The use of Platelet-rich plasma (PRP), a platelet concentrate made of autogenous blood, is becoming use in the treatment of some orthopaedic diseases. The aim of this study is to assess the effect of PRP on articular cartilage defects in a rabbit model (10 subjects). Twenty osteochondral defects created in the femoropatellar groove, were in ten cases left untreated and in ten cases treated with autogenous PRP. PRP was obtained using a double centrifugation of the rabbit’s blood harvested before the operation. 30 days after the lesion was made in both knee, the left one in each rabbit was treated by a PRP injection, followed by other two injection at 45 and 60 days. Tissue specimens were assessed by macroscopic examination and histological evaluation, that showed a better healing of the lesions in the knee treated with PRP injections.

Like other vascular tumors, epithelioid hemangioendothelioma (EHE) is multifocal in approximately 50% of cases, and it is unclear whether the separate lesions represent multifocal disease or metastases. We hypothesized that the identification of an identical WWTR1-CAMTA1 rearrangement in different EHEs from the same patient supports the monoclonal origin of EHE. To test our hypothesis, we undertook a molecular analysis of two multicentric EHEs of the liver, including separate tumor samples from each patient. Matherial and Methods: We retrieved two cases of EHE with available tissue for molecular analysis. In both cases, fluorescence in situ hybridization (FISH) was performed to identify the presence of the WWTR1-CAMTA1 rearrangement to confirm the histologic diagnosis of EHE, as previously described. The reverse transcription-polymerase chain reaction (RT-PCR) products were analyzed by electrophoresis and the RT-PCR–amplified products were sequenced using the Sanger method. Results: FISH analysis revealed signal abnormalities in both WWTR1 and CAMTA1. Combined results confirmed the presence of the t(1;3)(1p36.23;3q25.1) translocation in both cases of EHE. Using RT-PCR analysis, we found that the size of the rearranged bands was identical in the different tumors from each patient. The sequence of the fusion gene confirmed a different WWTR1-CAMTA1 rearrangement in each patient, but an identical WWTR1-CAMTA1 rearrangement in the different lesions from each patient. Discussion: Because of its generally indolent clinical course, EHE is commonly classified as a multifocal, rather than metastatic, disease. In this study, we examined two cases of multifocal liver EHE and found an identical WWTR1-CAMTA1 rearrangement in each lesion from the same patient, but not between the two patients. These findings suggest that multifocal EHE arises from metastasis of the same neoplastic clone rather than from the simultaneous formation of multiple neoplastic clones, which supports the monoclonal origin of multifocal EHE.

En la present tesi doctoral es contrasta la hipòtesi d’inducció a l’eficiència dels proveïdors sanitaris a través del poder de comprador. Per fer-ho s’analitza el cas de la concertació hospitalària a Catalunya. En primer lloc, s’ha construït un model principal-agent amb acció oculta que representa la compra de serveis per part de l’organisme públic competent a un proveïdor hospitalari. En segon lloc, a partir d’una mostra de 55 hospitals de la XHUP, s’ha construït un índex de mesura del poder de comprador relatiu del CatSalut sobre cadascun d’aquells proveïdors hospitalaris. Finalment, s’han obtingut els marcadors d’eficiència tècnica en la provisió de cada hospital emprant la tècnica Data Envelopment Analysis (DEA). D’altra banda, per tal de contrastar la hipòtesi s’ha emprat un model Tobit de regressió censurada. Els resultats de les estimacions aporten certa evidència en favor de l’existència d’un efecte d’inducció d’eficiència a través del poder de comprador. / In this thesis we test the hypothesis of efficiency induction through buyer power. To do so, we analyse the case of public hospital contracting in Catalonia. First, we build a principal-agent model with hidden action, which describes the relationship between the public buyer and a hospital provider. Second, we build a measure of buyer power based upon a sample of 55 hospitals from the public network. This is an index that measures the relative buyer power exercised by the public buyer agency over each hospital. Finally, efficiency scores have been obtained using a Data Envelopment Analysis (DEA) approach. In order to test the hypothesis we use a Tobit regression model. Estimation results provide some evidence concerning a positive effect of buyer power on hospital provision efficiency.

