Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.

Modelling cognitive impairment to improve universal access

The purpose of this study is to develop a model of cognitive impairment to help designers consider the range of issues which affect the lives of people living with such impairment. A series of interviews with experts of cognitive impairment was conducted to describe and assess the links between specific medical conditions, including learning disability, specific learning difficulties, autistic spectrum disorders, traumatic brain injury and schizophrenia, and the types of cognitive impairment associated with them. The results reveal some of the most prevalent and serious types of impairment, which - when transformed into design guidance - will help designers make mainstream products more inclusive also for people with cognitive impairment. © 2011 Springer-Verlag.

Adaptive modulation induced WDM impairment reduction in optical OFDM PONs

The transmission performance of multi-channel adaptively modulated optical OFDM (AMOOFDM) signals is numerically investigated, for the first time, in optical amplification- and chromatic dispersion compensation-free, intensity-modulation and direct-detection systems incorporating directly modulated DFB lasers (DMLs). It is shown that adaptive modulation not only reduces significantly the nonlinear WDM impairments induced by the effects of cross-phase modulation and four-wave mixing, but also compensates effectively for the DML-induced frequency chirp effect. In comparison with identical modulation, adaptive modulation improves the maximum achievable signal transmission capacity of a central channel by a factor of 1.3 and 3.6 for 40km and 80km SMFs, respectively, with corresponding dynamic input optical power ranges being extended by approximately 5dB. In addition, adaptive modulation also enables cross-channel complementary modulation format mapping, leading to an improved transmission capacity of the entire WDM system. Copyright © 2010 The authors.

A framework for studying cognitive impairment to inform inclusive design

Chapter 12 A Framework for Studying Cognitive Impairment to Inform Inclusive Design E. Jokisuu, PM Langdon and PJ Clarkson 12.1 Introduction Cognitive impairment is an exceptionally complicated phenomenon, for which no simple solutions ...

Simulating vision loss: What levels of impairment are actually represented?

Capability loss simulators give designers a brief experience of some of the functional effects of capability loss. They are an effective method of helping people to understand the impact of capability loss on product use. However, it is also important that designers know what levels of loss are being simulated and how they relate to the user population. The study in this paper tested the Cambridge Simulation Glasses with 25 participants to determine the effect of different numbers of glasses on a person's visual acuity. This data is also related to the glasses' use in usability assessment. A procedure is described for determining the number of simulator glasses with which the visual detail on a product is just visible. This paper then explains how to calculate the proportion of the UK population who would be unable to distinguish that detail.

Assessing the accessibility of everyday products

If a product is being designed to be genuinely inclusive, then the designers need to be able to assess the level of exclusion of the product that they are working on and to identify possible areas of improvement. To be of practical use, the assessments need to be quick, consistent and repeatable. The aim of this workshop is to invite attendees to participate in the evaluation of a number of everyday objects using an assessment technique being considered by the workshop organisers. The objectives of the workshop include evaluating the effectiveness of the assessment method, evaluating the accessibility of the products being assessed and to suggest revisions to the assessment scales being used. The assessment technique is to be based on the ONS capability measures [1]. This source recognises fourteen capability scales of which seven are particularly pertinent to product evaluation, namely: motion, dexterity, reach and stretch, vision, hearing, communication, and intellectual functioning. Each of these scales ranges from 0 (fully able) through 1 (minimal impairment) to 10 (severe impairment). The attendees will be asked to rate the products on these scales. Clearly the assessed accessibility of the product depends on the assumptions made about the context of use. The attendees will be asked to clearly note the assumptions that they are making about the context in which the product is being assessed. For instance, with a hot water bottle, assumptions have to be made about the availability of hot water and these can affect the overall accessibility rating. The workshop organisers will not specify the context of use as the aim is to identify how assessors would use the assessment method in the real world. The objects being assessed will include items such as remote controls, pill bottles, food packaging, hot water bottles and mobile telephones. the attendees will be encouraged to assess two or more products in detail. Helpers will be on hand to assist and observe the assessments. The assessments will be collated and compared and feedback about the assessment method sought from the attendees. Drawing on a preliminary review of the assessment results, initial conclusions will be presented at the end of the workshop. More detailed analyses will be made available in subsequent proceedings. It is intended that the workshop will provide workshop attendees with an opportunity to perform hands-on assessment of a number everyday products and identify features which are inclusive and those that are not. It is also intended to encourage an appreciation of the capabilities to be considered when evaluating accessibility.

