Showing papers by "University of York published in 1993"
TL;DR: The method has been applied to investigate the total plasma antioxidant capacity of neonates and how this may be compromised in prematurity, and an antioxidant ranking was established based on their reactivity relative to a 1.0 mmol/l Trolox standard.
Abstract: 1. A new method has been developed for measuring the total antioxidant capacity of body fluids and drug solutions, based on the absorbance of the ABTS.+ radical cation. 2. An automated method for use on a centrifugal analyser, as well as a manual method, is described. 3. The procedure has been applied to physiological antioxidant compounds and radical-scavenging drugs, and an antioxidant ranking was established based on their reactivity relative to a 1.0 mmol/l Trolox standard. 4. The Trolox equivalent antioxidant capacity of plasma from an adult reference population has been measured, and the method optimized and validated. 5. The method has been applied to investigate the total plasma antioxidant capacity of neonates and how this may be compromised in prematurity.
2,844 citations
TL;DR: The predicted functional properties of the pWD gene together with its strong homology to Mc1, genetic mapping data and identification of four independent disease–specific mutations, provide convincing evidence that pWD is the Wilson disease gene.
Abstract: Wilson disease (WD) is an autosomal recessive disorder characterized by the toxic accumulation of copper in a number of organs, particularly the liver and brain. As shown in the accompanying paper, linkage disequilibrium & haplotype analysis confirmed the disease locus to a single marker interval at 13q14.3. Here we describe a partial cDNA clone (pWD) which maps to this region and shows a particular 76% amino acid homology to the Menkes disease gene, Mc1. The predicted functional properties of the pWD gene together with its strong homology to Mc1, genetic mapping data and identification of four independent disease-specific mutations, provide convincing evidence that pWD is the Wilson disease gene.
1,245 citations
TL;DR: Age-specific prevalences are provided for nine disorders in a general population sample of ages 10-20 and the pattern of specific diagnoses varied greatly by both age and gender.
Abstract: Developmental aspects of psychiatric disorders may be inferred from patterns of age differences in prevalence. Age-specific prevalences are provided for nine disorders in a general population sample of ages 10-20. Age and gender patterns for several disorders suggest developmental stage-associated risks. These include oppositional disorder in both genders and conduct disorder and major depression in girls. Major depression shows a pattern suggestive of a role for the onset of puberty. The prevalence of one or more disorders did not differ by age or gender. However, the pattern of specific diagnoses varied greatly by both age and gender.
975 citations
TL;DR: It is suggested that equality of health should be the dominant principle and that equity in health care should therefore entail distributing care in such a way as to get as close as is feasible to an equal distribution of health.
756 citations
TL;DR: Testing a recent example of a general health measure designed to derive a single index, the Euroqol (EQ), and a comparison with a new, influential profile measure, the Short Form 36 (SF-36) Health Survey Instrument are presented.
Abstract: There is an interest in the consequences of deriving a single index measure of health for validity and sensitivity. This paper presents the results of testing a recent example of a general health measure designed to derive a single index, the Euroqol (EQ), and presents a comparison with a new, influential profile measure, the Short Form 36 (SF-36) Health Survey Instrument. The EQ and an anglicised version of the SF-36 health survey, both designed for self-completion, were included in a postal survey of a random sample of 1980 patients from two practice lists in Sheffield, UK. The response rate for the EQ questionnaire was 83%, and the rate of completion over 95%. Evidence was found for the construct validity of the EQ dimension responses and the derived total EQ health score in terms of distinguishing between groups with expected health differences. Considerable agreement was found between EQ responses and the total EQ score, and the UK SF-36 profile scores. There was substantial evidence of EQ being less sensitive at the ceiling (i.e. low levels of perceived ill-health) and throughout the range of health states. A recent restructuring of the EQ, may help overcome some of the problems with the physical dimensions by reducing their skewness.
708 citations
TL;DR: The findings suggest that the hyperph phosphorylation of τ in Alzheimer disease brain could result from a protein dephosphorylation defect in vivo, and the decrease in the phosphatase activities in Alzheimer diseased brains might also be involved in the formation of β‐amyloid by augmenting the amyloidogenic pathway processing of β-amyloids precursor protein.