Articular cartilage lesions, with their inherent limited healing potential, are hard to treat and remain a challenging problem for orthopedic surgeons. Despite the development of several treatment strategies, the real potential of each procedure in terms of clinical benefit and effects on the joint degeneration processes is not clear. Aim of this PhD project was to evaluate the results, both in terms of clinical and imaging improvement, of new promising procedures developed to address the challenging cartilage pathology. Several studies have been followed in parallel and completed over the 3-year PhD, and are reported in detail in the following pages. In particular, the studies have been focused on the evaluation of the treatment indications of a scaffold based autologous chondrocyte implantation procedure, documenting its results for the classic indication of focal traumatic lesions, as well as its use for the treatment of more challenging patients, older, with degenerative lesions, or even as salvage procedure for more advanced stages of articular degeneration. The second field of study involved the analysis of the results obtained treating lesions of the articular surface with a new biomimetic osteochondral scaffold, which showed promise for the treatment of defects where the entire osteochondral unit is involved. Finally, a new minimally invasive procedure based on the use of growth factors derived from autologous platelets has been explored, showing results and underlining indicatios for the treatment of cartilage lesions and different stages of joint degeneration. These studies shed some light on the potential of the evaluated procedures, underlining good results as well as limits, they give some indications on the most appropriate candidates for their application, and document the current knowledge on cartilage treatment procedures suggesting the limitations that need to be addressed by future studies to improve the management of cartilage lesions.

Restoring a correct implant kinematics and providing a good ligament balance and patellar tracking is mandatory to improve clinical and functional outcome after a Total Knee Replacement. Surgical navigation systems are a reliable and accurate tool to help the surgeon in achieving these goals. The aim of the present study was to use navigation system with an intra-operative surgical protocol to evaluate and determine an optimal implant kinematics during a Total Knee Replacement.

L’accoppiamento articolare in ceramica è sempre più utilizzato in chirurgia protesica dell’anca per le sue eccellenti proprietà tribologiche. Tuttavia la fragilità della ceramica è causa di fallimenti meccanici. Abbiamo quindi condotto una serie di studi al fine di individuare un metodo efficace di diagnosi precoce del fallimento della ceramica. Abbiamo analizzato delle componenti ceramiche espiantate e abbiamo trovato un pattern di usura pre-frattura che faceva supporre una dispersione di particelle di ceramica nello spazio articolare. Per la diagnosi precoce abbiamo validato una metodica basata sulla microanalisi del liquido sinoviale. Per validare la metodica abbiamo eseguito un agoaspirato in 12 protesi ben funzionanti (bianchi) e confrontato i risultati di 39 protesi con segni di rottura con quelli di 7 senza segni di rottura. Per individuare i pazienti a rischio rottura i dati demografici di 26 pazienti con ceramica rotta sono stati confrontati con 49 controlli comparabili in termini demografici, tipo di ceramica e tipo di protesi. Infine è stata condotta una revisione sistematica della letteratura sulla diagnosi della rottura della ceramica. Nell’aspirato la presenza di almeno 11 particelle ceramiche di dimensioni inferiori a 3 micron o di una maggiore di 3 micron per ogni campo di osservazione sono segno di rottura della ceramica. La metodica con agoaspirato ha 100% di sensibilità e 88 % di specificità nel predire rotture della ceramica. Nel gruppo delle ceramiche rotte è stato trovato un maggior numero di malposizionamenti della protesi rispetto ai controlli (p=0,001). Il rumore in protesi con ceramica dovrebbe sollevare il sospetto di fallimento ed indurre ad eseguire una TC e un agoaspirato. Dal confronto con la letteratura la nostra metodica risulta essere la più efficace. / Ceramic is increasingly used in total hip replacement for its excellent tribological properties. However, the brittleness of ceramics is of concern and mechanical failures are reported. We conducted a series of studies in order to identify an effective method of early diagnosis of ceramic failure. We have analyzed 20 ceramic components explanted and found a pattern of wear that would suggest a dispersion of ceramic particles in the joint space. We therefore investigated whether isolation, observation at scanning electron microscopy, and chemical identification with microanalysis of particles from synovial