Showing papers by "University College London published in 1996"

Reading Images: The Grammar of Visual Design

Abstract: Introduction 1. The Semiotic Landscape 2. Narrative Representations: Designing Social Action 3. Conceptual Representations: Designing Social Constructs 4. Representation and Interaction: Designing the Position of the Viewer 5. Morality: Designing Models of Reality 6. The Meaning of Composition 7. The Materiality of Meaning - Surface and Inscription 8. The Third Dimension

AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR

Abstract: The AQUA and PROCHECK-NMR programs provide a means of validating the geometry and restraint violations of an ensemble of protein structures solved by solution NMR. The outputs include a detailed breakdown of the restraint violations, a number of plots in PostScript format and summary statistics. These various analyses indicate both the degree of agreement of the model structures with the experimental dat, and the quality of their geometrical properties. They are intended to be of use both to support ongoing NMR structure determination and in the validation of the final results.

Principles of protein-protein interactions

Abstract: This review examines protein complexes in the Brookhaven Protein Databank to gain a better understanding of the principles governing the interactions involved in protein-protein recognition. The factors that influence the formation of protein-protein complexes are explored in four different types of protein-protein complexes--homodimeric proteins, heterodimeric proteins, enzyme-inhibitor complexes, and antibody-protein complexes. The comparison between the complexes highlights differences that reflect their biological roles.

The development and initial validation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for systemic lupus erythematosus.

Abstract: Objective. To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE). Methods. A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status. Results. Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients. Conclusion. This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.

Effect of skin impedance on image quality and variability in electrical impedance tomography: a model study

Abstract: A computer simulation is used to investigate the relationship between skin impedance and image artefacts in electrical impedance tomography. Sets of electrode impedance are generated with a pseudo-random distribution and used to introduce errors in boundary voltage measurements. To simplify the analysis, the non-idealities in the current injection circuit are replaced by a fixed common-mode error term. The boundary voltages are reconstructed into images and inspected. Where the simulated skin impedance remains constant between measurements, large impedances (> 2k omega) do not cause significant degradation of the image. Where the skin impedances 'drift' between measurements, a drift of 5% from a starting impedance of 100 omega is sufficient to cause significant image distortion. If the skin impedances vary randomly between measurements, they have to be less than 10 omega to allow satisfactory images. Skin impedances are typically 100-200 omega at 50 kHz on unprepared skin. These values are sufficient to cause image distortion if they drift over time. It is concluded that the patient's skin should be abraded to reduce impedance, and measurements should be avoided in the first 10 min after electrode placement.

Quality-of-service routing for supporting multimedia applications

Abstract: Several new architectures have been developed for supporting multimedia applications such as digital video and audio. However, quality-of-service (QoS) routing is an important element that is still missing from these architectures. In this paper, we consider a number of issues in QoS routing. We first examine the basic problem of QoS routing, namely, finding a path that satisfies multiple constraints, and its implications on routing metric selection, and then present three path computation algorithms for source routing and for hop-by-hop routing.

What Works for Whom?: A Critical Review of Psychotherapy Research

Abstract: Introduction 1. Defining the Psychotherapies 2. Research and Practice: Methodological Considerations and Their Influence on This Review 3. Psychotherapy Research, Health Policy, and Service Provision, Glenys Parry, Anthony Roth, and Peter Fonagy 4. Depression 5. Bipolar Disorder 6. Anxiety Disorders I: Specific Phobia, Social Phobia, Generalized Anxiety Disorder, and Panic Disorder with and without Agoraphobia 7. Anxiety Disorders II: Obsessive-Compulsive Disorder 8. Posttraumatic Stress Disorder 9. Eating Disorders: Anorexia Nervosa, Bulimia Nervosa, and Binge-Eating Disorder 10. Schizophrenia 11. Personality Disorders 12. Substance Abuse: Alcohol, Cocaine, and Opiate Dependence and Abuse 13. Sexual Dysfunctions 14. The Psychological Treatment of Child and Adolescent Psychiatric Disorders, Mary Target and Peter Fonagy 15. Effectiveness of Psychological Interventions with Older People, Robert Woods and Anthony Roth 16. The Contributions of Therapists and Patients to Outcome 17. Conclusions and Implications Appendix I. Converting Effect Sizes to Percentiles Appendix II. An Illustration of Commonly Used Clinically Intuitive Ways of Representing the Outcome of Trials Appendix III. Contrast between Prevalence Rates from Different Epidemiological Surveys

The Relation of Attachment Status, Psychiatric Classification, and Response to Psychotherapy.

