Informing Marine Spatial Planning (MSP) with numerical modelling: A case-study on shellfish aquaculture in Malpeque Bay (Eastern Canada)

A moratorium on further bivalve leasing was established in 1999–2000 in Prince Edward Island (Canada). Recently, a marine spatial planning process was initiated explore potential mussel culture expansion in Malpeque Bay. This study focuses on the effects of a projected expansion scenario on productivity of existing leases and available suspended food resources. The aim is to provide a robust scientific assessment using available datasets and three modelling approaches ranging in complexity: (1) a connectivity analysis among culture areas; (2) a scenario analysis of organic seston dynamics based on a simplified biogeochemical model; and (3) a scenario analysis of phytoplankton dynamics based on an ecosystem model. These complementary approaches suggest (1) new leases can affect existing culture both through direct connectivity and through bay-scale effects driven by the overall increase in mussel biomass, and (2) a net reduction of phytoplankton within the bounds of its natural variation in the area.

Modelling the development of an online learning resource by health care professionals

The aim of this study was to model the process of development for an Online Learning Resource (OLR) by Health Care Professionals (HCPs) to meet lymphoedema-related educational needs, within an asset-based management context. Previous research has shown that HCPs have unmet educational needs in relation to lymphoedema but details on their specific nature or context were lacking. Against this background, the study was conducted in two distinct but complementary phases. In Phase 1, a national survey was conducted of HCPs predominantly in community, oncology and palliative care services, followed by focus group discussions with a sample of respondents. In Phase 2, lymphoedema specialists (LSs) used an action research approach to design and implement an OLR to meet the needs identified in Phase 1. Study findings were analysed using descriptive statistics (Phase 1), and framework, thematic and dialectic analysis to explore their potential to inform future service development and education theory. Unmet educational need was found to be specific to health care setting and professional group. These resulted in HCPs feeling poorly-equipped to diagnose and manage lymphoedema. Of concern, when identified, lymphoedema was sometimes buried for fear of overwhelming stretched services. An OLR was identified as a means of addressing the unmet educational needs. This was successfully developed and implemented with minimal additional resources. The process model created has the potential to inform contemporary leadership theory in asset-based management contexts. This doctoral research makes a timely contribution to leadership theory since the resource constraints underpinning much of the contribution has salience to current public services. The process model created has the potential to inform contemporary leadership theory in asset-based management contexts. Further study of a leadership style which incorporates cognisance of Cognitive Load Theory and Self-Determination Theory is suggested. In addition, the detailed reporting of process and how this facilitated learning for participants contributes to workplace education theory

Geothermal district heating networks: modelling novel operational strategies incorporating heat storage

