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The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose-derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single-blind clinical trial, recruiting 57 patients. Forty-four patients were categorized as belonging to the intent-to-treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re-epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long-term and sustained fistula healing. © 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press

CH is partially supported by the Spanish grant MINECO-16-FPA2015-63667-P, the Ramon y Cajal fellowship RYC-2012- 10370 and GRUPIN 18-174 research grant from Principado de Asturias. JCS is supported by grants SGR-2017-754, FPA2016-76005-C2-1-P and MDM-2014-0367.

We study the structure of thermal spectral function of the stress-energy tensor in N=4 supersymmetric Yang-Mills theory at intermediate ‘t Hooft coupling and infinite number of colors. In gauge-string duality, this analysis reduces to the study of classical bulk supergravity with higher-derivative corrections, which correspond to (inverse) coupling corrections on the gauge theory side. We extrapolate the analysis of perturbative leading-order corrections to intermediate coupling by nonperturbatively solving the equations of motion of metric fluctuations dual to the stress-energy tensor at zero spatial momentum. We observe the emergence of a separation of scales in the analytic structure of the thermal correlator associated with two types of characteristic relaxation modes. As a consequence of this separation, the associated spectral function exhibits a narrow structure in the small frequency region which controls the dynamics of transport in the theory and may be described as a transport peak typically found in perturbative, weakly interacting thermal field theories. We compare our results with generic expectations drawn from perturbation theory, where such a structure emerges as a consequence of the existence of quasiparticles.

Since the 1980s, regulators in the U.S. and the U.K. have protected the collateral taker’s right to re-use securities collateral in securities financing and OTC derivatives markets on the understanding that it would promote liquidity and credit growth, and reduce systemic risk. However, this rationale was incomplete: it failed to acknowledge the full implications of collateral re-use for systemic risk. In this dissertation, I aim to complete that understanding by illustrating how the re-use of securities collateral in those markets can aggravate systemic risk. In particular, I describe two effects. First, re-using securities collateral multiplies the number of market participants that will be exposed to changes in the price of the collateral asset and can thus amplify the role of asset prices as channels of contagion. Second, by conferring a right to re-use, the collateral provider will effectively waive its proprietary interests in the collateral assets and retain a mere contractual claim against the collateral taker for the return of equivalent securities. This transformation will accentuate the incentive of the collateral provider to run from an over-collateralised collateral taker if the latter were to experience financial difficulty. Information asymmetries and a lack of coordination among collateral providers could push the collateral taker over the brink of insolvency. These risks pose an obvious question for regulators: what should we do about collateral re-use? At a time when international bodies are drawing their attention to this widespread market practice, the question is an invitation to a very timely reflection. The final chapter of the dissertation offers an answer to this question and assesses the potential efficacy of the most recent regulatory initiatives in relation to collateral re-use.

In contrast to transcriptional regulation, the function of alternative splicing (AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however, little is known about the in vivo significance of this regulation. We studied AS in a powerful in vivo model for stem cell biology, the planarian Schmidtea mediterranea. We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. We show that functional antagonism between CELF and MBNL factors directly controls stem cell-specific AS in planarians, placing the origin of this regulatory mechanism at the base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal regenerative capacities by affecting self-renewal and differentiation sets of genes, respectively. These results highlight the importance of AS in animal stem cell regulation across metazoans.

The Pacific or the Middle East? For the United States, that is now the primary strategic question. The violence in Gaza, coming as President Barack Obama was meeting Asia’s leaders in Phnom Penh, perfectly encapsulates America’s dilemma. Instead of being able to focus on US foreign policy’s ‘pivot’ to Asia, Obama was forced to spend many hours in conversation with the leaders of Egypt and Israel, and to dispatch Secretary of State Hillary Clinton from Asia, in order to facilitate a cease-fire in Gaza.

As a model of the longitudinal structure in heavy ion collisions, we simulate gravitational shock wave collisions in anti-de Sitter space in which each shock is composed of multiple constituents. We nd that all constituents act coherently, and their separation leaves no imprint on the resulting plasma, when this separation is . 0:26=Thyd, with Thyd the temperature of the plasma at the time when hydrodynamics rst becomes applicable. In particular, the center-of-mass of the plasma coincides with the center-of-mass of all the constituents participating in the collision, as opposed to the center-of-mass of the individual collisions. We discuss the implications for nucleus-nucleus and proton-nucleus collisions.

Cognitive impairment is the main cause of disability in developed societies. New interactive technologies help therapists in neurorehabilitation in order to increase patients' autonomy and quality of life. This work proposes Interactive Video (IV) as a technology to develop cognitive rehabilitation tasks based on Activities of Daily Living (ADL). ADL cognitive task has been developed and integrated with eye-tracking technology for task interaction and patients' performance monitoring.

