Prediction of transcriptional regulatory interactions in bacteria : a comparative genomics approach

Exponential growth of genomic data in the last two decades has made manual analyses impractical for all but trial studies. As genomic analyses have become more sophisticated, and move toward comparisons across large datasets, computational approaches have become essential. One of the most important biological questions is to understand the mechanisms underlying gene regulation. Genetic regulation is commonly investigated and modelled through the use of transcriptional regulatory network (TRN) structures. These model the regulatory interactions between two key components: transcription factors (TFs) and the target genes (TGs) they regulate. Transcriptional regulatory networks have proven to be invaluable scientific tools in Bioinformatics. When used in conjunction with comparative genomics, they have provided substantial insights into the evolution of regulatory interactions. Current approaches to regulatory network inference, however, omit two additional key entities: promoters and transcription factor binding sites (TFBSs). In this study, we attempted to explore the relationships among these regulatory components in bacteria. Our primary goal was to identify relationships that can assist in reducing the high false positive rates associated with transcription factor binding site predictions and thereupon enhance the reliability of the inferred transcription regulatory networks. In our preliminary exploration of relationships between the key regulatory components in Escherichia coli transcription, we discovered a number of potentially useful features. The combination of location score and sequence dissimilarity scores increased de novo binding site prediction accuracy by 13.6%. Another important observation made was with regards to the relationship between transcription factors grouped by their regulatory role and corresponding promoter strength. Our study of E.coli ��70 promoters, found support at the 0.1 significance level for our hypothesis | that weak promoters are preferentially associated with activator binding sites to enhance gene expression, whilst strong promoters have more repressor binding sites to repress or inhibit gene transcription. Although the observations were specific to �70, they nevertheless strongly encourage additional investigations when more experimentally confirmed data are available. In our preliminary exploration of relationships between the key regulatory components in E.coli transcription, we discovered a number of potentially useful features { some of which proved successful in reducing the number of false positives when applied to re-evaluate binding site predictions. Of chief interest was the relationship observed between promoter strength and TFs with respect to their regulatory role. Based on the common assumption, where promoter homology positively correlates with transcription rate, we hypothesised that weak promoters would have more transcription factors that enhance gene expression, whilst strong promoters would have more repressor binding sites. The t-tests assessed for E.coli �70 promoters returned a p-value of 0.072, which at 0.1 significance level suggested support for our (alternative) hypothesis; albeit this trend may only be present for promoters where corresponding TFBSs are either all repressors or all activators. Nevertheless, such suggestive results strongly encourage additional investigations when more experimentally confirmed data will become available. Much of the remainder of the thesis concerns a machine learning study of binding site prediction, using the SVM and kernel methods, principally the spectrum kernel. Spectrum kernels have been successfully applied in previous studies of protein classification [91, 92], as well as the related problem of promoter predictions [59], and we have here successfully applied the technique to refining TFBS predictions. The advantages provided by the SVM classifier were best seen in `moderately'-conserved transcription factor binding sites as represented by our E.coli CRP case study. Inclusion of additional position feature attributes further increased accuracy by 9.1% but more notable was the considerable decrease in false positive rate from 0.8 to 0.5 while retaining 0.9 sensitivity. Improved prediction of transcription factor binding sites is in turn extremely valuable in improving inference of regulatory relationships, a problem notoriously prone to false positive predictions. Here, the number of false regulatory interactions inferred using the conventional two-component model was substantially reduced when we integrated de novo transcription factor binding site predictions as an additional criterion for acceptance in a case study of inference in the Fur regulon. This initial work was extended to a comparative study of the iron regulatory system across 20 Yersinia strains. This work revealed interesting, strain-specific difierences, especially between pathogenic and non-pathogenic strains. Such difierences were made clear through interactive visualisations using the TRNDifi software developed as part of this work, and would have remained undetected using conventional methods. This approach led to the nomination of the Yfe iron-uptake system as a candidate for further wet-lab experimentation due to its potential active functionality in non-pathogens and its known participation in full virulence of the bubonic plague strain. Building on this work, we introduced novel structures we have labelled as `regulatory trees', inspired by the phylogenetic tree concept. Instead of using gene or protein sequence similarity, the regulatory trees were constructed based on the number of similar regulatory interactions. While the common phylogentic trees convey information regarding changes in gene repertoire, which we might regard being analogous to `hardware', the regulatory tree informs us of the changes in regulatory circuitry, in some respects analogous to `software'. In this context, we explored the `pan-regulatory network' for the Fur system, the entire set of regulatory interactions found for the Fur transcription factor across a group of genomes. In the pan-regulatory network, emphasis is placed on how the regulatory network for each target genome is inferred from multiple sources instead of a single source, as is the common approach. The benefit of using multiple reference networks, is a more comprehensive survey of the relationships, and increased confidence in the regulatory interactions predicted. In the present study, we distinguish between relationships found across the full set of genomes as the `core-regulatory-set', and interactions found only in a subset of genomes explored as the `sub-regulatory-set'. We found nine Fur target gene clusters present across the four genomes studied, this core set potentially identifying basic regulatory processes essential for survival. Species level difierences are seen at the sub-regulatory-set level; for example the known virulence factors, YbtA and PchR were found in Y.pestis and P.aerguinosa respectively, but were not present in both E.coli and B.subtilis. Such factors and the iron-uptake systems they regulate, are ideal candidates for wet-lab investigation to determine whether or not they are pathogenic specific. In this study, we employed a broad range of approaches to address our goals and assessed these methods using the Fur regulon as our initial case study. We identified a set of promising feature attributes; demonstrated their success in increasing transcription factor binding site prediction specificity while retaining sensitivity, and showed the importance of binding site predictions in enhancing the reliability of regulatory interaction inferences. Most importantly, these outcomes led to the introduction of a range of visualisations and techniques, which are applicable across the entire bacterial spectrum and can be utilised in studies beyond the understanding of transcriptional regulatory networks.

