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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
31

The analysis and interpretation of fragmented mammoth bone assemblages : experiments in bone fracture with archaeological applications

Karr, Landon Patrick January 2012 (has links)
The study of flaked mammoth bone tools from the Late Pleistocene is a topic that has inspired great interest in the archaeological community for the last 40 years. The interpretation of evidence of culturally modified mammoth bone tools has varied widely across both time and space. At different times and in different places, flaked bone toolmaking has been interpreted across the geographic expanse of the North American continent, from Beringia to central Mexico, and through a vast timeframe, from 120,000 years ago, until as recently as 10,000 years ago. The study of these purported flaked bone tool assemblages has taken many forms, and has involved efforts to understand broken mammoth bone assemblages by drawing analogies to stone toolmaking strategies, by understanding the multitude of taphonomic processes that affect archaeological bone assemblages, and by attempting to differentiate the effects of natural and cultural processes. This thesis reports on a series of experiments designed to lend new actualistic evidence to the debate surrounding flaked bone toolmaking. These experiments include investigations into the effect of different environmental conditions on the degradation of bones, the flaking characteristics of both fresh and frozen bones, and the effect of rockfall as a taphonomic process on bones exposed to different real-world environments. These experiments, paired with a body of previous research, provide a basis in actualistic and taphonomic research that allows for the reassessment of archaeological and paleontological broken mammoth bone assemblages. This thesis includes the reassessment and detailed taphonomic analysis of four mammoth bone assemblages relevant to understanding cultural bone modification and the effect of non-cultural taphonomic processes. New interpretations of zooarchaeological assemblages from Lange/Ferguson (South Dakota, USA), Owl Cave (Idaho, USA), Inglewood (Maryland, USA), and Kent’s Cavern (Devon, UK) reveal new data that revise the understanding of the nature of these assemblages, and the effect of both natural and cultural bone fracturing agencies.
32

