Showing papers by "University of Cambridge published in 1991"

Fetal and infant growth and impaired glucose tolerance at age 64.

Abstract: OBJECTIVE--To discover whether reduced fetal and infant growth is associated with non-insulin dependent diabetes and impaired glucose tolerance in adult life. DESIGN--Follow up study of men born during 1920-30 whose birth weights and weights at 1 year were known. SETTING--Hertfordshire, England. SUBJECTS--468 men born in east Hertfordshire and still living there. MAIN OUTCOME MEASURES--Fasting plasma glucose, insulin, proinsulin, and 32-33 split pro-insulin concentrations and plasma glucose and insulin concentrations 30 and 120 minutes after a 75 g glucose drink. RESULTS--93 men had impaired glucose tolerance or hitherto undiagnosed diabetes. They had had a lower mean birth weight and a lower weight at 1 year. The proportion of men with impaired glucose tolerance fell progressively from 26% (6/23) among those who had weighted 18 lb (8.16 kg) or less at 1 year to 13% (3/24) among those who had weighed 27 lb (12.25 kg) or more. Corresponding figures for diabetes were 17% (4/23) and nil (0/24). Plasma glucose concentrations at 30 and 120 minutes fell with increasing birth weight and weight at 1 year. Plasma 32-33 split proinsulin concentration fell with increasing weight at 1 year. All these trends were significant and independent of current body mass. Blood pressure was inversely related to birth weight and strongly related to plasma glucose and 32-33 split proinsulin concentrations. CONCLUSIONS--Reduced growth in early life is strongly linked with impaired glucose tolerance and non-insulin dependent diabetes. Reduced early growth is also related to a raised plasma concentration of 32-33 split proinsulin, which is interpreted as a sign of beta cell dysfunction. Reduced intrauterine growth is linked with high blood pressure, which may explain the association between hypertension and impaired glucose tolerance.

Probability with martingales

Abstract: Probability theory is nowadays applied in a huge variety of fields including physics, engineering, biology, economics and the social sciences. This book is a modern, lively and rigorous account which has Doob's theory of martingales in discrete time as its main theme. It proves important results such as Kolmogorov's Strong Law of Large Numbers and the Three-Series Theorem by martingale techniques, and the Central Limit Theorem via the use of characteristic functions. A distinguishing feature is its determination to keep the probability flowing at a nice tempo. It achieves this by being selective rather than encyclopaedic, presenting only what is essential to understand the fundamentals; and it assumes certain key results from measure theory in the main text. These measure-theoretic results are proved in full in appendices, so that the book is completely self-contained. The book is written for students, not for researchers, and has evolved through several years of class testing. Exercises play a vital role. Interesting and challenging problems, some with hints, consolidate what has already been learnt, and provide motivation to discover more of the subject than can be covered in a single introduction.

Inference to the best explanation

Abstract: How do we go about weighing evidence, testing hypotheses, and making inferences? According to this work, we infer the hypothesis that would, if correct, provide the best explanation of the available evidence. Articulating the model of "Inference to the Best Explanation" requires an account of what makes one explanation better than another. Lipton distinguishes between the explanation best supported by the evidence - the likeliest explanation - and the explanation that would, if true, provide the most understanding - the loveliest explanation. He argues that an illuminating version of "Inference to the Best Explanation" must rely on the latter notion, and provides a new account of what makes one explanation lovelier than another. He does this by analyzing the structure of contrastive explanations, explanations that answer the form "why P rather than Q?". The analysis of contrastive explanation is then shown to support a strong version of "Inference to the Best Explanation" that reveals how explanatory considerations can be a guide to inference.

X-ray reflection from cold matter in Active Galactic Nuclei and X-ray binaries

Abstract: Weak, broad emission lines due to low-ionisation stages of iron, and other spectral features, have recently been observed in the X-ray spectra of Active Galactic Nuclei and in some Galatic X-ray binaries. These features are due to X-ray irradiation of relatively cold, dense gas very close to the central compact object. The observed spectra consist of both direct radiation from the primary X-ray source and reflection' from the surrounding accretion flow. The reflected spectrum has features imprinted in it by photoabsorption, iron fluorescence and Compton scattering. The strength, shape and broadening of this reflected spectrum is a diagnostic of the geometry, ionisation state and iron abundance of the accretion flow, and through timing studies, may yield the mass of the central object.