Paradoxical roles of tumour necrosis factor-alpha in prostate cancer biology

Tumour necrosis factor (TNF) is a pleiotropic cytokine with dual roles in cancer biology including prostate cancer (PCa). On the one hand, there is evidence that it stimulates tumour angiogenesis, is involved in the initiation of PCa from an androgen-dependent to a castrate resistant state, plays a role in epithelial to mesenchymal plasiticity, and may contribute to the aberrant regulation of eicosanoid pathways. On the other hand, TNF has also been reported to inhibit neovascularisation, induce apoptosis of PCa cells, and stimulate anti-tumour immunity. Much of the confusion surrounding its seemingly paradoxical roles in cancer biology stems from the dependence of its effects on the biological model within which TNF is investigated. This review will address some of these issues, and also discuss on the therapeutic implications.

Spatial modelling of population health screening : the role of accessibility in predicting expected patient flows

This paper describes a generalised linear mixed model (GLMM) approach for understanding spatial patterns of participation in population health screening, in the presence of multiple screening facilities. The models presented have dual focus, namely the prediction of expected patient flows from regions to services and relative rates of participation by region- service combination, with both outputs having meaningful implications for the monitoring of current service uptake and provision. The novelty of this paper lies with the former focus, and an approach for distributing expected participation by region based on proximity to services is proposed. The modelling of relative rates of participation is achieved through the combination of different random effects, as a means of assigning excess participation to different sources. The methodology is applied to participation data collected from a government-funded mammography program in Brisbane, Australia.

