The use of modelling approaches to explore interactions in two aquatic host-pest systems

Modelling is a useful tool that has been applied in both human and animal epidemiological research. A model is a simplified system that represents a much more complex phenomenon. Various types of models are available. They are generally used for the purposes of explaining phenomena, making predictions, or exploring different scenarios. Several challenges have been encountered during the construction of models in aquatic animal health and are discussed in the dissertation. The research documented in this dissertation aimed to demonstrate the application of modelling to address specific health and production issues associated with two aquatic animal species (blue mussels and wild Pacific salmon). The first problem dealt with sea lice infestations in wild Pacific salmon populations on the west coast of British Columbia, Canada. The levels of sea lice infestations on wild chum and pink salmon were described and factors associated with inter-annual variation of the infestations were identified using a multivariable logistic regression model. This model included site information as a random effect, to account for spatial aggregation, which provided further details on the degree of clustering at the site level and suggested that the infestation levels depended on the location of fish. This raised the question as to where the risks were and, as a result, a spatial cluster analysis technique (i.e. spatial scan statistics) was used to identify when and where the clusters (of elevated sea lice infestation levels) occurred. The results from clustering analysis can facilitate the hypothesis-generating process for future studies. The second issue was the problem of mussel loss due to biofouling by tunicates (Ciona intestinalis) on Prince Edward Island mussel farms, which was assessed through the use of a mathematical model to describe the dynamics of C. intestinalis populations over the growing season. The model incorporated temperature dependencies, which allowed for the assessment of population dynamics under different temperatures, and was then used to evaluate the effectiveness of different mitigation strategies, using fewer resources than would be required if field trials were undertaken. The research documented in this dissertation demonstrates the use of modelling to address production and health issues in the context of aquatic animals. In addition to the use of field-based trials the research also suggests that modelling can be used as an alternative method to investigate various scenarios and facilitate management planning with advantages in time and cost savings

Dynamic soaring in the winds of change: The effects of wind and oceanography on the population and spatial ecology of seabirds

Seabirds are marine top predators regarded as indicators of the environmental changes occurring in their supporting ecosystems. The analytical lens of this thesis focusses on seabird belonging to the order Procellariiformes, which have similar life-histories characterised by high life expectancy and delayed sexual maturity. Furthermore, despite acting as central place foragers during breeding, most procellariiform seabirds can perform foraging trips covering thousands of kilometres by extracting energy from the wind through a flight behaviour known as "dynamic soaring". The overarching aim of my thesis is to understand the pathways through which wind and oceanographic processes affect the demography, population dynamics, foraging ecology and spatial distribution of seabirds. Focussing on the black-browed albatross (Thalassarche melanophris) as a model organism, we developed integrated population models to investigate the effects of wind and oceanographic fluctuations on the population breeding and survival processes. By analysing a demographic database spanning nearly two decades, we found that the population breeding parameters were negatively impacted by higher sea surface temperatures and positively affected by stronger winds, presumably through bottom-up environmental processes modulating food availability and accessibility. Survival was relatively constant and was only influenced by deeper ecosystem changes acting at larger spatio-temporal scales. Furthermore, our results revealed the high sensitivity of the population to the survival rate of the poorly understood sub-adult life history stages, which comprised approximately half of the total population size. We then studied the occurrence of albatross chick mortality events not caused by predation. Our results showed that, while albatross chicks weighed less in years with warmer sea temperatures, chick malnutrition and environmentally-driven food regulation did not explain the observed patterns of mortality. Rather, nestlings mortality events unrelated to predation were clustered at small scales in time and space, suggesting that part of the pronounced inter-annual variability in albatross breeding success was modulated by the prevalence of an unidentified infectious disease. By developing state-space models, we quantified a previously hypothesised, but never empirically documented "habitat-mediated" pathway linking environmental conditions to the breeding processes of a social monogamous population. Specifically, we found a higher prevalence of divorce in challenging years characterised by warmer sea surface temperatures, documenting the direct disruptive effects of ocean warming on the social monogamous bonds of albatrosses. Our work then focussed on the hypermobile Desertas petrel (Pterodroma deserta) and Bulwer's petrel (Bulweria bulwerii) as model organisms to investigate role of winds in shaping the flight behaviour and the foraging ecology of dynamic soaring seabirds during the breeding season. Desertas petrels used favourable winds to maximise their ground speed and distance covered throughout their round-trip foraging movements, among the longest recorded in any animal. Bulwer's petrels, on the other hand, exploited the stable North Atlantic trade winds, exhibiting a striking selectivity for crosswinds and engaging in crosswind zig-zag flight throughout large sections of their tracks. Under stable winds, this strategy enabled them to maximise the distance travelled and the probability of detecting odour plumes along the round trip. Crucially, the movement patterns of these two species suggest that seabirds have a priori knowledge of the regional winds and can plan their round-trip with an expectation of predicted wind conditions and costs of flight to return back to their colony. Collectively, the findings of my thesis highlight the sensitivity of seabirds to changes in oceanographic conditions and their reliance on winds to sustain their extreme life-history. Given the accelerating pace of global change and its dramatic effects on marine ecosystems, monitoring the diagnostic responses of these "sentinels" of the global ocean and, crucially, predicting their future performance is a conservation goal of upmost importance.Falkland Islands Government – Environmental Studies Budge

