Showing papers by "University of Manchester published in 2005"

Two-dimensional gas of massless Dirac fermions in graphene

Abstract: Quantum electrodynamics (resulting from the merger of quantum mechanics and relativity theory) has provided a clear understanding of phenomena ranging from particle physics to cosmology and from astrophysics to quantum chemistry. The ideas underlying quantum electrodynamics also influence the theory of condensed matter, but quantum relativistic effects are usually minute in the known experimental systems that can be described accurately by the non-relativistic Schrodinger equation. Here we report an experimental study of a condensed-matter system (graphene, a single atomic layer of carbon) in which electron transport is essentially governed by Dirac's (relativistic) equation. The charge carriers in graphene mimic relativistic particles with zero rest mass and have an effective 'speed of light' c* approximately 10(6) m s(-1). Our study reveals a variety of unusual phenomena that are characteristic of two-dimensional Dirac fermions. In particular we have observed the following: first, graphene's conductivity never falls below a minimum value corresponding to the quantum unit of conductance, even when concentrations of charge carriers tend to zero; second, the integer quantum Hall effect in graphene is anomalous in that it occurs at half-integer filling factors; and third, the cyclotron mass m(c) of massless carriers in graphene is described by E = m(c)c*2. This two-dimensional system is not only interesting in itself but also allows access to the subtle and rich physics of quantum electrodynamics in a bench-top experiment.

Two-dimensional atomic crystals

Abstract: We report free-standing atomic crystals that are strictly 2D and can be viewed as individual atomic planes pulled out of bulk crystals or as unrolled single-wall nanotubes. By using micromechanical cleavage, we have prepared and studied a variety of 2D crystals including single layers of boron nitride, graphite, several dichalcogenides, and complex oxides. These atomically thin sheets (essentially gigantic 2D molecules unprotected from the immediate environment) are stable under ambient conditions, exhibit high crystal quality, and are continuous on a macroscopic scale.

Consumption and Theories of Practice

Abstract: The huge corpus of work on consumption still lacks theoretical consolidation. This is most obvious when contemplating the situations of different disciplines, where there is very little common ground (see, for example, the review in Miller 1995). But the problem is no less great in individual disciplines like sociology, for example, where output seems to me to have been bipolar, generating either abstract and speculative social theory or detailed case studies. Moreover, case studies have been skewed towards favourite, but restricted, topics—fashion, advertising and some forms of popular recreational activity—with particular attention paid to their symbolic meanings and role in the formation of self-identity. These case studies, perhaps encouraged by prominent versions of the abstract theories which say that the consumer has no choice but to choose and will be judged in terms of the symbolic adequacy of that choice (e.g. Bauman 1988; Giddens 1991), very often operated with models of highly autonomous individuals preoccupied with symbolic communication. Believing that these approaches give a partial understanding of consumption, this chapter sketches an alternative, avoiding methodological individualist accounts of ‘the consumer’, which are concerned as much with what people do and feel as what they mean.

Realist review - a new method of systematic review designed for complex policy interventions

Abstract: Evidence-based policy is a dominant theme in contemporary public services but the practical realities and challenges involved in using evidence in policy-making are formidable. Part of the problem is one of complexity. In health services and other public services, we are dealing with complex social interventions which act on complex social systems--things like league tables, performance measures, regulation and inspection, or funding reforms. These are not 'magic bullets' which will always hit their target, but programmes whose effects are crucially dependent on context and implementation. Traditional methods of review focus on measuring and reporting on programme effectiveness, often find that the evidence is mixed or conflicting, and provide little or no clue as to why the intervention worked or did not work when applied in different contexts or circumstances, deployed by different stakeholders, or used for different purposes. This paper offers a model of research synthesis which is designed to work with complex social interventions or programmes, and which is based on the emerging 'realist' approach to evaluation. It provides an explanatory analysis aimed at discerning what works for whom, in what circumstances, in what respects and how. The first step is to make explicit the programme theory (or theories)--the underlying assumptions about how an intervention is meant to work and what impacts it is expected to have. We then look for empirical evidence to populate this theoretical framework, supporting, contradicting or modifying the programme theories as it goes. The results of the review combine theoretical understanding and empirical evidence, and focus on explaining the relationship between the context in which the intervention is applied, the mechanisms by which it works and the outcomes which are produced. The aim is to enable decision-makers to reach a deeper understanding of the intervention and how it can be made to work most effectively. Realist review does not provide simple answers to complex questions. It will not tell policy-makers or managers whether something works or not, but will provide the policy and practice community with the kind of rich, detailed and highly practical understanding of complex social interventions which is likely to be of much more use to them when planning and implementing programmes at a national, regional or local level.