Speaker attribution of multiple telephone conversations using a complete-linkage clustering approach

In this paper we propose and evaluate a speaker attribution system using a complete-linkage clustering method. Speaker attribution refers to the annotation of a collection of spoken audio based on speaker identities. This can be achieved using diarization and speaker linking. The main challenge associated with attribution is achieving computational efficiency when dealing with large audio archives. Traditional agglomerative clustering methods with model merging and retraining are not feasible for this purpose. This has motivated the use of linkage clustering methods without retraining. We first propose a diarization system using complete-linkage clustering and show that it outperforms traditional agglomerative and single-linkage clustering based diarization systems with a relative improvement of 40% and 68%, respectively. We then propose a complete-linkage speaker linking system to achieve attribution and demonstrate a 26% relative improvement in attribution error rate (AER) over the single-linkage speaker linking approach.

Efficient solution of multiple cracks in great number using eigen COD boundary integral equations with iteration procedure

A newly developed computational approach is proposed in the paper for the analysis of multiple crack problems based on the eigen crack opening displacement (COD) boundary integral equations. The eigen COD particularly refers to a crack in an infinite domain under fictitious traction acting on the crack surface. With the concept of eigen COD, the multiple cracks in great number can be solved by using the conventional displacement discontinuity boundary integral equations in an iterative fashion with a small size of system matrix to determine all the unknown CODs step by step. To deal with the interactions among cracks for multiple crack problems, all cracks in the problem are divided into two groups, namely the adjacent group and the far-field group, according to the distance to the current crack in consideration. The adjacent group contains cracks with relatively small distances but strong effects to the current crack, while the others, the cracks of far-field group are composed of those with relatively large distances. Correspondingly, the eigen COD of the current crack is computed in two parts. The first part is computed by using the fictitious tractions of adjacent cracks via the local Eshelby matrix derived from the traction boundary integral equations in discretized form, while the second part is computed by using those of far-field cracks so that the high computational efficiency can be achieved in the proposed approach. The numerical results of the proposed approach are compared not only with those using the dual boundary integral equations (D-BIE) and the BIE with numerical Green's functions (NGF) but also with those of the analytical solutions in literature. The effectiveness and the efficiency of the proposed approach is verified. Numerical examples are provided for the stress intensity factors of cracks, up to several thousands in number, in both the finite and infinite plates.

Interpersonal coupling in rowing : the mediating role of the environment

Evidence currently supports the view that intentional interpersonal coordination (IIC) is a self-organizing phenomenon facilitated by visual perception of co-actors in a coordinative coupling (Schmidt, Richardson, Arsenault, & Galantucci, 2007). The present study examines how apparent IIC is achieved in situations where visual information is limited for co-actors in a rowing boat. In paired rowing boats only one of the actors, [bow seat] gets to see the actions of the other [stroke seat]. Thus IIC appears to be facilitated despite the lack of important visual information for the control of the dyad. Adopting a mimetic approach to expert coordination, the present study qualitatively examined the experiences of expert performers (N=9) and coaches (N=4) with respect to how IIC was achieved in paired rowing boats. Themes were explored using inductive content analysis, which led to layered model of control. Rowers and coaches reported the use of multiple perceptual sources in order to achieve IIC. As expected(Kelso, 1995; Schmidt & O’Brien, 1997; Turvey, 1990), rowers in the bow of a pair boat make use of visual information provided by the partner in front of them [stroke]. However, this perceptual information is subordinate to perception Motor Learning and Control S111 of the relationship between the boat hull and water passing beside it. Stroke seat, in the absence of visual information about his/her partner, achieves coordination by picking up information about the lifting or looming of the boat’s stern along with water passage past the hull. In this case it appears that apparent or desired IIC is supported by the perception of extra-personal variables, in this case boat behavior; as this perceptual information source is used by both actors. To conclude, co-actors in two person rowing boats use multiple sources of perceptual information for apparent IIC that changes according to task constraints. Where visual information is restricted IIC is facilitated via extra-personal perceptual information and apparent IIC switches to intentional extra-personal coordination.

