Showing papers by "Newcastle University published in 2002"

Estimating prokaryotic diversity and its limits

Abstract: The absolute diversity of prokaryotes is widely held to be unknown and unknowable at any scale in any environment. However, it is not necessary to count every species in a community to estimate the number of different taxa therein. It is sufficient to estimate the area under the species abundance curve for that environment. Log-normal species abundance curves are thought to characterize communities, such as bacteria, which exhibit highly dynamic and random growth. Thus, we are able to show that the diversity of prokaryotic communities may be related to the ratio of two measurable variables: the total number of individuals in the community and the abundance of the most abundant members of that community. We assume that either the least abundant species has an abundance of 1 or Preston's canonical hypothesis is valid. Consequently, we can estimate the bacterial diversity on a small scale (oceans 160 per ml; soil 6,400-38,000 per g; sewage works 70 per ml). We are also able to speculate about diversity at a larger scale, thus the entire bacterial diversity of the sea may be unlikely to exceed 2 x 10(6), while a ton of soil could contain 4 x 10(6) different taxa. These are preliminary estimates that may change as we gain a greater understanding of the nature of prokaryotic species abundance curves. Nevertheless, it is evident that local and global prokaryotic diversity can be understood through species abundance curves and purely experimental approaches to solving this conundrum will be fruitless.

The anatomical basis of functional localization in the cortex

Abstract: The functions of a cortical area are determined by its extrinsic connections and intrinsic properties. Using the database CoCoMac, we show that each cortical area has a unique pattern of corticocortical connections — a ‘connectional fingerprint’. We present examples of such fingerprints and use statistical analysis to show that no two areas share identical patterns. We suggest that the connectional fingerprint underlies the observed cell-firing differences between areas during different tasks. We refer to this pattern as a ‘functional fingerprint’ and present examples of such fingerprints. In addition to electrophysiological analysis, functional fingerprints can be determined by functional brain imaging. We argue that imaging provides a useful way to define such fingerprints because it is possible to compare activations across many cortical areas and across a wide range of tasks.

Camassa-Holm, Korteweg-de Vries and related models for water waves

Abstract: In this paper we first describe the current method for obtaining the Camassa–Holm equation in the context of water waves; this requires a detour via the Green–Naghdi model equations, although the important connection with classical (Korteweg–de Vries) results is included. The assumptions underlying this derivation are described and their roles analysed. (The critical assumptions are, (i) the simplified structure through the depth of the water leading to the Green–Naghdi equations, and, (ii) the choice of submanifold in the Hamiltonian representation of the Green–Naghdi equations. The first of these turns out to be unimportant because the Green–Naghdi equations can be obtained directly from the full equations, if quantities averaged over the depth are considered. However, starting from the Green–Naghdi equations precludes, from the outset, any role for the variation of the flow properties with depth; we shall show that this variation is significant. The second assumption is inconsistent with the governing equations.)Returning to the full equations for the water-wave problem, we retain both parameters (amplitude, e, and shallowness, δ) and then seek a solution as an asymptotic expansion valid for, e → 0, δ → 0, independently. Retaining terms O(e), O(δ2) and O(eδ2), the resulting equation for the horizontal velocity component, evaluated at a specific depth, is a Camassa–Holm equation. Some properties of this equation, and how these relate to the surface wave, are described; the role of this special depth is discussed. The validity of the equation is also addressed; it is shown that the Camassa–Holm equation may not be uniformly valid: on suitably short length scales (measured by δ) other terms become important (resulting in a higher-order Korteweg–de Vries equation, for example). Finally, we indicate how our derivation can be extended to other scenarios; in particular, as an example, we produce a two-dimensional Camassa–Holm equation for water waves.