Abstract: Microtubule-associated protein tau is known to be hyperphosphorylated in Alzheimer disease brain and this abnormal hyperphosphorylation is associated with an inability of tau to promote the assembly of microtubule in the affected neurons. Our previous studies demonstrated that abnormally phosphorylated tau could be dephosphorylated after treatment with alkaline phosphatase, thereby suggesting that the abnormal phosphorylation of tau might in part be the result of a deficiency of the phosphoprotein phosphatase system in patients with Alzheimer disease. In the present study we used 32P-labeled phosphorylase kinase and poly(Glu, Tyr) 4:1 as substrates to measure phosphoprotein phosphatase activities in Alzheimer disease and control brains. The activities of phosphoseryl/phosphothreonyl-protein phosphatase types 1, 2A, 2B, and 2C and of phosphotyrosyl-protein phosphatase in frontal gray and white matters from 13 Alzheimer brains were determined and compared with those from 12 age-matched control brains. The activities of type 1 phosphatase and phosphotyrosyl phosphatase in gray matter and of type 2A phosphatase in both gray and white matters were significantly lower in Alzheimer disease brains than in controls. These findings suggest that the hyperphosphorylation of tau in Alzheimer disease brain could result from a protein dephosphorylation defect in vivo. The decrease in the phosphatase activities in Alzheimer disease might also be involved in the formation of beta-amyloid by augmenting the amyloidogenic pathway processing of beta-amyloid precursor protein.
509 citations
TL;DR: In this paper, the authors used graphical analysis to provide a solid understanding of the residual term as a subarea of the Lorenz diagram and its implications for inequality decomposition analysis are considered.
Abstract: The Gini coefficient has long been thought unsuitable for inequality decomposition analysis because of a troublesome and little-understood residual term that occurs when subgroup income ranges overlap after the between-groups and within-groups contributions to inequality have been separated out. In this paper, graphical analysis is used to provide a solid understanding of the residual term as a subarea of the Lorenz diagram. Implications for inequality decomposition analysis are considered. Copyright 1993 by Royal Economic Society.
470 citations
TL;DR: This work developed yeast artificial chromosome and cosmid contigs, and microsatellite markers which span the WD gene region, and predicts that approximately half of all WD mutations will be rare in the American and Russian populations.
Abstract: Wilson disease (WD) is an autosomal recessive disorder of copper transport which map to chromosome 13q14.3. In pursuit of the WD gene, we developed yeast artificial chromosome and cosmid contigs, and microsatellite markers which span the WD gene region. Linkage disequilibrium and haplotype analysis of 115 WD families confined the disease locus to a single marker interval. A candidate cDNA clone was mapped to this interval which, as shown in the accompanying paper, is very likely the WD gene. Our haplotype and mutation analyses predict that approximately half of all WD mutations will be rare in the American and Russian populations.
455 citations
TL;DR: Estimates of the direct costs associated with the treatment of patients in England and Wales amount to some £420 million annually, and pharmaceutical costs represent a relatively small proportion of this total.
Abstract: Depression is one of the commonest conditions seen by general practitioners. Conventional treatments are typically drug based, and usually involve one of the tricyclic preparations. The evaluation of new treatments requires an understanding of the costs and benefits of existing alternatives, to provide a comparative framework for general practitioners and others concerned with the treatment and management of depressed patients. This paper presents estimates of the direct costs associated with the treatment of patients in England and Wales. These amount to some 420 million pounds annually. Pharmaceutical costs represent a relatively small proportion of this total. Substantial indirect costs are generated through lost productivity, and these may exceed 3 billion pounds.
430 citations
Book•
31 Dec 1993423 citations
Journal Article•
TL;DR: It is shown that both conformation and sequence-specific DNA binding of p53 translated in vitro can be modulated by metal chelators and oxidizing agents, which could represent an important mechanism for the control of p 53 function.
Abstract: The p53 protein is a transcription factor, the function of which is abrogated by oncogenic mutations which affect a flexible domain in the central portion of p53, altering its reactivity with conformation-specific antibodies. Here we show that both conformation and sequence-specific DNA binding of p53 translated in vitro can be modulated by metal chelators and oxidizing agents. Oxidation disrupted wild-type p53 conformation and inhibited DNA binding. Conversely, reduction favored folding of p53 into the wild-type form and restored DNA binding. Redox regulation of p53 protein conformation could represent an important mechanism for the control of p53 function.
TL;DR: The data confirm the association between AD and APO‐ε4 and support the hypothesis that the APO'ε4 allele either confers genetic susceptibility to AD or may be in linkage disequilibrium with another susceptibility locus and Ethnic variability in the allelic frequency of APO•ε4 in the elderly warrants further investigation.
