The effect of consumption volume on profile and liking of oral nutritional supplements of varied sweetness: sequential profiling and boredom tests

Oral nutrition supplements (ONS) are routinely prescribed to those with, or at risk of, malnutrition. Previous research identified poor compliance due to taste and sweetness. This paper investigates taste and hedonic liking of ONS, of varying sweetness and metallic levels, over consumption volume; an important consideration as patients are prescribed large volumes of ONS daily. A sequential descriptive profile was developed to determine the perception of sensory attributes over repeat consumption of ONS. Changes in liking of ONS following repeat consumption were characterised by a boredom test. Certain flavour (metallic taste, soya milk flavour) and mouthfeel (mouthdrying, mouthcoating) attributes built up over increased consumption volume (p 0.002). Hedonic liking data from two cohorts, healthy older volunteers (n = 32, median age 73) and patients (n = 28, median age 85), suggested such build-up was disliked. Efforts made to improve the palatability of ONS must take account of the build up of taste and mouthfeel characteristics over increased consumption volume.

Action following the discovery of a global association between the whole genome and adverse event risk in a clinical drug-development programme

Observation of adverse drug reactions during drug development can cause closure of the whole programme. However, if association between the genotype and the risk of an adverse event is discovered, then it might suffice to exclude patients of certain genotypes from future recruitment. Various sequential and non-sequential procedures are available to identify an association between the whole genome, or at least a portion of it, and the incidence of adverse events. In this paper we start with a suspected association between the genotype and the risk of an adverse event and suppose that the genetic subgroups with elevated risk can be identified. Our focus is determination of whether the patients identified as being at risk should be excluded from further studies of the drug. We propose using a utility function to? determine the appropriate action, taking into account the relative costs of suffering an adverse reaction and of failing to alleviate the patient's disease. Two illustrative examples are presented, one comparing patients who suffer from an adverse event with contemporary patients who do not, and the other making use of a reference control group. We also illustrate two classification methods, LASSO and CART, for identifying patients at risk, but we stress that any appropriate classification method could be used in conjunction with the proposed utility function. Our emphasis is on determining the action to take rather than on providing definitive evidence of an association. Copyright (C) 2008 John Wiley & Sons, Ltd.

Transcriptional profiling of the LPS induced NF-kappaB response in macrophages

BACKGROUND: Exposure of macrophages to bacterial products such as lipopolysaccharide (LPS) results in activation of the NF-kappaB transcription factor, which orchestrates a gene expression programme that underpins the macrophage-dependent immune response. These changes include the induction or repression of a wide range of genes that regulate inflammation, cell proliferation, migration and cell survival. This process is tightly regulated and loss of control is associated with conditions such as septic shock, inflammatory diseases and cancer. To study this response, it is important to have in vitro model systems that reflect the behaviour of cells in vivo. In addition, it is necessary to understand the natural differences that can occur between individuals. In this report, we have investigated and compared the LPS response in macrophage derived cell lines and peripheral blood mononuclear cell (PBMC) derived macrophages. RESULTS: Gene expression profiles were determined following LPS treatment of THP-1 cells for 1 and 4 hours. LPS significantly induced or repressed 72 out of 465 genes selected as being known or putative NF-kappaB target genes, which exhibited 4 temporal patterns of expression. Results for 34 of these genes, including several genes not previously identified as LPS target genes, were validated using real time PCR. A high correlation between microarray and real time PCR data was found. Significantly, the LPS induced expression profile of THP-1 cells, as determined using real time PCR, was found to be very similar to that of human PBMC derived macrophages. Interestingly, some differences were observed in the LPS response between the two donor PBMC macrophage populations. Surprisingly, we found that the LPS response in U937 cells was dramatically different to both THP-1 and PBMC derived macrophages. CONCLUSION: This study revealed a dynamic and diverse transcriptional response to LPS in macrophages, involving both the induction and repression of gene expression in a time dependent manner. Moreover, we demonstrated that the LPS induced transcriptional response in the THP-1 cell line is very similar to primary PBMC derived macrophages. Therefore, THP-1 cells represent a good model system for studying the mechanisms of LPS and NF-kappaB dependent gene expression.

