Accurate quantification of atherosclerotic plaque volume by 3D vascular ultrasound using the volumetric linear array method.

Direct quantification of atherosclerotic plaque volume by three-dimensional vascular ultrasound (3DVUS) is more reproducible than 2DUS-based three-dimensional (2D/3D) techniques that generate pseudo-3D volumes from summed 2D plaque areas; however, its accuracy has not been reported. We aimed to determine 3DVUS accuracy for plaque volume measurement with special emphasis on small plaques (a hallmark of early atherosclerosis). The in vitro study consisted of nine phantoms of different volumes (small and medium-large) embedded at variable distances from the surface (superficial vs. >5 cm-depth) and comparison of 3DVUS data generated using a novel volumetric-linear array method with the real phantom volumes. The in vivo study was undertaken in a rabbit model of atherosclerosis in which 3DVUS and 2D/3D volume measurements were correlated against gold-standard histological measurements. In the in vitro setting, there was a strong correlation between 3DVUS measures and real phantom volume both for small (3.0-64.5 mm(3) size) and medium-large (91.1-965.5 mm(3) size) phantoms embedded superficially, with intraclass correlation coefficients (ICC) of 0.99 and 0.98, respectively; conversely, when phantoms were placed at >5 cm, the correlation was only moderate (ICC = 0.67). In the in vivo setting there was strong correlation between 3DVUS-measured plaque volumes and the histological gold-standard (ICC = 0.99 [4.02-92.5 mm(3) size]). Conversely, the correlation between 2D/3D values and the histological gold standard (sum of plaque areas) was weaker (ICC = 0.87 [49-520 mm(2) size]), with large dispersion of the differences between measurements in Bland-Altman plots (mean error, 79.2 mm(2)). 3DVUS using the volumetric-linear array method accurately measures plaque volumes, including those of small plaques. Measurements are more accurate for superficial arterial territories than for deep territories.S

Limb-girdle muscular dystrophy 1F is caused by a microdeletion in the transportin 3 gene

In 2001, we reported linkage of an autosomal dominant form of limb-girdle muscular dystrophy, limb-girdle muscular dystrophy 1F, to chromosome 7q32.1-32.2, but the identity of the mutant gene was elusive. Here, using a whole genome sequencing strategy, we identified the causative mutation of limb-girdle muscular dystrophy 1F, a heterozygous single nucleotide deletion (c.2771del) in the termination codon of transportin 3 (TNPO3). This gene is situated within the chromosomal region linked to the disease and encodes a nuclear membrane protein belonging to the importin beta family. TNPO3 transports serine/arginine-rich proteins into the nucleus, and has been identified as a key factor in the HIV-import process into the nucleus. The mutation is predicted to generate a 15-amino acid extension of the C-terminus of the protein, segregates with the clinical phenotype, and is absent in genomic sequence databases and a set of >200 control alleles. In skeletal muscle of affected individuals, expression of the mutant messenger RNA and histological abnormalities of nuclei and TNPO3 indicate altered TNPO3 function. Our results demonstrate that the TNPO3 mutation is the cause of limb-girdle muscular dystrophy 1F, expand our knowledge of the molecular basis of muscular dystrophies and bolster the importance of defects of nuclear envelope proteins as causes of inherited myopathies

The insulin-like growth factor I receptor regulates glucose transport by astrocytes

Previous findings indicate that reducing brain insulin-like growth factor I receptor (IGF-IR) activity promotes ample neuroprotection. We now examined a possible action of IGF-IR on brain glucose transport to explain its wide protective activity, as energy availability is crucial for healthy tissue function. Using 18FGlucose PET we found that shRNA interference of IGF-IR in mouse somatosensory cortex significantly increased glucose uptake upon sensory stimulation. In vivo microscopy using astrocyte specific staining showed that after IGF-IR shRNA injection in somatosensory cortex, astrocytes displayed greater increases in glucose uptake as compared to astrocytes in the scramble-injected side. Further, mice with the IGF-IR knock down in astrocytes showed increased glucose uptake in somatosensory cortex upon sensory stimulation. Analysis of underlying mechanisms indicated that IGF-IR interacts with glucose transporter 1 (GLUT1), the main facilitative glucose transporter in astrocytes, through a mechanism involving interactions with the scaffolding protein GIPC and the multicargo transporter LRP1 to retain GLUT1 inside the cell. These findings identify IGF-IR as a key modulator of brain glucose metabolism through its inhibitory action on astrocytic GLUT1 activity. GLIA 201

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/

Extravascular Lung Water and Pulmonary Vascular Permeability Index measured at the end of surgery are independent predictors of prolonged mechanical ventilation in patients undergoing liver transplantation.

