Intensity modulated radiation therapy and arc therapy: validation and evolution as applied to tumours of the head and neck, abdominal and pelvic regions

Intensiteitsgemoduleerde radiotherapie (IMRT) laat een betere controle over de dosisdistributie (DD) toe dan meer conventionele bestralingstechnieken. Zo is het met IMRT mogelijk om concave DDs te bereiken en om de risico-organen conformeel uit te sparen. IMRT werd in het UZG klinisch toegepast voor een hele waaier van tumorlocalisaties. De toepassing van IMRT voor de bestraling van hoofd- en halstumoren (HHT) vormt het onderwerp van het eerste deel van deze thesis. De planningsstrategie voor herbestralingen en bestraling van HHT, uitgaande van de keel en de mondholte wordt beschreven, evenals de eerste klinische resultaten hiervan. IMRT voor tumoren van de neus(bij)holten leidt tot minstens even goede lokale controle (LC) en overleving als conventionele bestralingstechnieken, en dit zonder stralingsgeïnduceerde blindheid. IMRT leidt dus tot een gunstiger toxiciteitprofiel maar heeft nog geen bewijs kunnen leveren van een gunstig effect op LC of overleving. De meeste hervallen van HHT worden gezien in het gebied dat tot een hoge dosis bestraald werd, wat erop wijst dat deze “hoge dosis” niet volstaat om alle clonogene tumorcellen uit te schakelen. We startten een studie op, om de mogelijkheid van dosisescalatie op geleide van biologische beeldvorming uit te testen. Naast de toepassing en klinische validatie van IMRT bestond het werk in het kader van deze thesis ook uit de ontwikkeling en het klinisch opstarten van intensiteitgemoduleerde arc therapie (IMAT). IMAT is een rotationele vorm van IMRT (d.w.z. de gantry draait rond tijdens de bestraling), waarbij de modulatie van de intensiteit bereikt wordt door overlappende arcs. IMAT heeft enkele duidelijke voordelen ten opzichte van IMRT in bepaalde situaties. Als het doelvolume concaaf rond een risico-orgaan ligt met een grote diameter, biedt IMAT eigenlijk een oneindig aantal bundelrichtingen aan. Een planningsstrategie voor IMAT werd ontwikkeld, en type-oplossingen voor totaal abdominale bestraling en rectumbestraling werden onderzocht en klinisch toegepast

Investigation of 3DP technology for fabrication of surgical simulation phantoms

The demand for affordable and realistic phantoms for training, in particular for functional endoscopic sinus surgery (FESS), has continuously increased in recent years. Conventional training methods, such as current physical models, virtual simulators and cadavers may have restrictions, including fidelity, accessibility, cost and ethics. In this investigation, the potential of three-dimensional printing for the manufacture of biologically representative simulation materials for surgery training phantoms has been investigated. A characterisation of sinus anatomical elements was performed through CT and micro-CT scanning of a cadaveric sinus portion. In particular, the relevant constituent tissues of each sinus region have been determined. Secondly, feedback force values experienced during surgical cutting have been quantified with an actual surgical instrument, specifically modified for this purpose. Force values from multiple post-mortem subjects and different areas of the paranasal sinuses have been gathered and used as a benchmark for the optimisation of 3D-printing materials. The research has explored the wide range of properties achievable in 3DP through post-processing methods and variation of printing parameters. For this latter element, a machine-vision system has been developed to monitor the 3DP in real time. The combination of different infiltrants allowed the reproduction of force values comparable to those registered from cadaveric human tissue. The internal characteristics of 3D printed samples were shown to influence their fracture behaviour under resection. Realistic appearance under endoscopic conditions has also been confirmed. The utilisation of some of the research has also been demonstrated in another medical (non-surgical) training application. This investigation highlights a number of capabilities, and also limitations, of 3DP for the manufacturing of representative materials for application in surgical training phantoms

