investigador Contract - FCT/MCTES (Portugal)European Commission Joint Research Centre European Social Fund (ESF)FCT - FCT-MEC (PIDDAC) FCOMP-01-0124-FEDER-029170 FCT PTDC/FIS-AST/3214/2012European Union (EU)Spanish Ministerio de Educacion, Cultura y Deporte by FPURamon y Cajal program from the Spanish Ministry of Economy and Competitiveness (MINECO) ATA2010-21322-C03-02European Union (EU) 303912European Career Re-integration GrantSpanish Government RyC-2011-09461 AYA2013-47742-C4-3-PEuropean Union (EU) FP7-PEOPLE-2013-IRSES-612701PTDC/FIS-AST/3214/2012Science & Technology Facilities Council (STFC) ST/K000985/

Overview of recent TJ-II stellarator results

The main results obtained in the TJ-II stellarator in the last two years are reported. The most important topics investigated have been modelling and validation of impurity transport, validation of gyrokinetic simulations, turbulence characterisation, effect of magnetic configuration on transport, fuelling with pellet injection, fast particles and liquid metal plasma facing components. As regards impurity transport research, a number of working lines exploring several recently discovered effects have been developed: the effect of tangential drifts on stellarator neoclassical transport, the impurity flux driven by electric fields tangent to magnetic surfaces and attempts of experimental validation with Doppler reflectometry of the variation of the radial electric field on the flux surface. Concerning gyrokinetic simulations, two validation activities have been performed, the comparison with measurements of zonal flow relaxation in pellet-induced fast transients and the comparison with experimental poloidal variation of fluctuations amplitude. The impact of radial electric fields on turbulence spreading in the edge and scrape-off layer has been also experimentally characterized using a 2D Langmuir probe array. Another remarkable piece of work has been the investigation of the radial propagation of small temperature perturbations using transfer entropy. Research on the physics and modelling of plasma core fuelling with pellet and tracer-encapsulated solid-pellet injection has produced also relevant results. Neutral beam injection driven Alfvénic activity and its possible control by electron cyclotron current drive has been examined as well in TJ-II. Finally, recent results on alternative plasma facing components based on liquid metals are also presentedThis work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014–2018 under Grant Agreement No. 633053. It has been partially funded by the Ministerio de Ciencia, Inovación y Universidades of Spain under projects ENE2013-48109-P, ENE2015-70142-P and FIS2017-88892-P. It has also received funds from the Spanish Government via mobility grant PRX17/00425. The authors thankfully acknowledge the computer resources at MareNostrum and the technical support provided by the Barcelona S.C. It has been supported as well by The Science and Technology Center in Ukraine (STCU), Project P-507F

Development of a Risk Prediction Score for Occult Cancer in Patients With VTE.

The benefits of a diagnostic workup for occult cancer in patients with VTE are controversial. Our aim was to provide and validate a risk score for occult cancer in patients with VTE. We designed a nested case-control study in a cohort of patients with VTE included in the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry from 2001 to 2014. Cases included cancer detected beyond the first 30 days and up to 24 months after VTE. Control subjects were defined as patients with VTE with no cancer in the same period. Of 5,863 eligible patients, 444 (7.6%; 95% CI, 6.8%-8.2%) were diagnosed with occult cancer. On multivariable analysis, variables selected were male sex, age > 70 years, chronic lung disease, anemia, elevated platelet count, prior VTE, and recent surgery. We built a risk score assigning points to each variable. Internal validity was confirmed using bootstrap analysis. The proportion of patients with cancer who scored ≤ 2 points was 5.8% (241 of 4,150) and that proportion in those who scored ≥ 3 points was 12% (203 of 1,713). We also identified scores divided by sex and age subgroups. This is the first risk score that has identified patients with VTE who are at increased risk for occult cancer. Our score needs to be externally validated

The brain-specific tissue-type plasminogen activator inhibitor, neuroserpin, protects neurons against excitotoxicity both in vitro and in vivo.

Considering its brain-specific expression, neuroserpin (NS), a potent inhibitor of tissue-type plasminogen activator (tPA), might be a good therapeutic target to limit the pro-excitotoxic effects of tPA within the cerebral parenchyma, without affecting the benefit from thrombolysis in stroke patients. Here, we aimed at determining the mechanisms of action responsible for the previously reported neuroprotective activity of NS in rodent experimental cerebral ischemia. First, we show in vivo that exogenous NS protects the cortex and the striatum against NMDA-induced injury. Then, the cellular mechanisms of this neuroprotection were investigated in primary cultures of cortical neurons. We show that NS fails to prevent serum deprivation-induced apoptotic neuronal death, while it selectively prevents NMDA- but not AMPA-induced excitotoxicity. This beneficial effect is associated to a decrease in NMDA receptor-mediated intracellular calcium influx. Altogether, these data suggest that an overexpression of neuroserpin in the brain parenchyma might limit the deleterious effect of tPA on NMDA receptor-mediated neuronal death, which occurs following experimental ischemia