Influence of previous surgery on patient-rated outcome after surgery for degenerative disorders of the lumbar spine.

PURPOSE Few studies have used multivariate models to quantify the effect of multiple previous spine surgeries on patient-oriented outcome after spine surgery. This study sought to quantify the effect of prior spine surgery on 12-month postoperative outcomes in patients undergoing surgery for different degenerative disorders of the lumbar spine. METHODS The study included 4940 patients with lumbar degenerative disease documented in the Spine Tango Registry of EUROSPINE, the Spine Society of Europe, from 2004 to 2015. Preoperatively and 12 months postoperatively, patients completed the multidimensional Core Outcome Measures Index (COMI; 0-10 scale). Patients' medical history and surgical details were recorded using the Spine Tango Surgery 2006 and 2011 forms. Multiple linear regression models were used to investigate the relationship between the number of previous surgeries and the 12-month postoperative COMI score, controlling for the baseline COMI score and other potential confounders. RESULTS In the adjusted model including all cases, the 12-month COMI score showed a 0.37-point worse value [95 % confidence intervals (95 % CI) 0.29-0.45; p < 0.001] for each additional prior spine surgery. In the subgroup of patients with lumbar disc herniation, the corresponding effect was 0.52 points (95 % CI 0.27-0.77; p < 0.001) and in lumbar degenerative spondylolisthesis, 0.40 points (95 % CI 0.17-0.64; p = 0.001). CONCLUSIONS We were able to demonstrate a clear "dose-response" effect for previous surgery: the greater the number of prior spine surgeries, the systematically worse the outcome at 12 months' follow-up. The results of this study can be used when considering or consenting a patient for further surgery, to better inform the patient of the likely outcome and to set realistic expectations.

Total disc arthroplasty versus anterior cervical interbody fusion: use of the Spine Tango registry to supplement the evidence from randomized control trials.

BACKGROUND CONTEXT Several randomized controlled trials (RCTs) have compared patient outcomes of anterior (cervical) interbody fusion (AIF) with those of total disc arthroplasty (TDA). Because RCTs have known limitations with regard to their external validity, the comparative effectiveness of the two therapies in daily practice remains unknown. PURPOSE This study aimed to compare patient-reported outcomes after TDA versus AIF based on data from an international spine registry. STUDY DESIGN AND SETTING A retrospective analysis of registry data was carried out. PATIENT SAMPLE Inclusion criteria were degenerative disc or disc herniation of the cervical spine treated by single-level TDA or AIF, no previous surgery, and a Core Outcome Measures Index (COMI) completed at baseline and at least 3 months' follow-up. Overall, 987 patients were identified. OUTCOME MEASURES Neck and arm pain relief and COMI score improvement were the outcome measures. METHODS Three separate analyses were performed to compare TDA and AIF surgical outcomes: (1) mimicking an RCT setting, with admission criteria typical of those in published RCTs, a 1:1 matched analysis was carried out in 739 patients; (2) an analysis was performed on 248 patients outside the classic RCT spectrum, that is, with one or more typical RCT exclusion criteria; (3) a subgroup analysis of all patients with additional follow-up longer than 2 years (n=149). RESULTS Matching resulted in 190 pairs with an average follow-up of 17 months that had no residual significant differences for any patient characteristics. Small but statistically significant differences in outcome were observed in favor of TDA, which are potentially clinically relevant. Subgroup analyses of atypical patients and of patients with longer-term follow-up showed no significant differences in outcome between the treatments. CONCLUSIONS The results of this observational study were in accordance with those of the published RCTs, suggesting substantial pain reduction both after AIF and TDA, with slightly greater benefit after arthroplasty. The analysis of atypical patients suggested that, in patients outside the spectrum of clinical trials, both surgical interventions appeared to work to a similar extent to that shown for the cohort in the matched study. Also, in the longer-term perspective, both therapies resulted in similar benefits to the patients.