Craniofacial growth and development in modern humans and Neanderthals

This thesis assesses craniofacial growth, development and the dynamics of developmental interactions among cranial regions in modern humans and Neanderthals. To these ends, virtual segmentation, landmarking and Geometric Morphometrics (GM) are applied to an ontogenetic series of the whole crania of 68 H. sapiens and 12 H. neanderthalensis. First, the ontogenetic shape and form changes in the cranial vault, base and face are explored, and the locations and magnitudes of these changes are discussed. Secondly, allometric scaling is tested for differences among different age classes in the three regions of the cranium. In addition, the degree of covariation among these and how it changes over time is investigated.The study then focuses on interactions among facial regions. First, similar analyses as those used in the study of the cranium are applied to compare growth, development and covariation among parts of the face in different age classes. Additionally, a sample of 227 modern humans from 0 to 6 years of age is analysed using path analysis, to investigate the cascade of interactions and relative contributions of soft tissue and skeletal elements to the overall growth and development of the face. Last, the facial morphology of H. sapiens is compared to that of H. neanderthalensis and their ontogenetic trajectories are tested for divergence. Novel method registration-free colour maps are used to visualise regional changes during growth and development and to compare the morphologies of the two species. Covariation among facial elements is also compared to assess potential differences in developmental interactions. In modern humans, the results show that allometry and covariation change significantly among age classes and between cranial regions during ontogeny and that covariation is stronger in younger subadults than in older subadults and adults. Among modern humans, significantly divergent trajectories are observed between age classes during ontogeny in all three cranial regions. In the modern human face, allometric scaling also differs among age stages in each region. Interestingly, covariation among facial regions becomes progressively non-significant with time, with the exception of those including the nose and maxilla. Path analysis in modern humans shows a large contribution of the proxy used for nasal septum to the overall facial development. Soft tissues contribute only locally to the development of some skeletal elements of the face. Major aspects of the differences between adult modern humans and Neanderthals are already present in the youngest individuals. However, additional differences arise through differences in the degree of change in facial size and significantly divergent allometric trajectories. Analyses of covariation among Neanderthal facial regions suffer from small sample size but, where significant, suggest that the interactions among cranial components are similar to those in modern humans, with some differences

Glosarium Matematika

273 p.; 24 cm

Automatic risk evaluation in elderly patients based on Autonomic Nervous System assessment

Dysfunction of Autonomic Nervous System (ANS) is a typical feature of chronic heart failure and other cardiovascular disease. As a simple non-invasive technology, heart rate variability (HRV) analysis provides reliable information on autonomic modulation of heart rate. The aim of this thesis was to research and develop automatic methods based on ANS assessment for evaluation of risk in cardiac patients. Several features selection and machine learning algorithms have been combined to achieve the goals. Automatic assessment of disease severity in Congestive Heart Failure (CHF) patients: a completely automatic method, based on long-term HRV was proposed in order to automatically assess the severity of CHF, achieving a sensitivity rate of 93% and a specificity rate of 64% in discriminating severe versus mild patients. Automatic identification of hypertensive patients at high risk of vascular events: a completely automatic system was proposed in order to identify hypertensive patients at higher risk to develop vascular events in the 12 months following the electrocardiographic recordings, achieving a sensitivity rate of 71% and a specificity rate of 86% in identifying high-risk subjects among hypertensive patients. Automatic identification of hypertensive patients with history of fall: it was explored whether an automatic identification of fallers among hypertensive patients based on HRV was feasible. The results obtained in this thesis could have implications both in clinical practice and in clinical research. The system has been designed and developed in order to be clinically feasible. Moreover, since 5-minute ECG recording is inexpensive, easy to assess, and non-invasive, future research will focus on the clinical applicability of the system as a screening tool in non-specialized ambulatories, in order to identify high-risk patients to be shortlisted for more complex investigations

Recent Advances in Forensic Anthropological Methods and Research

Forensic anthropology, while still relatively in its infancy compared to other forensic science disciplines, adopts a wide array of methods from many disciplines for human skeletal identification in medico-legal and humanitarian contexts. The human skeleton is a dynamic tissue that can withstand the ravages of time given the right environment and may be the only remaining evidence left in a forensic case whether a week or decades old. Improved understanding of the intrinsic and extrinsic factors that modulate skeletal tissues allows researchers and practitioners to improve the accuracy and precision of identification methods ranging from establishing a biological profile such as estimating age-at-death, and population affinity, estimating time-since-death, using isotopes for geolocation of unidentified decedents, radiology for personal identification, histology to assess a live birth, to assessing traumatic injuries and so much more

From Dynamics to Structure of Complex Networks: Exploiting Heterogeneity in the Sakaguchi-Kuramoto Model

