Nonuniform Power Changes and Spatial, Temporal and Spectral Diversity in High Gamma Band (\u3e60 Hz) Signals in Human Electrocorticography

High-gamma band: \u3e60Hz) power changes in cortical electrophysiology are a reliable indicator of focal, event-related cortical activity. In spite of discoveries of oscillatory subthreshold and synchronous suprathreshold activity at the cellular level, there is an increasingly popular view that high-gamma band amplitude changes recorded from cellular ensembles are the result of asynchronous firing activity that yields wideband and uniform power increases. Others have demonstrated independence of power changes in the low- and high-gamma bands, but to date, no studies have shown evidence of any such independence above 60Hz. Based on non-uniformities in time-frequency analyses of electrocorticographic: ECoG) signals, we hypothesized that induced high-gamma band: 60-500Hz) power changes are more heterogeneous than currently understood. We quantified this spectral non-uniformity with two different approaches using single-word repetition tasks in human subjects. First, we showed that the functional responsiveness of different ECoG high-gamma sub-bands can discriminate cognitive tasks: e.g., hearing, reading, speaking) and cortical locations. Power changes in these sub-bands of the high-gamma range are consistently present within single trials and have statistically different time courses within the trial structure. Moreover, when consolidated across all subjects within three task-relevant anatomic regions: sensorimotor, Broca\u27s area, and superior temporal gyrus), these behavior- and location- dependent power changes evidenced nonuniform trends across the population of subjects. Second, we studied the dynamics of multiple frequency bands in order to quantify the diversity present in the ECoG signals. Using a matched filter construct and receiver operating characteristic: ROC) analysis we show that power modulations correlated with phonemic content in spoken and heard words are represented diffusely in space, time and frequency. Correlating power modulation in multiple frequency bands above 60 Hz over broad cortical areas, with time varying envelopes significantly improved performed area under the ROC curve scores in phoneme prediction experiments. Finally we show preliminary evidence supporting our hypothesis in microarray ECoG data. Taken together, the nonuniformity of high frequency power changes and the information content captured in the spatio-temporal dynamics of those frequencies suggests that a new approach to evaluating high-gamma band cortical activity is necessary. These findings show that in addition to time and location, frequency is another fundamental dimension of high-gamma dynamics

Performance of a Spectrally Encoded Multi-carrier Phase Shift Keying Communications System in a Frequency-Selective, Slowly-Fading Multipath Channel

This research examines the performance of a spectrally encoded, multi-carrier, phase shift keying communications system in a frequency-selective, slowly-fading multipath channel. The specific communications system modeled is the transform domain communication system (TDCS) originally researched as an interference avoidance technique. Previous TDCS research assumed an additive white Gaussian noise channel, which is not representative of a realistic environment. This thesis presents overviews of previous TDCS research, the multipath fading channel, and the RAKE receiver. Analysis and Matlab simulations compare the performance of spectrally encoded and un-encoded signals through a multipath fading channel using an L-diversity TDCS RAKE receiver. Encoded signals take on the spectral shape of the multipath fading channel transfer function. Un-encoded signals have a flat magnitude spectrum. The research also evaluates the interference rejection capability of spectrally encoded signals in a multipath channel. Research results indicate for diversities ranging between 2 and 50, spectrally encoded signals need 1.0 to 2.75dB less transmitted normalized bit energy to noise power spectral density ratios to achieve the same probability of bit error as un-encoded signals. Results also demonstrate that spectrally encoded TDCS signals retain the interference rejection capability

Nonuniform high-gamma (60-500 Hz) power changes dissociate cognitive task and anatomy in human cortex