Evolutionary genomics : statistical and computational methods

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

Adverse paediatric outcomes of macrolide antibiotics treatment in pregnancy

Background: Over the last 20 years, concerns have been raised about rare but serious adverse outcomes associated with macrolide use during pregnancy. Currently there was no consensus about whether macrolides are considered safe in pregnancy or not. This PhD study aims to examine the association between maternal exposure of macrolide antibiotics during pregnancy and adverse paediatric outcomes where short-term fetal hypoxia could be aetiologically involved. Methods: I first conducted a systematic review and meta-analysis of both random controlled trials and observational studies to investigate the association. I prioritized comparisons of macrolides with alternative antibiotics (mainly penicillins) for comparability of indication and effect. I then performed a large cohort study using a mother-baby linkage derived from the Clinical Practice Research Datalink (CPRD), a UK-representative primary care database. The cohort study assessed the association between macrolide (versus penicillin) prescribing during pregnancy and major malformations, cerebral palsy, epilepsy, attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD) in children. Results: The systematic review and meta-analysis found consistent evidence for an association between macrolide antibiotics use during early pregnancy and an increased risk of miscarriage, inconsistent evidence for cerebral palsy and epilepsy, and insufficient evidence for malformations, stillbirth and neonatal death. The cohort study demonstrated that prescribing macrolides compared with penicillins during the first trimester of pregnancy (4 to 13 Gestational Week) was associated with increased risks of any major malformation and specifically cardiovascular malformations. Macrolide prescribing in any trimester was associated with an increased risk of genital malformations (mostly hypospadias). Erythromycin in the first trimester was found to be associated with an increased risk of any major malformation. Indication bias, unmeasured confounding, live-birth bias and outcome misclassification were unlikely to explain the findings. Conclusions: Considering the widespread use of macrolides during pregnancy, international collaboration is in urgent need to bring together existing datasets for large-scale analyses of high quality trial and observational cohorts that have accurate measurements of macrolides treatment and specific child outcomes. Analyses should pre-specify treatment exposure periods based on the critical period of specific outcomes. The findings of this study warrant cautious use of macrolides in pregnancy and recommendation of alternative antibiotics where feasible

Spatio-temporal modelling of bluetongue virus distribution in Northern Australia based on remotely sensed bioclimatic variables

The presence of Bluetongue virus (BTV) in Northern Australia poses an ongoing threat for animal health and although clinical disease has not been detected in livestock, it limits export of livestock from the infected areas. BTV presence is governed by variable environmental conditions, which influence vector and host habitats. The National Arbovirus Monitoring Program (NAMP) was established to determine the extent of virus activity and control the risk of infection spread. Groups of young cattle, previously unexposed to infection, are regularly tested to detect evidence of transmission. This approach is labour and cost intensive and difficult to operate in the remote areas of Northern Australia. The resulting data are therefore characterised by spatial and temporal gaps. The aim of this research is to assess the use of remotely sensed environmental and climatic data as a means of predicting the distribution of BTV seroprevalence throughout Northern Australia to complement conventional surveillance.Environmental factors relating to the viruses’ host and vector habitats and the transmission cycle of BTV have been identified based on the extensive review of virus ecology. Different data sources have been assessed to provide sufficient spatial and temporal coverage for the definition of spatio-temporal environmental variables that can be used to explain and predict the distribution of BTV. Following this assessment, satellite data products from the Moderate Resolution Imaging Spectroradiometer (MODIS) and the Tropical Rainfall Measuring Mission (TRMM) were acquired for the Pilbara in Western Australia, and the Northern Territory. These were reprojected and processed into spatio-temporal variables for the period between the years 2000 and 2009. Due to uncertainty in the precision of the geographic location and timing of animals tested for seropositivity, summary statistics of bioclimatic variables were generated at the station (i.e. property) level for each year. Different combinations of these variables, including vegetation greenness and phenology, land surface temperature and precipitation were screened for correlation with BTV presence using a Generalised Additive Model approach. A final model was developed to predict the presence or absence of BTV seropositivity on the basis of statistical significance of the remotely sensed predictor variables, and informed by knowledge of virus ecological principles.The model, based on the maximum seasonal Normalised Difference Vegetation Index (NDVI), and mean and maximum land surface temperature variables provided excellent discriminatory ability and the basis for the generation of prediction maps of BTV seropositivity for the first eight years. Besides internal assessment, the model’s predictive capabilities were validated using monitoring data from the season 2008/09.It has been demonstrated that the predictions are useful in complementing complement NAMP surveillance by identifying areas at higher risk for seropositivity in cattle, which aids planning of livestock movement and further monitoring activities. Uncertainty in the model was attributed to the spatio-temporal inconsistency in the precision of the available serosurveillance data. The discriminatory ability of models of this type could be further improved by ensuring that exact location details and date of NAMP BTV test events are consistently recorded

