Showing papers by "University of London published in 1997"

A Controlled Trial of Two Nucleoside Analogues plus Indinavir in Persons with Human Immunodeficiency Virus Infection and CD4 Cell Counts of 200 per Cubic Millimeter or Less

Abstract: Background The efficacy and safety of adding a protease inhibitor to two nucleoside analogues to treat human immunodeficiency virus type 1 (HIV-1) infection are not clear. We compared treatment with the protease inhibitor indinavir in addition to zidovudine and lamivudine with treatment with the two nucleosides alone in HIV-infected adults previously treated with zidovudine. Methods A total of 1156 patients not previously treated with lamivudine or protease inhibitors were stratified according to CD4 cell count (50 or fewer vs. 51 to 200 cells per cubic millimeter) and randomly assigned to one of two daily regimens: 600 mg of zidovudine and 300 mg of lamivudine, or that regimen with 2400 mg of indinavir. Stavudine could be substituted for zidovudine. The primary end point was the time to the development of the acquired immunodeficiency syndrome (AIDS) or death. Results The proportion of patients whose disease progressed to AIDS or death was lower with indinavir, zidovudine (or stavudine), and lamivudine (...

The role of conceptual frameworks in epidemiological analysis: a hierarchical approach.

Abstract: Background This paper discusses appropriate strategies for multivariate data analysis in epidemiological studies. Methods In studies where determinants of disease are sought, it is suggested that the complex hierarchical inter-relationships between these determinants are best managed through the use of conceptual frameworks. Failure to take these aspects into consideration is common in the epidemiological literature and leads to underestimation of the effects of distal determinants. Results An example of this analytical approach, which is not based purely on statistical associations, is given for assessing determinants of mortality due to diarrhoea in children. Conclusions Conceptual frameworks provide guidance for the use of multivariate techniques and aid the interpretation of their results in the light of social and biological knowledge.

Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent

Abstract: There are many strains of the agents that cause transmissible spongiform encephalopathies (TSEs) or 'prion' diseases. These strains are distinguishable by their disease characteristics in experimentally infected animals, in particular the incubation periods and neuropathology they produce in panels of inbred mouse strains. We have shown that the strain of agent from cattle affected by bovine spongiform encephalopathy (BSE) produces a characteristic pattern of disease in mice that is retained after experimental passage through a variety of intermediate species. This BSE 'signature' has also been identified in transmissions to mice of TSEs of domestic cats and two exotic species of ruminant, providing the first direct evidence for the accidental spread of a TSE between species. Twenty cases of a clinically and pathologically atypical form of Creutzfeldt-Jakob disease (CJD), referred to as 'new variant' CJD (vCJD), have been recognized in unusually young people in the United Kingdom, and a further case has been reported in France. This has raised serious concerns that BSE may have spread to humans, putatively by dietary exposure. Here we report the interim results of transmissions of sporadic CJD and vCJD to mice. Our data provide strong evidence that the same agent strain is involved in both BSE and vCJD.

A framework for immersive virtual environments five: Speculations on the role of presence in virtual environments

Abstract: This paper reviews the concepts of immersion and presence in virtual environments VEs. We propose that the degree of immersion can be objectively assessed as the characteristics of a technology, and has dimensions such as the extent to which a display system can deliver an inclusive, extensive, surrounding, and vivid illusion of virtual environment to a participant. Other dimensions of immersion are concerned with the extent of body matching, and the extent to which there is a self-contained plot in which the participant can act and in which there is an autonomous response. Presence is a state of consciousness that may be concomitant with immersion, and is related to a sense of being in a place. Presence governs aspects of autonomie responses and higher-level behaviors of a participant in a VE. The paper considers single and multiparticipant shared environments, and draws on the experience of ComputerSupported Cooperative Working CSCW research as a guide to understanding presence in shared environments. The paper finally outlines the aims of the FIVE Working Group, and the 1995 FIVE Conference in London, UK.

Another advanced test of theory of mind: evidence from very high functioning adults with autism or asperger syndrome.

