Showing papers by "Newcastle University published in 1990"

Analysis of serial measurements in medical research.

Abstract: In medical research data are often collected serially on subjects. The statistical analysis of such data is often inadequate in two ways: it may fail to settle clinically relevant questions and it may be statistically invalid. A commonly used method which compares groups at a series of time points, possibly with t tests, is flawed on both counts. There may, however, be a remedy, which takes the form of a two stage method that uses summary measures. In the first stage a suitable summary of the response in an individual, such as a rate of change or an area under a curve, is identified and calculated for each subject. In the second stage these summary measures are analysed by simple statistical techniques as though they were raw data. The method is statistically valid and likely to be more relevant to the study questions. If this method is borne in mind when the experiment is being planned it should promote studies with enough subjects and sufficient observations at critical times to enable useful conclusions to be drawn. Use of summary measures to analyse serial measurements, though not new, is potentially a useful and simple tool in medical research.

Diatoms and pH Reconstruction

Abstract: Palaeolimnological diatom data comprise counts of many species expressed as percentages for each sample. Reconstruction of past lake-water pH from such data involves two steps; (i) regression, where responses of modern diatom abundances to pH are modelled and (ii) calibration where the modelled responses are used to infer pH from diatom assemblages preserved in lake sediments. In view of the highly multivariate nature of diatom data, the strongly nonlinear response of diatoms to pH, and the abundance of zero values in the data, a compromise between ecological realism and computational feasability is essential. The two numerical approaches used are (i) the computationally demanding but formal statistical approach of maximum likelihood (ML) Gaussian logit regression and calibration and (ii) the computationally straightforward but heuristic approach of weighted averaging (WA) regression and calibration. When the Surface Water Acidification Project (SWAP) modern training set of 178 lakes is reduced by data-screening to 167 lakes, WA gives superior results in terms of lowest root mean squared errors of prediction in cross-validation. Bootstrapping is also used to derive prediction errors, not only for the training set as a whole but also for individual pH reconstructions by WA for stratigraphic samples from Round Loch of Glenhead, southwest Scotland covering the last 10 000 years. These reconstructions are evaluated in terms of lack-of-fit to pH and analogue measures and are interpreted in terms of rate of change by using bootstrapping of the reconstructed pH time-series.

The Re-Emergence of Regional Economies? The Mythical Geography of Flexible Accumulation:

Abstract: A critique of the potential of industrial districts for local and regional development in the present period is developed It focuses particularly on the influential arguments being put forward by

The epidermal growth factor receptor and the prognosis of bladder cancer

Abstract: Epidermal growth factor is found in high concentrations in urine, and its receptor (EGFr) has been identified in certain bladder tumors. This study was performed to determine whether receptor positivity in the tumor was associated with a poor clinical outcome. One hundred one patients with newly diagnosed bladder cancer were studied prospectively by immunohistochemical staining for the EGFr. There were 76 men and 25 women, with a mean follow-up of 30 months; 49 had tumors invading muscle: 18 were pTl (tumor invading lamina propia) and 34 were pTa (tumor confined to urothelium). Strong staining for the EGFr was found in 48% of tumors and was associated with high stage (P less than 0.001). Death of bladder cancer (40 of 101) was associated independently with high stage (P less than 0.0001) and EGFr positivity (P less than 0.001). In patients with pTa and pTl tumors, EGFr positivity was associated with multiplicity (P less than 0.01), time to recurrence (P less than 0.03), and recurrence rate (P less than 0.004). Tumor progression was associated with EGFr positivity (P less than 0.0001) and multiplicity (P less than 0.05). EGFr were found on a significant proportion of bladder tumors: such tumors were more likely to result in death, recurrence, and progression.

Stability theory for differential/algebraic systems with application to power systems

Abstract: Motivated by transient stability analysis of power systems, a framework for study of Lyapunov stability of equilibria in differential/algebraic (DA) systems is presented. Following a basic result on existence and uniqueness of solutions, it is easy to state general stability results. Several useful stability criteria for special DA structures are derived. One result for a Hamiltonian-type structure is applied to the study of undamped power systems. >

A review of calcium hydroxide

Abstract: Summary. Calcium hydroxide is a material which has been used for a variety of purposes since its introduction into dentistry in the early part of the twentieth century. In its pure form, the substance has a high pH, and its dental use relates chiefly to its ability to stimulate mineralization, and also to its antibacterial properties. A range of products has been formulated with different therapeutic actions, the effects of which are partially dependent upon the tissue to which they are applied. The material is reviewed under the following general headings: biochemical actions; dental formulation; uses.