Knockdown of Kiaa0319 Reduces Dendritic Spine Density

Developmental Dyslexia is a reading disorder that affects individuals that possess otherwise normal intelligence. Until the four candidate dyslexia susceptibility genes were discovered, the cause of cortical malformations found in post mortem dyslexic brains was unclear. Normal brain development is crucial for the proper wiring of the neural circuitry that allow an individual to perform cognitive tasks like reading. For years, familial and twin studies have suggested that there was a genetic basis to the causation of dyslexia. Kiaa0319 was among the candidate dyslexia susceptibility genes that were ascertained. KIAA0319 is located on Chromosome 6p22.2-22.3 and has been found to exhibit differential spatial-temporal expression patterns in the brain throughout development, which suggests that the polycystic kidney disease (PKD) domain encoded by KIAA0319 facilitates cell-cell adhesion to enable neuronal precursors to crawl up the radial glia during neuronal migration. With the knowledge of KIAA0319 involvement in early neurogenesis, we were interested in determining how different KIAA0319 expression may impact cortical neurons in layer II and III during early adulthood. We show that KIAA0319 knockdown in cortical pyramidal neurons significantly reduces the dendritic spine density. Studies have shown that changes in dendritic spine morphology and density affect properties of neural circuitry. Henceforth, this finding may reveal a link between the Kiaa0319 gene and the deficit of the neural processing task of reading due to reduced spines density. Finding a correlation between Kiaa0319 expression and its influence on dendritic spine development may lead to a greater insight of a direct link between the dyslexia susceptibility gene and the biological mechanism that causes dyslexia.

Flexibility and Academic Credits within Higher Education trends

La globalización en la Educación Superior y el nuevo marco de mercado dentro del sistema universitario ha introducido el concepto de flexibilidad. Uno de Ios instrumentos principales en el desarrollo de este proceso ha sido el Sistema de Crédito Académico (el Marco de Crédito), que es un modo de reestructurar el currículum hacia la Flexibilidad de Suministros. Muchos países en el mundo entero han introducido este modelo, después del Sistema de Crédito americano. Este trabajo explorará conceptualmente los eslabones entre las tendencias principales en la enseñanza superior y este nuevo concepto.

Flexibility in Airline Business Models with Core Competence as an Indicator.

The airline industry is often unstable and unpredictable forcing airlines to restructure and create flexible strategies that can respond to external operating environmental changes. In turbulent and competitive environments, firms with higher flexibility perform better and the value of these flexibilities depends on factors of uncertainty in the competitive environment. A model is sought for and arrived at, that shows how an airline business model will function in an uncertain environment with the least reduction in business performance over time. An analysis of the business model flexibility of 17 Airlines from Asia, Europe and Oceania, that is done with core competence as the indicator reveals a picture of inconsistencies in the core competence strategy of certain airlines and the corresponding reduction in business performance. The performance variations are explained from a service oriented core competence strategy employed by airlines that ultimately enables them in having a flexible business model that not only increases business performance but also helps in reducing the uncertainties in the internal and external operating environments.

The flexibility matrix o timber composite beams with a discrete connection system

This work presents a method for the analysis of timber composite beams which considers the slip in the connection system, based on assembling the flexibility matrix of the whole structure. This method is based on one proposed by Tommola and Jutila (2001). This paper extends the method to the case of a gap between two pieces with an arbitrary location at the first connector, which notably broadens its practical application. The addition of the gap makes it possible to model a cracked zone in concrete topping, as well as the case in which forming produces the gap. The consideration of induced stresses due to changes in temperature and moisture content is also described, while the concept of equivalent eccentricity is generalized. This method has important advantages in connection with the current European Standard EN 1995-1-1: 2004, as it is able to deal with any type of load, variable section, discrete and non-regular connection systems, a gap between the two pieces, and variations in temperature and moisture content. Although it could be applied to any structural system, it is specially suited for the case of simple supported and continuous beams. Working examples are presented at the end, showing that the arrangement of the connection notably modifies shear force distribution. A first interpretation of the results is made on the basis of the strut and tie theory. The examples prove that the use of EC-5 is unsafe when, as a rule of thumb, the strut or compression field between the support and the first connector is at an angle with the axis of the beam of less than 60º.