Alterations in the levels of iron, ferritin and other trace metals in Parkinson's disease and other neurodegenerative diseases affecting the basal ganglia.

Abstract: Levels of iron, copper, zinc and manganese were measured by inductively coupled plasma spectroscopy in frozen postmortem brain tissue from patients with Parkinson's disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy with strionigral degeneration (MSA), and Huntington's disease (HD) compared with control subjects. Total iron levels were found to be elevated in the areas of basal ganglia showing pathological change in these disorders. In particular, total iron content was increased in substantia nigra in PD, PSP and MSA, but not in HD. Total iron levels in the striatum (putamen and/or caudate nucleus) were increased in PSP, MSA and HD but not in PD. Total iron levels were decreased in the globus pallidus in PD. There were no consistent alterations of manganese levels in basal ganglia structures in any of the diseases studied. Copper levels were decreased in the substantia nigra in PD, and in the cerebellum in PSP, and were elevated in the putamen and possibly substantia nigra in HD. Zinc levels were only increased in PD, in substantia nigra and in caudate nucleus and lateral putamen. Levels of the iron binding protein ferritin were measured in the same patient groups using a radio-immunoassay technique. Increased iron levels in basal ganglia were generally associated with normal or elevated levels of ferritin immunoreactivity, for example, the substantia nigra in PSP and possibly MSA, and in putamen in MSA. The exception was PD where there was a generalized reduction in brain ferritin immunoreactivity, even in the substantia nigra. An increase in total iron content appears to be a response to neurodegeneration in affected basal ganglia regions in a number of movement disorders. However, only in PD was there an increased total iron level, decreased ferritin content, decreased copper content, and an increased zinc concentration in substantia nigra. These findings suggest an alteration of iron handling in the substantia nigra in PD. Depending on the form in which the excess iron load exists in nigra in PD, it may contribute to the neurodegenerative process.

On the “Downward Control” of Extratropical Diabatic Circulations by Eddy-Induced Mean Zonal Forces

Abstract: The situation considered is that of a zonally symmetric model of the middle atmosphere subject to a given quasi-steady zonal force F, conceived to be the result of irreversible angular momentum transfer due to the upward propagation and breaking of Rossby and gravity waves together with any other dissipative eddy effects that may be relevant. The model's diabatic heating is assumed to have the qualitative character of a relaxation toward some radiatively determined temperature field. To the extent that the force F may be regarded as given, and the extratropical angular momentum distribution is realistic, the extratropical diabatic mass flow across a given isentropic surface may be regarded as controlled exclusively by the F distribution above that surface (implying control by the eddy dissipation above that surface and not, for instance, by the frequency of tropopause folding below). This “downward control” principle expresses a critical part of the dynamical chain of cause and effect governin...

Autism and Asperger Syndrome

Abstract: List of illustrations Acknowledgements 1. Asperger and his syndrome 2. 'Autistic psychopathy' in childhood 3. The relationship between Asperger's syndrome and Kanner's autism 4. Clinical and neurobiological aspects of Asperger syndrome in six family studies 5. Asperger syndrome in adulthood 6. Living with Asperger's syndrome 7. The autobiographical writings of three Asperger syndrome adults: problems of interpretation and implications for theory Name index Subject index.

Animal welfare: concepts and measurement.

Abstract: The term “welfare” refers to the state of an individual in relation to its environment, and this can be measured. Both failure to cope with the environment and difficulty in coping are indicators of poor welfare. Suffering and poor welfare often occur together, but welfare can be poor without suffering and welfare should not be defined solely in terms of subjective experiences. The situations that result in poor welfare are reviewed in this study with special reference to those in which an hdividual lacks control over interactions with its environment. The indicators of poor welfare include the following: reduced life expectancy, impaired growth, impaired reproduction, body damage, disease, immunosup pression, adrenal activity, behavior anomalies, and self-narcotization. The uses of measures of responsiveness, stereotypies, and animal preferences in welfare assessment are discussed. The need to make direct measurement of poor welfare as well as to use sophisticated studies of animal preferences is emphasized.