Abstract: Previous studies have found a subgroup of people with autism or Asperger Syndrome who pass second-order tests of theory of mind. However, such tests have a ceiling in developmental terms corresponding to a mental age of about 6 years. It is therefore impossible to say if such individuals are intact or impaired in their theory of mind skills. We report the performance of very high functioning adults with autism or Asperger Syndrome on an adult test of theory of mind ability. The task involved inferring the mental state of a person just from the information in photographs of a person's eyes. Relative to age-matched normal controls and a clinical control group (adults with Tourette Syndrome), the group with autism and Asperger Syndrome were significantly impaired on this task. The autism and Asperger Syndrome sample was also impaired on Happe's strange stories tasks. In contrast, they were unimpaired on two control tasks: recognising gender from the eye region of the face, and recognising basic emotions from the whole face. This provides evidence for subtle mindreading deficits in very high functioning individuals on the autistic continuum.

Pulling cost-effectiveness analysis up by its bootstraps: a non-parametric approach to confidence interval estimation.

Abstract: The statistic of interest in the economic evaluation of health care interventions is the incremental cost effectiveness ratio (ICER), which is defined as the difference in cost between two treatment interventions over the difference in their effect. Where patient-specific data on costs and health outcomes are available, it is natural to attempt to quantify uncertainty in the estimated ICER using confidence intervals. Recent articles have focused on parametric methods for constructing confidence intervals. In this paper, we describe the construction of non-parametric bootstrap confidence intervals. The advantage of such intervals is that they do not depend on parametric assumptions of the sampling distribution of the ICER. We present a detailed description of the non-parametric bootstrap applied to data from a clinical trial, in order to demonstrate the strengths and weaknesses of the approach. By examining the bootstrap confidence limits successively as the number of bootstrap replications increases, we conclude that percentile bootstrap confidence interval methods provide a promising approach to estimating the uncertainty of ICER point estimates. However, successive bootstrap estimates of bias and standard error suggests that these may be unstable; accordingly, we strongly recommend a cautious interpretation of such estimates.

A shorter model theory

Abstract: 1. Naming of parts 2. Classifying structures 3. Structures that look alike 4. Interpretations 5. The first order case: compactness 6. The countable case 7. The existential case 8. Saturation 9. Structure and categoricity.

A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic feature, including new cases.

Abstract: The short-lasting primary headache syndromes may be conveniently divided into those exhibiting marked autonomic activation and those without autonomic activation. The former group comprise chronic and episodic paroxysmal hemicrania, short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT syndrome) and cluster headache. These headache syndromes are compared with other short-lasting headache disorders, such as hypnic headache, and persistent headache with milder autonomic features such as hemicrania continua. Cluster headache is included with the shorter-lasting headaches to attempt a nosological analysis of these syndromes. The paroxysmal hemicranias are characterized by frequent short-lasting attacks of unilateral pain usually in the orbital, supraorbital or temporal region that typically last minutes. The attack frequency usually ranges from 5 to 40 attacks per day. The pain is severe and associated with autonomic symptoms such as conjunctival injection, lacrimation, nasal congestion, rhinorrhoea, ptosis or eyelid oedema. Almost all reported cases respond to treatment with indomethacin, but respond poorly to other treatments including other nonsteroidal anti-inflammatory drugs. A recent case study demonstrated the release of both trigeminal and parasympathetic neuropeptides during a bout of pain in the same pattern previously described in cluster headache. The SUNCT syndrome is a distinctive rare condition characterized by less severe pain but marked autonomic activation during attacks. Consistent with previous reports, the present case of SUNCT syndrome was intractable to therapy. The similarites of these syndromes suggests a considerable shared pathophysiology. It is suggested that the syndromes are sufficiently well established for inclusion in the International Headache Society Classification system and that trigeminal-autonomic cephalalgias should be classified as a group together. A proposed re-classification is presented.

