Orientação semi-automática de imagens CBERS usando rodovias como controle de campo

In this paper is proposed a methodology for semiautomatic CBERS image orientation using roads as ground control. It is based on an iterative strategy involving three steps. In the first step, an operator identifies on the image the ground control roads and supplies along them a few seed points, which could be sparsely and coarsely distributed. These seed points are used by the dynamic programming algorithm for extracting the ground control roads from the image. In the second step, it is established the correspondences between points describing the ground control roads and the corresponding ones extracted from the image. In the last step, the corresponding points are used to orient the CBERS image by using the DLT (Direct Linear Transformation). The two last steps are iterated until the convergence of the orientation process is verified. Experimental results showed that the proposed methodology was efficient with several test images. In all cases the orientation process converged. Moreover, the estimated orientation parameters allowed the registration of check roads with pixel accuracy or better.

Análise da reconstrução 3D a partir de um par estereoscópico HR-CCD/CBERS-2 usando dois modelos matemáticos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Orientação semi-automática de imagens CBERS usando rodovias como controle de campo

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Análise cinematográfica tridimensional da articulação metacarpofalangiana de equinos submetidos à elevação da pinça ou talões

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Forensische Psychophysiologie

Dieses Experiment untersuchte die Effekte der unterschiedlichen Fragen- bzw. Itemtypen (Stimuli), des Wahrheitsgehalts der Antworten und der elektrodermalen Labilität auf die Hautleitfähigkeitsreaktionen (SCR) und die phasische Herzschlagfrequenz (HR) für zwei relativ neue Befragungstechniken der forensischen Psychophysiologie ('Lügendetektion'): Directed Lie Test (DLT) und Guilty Actions Test (GAT).Achtzig Männer begingen einen simulierten Schmuckdiebstahl. Jeweils die Hälfte entwendete entweder einen Ring oder eine Kette. Während dieser Tat wurden jedoch alle Probanden mit den kritischen Details beider Scheinverbrechen konfrontiert. Anschließend absolvierten sie entweder einen DLT oder einen GAT. Die relevanten Stimuli der Tests bezogen sich auf beide Scheinverbrechen und wurden - intraindividuell variiert - wahrheitswidrig und wahrheitsgemäß verneint. Darüber hinaus umfaßte der DLT inhaltlich parallelisierte Paare von Kontrollfragen. Die Probanden wurden instruiert, die jeweiligen Kontrollfragen eines Paars wahrheitswidrig versus wahrheitsgemäß zu verneinen. Die Testverfahren beinhalteten außerdem nicht tatbezogene, irrelevante Stimuli, die wahrheitsgemäß beantwortet wurden. Für beide Befragungstechniken fand man Reaktionsunterschiede zwischen den Stimulustypen, insbesondere stärkere SCR-Magnituden und eine niedrigere HR auf die wahrheitswidrig verneinten relevanten Stimuli. Bei den Kontrollfragen des DLT zeigten sich jedoch keine signifikanten Effekte des Wahrheitsgehalts. Die elektrodermale Labilität hatte keinen bedeutsamen Einfluß auf die Reaktionsunterschiede. Die Ergebnisse wurden vor allem anhand psychophysiologischer Theorien der Aufmerksamkeit, Konflikte und Informationsverarbeitung interpretiert.

Alternating one lung ventilation using a double lumen endobronchial tube and providing CPAP to the non-ventilated lung in a dog

INTRODUCTION: This case report describes the anaesthetic management of exploratory thoracoscopy and alternating one lung ventilation (OLV) in a dog with a pulmonary bulla, and the application of continuous positive airway pressure (CPAP) to the non-ventilated lung for preventing and treating hypoxia. CASE HISTORY: A 6-year-old, male castrated Border collie was scheduled for exploratory thoracoscopy to investigate spontaneous pnemothorax that had not resolved with repeated suction. Specific requirements for the thoracoscopy were alternating OLV to allow the surgical access to the right middle lobe and its removal, and the examination of the left hemithorax to rule out the presence of other lesions. DIAGNOSIS AND MANAGEMENT: Selective lung ventilation was performed with a double lumen endobronchial tube (DLT), inserted under endoscopic guidance. After a short period of two lung ventilation during preparation of the surgical field, alternating OLV was performed, combining CPAP, provided to the non-ventilated lung via a Mapleson D breathing system, and positive end-expiratory pressure (PEEP) applied to the ventilated lung. Left OLV occurred first and resection of the right middle pulmonary lobe was successfully performed; right OLV followed to allow the examination of the left hemithorax. DISCUSSION AND CONCLUSIONS: The combination of CPAP and PEEP resulted in a satisfactory intra-operative management of hypoxemia. Alternating OLV can be performed successfully by using a DLT. CPAP, commonly employed in human medicine, should be considered an important tool in the anaesthetic management of OLV in small animals.

Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial

This phase I trial was designed to develop a new effective and well-tolerated regimen for patients with aggressive B cell lymphoma not eligible for front-line anthracycline-based chemotherapy or aggressive second-line treatment strategies. The combination of rituximab (375 mg/m(2) on day 1), bendamustine (70 mg/m(2) on days 1 and 2), and lenalidomide was tested with a dose escalation of lenalidomide at three dose levels (10, 15, or 20 mg/day) using a 3 + 3 design. Courses were repeated every 4 weeks. The recommended dose was defined as one level below the dose level identifying ≥2/6 patients with a dose-limiting toxicity (DLT) during the first cycle. Thirteen patients were eligible for analysis. Median age was 77 years. WHO performance status was 0 or 1 in 12 patients. The Charlson Comorbidity Index showed relevant comorbidities in all patients. Two DLTs occurred at the second dose level (15 mg/day) within the first cycle: one patient had prolonged grade 3 neutropenia, and one patient experienced grade 4 cardiac adverse event (myocardial infarction). Additional grade 3 and 4 toxicities were as follows: neutropenia (31 %), thrombocytopenia (23 %), cardiac toxicity (31 %), fatigue (15 %), and rash (15 %). The dose of lenalidomide of 10 mg/day was recommended for a subsequent phase II in combination with rituximab 375 mg/m(2) on day 1 and bendamustine 70 mg/m(2) on days 1 and 2.

Dreidimensionale Bewegungserfassung mit Consumer-Highspeedkameras: Eine Systementwicklung unter besonderer Berücksichtigung der Messunsicherheit

Schwerpunkt dieser Arbeit ist die Entwicklung und der Test eines auf Consumer-Highspeedkameras basierenden Bewegungserfassungssystems. Consumer-Kameras sind flexibler einsetzbar als kommerzielle Bewegungserfassungssysteme, zugleich kostengünstiger und werden daher oft in der sportwissenschaftlichen Forschung verwendet. Durch ihren Einsatz entstehen jedoch prinzipbedingt höhere Messunsicherheiten, deren Bestimmung in der vorliegenden Arbeit ein besonderer Stellenwert eingeräumt wird. Nach einem Überblick über aktuelle Bewegungserfassungssysteme und deren Genauigkeiten folgt eine Betrachtung der Messunsicherheit aus metrologischer Perspektive. Anschließend werden die Prozesse der Bilderfassung bei digitalen Consumer-Kameras sowie die zur Modellierung des Kameraabbildungsverhaltens notwendigen Parameteridentifikationsmethoden dargestellt. Diese reichen vom häufig genutzten DLT-Verfahren über Methoden mit Verzeichnungskorrektur bis zu Bündelausgleichsverfahren. Im Anschluss werden die für die verwendeten Kameras geeigneten Methoden auf Basis funktionaler Hardwaretests ausgewählt und weitere für das Bewegungserfassungssystem notwendige Softwarekomponenten diskutiert. Dazu gehören neben der automatisierten Video- und Bildverarbeitung, spezielle Verfahren zur Korrektur von Consumer-Kamera-spezifischen Abweichungen, z.B. die Korrektur von Rolling-Shutter-Verzerrungen. Im zweiten Teil der Arbeit richtet sich der Fokus auf die Simulation der Effekte von Parameterungenauigkeiten auf die Systemgenauigkeit sowie auf die Validierung und den Test des implementierten Systems. Dabei konnte die Rekonstruktionsgenauigkeit von 11.86mm bei einer Referenzrahmenkalibration durch den Einsatz der Kalibrationsmethode mit Bündelausgleichsverfahren von Svoboda u. a. (2005) auf maximal 4.126mm (M=0.073 mm; SD=1.486 mm) reduziert werden. Diese Methode erlaubt zudem eine einfachere Kalibration größerer Messvolumen ohne aufwändige Referenzrahmen und ist daher ideal für den sportwissenschaftlichen Einsatz geeignet. Ein weiteres Ergebnis der Arbeit ist die theoretische Ableitung der Fehlerfortpflanzung für die Prozessschritte der Bewegungserfassung. In Kombination mit der entwickelten Simulationsumgebung wird damit die Grundlage für eine Prädiktion der erreichbaren Messunsicherheit bereits vor der eigentlichen Messung gelegt.

