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ACKNOWLEDGEMENTS I would like to take this moment to extend my utmost appreciation for all the support provided by my supervisor, Dr. Russell de Souza. He assisted me along the way and ensured that I was always on the right path to achieve all my goals and checkpoints in every circumstance. I would also like to thank my committee for providing me with fantastic support: Ms. Laura Banfield for always being there to help solve any problem in this process, and Dr. Zain Chagla for providing a plethora of knowledge from the technical perspective of infectious disease and being so patient. Special thanks to Dr. Alexandra Mayhew for her support in our prevalence meta-analysis. Finally, I would like to thank my family, my wife, Dr. Sanjida Rowshan Anannya, for whom I am here today, and my parents, siblings, and in-laws; you are always there for me in every walk of life. You are why I have gotten to where I am today and are my daily inspiration. / Background: Bacteria is a major cause of many infectious diseases, and the treatment for these diseases is antibiotics designed to kill or subdue the growth of the bacteria. However, bacteria evolve, and if an antibiotic prescription is not the right antibiotic for the right patient at the right time with the correct dose and the right route, Antimicrobial Resistance (AMR) may result. During this pandemic, the use of antibiotics to treat hospitalized COVID-19 patients without any bacterial coinfection threatens the effectiveness of antibiotic treatment for current and future bacterial infections. Methods: A systematic search was conducted of the Embase, Medline, Web of Science, and Cochrane Library databases by generating search terms using the concepts of “COVID-19,” “Bacterial Coinfection,” “Secondary bacterial infection,” and “Antimicrobial resistance” to identify studies that reported the prevalence of antibiotic prescription for the treatment of COVID-19 in hospitalized patients with and without bacterial coinfection. The pooled estimate of the percentage of the total and confirmed appropriate antibiotic prescriptions provided to hospitalized COVID-19 patients was generated using a random effect meta-analysis with inverse variance weighting. Result: Of 157,623 participants from 29 studies included in our review, 67% (CI 64% to 71%, P<0.00001) were prescribed antibiotics, among which 80% (CI 76% to 83%, P<0.00001) prescriptions were given for the COVID-19 patients without any bacterial coinfections. The use of antibiotics varied during the pre-immunosuppressive period (before 16 June 2020) and post-immunosuppressive period of the pandemic and between the High-Income Countries and Upper and Lower Middle-Income Countries. Conclusion: This Systematic Review and Meta-analysis finds greater than expected use of antibiotics to treat hospitalized COVID-19 patients without bacterial coinfections, which can worsen AMR globally. Clear and concrete guidelines for the use of antibiotic prescriptions to treat COVID-19 patients, strict monitoring, and compliance with Antimicrobial Stewardship are needed to prevent over-prescription. / Thesis / Master in Advanced Studies (MAS) / Bacteria is a major cause of many infectious diseases. Before the discovery of Antibiotics in 1928, hundreds of thousands of people used to die due to infectious diseases caused by bacteria. While Antibiotics are essential to treat bacterial infectious diseases, overuse or misuse can accelerate Antibiotic Resistance, a phenomenon when bacteria change and/or develop the ability to escape the drugs designed to kill them. Self-medication, availability of antibiotics without a prescription, and inappropriate dosing of antibiotics can worsen the situation. During the COVID-19 pandemic, antibiotics were commonly prescribed as part of the treatment regime for COVID-19, even when a clear bacterial infection was not identified. In our Systematic Review and Meta-analysis, we aimed to see the frequency of antibiotic prescriptions to treat hospitalized COVID-19 patients without any bacterial coinfections.

