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See detailThe picturesque Ardennian valleys: Plio-Quaternary incision of the drainage system in the uplifting Ardenne
Rixhon, Gilles; Demoulin, Alain ULiege

in Demoulin, Alain (Ed.) Landscapes and landforms of Belgium and Luxembourg (2018)

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See detailThe periglacial ramparted depressions of the Hautes Fagnes Plateau: traces of Late Weichselian lithalsas
Demoulin, Alain ULiege; Houbrechts, Geoffrey ULiege; Juvigné, Etienne ULiege

in Demoulin, Alain (Ed.) Landscapes and landforms of Belgium and Luxembourg (2018)

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See detailParents d'un enfant en rémission de cancer: Prédicteurs psychologiques et cognitifs de l'intolérance à l'incertitude dans le maintien des inquiétudes et dans l'orientation de l'attention sélective
Vander Haegen, Marie ULiege

Doctoral thesis (2017)

In spite of core medical advances realized these last years, the childhood cancer remains a distressing experience for the child and their parents. The cancer history is rarely linear and takes place into ... [more ▼]

In spite of core medical advances realized these last years, the childhood cancer remains a distressing experience for the child and their parents. The cancer history is rarely linear and takes place into a space and a particular time when marks are shaken. The stake in paediatric oncology is double: that the child is cured without side effects and that the child and parents cross this experience without psychological destabilization. When the cancer survivorship is diagnosed, new challenges are expecting for the child and parents. Indeed, the childhood cancer survivorship is considered as integrated into the field of chronic diseases where the factor of uncertainty coexists and requires continuous adjustments of the child and parents. Therefore, it is a period of progressive rehabilitation where the stake is double: control the relapse and treatments’ late effects (or aftereffects) of the child and allow the child and parents, “to pursue their life the most normally possible”. The survivorship experience is thus intense transforming deeply “the psyche” of the child and parents. Since a few years, empirical studies examine the child adjustment and parents in the course of treatments. These reveal namely some adaptation difficulties, anxious and depressive symptoms. However, the social/family support and the problem-focused coping seem positively moderate the distress intensity. Studies investigated the cancer survivorship were mainly centred on the child and showed its effects on the child’s psychological adjustment (e.g. anxiety, depression). Nevertheless, the distress intensity could be positively influenced in particular by social and family support factors. The thorough examination of the literature observes that studies rarely include the parent and that no study has associated the factor of uncertainty with the vulnerability factor of intolerance of uncertainty. The originality of this research lives in the interest centred on the concept of intolerance of uncertainty [IU] and its effects on the psychological and cognitive adjustment among parents of a child cancer survivor. This quasi-experimental, quantitative, longitudinal research combines standardized questionnaires (IUS, NPOQ, CAQ, Mini-CERTS, HADS, and WW-II), questionnaires created for the needs of the study (sociodemographic, QIPS-R15, OncoMed and SomaOnco) and two neuropsychological tasks (classic Stroop and emotional Stroop). The sample consists of 61 parents (45 mothers and 16 fathers) of a child cancer survivor (from 4 to 6 years of survivorship without relapse and with mainly a neoadjuvant chemotherapy during treatments). Three months later, parents returned to the laboratory and completed the same questionnaires and performed Stroop tasks (with the exception of words which are modified). The time was decided with medical teams. It seemed relevant to retest parents when the medical assessment of the child was completed in order to observe if the distress decreased. Besides, this time was sufficient to avoid memory biases. The first aim of this research is the study of parental distress. The proposed hypothesis is the existence of anxious, depressive, somatic symptoms and worries. Results showed that 70 % of parents had anxious symptoms (HADS), 39 % presented depressive symptoms (HADS), 14 % suffered from somatic symptoms (SomaOnco) and 70 % had worries (QIPS-R15). Results from moderation analyses indicated no main effect of gender, remission time, and couple on distress criteria (except the interaction of these three factors for worries). These results demonstrated the existence of a significant distress within the sample but also the presence of additional factors which may influence the parental adjustment. The second aim is the examination of IU and its maintaining factors (i.e. positive beliefs about worry, cognitive avoidance, negative attitude towards problems and repetitive thinking (ruminations)). The advanced hypothesis is the causal track between IU and its maintaining factors. Results of IUS questionnaire demonstrated on average that parents had a low tolerance of uncertainty (64 % of the sample) and that 60 % of the sample were located in a moderated to severe profile of generalized anxiety disorder (GAD). Concerning IU’s maintaining factors, results of NPOQ, CAQ, WW-II and Mini-CERTS questionnaires highlighted the existence of positive beliefs towards worry (WW-II: problem solving and positive trait of personality) and cognitive avoidance (CAQ: distraction and thought suppression). Results of regressions bear out the predictor status of IU for the development of its maintaining factors. Nevertheless, protective factors arose from analyses, particularly an effective problem orientation and the use of concrete experiential thinking mode (CET; Mini-CERTS), which could protect them from a deterioration of the mood (e.g. depression). These results indicated the negative influence of IU on the psychological adjustment, the protective effect of a positive attitude orientation and the use of CET among parents. The third aim concerns the study of cognitive processes in terms of orientation of selective attention and cognitive inhibition. The proposed hypothesis is the orientation of selective attention towards threat into the IU context. Results seem to indicate a longer latency for negative and coloured words during Stroop tasks. The within-group regression and mediation results reveal the mediating effect of IU between the orientation of selective attention towards threat and distress components (i.e. anxious, depressive, somatic symptoms and worries). Moreover, depressive symptoms contribute to predicting the coloured word latency (cognitive inhibition process). These results seem to demonstrate the negative influence of the IU on the orientation of selective attention and depressive symptoms for cognitive inhibition. Lastly, the fourth aim is the analysis of IU stability and its maintaining factors over time. The proposed hypothesis is the stability of IU and its maintaining factors because IU is considered as a feature of the personality. At the second assessment (n=51/N=61), three significant differences were observed. The first difference concerns a decrease for anxiety symptoms with nevertheless a score being located in the pathological border. The second difference relates to a decrease for the cognitive avoidance with a score situated in the superior border of the standards. Lastly, an increase for somatic symptoms level was observed at the second assessment. Concerning IU, results indicate no significant change. Parents who presented a high level of IU at the first assessment kept it at the second assessment. This observation is also true for parents who had a low level of IU. These results supported the hypothesis of IU stability and its maintaining factors over time. Overall, results emphasize the implication of IU in the psychological distress among parents and its effect on cognitive processes of the orientation of selective attention towards threatening words (negative words). This research brings out the necessity to identify parents who are at risk for IU (and its maintaining factors) at an early stage of the cancer management in order to avoid excessive worries and the use of dysfunctional strategies over time. Furthermore, this research allows future clinical avenues for the development of follow-up tools in paediatric oncology, and recommends the parents’ psychological adjustment follow-up in close collaboration with medical teams. Implications of this research are discussed into the "general discussion" part of the thesis. [less ▲]