Proteomic profiling of neuromas reveals alterations in protein composition and local protein synthesis in hyper-excitable nerves

Neuropathic pain may arise following peripheral nerve injury though the molecular mechanisms associated with this are unclear. We used proteomic profiling to examine changes in protein expression associated with the formation of hyper-excitable neuromas derived from rodent saphenous nerves. A two-dimensional difference gel electrophoresis ( 2D-DIGE) profiling strategy was employed to examine protein expression changes between developing neuromas and normal nerves in whole tissue lysates. We found around 200 proteins which displayed a > 1.75-fold change in expression between neuroma and normal nerve and identified 55 of these proteins using mass spectrometry. We also used immunoblotting to examine the expression of low-abundance ion channels Nav1.3, Nav1.8 and calcium channel alpha 2 delta-1 subunit in this model, since they have previously been implicated in neuronal hyperexcitability associated with neuropathic pain. Finally, S(35)methionine in vitro labelling of neuroma and control samples was used to demonstrate local protein synthesis of neuron-specific genes. A number of cytoskeletal proteins, enzymes and proteins associated with oxidative stress were up-regulated in neuromas, whilst overall levels of voltage-gated ion channel proteins were unaffected. We conclude that altered mRNA levels reported in the somata of damaged DRG neurons do not necessarily reflect levels of altered proteins in hyper-excitable damaged nerve endings. An altered repertoire of protein expression, local protein synthesis and topological re-arrangements of ion channels may all play important roles in neuroma hyper-excitability.

Profiling of composition and metabolic activities of the colonic microflora of growing pigs fed diets supplemented with prebiotic oligosaccharides

It is evident that quantitative information on different microbial groups and their contribution in terms of activity in the gastrointestinal (GI) tract of humans and animals is required in order to formulate functional diets targeting improved gut function and host health. In this work, quantitative information on levels and spatial distributions of Bacteroides spp, Eubacterium spp, Clostridium spp, Escherichia coli, Bifidobacterium spp and Lactobacillus/Enterococcus spp. along the porcine large intestine was investigated using 16S rRNA targeted probes and fluorescent in situ hybridisation (FISH). Caecum, ascending colon (AC) and rectum luminal digesta from three groups of individually housed growing pigs fed either a corn-soybean basal diet (CON diet) or a prebiotic diet containing 10 g/kg oligofructose (FOS diet) or trans-galactooligosaccharides (TOS diet) at the expense of cornstarch were analysed. DAPI staining was used to enumerate total number of cells in the samples. Populations of total cells, Bacteroides, Eubacterium, Clostridium and Bifidobacterium, declined significantly (P < 0.05) from caecum to rectum, and were not affected by dietary treatments. Populations of Lactobacillus/ Enterococcus and E coli did not differ throughout the large intestine. The relative percent (%) contribution of each bacterial group to the total cell count did not differ between caecum and rectum, with the exception of Eubacterium that was higher in the AC digesta. FISH analysis showed that the sum of all bacterial groups made up a small percentage of the total cells, which was 12.4%, 21.8% and 10.3% in caecum, AC and rectum, respectively. This supports the view that in swine, the diversity of GI microflora might be higher compared to other species. In terms of microflora metabolic activity, the substantially higher numerical trends seen in FOS and TOS treatments regarding total volatile fatty acid, acetate concentrations and glycolytic activities, it could be postulated that FOS and TOS promoted saccharolytic activities in the porcine colon. (c) 2006 Elsevier Ltd. All rights reserved.

Efficient modeling and inference for event-related fMRI data

Event-related functional magnetic resonance imaging (efMRI) has emerged as a powerful technique for detecting brains' responses to presented stimuli. A primary goal in efMRI data analysis is to estimate the Hemodynamic Response Function (HRF) and to locate activated regions in human brains when specific tasks are performed. This paper develops new methodologies that are important improvements not only to parametric but also to nonparametric estimation and hypothesis testing of the HRF. First, an effective and computationally fast scheme for estimating the error covariance matrix for efMRI is proposed. Second, methodologies for estimation and hypothesis testing of the HRF are developed. Simulations support the effectiveness of our proposed methods. When applied to an efMRI dataset from an emotional control study, our method reveals more meaningful findings than the popular methods offered by AFNI and FSL. (C) 2008 Elsevier B.V. All rights reserved.

