Showing papers by "University of London published in 1993"

Rethinking University Teaching: A Conversational Framework for the Effective Use of Learning Technologies

Abstract: Part I What Students Need From Learning Technologies 1. Teaching as Mediated Learning 2. What Students Bring to Learning 3. The Complexity of Coming to Know 4. Generating a Teaching Strategy Part II Analysing the Media for Learning and Teaching 5. Narrative Media 6. Interactive Media 7. Adaptive Media 8. Communicative Media 9. Productive Media Part III The Design Methodology 10. Designing Teaching Materials 11. Setting up the Learning Context 12. Designing an Effective Organisational Infrastructure

Government, authority and expertise in advanced liberalism

Abstract: This paper outlines Foucault's concept of governmentality and argues for its contemporary significance. It focuses upon the role that liberal modes of government accord to the exercise of authority over individual and collective conduct by expertise. The paper argues that nineteenth-century liberalism as a mode of rule produced a series of problems about the governability of individuals, families and markets and populations. Expertise provided a formula for resolving these problems instantiated in a range of complex and heterogenous ‘machines’ for the government of individual and collective conduct. Over the late nineteenth and early twentieth centuries one sees the rise of a new formula for the exercise of rule, which one can call ‘the welfare state’ - within which expertise becomes linked to the formal political apparatus in new ways. the strategies of rule generated under this formula of ‘the welfare state’ have changed fundamentally over the last fifty years. A new formula of rule is taking shape, one...

Herd Immunity: History, Theory, Practice

Abstract: Herd immunity has to do with the protection of populations from infection which is brought about by the presence of immune individuals. The concept has a special aura, in its implication of an extension of the protection imparted by an immunization program beyond vaccinated to unvaccinated individuals and in its apparent provision of a means to eliminate totally some infectious diseases. It is a recurrent theme in the medical literature and has been discussed frequently during the past decade. This new popularity comes as a consequence of several recent major achievements of vaccination programs, i.e.: the historic success of the global smallpox eradication program; dramatic increases in vaccination coverage stimulated by national programs and by the Expanded Programme on Immunization; the commitment of several countries to eradicate measles; and international dedication to eliminate neonatal tetanus and to eradicate poliomyelitis from the world by the year 2000.'

Golden age to separate spheres? A review of the categories and chronology of English women's history*

Abstract: Two very powerful stories structure the history of the changing roles of English women. The tale of the nineteenth-century separation of the spheres of public power and private domesticity relates principally to the experience of middle-class women. The other story, emerging from early modern scholarship, recounts the social and economic marginalization of propertied women and the degradation of working women as a consequence of capitalism. Both narratives echo each other in important ways, although strangely the capacity of women's history to repeat itself is rarely openly discussed. This paper critically reviews the two historiographies in order to open debate on the basic categories and chronologies we employ in discussing the experience, power and identity of women in past time.

Protective Effect of BCG against Tuberculous Meningitis and Miliary Tuberculosis: A Meta-Analysis

Abstract: The protective effect of BCG against tuberculosis (TB) estimated in randomized controlled trials and observational studies ranges from negative to close to a 100%. One of the many explanations offered for this is that different immunological mechanisms may be associated with protective effect against different forms and sites of disease. In this investigation, we recalculated vaccine protective effect separately for pulmonary disease and for meningeal/miliary disease in randomized controlled trials and case-control studies, tested for heterogeneity in site-specific estimates of protective effect and calculated a summary measure when appropriate. We found protective effect against pulmonary disease to be heterogeneous to a statistically significant degree, and thus we did not calculate a summary measure of protection. Protective effect against meningeal and miliary TB was higher than against pulmonary disease and, except for a single study with two cases only, appeared to be homogenous. Summary BCG protective effect against miliary or meningeal TB in randomized controlled trials was 86% (95% confidence interval [CI] 65, 95) and in case-control studies 75% (95% CI: 61, 84). The fact that protective effect appeared to be homogeneous against meningitis and miliary TB but not against pulmonary disease may result from the fact that patients with meningitis are on average younger and thus less likely to have been exposed to atypical bacteria; to a waning of the protective effect of BCG; or from the diversity of mechanisms of pathogenesis of pulmonary disease, which can originate from reinfection, reactivation or primary progression.

