Description and critical appraisal of principal components analysis (PCA) methodology applied to pulsed-field gel electrophoresis profiles of methicillin-resistant Staphylococcus aureus isolates

Principal components analysis (PCA) has been described for over 50 years; however, it is rarely applied to the analysis of epidemiological data. In this study PCA was critically appraised in its ability to reveal relationships between pulsed-field gel electrophoresis (PFGE) profiles of methicillin- resistant Staphylococcus aureus (MRSA) in comparison to the more commonly employed cluster analysis and representation by dendrograms. The PFGE type following SmaI chromosomal digest was determined for 44 multidrug-resistant hospital-acquired methicillin-resistant S. aureus (MR-HA-MRSA) isolates, two multidrug-resistant community-acquired MRSA (MR-CA-MRSA), 50 hospital-acquired MRSA (HA-MRSA) isolates (from the University Hospital Birmingham, NHS Trust, UK) and 34 community-acquired MRSA (CA-MRSA) isolates (from general practitioners in Birmingham, UK). Strain relatedness was determined using Dice band-matching with UPGMA clustering and PCA. The results indicated that PCA revealed relationships between MRSA strains, which were more strongly correlated with known epidemiology, most likely because, unlike cluster analysis, PCA does not have the constraint of generating a hierarchic classification. In addition, PCA provides the opportunity for further analysis to identify key polymorphic bands within complex genotypic profiles, which is not always possible with dendrograms. Here we provide a detailed description of a PCA method for the analysis of PFGE profiles to complement further the epidemiological study of infectious disease. © 2005 Elsevier B.V. All rights reserved.

An assessment of the industry cluster approach as a tool for local economic development:the case of the new media industry in Birmingham

Industry cluster policies are a current trend in local economic development programmes and represent a major shift from traditional approaches. This trend has been coupled by an increasing interest in new media industry as a significant focus for regional development strategies. In England clusters and new media industry have therefore come to be seen as important tools in promoting local and regional economic development. This study aimed to ascertain the success of these policies. In order to achieve the aims of the study, the Birmingham new media industry was chosen for the study. In addition to an extensive review of the literature, semi-structured interviews were conducted with new media firms and Business Support Agencies (BSAs) offering programmes to promote the development of the new media industry cluster. The key findings of the thesis are that the concerns of new media industry when choosing their location do not conform to the industry cluster theory. Moreover, close proximity in geographical location of the industries does not mean there is collaboration and any costs saved as a result of close proximity to similar firms are at present seen as irrelevant because of the type of products they offer. Building trust between firms is the key in developing the new media industry cluster and the BSAs can act as a broker and provide neutral ground to develop it. The key policy recommendations are that new media industry is continually changing and research must continuously track and analyse cluster dynamics in order to be aware of emerging trends and future developments that can positively and negatively affect the cluster. Policy makers need to keep in mind that there is no uniform tool kit to foster the different sectors in cluster development. It is also important for them to be winning support and trust of new media firms since this is key in the success of the cluster. When cluster programs are introduced they must explain their benefits to industries more effectively in order to encourage them to participate in programmes. The general conclusions of the thesis are that clusters are a potentially important tool in local economic development policy and that the new media industry has a considerable growth potential. The kinds of relationships which cluster theory suggests develop between do not, as yet, appear to exist within the new media cluster. There are however, steps that the BSAs can take to encourage their development. Thus, the BSAs need to ensure that they establish an environment that enables growth of the industry.

The development of an objective methodology to measure medication adherence to oral thiopurines in paediatric patients with acute lymphoblastic leukaemia - an exploratory study

Aims - To develop a method that prospectively assesses adherence rates in paediatric patients with acute lymphoblastic leukaemia (ALL) who are receiving the oral thiopurine treatment 6-mercaptopurine (6-MP). Methods - A total of 19 paediatric patients with ALL who were receiving 6-MP therapy were enrolled in this study. A new objective tool (hierarchical cluster analysis of drug metabolite concentrations) was explored as a novel approach to assess non-adherence to oral thiopurines, in combination with other objective measures (the pattern of variability in 6-thioguanine nucleotide erythrocyte concentrations and 6-thiouric acid plasma levels) and the subjective measure of self-reported adherence questionnaire. Results - Parents of five ALL patients (26.3%) reported at least one aspect of non-adherence, with the majority (80%) citing “carelessness at times about taking medication” as the primary reason for non-adherence followed by “forgetting to take the medication” (60%). Of these patients, three (15.8%) were considered non-adherent to medication according to the self-reported adherence questionnaire (scored ≥ 2). Four ALL patients (21.1%) had metabolite profiles indicative of non-adherence (persistently low levels of metabolites and/or metabolite levels clustered variably with time). Out of these four patients, two (50%) admitted non-adherence to therapy. Overall, when both methods were combined, five patients (26.3%) were considered non-adherent to medication, with higher age representing a risk factor for non-adherence (P < 0.05). Conclusions - The present study explored various ways to assess adherence rates to thiopurine medication in ALL patients and highlighted the importance of combining both objective and subjective measures as a better way to assess adherence to oral thiopurines.

Influence of birth cohort on age of onset cluster analysis in bipolar I disorder

PURPOSE: Two common approaches to identify subgroups of patients with bipolar disorder are clustering methodology (mixture analysis) based on the age of onset, and a birth cohort analysis. This study investigates if a birth cohort effect will influence the results of clustering on the age of onset, using a large, international database. METHODS: The database includes 4037 patients with a diagnosis of bipolar I disorder, previously collected at 36 collection sites in 23 countries. Generalized estimating equations (GEE) were used to adjust the data for country median age, and in some models, birth cohort. Model-based clustering (mixture analysis) was then performed on the age of onset data using the residuals. Clinical variables in subgroups were compared. RESULTS: There was a strong birth cohort effect. Without adjusting for the birth cohort, three subgroups were found by clustering. After adjusting for the birth cohort or when considering only those born after 1959, two subgroups were found. With results of either two or three subgroups, the youngest subgroup was more likely to have a family history of mood disorders and a first episode with depressed polarity. However, without adjusting for birth cohort (three subgroups), family history and polarity of the first episode could not be distinguished between the middle and oldest subgroups. CONCLUSION: These results using international data confirm prior findings using single country data, that there are subgroups of bipolar I disorder based on the age of onset, and that there is a birth cohort effect. Including the birth cohort adjustment altered the number and characteristics of subgroups detected when clustering by age of onset. Further investigation is needed to determine if combining both approaches will identify subgroups that are more useful for research.