An Innovative Phase I Trial Design Allowing for the Identification of Multiple Potential Maximum Tolerated Doses with Combination Therapy of Targeted Agents

Treatment for cancer often involves combination therapies used both in medical practice and clinical trials. Korn and Simon listed three reasons for the utility of combinations: 1) biochemical synergism, 2) differential susceptibility of tumor cells to different agents, and 3) higher achievable dose intensity by exploiting non-overlapping toxicities to the host. Even if the toxicity profile of each agent of a given combination is known, the toxicity profile of the agents used in combination must be established. Thus, caution is required when designing and evaluating trials with combination therapies. Traditional clinical design is based on the consideration of a single drug. However, a trial of drugs in combination requires a dose-selection procedure that is vastly different than that needed for a single-drug trial. When two drugs are combined in a phase I trial, an important trial objective is to determine the maximum tolerated dose (MTD). The MTD is defined as the dose level below the dose at which two of six patients experience drug-related dose-limiting toxicity (DLT). In phase I trials that combine two agents, more than one MTD generally exists, although all are rarely determined. For example, there may be an MTD that includes high doses of drug A with lower doses of drug B, another one for high doses of drug B with lower doses of drug A, and yet another for intermediate doses of both drugs administered together. With classic phase I trial designs, only one MTD is identified. Our new trial design allows identification of more than one MTD efficiently, within the context of a single protocol. The two drugs combined in our phase I trial are temsirolimus and bevacizumab. Bevacizumab is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF) pathway which is fundamental for tumor growth and metastasis. One mechanism of tumor resistance to antiangiogenic therapy is upregulation of hypoxia inducible factor 1α (HIF-1α) which mediates responses to hypoxic conditions. Temsirolimus has resulted in reduced levels of HIF-1α making this an ideal combination therapy. Dr. Donald Berry developed a trial design schema for evaluating low, intermediate and high dose levels of two drugs given in combination as illustrated in a recently published paper in Biometrics entitled “A Parallel Phase I/II Clinical Trial Design for Combination Therapies.” His trial design utilized cytotoxic chemotherapy. We adapted this design schema by incorporating greater numbers of dose levels for each drug. Additional dose levels are being examined because it has been the experience of phase I trials that targeted agents, when given in combination, are often effective at dosing levels lower than the FDA-approved dose of said drugs. A total of thirteen dose levels including representative high, intermediate and low dose levels of temsirolimus with representative high, intermediate, and low dose levels of bevacizumab will be evaluated. We hypothesize that our new trial design will facilitate identification of more than one MTD, if they exist, efficiently and within the context of a single protocol. Doses gleaned from this approach could potentially allow for a more personalized approach in dose selection from among the MTDs obtained that can be based upon a patient’s specific co-morbid conditions or anticipated toxicities.