The value of integrating a heat storage into a geothermal district heating system has been investigated. The behaviour of the system under a novel operational strategy has been simulated focusing on the energetic, economic and environmental effects of the new strategy of incorporation of the heat storage within the system. A typical geothermal district heating system consists of several production wells, a system of pipelines for the transportation of the hot water to end-users, one or more re-injection wells and peak-up devices (usually fossil-fuel boilers). Traditionally in these systems, the production wells change their production rate throughout the day according to heat demand, and if their maximum capacity is exceeded the peak-up devices are used to meet the balance of the heat demand. In this study, it is proposed to maintain a constant geothermal production and add heat storage into the network. Subsequently, hot water will be stored when heat demand is lower than the production and the stored hot water will be released into the system to cover the peak demands (or part of these). It is not intended to totally phase-out the peak-up devices, but to decrease their use, as these will often be installed anyway for back-up purposes. Both the integration of a heat storage in such a system as well as the novel operational strategy are the main novelties of this thesis. A robust algorithm for the sizing of these systems has been developed. The main inputs are the geothermal production data, the heat demand data throughout one year or more and the topology of the installation. The outputs are the sizing of the whole system, including the necessary number of production wells, the size of the heat storage and the dimensions of the pipelines amongst others. The results provide several useful insights into the initial design considerations for these systems, emphasizing particularly the importance of heat losses. Simulations are carried out for three different cases of sizing of the installation (small, medium and large) to examine the influence of system scale. In the second phase of work, two algorithms are developed which study in detail the operation of the installation throughout a random day and a whole year, respectively. The first algorithm can be a potentially powerful tool for the operators of the installation, who can know a priori how to operate the installation on a random day given the heat demand. The second algorithm is used to obtain the amount of electricity used by the pumps as well as the amount of fuel used by the peak-up boilers over a whole year. These comprise the main operational costs of the installation and are among the main inputs of the third part of the study. In the third part of the study, an integrated energetic, economic and environmental analysis of the studied installation is carried out together with a comparison with the traditional case. The results show that by implementing heat storage under the novel operational strategy, heat is generated more cheaply as all the financial indices improve, more geothermal energy is utilised and less fuel is used in the peak-up boilers, with subsequent environmental benefits, when compared to the traditional case. Furthermore, it is shown that the most attractive case of sizing is the large one, although the addition of the heat storage most greatly impacts the medium case of sizing. In other words, the geothermal component of the installation should be sized as large as possible. This analysis indicates that the proposed solution is beneficial from energetic, economic, and environmental perspectives. Therefore, it can be stated that the aim of this study is achieved in its full potential. Furthermore, the new models for the sizing, operation and economic/energetic/environmental analyses of these kind of systems can be used with few adaptations for real cases, making the practical applicability of this study evident. Having this study as a starting point, further work could include the integration of these systems with end-user demands, further analysis of component parts of the installation (such as the heat exchangers) and the integration of a heat pump to maximise utilisation of geothermal energy.

Investigating disease persistence in host vector systems: dengue as a case study

The investigation of pathogen persistence in vector-borne diseases is important in different ecological and epidemiological contexts. In this thesis, I have developed deterministic and stochastic models to help investigating the pathogen persistence in host-vector systems by using efficient modelling paradigms. A general introduction with aims and objectives of the studies conducted in the thesis are provided in Chapter 1. The mathematical treatment of models used in the thesis is provided in Chapter 2 where the models are found locally asymptotically stable. The models used in the rest of the thesis are based on either the same or similar mathematical structure studied in this chapter. After that, there are three different experiments that are conducted in this thesis to study the pathogen persistence. In Chapter 3, I characterize pathogen persistence in terms of the Critical Community Size (CCS) and find its relationship with the model parameters. In this study, the stochastic versions of two epidemiologically different host-vector models are used for estimating CCS. I note that the model parameters and their algebraic combination, in addition to the seroprevalence level of the host population, can be used to quantify CCS. The study undertaken in Chapter 4 is used to estimate pathogen persistence using both deterministic and stochastic versions of a model with seasonal birth rate of the vectors. Through stochastic simulations we investigate the pattern of epidemics after the introduction of an infectious individual at different times of the year. The results show that the disease dynamics are altered by the seasonal variation. The higher levels of pre-existing seroprevalence reduces the probability of invasion of dengue. In Chapter 5, I considered two alternate ways to represent the dynamics of a host-vector model. Both of the approximate models are investigated for the parameter regions where the approximation fails to hold. Moreover, three metrics are used to compare them with the Full model. In addition to the computational benefits, these approximations are used to investigate to what degree the inclusion of the vector population in the dynamics of the system is important. Finally, in Chapter 6, I present the summary of studies undertaken and possible extensions for the future work.

Global change and climate-driven invasion of the Pacific oyster (Crassostrea gigas) along European coasts: a bioenergetics modelling approach