Mapping of multiple quantitative trait loci affecting bovine spongiform encephalopathy

A whole-genome scan was conducted to map quantitative trait loci (QTL) for BSE resistance or susceptibility. Cows from four half-sib families were included and 173 microsatellite markers were used to construct a 2835-cM (Kosambi) linkage map covering 29 autosomes and the pseudoautosomal region of the sex chromosome. Interval mapping by linear regression was applied and extended to a multiple-QTL analysis approach that used identified QTL on other chromosomes as cofactors to increase mapping power. In the multiple-QTL analysis, two genome-wide significant QTL (BTA17 and X/Y ps) and four genome-wide suggestive QTL (BTA1, 6, 13, and 19) were revealed. The QTL identified here using linkage analysis do not overlap with regions previously identified using TDT analysis. One factor that may explain the disparity between the results is that a more extensive data set was used in the present study. Furthermore, methodological differences between TDT and linkage analyses may affect the power of these approaches.

The role of human factors when evaluating information accountability for eHealth systems

The availability of health information is rapidly increasing; its expansion and proliferation is inevitable. At the same time, breeding of health information silos is an unstoppable and relentless exercise. Information security and privacy concerns are therefore major barriers in the eHealth socio-eco system. We proposed Information Accountability as a measurable human factor that should eliminate and mitigate security concerns. Information accountability measures would be practicable and feasible if legislative requirements are also embedded. In this context, information accountability constitutes a key component for the development of effective information technology requirements for health information system. Our conceptual approach to measuring human factors related to information accountability in eHealth is presented in this paper with some limitations.

Ureaplasma parvum multiple banded antigen (MBA) size variation - association with fetal inflammation in a sheep model (Published abstract)

Background: Ureaplasma species are the most prevalent isolates from women who deliver preterm. The MBA, a surface exposed lipoprotein, is a key virulence factor of ureaplasmas. We investigated MBA variation after chronic and acute intra-amniotic (IA) ureaplasma infections. Method: U. parvum serovar 3 (2x104 colony-forming-units) was injected IA into pregnant ewes at: 55 days gestation (d, term = 145d) (n=8); 117d (n=8) and 121d (n=8). Fetuses were delivered surgically (124d) and ureaplasmas cultured from amniotic fluid (AF), chorioamnion, fetal lung (FL) and umbilical cord were tested by western blot and PCR assays to demonstrate MBA and mba gene variation respectively. Tissue sections were sectioned and stained by haemotoxylin and eosin and inflammatory cell counts and pathology were reported (blinded to outcome). Results: Numerous MBA/mba variants were generated in vivo after chronic exposure to ureaplasma infection but after acute infection no variants (3d) or very few variants (7d) were generated. Identical MBA variants were detected within the AF and FL but different ureaplasma variants were detected within chorioamnion specimens. The severity of inflammation within chronically infected tissues varied between animals ranging from no inflammation to severe inflammation with/without fibrosis. Chorioamnion, FL and cord from the same animal demonstrated the same degree of inflammation. Conclusions: MBA/mba variation in vivo occurred after the initiation of the host immune response and we propose that ureaplasmas vary the MBA antigen to evade the host immune response. In some animals there was no inflammation despite colonisation with high numbers of ureaplasmas.

Ureaplasma parvum serovar 3 multiple banded antigen size variation after chronic intra-amniotic infection/colonization