Abstract: The relation of patterns of attachment and psychiatric status was studied in 82 nonpsychotic inpatients and 85 case-matched controls using the Adult Attachment Interview (AAI). AAI transcripts rated (masked to case vs. control status and treatment) were classified using M. Main and R. Goldwyn's (1991) system. Psychiatric patients, diagnosed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.) I and II structured interviews, were more likely to be classified as preoccupied and unresolved with respect to loss or abuse. On Axis I, anxiety was associated with unresolved status, and AAI scales were able to discriminate depression and eating disorder. On Axis II, borderline personality disorder (BPD) was linked to experience of severe trauma and lack of resolution with respect to it. BPD patients were also rated significantly lower on a scale measuring awareness of mental states. Preliminary outcome results suggest that individuals rated as dismissing on the AAI are more likely to show improvements in psychotherapy.

A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons

Abstract: Dorsal root ganglion sensory neurons associated with C-fibres, many of which are activated by tissue-damage, express an unusual voltage-gated sodium channel that is resistant to tetrodotoxin. We report here that we have identified a 1,957 amino-acid sodium channel in these cells that shows 65% identity with the rat cardiac tetrodotoxin-insensitive sodium channel, and is not expressed in other peripheral and central neurons, glia or non-neuronal tissues. In situ hybridization shows that the channel is expressed only by small-diameter sensory neurons in neonatal and adult dorsal root and trigeminal ganglia. The channel is resistant to tetrodotoxin when expressed in Xenopus oocytes. The electrophysiological and pharmacological properties of the expressed channel are similar to those described for the small-diameter sensory neuron tetrodotoxin-resistant sodium channels. As some noxious input into the spinal cord is resistant to tetrodotoxin, block of expression or function of such a C-fibre-restricted sodium channel may have a selective analgesic effect.

Geometric determinants of the place fields of hippocampal neurons

Abstract: The human hippocampus has been implicated in memory, in particular episodic or declarative memory. In rats, hippocampal lesions cause selective spatial deficits, and hippocampal complex spike cells (place cells) exhibit spatially localized firing, suggesting a role in spatial memory, although broader functions have also been suggested. Here we report the identification of the environmental features controlling the location and shape of the receptive fields (place fields) of the place cells. This was done by recording from the same cell in four rectangular boxes that differed solely in the length of one or both sides. Most of our results are explained by a model in which the place field is formed by the summation of gaussian tuning curves, each oriented perpendicular to a box wall and peaked at a fixed distance from it.

PROMOTIF--a program to identify and analyze structural motifs in proteins.

Abstract: We describe a suite of programs, PROMOTIF, that analyzes a protein coordinate file and provides details about the structural motifs in the protein. The program currently analyzes the following structural features: secondary structure; beta-and gamma-turns; helical geometry and interactions; beta-strands and beta-sheet topology; beta-bulges; beta-hairpins; beta-alpha-beta units and psi-loops; disulphide bridges; and main-chain hydrogen bonding patterns. PROMOTIF creates postscript files showing the examples of each type of motif in the protein, and a summary page. The program can also be used to compare motifs in a group of related structures, such as an ensemble of NMR structures.

Nonparametric analysis of statistic images from functional mapping experiments

Abstract: The analysis of functional mapping experiments in positron emission tomography involves the formation of images displaying the values of a suitable statistic, summarising the evidence in the data for a particular effect at each voxel These statistic images must then be scrutinised to locate regions showing statistically significant effects The methods most commonly used are parametric, assuming a particular form of probability distribution for the voxel values in the statistic image Scientific hypotheses, formulated in terms of parameters describing these distributions, are then tested on the basis of the assumptions Images of statistics are usually considered as lattice representations of continuous random fields These are more amenable to statistical analysis There are various shortcomings associated with these methods of analysis The many assumptions and approximations involved may not be true The low numbers of subjects and scans, in typical experiments, lead to noisy statistic images with low degrees of freedom, which are not well approximated by continuous random fields Thus, the methods are only approximately valid at best and are most suspect in single-subject studies In contrast to the existing methods, we present a nonparametric approach to significance testing for statistic images from activation studies Formal assumptions are replaced by a computationally expensive approach In a simple rest-activation study, if there is really no activation effect, the labelling of the scans as “active” or “rest” is artificial, and a statistic image formed with some other labelling is as likely as the observed one Thus, considering all possible relabellings, a p value can be computed for any suitable statistic describing the statistic image Consideration of the maximal statistic leads to a simple nonparametric single-threshold test This randomisation test relies only on minimal assumptions about the design of the experiment, is (almost) exact, with Type I error (almost) exactly that specified, and hence is always valid The absence of distributional assumptions permits the consideration of a wide range of test statistics, for instance, “pseudo” t statistic images formed with smoothed variance images The approach presented extends easily to other paradigms, permitting nonparametric analysis of most functional mapping experiments When the assumptions of the parametric methods are true, these new nonparametric methods, at worst, provide for their validation When the assumptions of the parametric methods are dubious, the nonparametric methods provide the only analysis that can be guaranteed valid and exact

Exploring 'theory of mind' in people with schizophrenia.

