Showing papers by "University of London published in 2000"

Guidelines for using human event-related potentials to study cognition: Recording standards and publication criteria

Abstract: Event-related potentials ~ERPs! recorded from the human scalp can provide important information about how the human brain normally processes information and about how this processing may go awry in neurological or psychiatric disorders. Scientists using or studying ERPs must strive to overcome the many technical problems that can occur in the recording and analysis of these potentials. The methods and the results of these ERP studies must be published in a way that allows other scientists to understand exactly what was done so that they can, if necessary, replicate the experiments. The data must then be analyzed and presented in a way that allows different studies to be compared readily. This paper presents guidelines for recording ERPs and criteria for publishing the results.

The genome sequence of the food-borne pathogen Campylobacter jejuni reveals hypervariable sequences

Abstract: Campylobacter jejuni, from the delta-epsilon group of proteobacteria, is a microaerophilic, Gram-negative, flagellate, spiral bacterium—properties it shares with the related gastric pathogen Helicobacter pylori. It is the leading cause of bacterial food-borne diarrhoeal disease throughout the world1. In addition, infection with C. jejuni is the most frequent antecedent to a form of neuromuscular paralysis known as Guillain–Barre syndrome2. Here we report the genome sequence of C. jejuni NCTC11168. C. jejuni has a circular chromosome of 1,641,481 base pairs (30.6% G+C) which is predicted to encode 1,654 proteins and 54 stable RNA species. The genome is unusual in that there are virtually no insertion sequences or phage-associated sequences and very few repeat sequences. One of the most striking findings in the genome was the presence of hypervariable sequences. These short homopolymeric runs of nucleotides were commonly found in genes encoding the biosynthesis or modification of surface structures, or in closely linked genes of unknown function. The apparently high rate of variation of these homopolymeric tracts may be important in the survival strategy of C. jejuni.

Bootstrap confidence intervals : when, which, what? A practical guide for medical statisticians

Abstract: Since the early 1980s, a bewildering array of methods for constructing bootstrap confidence intervals have been proposed. In this article, we address the following questions. First, when should bootstrap confidence intervals be used. Secondly, which method should be chosen, and thirdly, how should it be implemented. In order to do this, we review the common algorithms for resampling and methods for constructing bootstrap confidence intervals, together with some less well known ones, highlighting their strengths and weaknesses. We then present a simulation study, a flow chart for choosing an appropriate method and a survival analysis example.

The DNA sequence of human chromosome 21

Abstract: Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

Government and Control

Abstract: Advanced liberal democracies are currently witnessing a bewildering variety of developments inregimes of control. These range from demands for execution or preventive detention of implacablydangerous or risky individuals—sexual predators, paedophiles, persistent violent offenders—to thedevelopment of dispersed, designed in-control regimes for the continual, silent and largely invisiblework of the assessment, management, communication and control of risk. Political programmes ofcrime control appear to have little stability, cycling rapidly through all the alternatives from ‘prisonworks’, ‘short, sharp shocks’ and ‘boot camps’, through ‘community corrections’ and ‘reintegrativeshaming’ via ‘therapeutic rehabilitation’ to ‘nothing works’ and ‘three strikes and you’re out’.Of course, programmes of crime control have always had less to do with control of crime than theyhave to do with more general concerns with the government of the moral order. And concerns aboutillegality and crime have been articulated as much, if not more, by institutions and practices whicharenotpartofthecriminaljusticesystemthanbythosethatareconventionallyconsideredtobepartofsuch a ‘system’. Nonetheless, even at this more general level, things seem confusing. Despite claimsthatweliveinapost-disciplinarysociety(Simon),thatdangerousnesshasgivenwaytorisk(Castel),that control in now continuous, immanent and cybernetic rather than discontinuous, localized andindividualizing (Deleuze), there appears to be little strategic coherence about these developments attheleveloftheirrationalities,andmuchdiversityandcontingencyattheleveloftheirtechnologies.This paper will attempt to explore this complexity along a number of dimensions. It will considerthewaysinwhichparticular‘regimesofillegalities’havebeenindividuatedandproblematized,andsuggest that, although these are diverse, some at least can be understood as infractions of freedom,that is to say, as problematic because they throw into question the very presuppositions of moralconsciousness, self-control and self-advancement through legitimate consumption upon whichgovernmental regimes of freedom depend. It will consider the ‘conceptions of the criminal’ thatcirculate within practices for the government of illegality, and suggest that, despite the apparentdiversity of these conceptions—where biological arguments about inherited tendencies cohabit withcommunitarian arguments about the virtues—the pervasive image of the perpetrator of crime is notone of the juridical subject of the rule of law, nor that of the bio-psychological subject of positivistcriminology, but of the responsible subject of moral community guided—or misguided—by ethicalself-steering mechanisms. And it will consider the forms of knowledge and modes of expertise that areimplicated in these new techniques and rationalities of control.Governing Conduct

Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study

Abstract: OBJECTIVE Polycystic ovary syndrome (PCOS) is associated with higher prevalence of cardiovascular risk factors but the relative prevalence of cardiovascular disease in women with PCOS has not previously been reported. We have compared cardiovascular mortality and morbidity in middle-aged women previously diagnosed with PCOS and age-matched control women. DESIGN A retrospective cohort study of women diagnosed with PCOS in the United Kingdom before 1979. PATIENTS Seventy cohort members died before 31 March 1999. Morbidity data were collected from 319 women with PCOS and 1060 age-matched control women. Sixty-one women with PCOS and 63 control women attended a clinical examination. MEASUREMENTS Data were collected from death certificates, general practitioners' records and questionnaires with measurement of cardiovascular risk factors in a subsample of questionnaire respondents. RESULTS All-cause and cardiovascular mortality in the cohort were similar to women in the general population (standardized mortality ratios (95% CI): 93 (72–117) and 78 (45–124), respectively). Women with PCOS had higher levels of several cardiovascular risk factors: diabetes (P = 0.002) hypertension (P = 0.04), hypercholesterolaemia (P < 0.001), hypertriglyceridaemia (P = 0.02) and increased waist:hip ratio (P = 0.004). After adjustment for BMI, odds ratios (OR) were 2.2 (0.9–5.2) for diabetes, 1.4 (0.9–2.0) for hypertension and 3.2 (1.7–6.0) for hypercholesterolaemia. A history of coronary heart disease (CHD) was not significantly more common in women with PCOS (crude OR (95%CI) 1.5 (0.7–2.9)) but the crude OR for cerebrovascular disease was 2.8 (1.1–7.1). CONCLUSION At long-term follow-up, a history of nonfatal cerebrovascular disease and cardiovascular risk factors including diabetes are more prevalent among women with polycystic ovary syndrome. Morbidity and mortality from of coronary heart disease among women with polycystic ovary syndrome is not as high as previously predicted. This finding challenges our understanding of the aetiology of coronary heart disease in women.

Stakeholder analysis: a review.

Abstract: The growing popularity of stakeholder analysis reflects an increasing recognition of how the characteristics of stakeholders--individuals, groups and organizations--influence decision-making processes. This paper reviews the origins and uses of stakeholder analysis, as described in the policy, health care management and development literature. Its roots are in the political and policy sciences, and in management theory where it has evolved into a systematic tool with clearly defined steps and applications for scanning the current and future organizational environment. Stakeholder analysis can be used to generate knowledge about the relevant actors so as to understand their behaviour, intentions, interrelations, agendas, interests, and the influence or resources they have brought--or could bring--to bear on decision-making processes. This information can then be used to develop strategies for managing these stakeholders, to facilitate the implementation of specific decisions or organizational objectives, or to understand the policy context and assess the feasibility of future policy directions. Policy development is a complex process which frequently takes place in an unstable and rapidly changing context, subject to unpredictable internal and external factors. As a cross-sectional view of an evolving picture, the utility of stakeholder analysis for predicting and managing the future is time-limited and it should be complemented by other policy analysis approaches.

Cancer patients' information needs and information seeking behaviour: in depth interview study

Abstract: Objectives: To explore why cancer patients do not want or seek information about their condition beyond that volunteered by their physicians at times during their illness. Design: Qualitative study based on in-depth interviews. Setting: Outpatient oncology clinics at a London cancer centre. Participants: 17 patients with cancer diagnosed in previous 6 months. Main outcome measures: Analysis of patients9 narratives to identify key themes and categories. Results: While all patients wanted basic information on diagnosis and treatment, not all wanted further information at all stages of their illness. Three overarching attitudes to their management of cancer limited patients9 deon with life as normal and could be maintained through silence and avoiding information, especially too detailed or “unsafe” information. Charity to fellow patients, especially those seen as more needy than themselves, was expressed in the recognition that scarce resources—including information and explanations—had to be shared and meant that limited information was accepted as inevitable. Conclusions: Cancer patients9 attitudes to cancer and their strategies for coping with their illness can constrain their wish for information and their efforts to obtain it. In developing recommendations, the government9s cancer information strategy should attend to variations in patients9 desires for information and the reasons for them.

