A verifiable solution to the MEG inverse problem

Magnetoencephalography (MEG) is a non-invasive brain imaging technique with the potential for very high temporal and spatial resolution of neuronal activity. The main stumbling block for the technique has been that the estimation of a neuronal current distribution, based on sensor data outside the head, is an inverse problem with an infinity of possible solutions. Many inversion techniques exist, all using different a-priori assumptions in order to reduce the number of possible solutions. Although all techniques can be thoroughly tested in simulation, implicit in the simulations are the experimenter's own assumptions about realistic brain function. To date, the only way to test the validity of inversions based on real MEG data has been through direct surgical validation, or through comparison with invasive primate data. In this work, we constructed a null hypothesis that the reconstruction of neuronal activity contains no information on the distribution of the cortical grey matter. To test this, we repeatedly compared rotated sections of grey matter with a beamformer estimate of neuronal activity to generate a distribution of mutual information values. The significance of the comparison between the un-rotated anatomical information and the electrical estimate was subsequently assessed against this distribution. We found that there was significant (P < 0.05) anatomical information contained in the beamformer images across a number of frequency bands. Based on the limited data presented here, we can say that the assumptions behind the beamformer algorithm are not unreasonable for the visual-motor task investigated.

The role of the cortical occipital spike in photosensitive epilepsy

Chapters one to three are an introduction to photosensitive epilepsy, electroencephalography (EEG) and the magnocellular and parvocellular visual pathways. Photoparoxysmal response (PPR) are strongly associated with photosensitive epilepsy. Chapters four to nine investigated whether occipital spikes were associated with PPR and hence with photosensitive epilepsy. The chapters investigated whether the response types showed similar dependence on stimulus characteristics using EEG. Chapters four and five found that occipital spikes and PPR showed different dependence on colour and luminance contrast. The differences were consistent with the magnocellular pathway mediating occipital spikes and the pavocellular pathway mediating PPR. The study in chapter eight found that monocular occlusion had a significantly greater effect on PPR than on occipital spikes, which is further evidence against an association between the two types of response. Chapters six and seven showed that occipital spikes and PPR had similar optimum spatial and temporal frequencies. Chapter nine showed that both response types could be generated via stimulation of the periphery of the retina. However, these three chapters are not strong evidence of an association, as the results do not contradict the theory that the responses are generated via different pathways. The magnocellular and pavocellular pathways have similar optimum temporal and spatial frequencies and both are present in the periphery. In chapter ten, magnetoencephalography was used to estimate the source of activity underlying the components of the VEP and occipital spike. Changes in the amplitude and latency in the components of the normal VEP are associated with epilepsy. However, the source underlying the occipital spikes was not related to that underlying the components of the VEP so this is also removed as a source of evidence for an association between occipital spikes and photosensitive epilepsy.

Stochastically driven instability in rotating shear flows

Origin of hydrodynamic turbulence in rotating shear flows is investigated. The particular emphasis is on flows whose angular velocities decrease but specific angular momenta increase with increasing radial coordinate. Such flows are Rayleigh stable, but must be turbulent in order to explain observed data. Such a mismatch between the linear theory and observations/experiments is more severe when any hydromagnetic/magnetohydrodynamic instability and the corresponding turbulence therein is ruled out. The present work explores the effect of stochastic noise on such hydrodynamic flows. We focus on a small section of such a flow which is essentially a plane shear flow supplemented by the Coriolis effect. This also mimics a small section of an astrophysical accretion disk. It is found that such stochastically driven flows exhibit large temporal and spatial correlations of perturbation velocities, and hence large energy dissipations, that presumably generate instability. A range of angular velocity profiles (for the steady flow), starting with the constant angular momentum to that of the constant circular velocity are explored. It is shown that the growth and roughness exponents calculated from the contour (envelope) of the perturbed flows are all identical, revealing a unique universality class for the stochastically forced hydrodynamics of rotating shear flows. This work, to the best of our knowledge, is the first attempt to understand origin of instability and turbulence in the three-dimensional Rayleigh stable rotating shear flows by introducing additive stochastic noise to the underlying linearized governing equations. This has important implications in resolving the turbulence problem in astrophysical hydrodynamic flows such as accretion disks.