Aim The spread of non-indigenous species in marine ecosystems world-wide is one of today's most serious environmental concerns. Using mechanistic modelling, we investigated how global change relates to the invasion of European coasts by a non-native marine invertebrate, the Pacific oyster Crassostrea gigas. Location Bourgneuf Bay on the French Atlantic coast was considered as the northern boundary of C. gigas expansion at the time of its introduction to Europe in the 1970s. From this latitudinal reference, variations in the spatial distribution of the C. gigas reproductive niche were analysed along the north-western European coast from Gibraltar to Norway. Methods The effects of environmental variations on C. gigas physiology and phenology were studied using a bioenergetics model based on Dynamic Energy Budget theory. The model was forced with environmental time series including in situ phytoplankton data, and satellite data of sea surface temperature and suspended particulate matter concentration. Results Simulation outputs were successfully validated against in situ oyster growth data. In Bourgneuf Bay, the rise in seawater temperature and phytoplankton concentration has increased C. gigas reproductive effort and led to precocious spawning periods since the 1960s. At the European scale, seawater temperature increase caused a drastic northward shift (1400 km within 30 years) in the C. gigas reproductive niche and optimal thermal conditions for early life stage development. Main conclusions We demonstrated that the poleward expansion of the invasive species C. gigas is related to global warming and increase in phytoplankton abundance. The combination of mechanistic bioenergetics modelling with in situ and satellite environmental data is a valuable framework for ecosystem studies. It offers a generic approach to analyse historical geographical shifts and to predict the biogeographical changes expected to occur in a climate-changing world.

Grain coarsening in contact metamorphic carbonates: effects of second-phase particles, fluid flow and thermal perturbations

Under contact metamorphic conditions, carbonate rocks in the direct vicinity of the Adamello pluton reflect a temperature-induced grain coarsening. Despite this large-scale trend, a considerable grain size scatter occurs on the outcrop-scale indicating local influence of second-order effects such as thermal perturbations, fluid flow and second-phase particles. Second-phase particles, whose sizes range from nano- to the micron-scale, induce the most pronounced data scatter resulting in grain sizes too small by up to a factor of 10, compared with theoretical grain growth in a pure system. Such values are restricted to relatively impure samples consisting of up to 10 vol.% micron-scale second-phase particles, or to samples containing a large number of nano-scale particles. The obtained data set suggests that the second phases induce a temperature-controlled reduction on calcite grain growth. The mean calcite grain size can therefore be expressed in the form D 1⁄4 C2 eQ*/RT(dp/fp)m*, where C2 is a constant, Q* is an activation energy, T the temperature and m* the exponent of the ratio dp/fp, i.e. of the average size of the second phases divided by their volume fraction. However, more data are needed to obtain reliable values for C2 and Q*. Besides variations in the average grain size, the presence of second-phase particles generates crystal size distribution (CSD) shapes characterized by lognormal distributions, which differ from the Gaussian-type distributions of the pure samples. In contrast, fluid-enhanced grain growth does not change the shape of the CSDs, but due to enhanced transport properties, the average grain sizes increase by a factor of 2 and the variance of the distribution increases. Stable d18O and d13C isotope ratios in fluid-affected zones only deviate slightly from the host rock values, suggesting low fluid/rock ratios. Grain growth modelling indicates that the fluid-induced grain size variations can develop within several ka. As inferred from a combination of thermal and grain growth modelling, dykes with widths of up to 1 m have only a restricted influence on grain size deviations smaller than a factor of 1.1.To summarize, considerable grain size variations of up to one order of magnitude can locally result from second-order effects. Such effects require special attention when comparing experimentally derived grain growth kinetics with field studies.

The Role of decision-analytic modelling in German health technology assessments

BACKGROUND: Decision-analytic modelling (DAM) has become a widespread method in health technology assessments (HTA), but the extent to which modelling is used differs among international HTA institutions. In Germany, the use of DAM is optional within HTAs of the German Institute of Medical Documentation and Information (DIMDI). Our study examines the use of DAM in DIMDI HTA reports and its effect on the quality of information provided for health policies. METHODS: A review of all DIMDI HTA reports (from 1998 to September 2012) incorporating an economic assessment was performed. All included reports were divided into two groups: HTAs with DAM and HTAs without DAM. In both groups, reports were categorized according to the quality of information provided for healthcare decision making. RESULTS: Of the sample of 107 DIMDI HTA reports, 17 (15.9%) used DAM for economic assessment. In the group without DAM, conclusions were limited by the quality of economic information in 51.1% of the reports, whereas we did not find limited conclusions in the group with DAM. Furthermore, 24 reports without DAM (26.7%) stated that using DAM would likely improve the quality of information of the economic assessment. CONCLUSION: The use of DAM techniques can improve the quality of HTAs in Germany. When, after a systematic review of existing literature within a HTA, it is clear that DAM is likely to positively affect the quality of the economic assessment DAM should be used.