fluid could be predictive of ceramic damage. Firstly, the level of ‘‘physiological wear’’ of well functioning hip prostheses was assessed with this method, then the test was validated as diagnostic method for liner fracture. Twelve asymptomatic patients were enrolled to demonstrate the first aim; 39 cases of noisy hip, and 7 cases of pending failure not related to ceramic were enrolled for the second aim. To detect risk factors for ceramic liner fractures we compared 26 ceramic hips revised because of ceramic liner fracture with 49 well-functioning hips. Finally a systematic review was done to compare our results with those reported in the litterature. In the aspirate the presence of at least 11 ceramic particles of size less than 3 microns or the presence of one greater than 3 microns for each field of observation are a sign of ceramic failure. The method with fine needle aspiration has 100% sensitivity and 88% specificity in predicting breakage of the ceramic. A cup anteversion angle out of the optimal range of 15 ̊+/-10 ̊ was found to be a risk factor for ceramic liner fracture. There are no other diagnostic methodologies described in the literature as specific and sensible as the one we have proposed.

E' stato sviluppato un algoritmo predittivo del rischio di consolidazione ossea (ARRCO – Algoritmo Rischio Ritardo Consolidazione Ossea - IGEA, Carpi, Italy) che combina diversi fattori correlati al rischio di ritardata o mancata guarigione di una frattura. Questo algoritmo ha permesso di idntificare una popolazione di pazienti affetti da fratture con aumentato rischio di ritardo di consolidazione o mancata guarigione. Questi pazienti sono stati sottoposti precocemente a stimolazione biofisica precoce mediante Campi Elettromagnetici Pulsati a bassa frequenza (CEMP), ottenendo la guarigione della frattura nella maggior parte dei casi e in tempi considerati fisiologici. Pertanto in un gruppo selezionato di pazienti, il trattamento può essere indirizzato all'applicazione precoce di CEMP, al fine di promuovere la consolidazione ossea di una frattura "a richio", il cui trattamento richiederebbe altrimenti tempi più prolungati e un costo virtuale maggiore dell'intero trattamento sanitario. / A predictive score for risk of delayed healing (ARRCO – Algoritmo Rischio Ritardo Consolidazione Ossea - IGEA, Carpi, Italy) has been developed in order to consider and combine different risk factors influencing the healing of a fracture, calculating a score correlated with healing potential, time of healing and risk of delayed healing or non-union. The ARRCO score provided a simple and effective tool for the orthopaedic surgeons to early identify fractures presenting risk of delayed healing. In these cases early application of Pulsing Low-frequency Electromagnetic Fields (PEMF) was performed, obtaining bone healing in most of cases reducing the time of healing. Therefore in a selected group of patients affected by "fractures at risk", the treatment may be directed to early application of electromagnetic bone growth stimulation with PEMF, in order to promote healing of the fracture, reducing consequently the time and the virtual cost of the treatment.

Tumors involving bone and soft tissues are extremely challenging situations. With the recent advances of multi-modal treatment, not only the type of surgery has moved from amputation to limb-sparing procedures, but also the survivorship has improved considerably and reconstructive techniques have the goal to allow a considerably higher quality of life. In bone reconstruction, tissue engineering strategies are the main area of research. Re-vascularization and re-vitalisation of a massive allograft would considerably improve the outcome of biological reconstructions. Using a rabbit animal model, in this study we showed that, by implanting a vascular pedicle inside a weight bearing massive cortical allograft, the bone regeneration inside the allograft was higher compared to the non-vascularized implants, given the patency of the vascular pedicle. Improvement in the animal model and the addition of Stem Cells and Growth factors will allow a further improvement in the results. In soft tissue tumors, free and pedicled flaps have been proven to be of great help as reconstruction strategies. In this study we analyzed the functional and overall outcome of 14 patients who received a re-innervated vascularized flap. We have demonstrated that the use of the innovative technique of motor re-innervated muscular flaps is effective when the resection involves important functional compartments of the upper or lower limb, with no increase of post-operative complications. Although there was no direct comparison between this type of reconstruction and the standard non-innervated reconstruction, we underlined the remarkable high overall functional scores and patient satisfaction following this procedure.