Making Sense of Management: A Critical Introduction

Abstract: The first edition of Making Sense of Management set out to provide a fresh perspective on management that was both broad and critical, exploring how the disruptive and constructive potential of critical theory can be realized in organizations. Along the way, it has proven to be a landmark contribution to critical management studies. As well as setting the agenda for current research, this revised edition has been written to appeal to a broader readership and open up critical theory for the general management student. New sections on HRM, brands, identity, ethics and leadership have been fully developed alongside the rest of the text to reflect the current state of play in critical management studies. The second edition of Making Sense of Management will be of interest to students and researchers in critical management studies and students on general management courses with a critical perspective.

Key Agreement Protocols and Their Security Analysis

Abstract: This paper proposes new protocols for two goals: authenticated key agreement and authenticated key agreement with key confirmation in the asymmetric (public-key) setting. A formal model of distributed computing is provided, and a definition of the goals within this model supplied. The protocols proposed are then proven correct within this framework in the random oracle model. We emphasize the relevance of these theoretical results to the security of systems used in practice. Practical implementation of the protocols is discussed. Such implementations are currently under consideration for standardization [2, 3, 18].

A human homologue of the Drosophila eyes absent gene underlies Branchio-Oto-Renal (BOR) syndrome and identifies a novel gene family

Abstract: A candidate gene for Branchio-Oto-Renal (BOR) syndrome was identified at chromosome 8q13.3 by positional cloning and shown to underlie the disease. This gene is a human homologue of the Drosophila eyes absent gene (eya), and was therefore called EYA1. A highly conserved 271-amino acid C-terminal region was also found in the products of two other human genes (EYA2 and EYA3), demonstrating the existence of a novel gene family. The expression pattern of the murine EYA1 orthologue, Eya1, suggests a role in the development of all components of the inner ear, from the emergence of the otic placode. In the developing kidney, the expression pattern is indicative of a role for Eya1 in the metanephric cells surrounding the 'just-divided' ureteric branches.

Walking to health.

Abstract: Walking is a rhythmic, dynamic, aerobic activity of large skeletal muscles that confers the multifarious benefits of this with minimal adverse effects. Walking, faster than customary, and regularly in sufficient quantity into the 'training zone' of over 70% of maximal heart rate, develops and sustains physical fitness: the cardiovascular capacity and endurance (stamina) for bodily work and movement in everyday life that also provides reserves for meeting exceptional demands. Muscles of the legs, limb girdle and lower trunk are strengthened and the flexibility of their cardinal joints preserved; posture and carriage may improve. Any amount of walking, and at any pace, expends energy. Hence the potential, long term, of walking for weight control. Dynamic aerobic exercise, as in walking, enhances a multitude of bodily processes that are inherent in skeletal muscle activity, including the metabolism of high density lipoproteins and insulin/glucose dynamics. Walking is also the most common weight-bearing activity, and there are indications at all ages of an increase in related bone strength. The pleasurable and therapeutic, psychological and social dimensions of walking, whilst evident, have been surprisingly little studied. Nor has an economic assessment of the benefits and costs of walking been attempted. Walking is beneficial through engendering improved fitness and/or greater physiological activity and energy turnover. Two main modes of such action are distinguished as: (i) acute, short term effects of the exercise; and (ii) chronic, cumulative adaptations depending on habitual activity over weeks and months. Walking is often included in studies of exercise in relation to disease but it has seldom been specifically tested. There is, nevertheless, growing evidence of gains in the prevention of heart attack and reduction of total death rates, in the treatment of hypertension, intermittent claudication and musculoskeletal disorders, and in rehabilitation after heart attack and in chronic respiratory disease. Walking is the most natural activity and the only sustained dynamic aerobic exercise that is common to everyone except for the seriously disabled or very frail. No special skills or equipment are required. Walking is convenient and may be accommodated in occupational and domestic routines. It is self-regulated in intensity, duration and frequency, and, having a low ground impact, is inherently safe. Unlike so much physical activity, there is little, if any, decline in middle age. It is a year-round, readily repeatable, self-reinforcing, habit-forming activity and the main option for increasing physical activity in sedentary populations. Present levels of walking are often low. Familiar social inequalities may be evident. There are indications of a serious decline of walking in children, though further surveys of their activity, fitness and health are required. The downside relates to the incidence of fatal and non-fatal road casualties, especially among children and old people, and the deteriorating air quality due to traffic fumes which mounting evidence implicates in the several stages of respiratory disease. Walking is ideal as a gentle start-up for the sedentary, including the inactive, immobile elderly, bringing a bonus of independence and social well-being. As general policy, a gradual progression is indicated from slow, to regular pace and on to 30 minutes or more of brisk (i.e. 6.4 km/h) walking on most days. These levels should achieve the major gains of activity and health-related fitness without adverse effects. Alternatively, such targets as this can be suggested for personal motivation, clinical practice, and public health. The average middle-aged person should be able to walk 1.6 km comfortably on the level at 6.4 km/h and on a slope of 1 in 20 at 4.8 km/h, however, many cannot do so because of inactivity-induced unfitness. The physiological threshold of 'comfort' represents 70% of maximum heart rate. (ABSTRACT TRUNCATED)