Diabetic neuropathies: a statement by the American Diabetes Association.

Abstract: The diabetic neuropathies are heterogeneous, affecting different parts of the nervous system that present with diverse clinical manifestations. They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor distal symmetric polyneuropathy (DPN) and the autonomic neuropathies. DPN is a diagnosis of exclusion. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons. 1 ) Nondiabetic neuropathies may be present in patients with diabetes. 2 ) A number of treatment options exist for symptomatic diabetic neuropathy. 3 ) Up to 50% of DPN may be asymptomatic, and patients are at risk of insensate injury to their feet. As >80% of amputations follow a foot ulcer or injury, early recognition of at-risk individuals, provision of education, and appropriate foot care may result in a reduced incidence of ulceration and consequently amputation. 4 ) Autonomic neuropathy may involve every system in the body. 5 ) Autonomic neuropathy causes substantial morbidity and increased mortality, particularly if cardiovascular autonomic neuropathy (CAN) is present. Treatment should be directed at underlying pathogenesis. Effective symptomatic treatments are available for the manifestations of DPN and autonomic neuropathy. This statement is based on two recent technical reviews (1,2), to which the reader is referred for detailed discussion and relevant references to the literature. An internationally agreed simple definition of DPN for clinical practice is “the presence of symptoms and/or signs of peripheral nerve dysfunction in people with diabetes after the exclusion of other causes” (3). However, the diagnosis cannot be made without a careful clinical examination of the lower limbs, as absence of symptoms should never be assumed to indicate an absence of signs. This definition conveys the important message that not all patients with peripheral nerve dysfunction have a neuropathy caused by diabetes. Confirmation can be established with …

Body mass index as a predictor of fracture risk: A meta-analysis

Abstract: Low body mass index (BMI) is a well-documented risk factor for future fracture. The aim of this study was to quantify this effect and to explore the association of BMI with fracture risk in relation to age, gender and bone mineral density (BMD) from an international perspective using worldwide data. We studied individual participant data from almost 60,000 men and women from 12 prospective population-based cohorts comprising Rotterdam, EVOS/EPOS, CaMos, Rochester, Sheffield, Dubbo, EPIDOS, OFELY, Kuopio, Hiroshima, and two cohorts from Gothenburg, with a total follow-up of over 250,000 person years. The effects of BMI, BMD, age and gender on the risk of any fracture, any osteoporotic fracture, and hip fracture alone was examined using a Poisson regression model in each cohort separately. The results of the different studies were then merged. Without information on BMD, the age-adjusted risk for any type of fracture increased significantly with lower BMI. Overall, the risk ratio (RR) per unit higher BMI was 0.98 (95% confidence interval [CI], 0.97–0.99) for any fracture, 0.97 (95% CI, 0.96–0.98) for osteoporotic fracture and 0.93 (95% CI, 0.91–0.94) for hip fracture (all p 0.30). After adjusting for BMD, these RR became 1 for any fracture or osteoporotic fracture and 0.98 for hip fracture (significant in women). The gradient of fracture risk without adjustment for BMD was not linearly distributed across values for BMI. Instead, the contribution to fracture risk was much more marked at low values of BMI than at values above the median. This nonlinear relation of risk with BMI was most evident for hip fracture risk. When compared with a BMI of 25 kg/m2, a BMI of 20 kg/m2 was associated with a nearly twofold increase in risk ratio (RR=1.95; 95% CI, 1.71–2.22) for hip fracture. In contrast, a BMI of 30 kg/m2, when compared with a BMI of 25 kg/m2, was associated with only a 17% reduction in hip fracture risk (RR=0.83; 95% CI, 0.69–0.99). We conclude that low BMI confers a risk of substantial importance for all fractures that is largely independent of age and sex, but dependent on BMD. The significance of BMI as a risk factor varies according to the level of BMI. Its validation on an international basis permits the use of this risk factor in case-finding strategies.