Reduced-Median-Network Analysis of Complete Mitochondrial DNA Coding-Region Sequences for the Major African, Asian, and European Haplogroups

Abstract: The evolution of the human mitochondrial genome is characterized by the emergence of ethnically distinct lineages or haplogroups. Nine European, seven Asian (including Native American), and three African mitochondrial DNA (mtDNA) haplogroups have been identified previously on the basis of the presence or absence of a relatively small number of restriction-enzyme recognition sites or on the basis of nucleotide sequences of the D-loop region. We have used reduced-median-network approaches to analyze 560 complete European, Asian, and African mtDNA coding-region sequences from unrelated individuals to develop a more complete understanding of sequence diversity both within and between haplogroups. A total of 497 haplogroup-associated polymorphisms were identified, 323 (65%) of which were associated with one haplogroup and 174 (35%) of which were associated with two or more haplogroups. Approximately one-half of these polymorphisms are reported for the first time here. Our results confirm and substantially extend the phylogenetic relationships among mitochondrial genomes described elsewhere from the major human ethnic groups. Another important result is that there were numerous instances both of parallel mutations at the same site and of reversion (i.e., homoplasy). It is likely that homoplasy in the coding region will confound evolutionary analysis of small sequence sets. By a linkage-disequilibrium approach, additional evidence for the absence of human mtDNA recombination is presented here.

Leber hereditary optic neuropathy

Abstract: Leber hereditary optic neuropathy (LHON) is a mitochondrial genetic disease that preferentially causes blindness in young adult males, affecting about 1 in 25 000 of the British population. It is characterised by bilateral subacute loss of central vision owing to focal degeneration of the retinal ganglion cell layer and optic nerve. Over 95% of LHON cases are primarily the result of one of three mitochondrial DNA (mtDNA) point mutations, G3460A, G11778A, and T14484C, which all involve genes encoding complex I subunits of the respiratory chain. An intriguing feature of LHON is that only approximately 50% of males and approximately 10% of females who harbour a pathogenic mtDNA mutation actually develop the optic neuropathy. This marked incomplete penetrance and gender bias imply that additional mitochondrial and/or nuclear genetic factors must be modulating the phenotypic expression of LHON. It is also likely that environmental factors contribute to the onset of visual failure. However, these secondary precipitating factors remain poorly defined at present. In this review, we describe the natural history of this optic nerve disorder and highlight issues relating to clinical diagnosis, management, and genetic counselling. We also discuss the findings of recently published studies and the light they shed on the complex aetiology and pathophysiology of LHON.

Systematic review of cost effectiveness studies of telemedicine interventions.

Abstract: Objectives: To systematically review cost benefit studies of telemedicine. Design: Systematic review of English language, peer reviewed journal articles. Data sources: Searches of Medline, Embase, ISI citation indexes, and database of Telemedicine Information Exchange. Studies selected: 55 of 612 identified articles that presented actual cost benefit data. Main outcome measures: Scientific quality of reports assessed by use of an established instrument for adjudicating on the quality of economic analyses. Results: 557 articles without cost data categorised by topic. 55 articles with data initially categorised by cost variables employed in the study and conclusions. Only 24/55 (44%) studies met quality criteria justifying inclusion in a quality review. 20/24 (83%) restricted to simple cost comparisons. No study used cost utility analysis, the conventional means of establishing the “value for money” that a therapeutic intervention represents. Only 7/24 (29%) studies attempted to explore the level of utilisation that would be needed for telemedicine services to compare favourably with traditionally organised health care. None addressed this question in sufficient detail to adequately answer it. 15/24 (62.5%) of articles reviewed here provided no details of sensitivity analysis, a method all economic analyses should incorporate. Conclusion: There is no good evidence that telemedicine is a cost effective means of delivering health care.

Prospective multicentre randomised trial of tension-free vaginal tape and colposuspension as primary treatment for stress incontinence

Abstract: Objective To compare tension›free vaginal tape with colposuspension as primary treatment for stress incontinence. Design Multicentred randomised comparative trial. Setting Gynaecology or urology departments in 14 centres in the United Kingdom and Eire, including university teaching hospitals and district general

Changing physicians' behavior: what works and thoughts on getting more things to work.