A unified transform method for solving linear and certain nonlinear PDEs

Abstract: A new transform method for solving initial boundary value problems for linear and for integrable nonlinear PDEs in two independent variables is introduced. This unified method is based on the fact that linear and integrable nonlinear equations have the distinguished property that they possess a Lax pair formulation. The implementation of this method involves performing a simultaneous spectral analysis of both parts of the Lax pair and solving a Riemann–Hilbert problem. In addition to a unification in the method of solution, there also exists a unification in the representation of the solution. The sine–Gordon equation in light–cone coordinates, the nonlinear Schrodinger equation and their linearized versions are used as illustrative examples. It is also shown that appropriate deformations of the Lax pairs of linear equations can be used to construct Lax pairs for integrable nonlinear equations. As an example, a new Lax pair of the nonlinear Schrodinger equation is derived.

Closure properties of constraints

Abstract: Many combinatorial search problems can be expressed as “constraint satisfaction problems” and this class of problems is known to be NP-complete in general. In this paper, we investigate the subclasses that arise from restricting the possible constraint types. We first show that any set of constraints that does not give rise to an NP-complete class of problems must satisfy a certain type of algebraic closure condition. We then investigate all the different possible forms of this algebraic closure property, and establish which of these are sufficient to ensure tractability. As examples, we show that all known classes of tractable constraints over finite domains can be characterized by such an algebraic closure property. Finally, we describe a simple computational procedure that can be used to determine the closure properties of a given set of constraints. This procedure involves solving a particular constraint satisfaction problem, which we call an “indicator problem.”

Localization of hydrogen peroxide accumulation during the hypersensitive reaction of lettuce cells to Pseudomonas syringae pv phaseolicola

Abstract: The active oxygen species hydrogen peroxide (H2O2) was detected cytochemically by its reaction with cerium chloride to produce electron-dense deposits of cerium perhydroxides. In uninoculated lettuce leaves, H2O2 was typically present within the secondary thickened walls of xylem vessels. Inoculation with wild-type cells of Pseudomonas syringae pv phaseolicola caused a rapid hypersensitive reaction (HR) during which highly localized accumulation of H2O2 was found in plant cell walls adjacent to attached bacteria. Quantitative analysis indicated a prolonged burst of H2O2 occurring between 5 to 8 hr after inoculation in cells undergoing the HR during this example of non-host resistance. Cell wall alterations and papilla deposition, which occurred in response to both the wild-type strain and a nonpathogenic hrpD mutant, were not associated with intense staining for H2O2, unless the responding cell was undergoing the HR. Catalase treatment to decompose H2O2 almost entirely eliminated staining, but 3-amino-1,2,4-triazole (catalase inhibitor) did not affect the pattern of distribution of H2O2 detected. H2O2 production was reduced more by the inhibition of plant peroxidases (with potassium cyanide and sodium azide) than by inhibition of neutrophil-like NADPH oxidase (with diphenylene iodonium chloride). Results suggest that CeCl3 reacts with excess H2O2 that is not rapidly metabolized during cross-linking reactions occurring in cell walls; such an excess of H2O2 in the early stages of the plant-bacterium interaction was only produced during the HR. The highly localized accumulation of H2O2 is consistent with its direct role as an antimicrobial agent and as the cause of localized membrane damage at sites of bacterial attachment.