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See detailLa spatialité de la gouvernance des régions urbaines intermédiaires en Europe
Breuer, Christophe ULiege

Doctoral thesis (2017)

The governance of urban regions is a central research topic of urban sciences, and a major challenge for urban actors. In this research, we contribute to the analysis of governance processes by studying ... [more ▼]

The governance of urban regions is a central research topic of urban sciences, and a major challenge for urban actors. In this research, we contribute to the analysis of governance processes by studying the transformation of its spatiality in intermediate European urban regions. Our research postulates the intrinsically spatial nature of urban governance, and is based on three hypotheses: (1) the territorial characteristics of urban regions relate to local politico-administrative fragmentation, (2) the characteristics of politico-administrative fragmentation relate to the construction of a governance scale for urban regions, and (3) governance structures at the level of urban regions relate to territorial characteristics. In order to test these hypotheses, we conducted a research in three complementary parts. The first part is devolted to the state of the art on governance, territorial rescaling and institutional change. The second part analyses quantitatively the politico-administrative fragmentation of 123 intermediate European urban regions, and its links with territorial indicators. The third part analyses qualitatively the processes of transformation of spatial governance in the urban regions of Saint-Étienne (France), Metz (France), Sheffield (United Kingdom) and Liège (Belgium). This complementary research confirms the existence of links between the different aspects of spatiality in the governance of intermediate urban regions in Europe, and concludes that the recomposition processes are intrinsically spatial, territorial and multiscalar. [less ▲]