Background: Pulmonary edema (PE) after orthotopic liver transplantation (OLT) may compromise the postoperative course and prolong the duration of mechanical ventilation (MV) and intensive care unit length of stay. Hemodynamic monitoring with transpulmonary thermodilution permits quantification of extravascular lung water index (ELWI) and calculation of the pulmonary vascular permeability index (PVPI), which is the ratio between the ELWI and the pulmonary blood volume. This ratio can discriminate between PE hydrostatic and nonhydrostatic PE. We investigated the relationship between ELWI and PVPI values, measured at the end of surgery, and prolonged MV (PMV) in patients after OLT. Methods: We retrospectively studied 93 consecutive patients who underwent OLT. We recorded preoperative data including spirometry, echocardiography, severity liver disease with the Model for End-Stage Liver Disease score, and the Child-Pugh classification scores. Intraoperatively, we performed hemodynamic measurements with transpulmonary thermodilution and pulmonary arterial catheters after the induction of anesthesia, 10 minutes before reperfusion, and at the end of surgery. Moreover, we recorded the length of surgery, the amount of IV volume infused, the results of blood coagulation analyses, and blood transfusion. Postoperatively, we recorded the duration of MV and intensive care unit length of stay, mortality, and graft function. Patients were then classified as requiring PMV (>48 hours after surgery) or not. Statistical analyses, preoperative and intraoperative variables between patients with and without PMV, were compared using Mann-Whitney U tests. Receiver-operating characteristic curves were used to evaluate the ability of preoperative and intraoperative variables to predict PMV. Results: Twelve patients required PMV after surgery. Patients who required PMV exhibited increased ELWI (11.6 ± 3 mL/kg vs 9.3 ± 2 mL/kg, P = 0.0099) and PVPI values (2.94 ± 1 vs 1.8 ± 0.6, P = 0.000015) at the end of surgery. The areas under the receiver-operating characteristic curve were 0.890 ± 0.04 for PVPI with a 99% confidence interval of 0.782 to 0.958 and 0.730 ± 0.08 for ELWI with a 99% confidence interval of 0.594 to 0.839. Using a cutoff of 2.3 for PVPI allowed a sensitivity = 91.7%, a specificity = 83.8, a positive predictive value = 45.8%, and a negative predictive value = 98.5% for predicting PMV. A cutoff of 12 for ELWI allowed a sensitivity of 50%, specificity of 85%, positive predictive value of 33.3%, and negative predictive value of 91.9% for PMV. Conclusions: PVPI and ELWI values obtained at the end of OLT are useful for predicting the need for postoperative PMV.Depto. de Farmacología y ToxicologíaFac. de MedicinaTRUEpu

Programmable VCSEL-based photonic system architecture for future agile Tb/s metro networks

To deal with the challenging requirements of metropolitan area networks (MANs), it is essential to design cost-effective systems that can support high capacity and dynamic adaptation, as well as a synergy of programmability and efficient photonic technologies. This becomes crucial for very large MANs that support 5G, where multihop connections will need to be dynamically established at target capacities beyond Tb/s. Programmability, automation, and modularity of network elements are key desired features. In this work, a modular photonic system, programmable via a software-defined networking platform, designed for dynamic 5G-supportive MANs, is described and analyzed. We consider modular sliceable bandwidth/bit rate variable transceivers (S-BVTs) based on vertical-cavity surface-emitting laser (VCSEL) technology and dense photonic integration. The proposed system and its programmability are experimentally assessed using a VCSEL with 10 GHz bandwidth. The experiments are performed over connections as long as six-hop and 160 km, from low-level aggregation nodes to metro-core nodes, thereby enabling IP off-loading. Furthermore, a numerical model is derived to estimate the performance when adopting higher bandwidth VCSELs (≥18 GHz) and integrated coherent receivers, as targeted in the proposed system. The analysis is performed for both 50 GHz and 25 GHz granularities. In the former case, 50 Gb/s capacity per flow can be supported over the targeted connections, for optical signal-to-noise ratio values above 26 dB. When the granularity is 25 GHz, the filter narrowing effect severely impacts the performance. Nevertheless, 1.2 Tb/s capacity (scalable to higher values if spectral/spatial dimensions are exploited) can be achieved when configuring the S-BVT to enable 40 VCSEL flows. This confirms that the system is promising to support Tb/s connections in future agile MANs

