Maternal diabetes during pregnancy – obstetrical considerations and long term effects

Maternal diabetes mellitus (DM) during pregnancy has detrimental health impacts on both the mother and fetus, and include increased risks of cardiac malformations, cesarean section (CS), and asphyxia. The aim of the thesis was to investigate short and long term cardiac effects after fetal exposure to DM, investigate the ability of a 5 minute Apgar score as a marker for obstetrical care, investigate the association between mode of delivery in diabetic pregnancies and a low 5 minute Apgar score, and to investigate the association between offspring birth weight and maternal risk of future DM. Paper 1: Fetuses to mothers with either type 1 DM (p = 0.0015) and gestational diabetes mellitus (GDM) (p = 0.006) showed increased pulsatility index in the ductus venosus (PI-DV) in relation to gestational age. After the exclusion of SGA fetuses and those with blood flow changes, the PI-DV was still increased in type 1 DM (p = 0.02) and GDM pregnancies (p = 0.035), presumably reflecting short term cardiac impact. Paper 2: Fetuses exposed to type 1 DM showed an increased risk of future cardiovascular disease, as measured by consumption of drugs for cardiovascular disease, OR 1.46 (95% CI 1.16-1.83), this increased risk was however no longer present when data was adjusted for offspring with insulin dependent DM, OR 1.22 (95% CI 0.97-1.54). As previous studies have showed, an increased risk of future cardiovascular disease was found when born SGA, OR 1.29 (95% CI 1.24-1.35). No increased risk was found after being born LGA. Paper 3: The Apgar score is a resourceful marker of obstetrical care, as a substantial risk increase of needing education in special schools, OR =1.93(95% CI 1.75-2.14) low, or no grades when graduating from compulsory school, in nearly all school subjects, was found after being born with a 5 minute Apgar score under 7. One of 44 children born with an Apgar-score <7 at 5 minutes after birth will need education in a special school due to the factors leading to the low Apgar score. Paper 4: A 50% decreased risk of an Apgar score<7 at 5 minutes was found in DM+GDM pregnancies after a planned CS in gestational week 38 as compared to planned vaginal birth (from gestational week 39 and beyond), (p= 0.021), but no decreased risk was found in the DM group (p=0.08), GDM group (p=0.12) or LGA group alone (p=0.06). Paper 5: Offspring birth weight is a direct mirror of the maternal metabolic status, as a profound risk increase of developing both type 1 OR=3.46 (95% CI 3.12-3.83) or type 2 DM OR= 2.90 (95% CI 2.80-3.01) was found subsequent to giving birth to a LGA or macrosomic fetus

Repository as a service (RaaS)

In his oft-quoted seminal paper ‘Institutional Repositories: Essential Infrastructure For Scholarship In The Digital Age’ Clifford Lynch (2003) described the Institutional Repository as “a set of services that a university offers to the members of its community for the management and dissemination of digital materials created by the institution and its community members.” This paper seeks instead to define the repository service at a more primitive level, without the specialism of being an ‘Institutional Repository’, and looks at how it can viewed as providing a service within appropriate boundaries, and what that could mean for the future development of repositories, our expectations of what repositories should be, and how they could fit into the set of services required to deliver an Institutional Repository service as describe by Lynch.<br/

The South African Medicines Control Council: Comparison of Its Registration Process With Australia, Canada, Singapore, and Switzerland

© 2019 Keyter, Salek, Banoo and Walker.Introduction: Comparisons between regulatory authorities of similar size and regulatory characteristics facilitate value-added benchmarking and provide insight into regulatory performance. Such comparisons highlight areas for improvement as authorities move toward achieving their regulatory goals and stakeholders’ demands. The aims of this study were to compare the registration process and the regulatory review model of the South African Medicines Control Council (MCC) to that of four other similar-sized regulatory authorities and to identify areas for improvement that may inform recommendations to the South African Health Products Regulatory Authority (SAHPRA) as it looks to re-engineer and enhance the registration process in South Africa. Methods: A questionnaire describing the organisational structure, the registration process, good review and decision-making practices of the MCC was completed by the author (AK) for the purpose of this study and validated by the Registrar of the MCC. Similar questionnaires were also completed and validated by Australia’s Therapeutic Goods Administration (TGA), Canada’s Health Canada, Singapore’s Health Science Authority (HSA) and Switzerland’s Swissmedic. Results: A comparison of the MCC regulatory process with the four comparative agencies indicated that they all have similar requirements and employ a full-review model although the timelines for the MCC were considerably longer. However, similar quality measures were implemented by all authorities as part of their good review practices (GRevP) including prioritising transparency, communication, continuous improvement initiatives and training. Conclusion: Comparisons made through this study provided insight into the areas of the MCC registration process that may be improved and have informed recommendations to SAHPRA including the implementation of facilitated regulatory pathways, definition of targets for key milestones in regulatory review and formal implementation and monitoring of GRevP. In order to build quality into the review process the application of a standardised template for the clinical assessment of medicines such as the Universal Methodology for Benefit-Risk Assessment (UMBRA) could be considered as well as enhancing transparency and communication through the application of an electronic management system and the development of publicly available summaries for the basis of approval.Peer reviewedFinal Published versio

A Game-Theoretic Approach to Energy-Efficient Modulation in CDMA Networks with Delay Constraints