Abstract: Mentalizing ability was studied in 46 symptomatic schizophrenic patients and 44 non-symptomatic controls. Subjects heard six stories and simultaneously were shown simple cartoon pictures depicting the action sequencing occurring in the stories. All the stories involved false belief or deception, so that it was necessary to infer the mental states of the characters in order to understand their behaviour. After each story, subjects were asked one memory/reality question (concerning an event in the story) and one question that depended on the ability to infer the mental state of one of the characters. Patients with paranoid delusions were impaired on the questions concerning mental states. Patients with behavioural signs (i.e. negative features or incoherence) were also impaired on the mental state questions, but this difficulty was associated with memory impairments. Patients with symptoms of passivity (e.g. delusions of control) and patients in remission did not differ from normal controls. These results are consistent with the hypothesis that certain of the positive symptoms of schizophrenia reflect an impairment in the ability to infer the mental states of others.

Intersalt revisited: further analyses of 24 hour sodium excretion and blood pressure within and across populations

Abstract: Objectives: To assess further the relation in Intersalt of 24 hour urinary sodium to blood pressure of individuals and populations, and the difference in blood pressure from young adulthood into middle age Design: Standardised cross sectional study within and across populations Setting: 52 population samples in 32 countries Subjects: 10 074 men and women aged 20-59 Main outcome measures: Association of sodium and blood pressure from within population and cross population multiple linear regression analyses with multivariate correction for regression dilution bias Relation of sample median daily urinary sodium excretion to difference in blood pressure with age Results: In within population analyses (n=10 074), individual 24 hour urinary sodium excretion higher by 100 mmol (for example, 170 v 70 mmol) was associated with systolic/diastolic blood pressure higher on average by 3/0 to 6/3 mm Hg (with and without body mass in analyses) Associations were larger at ages 40-59 In cross population analyses (n=52), sample median 24 hour sodium excretion higher by 100 mmol was associated with median systolic/diastolic pressure higher on average by 5-7/2-4 mm Hg, and estimated mean difference in systolic/diastolic pressure at age 55 compared with age 25 greater by 10-11/6 mm Hg Conclusions: The strong, positive association of urinary sodium with systolic pressure of individuals concurs with Intersalt cross population findings and results of other studies Higher urinary sodium is also associated with substantially greater differences in blood pressure in middle age compared with young adulthood These results support recommendations for reduction of high salt intake in populations for prevention and control of adverse blood pressure levels Key messages The within population findings were previously underestimated because of incomplete correction for the regression dilution problem Revised estimates of the within population association of sodium to blood pressure in Intersalt are concordant with the cross population findings for 52 samples Estimates of the effect of median sodium excretion higher by 100 mmol/day over a 30 year period (age 55 minus age 25) were a greater difference of 10-11 mm Hg in systolic blood pressure and 6 mm Hg in diastolic blood pressure These results lend further support to recommendations for mass reduction of high salt intake for the prevention and control of adverse blood pressure levels and high blood pressure in populations

Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABAA receptors.

Abstract: 1. To investigate the origin and functional significance of a recently described tonic GABA(A) receptor-mediated conductance in cerebellar granule cells we have made recordings from cells in cerebellar slices from rats of different ages (postnatal days P4 to P28).2. During development there was a dramatic change in the properties of GABA-mediated synaptic transmission. The contribution to GABA(A) receptor-mediated charge transfer from the tonic conductance (G(GABA)), relative to that resulting from discrete spontaneous postsynaptic currents (sPSCs), was increased from 5% at P7 to 99% at P21. G(GABA) was reduced by bicuculline, tetrodotoxin and by lowering extracellular Ca2+, and was initially present only in those cells which exhibited sPSCs.3. At P7 sPSCs were depolarizing, occasionally triggering a single action potential. By P18 the GABA reversal potential was shifted close to the resting potential and G(GABA) produced a shunting inhibition. Removal of G(GABA) by bicuculline increased granule cell excitability in response to current injection.4. This novel tonic inhibition is present despite the low number of Golgi cell synapses on individual granule cells and appears to result from 'overspill' of synaptically released GABA leading to activation of synaptic and extrasynaptic GABA(A) receptors.

The domain of supervisory processes and temporal organization of behaviour.

Abstract: The possibility that the supervisory system of Norman & Shallice (1986) can be fractionated into different subprocesses is discussed. It is argued that confronting a novel situation effectively requires a variety of different types of process. It is then argued that evidence of separability of different processes may be obtained by the observation of very low correlations across patients on more than one measure on each of which frontal patients show a performance deficit. Examples of this are provided by examining the Hayling sentence completion and the Brixton spatial anticipation tasks. Finally, differential localization of the subprocesses and hence the conclusion that they are separable is discussed with respect to the localization of monitoring and verification processes in memory.