Sexual selection and the potential reproductive rates of males and females

Abstract: PRONOUNCED sex differences in mating competition are a prominent feature of many animal breeding systems. These differences are widely attributed to sex differences in parental investment1,2which bias the ratio of sexually receptive females to males3 (the operational sex ratio), generating more intense competition between members of one sex, usually males3–5. Unfortunately, relative parental investment1 is usually impossible to measure in species where both sexes invest in their offspring6,7 and there is currently no empirical basis for predicting the pattern of mating competition in these species. In contrast, the potential rate of reproduction by males and females (measured as the maximum number of independent offspring that parents can produce per unit time) is both more directly related to the operational sex ratio and more easily estimated in natural populations7. Here we show that among species where males care for the young, the sex with the higher potential reproductive rate competes more intensely for mates than the sex with the lower potential rate of reproduction.

Crystal structure of insecticidal delta-endotoxin from Bacillus thuringiensis at 2.5 A resolution.

Abstract: The structure of the delta-endotoxin from Bacillus thuringiensis subsp. tenebrionis that is specifically toxic to Coleoptera insects (beetle toxin) has been determined at 2.5 A resolution. It comprises three domains which are, from the N- to C-termini, a seven-helix bundle, a three-sheet domain, and a beta sandwich. The core of the molecule encompassing all the domain interfaces is built from conserved sequence segments of the active delta-endotoxins. Therefore the structure represents the general fold of this family of insecticidal proteins. The bundle of long, hydrophobic and amphipathic helices is equipped for pore formation in the insect membrane, and regions of the three-sheet domain are probably responsible for receptor binding.

Dynamical effects of the cosmological constant.

Abstract: The possibility of measuring the density parameter OMEGA-0 and the cosmological constant lambda-0 = LAMBDA/(3H0(2)) using dynamical tests is explored in linear and non-linear theory. In linear theory we find that the rate of growth of the perturbations at the present epoch is approximated by f(z = 0) almost-equal-to-OMEGA-0(0.6) + 1/70 lambda-0(1 + 1/2 OMEGA-0). Therefore, dynamical tests such as infall around clusters and dipoles at the present epoch do not distinguish well between universes with and without a cosmological constant. At higher redshifts, the perturbations also depend mainly on the matter density at a particular epoch, f(z) almost-equal-to OMEGA-0.6(z), which has a strong dependence on lambda-0 at z almost-equal-to 0.5-2.0. Therefore, information on both parameters can be obtained by looking at clustering at different redshifts. In practice, however, the other observables also depend on the cosmology, and in some cases conspire to give a weak dependence on lambda-0. By using the non-linear spherical infall model for a family of Cold Dark Matter (CDM) power-spectra we also find that dynamics at z = 0 does not tell much about lambda-0. At higher redshifts there is unfortunately another conspiracy between conventional observables, which hides information about lambda-0. The final radius of a virialized cluster (relative to the turnaround radius) is approximated by R(f)/R(ta) almost-equal-to (1 - eta/2)/(2 - eta/2), where eta is the ratio of LAMBDA to the density at turn-around. Therefore a repulsive-LAMBDA gives a smaller final radius than a vanishing-LAMBDA.

Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells.

Abstract: We have used the nested polymerase chain reaction (PCR) combined with fluorescence-activated cell sorting to define sites of latency of human cytomegalovirus (HCMV) in the peripheral blood of healthy subjects. Peripheral blood mononuclear (PBM) cells were separated into T cell or non-T cell populations and monocytes, and were then analysed by PCR for the presence of HCMV DNA. In five of six seropositive subjects, HCMV was found predominantly in the non-T cell population. Further analysis suggested that the virus was present in adherent cells and CD14+ cells. In three of nine seronegative subjects we could demonstrate HCMV DNA, which we do not believe was due to contamination, reproducibly by PCR. In one of these seronegative subjects, HCMV DNA was present predominantly in the non-T cell fraction of PBM cells. No HCMV DNA was detectable in the remaining six seronegative subjects. We conclude that, within the PBM cells of normal asymptomatic seropositive and some seronegative subjects, HCMV is present predominantly in the monocyte fraction. In addition, the detection of HCMV sequences in seronegative subjects may indicate that infection with HCMV is more widespread than conventional seroepidemiology suggests.

