Principal component analysis: a review and recent developments.

Large datasets are increasingly common and are often difficult to interpret. Principal component analysis (PCA) is a technique for reducing the dimensionality of such datasets, increasing interpretability but at the same time minimizing information loss. It does so by creating new uncorrelated variables that successively maximize variance. Finding such new variables, the principal components, reduces to solving an eigenvalue/eigenvector problem, and the new variables are defined by the dataset at hand, not a priori, hence making PCA an adaptive data analysis technique. It is adaptive in another sense too, since variants of the technique have been developed that are tailored to various different data types and structures. This article will begin by introducing the basic ideas of PCA, discussing what it can and cannot do. It will then describe some variants of PCA and their application.

Alginate-antacid combinations: raft formation and gastric retention studies.

BACKGROUND: Alginate-based gastroesophageal reflux disease treatments have been used extensively and fall into two main categories. Those containing alginate as the principle active agent and those containing alginate in combination with a significant amount of antacid. METHOD: The effectiveness of the raft formed by a new alginate/antacid suspension (Gaviscon Double Action Liquid, GDAL), in which calcium carbonate was the main antacid ingredient, was compared with those of existing alginate/antacid suspensions. RESULT: GDAL had similar raft strength and improved raft resilience than Gaviscon Liquid (GL), and both were significantly greater than five other products tested. Gastric retention of GDAL was similar to that of GL. CONCLUSION: the in vitro and in vivo performance is maintained in the new GDAL formulation even with higher antacid levels and the product is as good as, or better than, previous formulations.

The role of an alginate suspension on pepsin and bile acids - key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease?

OBJECTIVES: During a reflux event the oesophagus is exposed to a heterogeneous mixture of gastric juice components. The role of non-acid components of the refluxate in causing damage to the oesophagus is now well established but no therapeutic option exists to address this. METHODS: The role of Gaviscon Advance (GA), a raft-forming alginate suspension, in protecting the oesophagus from damage by pepsin and bile acids (aggressors) was investigated using a series of in-vitro models. KEY FINDINGS: GA was able to dose-dependently inhibit pepsin activity over and above the neutralisation effect of the formulation. This was evident against both protein and collagen substrates using two distinct colorimetric assays. GA was able to retard the diffusion of pepsin and multiple bile acids using a Franz cell model. Using the raft-forming mode of action GA was able to remove both pepsin and multiple bile acids from a simulated reflux event. There was capacity in the GA raft to accommodate aggressors from multiple reflux events. CONCLUSIONS: GA can specifically remove both pepsin and bile acids from the refluxate, limit their diffusion and affect enzymatic activity of pepsin. There is a role for GA to reduce the damaging potential of the refluxate and thus protect the oesophagus.

Microscopic techniques as potential tools to quantify the extent of bioadhesion of liquid systems.

This work demonstrates the potential of fluorescence and confocal microscopy as techniques to quantify both the extent and duration of bioadhesion of alginate solutions to porcine oesophageal tissue using an in vitro model. The retention of low (40 kDa), medium (240 kDa) and high (416 kDa) MW alginates was quantified via three methods of analysis. Fluorimetric analysis of the dose removed from the oesophageal surface suggested that the percentage of the original dose retained at 30 min was 7.9 +/- 7.0%, 21.9 +/- 9.5% and 23.7 +/- 5.8% for the alginates in order of increasing MW. Analysis of the dose adhered at 30 min using fluorescence microscopy demonstrated that 5.5 +/- 1.9%, 7.1 +/- 2.7% and 18.2 +/- 1.7% of the original dose of the alginate solutions was retained at 30 min. The results found using confocal microscopy showed that the percentage of the original dose adhered at 30 min of the low, medium and high MW alginates were 4.5 +/- 1.9%, 7.2 +/- 5.3% and 11.8 +/- 4.3%, respectively. All techniques demonstrated significantly greater retention of the high MW solution at 30 min compared to the low MW solution. Both confocal and fluorescence microscopy may be used as techniques to evaluate the bioadhesion of liquid systems.

Echo-planar magnetic resonance imaging of Gaviscon alginate rafts in-vivo.

Liquid Gaviscon and Gaviscon Advance are established reflux suppressant formulations. This study describes the use of echo-planar magnetic resonance imaging (EPI) to visualise non-invasively intragastric alginate rafts of Liquid Gaviscon and Gaviscon Advance in healthy subjects. Secondly, the feasibility of using relaxation rate (T2(-1)) measurements to monitor changes in the physicochemical properties of the rafts in-vivo is evaluated. Six subjects ingested 500 mL of a liquid meal and received a single dose of 20 mL Liquid Gaviscon or 10 mL Gaviscon Advance on 2 separate visits each and were imaged every 15 min. An alginate raft was observed in the stomach for all subjects and both treatments. The raft was observed to consist of a few large fragments on the majority of the scans for both products. At t = 60 min a raft was still present in all cases. Three-dimensional volume reconstructions showed, for the first time, the spatial distribution of the rafts within the gastric lumen. The T2(-1) data showed potential for assessment of dynamic changes in the physicochemical properties of the alginate rafts in-vivo. We conclude that EPI shows great potential in assessing alginate rafts formation in-vivo.