Damage and recovery of coral reefs affected by El Niño related seawater warming in the Thousand Islands, Indonesia

Abstract: Extensive coral bleaching occurred during sea-water warming (as a result of the 1982/3 El Nino Southern Oscillation event) in 1983 on the shallow reefs in the Java Sea. Mean seawater temperatures rose by 2–3° C over a six month period with values greater than 33° C being recorded between 1200–1500 h. As many as 80–90% of corals died on the reef flats at the study sites, with the major casualties being branching species in the genera Acropora and Pocillopora. Five years after the event the community structure of the study sites has recovered significantly, though coral cover is still 50% of its former level. Contrasting patterns of recovery at two selected sites, in close proximity to each other, are discussed.

Structure and Agency in Land and Property Development Processes : Some Ideas for Research

Abstract: This paper reviews existing approaches to, and research on, land and property development processes. It is argued that while these approaches-institutional analysis, neo-classical location theory and land economics, and Marxist economics-provide useful directions for understanding the development process, they lack the capability to address a fundamental dimension of our understanding of development processes. This is the relation between the way actors behave in deploying resources to realise specific investments, with which much of the real estate literature is concerned, and the broader processes which drive the strategies and interests of the various actors involved. The paper proposes an approach which combines an understanding of structure and agency, focusing on the resources, rules and ideology which actors acknowledge, as a way forward to a richer understanding of land and property development processes. The paper concludes with some key research questions which follow from this perspective.

Localizing multiple X chromosome-linked retinitis pigmentosa loci using multilocus homogeneity tests

Abstract: Multilocus linkage analysis of 62 family pedigrees with X chromosome-linked retinitis pigmentosa (XLRP) was undertaken to determine the presence of possible multiple disease loci and to reliably estimate their map location. Multilocus homogeneity tests furnished convincing evidence for the presence of two XLRP loci, the likelihood ratio being 6.4 x 10(9):1 in favor of two versus a single XLRP locus and gave accurate estimates for their map location. In 60-75% of the families, location of an XLRP gene was estimated at 1 centimorgan distal to OTC, and in 25-40% of the families, an XLRP locus was located halfway between DXS14 (p58-1) and DXZ1 (Xcen), with an estimated recombination fraction of 25% between the two XLRP loci. There is also good evidence for a third XLRP locus, midway between DXS28 (C7) and DXS164 (pERT87), supported by a likelihood ratio of 293:1 for three versus two XLRP loci.

Myth and reality.

Abstract: Draft amendments to the Organic Foods Production Act of 1990 (OFPA) are currently being circulated for possible incorporation in to the Fiscal Year 2006 Agriculture Appropriation Bill to be considered by the full Senate in the near future. These amendments are being portrayed as minor clarifications of the Act necessitated by a recent adverse court ruling, and a return to the current “status quo.” Nothing could be farther from the truth. The justification for immediate action, and representations about potential adverse impact on the organic food industry make broad assumptions and are not supported by fact. These amendments in no way represent a consensus position of the industry as farmer, consumer and environmental organizations that have always been the core of the organic coalition had no input in the drafting of this proposal. It also ignores a pending rule-making petition before the USDA, which provides regulatory remedies that could be implemented quickly and without opening the law.

Xylanase B and an arabinofuranosidase from Pseudomonas fluorescens subsp. cellulosa contain identical cellulose-binding domains and are encoded by adjacent genes.

