Systems Engineering

The book "Systems Engineering: Practice and Theory" is a collection of articles written by developers and researches from all around the globe. Mostly they present methodologies for separate Systems Engineering processes; others consider issues of adjacent knowledge areas and sub-areas that significantly contribute to systems development, operation, and maintenance. Case studies include aircraft, spacecrafts, and space systems development, post-analysis of data collected during operation of large systems etc. Important issues related to "bottlenecks" of Systems Engineering, such as complexity, reliability, and safety of different kinds of systems, creation, operation and maintenance of services, system-human communication, and management tasks done during system projects are addressed in the collection. This book is for people who are interested in the modern state of the Systems Engineering knowledge area and for systems engineers involved in different activities of the area. Some articles may be a valuable source for university lecturers and students; most of case studies can be directly used in Systems Engineering courses as illustrative materials

Acute endomyocardial disease in infants and children : the relationship between acute myocarditis and endocardial fibroelastosis

This prospective study of acute myocarditis (AM) and endocardial fibroelastosis (EFE) was prompted by their common occurrence in infants and children in Cape Town, and by the persisting controversy regarding the possible relationship of these two conditions to each other, and to idiopathic, chronic, congestive cardiomyopathy (COCM). Patients with AM and EFE were analysed concurrently and over the long-term. The following hypotheses were investigated: A) that AM and EFE represent different phases of a common disease process, and B) that either AM or EFE evolves into COCM. From 1st June 1970 to 31st December 1976 (a study period of 6 years 7 months), 140 consecutive patients with AM or EFE were evaluated, and continually observed until 31st March 1979 (a total observation period of 8 years 10 months). Because there is no definitive, non-invasive, in-vivo diagnostic test for AM or EFE, an inclusive diagnosis of acute endomyocardial disease (EMD) was made in 123 patients who fulfilled all 4 rigid clinical criteria, i.e. a short history ( 0.55), and ST/T wave changes on electrocardiogram (ECG). Acute EMD was confirmed in all 20 patients who came to autopsy. A further 17 patients with insufficient clinical data had EMD at post-mortem

Performance-Based Quality Specifications: The Link between Product Development and Clinical Outcomes

The design of drug delivery systems and their corresponding dosing guidelines are critical product development functions supported by clinical pharmacokinetic (PK) and pharmacodynamic (PD) data. Largely, the importance of variance and covariance in product and patient attributes is poorly understood. The existence of PK/PD diversity among myriad patient sub-populations further complicates efforts to gauge the importance of product quality variation. Nevertheless, a platform capable of evaluating the effects of product and patient variability on clinical performance was constructed. This dissertation was predicated on requests to re-define pharmaceutical quality in terms of risk by relating clinical attributes to production characteristics. To avoid in vivo studies, simulated experimental trials were conducted using the model drug, theophylline, for which data and models could be acquired from the literature. Where comprehensive data were unavailable (e.g., production variability statistics), initial estimates were acquired via laboratory-scale experiments. Model asthmatic patients were generated using Monte Carlo simulation and published population distributions of various anothropometric measurements, disease rates, and lifestyle factors. Mathematical constructs for in vitro-in vivo correlations provide a linkage between Quality by Design (QbD) product and process models, PK/PD models, and patient population statistics. The combined models formed the foundation for Monte Carlo risk assessments, which characterized the risk of inefficacy and toxicity for dosing of extended-release theophylline tablets. Sensitivity analyses revealed that patient compliance and content uniformity significantly influenced the probability of observing an adverse event. The Monte Carlo risk assessment platform defined the link between the critical quality attributes (CQAs) and clinical performance (i.e., performance-based quality specifications (PBQS)). The PBQS were subsequently utilized to generate process independent design spaces conditioned on inefficacy and toxicity risk. These design spaces, which directly account for the conditional relationships between product quality and patient variability, can be transferred to a specific process via models that relate process critical control parameters to the CQAs. Process Analytical Technology, therefore, can be integrated into the QbD production environment to control the safety and efficacy of the final product. This work demonstrated that process and product knowledge can be used to estimate the risk that final product quality imparts to clinical performance

A record of research directed towards enhancement of the safety of clinical anaesthesia

Clinical Anaesthesia is an indispensable adjunct to the surgical treatment of disease. It directly affects the lives of a great number of people since every year no fewer than one in every twenty-five persons in the population is required to undergo a procedure which necessitates it. Of itself non-therapeutic, clinical anaesthesia must, above all else. be safe for the patient. Any adverse outcome to clinical anaesthesia and factors relevant to its administration results, at best, in postoperative morbidity for the patient and, at worst, his demise. Identification and examination of the factors and circumstances which have a material influence on the safety of anaesthesia for the patient, provided the motivation for and is the central theme of this collection of research publications which was submitted to the University of Cape Town in fulfilment of the requirements for the award of the Degree of Doctor of Science (Medicine). The publications submitted report the results of forty years of endeavour. In terms of their subject matter, these publications may be broadly grouped into the following five fields of interest: - 1) The Epidemiology of Death Attributable to Anaesthesia. 2) Pharmacogenetic States of concern to the Anaesthetist - a) The Malignant Hyperthermia Myopathy. b) The Acute Porphyrias. 3) The Effects of Anaesthetics on the Liver - Studies of Hepatic Drug Metabolism of relevance to post-Halothane Hepatitis and the hepatotoxicity of anaesthetic agents. b) The treatment of Fulminant Liver Failure. 4) Heat Homeostasis during Anaesthesia - a) Inadvertent Hypothermia during anaesthesia. b) Induced Hypothermia during anaesthesia. 5) Miscellaneous. Within these fields of interest, papers have been grouped in terms of related aspects of the main topic they cover. Editorial comment is included where appropriate. The nature and scope of many of the above investigations was such as to require, for their satisfactory conclusion, collaborative interdisciplinary research combining the endeavours of other clinicians and paramedical scientists. Appropriate recognition of such collaboration has resulted in the multiple authorship registered for many of the publications in this collection

Progress Report No. 12

Progress report of the Biomedical Computer Laboratory, covering period 1 July 1975 to 30 June 1976