Driven by recent technical advances, vehicle-based transportation systems in intralogistics are currently shifting from automated guided vehicles (AGVs) to autonomous mobile robots (AMRs). Unlike AGVs, AMRs are not bound to a physical or virtual track and autonomously determine their movements. While the increase in freedom for routing leads to improvements in terms of system flexibility and scalability, it also poses new challenges in terms of coordination and thus the high-performance routing behavior of an entire fleet. Accepted and widely used algorithms in the AGV field are often barely applicable to large fleets of free-ranging AMRs, while typical algorithms from the field of mobile robotics usually focus on different objectives. This thesis presents a novel concept for determining global routes, the so-called lanemap, that enables the synchronized movements of multiple free-ranging vehicles in arbitrary layouts without increasing calculation effort during online operations. The basic idea consists in creating a lanemap offline that provides the AMRs with a set of suggested global lanes from various starting positions to different destinations. On the one hand, the application of a lanemap lowers each AMRs’ individual degree of freedom. However, coordinating lanes sensibly beforehand enables short travel distances as well as a low probability of routing conflicts, which improves the performance of the entire AMR fleet on the other hand. Since the lanemap only provides an offline calculated global route as suggestion, the concept can be combined with any established online approach, such as a local conflict avoidance/resolution approach, or with in-depth coordination of all vehicle movements. This thesis presents a theoretical mathematical model and a practically applicable heuristic approach for the creation of a lanemap. As proof of concept, simulation experiments show that the heuristic is generally capable of creating lanemaps for all different kinds of layouts. Furthermore, the concept allows for the determination of customized routes for a specific fleet size and an anticipated transportation demand. Therefore, once system requirements are known, a beneficial set of lanemaps for typical constellations can be calculated in advance and integrated into routing as needed.

Die vorliegende Arbeit beschäftigt sich mit den Auswirkungen der Ionenimplantation auf die Materialeigenschaften verschiedener magnetischer Probensysteme. Durch die Implantation mit Ionen kann man auf vielfältige Art und Weise die Eigenschaften von magnetischen Materialien modifizieren und maßschneidern, so zum Beispiel die Sättigungsmagnetisierung und die magnetische Anisotropie. Aus der Untersuchung von drei verschiedenen Probensystemen ergibt sich die Dreigliederung des Ergebnisteils. Im ersten Teil der Arbeit, dem Hauptteil, wird die Strukturierung von Permalloyschichten durch Ionen und der Einfluss auf den anisotropen Magnetowiderstand (AMR) untersucht. Der AMR ist direkt abhängig von der Ausrichtung der Magnetisierung eines Materials zum angelegten Strom. Um die Magnetisierungsrichtung sichtbar zu machen wurde ein Kerrmikroskop benutzt. Dieses wurde im Rahmen dieser Arbeit technisch erweitert um gleichzeitig auch den AMR messen zu können. Damit war es erstmalig möglich den AMR und die magnetischen Domänenkonfigurationen direkt zu vergleichen. Durch eine weitere Modifikation des Kerrmikrosops ist es möglich quantitative Bilder eines kompletten Ummagnetisierungsvorganges zu messen. Es konnte gezeigt werden, dass der berechnete AMR des Bildausschnittes mit dem gemessenen übereinstimmt. Der AMR ist abhängig von der Streifenbreite, der Streifenausrichtung zum Strom, der Stärke der induzierten Anisotropie, dem angelegten Feldwinkel und der Sättigungsmagnetisierung. Im Fall von schmalen Streifen führt das zweistufige Schalten zu einem AMR-Maximum, wenn die Streifen mit der niedrigeren Sättigungsmagnetisierung geschaltet haben. Das Zusammensetzen der Streifenstruktur ermöglicht es den AMR gezielt zu manipulieren. Bei geringer induzierter Anisotropie sind verschiedene komplexe Domänen messbar, welche sich in einem asymmetrischen AMR widerspiegeln. So kann der AMR auf vielfältige Weise manipuliert und deren Abhängigkeit von den magnetischen Domänen mittels Kerrmikroskopie gemessen werden. Im zweiten Teil wurde die Erzeugung eines Anisotropiegradienten durch