Impact of the adaptive immune system in bone fracture healing

Schlundt, Claudia 29 August 2017 (has links)
Knochengewebe besitzt die einzigartige Fähigkeit sich nach einem Bruch komplett zu regenerieren. Dennoch zeigen 10-15% der Patienten einen gestörten Heilungsverlauf. Das Immunsystem spielt eine entscheidende Rolle in der Frakturheilung. Im Rahmen der hier präsentierten Doktorarbeit wurde der Einfluss der CD4+ regulatorischen T-Zellen (Treg) auf die Knochenheilung untersucht. In einem Maus-Osteotomie-Modell wurde die zeitliche und räumliche Verteilung ausgewählter Immun- und Knochenzellen im osteotomierten Knochen untersucht. Dabei konnte gezeigt werden, dass Immunzellen im gesamten Heilungsverlauf in der Frakturzone zu finden waren und oft eine direkte Kolokalisation mit den Knochenzellen aufwiesen. Diese Ergebnisse zeigen deutlich die starke Interaktion beider Systeme. Ein adaptiver Transfer muriner Treg vor Setzen der Osteotomie diente als immunmodulatorischer Ansatz zur Verbesserung des Frakturheilungsprozesses. Tiere mit einem unerfahrenen Immunsystem (SPF-Haltung) zeigten eine verbesserte Heilung nach Treg-Transfer. Mäuse mit einem erfahrenen Immunsystem (semi-sterile Haltung) zeigten einen kontroversen Heilungserfolg: eine Hälfte der Mäuse heilte signifikant besser und die andere Hälfte signifikant schlechter. Die Schlechtheiler zeigten eine höhere Ratio von CD8+ Effektoren zu Treg im Vergleich zu den Gutheilern. In einer darauffolgenden Proof-of-concept-Studie konnte gezeigt werden, dass eine prä-OP definierte Ratio von CD8+ Effektoren zu Treg mit dem Heilungserfolg nach Osteotomie korrelierte. Im Rahmen dieser Doktorarbeit konnte ein potentiell positiver Einfluss von CD4+ Treg auf den Frakturheilungsprozess bestätigt werden. Dennoch wurde auch der enorme Einfluss des prä-OP Immunstatus auf den Heilungserfolg deutlich. Für die Klinik ist es also im Rahmen einer Immuntherapie umso wichtiger Patienten-basierte Therapieformen zu entwickeln, bei denen der individuelle Immunstatus eines jeden Patienten vor Anwendung der Therapie berücksichtigt wird. / Bone tissue possesses the remarkable capacity to fully regenerate after injury. However, in 10-15% of patients, unsuccessful bone repair is still a present problem. Components of the adaptive immune system play an indispensable role in bone regeneration. The here presented PhD thesis focused on the interaction of CD4+ regulatory T cells (Treg) during fracture healing. In a murine osteotomy model, the spatiotemporal distribution of immune and bone cells was analyzed within the healing bone. Cells of the immune system were detectable throughout the whole healing cascade in the injured area und showed often a direct co-localization with bone cells. These results highlight the interconnectivity of immune and bone cells during regeneration. By adoptive transfer of murine CD4+ Treg prior to osteotomy, an immunomodulatory approach to improve bone healing was conducted. Mice possessing an unexperienced immune system (SPF housing) showed a consistent improved healing outcome after adoptive Treg transfer. However, mice with a more experienced immune system (semi-sterile housing) receiving an adoptive Treg transfer demonstrated a controversial healing outcome: half of the mice showed a significantly improved and the other half a significantly poorer healing outcome. In the mice with a poorer healing outcome, a higher ratio of CD8+ effector T cells and Treg was observed. In a following proof of concept study, a pre-osteotomy defined ratio of CD8+ effector T cells and Treg could predict the healing outcome after adoptive Treg transfer and osteotomy. A potential positive impact of Treg in bone repair was confirmed in this study. However, the tremendous impact of the environment and thereby of the immune status prior to immunomo-dulation was also clearly demonstrated. Hence, for the clinic, it is even more important to develop and to apply patient based immunomodulatory treatment approaches considering the individual immune status of each patient prior to treatment.
33

Asmenų, patyrusių dauginius kūno sužalojimus, kojų ilgųjų kaulų lūžių operacinio gydymo efektyvumas / Efficiency of lower extremity long bone fracture operative treatment on multiply injured patients

Pamerneckas, Algimantas 06 August 2007 (has links)
Disertacijoje nagrinėjama pacientų, dėl didelės energijos bukos traumos patyrusių dauginius kūno sužalojimus, kojų ilgųjų kaulų lūžių gydymo įtaka mirčiai. Ištirtas ir su tarptautiniu standartu palygintas pacientų su dauginiais kūno sužalojimais būklės vertinimas ir gaivinimas ikihospitaliniu laikotarpiu. Įvertintas asmenų, patyrusių dauginius kūno sužalojimus, sužalojimų pobūdis, sunkumas, komplikacijos ir baigtis. Įvertinti dauginių kūno sužalojimų gydymo rezultatai, atsižvelgiant į operacinį ar konservatyvų kojų ilgųjų kaulų lūžių gydymą suvienodintose pagal amžių ir sužalojimo sunkumą pacientų grupėse. Nustatyti veiksniai, turintys ���taką pacientų su dauginiais kūno sužalojimais mirčiai. / Influence of lower extremity long bone fracture treatment of severe polytrauma patients after high energy blunt trauma is evaluated. Pre-hospital initial assessment and management of patients with multiple injuries is estimated and compared with the international standard. The nature, injury severity, complications and the outcome of the patients who suffered multiple injuries are evaluated. The treatment results of multiple injuries taking into account lower extremity long bone fractures operative or conservative treatment in pair matching groups of patients are evaluated. The factors that has impact on mortality of the polytrauma patients are determinated.
34

Traumatisme de l'os temporal : de la caractérisation biomécanique à la régénération du nerf facial / Temporal bone trauma : from the biomechanical characterization to the facial nerve regeneration

