This thesis is dedicated to creating a new system with capabilities to create new generic, autonomous strategy computer game controlling elements based on multi-agent systems with social, intelligent decision-making and learning skills. Basic types of strategy games and problems of their playing will be introduced, along with currently used methods of intelligent game AI development. This thesis also presents design and implementation of the new system, working model for a specific game and results obtained while testing it.

Anaemia in chronic kidney disease (CKD) mostly results from a decrease in the production of erythropoietin (EPO) by the failing kidney. CKD progression requires treatment with erythropoiesis-stimulating agents and iron supplementation to ensure sufficient erythrocyte production. Best clinical practice guidelines should be adhered to in managing CKD to reduce morbidity and mortality related to anaemia associated cardiovascular disease. Likewise, guideline deviations create an increased strain on the resources of the treatment facility. It is uncertain to which extent these guidelines are followed by Nephrology Units in the public healthcare sector, or whether the documented international trends are prevalent locally due to the paucity of local data, and therefore further investigation is warranted. This study aimed to assess treatment trends in managing anaemia in CKD patients at the Steve Biko Academic Hospital (SBAH). Files of patients receiving treatment at the SBAH Nephrology Unit between 2 January 2018 - 31 August 2018 were reviewed. Only individuals with stage 5 CKD receiving either haemodialysis, or peritoneal dialysis were included, while those with less than three months’ treatment were excluded. Measured variables included demographical information, current EPO treatment and/or iron supplementation regimens versus serum haemoglobin/iron levels and quantity of administered blood products. Ninety-seven patients met the inclusion criteria. Haemodialysis accounted for 43% (n = 42), and peritoneal dialysis 57% (n = 55). Intergroup comparison between the number of results where both haemoglobin and iron were within the target range versus the number of results where both parameters fell outside the target range yielded a significant difference (p = 0.0031). Patients receiving peritoneal dialysis reached serum haemoglobin and iron levels closer to normal target values compared to those receiving haemodialysis. Managing anaemia in CKD is a complex process. More stringent iron control, especially for patients receiving haemodialysis, including the administration of long-acting EPO preparations once a month, is proposed. The latter will contribute to the improvement of clinical outcomes of patients with CKD. Keywords: Chronic kidney disease, anaemia, erythropoiesis stimulating agent, haemoglobin, iron / Dissertation (MSc (Pharmacology))--University of Pretoria, 2020. / Pharmacology / MSc (Pharmacology) / Unrestricted