GABAB Receptor Pharmacology

Abstract: In conclusion, GABAB receptors appear to be of major importance in synaptic processing within the brain and are present at both post- and presynaptic sites. Their activation can hyperpolarize neurones and diminish neurotransmitter release from presynaptic terminals. We already know that drugs, i.e. baclofen, that mimic this activation are therapeutically useful, although the full significance of their use both inside and outside the brain has yet to be realized. Drugs that interfere with GABAB receptor activation should also prove to be important therapeutic agents. A number of suggestions have been proposed but it will be many years before the potential effects can be consolidated or refuted in humans. Only now are brain-penetrating GABAB antagonists being discovered, due largely to the expertise of the research group at CIBA-Geigy, Basel. The emergence of such compounds makes future studies an exciting prospect. In particular, the discovery that GABAB antagonism can suppress absence seizures in rats has provided an important therapeutic target. It is now just over ten years since we first designated the term GABAB. Since then a wealth of information has been obtained, but perhaps the best is still to come.

A microwell cytotoxicity assay using Artemia salina (brine shrimp).

Abstract: A new microplate assay for cytotoxicity testing using A. salina has been developed and shown to give results comparable to a previously published test-tube method. The assay reliably detected all of the compounds toxic to KB cells in a series of 21 pharmacologically active agents, except for two which require metabolic activation in man. Four quassinoids with cytotoxic and antiplasmodial activity were also toxic to the brine shrimp while quassin itself was inactive in all three systems. It is proposed that this assay provides a convenient means by which the presence of cytotoxic quassinoids may be detected during the fractionation of plant extracts.

Association of early-onset coronary heart disease in South Asian men with glucose intolerance and hyperinsulinemia.

Abstract: BACKGROUNDRates of coronary heart disease are higher in South Asians (Indians, Pakistanis, and Bangladeshis) settled overseas than in other ethnic groups. We tested the hypothesis that this excess risk results from metabolic disturbances associated with insulin resistance.METHODS AND RESULTSThere were 1,421 South Asian men and 1,515 European men aged 40-69 years in London examined in the Southall Study. Prevalence of ischemic ECG abnormalities was higher in South Asians than in Europeans (17% versus 12%, p < 0.001), with an excess of major Q waves (Minnesota codes 1-1 or 1-2) in younger South Asian men (p = 0.01 for the age-ethnicity interaction). Major Q waves were strongly associated with glucose intolerance and hyperinsulinemia in younger South Asians; these factors accounted statistically for 73% of major Q waves in those aged 40-54 years. Age-standardized prevalence of a positive history of coronary heart disease was similar in South Asians and Europeans (8.5% versus 8.2%, NS), and positive history w...

Which Hough transform

Abstract: The Hough transform is recognized as being a powerful tool in shape analysis which gives good results even in the presence of noise and occlusion. Major shortcomings of the technique are excessive storage requirements and computational complexity. Solutions to these problems form the bulk of contributions to the literature concerning the Hough transform. An excellent comprehensive review of available methods up to and partially including 1988 is given by Illingworth and Kittler (Comput. Vision Graphics Image Process. 44, 1988, 87-116). In the years following this survey much new literature has been published. The present work offers an update on state of the art Hough techniques. This includes comparative studies of existing techniques, new perspectives on the theory, very many novel algorithms, parallel implementations, and additions to the task-specific hardware. Care is taken to distinguish between research that aims to further basic understanding of the technique without necessarily being computationally realistic and research that may be applicable in an industrial context. A new trend in Hough transform work, that of the probabilistic Houghs, is identified and reviewed in some detail. Attempts to link the low level perceptive processing offered by the Hough transform to high level knowledge driven processing are also included, together with the many recent successful applications appearing in the literature.