BAYESIAN PHASE I DOSE FINDING IN CANCER TRIALS

This dissertation explores phase I dose-finding designs in cancer trials from three perspectives: the alternative Bayesian dose-escalation rules, a design based on a time-to-dose-limiting toxicity (DLT) model, and a design based on a discrete-time multi-state (DTMS) model. We list alternative Bayesian dose-escalation rules and perform a simulation study for the intra-rule and inter-rule comparisons based on two statistical models to identify the most appropriate rule under certain scenarios. We provide evidence that all the Bayesian rules outperform the traditional ``3+3'' design in the allocation of patients and selection of the maximum tolerated dose. The design based on a time-to-DLT model uses patients' DLT information over multiple treatment cycles in estimating the probability of DLT at the end of treatment cycle 1. Dose-escalation decisions are made whenever a cycle-1 DLT occurs, or two months after the previous check point. Compared to the design based on a logistic regression model, the new design shows more safety benefits for trials in which more late-onset toxicities are expected. As a trade-off, the new design requires more patients on average. The design based on a discrete-time multi-state (DTMS) model has three important attributes: (1) Toxicities are categorized over a distribution of severity levels, (2) Early toxicity may inform dose escalation, and (3) No suspension is required between accrual cohorts. The proposed model accounts for the difference in the importance of the toxicity severity levels and for transitions between toxicity levels. We compare the operating characteristics of the proposed design with those from a similar design based on a fully-evaluated model that directly models the maximum observed toxicity level within the patients' entire assessment window. We describe settings in which, under comparable power, the proposed design shortens the trial. The proposed design offers more benefit compared to the alternative design as patient accrual becomes slower.

Early renal failure after domino hepatic transplantation using the liver from a compound heterozygous patient with primary hyperoxaluria.

BACKGROUND To cover the shortage of cadaveric organs, new approaches to expand the donor pool are needed. Here we report on a case of domino liver transplantation (DLT) using an organ harvested from a compound heterozygous patient with primary hyperoxaluria (PHO), who underwent combined liver and kidney transplantation. The DLT recipient developed early renal failure with oxaluria. The time to the progression to oxalosis with renal failure in such situations is unknown, but, based on animal data, we hypothesize that calcineurin inhibitors may play a detrimental role. METHODS A cadaveric liver and kidney transplantation was performed in a 52-year-old male with PHO. His liver was used for a 64-year-old patient with a non-resectable, but limited cholangiocarcinoma. RESULTS While the course of the PHO donor was uneventful, in the DLT recipient early post-operative, dialysis-dependent renal failure with hyperoxaluria developed. Histology of a kidney biopsy revealed massive calcium oxalate crystal deposition as the leading aetiological cause. CONCLUSIONS DLT using PHO organs for marginal recipients represents a possible therapeutic approach regarding graft function of the liver. However, it may negatively alter the renal outcome of the recipient in an unpredictable manner, especially with concomitant use of cyclosporin. Therefore, we suggest that, although DLT should be promoted, PHO organs are better excluded from such procedures.

Performance of undergraduate dental students on ICDAS clinical caries detection after different learning strategies

AIM This study aimed to evaluate the effect of a digital learning tool on undergraduate dental students' performance in detecting dental caries using ICDAS. METHODS An experimental digital learning tool (DLT) was created using digital photographs of sound and carious teeth. Thirty-nine students were divided into three groups (n = 13) and each assessed 12 randomly allocated patients before and after learning strategies: G1, ICDAS e-learning program; G2, ICDAS e-learning program plus DLT; G3, no learning strategy. Students (n = 32) reassessed patients 2 weeks after training. RESULTS Comparing before and after the learning strategies, any difference in the values of specificity and area under the ROC curve for all groups was found. Sensitivity was statistically significantly higher for G1 and G2. Comparing the groups, G2 showed a significant increase in sensitivity at the D2 and D3 thresholds. Spearman's correlations with the gold standard before and after the learning strategy were 0.60 and 0.61 for G1, 0.57 and 0.63 for G2, and 0.54 and 0.54 for G3, respectively. The Wilcoxon test showed a statistically significant difference between the values obtained before and after learning strategies for G1 and G2. CONCLUSIONS Use of the DLT after the ICDAS e-learning program tended to increase the sensitivity of ICDAS used by undergraduate dental students. The DLT appeared to improve dental students' ability to use ICDAS.

Análisis biomecánico del segmento de la carrera a pie de la competición en triatlón

