A Systems-Based Patient Aid Design Artifact for Active Medication Management in Type 2 Diabetes

In this dissertation, I explore the use of the Abstraction-Decomposition Space (ADS) alongside Hierarchical Task Analysis (HTA) to guide the design of a minimalist patient aid for active medication management in type 2 diabetes. The goal is to address a practical problem, but in addition, this study seeks to address a theoretical problem that is prevalent in design research in Information Systems (IS) today. The practical problem concerns the need for IT-based care delivery models to support patients in the interim period between in-person visits. In this vein, I present a bare-minimum design that focuses on the most essential functionality required to achieve remote insulin titration using the ADS and HTA. The theoretical problem, on the other hand, pertains to the limitations resulting from taking a tool-focused view in design research which inhibits our ability to produce generalized knowledge about IT systems in their contexts. The study proposes an alternative view based on work systems. The overarching thesis is that a work systems view provides for knowledge at a more abstract and generalizable level, yielding contributions beyond mere software packages. Moreover, the study highlights the artifact-building methodology used to delineate the rationale behind the design and to balance evaluation-dominant design research. In this vein, I conducted document analysis and semi-structured interviews with patients and care providers to develop the ADS, then used it alongside HTA to develop and test the usability of twelve user scenarios implemented on a large mobile form factor

Optimization and control of virus-host systems

Optimization and control are powerful tools to design a system that works as effectively as possible. In this thesis, we focus on applications of model-based optimization and control in complex virus-host systems at multiple scales. Viruses that infect bacteria, i.e., bacteriophage or ‘phage’, are increasingly considered as treatment options for the control and clearance of bacterial infections, particularly as compassionate use therapy for multi-drug resistant infections. Here, we evaluate principles underlying why careful application of multiple phage (i.e., a ‘cocktail’) might lead to therapeutic success in contrast to the failure of single-strain phage therapy to control an infection. We combine dynamical modeling of phage, bacteria, and host immune cell populations with control-theoretic principles (via optimal control theory) to devise phage cocktails and delivery schedules to control the bacterial populations. However, a risk in using cocktails of different phage is that bacteria could simultaneously develop resistance to all injected phage (i.e., selecting for multi-phage resistant). The next step is to understand how to pre-select phage that have adapted via co-evolution with bacterial strains and then to efficiently use these ‘future’ phage to clear the infection early on. In doing so, we develop the evolutionarily robust phage therapy in immunodeficient hosts given the infection networks that was identified in co-evolutionary training. Optimization and control not only can be applied to bacteria-phage-immune systems (i.e., at the microbial level) to help design phage therapy, but also can be applied to epidemiological systems (i.e., at the large-scale population level) to guide the development and deployment of efficient interventions. Lockdowns and stay-at-home orders have reduced the transmission of SARS-CoV-2 but have come with significant social and economic costs. Here, we describe a control theory framework combining population-scale viral and serological testing as part of an individualized approach to control COVID-19 spread. The aim is to develop policies for modulating individualize contact rates depending on both personalized disease status and the status of the epidemic at the population scale. Altogether in this thesis, we apply control strategies to alleviate the burden or spread of disease at multiple scales.Ph.D

Performance Problem Diagnostics by Systematic Experimentation

Diagnostics of performance problems requires deep expertise in performance engineering and entails a high manual effort. As a consequence, performance evaluations are postponed to the last minute of the development process. In this thesis, we introduce an automatic, experiment-based approach for performance problem diagnostics in enterprise software systems. With this approach, performance engineers can concentrate on their core competences instead of conducting repeating tasks

Determination of eleven steroid hormones and bioavailable testosterone in human serum using salting-out assisted liquid-liquid extraction with UHPLC-MS/MS