Abstract: Apolipoprotein E (APO-E) binds to the beta-amyloid peptide and is present in senile neuritic plaques in Alzheimer's disease (AD). The epsilon 4 isoform of APO-E has been associated with both sporadic and familial late-onset AD, implying a causal role. Among patients and control subjects similar in age, gender, and ethnic group from the New York City community of Washington Heights-Inwood, we found that the odds ratio (OR) for AD associated with homozygosity for APO-epsilon 4 was 17.9 (95% confidence interval [CI], 4.6-69.8) and that associated with heterozygosity for APO-epsilon 4 was 4.2 (95% CI, 1.8-9.5) compared with persons with other APO-E genotypes. The association was stronger among patients with sporadic disease (OR = 10.3; 95% CI, 3.4-31.1) than among those with a family history of dementia in a first-degree relative (OR = 0.9; 95% CI, 0.1-13.5). The association between APO-epsilon 4 and AD did not differ according to age at onset ( or = 65), but appeared to vary across the 3 ethnic groups investigated (black, Hispanic, and white). Our data confirm the association between AD and APO-epsilon 4 and support the hypothesis that the APO-epsilon 4 allele either confers genetic susceptibility to AD or may be in linkage disequilibrium with another susceptibility locus. Ethnic variability in the allelic frequency of APO-epsilon 4 in the elderly warrants further investigation.
TL;DR: In this article, Governance, democracy, and development in the Third World: Governance and democracy in the third world, 1993, Vol. 14, No. 3, pp. 605-624.
Abstract: (1993). Governance, democracy and development in the Third World. Third World Quarterly: Vol. 14, No. 3, pp. 605-624.
Columbia University1, University of Miami2, University of Florida3, Washington University in St. Louis4, University of California, Los Angeles5, Harvard University6, NewYork–Presbyterian Hospital7, University of Louisville8, Cleveland Clinic9, Hospital of the University of Pennsylvania10, University of Arizona11, University of Pittsburgh12, Hackensack University Medical Center13, Schering-Plough14, University of York15
TL;DR: These four histological lesions are useful pathological parameters in the diagnosis of liver disease caused by HCV and are likely to be seen in HCV than in HBV infection.
TL;DR: D dopamine likely contributes significantly to the pathophysiology of depression, however, the role of dopamine in this syndrome must be understood in the context of existing theories involving other neurotransmitters which may act independently, and interact with dopamine and other neurochemicals, to contribute to depression.
Abstract: The dopamine hypothesis of schizophrenia and the emphasis on other neurotransmitters, most notably norepinephirne, serotonin, and acetylcholine, in the pathogenesis of depression, have focused attention away from substantial evidence implicating dopamine in affective disorders. The clinical evidence includes alterations in depressive symptoms with aging (concomitant with possible changes in dopamine metabolism), potential dopaminergic involvement in several subtypes of depression, similarities between some of the symptoms of Parkinson's disease and those of depression (including psychomotor retardation and diminished motivation), and potential dopaminergic abnormalities in seasonal mood disorder. The biochemical evidence in patients with deprission derives from studies of homovanillic acid, a dopamine metabolite, indicating diminished dopamine turnover. In addition, there is a considerable amount of pharmacologic evidence regarding the efficacy of antidepressants with dopaminergic effects in the treatment of depression. We conclude that dopamine likely contributes significantly to the pathophysiology of depression. However, the role of dopamine in this syndrome must be understood in the context of existing theories involving other neurotransmitters which may act independently, and interact with dopamine and other neurochemicals, to contribute to depression.
TL;DR: In this paper, the authors describe the construction and validation of a new scale for measuring coping strategies entitled the Coping Styles Questionnaire (CSQ), which extracts factors concerned with problem-solving, emotion (Emotional Coping, EMCOP), avoidance and distancing or detachment.
01 May 1993
TL;DR: Earcons have been shown to be an effective method for communicating information in a human-computer interface and some guidelines were drawn up for use in the creation of earcons.
Abstract: An evaluation of earcons was carried out to see whether they are an effective means of communicating information in sound. An initial experiment showed that earcons were better than unstructured bursts of sound and that musical timbres were more effective than simple tones. A second experiment was then carried out which improved upon some of the weaknesses shown up in Experiment 1 to give a significant improvement in recognition. From the results of these experiments some guidelines were drawn up for use in the creation of earcons. Earcons have been shown to be an effective method for communicating information in a human-computer interface.