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See detailContribution à l'enseignement de la traduction au Niger : le renforcement du français langue cible dans la formation des futurs traducteurs.
Amadou Gazali, Alkassoum ULiege

Doctoral thesis (2017)

Teaching translation is a very old activity. While it often used to be performed in the context of language learning, it has changed fundamentally over the past few decades, i.e. since the ... [more ▼]

Teaching translation is a very old activity. While it often used to be performed in the context of language learning, it has changed fundamentally over the past few decades, i.e. since the institutionalization of translation as an autonomous scientific discipline with specific objects and methods. Now, it covers not only linguistics but also other fields including the operating aspect of knowledge and has undergone more methodological transformations over half a century than it did since the Middle-Age, or even since Cicero. In Niger, however, the situation has not yet changed. Teaching translation has remained part of language learning. In this context, the learners’ translation competence is directly associated to linguistic competence. But the latter is far from satisfactory for quite a lot of Niger students, whatever their field of study. In fact, several studies confirmed the poor performance of Niger students in relation to mastery of their working language, French. Indeed, despite its exclusive status as the language of administration and education, French is not mastered enough to be used as a basis for the learning of another language and even less for translation purposes. This is why this study is based on the hypothesis according to which improving the target language in translator training would largely contribute to upgrade their translation competence. It therefore aims to enhance Niger prospective translators’ translation competence by improving their knowledge of the working language. To this end, an experimental research method is used that relies on a classical type scheme involving pre- and post-experimentation observations. An experimental treatment is applied between the two observation stages, which consists of language remedial courses. The verification of the hypothesis depends on operational aspects of the study as well as on the results yielded by the interpreting of collected data. [less ▲]

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See detailDiscussant The institutional functioning of the European Central Bank
Van Cleynenbreugel, Pieter ULiege

Scientific conference (2017, December 12)

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See detailTowards a system of concepts for Family Medicine. Multilingual indexing in General Practice/ Family Medicine in the era of Semantic Web
Jamoulle, Marc ULiege

Doctoral thesis (2017)

UNIVERSITY OF LIÈGE, BELGIUM Executive Summary Faculty of Medicine Département Universitaire de Médecine Générale. Unité de recherche Soins Primaires et Santé Doctor in biomedical sciences Towards a ... [more ▼]