Improving the use of G-CSF during chemotherapy using physiological mathematical modelling : a quantitative systems pharmacology approach

La diminution des doses administrées ou même la cessation complète d'un traitement chimiothérapeutique est souvent la conséquence de la réduction du nombre de neutrophiles, qui sont les globules blancs les plus fréquents dans le sang. Cette réduction dans le nombre absolu des neutrophiles, aussi connue sous le nom de myélosuppression, est précipitée par les effets létaux non spécifiques des médicaments anti-cancéreux, qui, parallèlement à leur effet thérapeutique, produisent aussi des effets toxiques sur les cellules saines. Dans le but d'atténuer cet impact myélosuppresseur, on administre aux patients un facteur de stimulation des colonies de granulocytes recombinant humain (rhG-CSF), une forme exogène du G-CSF, l'hormone responsable de la stimulation de la production des neutrophiles et de leurs libération dans la circulation sanguine. Bien que les bienfaits d'un traitement prophylactique avec le G-CSF pendant la chimiothérapie soient bien établis, les protocoles d'administration demeurent mal définis et sont fréquemment déterminés ad libitum par les cliniciens. Avec l'optique d'améliorer le dosage thérapeutique et rationaliser l'utilisation du rhG-CSF pendant le traitement chimiothérapeutique, nous avons développé un modèle physiologique du processus de granulopoïèse, qui incorpore les connaissances actuelles de pointe relatives à la production des neutrophiles des cellules souches hématopoïétiques dans la moelle osseuse. À ce modèle physiologique, nous avons intégré des modèles pharmacocinétiques/pharmacodynamiques (PK/PD) de deux médicaments: le PM00104 (Zalypsis®), un médicament anti-cancéreux, et le rhG-CSF (filgrastim). En se servant des principes fondamentaux sous-jacents à la physiologie, nous avons estimé les paramètres de manière exhaustive sans devoir recourir à l'ajustement des données, ce qui nous a permis de prédire des données cliniques provenant de 172 patients soumis au protocol CHOP14 (6 cycles de chimiothérapie avec une période de 14 jours où l'administration du rhG-CSF se fait du jour 4 au jour 13 post-chimiothérapie). En utilisant ce modèle physio-PK/PD, nous avons démontré que le nombre d'administrations du rhG-CSF pourrait être réduit de dix (pratique actuelle) à quatre ou même trois administrations, à condition de retarder le début du traitement prophylactique par le rhG-CSF. Dans un souci d'applicabilité clinique de notre approche de modélisation, nous avons investigué l'impact de la variabilité PK présente dans une population de patients, sur les prédictions du modèle, en intégrant des modèles PK de population (Pop-PK) des deux médicaments. En considérant des cohortes de 500 patients in silico pour chacun des cinq scénarios de variabilité plausibles et en utilisant trois marqueurs cliniques, soient le temps au nadir des neutrophiles, la valeur du nadir, ainsi que l'aire sous la courbe concentration-effet, nous avons établi qu'il n'y avait aucune différence significative dans les prédictions du modèle entre le patient-type et la population. Ceci démontre la robustesse de l'approche que nous avons développée et qui s'apparente à une approche de pharmacologie quantitative des systèmes (QSP). Motivés par l'utilisation du rhG-CSF dans le traitement d'autres maladies, comme des pathologies périodiques telles que la neutropénie cyclique, nous avons ensuite soumis l'étude du modèle au contexte des maladies dynamiques. En mettant en évidence la non validité du paradigme de la rétroaction des cytokines pour l'administration exogène des mimétiques du G-CSF, nous avons développé un modèle physiologique PK/PD novateur comprenant les concentrations libres et liées du G-CSF. Ce nouveau modèle PK a aussi nécessité des changements dans le modèle PD puisqu’il nous a permis de retracer les concentrations du G-CSF lié aux neutrophiles. Nous avons démontré que l'hypothèse sous-jacente de l'équilibre entre la concentration libre et liée, selon la loi d'action de masse, n'est plus valide pour le G-CSF aux concentrations endogènes et mènerait en fait à la surestimation de la clairance rénale du médicament. En procédant ainsi, nous avons réussi à reproduire des données cliniques obtenues dans diverses conditions (l'administration exogène du G-CSF, l'administration du PM00104, CHOP14). Nous avons aussi fourni une explication logique des mécanismes responsables de la réponse physiologique aux deux médicaments. Finalement, afin de mettre en exergue l’approche intégrative en pharmacologie adoptée dans cette thèse, nous avons démontré sa valeur inestimable pour la mise en lumière et la reconstruction des systèmes vivants complexes, en faisant le parallèle avec d’autres disciplines scientifiques telles que la paléontologie et la forensique, où une approche semblable a largement fait ses preuves. Nous avons aussi discuté du potentiel de la pharmacologie quantitative des systèmes appliquées au développement du médicament et à la médecine translationnelle, en se servant du modèle physio-PK/PD que nous avons mis au point.