TL;DR: In this paper, the authors present a case study of the impact of the publication of outcome performance data in the maternity services in the UK National Health Service and conclude that the expected distortions arising from reliance on performance indicator schemes may have significant dysfunctional consequences.
Abstract: SUMMARY
There is increased interest in the widespread dissemination of outcome performance data to secure enhanced strategic control of public sector organizations. This paper adumbrates the rationale for such schemes, and outlines the potential distortions induced by excessive reliance on outcome-related performance indicators, inferred from experience in the management control and Soviet literature. The paper gives an outline of the performance review process in the United Kingdom National Health Service, and presents the results of a case study of the impact of the publication of outcome performance data in the maternity services. The research detected many of the expected distortions arising from reliance on performance indicator schemes, and concludes that they may have significant dysfunctional consequences. The paper does not however advocate the abandonment of performance audit in the public sector. Instead, it warns that great attention should be given to the managerial incentives implicit in any strategic control scheme, and that the style with which the scheme is applied will have important bearings on its effectiveness.
TL;DR: Findings were that abused children had lower peer status and less positive reciprocity with peers chosen as friends; they were rated by peers as more aggressive and less cooperative and by parents and teachers as more disturbed; and their social networks showed more insularity, atypicality, and negativity.
Abstract: Social behavior and peer status of 87 physically abused 8-12-year-old urban children were compared with those of 87 case-matched nonmaltreated classmates. Peer nominations and peer ratings were collected in classrooms, social networks were assessed by child interview, family variables were assessed by interviewing mothers, and behavior problems were rated by parents and teachers. Significant findings were that abused children had lower peer status and less positive reciprocity with peers chosen as friends; they were rated by peers as more aggressive and less cooperative and by parents and teachers as more disturbed; and their social networks showed more insularity, atypicality, and negativity. Social behavior as perceived by peers accounted for a significant portion of the variance in social status; global disturbance measures did not add to this association. Results are discussed in terms of a context of family violence in the development of social maladjustment.
TL;DR: Hydroperoxides and catechols are described as novel reactive products of radical attack on proteins, and it is proposed that they constitute both a marker and a mechanism of age-related pathologies.
TL;DR: In this article, the post-tax Gini coefficient across groups of pre-tax equals reveals the separate contributions to the redistributive effect of an income tax of the effective schedule, the unequal treatment of equals arising from departures from this effective schedule (the horizontal effect), and the reranking of unequals as a result of such departures (the reranking effect).
Abstract: Decomposing the post-tax Gini coefficient across groups of pre-tax equals reveals the separate contributions to the redistributive effect of an income tax of (1) the effective schedule (the vertical effect), (2) the unequal treatment of equals arising from departures from this effective schedule (the horizontal effect), and (3) the reranking of unequals as a result of such departures (the reranking effect). The methodology is applied to U.K. microdata. Throughout the period 1978-91, reranking understates the (negative) contribution to redistributive effect of unequal tax treatment by about one third and is far outweighed by the vertical effect. Copyright 1994 by Royal Economic Society.
TL;DR: It is concluded that, for league tables to be useful, decision makers should be able to assess the relevance and reliability of the evidence in their own setting and improve the methodology of economic evaluation studies and the construction and use of league tables.
TL;DR: This first demonstration of an age-related shift in the scalp distribution of the novelty P3 elicited by auditory stimuli was associated with anAge-associated differences in scalp distribution and false-alarm rate are consistent with a change in frontal lobe activity with increasing age.
Abstract: Event-related brain potentials (ERPs) were recorded from young, middle-aged, and older adults to infrequent target and novel stimuli during a version of the oddball paradigm. Analyses of scalp distribution suggested that the shift to a more frontally oriented topography with increasing age was confined to the P3 component (as compared to N1 and P2) elicited by both target and novel stimuli. This first demonstration of an age-related shift in the scalp distribution of the novelty P3 elicited by auditory stimuli was associated with an age-related increase in the false-alarm rate to novel stimuli. These age-associated differences in scalp distribution and false-alarm rate are consistent with a change in frontal lobe activity with increasing age.
TL;DR: The arguments for and against standardization are reviewed, attempts to date are assessed, the main areas of agreement and disagreement on methods for economic evaluation are outlined, and recommendations for further work are made.