El principal objetivo de la presente investigación fue el conocer el perfil de rendimiento técnico de los triatletas, desde un punto de vista biomecánica, en el segmento carrera a pie durante la competición en triatlón. Asimismo, como el genero y el nivel deportivo del triatleta podrían influir en su respuesta motriz durante la competicion. Para ello, se necesitaba desarrollar y validar una técnica experimental que fuera lo suficientemente precisa (validez interna), con una alta fiabilidad y con una gran validez externa (ecologica) debido al entorno de la competicion. La muestra la formaron un total de 64 deportistas: 32 triatletas participantes en la Copa del Mundo de Triatlon de Madrid-2008 (16 hombres y 16 mujeres) y 32 triatletas participantes en el Clasificatorio del Campeonato de Espana Elite (16 hombres y 16 mujeres). El análisis de la técnica de carrera de los deportistas se realizo mediante un sistema fotogramétrico en 2d que permitió calcular las coordenadas (x,y) de los centros articulares con un error de 1.66% en el eje x y de un 2.10% en el eje y. Las imágenes fueron obtenidas por una cámara que filmaba el movimiento en un plano antero-posterior del triatleta. Algoritmos basados en la DLT (Abdel-Aziz & Karara, 1971) permitieron conocer las coordenadas reales a partir de las coordenadas digitalizadas en el plano y posteriormente las distintas variables analizadas. El análisis biomecánica de la carrera se realizo en 4 ocasiones diferentes durante la competición, correspondiendo con cada una de las vueltas de 2,5 km, que el triatleta tenía que realizar. La velocidad de carrera resulto estar íntimamente ligada al nivel deportivo del triatleta. Del mismo modo, 3 de los 4 grupos analizados presentaron valores inferiores a 3 minutos 30 segundos por kilometro recorrido, poniendo de manifiesto el altísimo nivel de los sujetos analizados. Del mismo modo parece que las chicos consiguen una mayor velocidad gracias a una mayor longitud de ciclo en relación a las chicas, ya que estas muestran valores mayores en cuanto a frecuencia de zancada. La frecuencia de zancada presento los valores más altos en la primera vuelta en todos los deportistas analizados. Asimismo, los triatletas de nivel internacional y las chicas fueron los que mostraron los mayores valores. La longitud de zancada presento distintas tendencias en función del nivel y el género del deportista. Así pues, en los deportistas internacionales y en los chicos los mayores valores se encontraron en la primera vuelta mientras que la tendencia fue al descenso, siendo probablemente la fatiga acumulada la causante de dicha tendencia. En cambio, aquellos deportistas de nivel nacional y las chicas mostraron valores mayores en la segunda vuelta que en la primera, evidenciando que además de la fatiga, el ciclismo previo tiene una incidencia directa sobre su rendimiento. Los tiempos de vuelo permanecieron constantes durante toda la carrera, encontrando cierta evolución en los tiempos de apoyo, la cual provoca una modificación en los porcentajes relativos en los tiempos de vuelo. Los tiempos de apoyo más bajos se encontraron en la primera vuelta. Del mismo modo, los deportistas de nivel internacional y los chicos mostraron valores inferiores. También, estos grupos fueron más constantes en sus valores a lo largo de las vueltas. Por el contrario, se encontraron tendencias al aumento en los triatletas de nivel nacional y en las chicas, los cuales no fueron capaces de mantener el mismo rendimiento debido seguramente a su menor nivel deportivo. La oscilación vertical de la cadera se mostro constante en los triatletas de mayor nivel, encontrándose tendencias al aumento en los de menor nivel. Del mismo modo, los valores más altos correspondieron a las chicas y a los deportistas de nivel nacional. La distancia de la cadera al apoyo permaneció constante a lo largo de las vueltas en todos los grupos, obteniéndose valores mayores en los triatletas de nivel internacional y en los chicos. El ángulo de la rodilla apoyada en el momento del despegue no mostro una tendencia clara. Los deportistas de nivel internacional y los chicos presentaron los valores más bajos. El ángulo de la rodilla libre en el momento del despegue mostro una correlación muy alta con la velocidad de carrera. Del mismo modo, los ángulos más pequeños se encontraron en los triatletas internacionales y en los chicos, debido seguramente a los mayores valores de velocidad registrados por ambos grupos. Los ángulos de los tobillos no mostraron ninguna tendencia clara durante la competición analizada. Los cuatro grupos de población presentaron valores similares, por lo que parece que no representan una variable que