Steroid hormones are essential in various biological roles such as the regulation of sexual maturation, fertility, bone and muscle growth, stress-mediated responses, and inflammation, to name a few examples. Impaired steroidogenesis leads to anomalous steroid hormone concentrations and develops into endocrinological disorders, such as polycystic ovarian syndrome (PCOS) and hypogonadism, with physical and mental manifestations affecting life quality and possibly longevity. The detection of aberrant steroid concentrations is crucial for diagnosis and requires adequate biochemical assays to provide correct and reliable quantitation. Ultra-high-performance liquid chromatography (UHPLC-MS/MS) provides greater selectivity and sensitivity for endocrine analysis compared to modern direct immunoassays. This study optimized and validated an UHPLC-MS/MS method using salting-out assisted liquid-liquid extraction (SALLE) for sample clean-up and analyte extraction of 11 steroid hormones from human serum. The analyte panel includes glucocorticoids (cortisol, cortisone, corticosterone, deoxycorticosterone, 11-deoxycortisol), progestogens (progesterone, 17α-hydroxyprogesterone) and androgens (total testosterone, bioavailable testosterone, androstenedione, 11-ketotestosterone, 11β-hydroxyandrostenedione). Additionally, the study involved the analysis of 38 sera samples from healthy individuals through the project “Blood Reference in Stavanger (BRIS)”. The method exhibited its ability as a diagnostic tool by identifying three individuals with anomalous androgen concentrations, including the 11-oxygenated androgens, from the small population cohort studied. The proposed multiplex method demonstrated high-throughput performance with a 2.67-minute cycle time per injection and a fully automated sample preparation with large sample capacity and high time and cost efficiency. Sensitive detection for all analytes was achieved with detection limits (LOD) and quantification limits (LOQ) at 0.01 – 0.12 nmol/L and 0.03 – 0.29 nmol/L, respectively. Satisfactory intermediate precision was found for total testosterone (6%), cortisol (11%), cortisone (4%), progesterone (5%), 17α-hydroxyprogesterone (7%), androstenedione (11%), and corticosterone (6%) in the upper range of endogenous hormone concentrations in real human serum. Additionally, the imprecision of total testosterone in the lower concentration range, corresponding to female endogenous levels, was 8%. Higher imprecisions were observed for deoxycorticosterone (23%), 11-deoxycortisol (16%), 11-ketotestosterone (17%), 11β-hydroxyandrostenedione (11%) due to limitations in the endogenous levels of these steroid hormones, and bioavailable testosterone (21%). The method can simultaneously determine 11 steroid hormones from one single analysis, enabling the exploration of hormone patterns and the intracrine relationship in endocrinological conditions. Multiplex steroid analysis by UHPLC-MS/MS is advantageous in the exclusion of differential diagnoses, replacing multiple single-analyte assays, and expanding the analyte panel to include other steroid hormones such as 21-deoxycortisol and oestrogens

How do naloxone-based interventions work to reduce overdose deaths: a realist review

BACKGROUND: Naloxone-based interventions as part of health systems can reverse an opioid overdose. Previous systematic reviews have identified the effectiveness of naloxone; however, the role of context and mechanisms for its use has not been explored. This realist systematic review aims to identify a theory of how naloxone works based on the contexts and mechanisms that contribute to the success of the intervention for improved outcomes. METHODS: Pre-registered at PROSPERO, this realist review followed RAMESES standards of reporting. Keywords included 'naloxone' and ' opioid overdose'. All study designs were included. Data extraction using 55 relevant outputs based on realist logic produced evidence of two middle-range theories: Naloxone Bystander Intervention Theory and Skills Transfer Theory. RESULTS: Harm reduction and/or low threshold contexts provide a non-judgemental approach which support in-group norms of helping and empower the social identity of the trained and untrained bystander. This context also creates the conditions necessary for skills transfer and diffusion of the intervention into social networks. Stigma and negative attitudes held by first responders and stakeholders involved in the implementation process, such as police or GPs, can prohibit the bystander response by inducing fear in responding. This interferes with skills transfer, naloxone use and carriage of naloxone kits. CONCLUSIONS: The findings provide theoretically informed guidance regarding the harm reduction contexts that are essential for the successful implementation of naloxone-based interventions. Peer-to-peer models of training are helpful as it reinforces social identity and successful skills transfer between bystanders. Health systems may want to assess the prevalence of, and take steps to reduce opioid-related stigma with key stakeholders in contexts using a low threshold training approach to build an environment  to support positive naloxone outcomes. TRIAL REGISTRATION: PROSPERO 2019 CRD42019141003. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12954-022-00599-4