The natural history of tuberculosis: the implications of age-dependent risks of disease and the role of reinfection

Abstract: Many aspects of the natural history of tuberculosis are poorly understood. Though it is recognized that clinical tuberculosis may follow shortly after initial infection ('primary' disease), or many years thereafter through either endogenous reactivation or after reinfection, the relative importance of these mechanisms is often disputed. The issue is complicated by the fact that the risks of developing disease are age-dependent, and reflect infection risks which may change over time. This paper estimates the age-dependent risks of developing tuberculosis using an age-structured deterministic model of the dynamics of tuberculous infection and disease in England and Wales since 1900. The work extends the classical studies of Sutherland and colleagues. The best estimates of the risks of developing 'primary' disease (within 5 years of initial infection) were approximately 4%, 9% and 14% for individuals infected at ages 0-10, 15 years and over 20 years respectively, and a previous infection appeared to impart little protection against (further) reinfection, but 16-41% protection against disease subsequent to reinfection for adolescents and adults. We also provide evidence that reinfection made an important contribution to tuberculous morbidity in the past, as (i) exclusion of exogenous disease from the model considerably worsened the fit to observed notification rates, and (ii) the dramatic decline in the risk of tuberculous infection from 1950 in England and Wales accelerated the decline in morbidity among all individuals, even among the older age groups with a high prevalence of tuberculous infection. We conclude that the risk of infection is the single most important factor affecting the magnitude of the tuberculous morbidity in a population, as it determines both the age pattern of initial infection (and hence the risk of developing disease) and the risk of reinfection.

The oral absorption of micro- and nanoparticulates: neither exceptional nor unusual.

Abstract: This mini-review covers some of the historical and recent arguments over the experimental evidence on the uptake by and translocation from the intestinal mucosa of microparticulates after oral administration. It is concluded that there is now no dispute over the fact that this is a normal occurrence. Particulate uptake does take place, not only via the M-cells in the Peyer's patches and the isolated follicles of the gut-associated lymphoid tissue, but also via the normal intestinal enterocytes. Factors affecting uptake include particle size, surface charge and hydrophobicity and the presence or absence of surface ligands. The covalent attachment of lectin or invasin molecules to the surface of carrier particles leads to greater systemic uptake. Whether or not the route can be utilized for the routine administration of therapeutic agents which are not normally absorbed from the gut is not yet proven. Many studies show that 2−3% of the ingested dose of submicron particles can be absorbed. The increasing diversity of carrier systems, which includes dendrimers and liposomes, needs to be exploited fully. More also must be learned about the inter- and intra-subject variability of lymphoid tissue so that appropriate selectivity can be achieved through the design of specific carriers.

Road traffic injuries in developing countries: a comprehensive review of epidemiological studies

Abstract: Motor vehicle accidents are the leading cause of death in adolescents and young adults worldwide. Nearly three-quarters of road deaths occur in developing countries and men comprise a mean 80% of casualties. This review summarizes studies on the epidemiology of motor vehicle accidents in developing countries and examines the evidence for association with alcohol.