Evolutionary Genomics

This open access book addresses the challenge of analyzing and understanding the evolutionary dynamics of complex biological systems at the genomic level, and elaborates on some promising strategies that would bring us closer to uncovering of the vital relationships between genotype and phenotype. After a few educational primers, the book continues with sections on sequence homology and alignment, phylogenetic methods to study genome evolution, methodologies for evaluating selective pressures on genomic sequences as well as genomic evolution in light of protein domain architecture and transposable elements, population genomics and other omics, and discussions of current bottlenecks in handling and analyzing genomic data. Written for the highly successful Methods in Molecular Biology series, chapters include the kind of detail and expert implementation advice that lead to the best results. Authoritative and comprehensive, Evolutionary Genomics: Statistical and Computational Methods, Second Edition aims to serve both novices in biology with strong statistics and computational skills, and molecular biologists with a good grasp of standard mathematical concepts, in moving this important field of study forward

Efficient Decision Support Systems

This series is directed to diverse managerial professionals who are leading the transformation of individual domains by using expert information and domain knowledge to drive decision support systems (DSSs). The series offers a broad range of subjects addressed in specific areas such as health care, business management, banking, agriculture, environmental improvement, natural resource and spatial management, aviation administration, and hybrid applications of information technology aimed to interdisciplinary issues. This book series is composed of three volumes: Volume 1 consists of general concepts and methodology of DSSs; Volume 2 consists of applications of DSSs in the biomedical domain; Volume 3 consists of hybrid applications of DSSs in multidisciplinary domains. The book is shaped decision support strategies in the new infrastructure that assists the readers in full use of the creative technology to manipulate input data and to transform information into useful decisions for decision makers

Ultrasensitive detection of toxocara canis excretory-secretory antigens by a nanobody electrochemical magnetosensor assay.

peer reviewedHuman Toxocariasis (HT) is a zoonotic disease caused by the migration of the larval stage of the roundworm Toxocara canis in the human host. Despite of being the most cosmopolitan helminthiasis worldwide, its diagnosis is elusive. Currently, the detection of specific immunoglobulins IgG against the Toxocara Excretory-Secretory Antigens (TES), combined with clinical and epidemiological criteria is the only strategy to diagnose HT. Cross-reactivity with other parasites and the inability to distinguish between past and active infections are the main limitations of this approach. Here, we present a sensitive and specific novel strategy to detect and quantify TES, aiming to identify active cases of HT. High specificity is achieved by making use of nanobodies (Nbs), recombinant single variable domain antibodies obtained from camelids, that due to their small molecular size (15kDa) can recognize hidden epitopes not accessible to conventional antibodies. High sensitivity is attained by the design of an electrochemical magnetosensor with an amperometric readout with all components of the assay mixed in one single step. Through this strategy, 10-fold higher sensitivity than a conventional sandwich ELISA was achieved. The assay reached a limit of detection of 2 and15 pg/ml in PBST20 0.05% or serum, spiked with TES, respectively. These limits of detection are sufficient to detect clinically relevant toxocaral infections. Furthermore, our nanobodies showed no cross-reactivity with antigens from Ascaris lumbricoides or Ascaris suum. This is to our knowledge, the most sensitive method to detect and quantify TES so far, and has great potential to significantly improve diagnosis of HT. Moreover, the characteristics of our electrochemical assay are promising for the development of point of care diagnostic systems using nanobodies as a versatile and innovative alternative to antibodies. The next step will be the validation of the assay in clinical and epidemiological contexts