Montava, Marion 12 December 2014 (has links)
Les fractures de l'os temporal constituent une pathologie fréquente insuffisamment étudiée sur le plan biomécanique, et mal prise en charge sur le plan thérapeutique. Leur complexité biomécanique et leur polymorphisme clinique ont donc été analysés dans cette étude. Ainsi une base de données prospectives de patients pris en charge pour fractures temporales a été initiée afin d'évaluer les séquelles et leur impact sur la qualité de vie. Une étude expérimentale de traumatismes temporaux a été réalisée afin d'apporter des données dans la caractérisation biomécanique de l'os temporal. En complément, un modèle éléments finis d'os temporal a été developpé, et un traumatisme temporal a été simulé. La régénération du nerf facial traumatisé a été étudiée, et un effet thérapeutique de la vitamine D3 a été recherché par une étude expérimentale animale. Nos résultats montrent qu'une amélioration de la prévention des fractures temporales est nécessaire surtout par adaptation et utilisation des casques dans le cadre de la pratique du vélo. Cette prévention doit se reposer sur la caractérisation biomécanique des traumatismes temporaux par une double approche, expérimentale et numérique. La vitamine D3 augmente significativement la récupération fonctionnelle et la myélinisation dans un modèle animal de traumatisme du nerf facial. Cette étude ouvre la perspective d'essais cliniques. La fréquence des séquelles cochléo-vestibulaires invalidantes après fractures temporales et leur impact sur la qualité de vie montrent la nécessité d'un suivi des patients dans un cadre multidisciplinaire. / Temporal bone fracture is a frequent pathology insufficiently studied on terms of biomechanical, and poorly managed on terms of therapeutic. The biomechanical complexity and the clinical polymorphism of temporal bone trauma were analysed in this study. Our dynamic was to zoom from patient with temporal bone trauma to lesional process of temporal bone fracture. A prospective database of patients with temporal bone fracture was initiated to analyse sequelae and their impact on quality of life. An experimental study of temporal bone trauma was conducted to bring data in biomechanical characterization of temporal bone. In addition, a finite element model of the temporal bone was designed, and a lateral impact was simulated. The regeneration of traumatized facial nerve was studied, and a therapeutic effect of vitamin D3 (cholécalciférol) was evaluated with animal experimental study. Our results showed that an improvement of temporal fracture prevention is necessary by promoting the use of helmets and improvements in helmet design as part of cycling practice. This prevention must base on biomechanical characterization of temporal bone trauma with experimental and numerical approach. Vitamin D3 increases significantly functional recovery and myelination in an animal model of facial nerve trauma. It paves further the way for clinical trials. The frequency of cochleovestibular sequelae after temporal bone fracture and their impact on quality of life demonstrate the importance of, and the need for, on-going follow up with a multidisciplinary management.
35

Ultra-Wideband Imaging System For Medical Applications. Simulation models and Experimental Investigations for Early Breast Cancer & Bone Fracture Detection Using UWB Microwave Sensors