Depuis plus de 30 ans, les progrès thérapeutiques ont permis de réduire la morbi-mortalité liée à l’infarctus du myocarde. La reperfusion est une étape essentielle dans la prise en charge des patients, mais est également à l’origine de lésions tissulaires cardiaques. Plusieurs travaux ont montré que le conditionnement ischémique ou pharmacologique du coeur permet de réduire ces lésions de reperfusion, mais que cet effet bénéfique reste limité dans un contexte de diabète.Dans ce travail, nous avons tout d’abord étudié l’impact du diabète de type 2 sur la fonction mitochondriale. Les études ont été réalisées sur des trabécules d’oreillette humaine, et dans deux sous-populations mitochondriales, les mitochondries sous-sarcolemmales (SSM) et interfibrillaires (IFM), par des approches polarographique, spectrophotométrique et protéomique. Alors que des différences sont observées en termes d’activité enzymatique et d’expression protéique entre SSM et IFM, nous n’avons pas observé d’effet lié au diabète sur la fonction mitochondriale.Dans un second temps, nous avons développé un modèle d’étude des lésions d’ischémie reperfusion chez la souris en utilisant la technique de Langendorff. Nous avons étudié les effets sur la fonction cardiaque et sur le volume de nécrose, du post-conditionnement pharmacologique par différents agonistes et antagonistes opioïdes (morphine, [D-Pen2,D-Pen5]-enkephaline (DPDPE), naloxone, naltrindole) après une ischémie globale. Chacune des molécules testées réduit le volume de nécrose. La fonction cardiaque était également améliorée après 60 minutes de reperfusion en présence de morphine seule, de naloxone seule, et des associations morphine-naloxone et DPDPE-naltrindole. Les mécanismes moléculaires impliqués dans ces effets cardioprotecteurs nécessitent d’être mieux compris avant d'envisager une application chez l’Homme, en particulier chez le patient diabétique, afin de limiter les lésions de reperfusion dans un contexte d’infarctus du myocarde. / The morbidity and the mortality of the heart stroke have been reduced over the last 30 years and it was related to an improvement of patient care. The early reperfusion of the heart is an essential step, but is responsible for ischemia-reperfusion injuries. Both ischemic and pharmacological conditionings were shown to increase heart function, but these beneficial effects are reduced in a context of diabetes mellitus.First, we studied the effect of type 2 diabetes mellitus on mitochondrial function. Studies were performed on heart trabeculae, and in subsarcolemmal (SSM) or interfibrillar (IFM) mitochondria extracted from human atrial appendages using polarographic, spectrophotometric and proteomic analyses. Whereas differences on enzymatic activities and in protein expression were observed between SSM and IFM, we did not find any deleterious effect of diabetes mellitus on mitochondrial function. Second, using a Langendorff’s apparatus, we developed an experimental model in mouse to study ischemia-reperfusion injuries. Pharmacological post-conditioning was tested by using various opioid agonists and antagonists, including morphine, [D-Pen2,D-Pen5]-enkephalin (DPDPE), naloxone, and naltrindole. The effects were observed on heart function and the volume of necrosis. All treatments were effective to reduce the necrosis in the heart compared to control condition. After 60 minutes of reperfusion, cardiac function was also improved with morphine, naloxone, and the association of morphine-naloxone, and DPDPE-naltrindole. A better understanding of the molecular mechanisms is needed to improve pharmacological post-conditioning in patients, particularly in diabetics, presenting with heart stroke.

El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / The incidence of multiple primary neoplasms has been increasing over the years. Within this group, the coexistence of primary prostate cancer and primary colorectal cancer is one of the most frequent. The objective of this case report is to present the case of a 76-year-old male patient who presented the diagnosis of prostate cancer and synchronous rectal cancer. To this end, his clinical history in the oncological service of the Hospital Militar Central del Perú (tertiary hospital) has been reviewed. / Revisión por pares

In the study of multi-agent systems (MASs), cooperative control is one of the most fundamental issues. As it covers a broad spectrum of applications in many industrial areas, there is a desire to design cooperative control protocols for different system and network setups. Motivated by this fact, in this thesis we focus on elaborating consensus protocol design, via model predictive control (MPC), under two different scenarios: (1) general constrained linear MASs with bounded additive disturbance; (2) linear MASs with input constraints underlying distributed communication networks. In Chapter 2, a tube-based robust MPC consensus protocol for constrained linear MASs is proposed. For undisturbed linear MASs without constraints, the results on designing a centralized linear consensus protocol are first developed by a suboptimal linear quadratic approach. In order to evaluate the control performance of the suboptimal consensus protocol, we use an infinite horizon linear quadratic objective function to penalize the disagreement among agents and the size of control inputs. Due to the non-convexity of the performance function, an optimal controller gain is difficult or even impossible to find, thus a suboptimal consensus protocol is derived. In the presence of disturbance, the original MASs may not maintain certain properties such as stability and cooperative performance. To this end, a tube-based robust MPC framework is introduced. When disturbance is involved, the original constraints in nominal prediction should be tightened so as to achieve robust constraint satisfaction, as the predicted states and the actual states are not necessarily the same. Moreover, the corresponding robust constraint sets can be determined offline, requiring no extra iterative online computation in implementation. In Chapter 3, a novel distributed MPC-based consensus protocol is proposed for general linear MASs with input constraints. For the linear MAS without constraints, a pre-stabilizing distributed linear consensus protocol is developed by an inverse optimal approach, such that the corresponding closed-loop system is asymptotically stable with respect to a consensus set. Implementing this pre-stabilizing controller in a distributed digital setting is however not possible, as it requires every local decision maker to continuously access the state of their neighbors simultaneously when updating the control input. To relax these requirements, the assumed neighboring state, instead of the actual state of neighbors, is used. In our distributed MPC scheme, each local controller minimizes a group of control variables to generate control input. Moreover, an additional state constraint is proposed to bound deviation between the actual and the assumed state. In this way, consistency is enforced between intended behaviors of an agent and what its neighbors believe it will behave. We later show that the closed-loop system converges to a neighboring set of the consensus set thanks to the bounded state deviation in prediction. In Chapter 4, conclusions are made and some research topics for future exploring are presented. / Graduate / 2021-03-31