The Role of Oxygen Radicals in Human Disease, with Particular Reference to the Vascular System

Abstract: Free radicals, such as superoxide, hydroxyl and nitric oxide, and other reactive oxygen species (ROS), such as hydrogen peroxide, are formed in vivo. Imbalance between production of ROS and anti-oxidant defence can result in oxidative stress, which may arise either from deficiencies of anti-oxidants (such as glutathione, ascorbate or alpha-tocopherol) and/or from increased formation of ROS. Oxidative stress can result in glutathione depletion, lipid peroxidation, membrane damage and DNA strand breaks as well as activation of proteases, nucleases and protein kinases. Some degree of oxidative stress occurs in most, if not all, human diseases, and the major question to be answered is whether it makes a significant contribution to the disease pathology. In the case of atherosclerosis, evidence from studies with the chain-breaking anti-oxidant probucol and from epidemiological work suggests that oxidative damage does indeed make an important contribution to plaque development.

The influence of age on the development of the hepatitis B carrier state

Abstract: The relation between the age at infection with hepatitis B virus (HBV) and the development of the carrier state is examined by using data from a number of published and unpublished surveys. A remarkably consistent relation was found. Infants infected perinatally (within the first 6 months of life) were found to have a high probability of becoming carriers (0.885; 95% C.L. 0.84-0.93). Over the infant and early childhood age classes there was found to be a sharp decrease in the proportion of infections which lead to the carrier state. By adulthood (over 15 years) the probability of developing the carrier status was found to be about 0.1. A model was fitted to the data by using maximum likelihood, which provides a good empirical description of the observed data and can be used to predict the expected probability of developing the carrier state given the age at infection. It is postulated that, as a result of this rapid decline in the probability of becoming a carrier during early childhood, a mass childhood immunization campaign, which will tend to postpone the average age at infection in the unvaccinated community, will have a disproportionately large impact on the rate of generation of new carriers.

Arsenical-resistant trypanosomes lack an unusual adenosine transporter.

Abstract: The melaminophenyl arsenical melarsoprol is still used to treat African sleeping sickness, a disease caused by parasitic protozoa of the Trypanosoma brucei subgroup Based on the observation that melamine antagonizes the trypanocidal activity of this class of drugs, we investigated whether other physiological compounds could compete for the same receptor Here we report that the in vitro trypanolytic effect of melarsen oxide can be specifically abrogated by adenine, adenosine and dipyridamole, all of which compete for uptake by an adenosine transporter Melarsen-sensitive trypanosomes have two high-affinity adenosine transport systems: a P1 type, which also transports inosine; and a P2 type, which also transports adenine and the melaminophenyl arsenicals Melarsen-resistant trypanosomes lack P2 adenosine transport, suggesting that resistance to these arsenicals is due to loss of uptake

Safety-critical systems, formal methods and standards

Abstract: Standards concerned with the development of safety-critical systems, and the software in such systems in particular, abound today as the software crisis increasingly affects the world of embedded computer-based systems. The use of formal methods is often advocated as a way of increasing confidence in such systems. The paper examines the industrial use of these techniques, the recommendations concerning formal methods in a number of current and draft standards, and comments on the applicability and problems of using formal methods for the development of safety-critical systems on an industrial scale. Some possible future directions are suggested.< >

K+ channels of stomatal guard cells : abscisic-acid-evoked control of the outward rectifier mediated by cytoplasmic pH