High-gamma-band (\u3e60 Hz) power changes in cortical electrophysiology are a reliable indicator of focal, event-related cortical activity. Despite discoveries of oscillatory subthreshold and synchronous suprathreshold activity at the cellular level, there is an increasingly popular view that high-gamma-band amplitude changes recorded from cellular ensembles are the result of asynchronous firing activity that yields wideband and uniform power increases. Others have demonstrated independence of power changes in the low- and high-gamma bands, but to date, no studies have shown evidence of any such independence above 60 Hz. Based on nonuniformities in time-frequency analyses of electrocorticographic (ECoG) signals, we hypothesized that induced high-gamma-band (60-500 Hz) power changes are more heterogeneous than currently understood. Using single-word repetition tasks in six human subjects, we showed that functional responsiveness of different ECoG high-gamma sub-bands can discriminate cognitive task (e.g., hearing, reading, speaking) and cortical locations. Power changes in these sub-bands of the high-gamma range are consistently present within single trials and have statistically different time courses within the trial structure. Moreover, when consolidated across all subjects within three task-relevant anatomic regions (sensorimotor, Broca\u27s area, and superior temporal gyrus), these behavior- and location-dependent power changes evidenced nonuniform trends across the population. Together, the independence and nonuniformity of power changes across a broad range of frequencies suggest that a new approach to evaluating high-gamma-band cortical activity is necessary. These findings show that in addition to time and location, frequency is another fundamental dimension of high-gamma dynamics

Temporal evolution of gamma activity in human cortex during an overt and covert word repetition task

Several scientists have proposed different models for cortical processing of speech. Classically, the regions participating in language were thought to be modular with a linear sequence of activations. More recently, modern theoretical models have posited a more hierarchical and distributed interaction of anatomic areas for the various stages of speech processing. Traditional imaging techniques can only define the location or time of cortical activation, which impedes the further evaluation and refinement of these models. In this study, we take advantage of recordings from the surface of the brain [electrocorticography (ECoG)], which can accurately detect the location and timing of cortical activations, to study the time course of ECoG high gamma (HG) modulations during an overt and covert word repetition task for different cortical areas. For overt word production, our results show substantial perisylvian cortical activations early in the perceptual phase of the task that were maintained through word articulation. However, this broad activation is attenuated during the expressive phase of covert word repetition. Across the different repetition tasks, the utilization of the different cortical sites within the perisylvian region varied in the degree of activation dependent on which stimulus was provided (auditory or visual cue) and whether the word was to be spoken or imagined. Taken together, the data support current models of speech that have been previously described with functional imaging. Moreover, this study demonstrates that the broad perisylvian speech network activates early and maintains suprathreshold activation throughout the word repetition task that appears to be modulated by the demands of different conditions

Brain mapping in a patient with congenital blindness – A case for multimodal approaches

Recent advances in basic neuroscience research across a wide range of methodologies have contributed significantly to our understanding of human cortical electrophysiology and functional brain imaging. Translation of this research into clinical neurosurgery has opened doors for advanced mapping of functionality that previously was prohibitively difficult, if not impossible. Here we present the case of a unique individual with congenital blindness and medically refractory epilepsy who underwent neurosurgical treatment of her seizures. Pre-operative evaluation presented the challenge of accurately and robustly mapping the cerebral cortex for an individual with a high probability of significant cortical re-organization. Additionally, a blind individual has unique priorities in one's ability to read Braille by touch and sense the environment primarily by sound than the non-vision impaired person. For these reasons we employed additional measures to map sensory, motor, speech, language, and auditory perception by employing a number of cortical electrophysiologic mapping and functional magnetic resonance imaging methods. Our data show promising results in the application of these adjunctive methods in the pre-operative mapping of otherwise difficult to localize, and highly variable, functional cortical areas

Actitudes y estereotipos en estudiantes del área de la salud hacia personas con discapacidad motriz

El objetivo central de esta investigación fue analizar las actitudes y los estereotipos hacia personas con discapacidad motriz en una muestra de estudiantes del área de la salud. Para ello se aplicaron la Escala Multidimensional de Actitudes Hacia Personas con Discapacidad y un instrumento para medir estereotipos (calidez y competencia) hacia personas con discapacidad. Se trabajó con 232 estudiantes (edad promedio: 23 años, DT=5), a quienes se les aplicaron los instrumentos en línea. Los resultados del análisis factorial muestran una estructura teóricamente congruente y propiedades psicométricas adecuadas para ambos instrumentos. Los participantes reportaron actitudes positivas hacia las personas con discapacidad y percepciones similares de competencia hacia individuos con y sin discapacidad. Sin embargo, reportaron niveles significativamente más altos de calidez para las personas con discapacidad. Estos resultados sugieren una baja disposición a reportar estereotipos de incompetencia o desagrado hacia personas con discapacidad, pero una percepción compensatoria de mayor calidez