<div>In recent years, the collective behaviors in nature have motivated rapidly expanding research efforts in the control of multi-agent systems. A multi-agent system is composed of multiple interacting subsystems (agents). In order to seek approaches that respect the network nature of multi-agent systems, distributed algorithms has recently received a significant amount of research attention, the goal of which is allowing multi-agent systems to accomplish global objectives through only local coordination. </div><div> Under this scope, we consider three major problems in this dissertation, namely, distributed computation, distributed optimization, and the resilience of distributed algorithms. First, for distributed computation, we devise distributed algorithms for solving linear equations, which can eliminate the initialization step for agents; converge to the minimum $l_1$ and $l_2$ solutions of under-determined linear equations; achieve ultimate scalability inters of agents' local storage and local states. Second, for distributed optimization, we introduce a new method for algorithm discretization so that the agents no longer have to carefully choose their step-size. We also introduce a new distributed optimization approach that can achieve better convergence rate with lower bandwidth requirement. Finally, for the resilience of distributed algorithms, we propose a new approach that allow normal agents in the multi-agent system to automatically isolate any false information from malicious agents without identification process. Though out the dissertation, all mentioned results are theoretically guaranteed and numerically validated.</div>

In this article, a performance assessment of the evacuation system is established for educational buildings. Structural and geotechnical information of the building is collected and introduced into a database. A similar procedure was realized for the information related to the occupants. Using this information, a) the structural fragility and localized collapse were determined and b) the interaction of the person with the partial collapse was established. For the first aspect, nonlinear time history was used, and for the second, the agent-based modeling was applied to recreate the reaction of people that face the micro collapse. Therefore, the important results of this evaluation are: 1) To localize collapsed beans and columns that make inoperable evacuation routes, 2) to localize bottleneck areas that people concentration during evacuation, and 3) quantification of affected people, in terms of persons caught up in the building that cannot evacuate.

China’s state-led finance to overseas projects becomes increasingly important, represents a growing financial trend among emerging market economies, and leads to the puzzle: to what extent are state-owned (policy) bank driven by state or by its own interest. The project compares China’s practice of overseas energy finance with Japan – a well-studied case of state-supported development – to highlight the characteristics of Chinese public financiers and integrate their practice into development theories. The project speaks to three major development theories: the market model, in which banks pursue profit; the state model, in which banks are commanded by state; and the interest group model, in which conflicting goals clash in the repeating game between stakeholders. The project argues that banks balance their self-interest and state assignments depending on the regulator-bank and bank-client bargains. In the project, the first research article compiles publicly available data on policy bank loan and calculates the influence of various determinants on loans granted by policy banks. The findings are that Chinese and Japanese banks are driven by both profit and non-market goals and tend to invest in recipients with high risks. Going beyond large-N statistical modeling, the second article uses archives and interviews to investigate to what extent do investment in risky projects are driven by state goals. The article develops an interest-group bargaining model, in which the analysis focuses on four sets of actors in the process of project formation, crisis emergence, and resolution/or lack of resolution. While projects with innate high risk are often considered as economic diplomacy, evidences suggest the projects are mostly driven by recipient governments and for-profit banks. The third, and final, research article relies on elite interviews and archival analysis to investigate the domestic politics of policy bank regulation and the formation of loan policies. Between China and Japan, the article formulates two different institutional structures that govern the effectiveness of policy bank regulation. In Japan, the structure is vertical, with paired ministry-bank regulations. In China, the institutional structure is more like umbrella-shaped joint regulation. This leads to more interactions between the leading regulator and banks and occasionally more efficient policy implementation.

