The use of a formal sensitivity analysis on epidemic models with immune protection from maternally acquired antibodies

This paper considers the outcome of a formal sensitivity analysis on a series of epidemic model structures developed to study the population level effects of maternal antibodies. The analysis is used to compare the potential influence of maternally acquired immunity on various age and time domain observations of infection and serology, with and without seasonality. The results of the analysis indicate that time series observations are largely insensitive to variations in the average duration of this protection, and that age related empirical data are likely to be most appropriate for estimating these characteristics

Mathematical modelling of epidemic systems influenced by maternal antibodies and public health intervention

The general subject area of research considered in this thesis is population level epidemic modelling of infectious diseases, with specific application to the problems of model indeterminacy and systems that include processes associated with maternally acquired immunity. The work presents the derivation and analysis of a lumped systems model framework to study the influence of maternal antibodies on the population dynamics of infection among neonate and young infant age classes. The proposed models are defined by sets of ordinary and partial differential equations that describe the variation of distinct states in the natural history of infection with respect to time and/or age. The model framework is extended to explore the potential population level outcomes and consequences of mass maternal immunisation: an emerging targeted vaccine strategy that utilises the active transfer of neutralising antibodies during pregnancy in order to supplement neonatal immunity during the first few months of life. A qualitative analysis of these models has highlighted the importance of interaction with early childhood targeted vaccination campaigns, the potential to invoke transient epidemic behaviour and the prospective advantages of seasonal administration. The work considers the implications of structural identifiability, indistinguishability and formal sensitivity analyses on a number of fundamental model structures within the proposed framework. These methods are used to establish whether a postulated model structure, or the individual parameters within a known structure, are uniquely determinable from a given set of empirical observations. The main epidemiological measures available for the validation of epidemic models are inherently based on records of clinical disease or age serological surveys, which are not explicitly representative of infection and provide a very limited observation of the full system state. The analyses suggest that these issues give rise to problems of indeterminacy even in the most simple models, such that certain system characteristics cannot be uniquely estimated from available data

Systematic review of the current status of cadaveric simulation for surgical training

Background: There is growing interest in and provision of cadaveric simulation courses for surgical trainees. This is being driven by the need to modernize and improve the efficiency of surgical training within the current challenging training climate. The objective of this systematic review is to describe and evaluate the evidence for cadaveric simulation in postgraduate surgical training. Methods: A PRISMA‐compliant systematic literature review of studies that prospectively evaluated a cadaveric simulation training intervention for surgical trainees was undertaken. All relevant databases and trial registries were searched to January 2019. Methodological rigour was assessed using the widely validated Medical Education Research Quality Index (MERSQI) tool. Results: A total of 51 studies were included, involving 2002 surgical trainees across 69 cadaveric training interventions. Of these, 22 assessed the impact of the cadaveric training intervention using only subjective measures, five measured impact by change in learner knowledge, and 23 used objective tools to assess change in learner behaviour after training. Only one study assessed patient outcome and demonstrated transfer of skill from the simulated environment to the workplace. Of the included studies, 67 per cent had weak methodology (MERSQI score less than 10·7). Conclusion: There is an abundance of relatively low‐quality evidence showing that cadaveric simulation induces short‐term skill acquisition as measured by objective means. There is currently a lack of evidence of skill retention, and of transfer of skills following training into the live operating theatre

On the Lawrence–Doniach and Anisotropic Ginzburg–Landau Models for Layered Superconductors

The authors consider two models, the Lawrence-Doniach and the anisotropic Ginzburg-Landau models for layered superconductors such as the recently discovered high-temperature superconductors. A mathematical description of both models is given and existence results for their solution are derived. The authors then relate the two models in the sense that they show that as the layer spacing tends to zero, the Lawrence-Doniach model reduces to the anisotropic Ginzburg- Landau model. Finally, simplified versions of the models are derived that can be used to accurately simulate high-temperature superconductors

Mathematical modelling of epidemic systems influenced by maternal antibodies and public health intervention

The general subject area of research considered in this thesis is population level epidemic modelling of infectious diseases, with specific application to the problems of model indeterminacy and systems that include processes associated with maternally acquired immunity. The work presents the derivation and analysis of a lumped systems model framework to study the influence of maternal antibodies on the population dynamics of infection among neonate and young infant age classes. The proposed models are defined by sets of ordinary and partial differential equations that describe the variation of distinct states in the natural history of infection with respect to time and/or age. The model framework is extended to explore the potential population level outcomes and consequences of mass maternal immunisation: an emerging targeted vaccine strategy that utilises the active transfer of neutralising antibodies during pregnancy in order to supplement neonatal immunity during the first few months of life. A qualitative analysis of these models has highlighted the importance of interaction with early childhood targeted vaccination campaigns, the potential to invoke transient epidemic behaviour and the prospective advantages of seasonal administration. The work considers the implications of structural identifiability, indistinguishability and formal sensitivity analyses on a number of fundamental model structures within the proposed framework. These methods are used to establish whether a postulated model structure, or the individual parameters within a known structure, are uniquely determinable from a given set of empirical observations. The main epidemiological measures available for the validation of epidemic models are inherently based on records of clinical disease or age serological surveys, which are not explicitly representative of infection and provide a very limited observation of the full system state. The analyses suggest that these issues give rise to problems of indeterminacy even in the most simple models, such that certain system characteristics cannot be uniquely estimated from available data.EThOS - Electronic Theses Online ServiceUniversity of Warwick. Dept. of EngineeringEngineering and Physical Sciences Research Council (EPSRC)GBUnited Kingdo

