A novel Bayesian approach to drug design with simple and complex enzymes: Use with lens aldehyde dehydrogenase and the glyoxalase pathway

Purpose: Acquiring details of kinetic parameters of enzymes is crucial to biochemical understanding, drug development, and clinical diagnosis in ocular diseases. The correct design of an experiment is critical to collecting data suitable for analysis, modelling and deriving the correct information. As classical design methods are not targeted to the more complex kinetics being frequently studied, attention is needed to estimate parameters of such models with low variance. Methods: We have developed Bayesian utility functions to minimise kinetic parameter variance involving differentiation of model expressions and matrix inversion. These have been applied to the simple kinetics of the enzymes in the glyoxalase pathway (of importance in posttranslational modification of proteins in cataract), and the complex kinetics of lens aldehyde dehydrogenase (also of relevance to cataract). Results: Our successful application of Bayesian statistics has allowed us to identify a set of rules for designing optimum kinetic experiments iteratively. Most importantly, the distribution of points in the range is critical; it is not simply a matter of even or multiple increases. At least 60 % must be below the KM (or plural if more than one dissociation constant) and 40% above. This choice halves the variance found using a simple even spread across the range.With both the glyoxalase system and lens aldehyde dehydrogenase we have significantly improved the variance of kinetic parameter estimation while reducing the number and costs of experiments. Conclusions: We have developed an optimal and iterative method for selecting features of design such as substrate range, number of measurements and choice of intermediate points. Our novel approach minimises parameter error and costs, and maximises experimental efficiency. It is applicable to many areas of ocular drug design, including receptor-ligand binding and immunoglobulin binding, and should be an important tool in ocular drug discovery.

Under-investigation of older people with abnormal chest radiographs

Background: Whilst many authors have previously suggested that older people are under-represented in the investigation and management of lung cancer, few data are available as to the effect of age on the subsequent investigation and management of a patient with an abnormal chest radiograph. Methods: During a 3-month period in a university teaching hospital, all abnormal chest radiographs suggestive of a possible diagnosis of lung cancer were identified, and patients subsequently followed to determine investigation, management and date of death over a 5-year period. Results: Thirty-seven younger (less than or equal to69 years, median age 62 years) and 43 older patients ( 670 years, median age 80 years) were identified. Of the 80 patients with a possible bronchial carcinoma only 59% had a further chest radiograph performed. Bronchoscopy was performed in 34% of patients, but a biopsy of the lesion was undertaken in only 24% of patients. Sixteen of the 80 patients, irrespective of what investigations had been undertaken, were referred for an oncological or surgical opinion. During the study period ( 3 months), 24% of the patients died. At 6, 24 and 60 months, respectively, the total deaths were 40, 78 and 88%. Conclusion: Older patients compared with those aged less than 70 years were less likely to be investigated, further, were more likely to be managed differently (i.e., less aggressively) and more likely to die within each time interval. In more of the older group a presumed death certificate diagnosis of pneumonia was made. When an abnormal chest radiograph raises the possibility of an underlying bronchial carcinoma, the finding of this study suggests that an ageist attitude influences the subsequent management of some patients. Copyright (C) 2005 S. Karger AG, Basel.

A review of instruments developed to measure outcomes for carers of people with mental health problems

Objective: Community-based care for mental disorders places considerable burden on families and carers. Measuring their experiences has become a priority, but there is no consensus on appropriate instruments. We aimed to review instruments carers consider relevant to their needs and assess evidence for their use. Method: A literature search was conducted for outcome measures used with mental health carers. Identified instruments were assessed for their relevance to the outcomes identified by carers and their psychometric properties. Results: Three hundred and ninety two published articles referring to 241 outcome measures were identified, 64 of which were eligible for review (used in three or more studies). Twenty-six instruments had good psychometric properties; they measured (i) carers' well-being, (ii) the experience of caregiving and (iii) carers' needs for professional support. Conclusion: Measures exist which have been used to assess the most salient aspects of carer outcome in mental health. All require further work to establish their psychometric properties fully.