Performance Problem Diagnostics by Systematic Experimentation

In this book, we introduce an automatic, experiment-based approach for performance problem diagnostics in enterprise software systems. The proposed approach systematically searches for root causes of detected performance problems by executing series of systematic performance tests. The presented approach is evaluated by various case studies showing that the presented approach is applicable to a wide range of contexts

Maximising microprocessor reliability through game theory and heuristics

PhD ThesisEmbedded Systems are becoming ever more pervasive in our society, with most routine daily tasks now involving their use in some form and the market predicted to be worth USD 220 billion, a rise of 300%, by 2018. Consumers expect more functionality with each design iteration, but for no detriment in perceived performance. These devices can range from simple low-cost chips to expensive and complex systems and are a major cost driver in the equipment design phase. For more than 35 years, designers have kept pace with Moore's Law, but as device size approaches the atomic limit, layouts are becoming so complicated that current scheduling techniques are also reaching their limit, meaning that more resource must be reserved to manage and deliver reliable operation. With the advent of many-core systems and further sources of unpredictability such as changeable power supplies and energy harvesting, this reservation of capability may become so large that systems will not be operating at their peak efficiency. These complex systems can be controlled through many techniques, with jobs scheduled either online prior to execution beginning or online at each time or event change. Increased processing power and job types means that current online scheduling methods that employ exhaustive search techniques will not be suitable to define schedules for such enigmatic task lists and that new techniques using statistic-based methods must be investigated to preserve Quality of Service. A new paradigm of scheduling through complex heuristics is one way to administer these next levels of processor effectively and allow the use of more simple devices in complex systems; thus reducing unit cost while retaining reliability a key goal identified by the International Technology Roadmap for Semi-conductors for Embedded Systems in Critical Environments. These changes would be beneficial in terms of cost reduction and system exibility within the next generation of device. This thesis investigates the use of heuristics and statistical methods in the operation of real-time systems, with the feasibility of Game Theory and Statistical Process Control for the successful supervision of high-load and critical jobs investigated. Heuristics are identified as an effective method of controlling complex real-time issues, with two-person non-cooperative games delivering Nash-optimal solutions where these exist. The simplified algorithms for creating and solving Game Theory events allow for its use within small embedded RISC devices and an increase in reliability for systems operating at the apex of their limits. Within this Thesis, Heuristic and Game Theoretic algorithms for a variety of real-time scenarios are postulated, investigated, refined and tested against existing schedule types; initially through MATLAB simulation before testing on an ARM Cortex M3 architecture functioning as a simplified automotive Electronic Control Unit.Doctoral Teaching Account from the EPSRC

Improvement of power grid stability and load distribution using diesel excitation controller

One of the requirements for controlling hybrid power systems is designing an appropriate excitation system, flexibility, protection, and coordination of all components to improve system stability. In this paper, various types of equipment simulated in the linear form and non-linear models are connected to the power supply. In the same direction, while presenting a new controller for the diesel generator excitation system and a filter used to purify and attenuate current harmonics is reported on the stability of a grid-independent system. Finally, the variation of the mode for the voltage and power of the system has been confirmed at the time of error and complete system stability. Also, the important indicators in the analysis are obtained in the lowest values, which can be seen from the controlled harmonics of the system of this data. In addition, the variation of the mode for the voltage and power of the system has been confirmed and the important indicators in the analysis are obtained in the lowest values