EU-ASEAN relations in the post-Cold War era:an analysis of the impact of normative factors on interregionalism

This thesis examines the relationship between the European Union (EU) and the Association of Southeast Asian Nations (ASEAN) with a focus on why their normative elements, e.g. values and norms, affect their ties in the post-Cold War era. Since the end of the Cold War, policy-makers and academics have become interested in region-to-region interaction, termed interregionalism. Though interregionalism is considered to have become an indelible feature of post-Cold War international politics, there are question marks over its importance. It is often argued that interregionalism reinforces the collective identity of the regional organisations involved. It is also maintained that its overall relevance to the international system depends on the level of actorness, which is primarily measured in institutional and material terms, of the participant regional organisations. This thesis contends that the normative components of the EU and ASEAN are also fundamental constituents of their actorness and, consequently, define significantly their interregionalism. This is based on a crucial observation that normative factors are of importance to the regional and international relations of the EU and ASEAN. Yet, while they strongly espouse norms and values to guide their internal and external activities, their normative premises radically differ from each other. Furthermore, these normative differences jeopardise their cooperation. Building on this observation the inquiry takes the normative components of the EU and ASEAN as the criterion as well as the focus for investigating their interregionalism. In doing so, it hypothesises that the EU and ASEAN are two different regional actors that adopt two dissimilar sets of norms to conduct their regional and international affairs and that such normative differences hinder their relations. Within this hypothesis, it seeks to address three central questions. First, what are the normative features that constitute the EU and ASEAN as actors in world politics and that make them different from each other? Second, what are the main sources of their normative differences? Finally, why do their normative differences become an obstructive factor in their relationship? To address these issues, the inquiry adopts a constructivist interpretation (of International Relations) and opts for a narrative and empirical inquiry, which is based on information and data acquired from official documents, scholarly works and interviews and questionnaires. In doing so, it finds that as they were born and evolved in two dissimilar temporal and spatial settings, the EU and ASEAN are two different norm entrepreneurs and normative powers. The former advocates a set of liberal cosmopolitan norms whereas the latter champions a set of traditional communitarian principles. Their normative differences become a major obstacle to their cooperation, especially when one regional organisation’s norms are refused or violated by the other. Thus, a key lesson drawn from these findings is that in order to explain more fully EU-ASEAN interregionalism, it is essential to consider their norms, the reasons behind their normative differences and the implication of those differences to their relations

Stochastically driven instability in rotating shear flows

Origin of hydrodynamic turbulence in rotating shear flows is investigated. The particular emphasis is on flows whose angular velocities decrease but specific angular momenta increase with increasing radial coordinate. Such flows are Rayleigh stable, but must be turbulent in order to explain observed data. Such a mismatch between the linear theory and observations/experiments is more severe when any hydromagnetic/magnetohydrodynamic instability and the corresponding turbulence therein is ruled out. The present work explores the effect of stochastic noise on such hydrodynamic flows. We focus on a small section of such a flow which is essentially a plane shear flow supplemented by the Coriolis effect. This also mimics a small section of an astrophysical accretion disk. It is found that such stochastically driven flows exhibit large temporal and spatial correlations of perturbation velocities, and hence large energy dissipations, that presumably generate instability. A range of angular velocity profiles (for the steady flow), starting with the constant angular momentum to that of the constant circular velocity are explored. It is shown that the growth and roughness exponents calculated from the contour (envelope) of the perturbed flows are all identical, revealing a unique universality class for the stochastically forced hydrodynamics of rotating shear flows. This work, to the best of our knowledge, is the first attempt to understand origin of instability and turbulence in the three-dimensional Rayleigh stable rotating shear flows by introducing additive stochastic noise to the underlying linearized governing equations. This has important implications in resolving the turbulence problem in astrophysical hydrodynamic flows such as accretion disks.

Magnetohydrodynamic stability of stochastically driven accretion flows

We investigate the evolution of magnetohydrodynamic (or hydromagnetic as coined by Chandrasekhar) perturbations in the presence of stochastic noise in rotating shear flows. The particular emphasis is the flows whose angular velocity decreases but specific angular momentum increases with increasing radial coordinate. Such flows, however, are Rayleigh stable but must be turbulent in order to explain astrophysical observed data and, hence, reveal a mismatch between the linear theory and observations and experiments. The mismatch seems to have been resolved, at least in certain regimes, in the presence of a weak magnetic field, revealing magnetorotational instability. The present work explores the effects of stochastic noise on such magnetohydrodynamic flows, in order to resolve the above mismatch generically for the hot flows. We essentially concentrate on a small section of such a flow which is nothing but a plane shear flow supplemented by the Coriolis effect, mimicking a small section of an astrophysical accretion disk around a compact object. It is found that such stochastically driven flows exhibit large temporal and spatial autocorrelations and cross-correlations of perturbation and, hence, large energy dissipations of perturbation, which generate instability. Interestingly, autocorrelations and cross-correlations appear independent of background angular velocity profiles, which are Rayleigh stable, indicating their universality. This work initiates our attempt to understand the evolution of three-dimensional hydromagnetic perturbations in rotating shear flows in the presence of stochastic noise. © 2013 American Physical Society.