The application of travel demand management initiatives within a university setting

This research was undertaken as part of the UK Energy Research Centre (UKERC) research programme under the ADdressing Valuation of Energy and Nature Together (ADVENT) project, funded by the Natural Environment Research Council (NE/M019691/1) United Kingdom. Funding was also received from the School of Biological Sciences at the University of Aberdeen, United Kingdom. The authors would like to thank Dr Kate Pangbourne, The University of Leeds, for their detailed and constructive feedback on this paper. The authors would also like to acknowledge Dr Alex Douglas for their input in the methodology.Peer reviewedPostprin

Widespread and persistent invasions of terrestrial habitats coincident with larval feeding behavior transitions during snail-killing fly evolution (Diptera: Sciomyzidae)

BACKGROUND: Transitions in habitats and feeding behaviors were fundamental to the diversification of life on Earth. There is ongoing debate regarding the typical directionality of transitions between aquatic and terrestrial habitats and the mechanisms responsible for the preponderance of terrestrial to aquatic transitions. Snail-killing flies (Diptera: Sciomyzidae) represent an excellent model system to study such transitions because their larvae display a range of feeding behaviors, being predators, parasitoids or saprophages of a variety of mollusks in freshwater, shoreline and dry terrestrial habitats. The remarkable genus Tetanocera (Tetanocerini) occupies five larval feeding groups and all of the habitat types mentioned above. This study has four principal objectives: (i) construct a robust estimate of phylogeny for Tetanocera and Tetanocerini, (ii) estimate the evolutionary transitions in larval feeding behaviors and habitats, (iii) test the monophyly of feeding groups and (iv) identify mechanisms underlying sciomyzid habitat and feeding behavior evolution. RESULTS: Bayesian inference and maximum likelihood analyses of molecular data provided strong support that the Sciomyzini, Tetanocerini and Tetanocera are monophyletic. However, the monophyly of many behavioral groupings was rejected via phylogenetic constraint analyses. We determined that (i) the ancestral sciomyzid lineage was terrestrial, (ii) there was a single terrestrial to aquatic habitat transition early in the evolution of the Tetanocerini and (iii) there were at least 10 independent aquatic to terrestrial habitat transitions and at least 15 feeding behavior transitions during tetanocerine phylogenesis. The ancestor of Tetanocera was aquatic with five lineages making independent transitions to terrestrial habitats and seven making independent transitions in feeding behaviors. CONCLUSIONS: The preponderance of aquatic to terrestrial transitions in sciomyzids goes against the trend generally observed across eukaryotes. Damp shoreline habitats are likely transitional where larvae can change habitat but still have similar prey available. Transitioning from aquatic to terrestrial habitats is likely easier than the reverse for sciomyzids because morphological characters associated with air-breathing while under the water\u27s surface are lost rather than gained, and sciomyzids originated and diversified during a general drying period in Earth\u27s history. Our results imply that any animal lineage having aquatic and terrestrial members, respiring the same way in both habitats and having the same type of food available in both habitats could show a similar pattern of multiple independent habitat transitions coincident with changes in behavioral and morphological traits

Comparison of monophasic with single and dual capacitor biphasic waveforms for nonthoracotomy canine internal defibrillation

AbstractMonophasic and single capacitor and dual capacitor biphasic truncated exponential shocks were tested in pentobarbital-anesthetized dogs with use of a nonthoracotomy internal defibrillation pathway consisting of a right ventricular catheter electrode and a subcutaneous chest wall patch electrode. Seven dogs weighing 20.2 ± 0.5 kg were utilized. Monophasic pulses of 10 ms duration were compared with three biphasic pulses. All biphasic waveforms had an initial positive phase (PI) followed by a terminal negative phase (P2) and the total duration of Pt Plus P2 was 10 ms. The dual capacitor biphasic waveform (PI 9 ms, P2 1 ms) had equal initial voltages of Pt and P2. Two simulated single capacitor biphasic waveforms were also tested, the first designed to minimize the magnitude of P2 (P19 ms, P21 ms with initial voltage of P2 equal to 0.3 of the initial voltage of P1) and the second to maximize P2 (PI 5 ms, P2 5 ms with initial voltage of P2 = 0.5 PI).Alternating current was used to induce ventricular fibrillation and four trials of eight initial voltages from 100 to 800 V were performed for each of the four waveforms. Stepwise logistic regression was utilized to construct curves relating probability of successful defibrillation and energy.In the logistic model, the dual capacitor biphasic and single capacitor biphasic waveforms that maximized P2 were associated with significantly (p < 0.001) lower energy requirements for defibrillation than those of the monophasic waveform. The single capacitor biphasic waveform that minimized P2 was not significantly better than the monophasic waveform. The biphasic waveforms associated with the lowest energy requirements for defibrillation were characterized by a higher P2/PI energy ratio.These results demonstrate that single capacitor biphasic waveforms can be constructed that are superior to similar duration monophasic waveforms and comparable with some dual capacitor biphasic waveforms. The relative magnitude of PI and P2 appears to be an important determinant of defibrillation efficacy