'Equivalence' and the translation and adaptation of health-related quality of life questionnaires

Abstract: The increasing use of health-related quality of life (HRQOL) questionnaires in multinational studies has resulted in the translation of many existing measures Guidelines for translation have been published, and there has been some discussion of how to achieve and assess equivalence between source and target questionnaires Our reading in this area had led us, however, to the conclusion that different types of equivalence were not clearly defined, and that a theoretical framework for equivalence was lacking To confirm this we reviewed definitions of equivalence in the HRQOL literature on the use of generic questionnaires in multicultural settings The literature review revealed: definitions of 19 different types of equivalence; vague or conflicting definitions, particularly in the case of conceptual equivalence; and the use of many redundant terms We discuss these findings in the light of a framework adapted from cross-cultural psychology for describing three different orientations to cross-cultural research: absolutism, universalism and relativism We suggest that the HRQOL field has generally adopted an absolutist approach and that this may account for some of the confusion in this area We conclude by suggesting that there is an urgent need for a standardized terminology within the HRQOL field, by offering a standard definition of conceptual equivalence, and by suggesting that the adoption of a universalist orientation would require substantial changes to guidelines and more empirical work on the conceptualization of HRQOL in different cultures

Auctioning Conservation Contracts: A Theoretical Analysis and an Application

Abstract: Auction theory is used to analyze the potential benefits of auctions in allocating contracts for the provision of nonmarket goods in the countryside. A model of optimal bidding for conservation contracts is developed and applied to a hypothetical conservation program. Competitive bidding, compared to fixed-rate payments, can increase the cost effectiveness of conservation contracting significantly. The cost revelation mechanism inherent in the bidding process makes auctions a powerful means by which to reduce the problems of information asymmetry. Strategic bidding behavior, which may adversely affect the performance of sequential auctions, is difficult to address by means of auction design.

Cross sectional analysis of mortality by country of birth in England and Wales, 1970-92.

Abstract: Objective: To compare mortalities for selected groups of immigrants with the national average. Design: Analysis of mortality for adults aged 20-69 in 1970-2 and 1989-92 using population data from 1971 and 1991 censuses. Mortality of Scottish and Irish immigrants aged 25-74 was also compared with mortality in Scotland and Ireland for 1991. Setting: England and Wales. Main outcome measures: Standardised mortality ratios for deaths from all causes, ischaemic heart disease, cerebrovascular disease, lung cancer, and breast cancer. Results: In 1989-92 mortality from all causes was higher than the national average for Scottish immigrants, by 32% for men and 36% for women; for Irish immigrants it was higher by 39% for men and 20% for women; and for Caribbean born men it was lower by 23%. Ischaemic heart disease and lung cancer accounted for 30-40% of the excess mortality in Scottish and Irish immigrants. For south Asians, excess mortality from circulatory disease was balanced by lower mortality from cancer. Standardised mortality ratios for cerebrovascular disease in 1989-92 were highest for west African immigrants (271 for men and 181 for women). Conclusions: Widening differences in mortality ratios for migrants compared with the general population were not simply due to socioeconomic inequalities. The low mortality from all causes for Caribbean immigrants could largely be attributed to low mortality from ischaemic heart disease, which is unexplained. The excess mortality from cerebrovascular and hypertensive diseases in migrants from both west Africa and the Caribbean suggests that genetic factors underlie the susceptibility to hypertension in people of black African descent. Key messages Differences in mortality of immigrants in England and Wales widened between 1970 and 1992 and could not be explained by socioeconomic differences Mortality from all causes was higher than average for Scottish and Irish immigrants, and some of the excess could be accounted for by smoking habits, reflected by increased mortality ratios for lung cancer Mortality ratios for stroke and hypertension were highest in west African immigrants, indicating that better detection and treatment of hypertension is required in this group Mortality from all causes was low in Caribbean immigrants, largely due to low mortality from ischaemic heart disease Mortality from ischaemic heart disease remained high in south Asian immigrants and did not decline as fast as in the general population

Education, Globalization and the Nation State

Abstract: Globalization has become a topic of great interest to social scientists, not only in the field of economics, but also in political and cultural studies. Despite the volume of theoretical work in this area, however, the issues it throws up have only recently begun to be taken up by educational theorists and, even here, somewhat one-sidedly within the postmodernist tradition. The final chapter in this book examines theories of globalization, their use by education theorists, and the implications for education of recent global trends in economics and politics. Specifically, it seeks to assess the arguments put forward by postmodern educational theorists, such as Usher and Edwards (1995), that globalization portends the demise of national education and the national education system as we know it.