Evolution of the Properties of a Poly(L-lactic acid) Scaffold with Double Porosity During In Vitro Degradation in a Phosphate-Buffered Saline Solution

[EN] A poly(L-lactic acid) scaffold prepared by a combination of freeze-extraction and porogen-leaching methods was submitted to static degradation in a phosphate-buffered saline solution at pH 7.4 and 37 C for up to 12 months. After 6 months of degradation, the scaffold maintained its integrity, although noticeable changes in its permeability and pore size were recorded. After 12 months, scanning electron microscopy pictures showed that most of the trabeculae were broken, and the sample disaggregated under minimum loading. Neither weight loss nor crystallinity changes in the first heating calorimetric scan were observed during the degradation experiment. However, after 12 months, a rise in the crystallinity from 13 to 38% and a drop in the glass-transition temperature from 58 to 54 C were measured in the second heating scan. The onset of thermal degradation moved from 300 to 210 C after 12 months. Although the elastic modulus suffered only a very slight reduction with degradation time, the aggregate modulus decreased 44% after 6 months.The authors acknowledge the support of the Instituto de Salud Carlos III, Ministerio de Economıa y Competitividad, and the European Commission through FP7-ERANet EuroNanoMed 2011 PI11/03032 and FP7-PEOPLE-2012-IAPP (contract grant number PIAP-GA-2012–324386). The Biomedical Research Networking Center in Bioengineering, Biomaterials, and Nanomedicine is an initiative funded by the VI National R&D&i Plan 2008–2011, Iniciativa Ingenio 2010, and Consolider Program. Biomedical Research Networking Center actions are financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. The authors also thank the Tissue Characterization Platform of the Biomedical Research Networking Center in Bioengineering, Biomaterials, and Nanomedicine for its technical support. They also thank the Linguistic Assistance Services of the Language Centre, Universitat Politecnica de Valencia, for their help in revising this article.Deplaine, H.; Acosta-Santamaría, VA.; Vidaurre Garayo, AJ.; Gómez Ribelles, JL.; Doblare Castellano, M.; Ochoa-Garrido, I.; Gallego Ferrer, G. (2014). Evolution of the Properties of a Poly(L-lactic acid) Scaffold with Double Porosity During In Vitro Degradation in a Phosphate-Buffered Saline Solution. Journal of Applied Polymer Science. 131:40956-40966. https://doi.org/10.1002/APP.40956S4095640966131Zhao, J., Yuan, X., Cui, Y., Ge, Q., & Yao, K. (2003). Preparation and characterization of poly(L-lactide)/ poly(?-caprolactone) fibrous scaffolds for cartilage tissue engineering. Journal of Applied Polymer Science, 91(3), 1676-1684. doi:10.1002/app.13323Hutmacher, D. W. (2001). Scaffold design and fabrication technologies for engineering tissues — state of the art and future perspectives. Journal of Biomaterials Science, Polymer Edition, 12(1), 107-124. doi:10.1163/156856201744489Butler, D. L., Goldstein, S. A., & Guilak, F. (2000). Functional Tissue Engineering: The Role of Biomechanics. Journal of Biomechanical Engineering, 122(6), 570-575. doi:10.1115/1.1318906Budyanto, L., Goh, Y. Q., & Ooi, C. P. (2008). Fabrication of porous poly(L-lactide) (PLLA) scaffolds for tissue engineering using liquid–liquid phase separation and freeze extraction. Journal of Materials Science: Materials in Medicine, 20(1), 105-111. doi:10.1007/s10856-008-3545-8Woodruff, M. A., Lange, C., Reichert, J., Berner, A., Chen, F., Fratzl, P., … Hutmacher, D. W. (2012). Bone tissue engineering: from bench to bedside. Materials Today, 15(10), 430-435. doi:10.1016/s1369-7021(12)70194-3Hollister, S. J. (2005). Porous scaffold design for tissue engineering. Nature Materials, 4(7), 518-524. doi:10.1038/nmat1421Hutmacher, D. W. (2000). Scaffolds in tissue engineering bone and cartilage. Biomaterials, 21(24), 2529-2543. doi:10.1016/s0142-9612(00)00121-6Chiquet, M., Renedo, A. S., Huber, F., & Flück, M. (2003). How do fibroblasts translate mechanical signals into changes in extracellular matrix production? Matrix Biology, 22(1), 73-80. doi:10.1016/s0945-053x(03)00004-0Diego, R. B., Estellés, J. M., Sanz, J. A., García-Aznar, J. M., & Sánchez, M. S. (2007). Polymer scaffolds with interconnected spherical pores and controlled architecture for tissue engineering: Fabrication, mechanical properties, and finite element modeling. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 81B(2), 448-455. doi:10.1002/jbm.b.30683Pitt, C. G., Chasalow, F. I., Hibionada, Y. M., Klimas, D. M., & Schindler, A. (1981). Aliphatic polyesters. I. The degradation of poly(ϵ-caprolactone)in vivo. Journal of Applied Polymer Science, 26(11), 3779-3787. doi:10.1002/app.1981.070261124Lu, L., Peter, S. J., Lyman, M. D., Lai, H.-L., Leite, S. M., A. Tamada, J., … Mikos, A. G. (2000). In vitro degradation of porous poly(l-lactic acid) foams. Biomaterials, 21(15), 1595-1605. doi:10.1016/s0142-9612(00)00048-xLu, L., Peter, S. J., D. Lyman, M., Lai, H.-L., Leite, S. M., Tamada, J. A., … Mikos, A. G. (2000). In vitro and in vivo degradation of porous poly(dl-lactic-co-glycolic acid) foams. Biomaterials, 21(18), 1837-1845. doi:10.1016/s0142-9612(00)00047-8Odelius, K., Höglund, A., Kumar, S., Hakkarainen, M., Ghosh, A. K., Bhatnagar, N., & Albertsson, A.-C. (2011). Porosity and Pore Size Regulate the Degradation Product Profile of Polylactide. Biomacromolecules, 12(4), 1250-1258. doi:10.1021/bm1015464GONG, Y., ZHOU, Q., GAO, C., & SHEN, J. (2007). In vitro and in vivo degradability and cytocompatibility of poly(l-lactic acid) scaffold fabricated by a gelatin particle leaching method. Acta Biomaterialia, 3(4), 531-540. doi:10.1016/j.actbio.2006.12.008Zhao, J., Han, W., Tu, M., Huan, S., Zeng, R., Wu, H., … Zhou, C. (2012). Preparation and properties of biomimetic porous nanofibrous poly(l-lactide) scaffold with chitosan nanofiber network by a dual thermally induced phase separation technique. Materials Science and Engineering: C, 32(6), 1496-1502. doi:10.1016/j.msec.2012.04.031Hakkarainen, M., Albertsson, A.-C., & Karlsson, S. (1996). Weight losses and molecular weight changes correlated with the evolution of hydroxyacids in simulated in vivo degradation of homo- and copolymers of PLA and PGA. Polymer Degradation and Stability, 52(3), 283-291. doi:10.1016/0141-3910(96)00009-2Zhang, X., Espiritu, M., Bilyk, A., & Kurniawan, L. (2008). Morphological behaviour of poly(lactic acid) during hydrolytic degradation. Polymer Degradation and Stability, 93(10), 1964-1970. doi:10.1016/j.polymdegradstab.2008.06.007Chen, C.-C., Chueh, J.-Y., Tseng, H., Huang, H.-M., & Lee, S.-Y. (2003). Preparation and characterization of biodegradable PLA polymeric blends. Biomaterials, 24(7), 1167-1173. doi:10.1016/s0142-9612(02)00466-0Thomson, R. C., Wake, M. C., Yaszemski, M. J., & Mikos, A. G. (1995). Biodegradable polymer scaffolds to regenerate organs. Advances in Polymer Science, 245-274. doi:10.1007/3540587888_18Li, W.-J., & Tuan, R. S. (2005). Polymeric Scaffolds for Cartilage Tissue Engineering. Macromolecular Symposia, 227(1), 65-76. doi:10.1002/masy.200550906Ma, J., He, X., & Jabbari, E. (2010). Osteogenic Differentiation of Marrow Stromal Cells on Random and Aligned Electrospun Poly(l-lactide) Nanofibers. Annals of Biomedical Engineering, 39(1), 14-25. doi:10.1007/s10439-010-0106-3Dai, L., Li, D., & He, J. (2013). Degradation of graft polymer and blend based on cellulose and poly(L-lactide). Journal of Applied Polymer Science, 130(4), 2257-2264. doi:10.1002/app.39451Vieira, A. C., Vieira, J. C., Ferra, J. M., Magalhães, F. D., Guedes, R. M., & Marques, A. T. (2011). Mechanical study of PLA–PCL fibers during in vitro degradation. Journal of the Mechanical Behavior of Biomedical Materials, 4(3), 451-460. doi:10.1016/j.jmbbm.2010.12.006Gaona, L. A., Gómez