Bacterial Diversity in Bentonites, Engineered Barrier for Deep Geological Disposal of Radioactive Wastes

The long-term disposal of radioactive wastes in a deep geological repository is the accepted international solution for the treatment and management of these special residues. The microbial community of the selected host rocks and engineered barriers for the deep geological repository may affect the performance and the safety of the radioactive waste disposal. In this work, the bacterial population of bentonite formations of Almeria (Spain), selected as a reference material for bentonite-engineered barriers in the disposal of radioactive wastes, was studied. 16S ribosomal RNA (rRNA) gene-based approaches were used to study the bacterial community of the bentonite samples by traditional clone libraries and Illumina sequencing. Using both techniques, the bacterial diversity analysis revealed similar results, with phylotypes belonging to 14 different bacterial phyla: Acidobacteria, Actinobacteria, Armatimonadetes, Bacteroidetes, Chloroflexi, Cyanobacteria, Deinococcus-Thermus, Firmicutes, Gemmatimonadetes, Planctomycetes, Proteobacteria, Nitrospirae, Verrucomicrobia and an unknown phylum. The dominant groups of the community were represented by Proteobacteria and Bacteroidetes. A high diversity was found in three of the studied samples. However, two samples were less diverse and dominated by Betaproteobacteria

Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity

BACKGROUND: Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed. OBJECTIVES: The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model. METHODS: Twenty pigs were included. Of these, 5 received 5 biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) and were followed until sacrifice at 16 weeks. Another 5 pigs received 3 biweekly doxorubicin doses and were followed to 16 weeks. A third group was sacrificed after the third dose. All groups underwent weekly CMR examinations including anatomical and T2 and T1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR. RESULTS: The earliest doxorubicin-cardiotoxicity CMR parameter was T2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T1 mapping and ECV abnormalities coincided with LV motion defects: LV ejection fraction declined from week 10 (2 weeks after the fifth and final doxorubicin dose). Stopping doxorubicin therapy upon detection of T2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T2 prolongation occurs at a reversible disease stage. CONCLUSIONS: T2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T1 mapping, ECV, or LV motion defects. The occurrence of these changes at a reversible disease stage shows the clinical potential of this CMR marker for tailored anthracycline therapy.This study was partially supported by grants from the Ministerio de Ciencia, Innovacion y Universidades through the Carlos III Institute of Health-Fondo de Investigacion Sanitaria (P116/02110), the European Regional Development Fund (SAF2013-49663-EXP), and the Spanish Society of Cardiology (FEC basic science in cardiology grant). This research program is part of an institutional agreement between the CNIC and FIIS-Fundacion Jimenez Diaz. This study forms part of a Master Research Agreement between the CNIC and Philips Healthcare, and is part of a bilateral research program between Hospital de Salamanca Cardiology Department and the CNIC. The CNIC is supported by the Ministerio de Ciencia, Innovacion y Universidades, and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MEIC award SEV-2015-0505). Drs. Galan-Arriola and Villena-Gutierrez are P-FIS fellows (Instituto de Salud Carlos III). Dr. Fernandez-Jimenez has received funding through the European Union Horizon 2020 Research and Innovation program under grant MSCA-IF-GF-707642. Dr. Sanchez -Gonzalez is an employee of Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

Experimental Assessment of a Programmable VCSEL-Based Photonic System Architecture over a Multi-Hop Path with 19-Core MCF for Future Agile Tb/s Metro Networks

An SDN-enabled photonic system adopting VCSEL technology is experimentally analyzed targeting dynamic 5G-supportive MAN. Direct and coherent detection modules are compared and programmability assessed over up to 6-hop 160km HL4-HL2/1 connection including 25km 19-core MCF