8,093 research outputs found

    Advancing Model Pruning via Bi-level Optimization

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    The deployment constraints in practical applications necessitate the pruning of large-scale deep learning models, i.e., promoting their weight sparsity. As illustrated by the Lottery Ticket Hypothesis (LTH), pruning also has the potential of improving their generalization ability. At the core of LTH, iterative magnitude pruning (IMP) is the predominant pruning method to successfully find 'winning tickets'. Yet, the computation cost of IMP grows prohibitively as the targeted pruning ratio increases. To reduce the computation overhead, various efficient 'one-shot' pruning methods have been developed, but these schemes are usually unable to find winning tickets as good as IMP. This raises the question of how to close the gap between pruning accuracy and pruning efficiency? To tackle it, we pursue the algorithmic advancement of model pruning. Specifically, we formulate the pruning problem from a fresh and novel viewpoint, bi-level optimization (BLO). We show that the BLO interpretation provides a technically-grounded optimization base for an efficient implementation of the pruning-retraining learning paradigm used in IMP. We also show that the proposed bi-level optimization-oriented pruning method (termed BiP) is a special class of BLO problems with a bi-linear problem structure. By leveraging such bi-linearity, we theoretically show that BiP can be solved as easily as first-order optimization, thus inheriting the computation efficiency. Through extensive experiments on both structured and unstructured pruning with 5 model architectures and 4 data sets, we demonstrate that BiP can find better winning tickets than IMP in most cases, and is computationally as efficient as the one-shot pruning schemes, demonstrating 2-7 times speedup over IMP for the same level of model accuracy and sparsity.Comment: Thirty-sixth Conference on Neural Information Processing Systems (NeurIPS 2022

    Constrained Assortment Optimization under the Cross-Nested Logit Model

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    We study the assortment optimization problem under general linear constraints, where the customer choice behavior is captured by the Cross-Nested Logit model. In this problem, there is a set of products organized into multiple subsets (or nests), where each product can belong to more than one nest. The aim is to find an assortment to offer to customers so that the expected revenue is maximized. We show that, under the Cross-Nested Logit model, the assortment problem is NP-hard, even without any constraints. To tackle the assortment optimization problem, we develop a new discretization mechanism to approximate the problem by a linear fractional program with a performance guarantee of 1−ϵ1+ϵ\frac{1 - \epsilon}{1+\epsilon}, for any accuracy level ϵ>0\epsilon>0. We then show that optimal solutions to the approximate problem can be obtained by solving mixed-integer linear programs. We further show that our discretization approach can also be applied to solve a joint assortment optimization and pricing problem, as well as an assortment problem under a mixture of Cross-Nested Logit models to account for multiple classes of customers. Our empirical results on a large number of randomly generated test instances demonstrate that, under a performance guarantee of 90%, the percentage gaps between the objective values obtained from our approximation methods and the optimal expected revenues are no larger than 1.2%