Ionenimplantation in einem Speichermedium untersucht. Hierbei handelt es sich um eine Kooperation mit Peter Greene (University of California Davis) und Elke Arenholz (Lawrence Berkeley Laboratory). Nachdem die Ionenverteilung in dem Material mit TRIDYN simuliert wurde, erfolgte eine Implantation in die oberen Schichten der Co/Pd Multilagen. Dieses hat eine Veränderung der magnetischen Anisotropie zur Folge. Die Ummagnetisierungskurven sind mit dem polaren magnetooptische Kerreffekt (polaren MOKE) und Vibrationsmagnetometrie vermessen worden. Außerdem fand eine Strukturanalyse mit Röntgenreflektrometrie und Röntgendiffraktometrie statt. Die abschließende Beurteilung des Schaltverhaltens erfolgte durch die Auswertung der Ummagnetisierungskurven erster Ordnung. Es ist uns gelungen die oberen Schichten durch die Implantation weichmagnetisch zu machen. Die darunterliegenden Schichten sind noch hartmagnetisch und das Material zeigt textit{exchange spring} Verhalten. Es erfüllt somit die Voraussetzungen, um als Speichermedium genutzt zu werden. Damit konnte erfolgreich gezeigt werden, dass man mit Ionenimplantation einen Anisotropiegradienten in einem Speichermedium erzeugen kann und dadurch das gewünschte Schaltverhalten erzeugt. Im dritten Teil, in einem Projekt mit Björn Obry (TU Kaiserslautern), geht es um die Erzeugung eines Spinwellenleiters und eines magnonischen Kristalls durch die Ionenimplantation in Permalloy. Zur Herstellung des Spinwellenleiters und des magnonischen Kristalls macht man sich die lokale Reduzierung der Sättigungsmagnetisierung durch die Implantation zu nutze. Es wurden Messungen mit dem polaren MOKE gemacht. Die Spinwellencharakterisierung ist mit dem Brillouin-Lichtstreumikroskop durchgeführt worden. Es war möglich die Ionenimplantation zur Herstellung eines magnonischen Kristalls und eines Spinwellenleiters zu nutzen. Das Verändern von magnetischen Materialeigenschaften durch Implantation eröffnet somit verschiedene Möglichkeiten. Mit Ionenimplantation kann man Permalloy so strukturieren, dass man den AMR gezielt manipulieren kann. Außerdem wurde Ionenimplantation genutzt um einen Anisotropiegradienten in einem Speichermedium zu erzeugen. Durch diesen Anisotropiegradient konnte das Schaltverhalten gezielt modifiziert werden. Mit Hilfe von Ionenimplantation kann man auch ein magnonisches Kristall und einen Spinwellenleiter herstellen. / This thesis deals with magnetic modification of ferromagnetic films by ion implantation, such as induced changes of the magnetic anisotropy and changes in the saturation magnetization. Three different sample structures were investigated. Therefore the result section is divided into three parts. The influence of ion induced magnetic patterning on the anisotropic magnetoresistance (AMR) is investigated in the first part. The AMR directly depends on the angle between the applied current and the magnetization of the material. To investigate this relationship a Kerr microscopy,for observing the magnetic domains was combined with resistance measurements. The measurements were performed on stripe patterned permalloy samples. This is the main part of the thesis. The creation of an anisotropy gradient in a storage media by ion implantation is the topic of the second part. It was a collaborative project with Peter Greene (University of California Davis) and Elke Arenholz (Lawrence Berkeley Laboratory). The goal was to create a magnetic anisotropy gradient by introducing ions in the upper layer of the Co/Pd- multilayer. After TRIDYN simulations of the ion distribution, the implantation was performed and the magnetization curves were measured with polar magneto-optical Kerr effect and vibrating sample magnetometry. In addition to this, structural characterization was carried out by x-ray reflection and x-ray diffraction measurements. For the final determination of the switching behavior first order reversal curves were analyzed. The aim of the third part was to create a spin wave guide and a magnonic crystal by local ion implantation. In this project with Björn Obry (TU Kaiserslautern) the characteristic of the ions to reduce the saturation magnetization in permalloy was used and the effect on the spin wave propagation was analyzed. Polar MOKE was performed to determine the saturation magnetization. Brillouin light scattering microscopy was used to analyze the spin wave behavior inside the material.