Abstract: The complete nucleotide sequence of the Pseudomonas fluorescens subsp. cellulosa xynB gene, encoding an endo-beta-1,4-xylanase (xylanase B; XYLB) has been determined. The structural gene consists of an open reading frame (ORF) of 1775 bp coding for a protein of Mr 61,000. A second ORF (xynC) of 1712 bp, which starts 148 bp downstream of xynB, encodes a protein, designated xylanase C (XYLC), of Mr 59,000. XYLB hydrolyses oat spelt xylan to xylobiose and xylose, whereas XYLC releases only arabinose from the same substrate. Thus XYLB is a typical xylanase and XYLC is an arabinofuranosidase. Both enzymes bind to crystalline cellulose (Avicel), but not to xylan. The nucleotide sequences between residues 114 and 931 of xynB and xynC were identical, as were amino acid residues 39-311 of XYLB and XYLC. This conserved sequence is reiterated elsewhere in the P. fluorescens subsp. cellulosa genome. Truncated derivatives of XYLB and XYLC, in which the conserved sequence had been deleted, retained catalytic activity, but did not exhibit cellulose binding. A hybrid gene in which the 5' end of xynC, encoding residues 1-110 of XYLC, was fused to the Escherichia coli pho A' gene (encodes mature alkaline phosphatase) directed the synthesis of a fusion protein which exhibited alkaline phosphatase activity and bound to cellulose.

Impaired glucose tolerance.

Abstract: The classification of abnormalities of glucose tolerance introduced in 1979 by the National Diabetes Data Group and agreed by the World Health Organisation included the category of impaired glucose tolerance.' 2 The diagnosis depends on the blood glucose concentration two hours after a glucose load being above normal (6-7 mmol/l) and below the new diabetic value (10 mmol/l). This category satisfied a need for defining a level of glucose intolerance that was not clearly normal but that was also not sufficiently severe to predict microvascular disease, particularly retinopathy, in prospective studies. As a group, people with impaired glucose tolerance have raised concentrations of insulin both when fasting and after a glucose load3`5 and show insulin resistance when investigated with glucose clamp techniques.46 Several studies of the natural course in people with impaired glucose tolerance have shown that they are at increased risk of developing diabetes (table I),7-2' but there is less consensus about the excess risk of cardiovascular disease.22-27 Recently Saad et al reported an extremely high incidence of non-insulin dependent diabetes in Pima Indians with impaired glucose tolerance,'9 the rate of deterioration to diabetes of 5-6% a year over 10 years exceeding the rates of 1F5-4% reported in most studies in other populations. 10-12 1517 In a separate paper the same authors show that even \"transient\" impaired glucose tolerance is associated with an increased risk of \"deterioration to diabetes.\"20 Other recent studies have, however, cast doubt on the concept of impaired glucose tolerance, both because of its ephemeral nature (table II)28-30 and as a consequence of doubts about whether it warrants categorisation as a separate entity.3' Stern et al analysed the concept of impaired glucose tolerance, suggesting that the category represented a heterogeneous group of people.32 They used the model of a population with a bimodal distribution of two hour blood glucose concentrations to propose that the category of impaired glucose tolerance will contain some people in the upper tail of normal glucose tolerance (\"impaired glucose tolerance normals\"), some in the lower tail of diabetic patients (\"false negative diabetics\"), and some who are truly in the impaired glucose tolerance category. If the distribution oftwo hour blood glucose concentration is bimodal Stern et al suggested that for the nadir to remain apparent few people must have true impaired glucose tolerance, and, therefore, the rate of deterioration through the impaired glucose tolerance category must be fairly rapid. For this reason they defined the third category as \"impaired glucose tolerance in transition.\" Although their model is derived from an analysis of the overlap of two modes of a bimodal population, we believe that it may be more widely applicable and that both the intraindividual variance of the test and the interindividual differences in the population may contribute to blurring the classification. In this article we analyse the concept of deterioration to diabetes and the instability of the impaired glucose tolerance class in the light of data on the variability of the biological response to a glucose load. We conclude that additional criteria are required to categorise people with impaired glucose tolerance and that measures of insulin and of proinsulin like molecules are possible candidates for this task.

A Revision of Sphenosuchus acutus Haughton, a Crocodylomorph Reptile from the Elliot Formation (Late Triassic or Early Jurassic) of South Africa