Adaptive control of event integration

Identifying 2 target stimuli in a rapid stream of visual symbols is much easier if the 2nd target appears immediately after the 1st target (i.e., at Lag 1) than if distractor stimuli intervene. As this phenomenon comes with a strong tendency to confuse the order of the targets, it seems to be due to the integration of both targets into the same attentional episode or object file. The authors investigated the degree to which people can control the temporal extension of their (episodic) integration windows by manipulating the expectations participants had with regard to the time available for target processing. As predicted, expecting more time to process increased the number of order confusions at Lag 1. This was true for between-subjects and within-subjects (trial-to-trial) manipulations, suggesting that integration windows can be adapted actively and rather quickly.

Adaptive control of event integration: evidence from event-related potentials

We investigated whether it is possible to control the temporal window of attention used to rapidly integrate visual information. To study the underlying neural mechanisms, we recorded ERPs in an attentional blink task, known to elicit Lag-1 sparing. Lag-1 sparing fosters joint integration of the two targets, evidenced by increased order errors. Short versus long integration windows were induced by showing participants mostly fast or slow stimuli. Participants expecting slow speed used a longer integration window, increasing joint integration. Difference waves showed an early (200 ms post-T2) negative and a late positive modulation (390 ms) in the fast group, but not in the slow group. The modulations suggest the creation of a separate event for T2, which is not needed in the slow group, where targets were often jointly integrated. This suggests that attention can be guided by global expectations of presentation speed within tens of milliseconds.

Profiling management for personalised multimedia delivery on-demand within the AXMEDIS framework

Media content distribution on-demand becomes more complex when performed on a mass scale involving various channels with distinct and dynamic network characteristics, and, deploying a variety of terminal devices offering a wide range of capabilities. It is practically impossible to create and prepackage various static versions of the same content to match all the varying demand parameters of clients for various contexts. In this paper we present a profiling management approach for dynamically personalised media content delivery on-demand integrated with the AXMEDIS Framework. The client profiles comprise the representation of User, Device, Network and Context of content delivery based on MPEG-21:DIA. Although the most challenging proving ground for this personalised content delivery has been the mobile testbed i.e. the distribution to mobile handsets, the framework described here can be deployed for disribution, by the AXMEDIS PnP module, through other channels e.g. satellite, Internet to a range of client terminals e.g. desktops, kiosks, IPtv and other terrminals whose baseline terminal capabilities can be made availabe by the manufacturers as is normal.

Single-trial event-related potential analysis for brain-computer interfaces

Abstract. Different types of mental activity are utilised as an input in Brain-Computer Interface (BCI) systems. One such activity type is based on Event-Related Potentials (ERPs). The characteristics of ERPs are not visible in single-trials, thus averaging over a number of trials is necessary before the signals become usable. An improvement in ERP-based BCI operation and system usability could be obtained if the use of single-trial ERP data was possible. The method of Independent Component Analysis (ICA) can be utilised to separate single-trial recordings of ERP data into components that correspond to ERP characteristics, background electroencephalogram (EEG) activity and other components with non- cerebral origin. Choice of specific components and their use to reconstruct “denoised” single-trial data could improve the signal quality, thus allowing the successful use of single-trial data without the need for averaging. This paper assesses single-trial ERP signals reconstructed using a selection of estimated components from the application of ICA on the raw ERP data. Signal improvement is measured using Contrast-To-Noise measures. It was found that such analysis improves the signal quality in all single-trials.

Slogger: a profiling and analysis system based on semantic web technologies

Increasingly, distributed systems are being used to host all manner of applications. While these platforms provide a relatively cheap and effective means of executing applications, so far there has been little work in developing tools and utilities that can help application developers understand problems with the supporting software, or the executing applications. To fully understand why an application executing on a distributed system is not behaving as would be expected it is important that not only the application, but also the underlying middleware, and the operating system are analysed too, otherwise issues could be missed and certainly overall performance profiling and fault diagnoses would be harder to understand. We believe that one approach to profiling and the analysis of distributed systems and the associated applications is via the plethora of log files generated at runtime. In this paper we report on a system (Slogger), that utilises various emerging Semantic Web technologies to gather the heterogeneous log files generated by the various layers in a distributed system and unify them in common data store. Once unified, the log data can be queried and visualised in order to highlight potential problems or issues that may be occurring in the supporting software or the application itself.