Abstract: Health services research consistently demonstrates a gap between research-based best clinical practice and what doctors actually do. Traditionally, the profession of medicine has behaved as if dissemination of research findings in peer-reviewed journals will eliminate this gap, even though professionals typically have less than 1 hour per week to read. This problem is complicated by the fact that physicians have not been trained generally to appraise published research, which is of variable quality in any event. Physicians interested in changing their practices also encounter organizational, peer group, and individual barriers at the same time as they face information overload and patient expectations. In a word, physicians' abilities to manage information is overwhelmed. This article both summarizes initiatives to improve physicians' information management through efforts to synthesize available evidence and describes the current evidence base of effectiveness and efficiency of dissemination and implementation strategies. We conclude that there is an imperfect evidence base to support decisions regarding strategies that are likely to be appropriate and effective under varying circumstances. Since this problem is compounded by the lack of a theoretical base for conceptualizing physician behavior change, we suggest exploring the applicability of behavioral theories to the understanding of professional behavior change. We also suggest exploring the use of theory-based process evaluations alongside randomized trials of dissemination and implementation strategies to further test theories and to explore causal mechanisms. Further research is required to explore determinants of provider behavior to better identify modifiable and non-modifiable effect modifiers, to develop methods of identifying barriers and facilitators to change, and to estimate the efficiency of dissemination and implementation strategies in the presence of different barriers and effect modifiers.

Linearly concatenated cyclobutane lipids form a dense bacterial membrane

Abstract: Lipid membranes are essential to the functioning of cells, enabling the existence of concentration gradients of ions and metabolites. Microbial membrane lipids can contain three-, five-, six- and even seven-membered aliphatic rings, but four-membered aliphatic cyclobutane rings have never been observed. Here we report the discovery of cyclobutane rings in the dominant membrane lipids of two anaerobic ammonium-oxidizing (anammox) bacteria. These lipids contain up to five linearly fused cyclobutane moieties with cis ring junctions. Such 'ladderane' molecules are unprecedented in nature but are known as promising building blocks in optoelectronics. The ladderane lipids occur in the membrane of the anammoxosome, the dedicated intracytoplasmic compartment where anammox catabolism takes place. They give rise to an exceptionally dense membrane, a tight barrier against diffusion. We propose that such a membrane is required to maintain concentration gradients during the exceptionally slow anammox metabolism and to protect the remainder of the cell from the toxic anammox intermediates. Our results further illustrate that microbial membrane lipid structures are far more diverse than previously recognized.

Ischemic basis for deep white matter hyperintensities in major depression: a neuropathological study.

Abstract: Background White matter hyperintensities on magnetic resonance imaging are increased in major depression in the deep white matter, especially in frontal areas. These lesions have been hypothesized to be ischemic in origin, but there have been no previous neuropathological studies in depression. We investigated the neuropathological basis of these lesions in depression, hypothesizing that they would be more frequently ischemic in origin in depressed subjects. Methods We carried out in vitro magnetic resonance imaging on 3 slices of brain tissue (2 frontal, 1 occipital) from 20 elderly subjects who had a history of major depression and 20 elderly controls. The films were blindly rated, and sections were prepared for neuropathological analysis from the same slices and stained conventionally and by means of immunohistochemistry for microglia, macrophages, and astroglia. Lesions on the films were identified in the tissue, blindly described neuropathologically, and subsequently divided into ischemic and nonischemic lesions. Results All the deep white matter hyperintensities in the depressed group were found to be ischemic, compared with less than a third of those in the control group, a highly significant difference (P Conclusions Deep white matter hyperintensities are more frequently due to cerebral ischemia, and such ischemic lesions are more frequently located at the level of dorsolateral prefrontal cortex in depressed subjects. Our findings strongly support the "vascular depression" hypothesis of late-life depression.

Central auditory processing disorders.

Abstract: Central auditory processing is essential for the perception of speech, environmental sounds and music, and may be deranged in two ways. Lesions of the ascending auditory pathway or cortex can produce deficits. Abnormal activity of the central auditory system is becoming increasingly recognized in disorders such as tinnitus. Recent work has investigated sound processing by the unconscious brain; such investigations may provide a 'window' into residual brain function and prognosis.