Childhood trauma, psychosis and schizophrenia: a literature review with theoretical and clinical implications

Abstract: Objective: To review the research addressing the relationship of childhood trauma to psychosis and schizophrenia, and to discuss the theoretical and clinical implications. Method: Relevant studies and previous review papers were identified via computer literature searches. Results: Symptoms considered indicative of psychosis and schizophrenia, particularly hallucinations, are at least as strongly related to childhood abuse and neglect as many other mental health problems. Recent large-scale general population studies indicate the relationship is a causal one, with a dose-effect. Conclusion: Several psychological and biological mechanisms by which childhood trauma increases risk for psychosis merit attention. Integration of these different levels of analysis may stimulate a more genuinely integrated bio-psycho-social model of psychosis than currently prevails. Clinical implications include the need for staff training in asking about abuse and the need to offer appropriate psychosocial treatments to patients who have been abused or neglected as children. Prevention issues are also identified.

The relationship between job satisfaction and health: a meta-analysis

Abstract: Background: A vast number of published studies have suggested a link between job satisfaction levels and health. The sizes of the relationships reported vary widely. Narrative overviews of this relationship have been published, but no systematic meta-analysis review has been conducted. Methods: A systematic review and meta-analysis of 485 studies with a combined sample size of 267 995 individuals was conducted, evaluating the research evidence linking self-report measures of job satisfaction to measures of physical and mental wellbeing. Results: The overall correlation combined across all health measures was r = 0.312 (0.370 after Schmidt- Hunter adjustment). Job satisfaction was most strongly associated with mental/psychological problems; strongest relationships were found for burnout (corrected r = 0.478), self-esteem(r = 0.429), depression (r = 0.428), and anxiety(r = 0.420). The correlation with subjective physical illness was more modest (r = 0.287). Conclusions: Correlations in excess of 0.3 are rare in this context. The relationships found suggest that job satisfaction level is an important factor influencing the health of workers. Organisations should include the development of stress management policies to identify and eradicate work practices that cause most job dissatisfaction as part of any exercise aimed at improving employee health. Occupational health clinicians should consider counselling employees diagnosed as having psychological problems to critically evaluate their work—and help them to explore ways of gaining greater satisfaction from this important aspect of their life.

Association Between Duration of Untreated Psychosis and Outcome in Cohorts of First-Episode Patients: A Systematic Review

Abstract: Context Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. Objectives To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. Data Sources The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Study Selection Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data Extraction Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Data Synthesis Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. Conclusions There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.

Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus

Abstract: Aspergillus fumigatus is exceptional among microorganisms in being both a primary and opportunistic pathogen as well as a major allergen. Its conidia production is prolific, and so human respiratory tract exposure is almost constant. A. fumigatus is isolated from human habitats and vegetable compost heaps. In immunocompromised individuals, the incidence of invasive infection can be as high as 50% and the mortality rate is often about 50% (ref. 2). The interaction of A. fumigatus and other airborne fungi with the immune system is increasingly linked to severe asthma and sinusitis. Although the burden of invasive disease caused by A. fumigatus is substantial, the basic biology of the organism is mostly obscure. Here we show the complete 29.4-megabase genome sequence of the clinical isolate Af293, which consists of eight chromosomes containing 9,926 predicted genes. Microarray analysis revealed temperature-dependent expression of distinct sets of genes, as well as 700 A. fumigatus genes not present or significantly diverged in the closely related sexual species Neosartorya fischeri, many of which may have roles in the pathogenicity phenotype. The Af293 genome sequence provides an unparalleled resource for the future understanding of this remarkable fungus.