    Modelling and Solving the Single-Airport Slot Allocation Problem

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    Currently, there are about 200 overly congested airports where airport capacity does not suffice to accommodate airline demand. These airports play a critical role in the global air transport system since they concern 40% of global passenger demand and act as a bottleneck for the entire air transport system. This imbalance between airport capacity and airline demand leads to excessive delays, as well as multi-billion economic, and huge environmental and societal costs. Concurrently, the implementation of airport capacity expansion projects requires time, space and is subject to significant resistance from local communities. As a short to medium-term response, Airport Slot Allocation (ASA) has been used as the main demand management mechanism. The main goal of this thesis is to improve ASA decision-making through the proposition of models and algorithms that provide enhanced ASA decision support. In doing so, this thesis is organised into three distinct chapters that shed light on the following questions (I–V), which remain untapped by the existing literature. In parentheses, we identify the chapters of this thesis that relate to each research question. I. How to improve the modelling of airline demand flexibility and the utility that each airline assigns to each available airport slot? (Chapters 2 and 4) II. How can one model the dynamic and endogenous adaptation of the airport’s landside and airside infrastructure to the characteristics of airline demand? (Chapter 2) III. How to consider operational delays in strategic ASA decision-making? (Chapter 3) IV. How to involve the pertinent stakeholders into the ASA decision-making process to select a commonly agreed schedule; and how can one reduce the inherent decision-complexity without compromising the quality and diversity of the schedules presented to the decision-makers? (Chapter 3) V. Given that the ASA process involves airlines (submitting requests for slots) and coordinators (assigning slots to requests based on a set of rules and priorities), how can one jointly consider the interactions between these two sides to improve ASA decision-making? (Chapter 4) With regards to research questions (I) and (II), the thesis proposes a Mixed Integer Programming (MIP) model that considers airlines’ timing flexibility (research question I) and constraints that enable the dynamic and endogenous allocation of the airport’s resources (research question II). The proposed modelling variant addresses several additional problem characteristics and policy rules, and considers multiple efficiency objectives, while integrating all constraints that may affect airport slot scheduling decisions, including the asynchronous use of the different airport resources (runway, aprons, passenger terminal) and the endogenous consideration of the capabilities of the airport’s infrastructure to adapt to the airline demand’s characteristics and the aircraft/flight type associated with each request. The proposed model is integrated into a two-stage solution approach that considers all primary and several secondary policy rules of ASA. New combinatorial results and valid tightening inequalities that facilitate the solution of the problem are proposed and implemented. An extension of the above MIP model that considers the trade-offs among schedule displacement, maximum displacement, and the number of displaced requests, is integrated into a multi-objective solution framework. The proposed framework holistically considers the preferences of all ASA stakeholder groups (research question IV) concerning multiple performance metrics and models the operational delays associated with each airport schedule (research question III). The delays of each schedule/solution are macroscopically estimated, and a subtractive clustering algorithm and a parameter tuning routine reduce the inherent decision complexity by pruning non-dominated solutions without compromising the representativeness of the alternatives offered to the decision-makers (research question IV). Following the determination of the representative set, the expected delay estimates of each schedule are further refined by considering the whole airfield’s operations, the landside, and the airside infrastructure. The representative schedules are ranked based on the preferences of all ASA stakeholder groups concerning each schedule’s displacement-related and operational-delay performance. Finally, in considering the interactions between airlines’ timing flexibility and utility, and the policy-based priorities assigned by the coordinator to each request (research question V), the thesis models the ASA problem as a two-sided matching game and provides guarantees on the stability of the proposed schedules. A Stable Airport Slot Allocation Model (SASAM) capitalises on the flexibility considerations introduced for addressing research question (I) through the exploitation of data submitted by the airlines during the ASA process and provides functions that proxy each request’s value considering both the airlines’ timing flexibility for each submitted request and the requests’ prioritisation by the coordinators when considering the policy rules defining the ASA process. The thesis argues on the compliance of the proposed functions with the primary regulatory requirements of the ASA process and demonstrates their applicability for different types of slot requests. SASAM guarantees stability through sets of inequalities that prune allocations blocking the formation of stable schedules. A multi-objective Deferred-Acceptance (DA) algorithm guaranteeing the stability of each generated schedule is developed. The algorithm can generate all stable non-dominated points by considering the trade-off between the spilled airline and passenger demand and maximum displacement. The work conducted in this thesis addresses several problem characteristics and sheds light on their implications for ASA decision-making, hence having the potential to