General trends in oxygen stoichiometry effects on Tc in Bi and Tl superconductors

Abstract: We have previously shown that Tc for Bi2 (Sr, Ca)n+1CunO2n+4+δ (n=1, 2 and 3) varies with oxygen stoichiometry δ determined by annealing in a variety of oxygen partial pressures and temperatures. Annealing results are now also presented for several Tl-superconductors in the series Tlm(Ba, Sr)2Can−1CunO2n+m+2+δ, for both m=1 and 2, revealing two general results for this class of Bi or TI superconductors: (1) effects on Tc due to labile oxygen occur for all m=2 compounds but are absent in m = 1 compounds with Sr. m=1 compounds with Ba do have variable oxygen but the effects on the c-axis are the opposite to m=2 compounds. This suggests for the latter that the labile oxygen resides in interstitial sites within the Bi2O2 or Tl2O2 bi layers; (2) the hole concentration per Cu decreases in progressing from n = 1 to 2 to 3 in either class so that the parent n = 3 and n = 2 compounds lie respectively on the low- and high-hole concentration sides of the peak in Tc while the n = 1 compounds extend out into the non-superconducting domain at very high hole concentration.

The possibilities of accountability

Abstract: The concern of this paper is to extend the critique of accounting through an exploration of the more inclusive concept of accountability. The paper begins by stating the positive effects upon the individual of being held accountable, and then goes on to explore how different forms of accountability produce different senses of our self and our relationship to others. It is argued that hierarchical forms of accountability, in which accounting currently plays a central role, serve to produce and reproduce an individualized sense of self; a sense of the self as essentially solitary and singular, nervously preoccupied with how one is seen. These effects are contrasted with what are described as socializing forms of accountability which flourish in the informal spaces of organizations and which confirm self in a way that emphasizes the interdependence of self and others. The tensions and interdependencies between these two forms of accountability are then explored. It is argued that contemporary organizational accountability is constructed around an untenable and destructive split of ethical and strategic concerns to the detriment of both. The search for the possibilities of accountability should be oriented to the reconciliation of this divide.

Learning invariance from transformation sequences

Abstract: The visual system can reliably identify objects even when the retinal image is transformed considerably by commonly occurring changes in the environment. A local learning rule is proposed, which allows a network to learn to generalize across such transformations. During the learning phase, the network is exposed to temporal sequences of patterns undergoing the transformation. An application of the algorithm is presented in which the network learns invariance to shift in retinal position. Such a principle may be involved in the development of the characteristic shift invariance property of complex cells in the primary visual cortex, and also in the development of more complicated invariance properties of neurons in higher visual areas.

Forcing mechanisms of the Indian Ocean monsoon

Abstract: Sediments in the Arabian Sea provide biological, biogeochemical and lithogenic evidence of past changes in the Indian Ocean summer monsoon winds. For the past 350,000 years, this system has been externally forced by cyclical changes in solar radiation, and internally phase-locked to the transport of latent heat from the southern subtropical Indian Ocean to the Tibetan Plateau. In contrast to the results of general circulation models, these geological data suggest that the climate change associated with variability in global ice volume is not a primary factor in determining the strength and timing of the monsoon winds.

ML for the working programmer

Abstract: From the Publisher: In teaching the methods of functional programming--in particular, how to program in Standard ML, a functional language recently developed at Edinburgh University, the author shows how to use such concepts as lists, trees, higher-order functions and infinite data structures.

Medium-range structural order in covalent amorphous solids

Abstract: Despite their lack of long-range translational and orientational order, covalent amorphous solids can exhibit structural order over both short and medium length scales, the latter reaching to 20 A or so. Medium-range order is difficult to measure experimentally and to interpret unambiguously, but a variety of techniques have allowed several types of characteristic structural ordering to be identified and their origin elucidated.

Anatomy, pigmentation, ventral and dorsal subpopulations of the substantia nigra, and differential cell death in Parkinson's disease.

Abstract: In six control subjects pars compacta nerve cells in the ventrolateral substantia nigra had a lower melanin content than nerve cells in the dorsomedial region. This coincides with a natural anatomical division into ventral and dorsal tiers, which represent functionally distinct populations. In six cases of Parkinson's disease (PD) the ventral tier showed very few surviving nerve cells compared with preservation of cells in the dorsal tier. In 13 subjects without PD, but with nigral Lewy bodies and cell loss, the degenerative process started in the ventral tier, and spread to the dorsal tier. This pattern of selective degeneration of nigrostriatal neurons is not seen in ageing or after acute administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).