Predictive Value of BMD for Hip and Other Fractures

Abstract: The relationship between BMD and fracture risk was estimated in a meta-analysis of data from 12 cohort studies of approximately 39,000 men and women. Low hip BMD was an important predictor of fracture risk. The prediction of hip fracture with hip BMD also depended on age and z score. INTRODUCTION: The aim of this study was to quantify the relationship between BMD and fracture risk and examine the effect of age, sex, time since measurement, and initial BMD value. MATERIALS AND METHODS: We studied 9891 men and 29,082 women from 12 cohorts comprising EVOS/EPOS, EPIDOS, OFELY, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, DOES, Hiroshima, and 2 cohorts from Gothenburg. Cohorts were followed for up to 16.3 years and a total of 168,366 person-years. The effect of BMD on fracture risk was examined using a Poisson model in each cohort and each sex separately. Results of the different studies were then merged using weighted coefficients. RESULTS: BMD measurement at the femoral neck with DXA was a strong predictor of hip fractures both in men and women with a similar predictive ability. At the age of 65 years, risk ratio increased by 2.94 (95% CI = 2.02-4.27) in men and by 2.88 (95% CI = 2.31-3.59) in women for each SD decrease in BMD. However, the effect was dependent on age, with a significantly higher gradient of risk at age 50 years than at age 80 years. Although the gradient of hip fracture risk decreased with age, the absolute risk still rose markedly with age. For any fracture and for any osteoporotic fracture, the gradient of risk was lower than for hip fractures. At the age of 65 years, the risk of osteoporotic fractures increased in men by 1.41 per SD decrease in BMD (95% CI = 1.33-1.51) and in women by 1.38 per SD (95% CI = 1.28-1.48). In contrast with hip fracture risk, the gradient of risk increased with age. For the prediction of any osteoporotic fracture (and any fracture), there was a higher gradient of risk the lower the BMD. At a z score of -4 SD, the risk gradient was 2.10 per SD (95% CI = 1.63-2.71) and at a z score of -1 SD, the risk was 1.73 per SD (95% CI = 1.59-1.89) in men and women combined. A similar but less pronounced and nonsignificant effect was observed for hip fractures. Data for ultrasound and peripheral measurements were available from three cohorts. The predictive ability of these devices was somewhat less than that of DXA measurements at the femoral neck by age, sex, and BMD value. CONCLUSIONS: We conclude that BMD is a risk factor for fracture of substantial importance and is similar in both sexes. Its validation on an international basis permits its use in case finding strategies. Its use should, however, take account of the variations in predictive value with age and BMD.

Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae

Abstract: The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.

The experience of work‐related stress across occupations

Abstract: Purpose – To compare the experience of occupational stress across a large and diverse set of occupations. Three stress related variables (psychological well‐being, physical health and job satisfaction) are discussed and comparisons are made between 26 different occupations on each of these measures. The relationship between physical and psychological stress and job satisfaction at an occupational level is also explored.Design/methodology/approach – The measurement tool used is a short stress evaluation tool which provides information on a number of work related stressors and stress outcomes. Out of the full ASSET database 26 occupations were selected for inclusion in this paper.Findings – Six occupations are reporting worse than average scores on each of the factors – physical health, psychological well‐being and job satisfaction (ambulance workers, teachers, social services, customer services – call centres, prison officers and police). Differences across and within occupational groups, for example, teac...

A statistical study of 233 pulsar proper motions

Abstract: We present and analyse a catalogue of 233 pulsars with proper motion measurements. The sample contains a wide variety of pulsars including recycled objects and those associated with globular clusters or supernova remnants. After taking the most precise proper motions for those pulsars for which multiple measurements are available, the majority of the proper motions (58 per cent) are derived from pulsar timing methods, 41 per cent using interferometers and the remaining 1 per cent using optical telescopes. Many of the one-dimensional (1D) and two-dimensional (2D) speeds (referring to speeds measured in one coordinate only and the magnitudes of the transverse velocities, respectively) derived from these measurements are somewhat lower than earlier estimates because of the use of the most recent electron density model in determining pulsar distances. The mean 1D speeds for the normal and recycled pulsars are 152(10) and 54(6) km s −1 , respectively. The corresponding mean 2D speeds are 246(22) and 87(13) km s −1 . PSRs B2011+38 and B2224+64 have the highest inferred 2D speeds of ∼1600 km s −1 .W estudy the mean speeds for different subsamples and find that, in general, they agree with previous results. Applying a novel deconvolution technique to the sample of 73 pulsars with characteristic ages less than 3 Myr, we find the mean threedimensional (3D) pulsar birth velocity to be 400(40) km s −1 . The distribution of velocities is well described by a Maxwellian distribution with 1D rms σ = 265 km s −1 . There is no evidence for a bimodal velocity distribution. The proper motions for PSRs B1830−08 and B2334+61 are consistent with their proposed associations with the supernova remnants W41 and G114.3+0.3, respectively. Ke yw ords: stars: kinematics ‐ pulsars: general.