improve ASA decision-making. Our findings suggest that the consideration of airlines’ timing flexibility (research question I) results in improved capacity utilisation and scheduling efficiency. The endogenous consideration of the ability of the airport’s infrastructure to adapt to the characteristics of airline demand (research question II) enables a more efficient representation of airport declared capacity that results in the scheduling of additional requests. The concurrent consideration of airlines’ timing flexibility and the endogenous adaptation of airport resources to airline demand achieves an improved alignment between the airport infrastructure and the characteristics of airline demand, ergo proposing schedules of improved efficiency. The modelling and evaluation of the peak operational delays associated with the different airport schedules (research question III) provides allows the study of the implications of strategic ASA decision-making for operations and quantifies the impact of the airport’s declared capacity on each schedule’s operational performance. In considering the preferences of the relevant ASA stakeholders (airlines, coordinators, airport, and air traffic authorities) concerning multiple operational and strategic ASA efficiency metrics (research question IV) the thesis assesses the impact of alternative preference considerations and indicates a commonly preferred schedule that balances the stakeholders’ preferences. The proposition of representative subsets of alternative schedules reduces decision-complexity without significantly compromising the quality of the alternatives offered to the decision-making process (research question IV). The modelling of the ASA as a two-sided matching game (research question V), results in stable schedules consisting of request-to-slot assignments that provide no incentive to airlines and coordinators to reject or alter the proposed timings. Furthermore, the proposition of stable schedules results in more intensive use of airport capacity, while simultaneously improving scheduling efficiency. The models and algorithms developed as part of this thesis are tested using airline requests and airport capacity data from coordinated airports. Computational results that are relevant to the context of the considered airport instances provide evidence on the potential improvements for the current ASA process and facilitate data-driven policy and decision-making. In particular, with regards to the alignment of airline demand with the capabilities of the airport’s infrastructure (questions I and II), computational results report improved slot allocation efficiency and airport capacity utilisation, which for the considered airport instance translate to improvements ranging between 5-24% for various schedule performance metrics. In reducing the difficulty associated with the assessment of multiple ASA solutions by the stakeholders (question IV), instance-specific results suggest reductions to the number of alternative schedules by 87%, while maintaining the quality of the solutions presented to the stakeholders above 70% (expressed in relation to the initially considered set of schedules). Meanwhile, computational results suggest that the concurrent consideration of ASA stakeholders’ preferences (research question IV) with regards to both operational (research question III) and strategic performance metrics leads to alternative airport slot scheduling solutions that inform on the trade-offs between the schedules’ operational and strategic performance and the stakeholders’ preferences. Concerning research question (V), the application of SASAM and the DA algorithm suggest improvements to the number of unaccommodated flights and passengers (13 and 40% improvements) at the expense of requests concerning fewer passengers and days of operations (increasing the number of rejected requests by 1.2% in relation to the total number of submitted requests). The research conducted in this thesis aids in the identification of limitations that should be addressed by future studies to further improve ASA decision-making. First, the thesis focuses on exact solution approaches that consider the landside and airside infrastructure of the airport and generate multiple schedules. The proposition of pre-processing techniques that identify the bottleneck of the airport’s capacity, i.e., landside and/or airside, can be used to reduce the size of the proposed formulations and improve the required computational times. Meanwhile, the development of multi-objective heuristic algorithms that consider several problem characteristics and generate multiple efficient schedules in reasonable computational times, could extend the capabilities of the models propositioned in this thesis and provide decision support for some of the world’s most congested airports. Furthermore, the thesis models and evaluates the operational implications of strategic airport slot scheduling decisions. The explicit consideration of operational delays as an objective in ASA optimisation models and algorithms is an issue that merits investigation since it may further improve the operational performance of the generated schedules. In accordance with current practice, the models proposed in this work have considered deterministic capacity parameters. Perhaps, future research could propose formulations that consider stochastic representations of airport declared capacity and improve strategic ASA decision-making through the anticipation of operational uncertainty and weather-induced capacity reductions. Finally, in modelling airlines’ utility for each submitted request and available time slot the thesis proposes time-dependent functions that utilise available data to approximate airlines’ scheduling preferences. Future studies wishing to improve the accuracy of the proposed functions could utilise commercial data sources that provide route-specific information; or in cases that such data is unavailable, employ data mining and machine learning methodologies to extract airlines’ time-dependent utility and preferences