Using the Own Flexibility of a Climbing Robot as a Double Force Sensor

Force sensors are used when interaction tasks are carried out by robots in general, and by climbing robots in particular. If the mechanics and electronics systems are contained inside the own robot, the robot becomes portable without external control. Commercial force sensors cannot be used due to limited space and weight. By selecting the links material with appropriate stiffness and placing strain gauges on the structure, the own robot flexibility can be used such as force sensor. Thus, forces applied on the robot tip can be measured without additional external devices. Only gauges and small internal electronic converters are necessary. This paper illustrates the proposed algorithm to achieve these measurements. Additionally, experimental results are presented.

Flexibility, innovation and sustainability in business models as determinants of firm performance heterogeneity.

La comprensión actual de la heterogeneidad de las empresas académico rendimiento en el entorno entra industria necesita un mayor desarrollo. Gestión estratégica y el discurso sobre la literatura empresarial necesita mayor explicación de por qué los modelos de negocio aparentemente similares en el mismo sector actúan de forma diferente. También qué factores del entorno sectorial y operativo determina el surgimiento y funcionamiento de los modelos de negocio sostenibles e innovadoras permanecen sin explorar. Un marco se conceptualiza acompañado de estudios de caso sobre la compañía aérea y las industrias de energía renovable. El estudio lleva a una visión basada en los recursos de los modelos de negocio que las empresas alcancen posiciones heterogéneas de recursos. Una explicación para la heterogeneidad firme desempeño que se busca por intermediación conocimiento que genera valor a partir de la utilización eficaz de los recursos de conocimientos adquiridos a entornos entra y inter-empresa. Un marco para la aparición de nuevos modelos de negocios verdes se conceptualiza y deducciones se obtienen mediante un estudio de caso sobre la base de la industria de biocombustibles de energías renovables para explicar la dinámica de los mercados verdes y cómo se puede crear valor sostenible y capturó e innovadora de los modelos de negocios verdes. El marco desarrollado proporciona una visión cíclica de la flexibilidad del modelo de negocio en la que se propaga la acumulación de recursos basada en el conocimiento del modelo de negocio a través de los ambientes dentro y inter-empresa. Estrategias de conocimiento de corretaje del resultado ambientes inter e dentro-firma en un mejor desempeño del modelo de negocio. La flexibilidad del modelo de negocio que adquiere está determinada por la eficiencia con la acumulación de recursos está alineado con su ambiente externo. Las características de la que el modelo de negocio alcanza ventajas competitivas, como la innovación y la flexibilidad se atribuyen a la heterogeneidad de los recursos. La investigación se extiende a la literatura orientación de servicio al conceptualizar y medir la orientación a servicios como un requisito clave para la innovación del modelo de negocio, mientras que aboga por la necesidad de identificar correctamente las competencias básicas de la empresa, especialmente relevante en el contexto de la empresa orientada a los servicios, donde la creación de valor requiere recursos y la prestación eficiente de los servicios. La investigación trata de llegar a una descripción de los modelos de negocio sostenibles verdes y argumenta que la innovación, la flexibilidad y la sostenibilidad son los tres habilitadores básicos de los cuales el concepto de modelo de negocio verde puede evolucionar la explotación de nuevos mecanismos de mercado y los mercados para crear y capturar valor en el mantenimiento de su innovadora ambiente externo. La investigación integra efectivamente los conceptos de corretaje de conocimientos y modelos de negocio a partir de un recurso basado en la acumulación de vista y al mismo tiempo llega a la heterogeneidad rendimiento de los modelos de negocio aparentemente similares dentro de la misma industria. La investigación indica cómo se producen perturbaciones del mercado en una industria como resultado de modelos de negocio innovador y flexible, y cómo los nuevos modelos de negocio evolucionan en base a estos trastornos. Avanza la comprensión de cómo la estrategia de núcleo competencia y la innovación del modelo de negocio construcciones se comportan en el esfuerzo de la empresa de servicios para obtener una ventaja competitiva sostenible. Los resultados tienen implicaciones en el rendimiento de las empresas que empiezan sin recursos distintos de los suyos, o que utilizan un modelo de negocio imitado, para lograr un mejor rendimiento a través de la evolución del modelo de negocio alineado con las exitosas estrategias de conocimiento de corretaje. Dicho marco puede permitir a las empresas a evaluar y elegir un modelo de negocio basado en la innovación, la flexibilidad, la sostenibilidad y las opciones para el cambio. La investigación se suma a la literatura acumulación de recursos, explicando cómo los recursos pueden ser efectivamente adquirida para crear valor. La investigación también se suma a la literatura empresarial verde, explicando cómo las empresas crear y capturar valor en los nuevos mecanismos dinámicos de mercado.