Genome sequencing and analysis of Aspergillus oryzae

Abstract: The genome of Aspergillus oryzae, a fungus important for the production of traditional fermented foods and beverages in Japan, has been sequenced. The ability to secrete large amounts of proteins and the development of a transformation system have facilitated the use of A. oryzae in modern biotechnology. Although both A. oryzae and Aspergillus flavus belong to the section Flavi of the subgenus Circumdati of Aspergillus, A. oryzae, unlike A. flavus, does not produce aflatoxin, and its long history of use in the food industry has proved its safety. Here we show that the 37-megabase (Mb) genome of A. oryzae contains 12,074 genes and is expanded by 7-9 Mb in comparison with the genomes of Aspergillus nidulans and Aspergillus fumigatus. Comparison of the three aspergilli species revealed the presence of syntenic blocks and A. oryzae-specific blocks (lacking synteny with A. nidulans and A. fumigatus) in a mosaic manner throughout the genome of A. oryzae. The blocks of A. oryzae-specific sequence are enriched for genes involved in metabolism, particularly those for the synthesis of secondary metabolites. Specific expansion of genes for secretory hydrolytic enzymes, amino acid metabolism and amino acid/sugar uptake transporters supports the idea that A. oryzae is an ideal microorganism for fermentation.

Metabolomics: Current analytical platforms and methodologies

Abstract: During the previous decade, a new array of analytical methodologies and technologies were introduced related to the analysis of microbial, plant and animal metabolomes (complete collections of all low molecular weight compounds in a cell). The scientific field of metabolomics was born. In this review, we discuss advances in methodologies and technologies, and outline applications.

Substitution of doctors by nurses in primary care

Abstract: Background Demand for primary care services has increased in developed countries due to population ageing, rising patient expectations, and reforms that shift care from hospitals to the community. At the same time, the supply of physicians is constrained and there is increasing pressure to contain costs. Shifting care from physicians to nurses is one possible response to these challenges. The expectation is that nurse-doctor substitution will reduce cost and physician workload while maintaining quality of care. Objectives Our aim was to evaluate the impact of doctor-nurse substitution in primary care on patient outcomes, process of care, and resource utilisation including cost. Patient outcomes included: morbidity; mortality; satisfaction; compliance; and preference. Process of care outcomes included: practitioner adherence to clinical guidelines; standards or quality of care; and practitioner health care activity (e.g. provision of advice). Resource utilisation was assessed by: frequency and length of consultations; return visits; prescriptions; tests and investigations; referral to other services; and direct or indirect costs. Search methods The following databases were searched for the period 1966 to 2002: Medline; Cinahl; Bids, Embase; Social Science Citation Index; British Nursing Index; HMIC; EPOC Register; and Cochrane Controlled Trial Register. Search terms specified the setting (primary care), professional (nurse), study design (randomised controlled trial, controlled before-and-after-study, interrupted time series), and subject (e.g. skill mix). The searches for this review were conducted in 2002 and are now out-of-date and therefore the review findings should be used with caution. The review is currently being updated and the updated version should be published before the end of 2014. Selection criteria Studies were included if nurses were compared to doctors providing a similar primary health care service (excluding accident and emergency services). Primary care doctors included: general practitioners, family physicians, paediatricians, general internists or geriatricians. Primary care nurses included: practice nurses, nurse practitioners, clinical nurse specialists, or advanced practice nurses. Data collection and analysis Study selection and data extraction was conducted independently by two reviewers with differences resolved through discussion. Meta-analysis was applied to outcomes for which there was adequate reporting of intervention effects from at least three randomised controlled trials. Semi-quantitative methods were used to synthesize other outcomes. Main results 4253 articles were screened of which 25 articles, relating to 16 studies, met our inclusion criteria. In seven studies the nurse assumed responsibility for first contact and ongoing care for all presenting patients. The outcomes investigated varied across studies so limiting the opportunity for data synthesis. In general, no appreciable differences were found between doctors and nurses in health outcomes for patients, process of care, resource utilisation or cost. In five studies the nurse assumed responsibility for first contact care for patients wanting urgent consultations during office hours or out-of-hours. Patient health outcomes were similar for nurses and doctors but patient satisfaction was higher with nurse-led care. Nurses tended to provide longer consultations, give more information to patients and recall patients more frequently than did doctors. The impact on physician workload and direct cost of care was variable. In four studies the nurse took responsibility for the ongoing management of patients with particular chronic conditions. The outcomes investigated varied across studies so limiting the opportunity for data synthesis. In general, no appreciable differences were found between doctors and nurses in health outcomes for patients, process of care, resource utilisation or cost. Authors' conclusions The findings suggest that appropriately trained nurses can produce as high quality care as primary care doctors and achieve as good health outcomes for patients. However, this conclusion should be viewed with caution given that only one study was powered to assess equivalence of care, many studies had methodological limitations, and patient follow-up was generally 12 months or less. While doctor-nurse substitution has the potential to reduce doctors' workload and direct healthcare costs, achieving such reductions depends on the particular context of care. Doctors' workload may remain unchanged either because nurses are deployed to meet previously unmet patient need or because nurses generate demand for care where previously there was none. Savings in cost depend on the magnitude of the salary differential between doctors and nurses, and may be offset by the lower productivity of nurses compared to doctors.