An integral understanding of forest biodiversity requires the exploration of the many aspects it comprises and of the numerous potential determinants of their distribution. The landscape ecological approach provides a necessary complement to conventional local studies that focus on individual plots or forest ownerships. However, most previous landscape studies used equally-sized cells as units of analysis to identify the factors affecting forest biodiversity distribution. Stratification of the analysis by habitats with a relatively homogeneous forest composition might be more adequate to capture the underlying patterns associated to the formation and development of a particular ensemble of interacting forest species. Here we used a landscape perspective in order to improve our understanding on the influence of large-scale explanatory factors on forest biodiversity indicators in Spanish habitats, covering a wide latitudinal and altitudinal range. We considered six forest biodiversity indicators estimated from more than 30,000 field plots in the Spanish national forest inventory, distributed in 213 forest habitats over 16 Spanish provinces. We explored biodiversity response to various environmental (climate and topography) and landscape configuration (fragmentation and shape complexity) variables through multiple linear regression models (built and assessed through the Akaike Information Criterion). In particular, we took into account the inherent model uncertainty when dealing with a complex and large set of variables, and considered different plausible models and their probability of being the best candidate for the observed data. Our results showed that compositional indicators (species richness and diversity) were mostly explained by environmental factors. Models for structural indicators (standing deadwood and stand complexity) had the worst fits and selection uncertainties, but did show significant associations with some configuration metrics. In general, biodiversity increased in habitats covering wider topographic ranges and comprising forest patches with more complex shapes. Patterns in other relationships varied between indicators (e.g. species richness vs. diversity), or even were opposed (trees vs. shrubs). Our study (1) allowed deepening the understanding of biodiversity patterns in a large set of Spanish forest habitats and (2) highlighted the increasing complexity of identifying common landscape conditions favouring forest biodiversity as the range of analysed biodiversity aspects is widened beyond the more commonly assessed species richness indicators., El estudio integral de la biodiversidad requiere la exploración de sus numerosos componentes y de los diversos factores potencialmente determinantes de su distribución. El enfoque de la ecología y escala de paisaje representa un complemento necesario a los estudios locales centrados en parcelas de inventario o montes individuales. No obstante, la mayoría de los estudios a escala de paisaje han utilizado cuadrículas como unidad de análisis para la identificación de los factores responsables de la distribución de la biodiversidad. La estratificación del territorio por hábitats forestales con una composición relativamente más homogénea podría ser más adecuada de cara a la identificación de los patrones subyacentes asociados a la formación y desarrollo de un determinado conjunto de especies forestales relacionadas funcionalmente. En este estudio adoptamos una perspectiva de paisaje para profundizar en el conocimiento de la influencia de factores a grandes escalas espaciales sobre la biodiversidad forestal de los hábitats forestales españoles, cubriendo un amplio rango latitudinal y altitudinal. Consideramos seis indicadores de biodiversidad forestal estimados a partir de más de 30.000 parcelas del inventario forestal nacional de España, distribuidas en 213 hábitats forestales y 16 provincias diferentes. Exploramos la respuesta de la biodiversidad frente a diversas variables ambientales (clima y topografía) y de configuración del paisaje (fragmentación y complejidad de formas), a través de modelos de regresión lineal múltiple (creados y evaluados con el Criterio de Información de Akaike). En concreto, tenemos en cuenta la incertidumbre inherente a la selección del mejor modelo al analizar conjuntos de datos complejos, y consideramos diferentes modelos posibles y su probabilidad de ser considerados como el mejor candidato para explicar la variabilidad observada. Nuestros resultados mostraron que los indicadores de composición (riqueza y diversidad de especies) fueron principalmente explicados por los factores ambientales. Los modelos para los indicadores estructurales (madera muerta en pie y complejidad del rodal) tuvieron los peores ajustes e incertidumbres de selección, pero mostraron una asociación significativa con algunos de los índices de configuración. En general, la biodiversidad aumentó en los hábitats que abarcan un mayor rango altitudinal y con teselas de formas más complejas. El resto de patrones en las relaciones variaron entre indicadores (e.g. riqueza vs. diversidad de especies), o incluso presentaron tendencias opuestas (árboles vs. arbustos). Nuestro estudio permite profundizar en la comprensión de los patrones de biodiversidad a través de un amplio conjunto de hábitats forestales españoles y pone de manifiesto la creciente complejidad y dificultad de identificar un conjunto común de condiciones del paisaje que favorezcan la biodiversidad forestal a medida que se amplía el número de aspectos analizados más allá de los más habitualmente considerados indicadores de riqueza de especies.

This writeup is a compilation of the predictions for the forthcoming Heavy Ion Program at the Large Hadron Collider, as presented at the CERN Theory Institute 'Heavy Ion Collisions at the LHC - Last Call for Predictions', held from May 14th to June 10th 2007.