    GENDERED EMBODIMENT, STABILITY AND CHANGE: WOMEN’S WEIGHTLIFTING AS A TOOL FOR RECOVERY FROM EATING DISORDERS

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    This thesis explores the everyday embodied experiences of women who use amateur weightlifting as a vehicle for recovery from eating disorders. Within online spaces and on social media, women frequently share their experiences of using weightlifting to overcome issues relating to disordered eating, body image, and mental health. In particular, women with a history of eating disorders credit weightlifting to be integral to their recovery journey. However, there is a dearth of research on women’s experiences with exercise during eating disorder recovery and no research that identifies weightlifting as beneficial to this process. To the contrary, discursive links are drawn between the practices of self-surveillance exercised by both eating disorder sufferers and weightlifters alike. In this regard, engagement with weightlifting during eating disorder recovery may signal the transferal of pathology from one set of behaviours to another. That is, from disordered eating to rigid and self-regulatory exercise routines. This thesis examines how women subjectively navigate and make sense of this pathologisation. The data for this research comes from longitudinal semi-structured interviews and photo elicitation with 19 women, living in the United Kingdom, who engaged in weightlifting during their eating disorder recovery. In addition, to build up a holistic picture and to explore how this phenomenon also ‘takes place’ online, I conducted a netnography of the overlapping subcultures of female weightlifting and eating disorder recovery on Instagram. Women’s standpoint theory and interpretative phenomenological analysis are combined to form the underpinning theoretical and analytical tools used to engage with these three rich data sets. Moreover, throughout I draw on an eclectic range of disciplinary perspectives, in order to bring together multiple fields of research and develop novel theoretical frameworks. In the findings, I argue that women’s experiences using weightlifting as a tool for recovery from eating disorders manifests in an embodied sense of multiplicity. In this sense, understandings of the body that are often viewed as ontologically distinct (muscularity/thinness/fatness) hang-together at once in the lived experience of a single individual. I argue that women, particularly those who have previously struggled with an eating disorder, are too readily positioned as vulnerable to media and representation. To theoretically combat these ideas regarding women’s assumed passivity, I develop the concept of ‘digital pruning’ to account for women’s agency in relation to new media. I contend that weightlifting offers women in recovery from eating disorders a new framework for approaching eating and exercise. Specifically, weightlifting’s norms and values legitimate occupying a larger body, which gives women in recovery permission to eat and gain-weight in a way that is both culturally sanctioned and health-promoting. Finally, I explore identity transformation as a specific tenet of recovery from eating disorders. I argue that, on social media, recovery identities are characterised by personal empowerment, resilience, and independence. While offline, quieter and less culturally glorified aspects of recovery (such as relationships of care) are central to women’s accounts of developing a new sense of self as they transition away from an eating disorder identity. In summary, this thesis is an examination of the ways in which women strategically navigate pathology in relation to their bodies, social media, food/exercise practices, and identity. I argue that women develop a set of ‘DIY’ recovery practices that allow them to consciously channel and draw on their negative experiences with eating disorders, to develop new ways of living that serve their overall wellbeing. Weightlifting is integral to this process, as it provides women transitioning out of this difficult phase in their lives with new ways of relating to their bodies and of being in the world. I situate this phenomenon within a neoliberal socio-political climate in which individuals are required to take personal responsibility for their mental health and wellbeing, despite living within conditions which are not conducive to recovery

    Relaxations and Cutting Planes for Linear Programs with Complementarity Constraints

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    We study relaxations for linear programs with complementarity constraints, especially instances whose complementary pairs of variables are not independent. Our formulation is based on identifying vertex covers of the conflict graph of the instance and generalizes the extended reformulation-linearization technique of Nguyen, Richard, and Tawarmalani to instances with general complementarity conditions between variables. We demonstrate how to obtain strong cutting planes for our formulation from both the stable set polytope and the boolean quadric polytope associated with a complete bipartite graph. Through an extensive computational study for three types of practical problems, we assess the performance of our proposed linear relaxation and new cutting-planes in terms of the optimality gap closed