UNIVERSITY OF LIÈGE, BELGIUM Executive Summary Faculty of Medicine Département Universitaire de Médecine Générale. Unité de recherche Soins Primaires et Santé Doctor in biomedical sciences Towards a system of concepts for Family Medicine. Multilingual indexing in General Practice/ Family Medicine in the era of SemanticWeb by Dr. Marc JAMOULLE Introduction This thesis is about giving visibility to the often overlooked work of family physicians and consequently, is about grey literature in General Practice and Family Medicine (GP/FM). It often seems that conference organizers do not think of GP/FM as a knowledge-producing discipline that deserves active dissemination. A conference is organized, but not much is done with the knowledge shared at these meetings. In turn, the knowledge cannot be reused or reapplied. This these is also about indexing. To find knowledge back, indexing is mandatory. We must prepare tools that will automatically index the thousands of abstracts that family doctors produce each year in various languages. And finally this work is about semantics1. It is an introduction to health terminologies, ontologies, semantic data, and linked open data. All are expressions of the next step: Semantic Web for health care data. Concepts, units of thought expressed by terms, will be our target and must have the ability to be expressed in multiple languages. In turn, three areas of knowledge are at stake in this study: (i) Family Medicine as a pillar of primary health care, (ii) computational linguistics, and (iii) health information systems. Aim • To identify knowledge produced by General practitioners (GPs) by improving annotation of grey literature in Primary Health Care • To propose an experimental indexing system, acting as draft for a standardized table of content of GP/GM • To improve the searchability of repositories for grey literature in GP/GM. 1For specific terms, see the Glossary page 257 x Methods The first step aimed to design the taxonomy by identifying relevant concepts in a compiled corpus of GP/FM texts. We have studied the concepts identified in nearly two thousand communications of GPs during conferences. The relevant concepts belong to the fields that are focusing on GP/FM activities (e.g. teaching, ethics, management or environmental hazard issues). The second step was the development of an on-line, multilingual, terminological resource for each category of the resulting taxonomy, named Q-Codes. We have designed this terminology in the form of a lightweight ontology, accessible on-line for readers and ready for use by computers of the semantic web. It is also fit for the Linked Open Data universe. Results We propose 182 Q-Codes in an on-line multilingual database (10 languages) (www.hetop.eu/Q) acting each as a filter for Medline. Q-Codes are also available under the form of Unique Resource Identifiers (URIs) and are exportable in Web Ontology Language (OWL). The International Classification of Primary Care (ICPC) is linked to Q-Codes in order to form the Core Content Classification in General Practice/Family Medicine (3CGP). So far, 3CGP is in use by humans in pedagogy, in bibliographic studies, in indexing congresses, master theses and other forms of grey literature in GP/FM. Use by computers is experimented in automatic classifiers, annotators and natural language processing. Discussion To the best of our knowledge, this is the first attempt to expand the ICPC coding system with an extension for family physician contextual issues, thus covering non-clinical content of practice. It remains to be proven that our proposed terminology will help in dealing with more complex systems, such as MeSH, to support information storage and retrieval activities. However, this exercise is proposed as a first step in the creation of an ontology of GP/FM and as an opening to the complex world of Semantic Web technologies. Conclusion We expect that the creation of this terminological resource for indexing abstracts and for facilitating Medline searches for general practitioners, researchers and students in medicine will reduce loss of knowledge in the domain of GP/FM. In addition, through better indexing of the grey literature (congress abstracts, master’s and doctoral theses), we hope to enhance the accessibility of research results and give visibility to the invisible work of family physicians. [less ▲]

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See detailThe LBTI Fizeau imager – II. Sensitivity of the PSF and the MTF to adaptive optics errors and to piston errors
Patru, F.; Esposito, S.; Puglisi, A. et al

in Monthly Notices of the Royal Astronomical Society (2017), 472

We show numerical simulations with monochromatic light in the visible for the LBTI Fizeau imager, including opto-dynamical aberrations due here to adaptive optics (AO) errors and to differential piston ... [more ▼]

We show numerical simulations with monochromatic light in the visible for the LBTI Fizeau imager, including opto-dynamical aberrations due here to adaptive optics (AO) errors and to differential piston fluctuations, while other errors have been neglected. The achievable Strehl by the LBTI using two AO is close to the Strehl provided by a single standalone AO system, as long as other differential wavefront errors are mitigated. The LBTI Fizeau imager is primarily limited by the AO performance and by the differential piston/tip–tilt errors. Snapshots retain high-angular resolution and high-contrast imaging information by freezing the fringes against piston errors. Several merit functions have been critically evaluated in order to characterize point spread functions and the modulation transfer functions for high-contrast imaging applications. The LBTI Fizeau mode can provide an image quality suitable for standard science cases (i.e. a Strehl above 70 per cent) by performing both at a time: an AO correction better than ≈λ/18 RMS for both short and long exposures, and a piston correction better than ≈λ/8 RMS for long exposures or simply below the coherence length for short exposures. Such results, which can be applied to any observing wavelength, suggest that AO and piston control at the LBTI would already improve the contrast at near- and mid-infrared wavelengths. Therefore, the LBTI Fizeau imager can be used for high-contrast imaging, providing a high-Strehl regime (by both AO systems), a cophasing mode (by a fringe tracker) and a burst mode (by a fast camera) to record fringed speckles in short exposures. [less ▲]

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See detailSpecial issue: Twelfth Workshop on Models and Algorithms for Planning and Scheduling Problems (MAPSP 2015)
Crama, Yves ULiege; Goossens, Dries; Leus, Roel et al

in Journal of Scheduling (2017), 20(6),

This special issue of the Journal of Scheduling contains ten papers presented at the Twelfth Workshop on Models and Algorithms for Planning and Scheduling Problems (MAPSP 2015), held from June 8 to June ... [more ▼]