Mind-reading difficulties in the siblings of people with Asperger's syndrome: evidence for a genetic influence in the abnormal development of a specific cognitive domain

Background: Previous research suggests that the phenotype associated with Asperger's syndrome (AS) includes difficulties in understanding the mental states of others, leading to difficulties in social communication and social relationships. It has also been suggested that the first-degree relatives of those with AS can demonstrate similar difficulties, albeit to a lesser extent. This study examined 'theory of mind' (ToM) abilities in the siblings of children with AS relative to a matched control group. Method: 2 7 children who had a sibling with AS were administered the children's version of the 'Eyes Test'(Baron-Cohen, Wheelwright, Stone, & Rutherford, 1999). The control group consisted of 27 children matched for age, sex, and a measure of verbal comprehension, and who did not have a family history of AS/autism. Results: A significant difference was found between the groups on the Eyes Test, the 'siblings' group showing a poorer performance on this measure of social cognition. The difference was more pronounced among female siblings. Discussion: These results are discussed in terms of the familial distribution of a neuro-cognitive profile associated with AS, which confers varying degrees of social handicap amongst first-degree relatives. The implication of this finding with regard to the autism/AS phenotype is explored, with some discussion of why this neuro-cognitive profile (in combination with corresponding strengths) may have an evolutionary imperative.

Visual eye disease simulator

Visually impaired people have a very different view of the world such that seemingly simple environments as viewed by a ‘normally’ sighted people can be difficult for people with visual impairments to access and move around. This is a problem that can be hard to fully comprehend by people with ‘normal vision’ even when guidelines for inclusive design are available. This paper investigates ways in which image processing techniques can be used to simulate the characteristics of a number of common visual impairments in order to provide, planners, designers and architects, with a visual representation of how people with visual impairments view their environment, thereby promoting greater understanding of the issues, the creation of more accessible buildings and public spaces and increased accessibility for visually impaired people in everyday situations.

Designing Hospital Bedside Systems for use by Patients with Visual Impairments

This paper describes the development of an interface to a hospital portal system for information, communication and entertainment such that it can be used easily and effectively by all patients regardless of their age, disability, computer experience or native language. Specifically, this paper reports on the work conducted to ensure that the interface design took into account the needs of visually impaired users.

Semantic-associative visual content labelling and retrieval: A multimodal approach

A novel framework referred to as collaterally confirmed labelling (CCL) is proposed, aiming at localising the visual semantics to regions of interest in images with textual keywords. Both the primary image and collateral textual modalities are exploited in a mutually co-referencing and complementary fashion. The collateral content and context-based knowledge is used to bias the mapping from the low-level region-based visual primitives to the high-level visual concepts defined in a visual vocabulary. We introduce the notion of collateral context, which is represented as a co-occurrence matrix of the visual keywords. A collaborative mapping scheme is devised using statistical methods like Gaussian distribution or Euclidean distance together with collateral content and context-driven inference mechanism. We introduce a novel high-level visual content descriptor that is devised for performing semantic-based image classification and retrieval. The proposed image feature vector model is fundamentally underpinned by the CCL framework. Two different high-level image feature vector models are developed based on the CCL labelling of results for the purposes of image data clustering and retrieval, respectively. A subset of the Corel image collection has been used for evaluating our proposed method. The experimental results to-date already indicate that the proposed semantic-based visual content descriptors outperform both traditional visual and textual image feature models. (C) 2007 Elsevier B.V. All rights reserved.