Mirza, Ahmed F. January 2019 (has links)
Near field imaging using microwaves in medical applications is of great current interest for its capability and accuracy in identifying features of interest, in comparison with other known screening tools. Many imaging methods have been developed over the past two decades showing the potential of microwave imaging in medical applications such as early breast cancer detection, analysis of cardiac tissues, soft tissues and bones. Microwave imaging uses non-ionizing ultra wideband (UWB) electromagnetic signals and utilises tissue-dependent dielectric contrast to reconstruct signals and images using radar-based or tomographic imaging techniques. Microwave imaging offers low health risk, low operational cost, ease of use and user-friendliness. This study documents microwave imaging experiments for early breast cancer detection and bone fracture detection using radar approach. An actively tuned UWB patch antenna and a UWB Vivaldi antenna are designed and utilised as sensing elements in the aforementioned applications. Both UWB antennas were developed over a range of frequency spectrum, and then characteristics were tested against their ability for microwave imaging applications by reconstructing the 3D Inversion Algorithm. An experiment was conducted using patch antenna to test the detection of variable sizes of cancer tissues based on a simple phantom consisting of a plastic container with a low dielectric material emulating fatty tissue and high dielectric constant object emulating a tumour, is scanned between 4 to 8 GHz with the patch antenna. A 2-D image of the tumour is constructed using the reflected signal response to visualize the location and size of the tumour. A Vivaldi antenna is designed covering 3.1 to 10.6 GHz. The antenna is tested via simulation for detecting bone fractures of various sizes and 2-D images are generated using reflected pulses to show the size of fracture. The Vivaldi antenna is optimised for early breast cancer detection and detailed simulated study is carried out using different breast phantoms and tumour sizes. Simulations are backed with the experimental investigation with the test setup used for patch antenna. Generated images for simulations and experimental investigation show good agreement, and show the presence of tumour with good location accuracy. Measurements indicate that both prototype microwave sensors are good candidates for tested imaging applications.
36

Fracturation sur os frais ou sur os sec de la voûte crânienne : approche méthodologique et application archéologique / Skull vault fracturing on fresh bone or dry bone : methodological approach and archaeological application

Jordana, Fabienne 13 January 2010 (has links)
Etablir le diagnostic différentiel entre des fractures réalisées sur os frais de celles produites sur os sec permet, quelle que soit la période chronologique considérée, une approche interprétative relative à l’attitude comportementale humaine qu’ils s’agissent des relations au sein d’un groupe ou face à une autre population, ainsi que les gestes réservés aux morts. Ainsi peuvent être envisagés le cannibalisme, des comportements de violence, ou des pratiques funéraires originales. Si certaines méthodes analytiques existaient pour le squelette infracrânien, aucun référentiel permettant de différentier les fractures sur os frais (intentionnelles ou non) des cassures sur os secs n’est actuellement disponible pour le squelette crânien. Notre objectif de recherche s’est donc concentré sur un essai de détermination des critères statistiquement valides de distinction du moment de fracturation sur os fossiles. Une partie importante de ce travail est consacrée aux études expérimentales menées pour tenter de distinguer une différence de comportement mécanique entre une fracture réalisée sur os frais de celle réalisée sur os sec (essais mécaniques, rugosimétrie confocale, microtomographie ou numérisation des pièces osseuses). Puis, les critères de la médecine légale sont discutés à partir d’échantillons osseux provenant de séries archéologiques différentes d’un point de vue chronologique et géographique et relevant de problématiques différentes. Il ressort de ce travail que très peu de critères pris individuellement sont suffisamment pertinents pour différencier fracturation sur os frais et fracturation sur os sec (décollement de la lame corticale). Ils doivent toujours être discutés à l’échelle d’une série archéologique et non sur un échantillon isolé, seul ou sorti de son contexte. Dans le meilleur des cas, ils nous permettent de proposer des hypothèses (cannibalisme, pression des sédiments…) qui devront être corroborées en fonction du contexte archéologique et anthropologique par une analyse interdisciplinaire. / Establishing a differential diagnosis between fresh bone fractures and dry bone fractures allows, whatever the chronological period considered, an interpretative approach relating to the human behaviours within a group or another population, as well as the deaths gestures. Thus, cannibalism, violent behaviours, or original funerary practices can be considered. If some analytical methods existed for the infracranial skeleton, no references allowing for the differentiation between fresh bone fractures (intentional or not) and dry bone breaks were available for the cranial skeleton. Thus, our research objective concentrated on a determination trial of statistically valid criteria that distinguished the fracturing moment on fossil bones. An important part of our work concerned experimental studies undertaken to distinguish a mechanical behavioural difference between fresh bone fractures and dry bone fractures (mechanical tests, rugosimetry, microtomography, or bone pieces digitalization). Forensic medicine criteria was also discussed with osseous samples coming from different archeological series that were taken from chronological and geographical points of view and used to represent each different problem. It appears that there exist very few criteria taken individually that are sufficiently relevant to differentiate fracturing on fresh bone and fracturing on dry bone (delamination). They must always be discussed on an archeological series scale and not on an isolated sample, either alone or taken out of context. In the best of the cases, they enable us to propose assumptions (cannibalism, pressure of the sediments…) that will have to be corroborated according to the archaeological and anthropological context by an interdisciplinary analysis.
37