pueda incidir sobre el rendimiento biomecánica del triatleta. Los resultados obtenidos en el presente estudio de investigación avalan la utilización de la fotogrametría-video en 2d para el análisis de la técnica de carrera durante la competición en triatlón. Su aplicación en una competición de máximo nivel internacional ha posibilitado conocer el perfil técnico que presentan los triatletas a lo largo del segmento de carrera a pie. Del mismo modo, se ha podido demostrar como los estudios realizados en laboratorio no reflejan la realidad competitiva de un triatlón de máximo nivel. The aim of this research was to determine the running technique profile during a triathlon competition from a biomechanical perspective. Also, to analyze the triathlete gender’s and level of performance’s influence on this profile in competition. An accurate (internal validity) and reliable methodology with a high external validity (ecological) had to be developed to get those aims in competition. Sixty-four triathletes were analyzed. 32 (16 males, 16 females) took part in the Madrid 2008 Triathlon World Cup and 32 (16 males and 16 females) took part in the Spanish Triathlon National Championships. The biomechanical analyses were carried out by a photogrammetric system that allow to calculate the landmarks coordinates (x,y) with a 1.66% error in x axis, and a 2.10% error in y axis. The frames were obtained with a camera situated perpendicular to the triathletes’ trajectory, filming the saggittal plane. DLT based algorithms (Abdel-Aziz & Karara, 1971) were used to calculate the real coordinates from the digitalized ones and the final variables afterwards. The biomechanical analisys itself was performed in four different moments during the competition, according to each 2.5 km lap the triathletes had to do. Running speed was highly related to performance level. Also, 3 of the 4 analyzed groups showed speed values under the 3 minutes and 30 seconds per kilometer. It demonstrated the very high performance level of the analized triathletes. Furthermore, it seems that men get higher speeds because their longer stride length, while women shows higher stride frequency values. The highest stride frequency values were found in the first lap. Women and the international level triathletes showed the highest values. Stride length showed different tendencies according to the gender and level of performance. Men and international level triathletes showed the highest level in the first lap and a decreasing tendency after that. The accumulated fatigue was probably the reason of this tendency. On the other hand, higher values than in first lap were found in the second one in women and national level triathletes. It demonstrated the previous cycling can affect to those groups in terms of biomechanics. Flight times remained constant during the running part, while the contact times showed an increasing tendency that caused a variation in flight times percents. The lowest contact times were found in the first lap and in men and international triathletes’ values. Also, these two groups were more consistent during the whole running. On the other hand, increasing tendencies were found in women and national level triathletes, who were not able to maintain the same values probably due to their lower level of performance. Higher level triathletes showed more consistent hip vertical oscillation values than lower level triathletes, who presented increasing tendencies. The highest values were found in women and national level triathletes. The horizontal distance hip-toe cap remained constant among the laps in all the groups. Men and international level triathletes showed the highest values. The support knee angle at toe-off did not show a clear tendency. The lowest values were found in men and international level triathletes. A high correlation was found between the non-support knee angle and the running speed. Furthermore, men and international level triathletes showed the smallest values, due to the higher velocities reached by these two groups. Ankles angles did not show any tendency during the running part. Similar values were found in the four analyzed groups, so this variable does not seem to represent an important one within the triathlete’s performance. The results obtained in the present research support the use of the bidimensional photogrammetric video-system to analyze the running technique during a triathlon competition. Its application in international triathlon meetings has allowed determining the triathletes’ technique profile during the running part. Also, it has been demonstrated the laboratory-based studies does not reproduce a top-level competition.