Spatiotemporal variation of the abundance of calcareous green macroalgae in the Florida Keys: A study of synchrony within a macroalgal functional-form group

The abundance of calcareous green algae was recorded quarterly at 28 sites within the Florida Keys National Marine Sanctuary (FKNMS) for a period of 7 years as part of a sea grass monitoring program. To evaluate the validity of using the functional-form group approach, we designed a sampling method that included the functional-form group and the component genera. This strategy enabled us to analyze the spatiotemporal patterns in the abundance of calcareous green algae as a group and to describe synchronous behavior among its genera through the application of a nonlinear regression model to both categories of data. Spatial analyses revealed that, in general, all genera displayed long-term trends of increasing abundance at most sites; however, at some sites the long-term trends for genera opposed one another. Strong synchrony in the timing of seasonal changes was found among all genera, possibly reflecting similar reproductive and seasonal growth pattern, but the variability in the magnitude of seasonal changes was very high among genera and sites. No spatial patterns were found in long-term or seasonal changes; the only significant relation detected was for slope, with sites closer to land showing higher values, suggesting that some factors associated with land proximity are affecting this increase. We conclude that the abundances of genera behaved differently from the functional-form group, indicating that the use of the functionalform group approach may be unsuitable to detect changes in sea grass community structure in the FKNMS at the existing temporal and spatial scale of the monitoring program.

A conceptual ecological model to facilitate understanding the role of invasive species in large-scale ecosystem restoration

We developed a conceptual ecological model (CEM) for invasive species to help understand the role invasive exotics have in ecosystem ecology and their impacts on restoration activities. Our model, which can be applied to any invasive species, grew from the eco-regional conceptual models developed for Everglades restoration. These models identify ecological drivers, stressors, effects and attributes; we integrated the unique aspects of exotic species invasions and effects into this conceptual hierarchy. We used the model to help identify important aspects of invasion in the development of an invasive exotic plant ecological indicator, which is described a companion paper in this special issue journal. A key aspect of the CEM is that it is a general ecological model that can be tailored to specific cases and species, as the details of any invasion are unique to that invasive species. Our model encompasses the temporal and spatial changes that characterize invasion, identifying the general conditions that allow a species to become invasive in a de novo environment; it then enumerates the possible effects exotic species may have collectively and individually at varying scales and for different ecosystem properties, once a species becomes invasive. The model provides suites of characteristics and processes, as well as hypothesized causal relationships to consider when thinking about the effects or potential effects of an invasive exotic and how restoration efforts will affect these characteristics and processes. In order to illustrate how to use the model as a blueprint for applying a similar approach to other invasive species and ecosystems, we give two examples of using this conceptual model to evaluate the status of two south Florida invasive exotic plant species (melaleuca and Old World climbing fern) and consider potential impacts of these invasive species on restoration.

Nutrient effects on seagrass epiphyte community structure in Florida Bay

A field experiment was employed in Florida Bay investigating the response of seagrass epiphyte communities to nitrogen (N) and phosphorus (P) additions. While most of the variability in epiphyte community structure was related to uncontrolled temporal and spatial environmental heterogeneity, P additions increased the relative abundance of the red algae–cyanobacterial complex and green algae, with a concomitant decrease in diatoms. When N was added along with P, the observed changes to the diatoms and the red algae–cyanobacterial complex were in the same direction as P-only treatments, but the responses were decreased in magnitude. Within the diatom community, species relative abundances, species richness, and diversity responded weakly to nutrient addition. P additions produced changes in diatom community structure that were limited to summer and were stronger in eastern Florida Bay than in the western bay. These changes were consistent with well-established temporal and spatial patterns of P limitation. Despite the significant change in community structure resulting from P addition, diatom communities from the same site and time, regardless of nutrient treatment, remained more similar to one another than to the diatom communities subject to identical nutrient treatments from different sites and times. Overall, epiphyte communities exhibited responses to P addition that were most evident at the division level.