Ribelles, J. L., Perilla, J. E., & Lebourg, M. (2012). Hydrolytic degradation of PLLA/PCL microporous membranes prepared by freeze extraction. Polymer Degradation and Stability, 97(9), 1621-1632. doi:10.1016/j.polymdegradstab.2012.06.031Tsuji, H., Mizuno, A., & Ikada, Y. (2000). Properties and morphology of poly(L-lactide). III. Effects of initial crystallinity on long-termin vitro hydrolysis of high molecular weight poly(L-lactide) film in phosphate-buffered solution. Journal of Applied Polymer Science, 77(7), 1452-1464. doi:10.1002/1097-4628(20000815)77:73.0.co;2-sTsuji, H., & Ikada, Y. (2000). Properties and morphology of poly( l -lactide) 4. Effects of structural parameters on long-term hydrolysis of poly( l -lactide) in phosphate-buffered solution. Polymer Degradation and Stability, 67(1), 179-189. doi:10.1016/s0141-3910(99)00111-1Freyman, T. M., Yannas, I. V., & Gibson, L. J. (2001). Cellular materials as porous scaffolds for tissue engineering. Progress in Materials Science, 46(3-4), 273-282. doi:10.1016/s0079-6425(00)00018-9Li, S., de Wijn, J. R., Li, J., Layrolle, P., & de Groot, K. (2003). Macroporous Biphasic Calcium Phosphate Scaffold with High Permeability/Porosity Ratio. Tissue Engineering, 9(3), 535-548. doi:10.1089/107632703322066714Wagoner Johnson, A. J., & Herschler, B. A. (2011). A review of the mechanical behavior of CaP and CaP/polymer composites for applications in bone replacement and repair. Acta Biomaterialia, 7(1), 16-30. doi:10.1016/j.actbio.2010.07.012Rezwan, K., Chen, Q. Z., Blaker, J. J., & Boccaccini, A. R. (2006). Biodegradable and bioactive porous polymer/inorganic composite scaffolds for bone tissue engineering. Biomaterials, 27(18), 3413-3431. doi:10.1016/j.biomaterials.2006.01.039Santamaría, V. A., Deplaine, H., Mariggió, D., Villanueva-Molines, A. R., García-Aznar, J. M., Ribelles, J. L. G., … Ochoa, I. (2012). Influence of the macro and micro-porous structure on the mechanical behavior of poly(l-lactic acid) scaffolds. Journal of Non-Crystalline Solids, 358(23), 3141-3149. doi:10.1016/j.jnoncrysol.2012.08.001Izal, I., Aranda, P., Sanz-Ramos, P., Ripalda, P., Mora, G., Granero-Moltó, F., … Prósper, F. (2012). Culture of human bone marrow-derived mesenchymal stem cells on of poly(l-lactic acid) scaffolds: potential application for the tissue engineering of cartilage. Knee Surgery, Sports Traumatology, Arthroscopy, 21(8), 1737-1750. doi:10.1007/s00167-012-2148-6Deplaine, H., Lebourg, M., Ripalda, P., Vidaurre, A., Sanz-Ramos, P., Mora, G., … Gallego Ferrer, G. (2012). Biomimetic hydroxyapatite coating on pore walls improves osteointegration of poly(L-lactic acid) scaffolds. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 101B(1), 173-186. doi:10.1002/jbm.b.32831Ho, M.-H., Kuo, P.-Y., Hsieh, H.-J., Hsien, T.-Y., Hou, L.-T., Lai, J.-Y., & Wang, D.-M. (2004). Preparation of porous scaffolds by using freeze-extraction and freeze-gelation methods. Biomaterials, 25(1), 129-138. doi:10.1016/s0142-9612(03)00483-6Alberich-Bayarri, A., Moratal, D., Ivirico, J. L. E., Hernández, J. C. R., Vallés-Lluch, A., Martí-Bonmatí, L., … Salmerón-Sánchez, M. (2009). Microcomputed tomography and microfinite element modeling for evaluating polymer scaffolds architecture and their mechanical properties. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 91B(1), 191-202. doi:10.1002/jbm.b.31389Mollica, F., Ventre, M., Sarracino, F., Ambrosio, L., & Nicolais, L. (2007). Implicit constitutive equations in the modeling of bimodular materials: An application to biomaterials. Computers & Mathematics with Applications, 53(2), 209-218. doi:10.1016/j.camwa.2006.02.020TURNER, C. H. (2006). Bone Strength: Current Concepts. Annals of the New York Academy of Sciences, 1068(1), 429-446. doi:10.1196/annals.1346.039HARLEY, B., LEUNG, J., SILVA, E., & GIBSON, L. (2007). Mechanical characterization of collagen–glycosaminoglycan scaffolds. Acta Biomaterialia, 3(4), 463-474. doi:10.1016/j.actbio.2006.12.009DiSilvestro, M. R., & Suh, J.