Developmental psychopathology: concepts and challenges.

Abstract: The defining features of developmental psychopathology concepts include attention to the understanding of causal processes, appreciation of the role of developmental mechanisms, and consideration of continuities and discontinuities between normality and psychopathology. Accomplishments with respect to these issues are reviewed in relation to attachment disorders, antisocial behavior, autism, depressive disorder, schizophrenia, and intellectual development. Major research challenges remain in relation to measurement issues, comorbidity, gender differences, cognitive processing, nature-nurture interplay, heterotypic continuity, continuities between normal variations and disorders, developmental programming, and therapeutic mechanisms in effective treatments.

Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis.

Abstract: The aim was to systematically review studies of male circumcision and the risk of HIV-1 infection in men in sub-Saharan Africa and to summarize the findings in a meta-analysis. A systematic literature review was carried out of studies published up to April 1999 that included circumcision as a risk factor for HIV-1 infection among men in sub-Saharan Africa. A random effects meta- analysis was used to calculate a pooled relative risk (RR) and 95% confidence interval (CI) for all studies combined and stratified by type of study population. Further analyses were conducted among those studies that adjusted for potential confounding factors. 27 studies were included. Of these 21 showed a reduced risk of HIV among circumcised men being approximately half that in uncircumcised men (crude RR = 0.52 CI 0.40-0.68). In 15 studies that adjusted for potential confounding factors the association was even stronger (adjusted RR = 0.42 CI 0.34-0.54). The association was stronger among men at high risk of HIV (crude RR = 0.27; adjusted RR = 0.29 CI 0.20-0.41) than among men in general populations (crude RR = 0.93; adjusted RR = 0.56 CI 0.44- 0.70). Male circumcision is associated with a significantly reduced risk of HIV infection among men in sub-Saharan Africa particularly those at high risk of HIV. These results suggest that consideration should be given to the acceptability and feasibility of providing safe services for male circumcision as an additional HIV prevention strategy in areas of Africa where men are not traditionally circumcised. (authors)

Genetic risk and the birth of the somatic individual

Abstract: This paper considers the implications of the rise of the new molecular genetics for the ways in which we are governed and the ways in which we govern ourselves. Using examples of genetic screening and genetic discrimination in education, employment and insurance, and a case study of debates among those at risk of developing Huntington's Disease and their relatives, we suggest that some of the claims made by critics of these new developments are misplaced. While there are possibilities of genetic discrimination, the key event is the creation of the person 'genetically at risk'. But genetic risk does not imply resignation in the face of an implacable biological destiny: it induces new and active relations to oneself and one's future. In particular, it generates new forms of 'genetic responsibility', locating actually and potentially affected individuals within new communities of obligation and identification. Far from generating fatalism, the rewriting of personhood at a genetic level and its visualization ...

Community, Citizenship, and the third Way:

Abstract: This article analyses recent debates about the Third Way in politics in Britain and the United States. It suggests that what is most significant is the emergence of a new politics of conduct that seeks to reconstruct citizens as moral subjects of responsible communities. The author considers the presuppositions of such a politics and its implications for technologies of government.

Language Play, Language Learning

Abstract: This book has two related purposes. The first is to demonstrate the extent and importance of language play in human life; the second is to draw out the implications for applied linguistics and language teaching. Language play should not be thought of as a trivial or peripheral activity, but as central to human thought and culture, to learning, creativity, and intellectual enquiry. It fulfils a major function of language, underpinning the human capacity to adapt: as individuals, as societies, and as a species.

Presence: concept, determinants, and measurement

Abstract: The concept of presence, i.e. the sensation of 'being there' in a mediated environment, has received substantial attention from the virtual reality community, and is becoming increasingly relevant both to broadcasters and display developers. Although research into presence is still at an early stage of development, there is a consensus that presence has multiple determinants. To identify and test which parameters affect presence, a reliable, robust and valid means of measuring presence is required. In this paper, we describe the categories of factors thought to have an impact on presence. Furthermore, we present an overview of various approaches taken to measuring presence, which can be divided into two general categories: subjective measures and objective corroborative measures. Since presence is a subjective experience, the most direct way of assessment is through users' subjective report. This approach has serious limitations however, and should be used judiciously. Objective measures, such as postural, physiological or social responses to media, can be used to corroborate subjective measures, thereby overcoming some of their limitations. At present, the most promising direction for presence measurement is to develop and use an aggregate measure of presence that is comprised of both subjective and objective components, tailored to the specific medium under study.

Color categories are not universal: replications and new evidence from a stone-age culture.