This special issue of the Journal of Scheduling contains ten papers presented at the Twelfth Workshop on Models and Algorithms for Planning and Scheduling Problems (MAPSP 2015), held from June 8 to June 12, 2015, in La Roche-en-Ardenne, Belgium. [less ▲]

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See detailTwo-dimensional speckle tracking echocardiography in calves: feasibility and repeatability study
Lecoq, Laureline ULiege; Moula, Nassim ULiege; Amory, Hélène ULiege et al

in Journal of Veterinary Cardiology : The Official Journal of the European Society of Veterinary Cardiology (2017)

Objectives: To assess the feasibility and repeatability of two-dimensional speckle tracking echocardiography for the evaluation of left ventricular function in healthy calves. Animals: 12 Holstein calves ... [more ▼]

Objectives: To assess the feasibility and repeatability of two-dimensional speckle tracking echocardiography for the evaluation of left ventricular function in healthy calves. Animals: 12 Holstein calves, 62 ± 11.6 days old; 75.25 ± 5.4 Kg. Methods: Observational study. Right parasternal short-axis views at papillary muscle level were recorded in standing calves and subsequently analysed by two-dimensional speckle tracking for global and regional radial and circumferential strains and strain rates and radial displacement. Echocardiographic examinations were performed by 2 observers to evaluate intra- and interobserver repeatability and variability. Results: Two-dimensional speckle tracking was feasible in all calves. Automated tracking was better in systole than in diastole. Repeatability of the technique was good in calves. Systolic radial strain and strain rate peak values showed little variability compared to systolic circumferential strain and strain rate and to all diastolic measurements. Variability of the interobserver measurements was greater than the intraobserver measurements. Conclusions: Two-dimensional speckle tracking is feasible in calves. As in other species, evaluation of systolic radial left ventricular function is more reliable than circumferential and diastolic left ventricular function. [less ▲]

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See detailEmergent vortex phenomena in spatially and temporally modulated superconducting condensates
Jelic, Zeljko ULiege

Doctoral thesis (2017)

Superconductivity is an electronic state of matter arising from the existence of a common wave function with a coherent phase extending on a truly macroscopic scale. One major manifestation of this ... [more ▼]

Superconductivity is an electronic state of matter arising from the existence of a common wave function with a coherent phase extending on a truly macroscopic scale. One major manifestation of this striking quantum phenomenon is the dissipationless transport of electrical current, an asset deserving particular attention in the present times where the efficient energy distribution has become of utmost importance. Unfortunately, the motion of quantum units of magnetic flux (so-called vortices or fluxons), which is an unavoidable side-effect found in superconductors in the presence of transport currents and magnetic fields, severely limits the conditions to preserve dissipationless transport. This poses a challenge for achieving the functionalization of superconducting materials and threatens their spectrum of applications. It is widely known that any inhomogeneities (either material imperfections, or ones made artificially), which locally suppress superconductivity on the scale comparable to the core of the vortex, can pin the vortex and delay the onset of the vortex motion to higher applied currents. In recent years a substantial effort has been made to minimize the effects of current-induced vortex motion by tailoring arrays of artificial pinning centers. Besides improving the critical parameters of the superconducting state, a pinning matrix can be used for the manipulation of vortex matter, thus directly affecting the vortex dynamics, such as rectification of vortex motion under an ac drive (vortex diode) by introducing asymmetric pinning landscapes. In the literature one can find that the realization of the anchoring of the vortices can be based on nanostructured arrays of perforations, chemically grown defects, permanent nanomagnets, or even pinning sites produced by heavy ion bombardment. All of those realizations are based on a permanent imprint on the superconductor, without any possibility for subsequent modifications in the distribution and strength of the pinning. The principal objective of this thesis is to investigate the dynamical behavior of vortex matter under an entirely new kind of pinning landscape consisting of spatial and temporal modulation of the superconducting condensate. A particular case of spatial modulation is considered in a constricted structure where current lensing can cause extremely high vortex velocities. Subsequently, a time-dependent thermal potential introduced to the superconducting condensate will cause stroboscopic resonances during the vortex motion - a phenomenon that cannot be observed in the systems with static pinning imprints. Finally, a study of electronic gating is presented, where the local properties of superconductor, such as mean free path, or electronic band structure in general, can be influenced electronically. This is a completely unexplored interdisciplinary research topic, which will eventually allow one to manipulate individual vortices in superconducting materials by means of spatially confined and temporally controlled thermal and electromagnetic excitations. Furthermore, such techniques can provide one fundamental insight in different states of the vortex matter with respect to variation of the transport current, highly relevant for understanding the resistive state of superconducting materials and their applications. [less ▲]