User responses to the learning demands of consumer products

Designers are typically male, under 35 years old and unimpaired. Users can be of any age and currently over 15% will have some form of impairment. As a result a vast array of consumer products suit youthful males and in many cases exclude other demographics (e.g. Keates and Clarkson, 2004). In studying the way a range of users learn how to use new products, key cognitive difficulties are revealed and linked back to the areas of the product causing the problems. The trials were structured so each user had to complete a specific set of tasks and were consistent across the user spectrum. The tasks set aimed to represent both everyday usage and less familiar functions. Whilst the knowledge gained could provide designers with valuable guidelines for the specific products examined, a more general abstraction provides knowledge of the pitfalls to avoid in the design of other product families.

Designing inclusive interfaces through user modeling and simulation

Elderly and disabled people can be hugely benefited through the advancement of modern electronic devices, as those can help them to engage more fully with the world. However, existing design practices often isolate elderly or disabled users by considering them as users with special needs. This article presents a simulator that can reflect problems faced by elderly and disabled users while they use computer, television, and similar electronic devices. The simulator embodies both the internal state of an application and the perceptual, cognitive, and motor processes of its user. It can help interface designers to understand, visualize, and measure the effect of impairment on interaction with an interface. Initially a brief survey of different user modeling techniques is presented, and then the existing models are classified into different categories. In the context of existing modeling approaches the work on user modeling is presented for people with a wide range of abilities. A few applications of the simulator, which shows the predictions are accurate enough to make design choices and point out the implication and limitations of the work, are also discussed. © 2012 Copyright Taylor and Francis Group, LLC.

A crowding model of visual clutter.

Visual information is difficult to search and interpret when the density of the displayed information is high or the layout is chaotic. Visual information that exhibits such properties is generally referred to as being "cluttered." Clutter should be avoided in information visualizations and interface design in general because it can severely degrade task performance. Although previous studies have identified computable correlates of clutter (such as local feature variance and edge density), understanding of why humans perceive some scenes as being more cluttered than others remains limited. Here, we explore an account of clutter that is inspired by findings from visual perception studies. Specifically, we test the hypothesis that the so-called "crowding" phenomenon is an important constituent of clutter. We constructed an algorithm to predict visual clutter in arbitrary images by estimating the perceptual impairment due to crowding. After verifying that this model can reproduce crowding data we tested whether it can also predict clutter. We found that its predictions correlate well with both subjective clutter assessments and search performance in cluttered scenes. These results suggest that crowding and clutter may indeed be closely related concepts and suggest avenues for further research.

Functional magnetic resonance imaging of impaired sensory prediction in schizophrenia.

IMPORTANCE: Forward models predict the sensory consequences of planned actions and permit discrimination of self- and non-self-elicited sensation; their impairment in schizophrenia is implied by an abnormality in behavioral force-matching and the flawed agency judgments characteristic of positive symptoms, including auditory hallucinations and delusions of control. OBJECTIVE: To assess attenuation of sensory processing by self-action in individuals with schizophrenia and its relation to current symptom severity. DESIGN, SETTING, AND PARTICIPANTS: Functional magnetic resonance imaging data were acquired while medicated individuals with schizophrenia (n = 19) and matched controls (n = 19) performed a factorially designed sensorimotor task in which the occurrence and relative timing of action and sensation were manipulated. The study took place at the neuroimaging research unit at the Institute of Cognitive Neuroscience, University College London, and the Maudsley Hospital. RESULTS: In controls, a region of secondary somatosensory cortex exhibited attenuated activation when sensation and action were synchronous compared with when the former occurred after an unexpected delay or alone. By contrast, reduced attenuation was observed in the schizophrenia group, suggesting that these individuals were unable to predict the sensory consequences of their own actions. Furthermore, failure to attenuate secondary somatosensory cortex processing was predicted by current hallucinatory severity. CONCLUSIONS AND RELEVANCE: Although comparably reduced attenuation has been reported in the verbal domain, this work implies that a more general physiologic deficit underlies positive symptoms of schizophrenia.