Abstract: A detailed description is given of the osteology of the holotype of Sphenosuchus. The skull, particularly the braincase, is excellently preserved and shows a wealth of anatomical detail. Sphenosuchus was one of the largest of the early crocodylomorphs, with a skull length of 192 mm and an estimated total length of 1.4 m. The primary head of the quadrate meets the prootic and squamosal but not the opisthotic (or laterosphenoid); quadrate and pterygoid are not fused to the braincase and the basipterygoid articulation is free. The braincase and some other skull bones are pneumatized. The otic capsule is crocodilian but the subcapsular buttress (ossified subcapsular process) does not enclose the vagus nerve or the internal carotid artery. The scapula blade is triangular; the coracoid has a long posteroventral extension which is thought to have articulated firmly with a large interclavicle. Clavicles were absent. Metatarsal I is reduced; metatarsals II and IV are symmetrical about III, which is longest. A paired series of dorsal scutes was present. Sphenosuchus is considered to have been cursorial and carnivorous. Comparison is made between the pneumatic spaces in the Sphenosuchus skull and those of modern crocodiles and birds, and homologies are discussed. Representatives of the main cavities found in the crocodilian skull are present in the skull of Sphenosuchus, in some cases in a less clearly defined state. On the other hand, certain pneumatic spaces in the Sphenosuchus skull are not found in the modern crocodile but resemble cavities in the bird skull. The courses of the internal carotid and stapedial arteries are reconstructed; the latter is considered to have passed through the postquadrate foramen, temporal canal and anterior temporal foramen as it does in modern forms. The problem of the position of the stapedial artery in the crocodile is discussed. It is believed that enclosure of the artery took place as a result of the forward migration of the quadrate head, leading to the formation of a temporal canal. Detailed comparisons are made between the otic capsule of Sphenosuchus and those of modern crocodiles and birds, which it closely resembles. Changes in otic capsule structure in archosaurs to give the crocodilian or bird condition, starting from a primitive form like Euparkeria, are outlined. The skull is believed to have been kinetic, and the quadrate streptostylic, in the juvenile Sphenosuchus. The parts of the proximal end of the crocodilian quadrate are differentiated; in particular, the \`true' head is distinguished from the anterodorsal process. Although very reduced in the modern crocodile, the \`true' head is in the same morphological position as in Sphenosuchus; contact with the laterosphenoid has been brought about, not by further forward movement of the head, but by geniculation of the upper portion of the bone. The anterodorsal process is considered to have arisen as a result of the dorsal migration of an anterolateral projection somewhat similar to that of the thecodontian Stagonolepis. This change was also responsible for the elongation of the quadratojugal in crocodylomorphs. The validity of the order Crocodylomorpha is discussed. It is concluded that the most important steps in crocodylomorph evolution, particularly in the skull, had taken place in sphenosuchians, hence they should be included in the same taxon as protosuchians and more advanced crocodilians, rather than with thecodontians.

Avoidable factors contributing to death of children with head injury.

Abstract: OBJECTIVE--To assess the incidence of potentially avoidable complications contributing to death of children with head injuries. DESIGN--Retrospective review of children who died with head injuries from 1979 to 1986 from data of the Office of Population Censuses and Surveys, Hospital Activity Analyses, case notes, coroners9 records, and necropsy reports. SETTING--District general hospitals and two regional neurosurgical centres in Northern region. RESULTS--255 Children died from head injury in the region, the mortality being 5.3 per 100,000 children per year. Head injury was the single most important cause of death in children aged greater than 1 year, accounting for 15% of deaths in children aged 1-15 years and a quarter for those aged 5-15 years. 121 Potentially avoidable factors possibly or probably contributing to death occurred in 81 children (32%). Half the children (125) died before admission, 27 of whom (22%) had potentially avoidable factors possibly or probably contributing to death, and 130 died after admission, 54 of whom (42%) had 93 such factors, which included failure of diagnosis or delayed recognition of intracranial haemorrhage or associated injury, inadequate management of the airways, and poor management of the transfer between hospitals. IMPLICATIONS--Regions should revise urgently their guidelines for optimal management and indications for neurosurgical referral to include children with severe head injuries and audit their systems of care for all patients with head injuries.

Analysis of a Kanban discipline for cell coordination in production lines

Abstract: We describe and analyze a discipline called kanban for the coordination of cells in a large-scale manufacturing facility. There are many cells in a tandem configuration and a fixed number of cards or kanbans in Japanese usage in each cell. The cards circulate within the cell and their presence at designated positions signals to the neighboring cells the status of the cell's inventory; rules specify the timing of the movement of parts from cell to cell. We construct a stochastic model of the whole manufacturing facility and give our results in three parts. First, the kanban discipline is compared to the classical production discipline and it is shown to dominate the classical discipline in terms of throughput. Secondly, we give a scheme for analyzing approximately the performance of the kanban system by examining first a single cell in isolation and then combining the isolated cells through fixed-point equations. Thirdly, we report on extensive experiments and on their numerical results which are obtained from simulations and our method of analysis. The throughput-inventory relationship of the kanban scheme is observed to be superior to that of the classical discipline.