Lanthanide-based nanoparticles (Ln3+-based NPs) are promising candidates as magnetic resonance imaging (MRI) contrast agents. The present thesis aims to investigate the effect of the crystalline phase of Ln3+-based NPs on their MRI contrast performance. Understanding the phase-dependent MRI contrast behaviour of Ln3+-based NPs will provide insights into the development of brighter MRI contrast agents for future in vivo biomedical applications. A set of NaGdF4 NPs (6-8 nm) in cubic and hexagonal phases in the same size range was synthesized by employing a microwave-assisted approach, allowing the influence of host crystallinity on MRI T1 relaxivity to be investigated (chapter 4). The results showed that cubic NaGdF4 NPs exhibited superior performance as MRI T1 contrast agents than their hexagonal analogues, irrespective of the chosen surface modification, e.g. small citrate groups or longer chain poly(acrylic acid). NaDyF4 NPs (3 nm) were synthesized in both phases to assess whether phase-dependent MRI contrast behaviour consistently exists in other Ln3+-base NPs of the NaLnF4 family (chapter 5). Again, it was demonstrated that cubic NaDyF4 NPs had a better contrast performance as T2 contrast agents than the hexagonal NPs. Alternatively, cubic NaEuF4 NPs, exhibiting additional optical properties (e.g. red emission under UV excitation), were prepared as potential candidates for the preparation of chemical exchange saturation transfer (CEST) contrast agents (chapter 5). Chapter 6 introduces preliminary dispersion stability studies of cubic NaGdF4 NPs dispersed in different buffer solutions, the obtained hydrodynamic diameters indicated that NaGdF4 NPs possessed better dispersity in saline than that in PBS solution.

Background Efficacy and safety of treatments for hospitalized COVID-19 are uncertain. We systematically reviewed efficacy and safety of remdesivir for the treatment of COVID-19. Methods Studies evaluating remdesivir in adults with hospitalized COVID-19 were searched in several engines until August 21, 2020. Primary outcomes included all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAEs). Inverse variance random effects meta-analyses were performed. Results We included four randomized controlled trials (RCTs) (n = 2296) [two vs. placebo (n = 1299) and two comparing 5-day vs. 10-day regimens (n = 997)], and two case series (n = 88). Studies used intravenous remdesivir 200mg the first day and 100mg for four or nine more days. One RCT (n = 236) was stopped early due to AEs; the other three RCTs reported outcomes between 11 and 15 days. Time to recovery was decreased by 4 days with remdesivir vs. placebo in one RCT (n = 1063), and by 0.8 days with 5-days vs. 10-days of therapy in another RCT (n = 397). Clinical improvement was better for 5-days regimen vs. standard of care in one RCT (n = 600). Remdesivir did not decrease all-cause mortality (RR 0.71, 95% CI 0.39 to 1.28, I2 = 43%) and need for invasive ventilation (RR 0.57, 95%CI 0.23 to 1.42, I2 = 60%) vs. placebo at 14 days but had fewer SAEs; 5-day decreased need for invasive ventilation and SAEs vs. 10-day in one RCT (n = 397). No differences in all-cause mortality or SAEs were seen among 5-day, 10-day and standard of care. There were some concerns of bias to high risk of bias in RCTs. Heterogeneity between studies could be due to different severities of disease, days of therapy before outcome determination, and how ordinal data was analyzed. Conclusions There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in hospitalized COVID-19 patients. Until stronger evidence emerges, we cannot conclude that remdesivir is efficacious for treating COVID-19. / Revisión por pares