TARGETED DELIVERY OF BONE ANABOLICS TO BONE FRACTURES FOR ACCELERATED HEALING

Jeffery J H Nielsen (8787002) 21 June 2022 (has links)
<div>Delayed fracture healing is a major health issue involved with aging. Therefore, strategies to improve the pace of repair and prevent non-union are needed in order to improve patient outcomes and lower healthcare costs. In order to accelerate bone fracture healing noninvasively, we sought to develop a drug delivery system that could safely and effectively be used to deliver therapeutics to the site of a bone fracture. We elected to pursue the promising strategy of using small-molecule drug conjugates that deliver therapeutics to bone in an attempt to increase the efficacy and safety of drugs for treating bone-related diseases.</div><div>This strategy also opened the door for new methods of administering drugs. Traditionally, administering bone anabolic agents to treat bone fractures has relied entirely on local surgical application. However, because it is so invasive, this method’s use and development has been limited. By conjugating bone anabolic agents to bone-homing molecules, bone fracture treatment can be performed through minimally invasive subcutaneous administration. The exposure of raw hydroxyapatite that occurs with a bone fracture allows these high-affinity molecules to chelate the calcium component of hydroxyapatite and localize primarily to the fracture site.</div><div>Many bone-homing molecules (such as bisphosphonates and tetracycline targeting) have been developed to treat osteoporosis. However, many of these molecules have toxicity associated with them. We have found that short oligopeptides of acidic amino acids can localize to bone fractures with high selectivity and with very low toxicity compared to bisphosphonates and tetracyclines.</div><div>We have also demonstrated that these molecules can be used to target peptides of all chemical classes: hydrophobic, neutral, cationic, anionic, short, and long. This ability is particularly useful because many bone anabolics are peptidic in nature. We have found that acidic oligopeptides have better persistence at the site of the fracture than bisphosphonate-targeted therapeutics. This method allows for a systemic administration of bone anabolics to treat bone fractures, which it achieves by accumulating the bone anabolic at the fracture site. It also opens the door for a new way of treating the prevalent afflictions of broken bones and the deaths associated with them.</div><div>We further developed this technology by using it to deliver anabolic peptides derived from growth factors, angiogenic agents, neuropeptides, and extracellular matrix fragments. We found several promising therapeutics that accelerated the healing of bone fractures by improving the mineralization of the callus and improving the overall strength. We optimized the performance of these molecules by improving their stability, targeting ligands, linkers, dose, and dosing frequency.</div><div>We also found that these therapeutics could be used to accelerate bone fracture repair even in the presence of severe comorbidities (such as diabetes and osteoporosis) that typically slow the repair process. We found that, unlike the currently approved therapeutic for fracture healing (BMP2), our therapeutics improved functionality and reduced pain in addition to strengthening the bone. These optimized targeted bone anabolics were not only effective at healing bone fractures but they also demonstrated that they could be used to speed up spinal fusion. Additionally, we demonstrated that acidic oligopeptides have potential to be used to treat other bone diseases with damaged bone.</div><div>With these targeted therapeutics, we no longer have to limit bone fracture healing to casts or invasive surgeries. Rather, we can apply these promising therapeutics that can be administered non-invasively to augment existing orthopedic practices. As these therapeutics move into clinical development, we anticipate that they will be able to reduce the immobilization time that is the source of so many of the deadly complications associated with bone fracture healing, particularly in the elderly.</div>

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