[eng] Most of the real-world complex systems are best described as complex networks and can be mathematically described as oscillatory systems, coupled with the neighbours through the connections of the network. The flashing of fireflies, the neuronal brain signals or the energy flow through the power grid are some examples. Yoshiki Kuramoto came up with a tractable mathematical model that could capture the phenomenology of collective synchronization by suggesting that oscillators were coupled by a sinusoidal function of their phase differences. Later, Yoshiki Kuramoto together with Hidetsugu Sakaguchi presented a generalization of the previous limit-cycle set of oscillators Kuramoto’s model which incorporated a constant phase lag between oscillators. Subsequent studies of the model included the network structure within the model together with the global shift. For a wide range of the phase lag values, the system becomes synchronized to a resulting frequency, i.e., the dynamics reaches a stationary state. In the original work of Kuramoto and Sakaguchi and in most of the consequent later studies, a uniform distribution of phase lag parameters is customarily assumed. However, the intrinsic properties of nodes – that assuredly represent the constituents of real systems – do not need be identical but distributed non-homogeneously among the population. This thesis contributes to the understanding of the Kuramoto-Sakaguchi model with a generalization for nonhomogeneous phase lag parameter distribution. Considering different scenarios concerning the distribution of the frustration parameter among the oscillators represents a major step towards the extension of the original model and provides significant novel insights into the structure and function of the considered network. The first setting that the present thesis considers consists in perturbing the stationary state of the system by introducing a non-zero phase lag shift into the dynamics of a single node. The aim of this work is to sort the nodes by their potential effect on the whole network when a change on their individual dynamics spreads over the entire oscillatory system by disrupting the otherwise synchronized state. In particular, we define functionability, a novel centrality measure that addresses the question of which are the nodes that, when individually perturbed, are best able to move the system away from the fully synchronized state. This issue may be relevant for the identification of critical nodes that are either beneficial – by enabling access to a broader spectrum of states – or harmful – by destroying the overall synchronization. The second scenario that the present thesis addresses considers a more general configuration in which the phase lag parameter is an intrinsic property of each node, not necessarily zero, and hence exploring the potential heterogeneity of the frustration among oscillators. We obtain the analytical solution of frustration parameters so as to achieve any phase configuration, by linearizing the most general model. We also address the fact that the question ’among all the possible solutions, which is the one that makes the system achieve a particular phase configuration with the minimum required cost?’ is of particular relevance when we consider the plausible real nature of the system. Finally, the homogenous distribution of phase lag parameters is revisited in the last scenario. As studied in the literature, a certain degree of symmetry is an attribute of real-world networks. Nevertheless, beyond structural or topological symmetry, one should consider the fact that real- world networks are exposed to fluctuations or errors, as well as mistaken insertions or removals. In the present thesis, we provide an alternative notion to approximate symmetries, which we call ‘Quasi-Symmetries’ and are defined such that they remain free to impose any invariance of a particular network property and are obtained from the stationary state of the Kuramoto-Sakaguchi model with a homogeneous phase lag distribution. A first contribution is exploring the distributions of structural similarity among all pairs of nodes. Secondly, we define the ‘dual network’, a weighted network –and its corresponding binarized counterpart– that effectively encloses all the information of quasi-symmetries in the original one.[cat] La major part dels sistemes complexos presents en la natura i la societat es poden descriure com a xarxes complexes. Molts d’aquests sistemes es poden modelitzar matemàticament com un sistema oscil·latori, on les unitats queden acoblades amb els components veïns a través de les connexions de la xarxa. Yoshiki Kuramoto i Hidetsugu Sakaguchi van presentar la generalització del ben conegut model d’oscil·ladors de Kuramoto, on s’incorporava un terme de desfasament entre parelles d’oscil·ladors. Aquesta tesi contribueix en la comprensió d’aquest model, tot considerant una distribució no homogènia d’aquest paràmetre de desfasament o frustració. S’han considerat tres escenaris diferents, tots ells donant lloc a resultats que permeten una millor descripció de l’estructura i funció de la xarxa que s’està considerant. Una primera configuració consisteix en pertorbar l’estat estacionari tot introduint un desfasament en la dinàmica d’un node de manera aïllada. Seguidament, definim la funcionabilitat, una mesura de centralitat única que respon a la pregunta de, quins nodes, quan són pertorbats individualment, són més capaços d’allunyar el sistema de l’estat sincronitzat. Aquest fet podria suposar un comportament beneficiós o perjudicial per sistemes reals. El segon escenari considera la configuració més flexible, explorant la potencial heterogeneïtat dels paràmetres de frustració dels diferents nodes. Obtenim la solució analítica d’aquesta distribució per tal d’assolir qualsevol configuració de les fases dels oscil·ladors, a través de la linearització del model. També contestem a la pregunta: “de totes les possibles solucions, quina és la que implica un menor cost per tal d’assolir una configuració en particular?”. Finalment, en l’últim escenari, proporcionem una definició alternativa al concepte de simetria aproximada d’una xarxa, i que anomenem “Quasi simetries”. Aquestes són definides sense imposar invariàncies en les propietats del sistema, sinó que s’obtenen de l’estat estacionari del model de Kuramoto-Sakaguchi model, tot considerant una distribució homogènia dels paràmetres de frustració