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See detailHypogonadisme chez l’homme diabétique: actualités diagnostiques & thérapeutiques
VALDES SOCIN, Hernan Gonzalo ULiege

in VALDES SOCIN, Hernan Gonzalo (Ed.) RENCONTRES D’ENDOCRINOLOGIE 2017 (2017, November 25)

Résumé L’hypogonadisme chez l’homme diabétique est un syndrome clinique fréquemment sous-estimé, caractérisé par des signes et symptômes de déficience androgénique mais également par des troubles de la ... [more ▼]

Résumé L’hypogonadisme chez l’homme diabétique est un syndrome clinique fréquemment sous-estimé, caractérisé par des signes et symptômes de déficience androgénique mais également par des troubles de la fertilité. La physiopathologie de cet hypogonadisme est complexe et multifactorielle. Les troubles de la régulation glycémique, l’hyperinsulinisme et l’obésité déterminent un dysfonctionnement au niveau hypothalamique mais également au niveau gonadique. Un faisceau d’arguments nouveaux soulèvent l’intérêt de rechercher et de traiter l’hypogonadisme chez l’homme diabétique. Tout d’abord, plusieurs études épidémiologiques (1) montrent que le déficit en testostérone prédit la survenue d’un syndrome métabolique et du diabète, et que ce déficit s’accompagne d’une mortalité cardiovasculaire plus élevée (2). Ensuite, neuf études récentes démontrent que la perte pondérale intensive obtenue par régime et/ou chirurgie bariatrique normalise les taux de testostérone (3). Par ailleurs, une méta analyse portant sur cinq études confirme que la supplémentation en testostérone chez le diabétique hypogonadique se traduit par une réduction modeste de la circonférence abdominale, par une diminution de la glycémie et de l’HbA1c (4). Enfin, certaines études indiquent que la supplémentation en testostérone chez ces patients améliore leur survie (5). Si l’ensemble de ces études d’observation et d’intervention suggèrent des effets cardiométaboliques avantageux induits par la testostérone, on peut regretter un manque d’études randomisées, à large cohorte, évaluant les risques et bénéfices sur le long terme de ce traitement hormonal de supplémentation chez les patients diabétiques. Cette présentation fait le point sur les évidences actuelles reliant le déficit androgénique avec le diabète de type 2 et ses implications sur le risque cardiométabolique. [less ▲]

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See detailAllocution de clôture
Van Cleynenbreugel, Pieter ULiege

Speech/Talk (2017)

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See detailState Aid law in the European Union - the issue of tax rulings
Van Cleynenbreugel, Pieter ULiege

Speech/Talk (2017)

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See detailHorizontal integration under yardstick competition
Teusch, Jonas ULiege

Doctoral thesis (2017)

Horizontal integration through mergers and cross-ownership is ubiquitous; industries regulated by yardstick competition are no exception in this regard. However, even though yardstick competition is ... [more ▼]