Ureaplasma species are the microorganisms most frequently associated with adverse pregnancy outcomes. The multiple banded antigen (MBA), a surface-exposed lipoprotein, is a key virulence factor of ureaplasmas. The MBA demonstrates size variation, which we have shown previously to be correlated with the severity of chorioamnion inflammation. We aimed to investigate U. parvum serovar 3 pathogenesis in vivo, using a sheep model, by investigating: MBA variation after long term (chronic) and short term (acute) durations of in utero ureaplasma infections, and the severity of chorioamnionitis and inflammation in other fetal tissues. Inocula of 2x107 colony-forming-units (CFU) of U. parvum serovar 3 (Up) or media controls (C) were injected intra-amniotically into pregnant ewes at one of three time points: day 55 (69d Up, n=8; C69, n=4); day 117 (7d Up, n=8; C7, n=2); and day 121 (3d Up, n=8; C3, n=2) of gestation (term=145-150d). At day 124, preterm fetuses were delivered surgically. Samples of chorioamnion, fetal lung, and umbilical cord were: (i) snap frozen for subsequent ureaplasma culture, and (ii) fixed, embedded, sectioned and stained by haematoxylin and eosin stain for histological analysis. Selected fetal lung clinical ureaplasma isolates were cloned and filtered to obtain cultures from a single CFU. Passage 1 and clone 2 ureaplasma cultures were tested by western blot to demonstrate MBA variation. In acute durations of ureaplasma infection no MBA variants (3d Up) or very few MBA variants (7d Up) were present when compared to the original inoculum. However, numerous MBA size variants were generated in vivo (alike within contiguous tissues, amniotic fluid and fetal lung, but different variants were present within chorioamnion), during chronic, 69d exposure to ureaplasma infection. For the first time we have shown that the degree of ureaplasma MBA variation in vivo increased with the duration of gestation.

Ureaplasma species multiple banded antigen (MBA) variation is associated with the severity of chorioamnionitis in late preterm placentas

Background: Intra-amniotic infection accounts for 30% of all preterm births (PTB), with the human Ureaplasma species being the most frequently identified microorganism from the placentas of women who deliver preterm. The highest prevalence of PTB occurs late preterm (32-36 weeks) but no studies have investigated the role of infectious aetiologies associated with late preterm birth. Method: Placentas from women with late PTB were dissected aseptically and samples of chorioamnion tissue and membrane swabs were collected. These were tested for Ureaplasma spp. and aerobic/anaerobic bacteria by culture and real-time PCR. Western blot was used to assess MBA variation in ureaplasma clinical isolates. The presence of microorganisms was correlated with histological chorioamnionitis. Results: Ureaplasma spp. were isolated from 33/466 (7%) of placentas by culture or PCR. The presence of ureaplasmas, but not other microorganisms, was associated with histological chorioamnionitis (21/33 ureaplasma-positive vs. 8/42 other bacteria; p= 0.001). Ureaplasma clinical isolates demonstrating no MBA variation were associated with histological chorioamnionitis. By contrast, ureaplasmas displaying MBA variation were isolated from placentas with no significant histological chorioamnionitis (p= 0.001). Conclusion: Ureaplasma spp. within placentas delivered late preterm (7%) is associated with histological chorioamnionitis (p = 0.001). Decreased inflammation within chorioamnion was observed when the clinical ureaplasma isolates demonstrated variation of their surface-exposed lipoproteins (MBA). This variation may be a mechanism by which ureaplasmas modulate and evade the host immune response. So whilst ureaplasmas are present intra-amniotically they are not suspected because of the normal macroscopic appearance of the placentas and the amniotic fluid.

Intracellular trafficking and secretion of inflammatory cytokines

The secretion of cytokines by immune cells plays a significant role in determining the course of an inflammatory response. The levels and timing of each cytokine released are critical for mounting an effective but confined response, whereas excessive or dysregulated inflammation contributes to many diseases. Cytokines are both culprits and targets for effective treatments in some diseases. The multiple points and mechanisms that have evolved for cellular control of cytokine secretion highlight the potency of these mediators and the fine tuning required to manage inflammation. Cytokine production in cells is regulated by cell signaling, and at mRNA and protein synthesis levels. Thereafter, the intracellular transport pathways and molecular trafficking machinery have intricate and essential roles in dictating the release and activity of cytokines. The trafficking machinery and secretory (exocytic) pathways are complex and highly regulated in many cells, involving specialized membranes, molecules and organelles that enable these cells to deliver cytokines to often-distinct areas of the cell surface, in a timely manner. This review provides an overview of secretory pathways - both conventional and unconventional - and key families of trafficking machinery. The prevailing knowledge about the trafficking and secretion of a number of individual cytokines is also summarized. In conclusion, we present emerging concepts about the functional plasticity of secretory pathways and their modulation for controlling cytokines and inflammation.