Large areas initially consisted of contiguous forests, particularly in Europe, have been influenced by human activities to a large extent. This influence contributed to the fragmentation of the rural landscape and forested areas were found surrounded by or intermixed with urban development. Urban and economic development in or near wildland vegetation poses a major threat to the environment (Johnson 2001, Radeloff et al. 2005). They are areas of humanenvironment conflicts, such as the destruction of homes by wildfires, natural habitat fragmentation, introduction of exotic species, and biodiversity decline (Radeloff et al. 2005). These areas that characterized of increased human activities and land use conversion make up the Wildland/Urban Interfaces. The significance of Wildland/Urban Interfaces (WUIs) has grown in recent years mainly because WUI, as a landscape unit, has grown worldwide (Steward et al. 2003). Essentially in USA, Canada and Australia interest for WUI study appeared after the huge fires of 1985 in the WUI (Davis, 1990) and in Europe this interest appeared ten years ago with increasing of damages on goods and people due to WUI fire. Large efforts aiming at the identification and mapping of existing or potential wildland urban interface areas have already been recorded in North America but they have to be developed in Europe. In the European project Fireparadox, several research and engineering teams are working together with a view to develop a methodology to characterize and to map WUI through spatial analysis of the territory according to regional and local approach. The objective at term is to be able to assess and to map vulnerability level or index according to each WUI types and also damages in case of fire. Theses results will allow to develop appropriated prevention actions, to help firefighters adapting their fighting strategy (concentration or dispersal of crews and facilities according to the stakes, positioning on the most vulnerable zones of interface ). The presentation presents an application of the method of WUI characterization and mapping on a case study area in Sardinia.

In high energy nuclear collisions, QCD jets deposit a large fraction of their energy into the produced matter. It has been proposed that as such matter behaves as a liquid with a very small viscosity, a fraction of this energy goes into a collective excitation called the ``conical flow'', similar e.g. to the sonic booms generated by the supersonic planes. In this work we study the effect of time-dependent speed of sound on the development of the conical wave. We show that the expansion of matter and the decrease of $c_s$ leads to an increase of observable manifestations of the conical flow. We also show that if the QCD phase transition is of the first order (and thus with vanishing speed of sound in the mixed phase) the wave must split into two, with opposite directions. We then argue that it is not the case experimentally, which supports the conclusion that the QCD phase transition is $not$ of the first order.

We propose a model aimed at explaining jet quenching, large azimuthal asymmetry and baryon/meson ratio at large transverse momenta pt=2-10 GeV observed at RHIC. Its main point is that a QCD string can be cut by matter quarks and/or diquarks before its natural breaking. We model the early quark/diquark production via QCD sphalerons., Comment: 4 pages, 4 figures

The transseries is an ansatz for generating solutions to classical problems which are both perturbative and non-perturbative in some limit of parameter space. In this thesis we apply this technique to three systems described by classical gravity with relevance to holographic plasmas of strongly coupled gauge theories. To begin we compute the gradient expansion to arbitrarily high orders for an N=4 Super Yang-Mills (SYM) plasma at infinite 't Hooft coupling undergoing Bjorken evolution, later finding the full transseries by including non-perturbative (in gradient) terms. Mathematical relations exist between these transseries sectors, which we verify by calculating the leading terms of the first non-hydrodynamic series solution entirely through the coefficients of the gradient expansion. Relaxing the limit of infinite 't Hooft coupling we compute the leading transseries solution for a family of finitely coupled gauge theories, and estimate the typical path of Bjorken evolution a far-from-equilibrium system might take while evolving to the hydrodynamic regime. Next we consider a holographic Bjorken expanding system in arbitrary spacetime dimensions D, now instead using the number of dimensions as our large parameter. Due to a greater degree of analytic control we can compute combinations of transport coefficients relevant for Bjorken flow up to 6-th order in gradients to 3rd order in 1/D, finding that our perturbative solution recovers the same dynamics controlled by the hydrodynamic gradient expansion. Computing the non-perturbative (in 1/D) contributions of this set up we demonstrate an identification between these terms and the non-hydrodynamic solutions of the small gradient transseries. Lastly we apply the transseries to study the near equilibrium dynamics of blackbranes. Due to the simplicity of this system we can analytically find the time-evolving divergence of the entropy current to second order in the transseries, determined entirely the blackbrane's quasinormal modes frequencies and equilibrium temperature. This pedogogical example demonstrates the power of the expansion which can be easily applied to wider contexts.

Statistical thermodynamics of protein solutions is often studied in terms of simple, microscopic models of particles interacting via pairwise potentials. Such modelling can reproduce the short range structure of protein solutions at equilibrium and predict thermodynamics instabilities of these systems. We introduce a square well model of effective protein-protein interaction that embeds the solvent's action. We modify an existing model [45] by considering a well depth having an explicit dependence on temperature, i.e. an explicit free energy character, thus encompassing the statistically relevant configurations of solvent molecules around proteins. We choose protein solutions exhibiting demixing upon temperature decrease (lysozyme, enthalpy driven) and upon temperature increase (haemoglobin, entropy driven). We obtain satisfactory fits of spinodal curves for both the two proteins without adding any mean field term, thus extending the validity of the original model. Our results underline the solvent role in modulating or stretching the interaction potential. © 2013 Elsevier B.V. All rights reserved.