Detection and quantification of mitochondrial DNA deletions in individual cells by real-time PCR

Abstract: Defects of mitochondrial DNA (mtDNA) are an important cause of disease and play a role in the ageing process. There are multiple copies of the mitochondrial genome in a single cell. In many patients with acquired or inherited mtDNA mutations, there exists a mixture of mutated and wild type genomes (termed heteroplasmy) within individual cells. As a biochemical and clinical defect is only observed when there are high levels of mutated mtDNA, a crucial investigation is to determine the level of heteroplasmic mutations within tissues and individual cells. We have developed an assay to determine the relative amount of deleted mtDNA using real-time fluorescence PCR. This assay detects the vast majority of deleted molecules, thus eliminating the need to develop specific probes. We have demonstrated an excellent correlation with other techniques (Southern blotting and three- primer competitive PCR), and have shown this technique to be sensitive to quantify the level of deleted mtDNA molecules in individual cells. Finally, we have used this assay to investigate patients with mitochondrial disease and shown in individual skeletal muscle fibres that there exist different patterns of abnormalities between patients with single or multiple mtDNA deletions. We believe that this technique has significant advantages over other methods to quantify deleted mtDNA and, employed alongside our method to sequence the mitochondrial genome from single cells, will further our understanding of the role of mtDNA mutations in human disease and ageing.

In situ dissection of the graft-versus-host activities of cytotoxic T cells specific for minor histocompatibility antigens

Abstract: Minor histocompatibility antigens (mHags) are immunogenic peptides from polymorphic cellular proteins that induce strong T-cell responses after human leukocyte antigen (HLA)-matched, mHag-mismatched stem-cell transplantation. mHags with broad or limited tissue expression are target antigens for graft-versus-host (GvH) and graft-versus-leukemia (GvL) reactivities. Separation of these activities is crucial for adoptive immunotherapy of leukemia without GvH disease. Therefore, using a skin-explant assay we investigated the in situ activities of cytotoxic T lymphocytes (CTLs) specific for the ubiquitously expressed mHag H-Y and for the hematopoietic-restricted mHags HA-1 and HA-2. H-Y-specific CTLs, visualized by tetrameric HLA-mHag peptide complexes, infiltrated male skin sections within 24 hours, induced severe GvH reactions of grade III-IV and produced high levels of IFN-gamma. In contrast, CTLs specific for the hematopoietic system-specific mHags HA-1 and HA-2 induced no or low GvH reactions above background and produced little or no interferon-gamma, unless the skin sections were preincubated with HA-1/HA-2 synthetic peptides. These results provide the first in situ dissection of GvH effects by mHag-specific CTLs and show that ubiquitously expressed mHags are the prime targets of GvH disease.

Characterization of the bacterial consortium associated with black band disease in coral using molecular microbiological techniques.

Abstract: The bacterial community associated with black band disease (BBD) of the scleractinian corals Diploria strigosa, Montastrea annularis and Colpophyllia natans was examined using culture-independent techniques. Two complementary molecular screening techniques of 16S rDNA genes [amplified 16S ribosomal DNA restriction analysis (ARDRA) of clone libraries and denaturing gradient gel electrophoresis (DGGE)] were used to give a comprehensive characterization of the community. Findings support previous studies indicating low bacterial abundance and diversity associated with healthy corals. A single cyanobacterial ribotype was present in all the diseased samples, but this was not the same as that identified from Phormidium corallyticum culture isolated from BBD. The study confirms the presence of Desulfovibrio spp. and sulphate-reducing bacteria that have previously been associated with the BBD consortium. However, the species varied between diseased coral samples. We found no evidence of bacteria from terrestrial, freshwater or human sources in any of the samples. We report the presence of previously unrecognized potential pathogens [a Cytophaga sp. and an alpha-proteobacterium identified as the aetiological agent of juvenile oyster disease (JOD)] that were consistently present in all the diseased coral samples. The molecular biological approach described here gives an increasingly comprehensive and more precise picture of the bacterial population associated with BBD. To understand the pathogenesis of BBD, our attention should be focused on the pervasive ribotypes identified in this study (the Cyanobacterium sp., the Cytophaga sp. and the JOD pathogen).