Technological innovation and operational effectiveness : their role in achieving performance improvements

The purpose of this article is to examine the role of the alignment between technological innovation effectiveness and operational effectiveness after the implementation of enterprise information systems, and the impact of this alignment on the improvement in operational performance. Confirmatory factor analysis was used to examine structural relationships between the set of observed variables and the set of continuous latent variables. The findings from this research suggest that the dimensions stemming from technological innovation effectiveness such as system quality, information quality, service quality, user satisfaction and the performance objectives stemming from operational effectiveness such as cost, quality, reliability, flexibility and speed are important and significantly well-correlated factors. These factors promote the alignment between technological innovation effectiveness and operational effectiveness and should be the focus for managers in achieving effective implementation of technological innovations. In addition, there is a significant and direct influence of this alignment on the improvement of operational performance. The principal limitation of this study is that the findings are based on investigation of small sample size.

New and young firms Entrepreneurship policy and the role of government – evidence from the Federation of Small Businesses survey

Purpose – The purpose of this paper is to investigate whether new and young firms are different from older firms. This analysis is undertaken to explore general characteristics, use of external resources and growth orientation. Design/methodology/approach – Data from the 2008 UK Federation of Small Businesses survey provided 8,000 responses. Quantitative analysis identified significantly different characteristics of firms from 0-4, 4-9, 9-19 and 20+ years. Factor analysis was utilised to identify the advice sets, finance and public procurement customers of greatest interest, with ANOVA used to statistically compare firms in the identified age groups with different growth aspirations. Findings – The findings reveal key differences between new, young and older firms in terms of characteristics including business sector, owner/manager age, education/business experience, legal status, intellectual property and trading performance. New and young firms were more able to access beneficial resources in terms of finance and advice from several sources. New and young firms were also able to more easily access government and external finance, as well as government advice, but less able to access public procurement. Research limitations/implications – New and young firms are utilising external networks to access several resources for development purposes, and this differs for older firms. This suggests that a more explicit age-differentiated focus is required for government policies aimed at supporting firm growth. Originality/value – The study provides important baseline data for future quantitative and qualitative studies focused on the impact of firm age and government policy.

The contribution of psychosocial factors to socioeconomic differences in food purchasing