Esta tesis recoge las conclusiones de un trabajo de campo realizado en cuatro lugares vinculados entre ellos por cadenas migratorias: los cantones de Paute y Saraguro en Ecuador; algunas zonas de la ciudad de Nueva York y sus alrededores; y algunas localidades del sureste español. El objetivo en Ecuador era el de investigar con detalle los usos dados a las remesas que los migrantes enviaban a sus familiares: en qué se convertían y las decisiones detrás de estos usos. También prestamos atención a las historias particulares de migración al extranjero. Más tarde viajamos a Nueva York y a algunas localidades de España para localizar a los familiares y amigos de aquellos que habíamos conocido en Ecuador, de modo que tuviésemos la otra parte de aquellas historias. Con ellos hablamos de sus trayectorias personales, de sus problemas y anhelos, y también de las decisiones detrás de la migración y los usos de las remesas. Para nuestro trabajo hemos contado además con la aportación de numerosas personas expertas en distintos aspectos del fenómeno que hemos abordado. A todos ellos ―a los expertos, a los migrantes y sus familiares― les hemos entrevistado, sumando un total de ciento diez entrevistas realizadas a un lado y otro del Atlántico, las cuales hemos utilizado para componer una descripción etnográfica y profunda del fenómeno de las remesas y la migración en aquellos dos cantones del Ecuador. Además, a esa investigación sobre el terreno y su posterior exposición, le hemos añadido un trabajo teórico en el que hemos tenido en cuenta tanto las características sociales, históricas y económicas de las personas protagonistas de nuestro estudio; así como otros aspectos que tienen que ver con la migración, las remesas y la toma de decisiones. De nuestro análisis cualitativo hemos extraído algunas ideas con las que hemos elaborado una teoría de cómo las personas tomamos nuestras decisiones, así como la manera en que se configuran nuestros gustos, que hemos utilizado para explicar nuestro trabajo etnográfico. En esa teoría hablamos de cómo los seres humanos no tomamos nuestras decisiones en base a criterios maximizadores y economicistas; sino que las tomamos según las ideas que compartimos con las personas con las que vivimos. Es decir, nuestras decisiones están irremediablemente influidas por la cultura, y muchas de ellas adquieren un significado social que va más allá de la mera utilidad. Nos identificamos con, y en base a nuestras elecciones. Pero también nuestra personalidad y nuestra experiencia determinarán en gran parte nuestras preferencias, haciendo que nos inclinemos más hacia ciertas ideas y actitudes en detrimento de otras. Esta manera de proceder del ser humano para tomar sus decisiones se haría especialmente visible en aquellas elecciones que tienen que ver con el migrar y con gastar el dinero de las remesas. Nosotros lo demostramos en este trabajo, en el cual defendemos que muchas de las personas que migraron al extranjero desde Paute y Saraguro lo hicieron siguiendo un ideal, al que nosotros hemos llamado motivo de vida, que fue creándose socialmente con las historias de aquellos que se habían marchado primero al extranjero y con las habladurías de los vecinos con respecto al nivel de vida que habrían adquirido los familiares de esos migrantes. Había ocurrido en esos dos lugares un catasterismo: la emergencia de una historia con características míticas, que tiene el poder de orientar los anhelos y cambiar las expectativas de las personas que viven en un lugar o que forman parte de una comunidad. Dicho de otro modo: se había creado la misma necesidad de migrar, y las remesas contribuyeron alimentando ese fenómeno. / This thesis compiles the conclusions of a field work done in four places bound each other by migratory chains: Paute and Saraguro cantons in Ecuador; some areas in New York City and its vicinity, and some localities in the southeast of Spain. The aim in Ecuador was to investigate in detail the uses given to the remittances sent by the migrants to their families: what they became and the decision behind these uses. We also paid attention to the individual stories concerning migrations to foreign countries. Later, we went to New York and some Spanish localities in order to locate the relatives and friends of those who we had met previously in Ecuador so that we could listen to their own version of those stories about migration. We conversed about their personal development, their problems and wishes, and also about the decisions for migrating and the uses of the remittances. In this research we have also relied on the contribution of a big number of experts in different fields of the