    Multi-parametric Analysis for Mixed Integer Linear Programming: An Application to Transmission Planning and Congestion Control

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    Enhancing existing transmission lines is a useful tool to combat transmission congestion and guarantee transmission security with increasing demand and boosting the renewable energy source. This study concerns the selection of lines whose capacity should be expanded and by how much from the perspective of independent system operator (ISO) to minimize the system cost with the consideration of transmission line constraints and electricity generation and demand balance conditions, and incorporating ramp-up and startup ramp rates, shutdown ramp rates, ramp-down rate limits and minimum up and minimum down times. For that purpose, we develop the ISO unit commitment and economic dispatch model and show it as a right-hand side uncertainty multiple parametric analysis for the mixed integer linear programming (MILP) problem. We first relax the binary variable to continuous variables and employ the Lagrange method and Karush-Kuhn-Tucker conditions to obtain optimal solutions (optimal decision variables and objective function) and critical regions associated with active and inactive constraints. Further, we extend the traditional branch and bound method for the large-scale MILP problem by determining the upper bound of the problem at each node, then comparing the difference between the upper and lower bounds and reaching the approximate optimal solution within the decision makers' tolerated error range. In additional, the objective function's first derivative on the parameters of each line is used to inform the selection of lines to ease congestion and maximize social welfare. Finally, the amount of capacity upgrade will be chosen by balancing the cost-reduction rate of the objective function on parameters and the cost of the line upgrade. Our findings are supported by numerical simulation and provide transmission line planners with decision-making guidance

    Evaluación estructural probabilística de una cubierta de hormigón suspendida con cables: el Estadio de Braga (Portugal)

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    Cable structures often pose a signi cant challenge, particularly due to the struggle in foreseeing the structural response during the design. Because of this we rely on nite element models, despite their complexity, especially when facing dynamic forces. Hence the need of simpli ed models, optimized to retrace speci c behaviours of the structure and reduce the computational burden. This Master’s degree thesis deals with the case of the Braga Stadium, characterised by a roof of concrete shells supported by suspended cables. The aim is to assess whether reliable results regarding its seismic response can be obtained from simpli ed models. Starting from the provided designs and information, we calculate the cables geometry and performed a static analysis of the cables and the East stand, whose results re exploited to calibrate the simpli ed models. The structural layout on parallel elements allows us to simplify the structure as a planar one: we have assembled three models with increasing amount of simpli cation, that include the cables and the East stand upright. The West stand is not included as on its side the cables are anchored directly to the rock. The models are evaluated through a multi-support analysis, considering the two uttermost cases: with perfectly correlated accelerograms and with uncorrelated accelerograms. We perform several simulations, extrapolating from each one the peak values of the maximum cable force and the maximum relative displacement of its ends. We then processed these data, calculating the main statistical parameters and the empirical distribution functions for each model. [EN] The comparison shows that using simpli ed models we can obtain reliable results for the maximum cable forces, but not for the maximum relative displacements. Furthermore, cable modelling cannot be ignored: any simpli cation must be applied solely to the support structures. Finally, the use of uncorrelated accelerograms causes a signi cant increase of cable forces, even if a realistic scenario would be intermediate to the two considered. This result enhances the need of a multi-support analysis in this kind of structures, especially in case of large span suspended roofs like the one studied here.Gerussi, R. (2022). Evaluación estructural probabilística de una cubierta de hormigón suspendida con cables: el Estadio de Braga (Portugal). Universitat Politècnica de València. http://hdl.handle.net/10251/181531TFG

    Novel Cardiac Mapping Approaches and Multimodal Techniques to Unravel Multidomain Dynamics of Complex Arrhythmias Towards a Framework for Translational Mechanistic-Based Therapeutic Strategies