Is developmental dyslexia a disconnection syndrome? Evidence from PET scanning

Abstract: Summary A rhyming and a short-term memory task with visually presented letters were used to study brain activity in five compensated adult developmental dyslexics. Their only cognitive difficulty was in phonological processing, manifest in a wide range of tasks including spoonerisms, phonemic fluency and digit naming speed. PET scans showed that for the dyslexics, a subset only of the brain regions normally involved in phonological processing was activated: Broca 's area during the rhyming task, temporo-parietal cortex during the short-term memory task. In contrast to normal controls these areas were not activated in concert. Furthermore the left insula was never activated. We propose that the defective phonological system of these dyslexics is due to weak connectivity between anterior and posterior language areas. This could be due to a dysfunctional left insula which may normally act as an anatomical bridge between Broca's area, superior temporal and inferior parietal cortex. The independent activation of the posterior and anterior speech areas in dyslexics supports the notion that representations of unsegmented and segmented phonology are functionally and anatomically separate.

Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study

Abstract: The EURODIAB IDDM Complications Study involved the examination of 3250 randomly selected insulin-dependent diabetic patients, from 31 centres in 16 European countries. Part of the examination included an assessment of neurological function including neuropathic symptoms and physical signs, vibration perception threshold, tests of autonomic function and the prevalence of impotence. The prevalence of diabetic neuropathy across Europe was 28% with no significant geographical differences. Significant correlations were observed between the presence of diabetic peripheral neuropathy with age (p < 0.05), duration of diabetes (p < 0.001), quality of metabolic control (p < 0.001), height (p < 0.01), the presence of background or proliferative diabetic retinopathy (p < 0.01), cigarette smoking (p < 0.001), high-density lipoprotein cholesterol (p < 0.001) and the presence of cardiovascular disease (p < 0.05), thus confirming previous associations. New associations have been identified from this study - namely with elevated diastolic blood pressure (p < 0.05), the presence of severe ketoacidosis (p < 0.001), an increase in the levels of fasting triglyceride (p < 0.001), and the presence of microalbuminuria (p < 0.01). All the data were adjusted for age, duration of diabetes and HbA1c. Although alcohol intake correlated with absence of leg reflexes and autonomic dysfunction, there was no overall association of alcohol consumption and neuropathy. The reported problems of impotence were extremely variable between centres, suggesting many cultural and attitudinal differences in the collection of such information in different European countries. In conclusion, this study has identified previously known and new potential risk factors for the development of diabetic peripheral neuropathy.

Characterization of a cage form of the water hexamer

Abstract: WATER has been studied more extensively than any other liquid, yet its microscopic properties remain poorly understood. The difficulty in obtaining a rigorous molecular-scale description of water structure is largely a consequence of the extended, dynamic hydrogen-bonded network that exists throughout the liquid1. Studies of the structure and dynamics of isolated small clusters of water molecules2–6 provide a means of quantifying the intermolecular forces and hydrogen-bond rearrangements that occur in condensed phases. Experiments2–7 and theory8 strongly suggest that the water trimer, tetramer and pentamer have cyclic minimum energy structures. Larger water clusters are expected8 to have three-dimensional geometries, with the hexamer representing the transition from cyclic to such three-dimensional structures. Here we report investigations by terahertz laser vibration–rotation tunnelling spectroscopy3 of the structure of the water hexamer. A comparison of our results with quantum Monte Carlo simulations of this species suggests that the most stable form of (H2O)6 is indeed a cage-like structure, held together by eight hydrogen bonds (Fig. 1).

Inflammatory pain hypersensitivity mediated by phenotypic switch in myelinated primary sensory neurons

Abstract: Pain is normally evoked only by stimuli that are sufficiently intense to activate high-threshold A(delta) and C sensory fibres, which relay the signal to the spinal cord. Peripheral inflammation leads to profoundly increased pain sensitivity: noxious stimuli generate a greater response and stimuli that are normally innocuous elicit pain. Inflammation increases the sensitivity of the peripheral terminals of A(delta) and C fibres at the site of inflammation. It also increases the excitability of spinal cord neurons, which now amplify all sensory inputs including the normally innocuous tactile stimuli that are conveyed by low-threshold A(beta) fibres. This central sensitization has been attributed to the enhanced activity of C fibres, which increase the excitability of their postsynaptic targets by releasing glutamate and the neuropeptide substance P. Here we show that inflammation results in A(beta) fibres also acquiring the capacity to increase the excitability of spinal cord neurons. This is due to a phenotypic switch in a subpopulation of these fibres so that they, like C-fibres, now express substance P. A(beta) fibres thus appear to contribute to inflammatory hypersensitivity by switching their phenotype to one resembling pain fibres, thereby enhancing synaptic transmission in the spinal cord and exaggerating the central response to innocuous stimuli.