Modeling seasonal dynamics of small fish cohorts in fluctuating freshwater marsh landscapes

Small-bodied fishes constitute an important assemblage in many wetlands. In wetlands that dry periodically except for small permanent waterbodies, these fishes are quick to respond to change and can undergo large fluctuations in numbers and biomasses. An important aspect of landscapes that are mixtures of marsh and permanent waterbodies is that high rates of biomass production occur in the marshes during flooding phases, while the permanent waterbodies serve as refuges for many biotic components during the dry phases. The temporal and spatial dynamics of the small fishes are ecologically important, as these fishes provide a crucial food base for higher trophic levels, such as wading birds. We develop a simple model that is analytically tractable, describing the main processes of the spatio-temporal dynamics of a population of small-bodied fish in a seasonal wetland environment, consisting of marsh and permanent waterbodies. The population expands into newly flooded areas during the wet season and contracts during declining water levels in the dry season. If the marsh dries completely during these times (a drydown), the fish need refuge in permanent waterbodies. At least three new and general conclusions arise from the model: (1) there is an optimal rate at which fish should expand into a newly flooding area to maximize population production; (2) there is also a fluctuation amplitude of water level that maximizes fish production, and (3) there is an upper limit on the number of fish that can reach a permanent waterbody during a drydown, no matter how large the marsh surface area is that drains into the waterbody. Because water levels can be manipulated in many wetlands, it is useful to have an understanding of the role of these fluctuations.

Mundos prohibidos: El poder en el discurso epistolar de Gertrudis Gómez de Avellaneda y Juana Borrero

This dissertation analyses, through a theoretical framework and a critical approach, letters of Cuban writers Gertrudis Gómez de Avellaneda and Juana Borrero. While love letters have captured the interest of some scholars, such as Claudio Guillén, Cintio Vitier and Alexander Roselló Selimov, the conflict that the analysis of non-literary texts poses has prevented further research in this field. Therefore, I propose a systematic method of analysis encompassing but not limited to evaluating letters based on their purpose, intent, interpretation, and temporal and spatial composition; analyzing the perspective and function of epistolary entities, and examining the textual signs that distinguish the epistolary forms from the literary forms. With this analytical tool, I examine a selection of letters of Gómez de Avellaneda and demonstrate that the writer displaces her identify from the autobiographic self to the epistolary self, in order to manipulate the perspective of her addressee. Caught between the Neoclassical way of thinking and the Romantic aesthetics, her assertive discourse, also reflected in her epistolary work, contributed to the incursion of women writers into the social and professional life of the nineteen century. Following the same method of investigation, an analysis of letters written by Borrero proves that, by building a world of delusion, hallucination and fantasy the writer brings to prose what first generation of female modernistas had done in poetry. In both cases, my focus is on the strategies that turn these letters into instruments of power, process that transformed the love-letter paradigm and forever renovated the women epistolary genre. This dissertation further explores the possibility of initiating a cycle in the study of personal letters to uncover a forgotten genre, mission that might build a bridge to embrace the new forms of written communication that scholars have already begun to explore in contemporary literature.