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    [ES] Las arritmias cardíacas son un problema importante para los sistemas de salud en el mundo desarrollado debido a su alta incidencia y prevalencia a medida que la población envejece. La fibrilación auricular (FA) y la fibrilación ventricular (FV) se encuentran entre las arritmias más complejas observadas en la práctica clínica. Las consecuencias clínicas de tales alteraciones arrítmicas incluyen el desarrollo de eventos cardioembólicos complejos en la FA, y repercusiones dramáticas debido a procesos fibrilatorios sostenidos que amenazan la vida infringiendo daño neurológico tras paro cardíaco por FV, y que pueden provocar la muerte súbita cardíaca (MSC). Sin embargo, a pesar de los avances tecnológicos de las últimas décadas, sus mecanismos intrínsecos se comprenden de forma incompleta y, hasta la fecha, las estrategias terapéuticas carecen de una base mecanicista suficiente y poseen bajas tasas de éxito. Entre los mecanismos implicados en la inducción y perpetuación de arritmias cardíacas, como la FA, se cree que las dinámicas de las fuentes focales y reentrantes de alta frecuencia, en sus diferentes modalidades, son las fuentes primarias que mantienen la arritmia. Sin embargo, se sabe poco sobre los atractores, así como, de la dinámica espacio-temporal de tales fuentes fibrilatorias primarias, específicamente, las fuentes focales o rotacionales dominantes que mantienen la arritmia. Por ello, se ha desarrollado una plataforma computacional, para comprender los factores (activos, pasivos y estructurales) determinantes, y moduladores de dicha dinámica. Esto ha permitido establecer un marco para comprender la compleja dinámica de los rotores con énfasis en sus propiedades deterministas para desarrollar herramientas basadas en los mecanismos para ayuda diagnóstica y terapéutica. Comprender los procesos fibrilatorios es clave para desarrollar marcadores y herramientas fisiológica- y clínicamente relevantes para la ayuda de diagnóstico temprano. Específicamente, las propiedades espectrales y de tiempo-frecuencia de los procesos fibrilatorios han demostrado resaltar el comportamiento determinista principal de los mecanismos intrínsecos subyacentes a las arritmias y el impacto de tales eventos arrítmicos. Esto es especialmente relevante para determinar el pronóstico temprano de los supervivientes comatosos después de un paro cardíaco debido a fibrilación ventricular (FV). Las técnicas de mapeo electrofisiológico, el mapeo eléctrico y óptico cardíaco, han demostrado ser recursos muy valiosos para dar forma a nuevas hipótesis y desarrollar nuevos enfoques mecanicistas y estrategias terapéuticas mejoradas. Esta tecnología permite además el trabajo multidisciplinar entre clínicos y bioingenieros, para el desarrollo y validación de dispositivos y metodologías para identificar biomarcadores multi-dominio que permitan rastrear con precisión la dinámica de las arritmias identificando fuentes dominantes y atractores con alta precisión para ser dianas de estrategias terapeúticas innovadoras. Es por ello que uno de los objetivos fundamentales ha sido la implantación y validación de nuevos sistemas de mapeo en distintas configuraciones que sirvan de plataforma de desarrollo de nuevas estrategias terapeúticas. Aunque el mapeo panorámico es el método principal y más completo para rastrear simultáneamente biomarcadores electrofisiológicos, su adopción por la comunidad científica es limitada principalmente debido al coste elevado de la tecnología. Aprovechando los avances tecnológicos recientes, nos hemos enfocado en desarrollar, y validar, sistemas de mapeo óptico de alta resolución para registro panorámico cardíaco, utilizando modelos clínicamente relevantes para la investigación básica y la bioingeniería.[CA] Les arítmies cardíaques són un problema important per als sistemes de salut del món desenvolupat a causa de la seva alta incidència i prevalença a mesura que la població envelleix. La fibril·lació auricular (FA) i la fibril·lació ventricular (FV), es troben entre les arítmies més complexes observades a la pràctica clínica. Les conseqüències clíniques d'aquests trastorns arítmics inclouen el desenvolupament d'esdeveniments cardioembòlics complexos en FA i repercussions dramàtiques a causa de processos fibril·latoris sostinguts que posen en perill la vida amb danys neurològics posteriors a la FV, que condueixen a una aturada cardíaca i a la mort cardíaca sobtada (SCD). Tanmateix, malgrat els avanços tecnològics de les darreres dècades, els seus mecanismes intrínsecs s'entenen de forma incompleta i, fins a la data, les estratègies terapèutiques no tenen una base mecanicista suficient i tenen baixes taxes d'èxit. La majoria dels avenços en el desenvolupament de biomarcadors òptims i noves estratègies terapèutiques en aquest camp provenen de tècniques valuoses en la investigació de mecanismes d'arítmia. Entre els mecanismes implicats en la inducció i perpetuació de les arítmies cardíaques, es creu que les fonts primàries subjacents a l'arítmia són les fonts focals reingressants d'alta freqüència dinàmica i AF, en les seves diferents modalitats. Tot i això, se sap poc sobre els atractors i la dinàmica espaciotemporal d'aquestes fonts primàries fibril·ladores, específicament les fonts rotacionals o focals dominants que mantenen l'arítmia. Per tant, s'ha desenvolupat una plataforma