Análisis biomecánico zancada a zancada de la prueba "60 metros vallas" durante los campeonatos del mundo y de España de pista cubierta Valencia 2008

El principal objetivo del presente trabajo de investigación fue determinar las diferencias en distintas variables relacionadas con el rendimiento físico entre atletas de distinto nivel durante la prueba de los 60 metros vallas. Un total de 59 vallistas masculinos (los 31 participantes en el Campeonato del Mundo Absoluto de Pista Cubierta y los 28 participantes en el Campeonato de España Absoluto de Pista Cubierta, ambos celebrados en Valencia en el año 2008) formaron la muestra del estudio. El análisis biomecánico se realizó mediante un sistema fotogramétrico en dos dimensiones que permitió calcular, aplicando algoritmos basados en el procedimiento de la DLT (Abdel-Aziz y Karara, 1971), las coordenadas (x, y) de los sucesivos apoyos de los pies de los atletas sobre toda la superficie de competición. La filmación de las pruebas se llevó a cabo con seis cámaras de vídeo, ubicadas sobre la gradas, con una frecuencia de muestreo para el tratamiento de los datos de 50 Hz. En la fase de salida, los atletas de nivel superior mostraron una menor longitud (p<0,05) y tiempo de zancada (p<0,001), debido a un menor tiempo de vuelo (p<0,05). En la fase de vallas, los atletas de nivel más elevado presentaron mayores distancia de ataque a la valla (p<0,001), así como menores distancias de caída de la valla (p<0,001), tiempos de zancada (p<0,01-0,001) y de apoyo (p<0,01-0,001 ) en los cuatro pasos que conforman cada ciclo de vallas, así como un menor tiempo de vuelo en el paso de valla (p<0,001) y en el paso de transición (p<0,001). De manera adicional, se encontraron importantes diferencias en el reparto de los pasos entre vallas entre la primera y tercera valla y el resto de obstáculos. En la fase final, se observó una mayor longitud de zancada en los atletas de nivel superior (p<0,001), así como un menor tiempo de zancada (p<0,01) y de apoyo (p<0,01). Los resultados obtenidos en el presente estudio de investigación avalan la utilización de la fotogrametría en dos dimensiones para el análisis biomecánico de la prueba de 60 metros vallas en competición. Su aplicación en competiciones del máximo nivel internacional ha posibilitado conocer las características de los vallistas a lo largo de toda la prueba y determinar posibles implicaciones de cara al proceso de entrenamiento. ABSTRACT The aim of this research was to determine the differences in different variables related to physical performance among athletes of different levels during the race of 60 meter hurdles. A total of 59 male hurdlers (the 31 participants in the World Indoor Championship and the 28 participants in the Spanish Indoor Championship, both held in Valencia in 2008) formed the sample of the study. The biomechanical analysis of athletes was performed using a two-dimensional photogrammetric system which enabled calculation, applying algorithms based on the DLT method (Abdel -Aziz y Karara , 1971), the coordinates (x , y) of the successive supports of the feet on the entire competition surface. Filming test was conducted with six video cameras, located on the bleachers, with a sampling frequency for data processing of 50 Hz. In the approach run phase, the top-level athletes showed a smaller length step (p<0.05), and shorter step time (p<0.001), due to a shorter step flight time (p<0.05). In the hurdle unit phase, the higher level athletes had greater take-off distances (p<0.001), shorter landing distances (p<0.001), smaller step times (p<0.01-0.001), and support times (p<0.01- 0.001) in the four steps that comprised each hurdle unit, and smaller flight times in the hurdle step (p < 0.001), and the recovery step (p<0.001). Additionally, differences in the distribution of hurdle unit steps between the first and third hurdle, and other hurdles were found. In the run-in phase, a greater step length in top-level athletes (p<0.001), and a shorter step time (p<0.01) and contact time (p<0.01) was observed. The results obtained in this study support the use of photogrammetry in two dimensions for biomechanical analysis in 60 meter hurdles competition events. Its application at the highest international level competitions has allowed to know the characteristics of the hurdlers over the entire race and identify possible implications for the training process.

The role of mechanistic target of rapamycin (mTOR) pathway and synaptic protein GABAA-R in cortical GABAergic cell connectivity