Dans cette thèse nous étudions l'accélération des rayons cosmiques (RC), ces particules très énergétiques qui emplissent l'univers. Il est admis que les RC galactiques sont produits par accélération diffusive par onde de choc dans les restes de supernovae. La théorie linéaire explique la formation de spectres en loi de puissance, mais elle doit être modifiée du fait de la rétroaction des RC. Nous nous concentrons sur l'accélération répétée par chocs successifs, qui durcit les spectres, et qui dépend du transport des rayons cosmiques entre les chocs.<br />Pour cette étude nous avons développé un outil numérique qui couple l'évolution hydrodynamique du plasma et le transport cinétique des RC. Nous l'avons validé grâce à des résultats déjà connus. Pour résoudre toutes les échelles induites par la dépendance en énergie du coefficient de diffusion des RC nous avons implémenté une technique de grille adaptative. Pour réduire le temps de calcul nous avons aussi parallélisé notre code, dans la dimension d'énergie. Cela nous permet de présenter les premières simulations de l'accélération non-linéaire par chocs multiples. <br />Nous appliquons notre outil aux superbulles, les vastes structures chaudes et peu denses entourant les associations OB, car c'est probablement là que la plupart des supernovae explose en fait -- ce qui induit des modifications substantielles du modèle standard de production des RC galactiques. Plus précisément nous avons commencé à explorer les effets de chocs multiples, par une étude du rôle de RC pré-existants en amont d'une onde de choc. Pour finir nous passons en revue l'émission haute énergie des superbulles dans l'optique d'une production efficace de RC.

Antimicrobial resistance (AMR) has been classified as one of the phenomena that belongs to the current top threats to human health. AMR is the process where bacteria become resistant to the antimicrobial drug and renders the antibiotic ineffective. This phenomenon is increasing exponentially due to misuse and overuse of antibiotics and is responsible for 700,000 annual deaths globally. If the contributing factors to AMR remain persistent, the estimated amount of annual deaths will increase to the exorbitant figure of 10 million by 2050. The inappropriate waste discharge from antibiotic manufacturing plants is the third major cause contributing to AMR. For this reason, environmental sustainability within the pharmaceutical industry is tightly linked to human health, and therefore, the importance of environmental risk management becomes crucial. Pharmaceutical supply chains are extremely complex, fragmented, and rigid due to the highly regulated environment and global distribution of the chains. Constant availability is sometimes compromised, and this leads to national shortages of antibiotics, which increase AMR. Therefore, supply chain sustainability risks (SCSRs) need to be thoroughly assessed and managed. The thesis aims to identify the sustainability risks that threaten the constant supply of antibiotics and further provide a comprehensive and sufficient framework on how to assess and manage SCSRs within the pharmaceutical industry. This research is based on the review of existing literature, followed by an empirical study that included a case study of two specific antibiotics relevant to the Swedish market. The analysis of publicly available databases, together with the qualitative interviews, revealed that the most susceptible node of the supply chain resides in the primary manufacturing stage. The most relevant SCSRs have been identified, and an adapted framework is suggested. The role of regulatory agencies has been demonstrated to be fundamental to achieve change concerning environmental progress. Further research needs to be implemented for the validation of the suggested framework within a practical context.

Rising Antimicrobial Resistance is a threat faced all over the world. Bacterial infections that were treatable with antibiotics only a few years ago can now lead to life-threatening conditions. This thesis is part of the work of a large platform, PLATINEA, trying to reduce the rate of new resistances occurring in Sweden by preventing non optimal treatment. Due to shortages of the right antibiotics, suboptimal antibiotics are prescribed, which has shown to be accelerating the resistances among the bacterial populations. This study proposes an information exchange database and a central storage model for critical antibiotics to circumvent stock outs and inconveniences resulting from shortages of medically valuable antibiotics. Through interviewing prominent actors in the Swedish pharmaceutical supply chain an inside into the procurement of antibiotic in Sweden and what concerns are faced by the organs involved was created. Literature studies on occurred shortages of antibiotics in Sweden and the world were examined and possible reasons for these were identified. Examination of governmental efforts and assignments created the context in which gaps were identified that this thesis work could fill. A focus on Benzylpenicillin and Rifampicin were kept throughout the study. The collected data led to the implementation recommendation of two models by this study. An information platform suggested to allow better, faster and more accurate information exchange between all involved actors of the supply chain as well as a centralized storage model for the storage of antibiotics with medically high value in Sweden.  Through the implementation of the model systems shortages of critical antibiotics can be circumvented and better availability of information leads to quicker reactions ability to stock outs of other antibiotics.