The Internationalization of R & D and the Development of Global Research Networks

Abstract: HOWELLS J. (1990) The internationalization of R & D and the development of global research networks, Reg. Studies 24, 495–512. The paper considers processes associated with, and conceptualization of, the internationalization of R & D, using the pharmaceuticals and chemical/energy sectors as ways of illustration. Wider issues relating to research internationalization are considered, including changes in the macro research and technological environment and the growth of inter-organizational research collaboration. Other wider organizational changes are considered, including the impact of information and communication technologies, in relation to research location and structure, before the paper concludes with a re-assessment of current conceptualization of R & D in light of these changes. HOWELLS J. (1990) L'internationalisation de la R et D, et le developpement de reseaux mondiaux pour la recherche, Reg. Studies 24, 495–512. Get article met en consideration les demarches necessaires a l'internationalisatio...

Reactivity of primary biliary cirrhosis sera with Escherichia coli dihydrolipoamide acetyltransferase (E2p): characterization of the main immunogenic region

Abstract: Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in the serum. The major antigens recognized by the antibodies are the E2 components of the 2-oxo acid dehydrogenase complexes, all of which possess covalently attached lipoic acid cofactors. A bacterial etiology has been proposed for the disease, and patients' antibodies are known to recognize the E2 subunits (E2p) of both mammalian and bacterial pyruvate dehydrogenase complexes. Immunoblotting and ELISA inhibition techniques using extracts of Escherichia coli deletion strains, genetically restructured E2 polypeptides, and isolated lipoyl domains demonstrate that (i) the E2o subunit of the E. coli 2-oxoglutarate dehydrogenase complex is recognized by patients' antibodies; (ii) the main immunogenic region of E2p lies within the lipoly domains; (iii) the presence of a lipoly residue within the domain is crucial for effective recognition by the antibodies; and (iv) octanoylated E2p, octanoylated E2o, and octanoylated lipoyl domain, produced by a mutant deficient in lipoate biosynthesis, are recognized by patients' antibodies but not as effectively as their lipoylated counterparts. These findings indicate that antibodies in PBC patients' sera bind to a unique peptide-cofactor conformation within the lipoyl domains of the E2 polypeptides and that this epitope is partially mimicked by substituting the lipoyl cofactor with an octanoyl group.

Prognostic significance of the estrogen-regulated protein, cathepsin D, in breast cancer: an immunohistochemical study

Abstract: Expression of the estrogen-regulated lysosomal protease, cathepsin D, was studied in a series of 94 breast cancers using an immunohistochemical technique. Granular staining of tumor cell cytoplasm was detected in 62 cases. Positive staining was associated with a significant increase in overall time to relapse and when survival was analyzed in terms of intensity of cathepsin D staining there was a significant trend for both increased time to relapse and increased length of survival. The presence of estrogen receptor was associated with positive cathepsin D immunostaining, and in the subgroup of estrogen receptor-positive tumors cathepsin D staining was associated with significantly prolonged survival; this was not the case for estrogen receptor-negative tumors. Positive cathepsin D immunostaining was associated with significant prognostic advantage in patients with confirmed lymph node metastasis but not in node-negative patients. It is suggested that cathepsin D expression reflects the functional integrity of the estrogen response pathway. Cathepsin D may prove a clinically useful adjunct to assessment of estrogen receptor status.