-K. F. (2001). A cross-validation of the biphasic poroviscoelastic model of articular cartilage in unconfined compression, indentation, and confined compression. Journal of Biomechanics, 34(4), 519-525. doi:10.1016/s0021-9290(00)00224-4Jurvelin, J. S., Buschmann, M. D., & Hunziker, E. B. (1997). Optical and mechanical determination of poisson’s ratio of adult bovine humeral articular cartilage. Journal of Biomechanics, 30(3), 235-241. doi:10.1016/s0021-9290(96)00133-9Korhonen, R. ., Laasanen, M. ., Töyräs, J., Rieppo, J., Hirvonen, J., Helminen, H. ., & Jurvelin, J. . (2002). Comparison of the equilibrium response of articular cartilage in unconfined compression, confined compression and indentation. Journal of Biomechanics, 35(7), 903-909. doi:10.1016/s0021-9290(02)00052-0Acosta Santamaría, V. A., García Aznar, J. M., Ochoa, I., & Doblare, M. (2012). Effect of Sample Pre-Contact on the Experimental Evaluation of Cartilage Mechanical Properties. Experimental Mechanics, 53(6), 911-917. doi:10.1007/s11340-012-9698-xOchoa, I., Sanz-Herrera, J. A., García-Aznar, J. M., Doblaré, M., Yunos, D. M., & Boccaccini, A. R. (2009). Permeability evaluation of 45S5 Bioglass®-based scaffolds for bone tissue engineering. Journal of Biomechanics, 42(3), 257-260. doi:10.1016/j.jbiomech.2008.10.030Chor, M. V., & Li, W. (2006). A permeability measurement system for tissue engineering scaffolds. Measurement Science and Technology, 18(1), 208-216. doi:10.1088/0957-0233/18/1/026Al-Munajjed, A. A., Hien, M., Kujat, R., Gleeson, J. P., & Hammer, J. (2008). Influence of pore size on tensile strength, permeability and porosity of hyaluronan-collagen scaffolds. Journal of Materials Science: Materials in Medicine, 19(8), 2859-2864. doi:10.1007/s10856-008-3422-5Sanz-Herrera, J. A., Kasper, C., van Griensven, M., Garcia-Aznar, J. M., Ochoa, I., & Doblare, M. (2008). Mechanical and flow characterization of Sponceram® carriers: Evaluation by homogenization theory and experimental validation. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 87B(1), 42-48. doi:10.1002/jbm.b.31065Truscello, S., Kerckhofs, G., Van Bael, S., Pyka, G., Schrooten, J., & Van Oosterwyck, H. (2012). Prediction of permeability of regular scaffolds for skeletal tissue engineering: A combined computational and experimental study. Acta Biomaterialia, 8(4), 1648-1658. doi:10.1016/j.actbio.2011.12.021Castilla-Cortázar, I., Más-Estellés, J., Meseguer-Dueñas, J. M., Escobar Ivirico, J. L., Marí, B., & Vidaurre, A. (2012). Hydrolytic and enzymatic degradation of a poly(ε-caprolactone) network. Polymer Degradation and Stability, 97(8), 1241-1248. doi:10.1016/j.polymdegradstab.2012.05.038Tsuji, H., & Ikada, Y. (1996). Blends of isotactic and atactic poly(lactide)s: 2. Molecular-weight effects of atactic component on crystallization and morphology of equimolar blends from the melt. Polymer, 37(4), 595-602. doi:10.1016/0032-3861(96)83146-6Lebourg, M., Antón, J. S., & Ribelles, J. L. G. (2008). Porous membranes of PLLA–PCL blend for tissue engineering applications. European Polymer Journal, 44(7), 2207-2218. doi:10.1016/j.eurpolymj.2008.04.033Hernández Sánchez, F., Molina Mateo, J., Romero Colomer, F. J., Salmerón Sánchez, M., Gómez Ribelles, J. L., & Mano, J. F. (2005). Influence of Low-Temperature Nucleation on the Crystallization Process of Poly(l-lactide). Biomacromolecules, 6(6), 3283-3290. doi:10.1021/bm050323tHöglund, A., Odelius, K., Hakkarainen, M., & Albertsson, A.-C. (2007). Controllable Degradation Product Migration from Cross-Linked Biomedical Polyester-Ethers through Predetermined Alterations in Copolymer Composition. Biomacromolecules, 8(6), 2025-2032. doi:10.1021/bm070292xPersenaire, O., Alexandre, M., Degée, P., & Dubois, P. (2001). Mechanisms and Kinetics of Thermal Degradation of Poly(ε-caprolactone). Biomacromolecules, 2(1), 288-294. doi:10.1021/bm005631