Abstract: There has been an exponential growth in the literature on economic evaluation in health care. As the range and quality of analytical work has improved, economic studies are becoming more influential with health care decision makers. The development of standards for economic evaluation methods would help maintain the scientific quality of studies, facilitate the comparison of economic evaluation results for different health care interventions, and assist in the interpretation of results from setting to setting. However, standardization might unnecessarily stifle methodological developments. This paper reviews the arguments for and against standardization, assesses attempts to date, outlines the main areas of agreement and disagreement on methods for economic evaluation, and makes recommendations for further work.
TL;DR: In this paper, the authors investigated whether the changes in colour and surface morphology recognized for large mammal bone can be observed on other vertebrate bone, and if so whether at the same temperatures.
TL;DR: This work provides a guide to the available algorithms in pre-run-time scheduling and considers what formulations of mathematical scheduling problems can be used to address some of the major concerns.
Abstract: The authors explain why pre-run-time scheduling is essential if one wishes to guarantee that timing constraints will be satisfied in a large complex hard-real-time system. They examine some of the major concerns in pre-run-time scheduling and consider what formulations of mathematical scheduling problems can be used to address those concerns. This work provides a guide to the available algorithms. >
TL;DR: The results are consistent with the hypothesis that severe head injury and genetic susceptibility are associated with AD and concur with current concepts regarding the role of amyloid in AD.
Abstract: We performed a community-based study to investigate the relationship of genetic susceptibility and head injury to Alzheimer's disease (AD) in 138 patients with AD and 193 healthy elderly control subjects. Data concerning presence or absence of dementia and certain exposures were also obtained from 799 first-degree relatives of the patients and 1,238 first-degree relatives of the control subjects. Adjusting for age, gender, and other risk factors, the odds ratio for AD associated with head injury was 3.7 (95% confidence interval [CI], 1.4-9.7). The association was highest for head injuries that occurred after age 70. The risk of AD was higher in first-degree relatives of patients with onset prior to age 70 than in relatives of control subjects (risk ratio [RR] = 2.5; 95% CI, 1.1-5.6). The risk was not increased for relatives of patients with onset of AD at age 70 or older. Compared with relatives without head injury, the risk of AD was increased among both head-injured relatives of patients (RR = 5.9; 95% CI, 2.3-14.8) and head-injured relatives of control subjects (RR = 6.9; 95% CI, 2.5-18.9). Our results are consistent with the hypothesis that severe head injury and genetic susceptibility are associated with AD. Both associations concur with current concepts regarding the role of amyloid in AD. Although we regard head injury, like genetic susceptibility, to be a putative risk factor for AD, the temporal relationship between head injury and AD warrants further investigation.
TL;DR: In this article, it was hypothesized that individuals may have a predisposition for "reinvestment" of controlled processing, which will lead to skill failure under stress as a result of disruption of the automatic functioning of the skill.
TL;DR: Some of the methodological problems surrounding cost effectiveness league tables are showed and how such difficulties could be reduced in future are shown.
Abstract: Decisions to allocate resources in health care are increasingly influenced by relative cost effectiveness. To warn decision makers of some of the pitfalls currently found in cost effectiveness league tables and to suggest how meaningful comparisons may be made between health care technologies a published league table was scrutinised by examining its sources. This showed some of the methodological problems surrounding such tables and how such difficulties could be reduced in future. The source studies in the table featured different years of origin, discount rates, health state evaluations, settings, and types of comparison programmes; all of these differences may raise problems for meaningful comparison. Decision makers need to assess the relative value for money of competing health care interventions. In the absence of systematic comparisons such assessments are likely to take place informally. This will probably have a worse risk-benefit trade off than the formalized use of league tables.
TL;DR: Results indicated that exercise was strongly related to weight preoccupation among women and men and that, among men, obsessive-compulsiveness was also positively related—findings which support claims that exercising and dieting tend to coexist, and they are associated with an obsessive-Compulsive personality profile.
Abstract: Efforts to understand the associations among exercising, personality factors, and disordered eating have been the focus of much debate. However, research has been plagued by inconsistent findings, and there is evidence that classification and measurement differences are fundamental to these problems. To date, there are no studies which have defined exercise as a multifaceted construct. The purposes of this study were to establish the factor structure of a questionnaire developed to assess the core features believed to characterize excessive exercisers and to assess relationships between exercise (operationally defined as a function of behaviors and attitudes) and a number of putative risk factors. Results indicated that exercise was strongly related to weight preoccupation among women and men and that, among men, obsessive-compulsiveness was also positively related--findings which support claims that exercising and dieting tend to coexist, and they are associated with an obsessive-compulsive personality profile.