Advanced parametrical modelling of 24 GHz radar sensor IC packaging components

This paper deals with the development of an advanced parametrical modelling concept for packaging components of a 24 GHz radar sensor IC used in automotive driver assistance systems. For fast and efficient design of packages for system-in-package modules (SiP), a simplified model for the description of parasitic electromagnetic effects within the package is desirable, as 3-D field computation becomes inefficient due to the high density of conductive elements of the various signal paths in the package. By using lumped element models for the characterization of the conductive components, a fast indication of the design's signal-quality can be gained, but so far does not offer enough flexibility to cover the whole range of geometric arrangements of signal paths in a contemporary package. This work pursues to meet the challenge of developing a flexible and fast package modelling concept by defining parametric lumped-element models for all basic signal path components, e.g. bond wires, vias, strip lines, bumps and balls. © Author(s) 2011. CC Attribution 3.0 License.

A two-fluid model for tissue growth within a dynamic flow environment

We study the growth of a tissue construct in a perfusion bioreactor, focussing on its response to the mechanical environment. The bioreactor system is modelled as a two-dimensional channel containing a tissue construct through which a flow of culture medium is driven. We employ a multiphase formulation of the type presented by G. Lemon, J. King, H. Byrne, O. Jensen and K. Shakesheff in their study (Multiphase modelling of tissue growth using the theory of mixtures. J. Math. Biol. 52(2), 2006, 571–594) restricted to two interacting fluid phases, representing a cell population (and attendant extracellular matrix) and a culture medium, and employ the simplifying limit of large interphase viscous drag after S. Franks in her study (Mathematical Modelling of Tumour Growth and Stability. Ph.D. Thesis, University of Nottingham, UK, 2002) and S. Franks and J. King in their study Interactions between a uniformly proliferating tumour and its surrounding: Uniform material properties. Math. Med. Biol. 20, 2003, 47–89). The novel aspects of this study are: (i) the investigation of the effect of an imposed flow on the growth of the tissue construct, and (ii) the inclusion of a chanotransduction mechanism regulating the response of the cells to the local mechanical environment. Specifically, we consider the response of the cells to their local density and the culture medium pressure. As such, this study forms the first step towards a general multiphase formulation that incorporates the effect of mechanotransduction on the growth and morphology of a tissue construct. The model is analysed using analytic and numerical techniques, the results of which illustrate the potential use of the model to predict the dominant regulatory stimuli in a cell population.