Abstract: The activation by abscisic acid (ABA) of current through outward-rectifying K+ channels and its dependence on cytoplasmic pH (pHi) was examined in stomatal guard cells of Vicia faba L. Intact guard cells were impaled with multibarrelled and H+-selective microelectrodes to record membrane potentials and pHi during exposures to ABA and the weak acid butyrate. Potassium channel currents were monitored under voltage clamp and, in some experiments, guard cells were loaded with pH buffers by iontophoresis to suppress changes in pHi. Following impalements, stable pHi values ranged between 7.53 and 7.81 (7.67±0.04, n = 17). On adding 20 μM ABA, pHi rose over periods of 5–8 min to values 0.27±0.03 pH units above the pHi before ABA addition, and declined slowly thereafter. Concurrent voltage-clamp measurements showed a parallel rise in the outward-rectifying K+ channel current (IK, out) and, once evoked, both pHi and IK, out responses were unaffected by ABA washout. Acid loads, imposed with external butyrate, abolished the ABA-evoked rise in IK, out. Butyrate concentrations of 10 and 30 mM (pH0 6.1) caused pHi to fall to values near 7.0 and below, both before and after adding ABA, consistent with a cytoplasmic buffer capacity of 128±12 mM per pH unit (n = 10) near neutrality. Butyrate washout was characterised by an appreciable alkaline overshoot in pHi and concomitant swell in the steady-state conductance of IK, out. The rise in pHi and iK, out in ABA were also virtually eliminated when guard cells were first loaded with pH buffers to raise the cytoplasmic buffer capacity four- to sixfold; however, buffer loading was without appreciable effect on the ABA-evoked inactivation of a second, inward-rectifying class of K+ channels (IK, in). The pHi dependence of IK, out was consistent with a cooperative binding of at least 2H+ (apparent pKa = 8.3) to achieve a voltage-independent block of the channel. These results establish a causal link previously implicated between cytoplasmic alkalinisation and the activation of IK, out in ABA and, thus, affirm a role for H+ in signalling and transport control in plants distinct from its function as a substrate in H+-coupled transport. Additional evidence implicates a coordinate control of IK, in by cytoplasmic-free [Ca2+] and pHi.

Decision making style, driving style and self-reported involvement in road traffic accidents

Abstract: In an exploratory postal survey of 711 drivers stratified by age, sex, annual mileage, and accident involvement, decision-making style was measured using a Decision-Making Questionnaire (DMQ) and driving style was assessed using a Driving Style Questionnaire (DSQ). Responses to 21 items of the DMQ formed seven independent and internally coherent dimensions according to a principal components (PC) analysis. These were labelled: control, thoroughness, instinctiveness, social resistance, hesitancy, perfectionism, and idealism. PC analysis also revealed that responses to 15 items of the DSQ formed six independent dimensions of driving style. These were labelled: speed, calmness, social resistance, focus, planning, and deviance. Multiple regression analysis indicated that drivers of 60 years and under who scored lower on thoroughness were at greater risk of a traffic accident and that this relationship was mediated by faster driving. This relationship was independent of age, sex, annual mileage and all other factors measured. In the drivers over 60 years, lower thoroughness, greater hesitancy, and faster driving were independently associated with higher accident rates independent of all other factors measured. The results provide preliminary support for the view that people import aspects of their general decision-making style into the driving situation, and that in so doing they put themselves at differential risk of having a road traffic accident.

Characterization of protein kinase C isotype expression in adult rat heart. Protein kinase C-epsilon is a major isotype present, and it is activated by phorbol esters, epinephrine, and endothelin.

Abstract: The pattern of protein kinase C (PKC) isotype expression in whole extracts of dispersed, freshly isolated adult rat ventricular myocytes and adult rat heart ventricle was examined by immunoblot analysis using antisera specific for PKC-alpha, -beta 1, -gamma, -delta, -epsilon, -zeta, or -eta isotypes. This analysis revealed significant levels of expression of the Ca(2+)-independent isotype PKC-epsilon, which was detected as band of 97-kd molecular mass. PKC-zeta was detected principally as a 66-kd band that probably represented a proteolytic product of the holoenzyme. PKC-eta was detected only in whole ventricle as a doublet at 75 and 81 kd and was therefore probably present in nonmyocytic cells. PKC-alpha, -beta 1, -gamma, and -delta could not be detected. Because of our inability to detect PKC-alpha, -beta 1, -gamma, and -delta in whole extracts, PKC isotypes were partially purified from whole heart by DEAE Sepharose chromatography. PKC-alpha, -beta 1, -gamma, and -delta could still not be detected in the appropriate fractions. All PKC isotypes were detectable in appropriate positive control extracts (brain or certain cultured cell lines). In unstimulated isolated cardiomyocytes, the majority (80-95%) of the PKC-epsilon immunoreactivity was present in the soluble fraction of the extract. On exposure of the cardiomyocytes to 1 microM phorbol 12-myristate 13-acetate (PMA), PKC-epsilon undergoes a rapid (< 30 seconds), sustained (at least 60 minutes), and virtually complete association with the Triton X-100-soluble membrane fraction. There was an associated loss of PKC-epsilon from the soluble fraction. The EC50 for PMA of the translocation event was 15-37 nM. Exposure of cardiomyocytes to 1 microM 4 beta-phorbol 12,13-didecanoate or 1 microM phorbol 12,13-dibutyrate also resulted in translocation of PKC-epsilon to the membrane fraction, whereas exposure to 1 microM 4 alpha-phorbol 12,13-didecanoate was without effect. PKC-epsilon also translocated on exposure of cardiomyocytes to 50 microM epinephrine or 100 nM endothelin-1. However, in both cases, the extent of translocation was significantly less than that after exposure to PMA. We conclude that interventions that lead to hypertrophy of cardiomyocytes (phorbol esters, epinephrine, and endothelin-1) activate PKC-epsilon.