Heterogeneity of dystrophin expression in patients with Duchenne and Becker muscular dystrophy

Abstract: This report documents the results of an integrated biochemical and immunocytochemical investigation into the expression of dystrophin (the protein product of the Duchenne muscular dystrophy gene) in muscle biopsies from 226 patients. It is the first study in which dystrophin has been analysed on blots and on tissue sections in such a large number of patients using the same (monoclonal) antibody. The 140 patients with Xp21 muscular dystrophy who were included in this study represent a continuous spectrum of disease severity and this range was reflected in the heterogeneity of dystrophin expression which was observed with respect to abundance, size and the pattern of tissue localisation. Approximately 40% of biopsies obtained from patients diagnosed as having Duchenne muscular, dystrophy (DMD) contained isolated clearly positive fibres and a further 20% had very weak labelling on a large number of fibres. Biopsies from patients with Becker muscular dystrophy (BMD) showed labelling patterns which varied from weak labelling on the majority of fibres to clear labelling on all fibres. Typically, however, there was inter-and intra-fibre variation in labelling intensity. Approximately 85% of the 52 BMD and 54 DMD patients who had unequivocal labelling on blots demonstrated a protein of abnormal size. The remaining 15% had a protein of normal size but reduced abundance. Overall, the estimated abundance of dystrophin correlated well with clinical assessments of the disease severity expressed in patients: We conclude that dystrophin analysis is an essential and dependable technique for the differential diagnosis of patients with Xp21 muscular dystrophy.

'Lost and found': some logical and methodological limitations of self-report questionnaires as tools to study cognitive ageing.

Abstract: Laboratory tests show a decline in memory efficiency with age, but may not reflect highly practiced everyday memory skills. Self-rating questionnaires probe memory efficiency in everyday life, but seven logical and methodological problems ambiguate interpretation of the data they yield. To explore these problems, 442 volunteers aged from 50 to 85 years were given the AH 4 IQ tests, Mill Hill Vocabulary Tests, Beck Depression Inventory (BDI), Broadbent Cognitive Failures Questionnaire (CFQ), Sunderland & Harris Memory Failure Questionnaire (MFQ), the 'Lost and Found' Questionnaire (LF, a new domain-specific probe of the variety, frequency and aetiologies of losses of possessions) and two laboratory memory tests. All self-rating questionnaire scores correlated modestly with each other. Counter-intuitively, individuals over 60 years old reported fewer lapses on the LF and on the CFQ. No SRQ scores correlated with performance on laboratory tasks. CFQ scores did not correlate with IQ test scores but high IQ test scorers reported greater recent decline in memory efficiency (MFQ) and greater current frequency of losses of objects (LF). CFQ and LF scores correlated positively with Beck Depression Inventory scores, suggesting some common loading for poor self-regard. The results suggest that subjective self-ratings cannot reflect absolute levels of everyday competence, but only the relative success of individuals' adaptations to idiosyncratic environments which, as they age, may change faster than their abilities. However, besides exposing the limitations of self-report techniques, these analyses also suggest practical ways of adapting and using SRQs which may allow us to gain better insights into changes and individual differences in functional efficiency in everyday life.

The Discharge of Elderly Patients from an Accident and Emergency Department: Functional Changes and Risk of Readmission

Abstract: Four hundred and fifty patients aged 75 years or older were followed up after discharge from an accident and emergency department. Forty-three per cent of all patients experienced some loss of functional independence. A small number, 5.6%, were readmitted to hospital within 14 days. This group were significantly less able to perform certain activities of daily living than those not readmitted. Attention to functional assessment by casualty staff may help to prevent readmission to hospital of this frail elderly group of patients.

Epidemiology of diabetes in Asians of the Indian subcontinent

Abstract: Asians from the Indian subcontinent have received greater attention in diabetes studies because of their migration in large numbers. The prevalence of non-insulin-dependent diabetes mellitus (NIDDM) in migrant Indians is higher than that in the population residing in the Indian subcontinent and is also usually higher than in the other racial groups in the host country. However, before drawing any conclusions with reference to the high prevalence of NIDDM in the migrant Indians, careful comparisons are required with more up-to-date information available from the Indian subcontinent itself. Recent data from India indeed indicate that the prevalence rates have either been underestimated in the past or are rising. The problem is compounded by the different diagnostic criteria used for defining diabetes. Some of the possible factors which cause variations in the rates of NIDDM in this population are discussed.

Stability of black holes in de Sitter space.

Abstract: The theory of black-hole perturbations is extended to charged black holes in de Sitter space. These spacetimes have wormholes connecting different asymptotic regions. It appears that, at least in some cases, these holes are stable even at the Cauchy horizon. It follows that they violate cosmic censorship and an observer could in principle travel through the black hole to another universe. The stability of these spacetimes also implies the existence of a cosmological "no hair" theorem.