Abstract: The authors sought to replicate and extend the work of E. Rosch Heider (1972) on the Dani with a comparable group from Papua, New Guinea, who speak Berinmo, which has 5 basic color terms. Naming and memory for highly saturated focal, non-focal, and low-saturation stimuli from around the color space were investigated. Recognition of desaturated colors was affected by color vocabulary. When response bias was controlled, there was no recognition advantage for focal stimuli. Paired-associate learning also failed to show an advantage for focal stimuli. Categorical Perception effects for both English and Berinmo were found, but only at the boundaries of existing linguistic categories. It is concluded that possession of linguistic categories facilitates recognition and influences perceptual judgments.

A common polymorphism acts as an intragenic modifier of mutant p53 behaviour

Abstract: The p73 protein, a homologue of the tumour-suppressor protein p53, can activate p53-responsive promoters and induce apoptosis in p53-deficient cells. Here we report that some tumour-derived p53 mutants can bind to and inactivate p73. The binding of such mutants is influenced by whether TP53 (encoding p53) codon 72, by virtue of a common polymorphism in the human population, encodes Arg or Pro. The ability of mutant p53 to bind p73, neutralize p73-induced apoptosis and transform cells in cooperation with EJ-Ras was enhanced when codon 72 encoded Arg. We found that the Arg-containing allele was preferentially mutated and retained in squamous cell tumours arising in Arg/Pro germline heterozygotes. Thus, inactivation of p53 family members may contribute to the biological properties of a subset of p53 mutants, and a polymorphic residue within p53 affects mutant behaviour.

The urban environment and health in a world of increasing globalization: issues for developing countries.

Abstract: Urban living is the keystone of modern human ecology. Cities have multiplied and expanded rapidly worldwide over the past two centuries. Cities are sources of creativity and technology, and they are the engines for economic growth. However, they are also sources of poverty, inequality, and health hazards from the environment. Urban populations have long been incubators and gateways for infectious diseases. The early industrializing period of unplanned growth and laissez-faire economic activity in cities in industrialized countries has been superseded by the rise of collective management of the urban environment. This occurred in response to environmental blight, increasing literacy, the development of democratic government, and the collective accrual of wealth. In many low-income countries, this process is being slowed by the pressures and priorities of economic globalization. Beyond the traditional risks of diarrhoeal disease and respiratory infections in the urban poor and the adaptation of various vector-borne infections to urbanization, the urban environment poses various physicochemical hazards. These include exposure to lead, air pollution, traffic hazards, and the "urban heat island" amplification of heatwaves. As the number of urban consumers and their material expectations rise and as the use of fossil fuels increases, cities contribute to the large-scale pressures on the biosphere including climate change. We must develop policies that ameliorate the existing, and usually unequally distributed, urban environmental health hazards and larger-scale environmental problems.

Use of a flexible cassette method to generate a double unmarked Mycobacterium tuberculosis tlyA plcABC mutant by gene replacement.

Abstract: Progress in the field of mycobacterial research has been hindered by the inability to readily generate defined mutant strains of the slow-growing mycobacteria to investigate the function of specific genes. An efficient method is described that has been used to generate several mutants, including the first double unmarked deletion strain of Mycobacterium tuberculosis. Four mutants were constructed: a marked deletion of the plcABC cluster, which encodes three phospholipases C; separate unmarked deletions in plcABC and tlyA (encoding a haemolysin); and a double unmarked mutant tlyAΔ plcABCΔ. To accomplish this, two series of vectors were designed, the first of which, named pNIL, allows manipulation of the target gene sequence at a variety of convenient restriction sites. The second series, named pGOAL, contains marker cassettes flanked by PacI restriction enzyme sites. The final suicide plasmid vectors were then obtained by cloning a marker cassette from a pGOAL vector into the single PacI site of the pNIL vector with the modified gene of interest. Finally, a two-step strategy was employed whereby single cross-over events were first selected, then screening for the second cross-over was carried out to yield the mutant strains. This technique will now allow the construction of potential vaccine strains without the inclusion of antibiotic resistance markers, the ability to make multiple defined mutations and the possibility of making more subtle defined mutations, such as point mutations.