Quelque 30 % de la population neuronale du cortex mammalien est composée d’une population très hétérogène d’interneurones GABAergiques. Ces interneurones diffèrent quant à leur morphologie, leur expression génique, leurs propriétés électrophysiologiques et leurs cibles subcellulaires, formant une riche diversité. Après leur naissance dans les éminences ganglioniques, ces cellules migrent vers les différentes couches corticales. Les interneurones GABAergiques corticaux exprimant la parvalbumin (PV), lesquels constituent le sous-type majeur des interneurones GABAergiques, ciblent spécifiquement le soma et les dendrites proximales des neurones principaux et des neurones PV+. Ces interneurones sont nommés cellules à panier (Basket Cells –BCs) en raison de la complexité morphologique de leur axone. La maturation de la connectivité distincte des BCs PV+, caractérisée par une augmentation de la complexité de l’axone et de la densité synaptique, se déroule graduellement chez la souris juvénile. Des travaux précédents ont commencé à élucider les mécanismes contrôlant ce processus de maturation, identifiant des facteurs génétiques, l’activité neuronale ainsi que l’expérience sensorielle. Cette augmentation marquante de la complexité axonale et de la synaptogénèse durant cette phase de maturation suggère la nécessité d’une synthèse de protéines élevée. La voie de signalisation de la cible mécanistique de la rapamycine (Mechanistic Target Of Rapamycin -mTOR) a été impliquée dans le contrôle de plusieurs aspects neurodéveloppementaux en régulant la synthèse de protéines. Des mutations des régulateurs Tsc1 et Tsc2 du complexe mTOR1 causent la sclérose tubéreuse (TSC) chez l’humain. La majorité des patients TSC développent des problèmes neurologiques incluant des crises épileptiques, des retards mentaux et l’autisme. D’études récentes ont investigué le rôle de la dérégulation de la voie de signalisation de mTOR dans les neurones corticaux excitateurs. Toutefois, son rôle dans le développement des interneurones GABAergiques corticaux et la contribution spécifique de ces interneurones GABAergiques altérés dans les manifestations de la maladie demeurent largement inconnus. Ici, nous avons investigué si et comment l’ablation du gène Tsc1 perturbe le développement de la connectivité GABAergique, autant in vitro que in vivo. Pour investiguer le rôle de l’activation de mTORC1 dans le développement d’une BC unique, nous avons délété le gène Tsc1 en transfectant CRE-GFP dirigé par un promoteur spécifique aux BCs dans des cultures organotypiques provenant de souris Tsc1lox. Le knockdown in vitro de Tsc1 a causé une augmentation précoce de la densité des boutons et des embranchements terminaux formés par les BCs mutantes, augmentation renversée par le traitement à la rapamycine. Ces données suggèrent que l’hyperactivation de la voie de signalisation de mTOR affecte le rythme de la maturation des synapses des BCs. Pour investiguer le rôle de mTORC1 dans les interneurones GABAergiques in vivo, nous avons croisé les souris Tsc1lox avec les souris Nkx2.1-Cre et PV-Cre. À P18, les souris Tg(Nkx2.1-Cre);Tsc1flox/flox ont montré une hyperactivation de mTORC1 et une hypertrophie somatique des BCs de même qu’une augmentation de l’expression de PV dans la région périsomatique des neurones pyramidaux. Au contraire, à P45 nous avons découvert une réduction de la densité des punctas périsomatiques PV-gephyrin (un marqueur post-synaptique GABAergique). L’étude de la morphologie des BCs en cultures organotypiques provenant du knock-out conditionnel Nkx2.1-Cre a confirmé l’augmentation initiale du rythme de maturation, lequel s’effondre ensuite aux étapes développementales tardives. De plus, les souris Tg(Nkx2.1Cre);Tsc1flox/flox montrent des déficits dans la mémoire de travail et le comportement social et ce d’une façon dose-dépendante. En somme, ces résultats suggèrent que l’activation contrôlée de mTOR régule le déroulement de la maturation et la maintenance des synapses des BCs. Des dysfonctions de la neurotransmission GABAergique ont été impliquées dans des maladies telles que l’épilepsie et chez certains patients, elles sont associées avec des mutations du récepteur GABAA. De quelle façon ces mutations affectent le processus de maturation des BCs demeuret toutefois inconnu. Pour adresser cette question, nous avons utilisé la stratégie Cre-lox pour déléter le gène GABRA1, codant pour la sous-unité alpha-1 du récepteur GABAA dans une unique BC en culture organotypique. La perte de GABRA1 réduit l’étendue du champ d’innervation des BCs, suggérant que des variations dans les entrées inhibitrices en raison de l’absence de la sous-unité GABAAR α1 peuvent affecter le développement des BCs. La surexpression des sous-unités GABAAR α1 contenant des mutations identifiées chez des patients épileptiques ont montré des effets similaires en termes d’étendue du champ d’innervation des BCs. Pour approfondir, nous avons investigué les effets de ces mutations identifiées chez l’humain dans le développement des épines des neurones pyramidaux, lesquelles sont l’endroit privilégié pour la formation des synapses excitatrices. Somme toute, ces données montrent pour la première fois que différentes mutations de GABRA1 associées à des syndromes épileptiques peuvent affecter les épines dendritiques et la formation des boutons GABAergiques d’une façon mutation-spécifique.