computacional per entendre determinants actius, passius, estructurals i moduladors d'aquestes dinàmiques. Això va permetre establir un marc per entendre la complexa dinàmica multidomini dels rotors amb ènfasi en les seves propietats deterministes per desenvolupar enfocaments mecanicistes per a l'ajuda i la teràpia diagnòstiques. La comprensió dels processos fibril·latoris és clau per desenvolupar puntuacions i eines rellevants fisiològicament i clínicament per ajudar al diagnòstic precoç. Concretament, les propietats espectrals i de temps-freqüència dels processos fibril·latoris han demostrat destacar un comportament determinista important dels mecanismes intrínsecs subjacents a les arítmies i l'impacte d'aquests esdeveniments arítmics. Mitjançant coneixements previs, processament de senyals, tècniques d'aprenentatge automàtic i anàlisi de dades, es va desenvolupar una puntuació de risc mecanicista a la aturada cardíaca per FV. Les tècniques de cartografia òptica cardíaca i electrofisiològica han demostrat ser recursos inestimables per donar forma a noves hipòtesis i desenvolupar nous enfocaments mecanicistes i estratègies terapèutiques. Aquesta tecnologia ha permès durant molts anys provar noves estratègies terapèutiques farmacològiques o ablatives i desenvolupar mètodes multidominis per fer un seguiment precís de la dinàmica d'arrímies que identifica fonts i atractors dominants. Tot i que el mapatge panoràmic és el mètode principal per al seguiment simultani de paràmetres electrofisiològics, la seva adopció per part de la comunitat multidisciplinària d'investigació cardiovascular està limitada principalment pel cost de la tecnologia. Aprofitant els avenços tecnològics recents, ens centrem en el desenvolupament i la validació de sistemes de mapes òptics de baix cost per a imatges panoràmiques mitjançant models clínicament rellevants per a la investigació bàsica i la bioenginyeria.[EN] Cardiac arrhythmias are a major problem for health systems in the developed world due to their high incidence and prevalence as the population ages. Atrial fibrillation (AF) and ventricular fibrillation (VF), are amongst the most complex arrhythmias seen in the clinical practice. Clinical consequences of such arrhythmic disturbances include developing complex cardio-embolic events in AF, and dramatic repercussions due to sustained life-threatening fibrillatory processes with subsequent neurological damage under VF, leading to cardiac arrest and sudden cardiac death (SCD). However, despite the technological advances in the last decades, their intrinsic mechanisms are incompletely understood, and, to date, therapeutic strategies lack of sufficient mechanistic basis and have low success rates. Most of the progress for developing optimal biomarkers and novel therapeutic strategies in this field has come from valuable techniques in the research of arrhythmia mechanisms. Amongst the mechanisms involved in the induction and perpetuation of cardiac arrhythmias such AF, dynamic high-frequency re-entrant and focal sources, in its different modalities, are thought to be the primary sources underlying the arrhythmia. However, little is known about the attractors and spatiotemporal dynamics of such fibrillatory primary sources, specifically dominant rotational or focal sources maintaining the arrhythmia. Therefore, a computational platform for understanding active, passive and structural determinants, and modulators of such dynamics was developed. This allowed stablishing a framework for understanding the complex multidomain dynamics of rotors with enphasis in their deterministic properties to develop mechanistic approaches for diagnostic aid and therapy. Understanding fibrillatory processes is key to develop physiologically and clinically relevant scores and tools for early diagnostic aid. Specifically, spectral and time-frequency properties of fibrillatory processes have shown to highlight major deterministic behaviour of intrinsic mechanisms underlying the arrhythmias and the impact of such arrhythmic events. Using prior knowledge, signal processing, machine learning techniques and data analytics, we aimed at developing a reliable mechanistic risk-score for comatose survivors of cardiac arrest due to VF. Cardiac optical mapping and electrophysiological mapping techniques have shown to be unvaluable resources to shape new hypotheses and develop novel mechanistic approaches and therapeutic strategies. This technology has allowed for many years testing new pharmacological or ablative therapeutic strategies, and developing multidomain methods to accurately track arrhymia dynamics identigying dominant sources and attractors. Even though, panoramic mapping is the primary method for simultaneously tracking electrophysiological parameters, its adoption by the multidisciplinary cardiovascular research community is limited mainly due to the cost of the technology. Taking advantage of recent technological advances, we focus on developing and validating low-cost optical mapping systems for panoramic imaging using clinically relevant models for basic research and bioengineering.Calvo Saiz, CJ. (2022). Novel Cardiac Mapping Approaches and Multimodal Techniques to Unravel Multidomain Dynamics of Complex Arrhythmias Towards a Framework for Translational Mechanistic-Based Therapeutic Strategies [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/182329TESI