Podocyte Number in Normotensive Type 1 Diabetic Patients With Albuminuria

Abstract: We estimated glomerular cell number in 50 normotensive type 1 diabetic patients with raised albumin excretion rate (AER) and investigated any change after 3 years in a subgroup of 16 placebo-treated patients. Biopsies from 10 normal kidney donors were used as controls. Mesangial and endothelial cell number was increased in the 50 diabetic patients at the start of the study compared with control subjects. There was no difference in podocyte number. Glomerular volume was increased in diabetic patients, but surface area of glomerular basement membrane (GBM) underlying the podocytes did not differ between groups. AER correlated positively with mesangial cell number in microalbuminuric patients (r = 0.44, P = 0.012) and negatively with podocyte number in proteinuric patients (r = -0.48, P = 0.040). In the 16 placebo-treated patients, glomerular volume increased after 3 years owing to matrix accumulation and increased GBM surface area. Although overall cell number did not differ significantly from baseline, the decrease in podocyte number during follow-up correlated with AER at follow-up (r = -0.72, P = 0.002). In conclusion, cross-sectional analysis of podocyte number in type 1 diabetic patients with raised AER but normal blood pressure shows no significant reduction compared with nondiabetic control subjects. Longitudinal data provide evidence for an association between podocyte loss and AER, but whether cellular changes are a response to, a cause of, or concomitant with the progression of nephropathy remains uncertain.

Physical activity and its relationship with obesity, hypertension and diabetes in urban and rural Cameroon

Abstract: Objectives: To evaluate and compare physical activity patterns of urban and rural dwellers in Cameroon, and study their relationship with obesity, diabetes and hypertension Methods: We studied 2465 subjects aged ≥15 y, recruited on the basis of a random sampling of households, of whom 1183 were urban dwellers from Yaounde, the capital city of Cameroon and 1282 rural subjects from Bafut, a village of western Cameroon They all had an interviewer-administered questionnaire for the assessment of their physical activity and anthropometric measurements, blood pressure and fasting blood glucose determination The procedure was satisfactorily completed in 2325 (943%) subjects Prevalences were age-adjusted and subjects compared according to their region, sex and age group Results: Obesity was diagnosed in 171 and 30% urban and rural women, respectively (P<0001), and in 54 vs 12% urban and rural men, respectively (P<0001) The prevalence of hypertension was significantly higher in urban vs rural dwellers (114 vs 66% and 176 vs 91% in women and men, respectively; P<0001) Diabetes was more prevalent in urban compared to rural women (P<005), but not men Urban subjects were characterized by lower physical activity (P<0001), light occupation, high prevalence of multiple occupations, and reduced walking and cycling time compared to rural subjects Univariate analysis showed significant associations between both physical inactivity and obesity and high blood pressure The relationship of physical inactivity with hypertension and obesity were independent in both urban and rural men, but not in women Body mass index, blood pressure and glycaemia were higher in the first compared with the fourth quartiles of energy expenditure Conclusion: Obesity, diabetes and hypertension prevalence is higher in urban compared to rural dwellers in the populations studied Physical activity is significantly lower and differs in pattern in urban subjects compared to rural Physical inactivity is associated with these diseases, although not always significant in women