In developed countries the relationship between socioeconomic position (SEP) and health is unequivocal. Those who are socioeconomically disadvantaged are known to experience higher morbidity and mortality from a range of chronic diet-related conditions compared to those of higher SEP. Socioeconomic inequalities in diet are well established. Compared to their more advantaged counterparts, those of low SEP are consistently found to consume diets less consistent with dietary guidelines (i.e. higher in fat, salt and sugar and lower in fibre, fruit and vegetables). Although the reasons for dietary inequalities remain unclear, understanding how such differences arise is important for the development of strategies to reduce health inequalities. Both environmental (e.g. proximity of supermarkets, price, and availability of foods) and psychosocial (e.g. taste preference, nutrition knowledge) influences are proposed to account for inequalities in food choices. Although in the United States (US), United Kingdom (UK), and parts of Australia, environmental factors are associated with socioeconomic differences in food choices, these factors do not completely account for the observed inequalities. Internationally, this context has prompted calls for further exploration of the role of psychological and social factors in relation to inequalities in food choices. It is this task that forms the primary goal of this PhD research. In the small body of research examining the contribution of psychosocial factors to inequalities in food choices, studies have focussed on food cost concerns, nutrition knowledge or health concerns. These factors are generally found to be influential. However, since a range of psychosocial factors are known determinants of food choices in the general population, it is likely that a range of factors also contribute to inequalities in food choices. Identification of additional psychosocial factors of relevance to inequalities in food choices would provide new opportunities for health promotion, including the adaption of existing strategies. The methodological features of previous research have also hindered the advancement of knowledge in this area and a lack of qualitative studies has resulted in a dearth of descriptive information on this topic. This PhD investigation extends previous research by assessing a range of psychosocial factors in relation to inequalities in food choices using both quantitative and qualitative techniques. Secondary data analyses were undertaken using data obtained from two Brisbane-based studies, the Brisbane Food Study (N=1003, conducted in 2000), and the Sixty Families Study (N=60, conducted in 1998). Both studies involved main household food purchasers completing an interviewer-administered survey within their own home. Data pertaining to food-purchasing, and psychosocial, socioeconomic and demographic characteristics were collected in each study. The mutual goals of both the qualitative and quantitative phases of this investigation were to assess socioeconomic differences in food purchasing and to identify psychosocial factors relevant to any observed differences. The quantitative methods then additionally considered whether the associations examined differed according to the socioeconomic indicator used (i.e. income or education). The qualitative analyses made a unique contribution to this project by generating detailed descriptions of socioeconomic differences in psychosocial factors. Those with lower levels of income and education were found to make food purchasing choices less consistent with dietary guidelines compared to those of high SEP. The psychosocial factors identified as relevant to food-purchasing inequalities were: taste preferences, health concerns, health beliefs, nutrition knowledge, nutrition concerns, weight concerns, nutrition label use, and several other values and beliefs unique to particular socioeconomic groups. Factors more tenuously or inconsistently related to socioeconomic differences in food purchasing were cost concerns, and perceived adequacy of the family diet. Evidence was displayed in both the quantitative and qualitative analyses to suggest that psychosocial factors contribute to inequalities in food purchasing in a collective manner. The quantitative analyses revealed that considerable overlap in the socioeconomic variation in food purchasing was accounted for by key psychosocial factors of importance, including taste preference, nutrition concerns, nutrition knowledge, and health concerns. Consistent with these findings, the qualitative transcripts demonstrated the interplay between such influential psychosocial factors in determining food-purchasing choices. The qualitative analyses found socioeconomic differences in the prioritisation of psychosocial factors in relation to food choices. This is suggestive of complex cultural factors that distinguish advantaged and disadvantaged groups and result in socioeconomically distinct schemas related to health and food choices. Compared to those of high SEP, those of lower SEP were less likely to indicate that health concerns, nutrition concerns, or food labels influenced food choices, and exhibited lower levels of nutrition knowledge. In the absence of health or nutrition-related concerns, taste preferences tended to dominate the food purchasing choices of those of low SEP. Overall, while cost concerns did not appear to be a main determinant of socioeconomic differences in food purchasing, this factor had a dominant influence on the food choices of some of the most disadvantaged respondents included in this research. The findings of this study have several implications for health promotion. The integrated operation of psychosocial factors on food purchasing inequalities indicates that multiple psychosocial factors may be appropriate to target in health promotion. It also seems possible that the inter-relatedness of psychosocial factors would allow health promotion targeting a single psychosocial factor to have a flow-on affect in terms of altering other influential psychosocial factors. This research also suggests that current mass marketing approaches to health promotion may not be effective across all socioeconomic groups due to differences in the priorities and main factors of influence in food purchasing decisions across groups. In addition to the practical recommendations for health promotion, this investigation, through the critique of previous research, and through the substantive study findings, has highlighted important methodological considerations for future research. Of particular note are the recommendations pertaining to the selection of socioeconomic indicators, measurement of relevant constructs, consideration of confounders, and development of an analytical approach. Addressing inequalities in health has been noted as a main objective by many health authorities and governments internationally. It is envisaged that the substantive and methodological findings of this thesis will make a useful contribution towards this important goal.