Engineering Rock Mechanics: An Introduction to the Principles

Abstract: Preface Units and Symbols Part A: Illustrative Worked Examples - Questions and Answers Introduction Geological setting Stress In situ rock stress Strain and the theory of elasticity Intact rock: deformability, strength and failure Fractures and hemispherical projection Rock masses: deformability, strength, failure and Permeability Anisotropy and inhomogeneity Testing techniques Rock mass classification Rock dynamics and time dependency Rock mechanics interactions and rock engineering systems Excavation principles Rock reinforcement and rock support Foundations and slopes - instability mechanisms Design of surface excavations Underground excavation instability mechanisms Design of underground excavations Part B: Questions Only The questions in Part A are repeated here without the answers for those who wish to attempt the questions without the answers being visible Questions 1.1-1.5: Introduction. Questions 2.1-2.10: Geological setting. Questions 3.1-3.10: Stress. Questions 4.1-4.10: In situ rock stress. Questions 5.1-5.10: Strain and the theory of elasticity. Questions 6.1-6.10: Intact rock. Questions 7.1-7.10: Fractures and hemispherical projection. Questions 8.1-8.10: Rock masses. Questions 9.1-9.10: Permeability. Questions 10.1-10.10: Anisotropy and inhomogeneity. Questions 11.1-11.10: Testing techniques. Questions 12.1-12.10: Rock mass classification. Questions 13.1-13.10: Rock dynamics and time dependency. Questions 14.1-14.10: Rock mechanics interactions and rock engineering systems. Questions 15.1-15.10: Excavation principles. Questions 16.1-16.10: Rock reinforcement and rock support. Questions 17.1-17.10: Foundations and slopes - instability mechanisms. Questions 18.1-18.10: Design of surface excavations. Questions 19.1-19.10: Underground excavation instability mechanism. Questions 20.1-20.10: Design of underground excavations. Appendix 1. 3-D stress cube model Appendix 2. Hemispherical projection sheet Appendix 3. Rock mass classification tables: RMR and Q References Index

X-linked Alport Syndrome Natural History in 195 Families and Genotype- Phenotype Correlations in Males

Abstract: Alport syndrome (AS) is a type IV collagen hereditary disease characterized by the association of progressive hematuric nephritis, hearing loss, and, frequently, ocular changes. Mutations in the COL4A5 collagen gene are responsible for the more common X-linked dominant form of the disease. Considerable allelic heterogeneity has been observed. A "European Community Alport Syndrome Concerted Action" has been established to delineate accurately the AS phenotype and to determine genotype-phenotype correlations in a large number of families. Data concerning 329 families, 250 of them with an X-linked transmission, were collected. Characteristics of the 401 male patients belonging to the 195 families with COL4A5 mutation are presented. All male patients were hematuric, and the rate of progression to end-stage renal failure and deafness was mutation-dependent. Large deletions, non-sense mutations, or small mutations changing the reading frame conferred to affected male patients a 90% probability of developing end-stage renal failure before 30 yr of age, whereas the same risk was of 50 and 70%, respectively, in patients with missense or splice site mutation. The risk of developing hearing loss before 30 yr of age was approximately 60% in patients with missense mutations, contrary to 90% for the other types of mutations. The natural history of X-linked AS and correlations with COL4A5 mutations have been established in a large cohort of male patients. These data could be used for further evaluation of therapeutic approaches.

Risk of Second Malignancy After Hodgkin’s Disease in a Collaborative British Cohort: The Relation to Age at Treatment

Abstract: PURPOSE: To assess long-term site-specific risks of second malignancy after Hodgkin’s disease in relation to age at treatment and other factors. PATIENTS AND METHODS: A cohort of 5,519 British patients with Hodgkin’s disease treated during 1963 through 1993 was assembled and followed-up for second malignancy and mortality. Follow-up was 97% complete. RESULTS: Three hundred twenty-two second malignancies occurred. Relative risks of gastrointestinal, lung, breast, and bone and soft tissue cancers, and of leukemia, increased significantly with younger age at first treatment. Absolute excess risks and cumulative risks of solid cancers and leukemia, however, were greater at older ages than at younger ages. Gastrointestinal cancer risk was greatest after mixed-modality treatment (relative risk [RR] = 3.3; 95% confidence interval [CI], 2.1 to 4.8); lung cancer risks were significantly increased after chemotherapy (RR = 3.3; 95% CI, 2.4 to 4.7), mixed-modality treatment (RR = 4.3; 95% CI, 2.9 to 6.2), and radioth...

Cholera dynamics and El Niño-Southern Oscillation.

Abstract: Analysis of a monthly 18-year cholera time series from Bangladesh shows that the temporal variability of cholera exhibits an interannual component at the dominant frequency of El Nino-Southern Oscillation (ENSO). Results from nonlinear time series analysis support a role for both ENSO and previous disease levels in the dynamics of cholera. Cholera patterns are linked to the previously described changes in the atmospheric circulation of south Asia and, consistent with these changes, to regional temperature anomalies.