A malaria control trial using insecticide-treated bed nets and targeted chemoprophylaxis in a rural area of The Gambia, West Africa

Abstract: Background data on child mortality and morbidity from malaria were obtained in a new study area in the centre of The Gambia, south of the river, chosen as the site for a malaria intervention trial. Infant and child mortality rates were 120 and 41 per 1000 respectively. Results obtained using post-mortem questionnaires suggested that malaria was an uncommon cause of death in children under the age of one year but responsible for about 40% of deaths in children aged 1–4 years. Ninety-two percent of deaths attributed to malaria occurred during or immediately after the rainy season. Parasite and spleen rates in children aged 1–5 years at the end of the malaria transmission season were 66% and 64% respectively. Malariometric indices were similar in primary health care (PHC) villages, selected as sites for an intervention with insecticide-treated bed nets and targeted chemoprophylaxis, and in smaller, non-PHC, control villages.

Evaluation of the Antioxidant Actions of Ferulic Acid and Catechins

Abstract: We have evaluated the abilities of ferulic acid, (+/-) catechin, (+) catechin and (-) epicatechin to scavenge the reactive oxygen species hydroxyl radical (OH.), hypochlorous acid (HOCl) and peroxyl radicals (RO2.). Ferulic acid tested at concentrations up to 5 mM inhibited the peroxidation of phospholipid liposomes. Both (+/-) and (+) catechin and (-) epicatechin were much more effective. All the compounds tested reacted with trichloromethyl peroxyl radical (CCl3 O2.) with rate constants > 1 x 10(6) M-1 s-1. A mixture of FeCl3-EDTA, hydrogen peroxide (H2O2) and ascorbic acid at pH 7.4, has often been used to generate hydroxyl radicals (OH.) which are detected by their ability to cause damage to the sugar deoxyribose. Ferulic acid, (+) and (+/-) catechin and (-) epicatechin inhibited deoxyribose damage by reacting with OH. with rate constants of 4.5 x 10(9)M-1 s-1, 3.65 x 10(9) M-1 s-1, 2.36 x 10(9) M-1 s-1 and 2.84 x 10(9) M-1 s-1 respectively. (-) Epicatechin, ferulic acid and the (+) and (+/-) catechins exerted pro-oxidant action, accelerating damage to DNA in the presence of a bleomycin-iron complex. On a molar basis, ferulic acid was less effective in causing damage to DNA compared with the catechins. A mixture of hypoxanthine and xanthine oxidase generates O2-. which reduces cytochrome c to ferrocytochrome c. (+) Catechin and (-) epicatechin inhibited the reduction of cytochrome c in a concentration dependent manner. Ferulic acid and (+/-) catechin had only weak effects. All the compounds tested were able to scavenge hypochlorous acid at a rate sufficient to protect alpha-1-antiproteinase against inactivation. Our results show that catechins and ferulic acid possess antioxidant properties. This may become important given the current search for "natural" replacements for synthetic antioxidant food additives.

Topography of pyramidal neuron intrinsic connections in macaque monkey prefrontal cortex (areas 9 and 46).