    Development of a light-sheet fluorescence microscope employing an ALPAO deformable mirror to achieve video-rate remote refocusing and volumetric imaging.

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    There are numerous situations in microscopy where it is desirable to remotely refocus a microscope employing a high numerical aperture (NA) objective lens. This thesis describes the characterisation, development and implementation of an Alpao membrane deformable mirror-based system to achieve this goal for a light-sheet fluorescence microscope (LSFM). The Alpao deformable mirror (DM) DM97-15 used is this work has 97 actuators and was sufficiently fast to perform refocus sweeps at 25 Hz and faster. However, a known issue with using Alpao deformable mirrors in open-loop mode is that they exhibit viscoelastic creep and temperature- dependent variations in the mirror response. The effect of visco-elastic creep was reduced by ensuring that the mirror profile was on average constant on timescales shorter than the characteristic time of the visco-elastic creep. The thermal effect was managed by ensuring that the electrical power delivered to the actuators was constant prior to optimisation and use. This was achieved by ensuring that the frequency and amplitude of oscillation of the mirror was constant prior to optimisation, so that it reached a thermal steady state, was approximately constant during optimisation and constant during use. The image-based optimisation procedure employed used an estimate of the Strehl ratio of the optical system calculated from an image of an array of 1 μm diameter holes. The optimisation procedure included optimising the amount of high-NA defocus and the Zernike modes from Noll indices 4 to 24. The system was tested at 26.3 refocus sweeps per second over a refocus range of -50 to 50 μm with a 40x/0.85 air objective and a 40x/0.80 water immersion objective. The air objective enabled a mean Strehl metric of more than 0.6 over a lateral field of view of 200x200 microns and for a refocus range of 45 microns. The water objective achieved a mean Strehl metric of more than 0.6 over a lateral field of view of 200x200 microns over a larger refocus range of 77 microns. The DM-based refocusing system was then incorporated into a LSFM setup. The spatial resolution of the system was characterised using fluorescent beads imaged volumetrically at 26.3 volumes per second. The performance of the system was also demonstrated for imaging fluorescence pollen grain samples.Open Acces
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