Oceanographic investiations from the Sea of Ochotsk

The Sea of Okhotsk is a marginal sea of the Pacific Ocean, which is characterized by strong variations in the productivity and sediment supply due to sea ice transport and river input. Furthermore the variations in the hydrological cycle determine the formation of the SOIW (Sea of Okhotsk Intermediate Water) which plays an important role in the ventilation processes in the intermediate water of the N-Pacific. Isotope data measured on planktonic and benthic foraminifera, sedimentological and geochemical studies of sediment cores and surface samples from the Sea of Okhotsk are used to reconstruct the paleoceanography during the past 350.000 years. The dating and correlation of the sediments are based on oxygen isotope stratigraphy, absolute ages, magnetic susceptibility as well as a detailled tephrachronology of the entire basin. The sedimentation rates are characterized by temporal and spatial variations. The maximum sedimentation rate takes place at the continental slope off Sakhalin due to the input of the Amur River, the sea ice drift and the high productivity. The sedimentation rate in the eastern part of the Sea of Okhotsk is generelly high because of the influence of the nutrient-rich Kamchatka Current. In the central and northern parts of the Sea of Okhotsk, areas with low productivity and reduced terrestrial supply, the sedimentation rate is the lowest. The analyses of the surface sediment samples make it possible to characterize the (sub)- recent sediment supply and transportation processes. The bulk sediment measurements, isotope data and the accumulation rate of ice-rafted debris (IRD) show a dominant sea ice cover and a region with a high productivity as well as a high Amur River input in the western part of the sea. The eastern part of the Sea of Okhotsk, however, is marked by the predominance of warm and nutrient-rich water masses coming from the Kamchatka Current which restricts the sea ice cover. This is reflected in low content of ice-rafted debris and high productivity proxies as well as in isotope data. The deposits of the Sea of Okhotsk are characterized by terrestrial, biogenic and volcanogenic sediment input which varies temporally and spatially. Here, the sedimentation pattern is dominated by the terrestrial input. Bulk sediment measurements and sample analyses of the > 63 micron particle input make it possible to distinguish glacial and interglacial fluctuations. The sedimentation processes during glacial times are determined by a high content of ice-rafted debris, whereas the primary production is higher during interglacial periods. During the last glacial/interglacial cycle the IRD-distribution pattern indicates a strong sea ice transport in the western part and in large areas of the open sea in the eastern part of the Sea of Okhotsk with a relatively constant ice-drift system. The IRD flux in sediments of the oxygen isotope Stage 6 reflects a new sedimentation pattern in the eastern part of the sea. This high IRD accumulation rate indicates ice advances beyond the shelf margin and an iceberg transport from NE-E direction into the Sea of Okhotsk. The several large, brief, negative anomalies in d13C values of Neogloboquadrina pachyderma (s) show releases of methane from basin sediments which correspond to periods of relative sea level falls. The high sedimentation rates on the Sakhalin slope allow insights into the climatic history in Holocene and indicate shorter-scale variations oscillation in Stage 3, which correlate with the global climatic changes. These variations are described as Dansgaard-Oeschger cycles in Greenland ice cores and as Heinrich-Events in several marine sediment cores from the N-Atlantic.

Infecções por enterobacteriaceae resistente aos carbapenêmicos em hospital de ensino: epidemiologia e caracterização molecular

Introduction: The production of KPC (Klebsiella pneumoniae carbapenemase) has become an important mechanism of carbapenem-resistance among Enterobacteriaceae strains. In Brazil, KPC is already widespread and its incidence has increased significantly, reducing treatment options. The “perfect storm” combination of the absence of new drug developmentand the emergence of multidrug-resistant strains resulted in the need for the use of older drugs, with greater toxicity, such as polymyxins. Aims: To determine the occurrence of carbapenemase-producing strains in carbapenem-resistant Enterobacteriaceae isolated from patients with nosocomial infection/colonization during September/2014 to August/2015, to determine the risk factors associated with 30-day- mortality and the impact of inappropriate therapy. Materials and Methods: We performed a case control study to assess the risk factors (comorbidities, invasive procedures and inappropriate antimicrobial therapy) associated with 30-day-mortality, considering the first episode of infection in 111 patients. The resistance genes blaKPC, blaIMP, blaVIM and blaNDM-1 were detected by polymerase chain reaction technique. Molecular typing of the strains involved in the outbreak was performed by pulsed field gel electrophoresis technique. The polymyxin resistance was confirmed by the microdilution broth method. Results: 188 episodes of carbapenem-resistant Enterobacteriaceae infections/colonizations were detected; of these, 122 strains were recovered from the hospital laboratory. The presence of blaKPC gene were confirmed in the majority (74.59%) of these isolates. It was not found the presence of blaIMP , blaVIM and blaNDM-1 genes. K. pneumoniae was the most frequent microorganism (77,13%), primarily responsible for urinary tract infections (21,38%) and infections from patients of the Intensive Care Unit (ICU) (61,38%). Multivariate statistical analysis showed as predictors independently associated with mortality: dialysis and bloodstream infection. The Kaplan-Meier curve showed a lower probability of survival in the group of patients receiving antibiotic therapy inappropriately. Antimicrobial use in adult ICU varied during the study period, but positive correlation between increased incidence of strains and the consumption was not observed. In May and July 2015, the occurrence rates of carbapenem-resistant Enterobacteriaceae KPC-producing per 1000 patient-days were higher than the control limit established, confirming two outbreaks, the first caused by colistin-susceptible KPC-producing K. pneumoniae isolates, with a polyclonal profile and the second by a dominant clone of colistin-resistant (≥ 32 μg/mL) KPC-producing K. pneumoniae. The cross transmission between patients became clear by the temporal and spatial relationships observed in the second outbreak, since some patients occupied the same bed, showing problems in hand hygiene adherence among healthcare workers and inadequate terminal disinfection of environment. The outbreak was contained when the ICU was closed to new admissions. Conclusions: The study showed an endemicity of K. pneumoniae KPC-producing in adult ICU, progressing to an epidemic monoclonal expansion, resulted by a very high antibiotic consumption of carbapenems and polymyxins and facilitated by failures in control measures the unit.