Abstract: An understanding of the normal organization of prefrontal cortex is essential to the recognition of pathology underlying human behavioral disorders believed to depend on this region. We have therefore studied the pattern of intrinsic intra- and interlaminar pyramidal neuron connectivity in prefrontal areas 9 and 46 (of Walker) in macaque monkey cerebral cortex (anterior to the arcuate sulcus between the principal sulcus and midline). We made focal (200-400 microns) injections of biocytin and mapped the pattern of orthogradely transported label. Injections made into the superficial layers label wide-ranging lateral projections within the same areas of prefrontal cortex. Projections local to such small injections form a narrow band of terminals in layers 1-3 (200-400 microns wide, 2-4 mm long) centered on the injection site. Collateral fibers spread orthogonal to this terminal band, making frequent bifurcations, to establish a series of parallel bands of terminals with uninnervated bands between, spaced regularly across the cortex (center to center 500-600 microns). The entire pattern of terminal label is stripe-like, with occasional narrower interbands and crosslinks between the bands, and can extend over 7-8 mm across the cortex. These projections arise from pyramidal neurons in layers 2, 3, and 5 and terminate in layers 1-3. The stripe-like pattern contrasts with patch-like patterns in other cortical regions (V1, V2, V4, motor, somatosensory) and is smaller in scale than stripe-like zones of corticocortical afferent terminals to this region, reported to be 300-750 microns wide and spaced 1.0-1.5 mm center to center.

Oxidative DNA damage and cellular sensitivity to oxidative stress in human autoimmune diseases.

Abstract: OBJECTIVES--To estimate the extent of genomic DNA damage and killing of lymphocytes by reactive oxygen intermediates in autoimmune diseases. METHODS--8-Oxo-7-hydrodeoxyguanosine (8-oxodG), a promutagenic DNA lesion induced by reactive oxygen intermediates, was measured by high performance liquid chromatography, coupled with electrochemical detection, in hydrolysates of DNA which had been extracted from lymphocyte and polymorphonuclear leucocyte fractions of human blood. In addition, human primary blood lymphocytes stimulated by concanavalin A were assayed for cytotoxicity induced by hydrogen peroxide on day 0, by assessing cell proliferation during seven days of culture. RESULTS--Constitutive 8-oxodG was detectable (mean (2 SEM) moles 8-oxodG/10(6) moles deoxyguanosine) in DNA isolated from normal human blood lymphocytes (68 (8), n = 26) and polymorphonuclear leucocytes (118 (24), n = 24). Lymphocyte DNA from donors with the following inflammatory autoimmune diseases contained significantly higher levels of 8-oxodG than that from healthy donors: rheumatoid arthritis (98 (16)), systemic lupus erythematosus (137 (28)), vasculitis (100 (32)), and Behcet's disease (92 (19)). Lymphocyte 8-oxodG levels in non-autoimmune controls and patients with scleroderma were not significantly different from those of healthy controls. The levels of 8-oxodG were significantly higher in the DNA from normal polymorphonuclear leucocytes than in paired DNA samples from normal lymphocytes, but there were no differences between levels of 8-oxodG in polymorphonuclear leucocytes from normal subjects and the patients studied. Levels of 8-oxodG did not correlate with disease duration, disease severity, or age. Lymphocytes from patients with systemic lupus erythematosus and rheumatoid arthritis, but not those with scleroderma, also showed cellular hypersensitivity to the toxic effects of hydrogen peroxide. CONCLUSION--There was increased genomic DNA damage, and increased susceptibility to cytotoxic killing by hydrogen peroxide, in lymphocytes from patients with certain autoimmune diseases. These results might be explained by defective repair of DNA damage or by increased production of reactive oxygen intermediates in inflammation. Although more direct studies are needed, the evidence available favours the former explanation.

Do children with autism recognise surprise? A research note

Abstract: We take a fresh look at emotion recognition in autistic children, by testing their recognition of three different emotions (happy, sad, and surprise). The interest in selecting these is that whereas the first two are typical “simple” emotions (caused by situations), the third is typically a “cognitive” emotion (caused by beliefs). Because subjects with autism have clear difficulties in understanding beliefs, we predicted they would show more difficulty in recognising surprise. In contrast, as they have no difficulty in understanding situations as causes of emotion, we predicted they would not show deficits in recognising happy and sad. These predictions were borne out, in a comparison with a group of normal children and in a group of subjects with mental handicap. This result shows the importance of fine-grain analysis in emotion-recognition tasks, and is discussed in relation to affective and theory of mind models of autism.