The effects of cocaine self-administration on dendritic spine density in the rat hippocampus are dependent on genetic background

Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds.

Volume Haptics and Dendritic Spine Editing

Esta tesis se ha desarrollado en el contexto del proyecto Cajal Blue Brain, una iniciativa europea dedicada al estudio del cerebro. Uno de los objetivos de esta iniciativa es desarrollar nuevos métodos y nuevas tecnologías que simplifiquen el análisis de datos en el campo neurocientífico. El presente trabajo se ha centrado en diseñar herramientas que combinen información proveniente de distintos canales sensoriales con el fin de acelerar la interacción y análisis de imágenes neurocientíficas. En concreto se estudiará la posibilidad de combinar información visual con información háptica. Las espinas dendríticas son pequeñas protuberancias que recubren la superficie dendrítica de muchas neuronas del cerebro. A día de hoy, se cree que tienen un papel clave en la transmisión de señales neuronales. Motivo por el cual, el interés por parte de la comunidad científica por estas estructuras ha ido en aumento a medida que las técnicas de adquisición de imágenes mejoraban hasta alcanzar una calidad suficiente para analizar dichas estructuras. A menudo, los neurocientíficos utilizan técnicas de microscopía con luz para obtener los datos que les permitan analizar estructuras neuronales tales como neuronas, dendritas y espinas dendríticas. A pesar de que estas técnicas ofrezcan ciertas ventajas frente a su equivalente electrónico, las técnicas basadas en luz permiten una menor resolución. En particular, estructuras pequeñas como las espinas dendríticas pueden capturarse de forma incorrecta en las imágenes obtenidas, impidiendo su análisis. En este trabajo, se presenta una nueva técnica, que permite editar imágenes volumétricas, mediante un dispositivo háptico, con el fin de reconstruir de los cuellos de las espinas dendríticas. Con este objetivo, en un primer momento se desarrolló un algoritmo que proporciona retroalimentación háptica en datos volumétricos, completando la información que provine del canal visual. Dicho algoritmo de renderizado háptico permite a los usuarios tocar y percibir una isosuperficie en el volumen de datos. El algoritmo asegura un renderizado robusto y eficiente. Se utiliza un método basado en las técnicas de “marching tetrahedra” para la extracción local de una isosuperficie continua, lineal y definida por intervalos. La robustez deriva tanto de una etapa de detección de colisiones continua de la isosuperficie extraída, como del uso de técnicas eficientes de renderizado basadas en un proxy puntual. El método de “marching tetrahedra” propuesto garantiza que la topología de la isosuperficie extraída coincida con la topología de una isosuperficie equivalente determinada utilizando una interpolación trilineal. Además, con el objetivo de mejorar la coherencia entre la información háptica y la información visual, el algoritmo de renderizado háptico calcula un segundo proxy en la isosuperficie pintada en la pantalla. En este trabajo se demuestra experimentalmente las mejoras en, primero, la etapa de extracción de isosuperficie, segundo, la robustez a la hora de mantener el proxy en la isosuperficie deseada y finalmente la eficiencia del algoritmo. En segundo lugar, a partir del algoritmo de renderizado háptico propuesto, se desarrolló un procedimiento, en cuatro etapas, para la reconstrucción de espinas dendríticas. Este procedimiento, se puede integrar en los cauces de segmentación automática y semiautomática existentes como una etapa de pre-proceso previa. El procedimiento está diseñando para que tanto la navegación como el proceso de edición en sí mismo estén controlados utilizando un dispositivo háptico. Se han diseñado dos experimentos para evaluar esta técnica. El primero evalúa la aportación de la retroalimentación háptica y el segundo se centra en evaluar la idoneidad del uso de un háptico como dispositivo de entrada. En ambos casos, los resultados demuestran que nuestro procedimiento mejora la precisión de la reconstrucción. En este trabajo se describen también dos casos de uso de nuestro procedimiento en el