Investigation of language and motor skills in Serbian speaking children with specific language impairment and in typically developing children

Specific language impairment (SLI) is usually defined as a developmental language disorder which does not result from a hearing loss, autism, neurological and emotional difficulties, severe social deprivation, low non-verbal abilities. Children affected with SLI typically have difficulties with the acquisition of different aspects of language and by definition, their impairment is specific to language and no other skills are affected. However, there has been a growing body of literature to suggest that children with SLI also have non-linguistic deficits, including impaired motor abilities. The aim of the current study is to investigate language and motor abilities of a group of thirty children with SLI (aged between 4 and 7) in comparison to a group of 30 typically developing children matched for chronological age. The results showed that the group of children with SLI had significantly more difficulties on the language and motor assessments compared to the control group. The SLI group also showed delayed onset in the development of all motor skills under investigation in comparison to the typically developing group. More interestingly, the two groups differed with respect to which language abilities were correlated with motor abilities, however Imitation of Complex Movements was the unique skill which reliably predicted expressive vocabulary in both typically developing children and in children with SLI.

Modeling camera orientation and 3D structure from a sequence of images taken by a perambulating commercial video camera

In this paper we report the degree of reliability of image sequences taken by off-the-shelf TV cameras for modeling camera rotation and reconstructing 3D structure using computer vision techniques. This is done in spite of the fact that computer vision systems usually use imaging devices that are specifically designed for the human vision. Our scenario consists of a static scene and a mobile camera moving through the scene. The scene is any long axial building dominated by features along the three principal orientations and with at least one wall containing prominent repetitive planar features such as doors, windows bricks etc. The camera is an ordinary commercial camcorder moving along the axial axis of the scene and is allowed to rotate freely within the range +/- 10 degrees in all directions. This makes it possible that the camera be held by a walking unprofessional cameraman with normal gait, or to be mounted on a mobile robot. The system has been tested successfully on sequence of images of a variety of structured, but fairly cluttered scenes taken by different walking cameramen. The potential application areas of the system include medicine, robotics and photogrammetry.

A virtual headstick for people with spinal cord injuries

This paper presents a virtual headstick system as an alternative to the conventional passive headstick for persons with limited upper extremity function. The system is composed of a pair of kinematically dissimilar master-slave robots with the master robot being operated by the user's head. At the remote site, the end-effector of the slave robot moves as if it were at the tip of an imaginary headstick attached to the user's head. A unique feature of this system is that through force-reflection, the virtual headstick provides the user with proprioceptive information as in a conventional headstick, but with an augmentation of workspace volume and additional mechanical power. This paper describes the test-bed development, system identification, bilateral control implementation, and system performance evaluation.

Beyond words: Visual metaphors that can demonstrate comprehension of KM as a paradoxical activity system

Following criticism that, in business and management, metaphor is largely verbal and primarily used to convey similarity, this paper explores how visual metaphors can communicate the anomalous and the paradoxical aspects of KM more concisely than words, whilst simultaneously presenting more tacit associations to stimulate creative thinking. It considers a series of 30 assessed posters that aimed to re-present six basic KM paradoxes through imagery that captures both the analogous and the anomalous. We found six categories of radial metaphors able to convey paradoxical complexity in a concise way. This has implications for organizations thinking about how to engage people with both the familiar and the strange. Copyright © 2011 John Wiley & Sons, Ltd.

Anxiety problems in young people with Asperger syndrome: a case series

It is now well established that the prevalence of mental health difficulties in individuals with autism spectrum disorders (ASD) is considerably higher than in the general population. With recent estimates of the prevalence of autism spectrum disorders being as high as one percent, increasing numbers of children and young people are presenting to local and specialist services with mental health problems in addition to a diagnosis of ASD. Many families report that the impact of the mental health problems can be as or more impairing than the autism spectrum difficulties themselves. Clinical services are frequently called upon to treat these difficulties; however, there is limited evidence for the effectiveness of treatments in this population. This paper reports a case series of children and adolescents with ASD and an anxiety disorder who were treated with a standard cognitive behaviour therapy (CBT) rationale adapted to take account of the neuropsychological features of ASD. Common features of the presentation of the disorders and also treatment processes are discussed.