Sickness absence: an international comparison*

Abstract: This paper shows how internationally and intertemporally consistent information on sickness absence can be constructed from Labour Force Surveys, and describes some important features of data that we have generated using the Luxembourg Employment Study. We also analyse sickness absence rates by age, gender and other socio-economic characteristics of workers. These relationships prove to be similar across countries with widely differing mean rates of absence. In this dataset, workers with longer tenure tend to have higher absence rates even when age is controlled for. Absence is also positively correlated with higher usual hours of work. We show how internationally and intertemporally consistent information on sickness absence can be constructed from Labour Force Surveys (LFS), and describe some important features of data that we have generated using the Luxembourg Employment Study (LES). Such data fill an important gap in available information about absence, since they have the potential to provide answers to a number of issues that remain unresolved in its study. There is now substantial evidence, going back to the work of the Industrial Fatigue Research Board in the 1920s and 1930s,I that sickness absence is not purely a response to a medical condition. Workers who have access to compensation payments are more likely to be absent than those without (Buzzard and Shaw, 1952); the higher the rate of compensation, the more absences workers are likely to take (Buzzard and Shaw, 1952); furthermore, the higher the rate of compensation, the longer absences are likely to be (Barmby et al., 1991). The analysis of sickness absence is placed firmly in the agenda of economics by the idea that sickness absence rates are the consequence of choices that can be mediated by financial (and other) incentives. The provision and level of sickpay is typically determined at two levels: by negotiation between firms and their workforces, and by government regulation. Interfirm variations in absence and their correlates are not well understood. Coles and Treble (1996) have argued that the marginal cost of an absence is partially in the control of firms, and can be usefully seen as driven by the nature of the technology adopted. These theoretical arguments remain largely unexplored empirically, but the ability to compare similar industries across different countries is likely to be revealing. * This paper was drafted during a visit to CEPS/INSTEAD in the Summer of 1999. The research was funded by a grant of the European Commission under the TMR Programme, Access to Large Scale Facilities, hosted by IRISS-C/I at CEPS/INSTEAD in Differdange, Luxembourg. We are also grateful for support from the Leverhulme Foundation through a grant to the Institute for Labour Research at the University of Essex and to colleagues at the ILR for their constructive comments. Acknowledgements to LES data providers are given at the end of the paper. We would also like to thank Paul Alkemade, Elena Bardasi and Pascal Garin for their help. Any remaining errors are our own, and the views expressed herein are not necessarily those of CEPS/INSTEAD. 1 See, for example, Vernon and Bedford (1928).

Adsorption of metal ions on nitrogen surface functional groups in activated carbons

Abstract: A commercially available coconut-shell-derived active carbon was oxidized with nitric acid, and both the original and oxidized active carbons were treated with ammonia at 1073 K to incorporate nitrogen functional groups into the carbon. An active carbon with very high nitrogen content (∼9.4 wt % daf) was also prepared from a nitrogen-rich precursor, polyacrylonitrile (PAN). These nitrogen-rich carbons had points of zero charge (pHpzc) similar to H-type active carbons. X-ray absorption near-edge structure (XANES) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, and temperature-programmed desorption (TPD) were used to characterize the nitrogen functional groups in the carbons. The nitrogen functional groups present on the carbon surface were pyridinic, pyrrolic (or indolic), and pyridonic structures. The adsorption of transition metal cations Cd2+, Ni2+, and Cu2+ from aqueous solution on the suite of active carbons showed that adsorption was markedly higher for carbons with nitrogen functional ...

Genotype at a promoter polymorphism of the interleukin-6 gene is associated with baseline levels of plasma C-reactive protein.

Abstract: Objective: Baseline concentrations of plasma C-reactive protein (CRP) are associated with coronary heart disease. Interleukin-6 (IL-6) regulates CRP gene expression; a promoter polymorphism (–174G/C) of the IL-6 gene has been shown to influence IL-6 transcription but the relationship between genotype at this polymorphism and circulating levels of inflammatory markers remains unclear. We hypothesised that plasma CRP would be a heritable phenotype that would be influenced by genotype at this polymorphism. Methods: We measured baseline plasma CRP and determined genotypes at the –174G/C polymorphism of the IL-6 gene in 588 members of 98 nuclear families. The heritability of plasma CRP and the association of plasma CRP with genotype were determined using variance components methods. Results: Baseline CRP levels were highly heritable ( h 2=0.39, P <0.0000001). Presence of the –174C allele was associated with higher baseline CRP levels, both in the whole population ( P =0.01), and in the founders only ( n =128, P =0.001). Family-based analyses confirmed the association ( P =0.02) suggesting that it arises from chromosomal proximity or identity of the typed polymorphism with a genetic variant influencing baseline CRP levels. Conclusions: Baseline plasma CRP is a significantly heritable cardiovascular risk factor. Levels are associated with genotype at the –174G/C polymorphism of the IL-6 gene.