ámbito de la neurociencia: el primero aplicado a neuronas situadas en la corteza cerebral humana y el segundo aplicado a espinas dendríticas situadas a lo largo de neuronas piramidales de la corteza del cerebro de una rata. Por último, presentamos el programa, Neuro Haptic Editor, desarrollado a lo largo de esta tesis junto con los diferentes algoritmos ya mencionados. ABSTRACT This thesis took place within the Cajal Blue Brain project, a European initiative dedicated to the study of the brain. One of the main goals of this project is the development of new methods and technologies simplifying data analysis in neuroscience. This thesis focused on the development of tools combining information originating from distinct sensory channels with the aim of accelerating both the interaction with neuroscience images and their analysis. In concrete terms, the objective is to study the possibility of combining visual information with haptic information. Dendritic spines are thin protrusions that cover the dendritic surface of numerous neurons in the brain and whose function seems to play a key role in neural circuits. The interest of the neuroscience community toward those structures kept increasing as and when acquisition methods improved, eventually to the point that the produced datasets enabled their analysis. Quite often, neuroscientists use light microscopy techniques to produce the dataset that will allow them to analyse neuronal structures such as neurons, dendrites and dendritic spines. While offering some advantages compared to their electronic counterpart, light microscopy techniques achieve lower resolutions. Particularly, small structures such as dendritic spines might suffer from a very low level of fluorescence in the final dataset, preventing further analysis. This thesis introduces a new technique enabling the edition of volumetric datasets in order to recreate dendritic spine necks using a haptic device. In order to fulfil this objective, we first presented an algorithm to provide haptic feedback directly from volumetric datasets, as an aid to regular visualization. The haptic rendering algorithm lets users perceive isosurfaces in volumetric datasets, and it relies on several design features that ensure a robust and efficient rendering. A marching tetrahedra approach enables the dynamic extraction of a piecewise linear continuous isosurface. Robustness is derived using a Continuous Collision Detection step coupled with acknowledged proxy-based rendering methods over the extracted isosurface. The introduced marching tetrahedra approach guarantees that the extracted isosurface will match the topology of an equivalent isosurface computed using trilinear interpolation. The proposed haptic rendering algorithm improves the coherence between haptic and visual cues computing a second proxy on the isosurface displayed on screen. Three experiments demonstrate the improvements on the isosurface extraction stage as well as the robustness and the efficiency of the complete algorithm. We then introduce our four-steps procedure for the complete reconstruction of dendritic spines. Based on our haptic rendering algorithm, this procedure is intended to work as an image processing stage before the automatic segmentation step giving the final representation of the dendritic spines. The procedure is designed to allow both the navigation and the volume image editing to be carried out using a haptic device. We evaluated our procedure through two experiments. The first experiment concerns the benefits of the force feedback and the second checks the suitability of the use of a haptic device as input. In both cases, the results shows that the procedure improves the editing accuracy. We also report two concrete cases where our procedure was employed in the neuroscience field, the first one concerning dendritic spines in the human cortex, the second one referring to an ongoing experiment studying dendritic spines along dendrites of mouse cortical pyramidal neurons. Finally, we present the software program, Neuro Haptic Editor, that was built along the development of the different algorithms implemented during this thesis, and used by neuroscientists to use our procedure.