Modelling and analysis of planar cell polarity

Planar cell polarity (PCP) occurs in the epithelia of many animals and can lead to the alignment of hairs, bristles and feathers; physiologically, it can organise ciliary beating. Here we present two approaches to modelling this phenomenon. The aim is to discover the basic mechanisms that drive PCP, while keeping the models mathematically tractable. We present a feedback and diffusion model, in which adjacent cell sides of neighbouring cells are coupled by a negative feedback loop and diffusion acts within the cell. This approach can give rise to polarity, but also to period two patterns. Polarisation arises via an instability provided a sufficiently strong feedback and sufficiently weak diffusion. Moreover, we discuss a conservative model in which proteins within a cell are redistributed depending on the amount of proteins in the neighbouring cells, coupled with intracellular diffusion. In this case polarity can arise from weakly polarised initial conditions or via a wave provided the diffusion is weak enough. Both models can overcome small anomalies in the initial conditions. Furthermore, the range of the effects of groups of cells with different properties than the surrounding cells depends on the strength of the initial global cue and the intracellular diffusion.

Rotation of Vibrio fischeri Flagella Produces Outer Membrane Vesicles That Induce Host Development

Using the squid-vibrio association, we aimed to characterize the mechanism through which Vibrio fischeri cells signal morphogenesis of the symbiotic light-emitting organ. The symbiont releases two cell envelope molecules, peptidoglycan (PG) and lipopolysaccharide (LPS) that, within 12 h of light organ colonization, act in synergy to trigger normal tissue development. Recent work has shown that outer membrane vesicles (OMVs) produced by V. fischeri are sufficient to induce PG-dependent morphogenesis; however, the mechanism(s) of OMV release by these bacteria has not been described. Like several genera of both beneficial and pathogenic bacteria, V. fischeri cells elaborate polar flagella that are enclosed by an extension of the outer membrane, whose function remains unclear. Here, we present evidence that along with the well-recognized phenomenon of blebbing from the cell's surface, rotation of this sheathed flagellum also results in the release of OMVs. In addition, we demonstrate that most of the development-inducing LPS is associated with these OMVs and that the presence of the outer membrane protein OmpU but not the LPS O antigen on these OMVs is important in triggering normal host development. These results also present insights into a possible new mechanism of LPS release by pathogens with sheathed flagella. IMPORTANCE Determining the function(s) of sheathed flagella in bacteria has been challenging, because no known mutation results only in the loss of this outer membrane-derived casing. Nevertheless, the presence of a sheathed flagellum in such host-associated genera as Vibrio, Helicobacter, and Brucella has led to several proposed functions, including physical protection of the flagella and masking of their immunogenic flagellins. Using the squid-vibrio light organ symbiosis, we demonstrate another role, that of V. fischeri cells require rotating flagella to induce apoptotic cell death within surface epithelium, which is a normal step in the organ's development. Further, we present evidence that this rotation releases apoptosis-triggering lipopolysaccharide in the form of outer membrane vesicles. Such release may also occur by pathogens but with different outcomes for the host.

Modelling and simulating retail management practices: a first approach

Multi-agent systems offer a new and exciting way of understanding the world of work. We apply agent-based modeling and simulation to investigate a set of problems in a retail context. Specifically, we are working to understand the relationship between people management practices on the shop-floor and retail performance. Despite the fact we are working within a relatively novel and complex domain, it is clear that using an agent-based approach offers great potential for improving organizational capabilities in the future. Our multi-disciplinary research team has worked closely with one of the UK’s top ten retailers to collect data and build an understanding of shop-floor operations and the key actors in a department (customers, staff, and managers). Based on this case study we have built and tested our first version of a retail branch agent-based simulation model where we have focused on how we can simulate the effects of people management practices on customer satisfaction and sales. In our experiments we have looked at employee development and cashier empowerment as two examples of shop floor management practices. In this paper we describe the underlying conceptual ideas and the features of our simulation model. We present a selection of experiments we have conducted in order to validate our simulation model and to show its potential for answering “what-if” questions in a retail context. We also introduce a novel performance measure which we have created to quantify customers’ satisfaction with service, based on their individual shopping experiences.

Protein disulfide isomerase as a target for besnoitiosis therapy : molecular characterization and studies of its role in infection and host immune response

Tese de Doutoramento em Ciências Veterinárias na especialidade de Sanidade Animal

Escherichia coli : host interactions in the pathogenesis of canine pyometra

Tese de Doutoramento em Ciências Veterinárias na Especialidade de Ciências Biológicas e Biomédicas