phenomenon addressed. We have interviewed all of them ―experts, migrants and their relatives― making a total of 101 interviews at both sides of the Atlantic ocean. These interviews have been used to form a deep ethnographic description of the remittances phenomenon and the migrations to the previously mentioned cantons. Furthermore, to this field work and its subsequent explanation, we have added a theoretical work in which he have taken into account both the social, historical and economical characteristics of the main characters of our study, and those other aspects concerning migrations, remittances and decisions making. From our qualitative analysis, we have taken four main ideas with which we have worked out a hypothesis about how people make their own decisions, as in the way in which our tastes are formed and configured. This theory has been used to explain our ethnographical work. In this theory we talk about how human beings do not make decisions based on maximizer and economic criteria, but according to the ideas we share with the people who surrounds us, i.e. our decisions are unavoidably influenced by culture, and many of these ideas acquire a social meaning which goes beyond the mere utility. We identify ourselves with, and according to, our decisions. Nevertheless, our personality and our experience will determine our preferences into a great extent, as well, making us to lean towards some specific ideas to the detriment of others. This way of proceeding when taking decisions ―typical from the human being― would be specially visible in those decisions concerning the migration to other countries and how the money of the remittances is spent. This fact is proved in this work, in which we defend the idea that a big percentage of the people who migrated abroad from Paute and Saraguro was following and ideal to which we call life motif. This ideal was created by means of the stories of those who had moved to foreign countries and the gossips of the social setting about the lifestyle acquired by those migrants' relatives. A phenomenon that we called catasterismi had happened in those places. For us, this phenomenon is the emergency of a story with mythical characteristics, having this story the power of orienting the wishes and changing the expectations of the people who live in a specific place or belong to a community. In other words, it has been created the same need for migrating, and the remittances favoured this phenomenon.

El interés de los investigadores de la ciencia económica por la teoría del caos comenzó en la década de los 80 y una de la razones del mismo es el comportamiento aparentemente aleatorio de sistemas dinámicos no lineales simples y con pocos grados de libertad. Conocer esta especial dinámica a partir de series temporales obtenidas de estos sistemas dinámicos es lo que nos ha llevado a realizar esta Memoria, donde se estudian herramientas utilizadas en el análisis de sistemas dinámicos no lineales. La Memoria está estructurada en 5 capítulos, el primero es una introducción donde se incluyen generalidades sobre sistemas dinámicos discretos y una panorámica general de los distintos aspectos que se van a tratar en la misma. El segundo capítulo está dedicado a la teoría del embedding donde el teorema de Takens supone una de las justificaciones teóricas que permite construir una órbita de un sistema dinámico determinista desconocido a partir de una serie temporal de medidas obtenida de una órbita del mismo. Un teorema previo al de Takens, y básico en la demostración de éste, es el Teorema de Whitney. En este capítulo se dan dos nuevas demostraciones del Teorema de Whitney y se demuestra una extensión del teorema de Takens (resultado publicado en Acta Mathematica Hungarica, 88(4)). En el Capítulo 3 se profundiza en las implicaciones del signo del exponente de Lyapunov de un sistema dinámico unidimensional y se obtiene un resultado que complementa el dado por Koçak y Palmer (2010), así como nuevos ejemplos de sistemas dinámicos unidimensionales y bidimensionales con el comportamiento paradójico de los sistemas dinámicos mostrados en Demir y Koçak (2001) (resultados publicados en International Journal of Bifurcation and Chaos, 23). El Capítulo 4 está dedicado a los gráficos de recurrencia que son una herramienta que permite visualizar el concepto de correlación integral de un conjunto (entre otros). En las últimas décadas este tipo de gráficos, y en particular las medidas definidas sobre ellos, se han utilizado en el análisis de series temporales económicas, siendo uno de sus principales objetivos encontrar los puntos de cambio del comportamiento dinámico del modelo