<p>Over the last three decades, computer architects have been able to achieve an increase in performance for single processors by, e.g., increasing clock speed, introducing cache memories and using instruction level parallelism. However, because of power consumption and heat dissipation constraints, this trend is going to cease. In recent times, hardware engineers have instead moved to new chip architectures with multiple processor cores on a single chip. With multi-core processors, applications can complete more total work than with one core alone. To take advantage of multi-core processors, we have to develop parallel applications that assign tasks to different cores. On each core, pipeline, data and task parallelization can be used to achieve higher performance. Dataflow programming languages are attractive for achieving parallelism because of their high-level, machine-independent, implicitly parallel notation and because of their fine-grain parallelism. These features are essential for obtaining effective, scalable utilization of multi-core processors.</p><p>In this thesis work we have parallelized an existing audio codec - Adaptive Multi-Rate Wide Band (AMR-WB) - written in the C language for single core processor. The target platform is a multi-core AMR11 MP developer board. The final result of the efforts is a working AMR-WB encoder implemented in CAL and running in the OpenDF simulator. The C specification of the AMR-WB encoder was analysed with respect to dataflow and parallelism. The final implementation was developed in the CAL Actor Language, with the goal of exposing available parallelism - different dataflows - as well as removing unwanted data dependencies. Our thesis work discusses mapping techniques and guidelines that we followed and which can be used in any future work regarding mapping C based applications to CAL. We also propose solutions for some specific dependencies that were revealed in the AMR-WB encoder analysis and suggest further investigation of possible modifications to the encoder to enable more efficient implementation on a multi-core target system.</p>

A three-dimensional, parallel, anisotropic, block-based, adaptive mesh refinement (AMR) algorithm is proposed and described for the solution of fluid flows on body-fitted, multi-block, hexahedral meshes. Refinement and de-refinement in any grid block computational direction, or combination of directions, allows the mesh to rapidly adapt to anisotropic flow features such as shocks, boundary layers, or flame fronts, common to complex flow physics. Anisotropic refinements and an efficient and highly scalable parallel implementation lead to a potential for significant reduction in computational cost as compared to a more typical isotropic approach. Unstructured root-block topology allows for greater flexibility in the treatment of complex geometries. The AMR algorithm is coupled with an upwind finite-volume scheme for the solution of the Euler equations governing inviscid, compressible, gaseous flow. Steady-state and time varying, three-dimensional, flow problems are investigated for various geometries, including the cubed-sphere mesh.

A three-dimensional, parallel, anisotropic, block-based, adaptive mesh refinement (AMR) algorithm is proposed and described for the solution of fluid flows on body-fitted, multi-block, hexahedral meshes. Refinement and de-refinement in any grid block computational direction, or combination of directions, allows the mesh to rapidly adapt to anisotropic flow features such as shocks, boundary layers, or flame fronts, common to complex flow physics. Anisotropic refinements and an efficient and highly scalable parallel implementation lead to a potential for significant reduction in computational cost as compared to a more typical isotropic approach. Unstructured root-block topology allows for greater flexibility in the treatment of complex geometries. The AMR algorithm is coupled with an upwind finite-volume scheme for the solution of the Euler equations governing inviscid, compressible, gaseous flow. Steady-state and time varying, three-dimensional, flow problems are investigated for various geometries, including the cubed-sphere mesh.