A game-theoretic framework is used to study the effect of constellation size on the energy efficiency of wireless networks for M-QAM modulation. A non-cooperative game is proposed in which each user seeks to choose its transmit power (and possibly transmit symbol rate) as well as the constellation size in order to maximize its own utility while satisfying its delay quality-of-service (QoS) constraint. The utility function used here measures the number of reliable bits transmitted per joule of energy consumed, and is particularly suitable for energy-constrained networks. The best-response strategies and Nash equilibrium solution for the proposed game are derived. It is shown that in order to maximize its utility (in bits per joule), a user must choose the lowest constellation size that can accommodate the user's delay constraint. Using this framework, the tradeoffs among energy efficiency, delay, throughput and constellation size are also studied and quantified. The effect of trellis-coded modulation on energy efficiency is also discussed.Comment: Appeared in the Proceedings of the 2007 IEEE Radio and Wireless Symposium, Long Beach, CA, January 9-11, 200

A Game-Theoretic Approach to Energy-Efficient Modulation in CDMA Networks with Delay QoS Constraints

A game-theoretic framework is used to study the effect of constellation size on the energy efficiency of wireless networks for M-QAM modulation. A non-cooperative game is proposed in which each user seeks to choose its transmit power (and possibly transmit symbol rate) as well as the constellation size in order to maximize its own utility while satisfying its delay quality-of-service (QoS) constraint. The utility function used here measures the number of reliable bits transmitted per joule of energy consumed, and is particularly suitable for energy-constrained networks. The best-response strategies and Nash equilibrium solution for the proposed game are derived. It is shown that in order to maximize its utility (in bits per joule), a user must choose the lowest constellation size that can accommodate the user's delay constraint. This strategy is different from one that would maximize spectral efficiency. Using this framework, the tradeoffs among energy efficiency, delay, throughput and constellation size are also studied and quantified. In addition, the effect of trellis-coded modulation on energy efficiency is discussed.Comment: To appear in the IEEE Journal on Selected Areas in Communications (JSAC): Special Issue on Non-Cooperative Behavior in Networking, August 200

Is the Emergence of Life an Expected Phase Transition in the Evolving Universe?

We propose a novel definition of life in terms of which its emergence in the universe is expected, and its ever-creative open-ended evolution is entailed by no law. Living organisms are Kantian Wholes that achieve Catalytic Closure, Constraint Closure, and Spatial Closure. We here unite for the first time two established mathematical theories, namely Collectively Autocatalytic Sets and the Theory of the Adjacent Possible. The former establishes that a first-order phase transition to molecular reproduction is expected in the chemical evolution of the universe where the diversity and complexity of molecules increases; the latter posits that, under loose hypotheses, if the system starts with a small number of beginning molecules, each of which can combine with copies of itself or other molecules to make new molecules, over time the number of kinds of molecules increases slowly but then explodes upward hyperbolically. Together these theories imply that life is expected as a phase transition in the evolving universe. The familiar distinction between software and hardware loses its meaning in living cells. We propose new ways to study the phylogeny of metabolisms, new astronomical ways to search for life on exoplanets, new experiments to seek the emergence of the most rudimentary life, and the hint of a coherent testable pathway to prokaryotes with template replication and coding

Emergence of Organisms.

Since early cybernetics studies by Wiener, Pask, and Ashby, the properties of living systems are subject to deep investigations. The goals of this endeavour are both understanding and building: abstract models and general principles are sought for describing organisms, their dynamics and their ability to produce adaptive behavior. This research has achieved prominent results in fields such as artificial intelligence and artificial life. For example, today we have robots capable of exploring hostile environments with high level of self-sufficiency, planning capabilities and able to learn. Nevertheless, the discrepancy between the emergence and evolution of life and artificial systems is still huge. In this paper, we identify the fundamental elements that characterize the evolution of the biosphere and open-ended evolution, and we illustrate their implications for the evolution of artificial systems. Subsequently, we discuss the most relevant issues and questions that this viewpoint poses both for biological and artificial systems

A Third Transition in Science?

Since Newton, classical and quantum physics depend upon the "Newtonian Paradigm". The relevant variables of the system are identified. For example, we identify the position and momentum of classical particles. Laws of motion in differential form connecting the variables are formulated. An example is Newton's three Laws of Motion. The boundary conditions creating the phase space of all possible values of the variables are defined. Then, given any initial condition, the differential equations of motion are integrated to yield an entailed trajectory in the pre-stated phase space. It is fundamental to the Newtonian Paradigm that the set of possibilities that constitute the phase space is always definable and fixed ahead of time. This fails for the diachronic evolution of ever-new adaptations in any biosphere. Living cells achieve Constraint Closure and construct themselves. Thus, living cells, evolving via heritable variation and Natural selection, adaptively construct new-in-the-universe possibilities. We can neither define nor deduce the evolving phase space: We can use no mathematics based on Set Theory to do so. We cannot write or solve differential equations for the diachronic evolution of ever-new adaptations in a biosphere. Evolving biospheres are outside the Newtonian Paradigm. There can be no Theory of Everything that entails all that comes to exist. We face a third major transition in science beyond the Pythagorean dream that ``All is Number'' echoed by Newtonian physics. However, we begin to understand the emergent creativity of an evolving biosphere: Emergence is not engineering

The world is not a theorem

The evolution of the biosphere unfolds as a luxuriant generative process of new living forms and functions. Organisms adapt to their environment, exploit novel opportunities that are created in this continuous blooming dynamics. Affordances play a fundamental role in the evolution of the biosphere, for organisms can exploit them for new morphological and behavioral adaptations achieved by heritable variations and selection. This way, the opportunities offered by affordances are then actualized as ever novel adaptations. In this paper we maintain that affordances elude a formalization that relies on set theory: we argue that it is not possible to apply set theory to affordances, therefore we cannot devise a set-based mathematical theory of the diachronic evolution of the biosphere.Comment: Minor changes in abstract and sec.2 Added a paragraph in sec.3 on the role of non-ergodicity; added also a paragraph on Turing machines and syntactic information. Sec.5 added a paragraph for clarifying the difference between our statement and the case of chaotic dynamical system