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Actitudes y estereotipos en estudiantes del área de la salud hacia personas con discapacidad motriz

El objetivo central de esta investigación fue analizar las actitudes y los estereotipos hacia personas con discapacidad motriz en una muestra de estudiantes del área de la salud. Para ello se aplicaron la Escala Multidimensional de Actitudes Hacia Personas con Discapacidad y un instrumento para medir estereotipos (calidez y competencia) hacia personas con discapacidad. Se trabajó con 232 estudiantes (edad promedio: 23 años, DT=5), a quienes se les aplicaron los instrumentos en línea. Los resultados del análisis factorial muestran una estructura teóricamente congruente y propiedades psicométricas adecuadas para ambos instrumentos. Los participantes reportaron actitudes positivas hacia las personas con discapacidad y percepciones similares de competencia hacia individuos con y sin discapacidad. Sin embargo, reportaron niveles significativamente más altos de calidez para las personas con discapacidad. Estos resultados sugieren una baja disposición a reportar estereotipos de incompetencia o desagrado hacia personas con discapacidad, pero una percepción compensatoria de mayor calidez

Detection of rabies virus in organs unrelated to the central nervous system of experimentally-inoculated vampire bats

The aim of this research was to detect rabies virus in peripheral tissues in captive vampires. Vampire bats were inoculated with 106 MICLD50 of homologous rabies virus. Bats displayed clinical signs of rabies beginning on d 8 until the 19th d post-inoculation (pi). Rabies virus antigens were found in the brain of all rabid bats. Viral RNA was detected in brain, salivary gland and tongue tissue by RT-PCR and nested PCR (nPCR). Viral genome was also detected in organs unrelated to the central nervous system. Rabies virus was not detected in saliva nor documented from any tissues without occurrence of viral antigens in the brain. Host humoral response was most pronounced via the induction of viral neutralizing antibodies (VNA) from d 8 to 20 pi, having a peak at d 14 with 0.9 IU. Antibody levels were variable, but tended to remain high after inoculation, showing significant differences to the negative control group (P=0.001). This research is one of the few recent studies focused upon Desmodus rotundus and contributes to the basic knowledge of rabies virus pathogenesis, which is required for an understanding of perpetuation in a major viral reservoir in Latin America