generador de datos. En este capítulo se utilizan las medidas cuantitativas definidas sobre estos gráficos con una serie no estacionaria obtenida del sistema dinámico de Liu para aproximarnos a sus puntos de bifurcación (resultado en Chaos, Solitons and Fractals, 36(3)). Un contraste no paramétrico de independencia se desarrolla en el Capítulo 5 y resulta de aplicar el principal teorema, que demostramos, sobre la distribución asintótica de una transformación lineal del estadístico que estima la correlación integral simbólica de una serie independiente e idénticamente distribuida. El concepto de correlación integral simbólica se define para cualquier conjunto compacto de un espacio vectorial m-dimensional y está basado en su simbolización, que consiste en asignar a cada elemento la permutación del conjunto {1,2,...,m} que representa el orden de sus componentes. Para este contraste, cuya hipótesis nula es que la serie sea independiente e idénticamente distribuida frente a cualquier dependencia, se ha estudiado el tamaño del test y su potencia. Los resultados obtenidos muestran un buen comportamiento del estadístico utilizado. Se finaliza el capítulo definiendo gráfico de recurrencia simbólico y simbólico coloreado y se calculando distintas medidas sobre los mismos. La última sección de cada capítulo se dedica a las conclusiones sobre los resultados obtenidos y las cuestiones que han quedado abiertas y que intentaremos cerrar en próximos trabajos. / The interest of economists in chaos theory started in the 1980s. One of the reasons is the apparently random behavior of simple nonlinear dynamical systems with few degrees of freedom. The knowledge of this particular behavior from time series obtained from these dynamical systems has motivated us to study some of the tools used in the analysis of nonlinear dynamical systems. The thesis is divided into five chapters. The first is the introduction which includes an overview of discrete dynamical systems and outlines the contents of the following chapters. The second chapter is devoted to the embedding theory, where a Takens theorem is one of the theoretical justifications that allows us to construct an orbit of an unknown deterministic dynamical systems from a time series of measurements obtained from this system. The Whitney theorem is fundamental in the proof of the Takens theorem. In this chapter we provide two new proofs of the Whitney theorem and an extension of the Takens theorem (results published in Acta Mathematica Hungarica, 88 (4)). In chapter 3 we examine in depth the implications of the sign of the Lyapunov exponent of an orbit of a one-dimensional dynamical system and we prove a result that complements another given by Koçak and Palmer (2010) as well as new examples of one-dimensional and two-dimensional dynamical systems having the paradoxical behavior of dynamical systems shown by Demir and Koçak (2001) (results published in the International Journal of Bifurcation and Chaos, 23). The chapter 4 is devoted to Recurrence Plots. These graphics are a tool for visualizing the correlation integral of a vectorial time series. In recent decades recurrence plots and the measures defined on them have been used to analyze economic time series, where the main objective is to approach the shift points of the dynamic behavior of the process generator of data. In this chapter we use the recurrence quantitative analysis with a non-stationary time series obtained from Liu's dynamical system to approach Liu bifurcation points (results in Chaos, Solitons and Fractals, 36 (3)). A nonparametric test of independence is developed in Chapter 5. This test is the result of applying the main theorem that we show to the asymptotic distribution of a linear transformation of the statistic that estimates the symbolic correlation integral of an embedded independent and identically distributed series. The concept of symbolic correlation integral is also defined for any compact set of a m-dimensional vectorial space, and is based on its symbolization, that is, assign to each element a permutation of the set {1,2, ..., m}, which represents the order of its components. For this test the null hypothesis is that the time series is independent and identically distributed against any type of dependence in the time series. We studied the size and power of this test and the results show good statistical properties. The chapter ends defining symbolic recurrence plots and colored symbolic recurrence plots and we have calculate measures on them. Each chapter ends with a conclusions section on the results proven and questions that remain open, which we will seek to close in futur works.