MRI-Guided Radiation Therapy: Investigating the Accuracy of Treatment Delivery

Purpose: To develop, evaluate and apply a novel high-resolution 3D remote dosimetry protocol for validation of MRI guided radiation therapy treatments (MRIdian® by ViewRay®). We demonstrate the first application of the protocol (including two small but required new correction terms) utilizing radiochromic 3D plastic PRESAGE® with optical-CT readout.

Methods: A detailed study of PRESAGE® dosimeters (2kg) was conducted to investigate the temporal and spatial stability of radiation induced optical density change (ΔOD) over 8 days. Temporal stability was investigated on 3 dosimeters irradiated with four equally-spaced square 6MV fields delivering doses between 10cGy and 300cGy. Doses were imaged (read-out) by optical-CT at multiple intervals. Spatial stability of ΔOD response was investigated on 3 other dosimeters irradiated uniformly with 15MV extended-SSD fields with doses of 15cGy, 30cGy and 60cGy. Temporal and spatial (radial) changes were investigated using CERR and MATLAB’s Curve Fitting Tool-box. A protocol was developed to extrapolate measured ΔOD readings at t=48hr (the typical shipment time in remote dosimetry) to time t=1hr.

Results: All dosimeters were observed to gradually darken with time (<5% per day). Consistent intra-batch sensitivity (0.0930±0.002 ΔOD/cm/Gy) and linearity (R2=0.9996) was observed at t=1hr. A small radial effect (<3%) was observed, attributed to curing thermodynamics during manufacture. The refined remote dosimetry protocol (including polynomial correction terms for temporal and spatial effects, CT and CR) was then applied to independent dosimeters irradiated with MR-IGRT treatments. Excellent line profile agreement and 3D-gamma results for 3%/3mm, 10% threshold were observed, with an average passing rate 96.5%± 3.43%.

Conclusion: A novel 3D remote dosimetry protocol is presented capable of validation of advanced radiation treatments (including MR-IGRT). The protocol uses 2kg radiochromic plastic dosimeters read-out by optical-CT within a week of treatment. The protocol requires small corrections for temporal and spatially-dependent behaviors observed between irradiation and readout.

The application of next generation sequencing to profile microbe related cheese quality defects

High throughput next generation sequencing, together with advanced molecular methods, has considerably enhanced the field of food microbiology. By overcoming biases associated with culture dependant approaches, it has become possible to achieve novel insights into the nature of food-borne microbial communities. In this thesis, several different sequencing-based approaches were applied with a view to better understanding microbe associated quality defects in cheese. Initially, a literature review provides an overview of microbe-associated cheese quality defects as well as molecular methods for profiling complex microbial communities. Following this, 16S rRNA sequencing revealed temporal and spatial differences in microbial composition due to the time during the production day that specific commercial cheeses were manufactured. A novel Ion PGM sequencing approach, focusing on decarboxylase genes rather than 16S rRNA genes, was then successfully employed to profile the biogenic amine producing cohort of a series of artisanal cheeses. Investigations into the phenomenon of cheese pinking formed the basis of a joint 16S rRNA and whole genome shotgun sequencing approach, leading to the identification of Thermus species and, more specifically, the pathway involved in production of lycopene, a red coloured carotenoid. Finally, using a more traditional approach, the effect of addition of a facultatively heterofermentative Lactobacillus (Lactobacillus casei) to a Swiss-type cheese, in which starter activity was compromised, was investigated from the perspective of its ability to promote gas defects and irregular eye formation. X-ray computed tomography was used to visualise, using a non-destructive method, the consequences of the undesirable gas formation that resulted. Ultimately this thesis has demonstrated that the application of molecular techniques, such as next generation sequencing, can provide a detailed insight into defect-causing microbial populations present and thereby may underpin approaches to optimise the quality and consistency of a wide variety of cheeses.