Two binding modes reveal flexibility in kinase/response regulator interactions in the bacterial chemotaxis pathway

The crystal structure at 2.0-Å resolution of the complex of the Escherichia coli chemotaxis response regulator CheY and the phosphoacceptor-binding domain (P2) of the kinase CheA is presented. The binding interface involves the fourth and fifth helices and fifth β-strand of CheY and both helices of P2. Surprisingly, the two heterodimers in the asymmetric unit have two different binding modes involving the same interface, suggesting some flexibility in the binding regions. Significant conformational changes have occurred in CheY compared with previously determined unbound structures. The active site of CheY is exposed by the binding of the kinase domain, possibly to enhance phosphotransfer from CheA to CheY. The conformational changes upon complex formation as well as the observation that there are two different binding modes suggest that the plasticity of CheY is an essential feature of response regulator function.

Adjustment of conformational flexibility is a key event in the thermal adaptation of proteins

3-Isopropylmalate dehydrogenase (IPMDH, E.C. 1.1.1.85) from the thermophilic bacterium Thermus thermophilus HB8 is homologous to IPMDH from the mesophilic Escherichia coli, but has an approximately 17°C higher melting temperature. Its temperature optimum is 22–25°C higher than that of the E. coli enzyme; however, it is hardly active at room temperature. The increased conformational rigidity required to stabilize the thermophilic enzyme against heat denaturation might explain its different temperature-activity profile. Hydrogen/deuterium exchange studies were performed on this thermophilic-mesophilic enzyme pair to compare their conformational flexibilities. It was found that Th. thermophilus IPMDH is significantly more rigid at room temperature than E. coli IPMDH, whereas the enzymes have nearly identical flexibilities under their respective optimal working conditions, suggesting that evolutionary adaptation tends to maintain a “corresponding state” regarding conformational flexibility. These observations confirm that conformational fluctuations necessary for catalytic function are restricted at room temperature in the thermophilic enzyme, suggesting a close relationship between conformational flexibility and enzyme function.

Structural flexibility in transcription complex formation revealed by protein–DNA photocrosslinking

The Oct-1 POU domain binds diverse DNA-sequence elements and forms a higher-order regulatory complex with the herpes simplex virus coregulator VP16. The POU domain contains two separate DNA-binding domains joined by a flexible linker. By protein–DNA photocrosslinking we show that the relative positioning of the two POU DNA-binding domains on DNA varies depending on the nature of the DNA target. On a single VP16-responsive element, the POU domain adopts multiple conformations. To determine the structure of the Oct-1 POU domain in a multiprotein complex with VP16, we allowed VP16 to interact with previously crosslinked POU-domain–DNA complexes and found that VP16 can associate with multiple POU-domain conformations. These results reveal the dynamic potential of a DNA-binding domain in directing transcriptional regulatory complex formation.

Developmental regulation of spine motility in the mammalian central nervous system

The function of dendritic spines, postsynaptic sites of excitatory input in the mammalian central nervous system (CNS), is still not well understood. Although changes in spine morphology may mediate synaptic plasticity, the extent of basal spine motility and its regulation and function remains controversial. We investigated spine motility in three principal neurons of the mouse CNS: cerebellar Purkinje cells, and cortical and hippocampal pyramidal neurons. Motility was assayed with time-lapse imaging by using two-photon microscopy of green fluorescent protein-labeled neurons in acute and cultured slices. In all three cell types, dendritic protrusions (filopodia and spines) were highly dynamic, exhibiting a diversity of morphological rearrangements over short (<1-min) time courses. The incidence of spine motility declined during postnatal maturation, but dynamic changes were still apparent in many spines in late-postnatal neurons. Although blockade or induction of neuronal activity did not affect spine motility, disruption of actin polymerization did. We hypothesize that this basal motility of dendritic protrusions is intrinsic to the neuron and underlies the heightened plasticity found in developing CNS.