Horizontal integration through mergers and cross-ownership is ubiquitous; industries regulated by yardstick competition are no exception in this regard. However, even though yardstick competition is applied to sectors of vital economic importance, such as energy and water networks, the welfare effects of horizontal integration in these settings have largely escaped scientific scrutiny. The dissertation therefore studies the welfare implications of horizontal integration under yardstick competition and identifies potential trade-offs. Specifically, whereas mergers and cross-ownership may bring about efficiency gains, there is a possibility that horizontal integration simultaneously decreases the effectiveness of regulation, benefiting certain firms at the expense of consumers and competitors. Key conditions for such strategic effects to occur and to dominate efficiency effects are derived in a principal-agent model. The thesis also demonstrates that the issue is not merely of academic interest, but has affected the practical application of yardstick competition in the electricity distribution industries of both Belgium and Norway. Chapter 1 analyses how horizontal mergers, joint ventures and regulatory decentralisation complicate the application of yardstick competition in Belgian electricity distribution. Chapter 2 develops a theoretical model of mergers under yardstick competition - formalising the welfare trade-offs at the heart of this dissertation. Chapter 3 leverages Data Envelopment Analysis to quantify both efficiency and strategic effects of horizontal restructuring in Norwegian electricity distribution and points to a recent merger that appears to have been driven by strategic motivations. Chapter 4 uses several econometric identification strategies - dynamic regression, matching on observables and instrumental variables - to establish that between 2007 and 2015, cross-ownership increased firm performance in Norwegian electricity distribution, which suggests that the net welfare effects were positive in this application. [less ▲]

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See detailIn silico modeling of bone formation under the influence of calcium phosphate-based biomaterials and osteochondrogenic growth factors
Manhas, Varun ULiege

Doctoral thesis (2017)

Bone regeneration is a complex process that involves regulation of different cell types by multiple biochemical, physical and mechanical factors. Unlike other biological tissues, bone can heal scarlessly ... [more ▼]

Bone regeneration is a complex process that involves regulation of different cell types by multiple biochemical, physical and mechanical factors. Unlike other biological tissues, bone can heal scarlessly and recover its original shape, size and strength. However, about 5% of bone defects result in non-unions. To tackle these non-unions, tissue engineering (TE) aims to develop bone substitutes or intelligent TE constructs to replace damaged, diseased or aging tissue. These bone substitutes/TE constructs are designed to support the chemotaxis, proliferation and differentiation of bone progenitor cells as well as being a biochemical agent delivery system. However, these delivery systems have a few limitations such as structural weakness of the carrier, high doses of biochemical agents being delivered due to burst release, unknown optimal concentrations of implanted cells and their high cost. Another drawback of these systems is the limited understanding on the relationship between biochemical agent dose, implanted cells, carrier volume, carrier material type and resultant bone formation. Given their significant medical potential, there is an increasing demand to design and develop improved bone substitutes/TE constructs. This PhD work fits in the long-term vision that mathematical models can be used as a part of design and manufacturing processes to develop improved treatment strategies and ultimately save experimental time and costs. In the first part of this work, a novel computational model was developed to predict the in vitro release of Ca2+ ions from calcium phosphate (CaP)-based scaffolds. The developed model was based on the Noyes-Whitney equation, the Fick’s second law of diffusion equation and the level-set method (LSM). The model was dependent on biophysicochemical phenomena such as dissolution, diffusion and degradation along with specific scaffold characteristics such as composition, size and shape. The predictions of the model were compared to dedicated experimental results. In the second part of this work, we investigated the use of a previously reported oxygen-dependent fracture healing model to elucidate the in vivo bone formation capacity of bone morphogenetic protein-2 (BMP-2) delivery systems in an ectopic environment. Specific attention was paid to the influence of BMP-2 dose and carrier volume on ectopic bone formation. The performance of this mathematical model was corroborated by comparison with experimental results published in the literature. Finally, the model was applied to investigate the influence of different BMP-2 release profiles on ectopic bone formation. In the third part of this work, we developed a novel computational model to predict the CaP and BMP-dependent ectopic bone formation in nude mice with and without incorporation of donor cells. The model specifically investigated the influence of BMP-2 dose, donor cell concentrations and calcium ion release on ectopic bone formation. The performance of this mathematical model was compared to the results of dedicated in-house experiments. The model was able to capture essential elements of the experimental results yet at the same time, a number of points for further improvement were identified. In the final part of this work, we investigated the application of the aforementioned CaP and BMP-dependent bone formation model to an orthotopic setting in sheep. The performance of the mathematical model was corroborated by comparing the model predictions with experimental results published in the literature. Subsequently, the model was applied to investigate the influence of different CaP-BMP-cell combinations on orthotopic bone formation, simulating in-house ongoing experiments. In conclusion, this PhD work illustrates a computational step taken towards enhancing the understanding on the role of CaP and BMPs in healing large bone defects. [less ▲]

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