Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis

Ulcerative colitis (UC) is characterized by impairment of the epithelial barrier and the formation of ulcer-type lesions, which result in local leaks and generalized alterations of mucosal tight junctions. Ultimately, this results in increased basal permeability. Although disruption of the epithelial barrier in the gut is a hallmark of inflammatory bowel disease and intestinal infections, it remains unclear whether barrier breakdown is an initiating event of UC or rather a consequence of an underlying inflammation, evidenced by increased production of proinflammatory cytokines. UC is less common in smokers, suggesting that the nicotine in cigarettes may ameliorate disease severity. The mechanism behind this therapeutic effect is still not fully understood, and indeed it remains unclear if nicotine is the true protective agent in cigarettes. Nicotine is metabolized in the body into a variety of metabolites and can also be degraded to form various breakdown products. It is possible these metabolites or degradation products may be the true protective or curative agents. A greater understanding of the pharmacodynamics and kinetics of nicotine in relation to the immune system and enhanced knowledge of out permeability defects in UC are required to establish the exact protective nature of nicotine and its metabolites in UC. This review suggests possible hypotheses for the protective mechanism of nicotine in UC, highlighting the relationship between gut permeability and inflammation, and indicates where in the pathogenesis of the disease nicotine may mediate its effect.

Perceptual grouping and distance estimates in typical and atypical development: comparing performance across perception, drawing and construction tasks

Perceptual grouping is a pre-attentive process which serves to group local elements into global wholes, based on shared properties. One effect of perceptual grouping is to distort the ability to estimate the distance between two elements. In this study, biases in distance estimates, caused by four types of perceptual grouping, were measured across three tasks, a perception, a drawing and a construction task in both typical development (TD: Experiment 1) and in individuals with Williams syndrome (WS: Experiment 2). In Experiment 1, perceptual grouping distorted distance estimates across all three tasks. Interestingly, the effect of grouping by luminance was in the opposite direction to the effects of the remaining grouping types. We relate this to differences in the ability to inhibit perceptual grouping effects on distance estimates. Additive distorting influences were also observed in the drawing and the construction task, which are explained in terms of the points of reference employed in each task. Experiment 2 demonstrated that the above distortion effects are also observed in WS. Given the known deficit in the ability to use perceptual grouping in WS, this suggests a dissociation between the pre-attentive influence of and the attentive deployment of perceptual grouping in WS. The typical distortion in relation to drawing and construction points towards the presence of some typical location coding strategies in WS. The performance of the WS group differed from the TD participants on two counts. First, the pattern of overall distance estimates (averaged across interior and exterior distances) across the four perceptual grouping types, differed between groups. Second, the distorting influence of perceptual grouping was strongest for grouping by shape similarity in WS, which contrasts to a strength in grouping by proximity observed in the TD participants. (c) 2008 Elsevier Inc. All rights reserved.

Articulation of information requirements for personalised knowledge and construction

The quality of information provision influences considerably knowledge construction driven by individual users’ needs. In the design of information systems for e-learning, personal information requirements should be incorporated to determine a selection of suitable learning content, instructive sequencing for learning content, and effective presentation of learning content. This is considered as an important part of instructional design for a personalised information package. The current research reveals that there is a lack of means by which individual users’ information requirements can be effectively incorporated to support personal knowledge construction. This paper presents a method which enables an articulation of users’ requirements based on the rooted learning theories and requirements engineering paradigms. The user’s information requirements can be systematically encapsulated in a user profile (i.e. user requirements space), and further transformed onto instructional design specifications (i.e. information space). These two spaces allow the discovering of information requirements patterns for self-maintaining and self-adapting personalisation that enhance experience in the knowledge construction process.

Nonlinear model structure design and construction using orthogonal least squares and D-optimality design

A very efficient learning algorithm for model subset selection is introduced based on a new composite cost function that simultaneously optimizes the model approximation ability and model robustness and adequacy. The derived model parameters are estimated via forward orthogonal least squares, but the model subset selection cost function includes a D-optimality design criterion that maximizes the determinant of the design matrix of the subset to ensure the model robustness, adequacy, and parsimony of the final model. The proposed approach is based on the forward orthogonal least square (OLS) algorithm, such that new D-optimality-based cost function is constructed based on the orthogonalization process to gain computational advantages and hence to maintain the inherent advantage of computational efficiency associated with the conventional forward OLS approach. Illustrative examples are included to demonstrate the effectiveness of the new approach.

Auditory hallucinations and Posttraumatic Stress Disorder within schizophrenia and substance abuse

There is a high prevalence of traumatic events within individuals diagnosed with schizophrenia, and of auditory hallucinations within individuals diagnosed with posttraumatic stress disorder (PTSD). However, the relationship between the symptoms associated with these disorders remains poorly understood. We conducted a multidimensional assessment of auditory hallucinations within a sample diagnosed with schizophrenia and substance abuse, both with and without co-morbid PTSD. Results suggest a rate of co-morbid PTSD similar to those reported within other studies. Patients who suffered co-morbid PTSD reported more distressing auditory hallucinations. However, the hallucinations were not more frequent or of longer duration. The need for a multidimensional assessment is supported. Results are discussed within current theoretical accounts of traumatic psychosis.