Relations in biomedical ontologies

Abstract: To enhance the treatment of relations in biomedical ontologies we advance a methodology for providing consistent and unambiguous formal definitions of the relational expressions used in such ontologies in a way designed to assist developers and users in avoiding errors in coding and annotation. The resulting Relation Ontology can promote interoperability of ontologies and support new types of automated reasoning about the spatial and temporal dimensions of biological and medical phenomena.

Cationic antiseptics: diversity of action under a common epithet.

Abstract: Cationic antimicrobials have been in general use within clinical and domestic settings for over half a century. Recently, the use of antiseptics and disinfectants has been questioned in such settings because of the possibility that chronic exposure of the environment to such agents might select for less susceptible strains towards these agents and towards third party antibiotics. Whilst no supportive evidence has emerged from retrospective field studies of high use environments such debate has tempered new applications for these molecules. In the clinic, use of antiseptics, together with products, such as dressings, catheters and sutures, which are impregnated with biocides has increased. Prominent amongst these biocides are the cationics. Much of the research pertaining to the mechanisms of action of cationic antibacterials was conducted in the 1960s and 1970s and has not been subject to extensive review. Analysis of available publications suggest that monoquaternary ammonium compounds (QAC, cetrimide, benzalkonium chloride), biquaternaries and bisbiguanides (Chlorhexidine, Barquat), and polymeric biguanides (Vantocil, Cosmocil) whilst having similarities in action mechanism, differ substantially in the nature of their interaction with cell envelopes. This has profound implications in terms of cross-resistance where changes in susceptibility towards QAC is not reflected in changes towards other cationics. This review examines action mechanisms for these agents and highlights key differences that render them distinct categories of antibacterial agent.

Interleukin-1 and neuronal injury

Abstract: Interleukin-1 is a pro-inflammatory cytokine that has numerous biological effects, including activation of many inflammatory processes (through activation of T cells, for example), induction of expression of acute-phase proteins, an important function in neuroimmune responses and direct effects on the brain itself. There is now extensive evidence to support the direct involvement of interleukin-1 in the neuronal injury that occurs in both acute and chronic neurodegenerative disorders. This article discusses the key evidence of a role for interleukin-1 in acute neurodegeneration - for example, stroke and brain trauma - and provides a rationale for targeting the interleukin-1 system as a therapeutic strategy.

Computational cluster validation in post-genomic data analysis

Abstract: Motivation: The discovery of novel biological knowledge from the ab initio analysis of post-genomic data relies upon the use of unsupervised processing methods, in particular clustering techniques. Much recent research in bioinformatics has therefore been focused on the transfer of clustering methods introduced in other scientific fields and on the development of novel algorithms specifically designed to tackle the challenges posed by post-genomic data. The partitions returned by a clustering algorithm are commonly validated using visual inspection and concordance with prior biological knowledge---whether the clusters actually correspond to the real structure in the data is somewhat less frequently considered. Suitable computational cluster validation techniques are available in the general data-mining literature, but have been given only a fraction of the same attention in bioinformatics. Results: This review paper aims to familiarize the reader with the battery of techniques available for the validation of clustering results, with a particular focus on their application to post-genomic data analysis. Synthetic and real biological datasets are used to demonstrate the benefits, and also some of the perils, of analytical clustervalidation. Availability: The software used in the experiments is available at http://dbkweb.ch.umist.ac.uk/handl/clustervalidation/ Contact: J.Handl@postgrad.manchester.ac.uk Supplementary information: Enlarged colour plots are provided in the Supplementary Material, which is available at http://dbkweb.ch.umist.ac.uk/handl/clustervalidation/

Measuring the metabolome: current analytical technologies

Abstract: The post-genomics era has brought with it ever increasing demands to observe and characterise variation within biological systems. This variation has been studied at the genomic (gene function), proteomic (protein regulation) and the metabolomic (small molecular weight metabolite) levels. Whilst genomics and proteomics are generally studied using microarrays (genomics) and 2D-gels or mass spectrometry (proteomics), the technique of choice is less obvious in the area of metabolomics. Much work has been published employing mass spectrometry, NMR spectroscopy and vibrational spectroscopic techniques, amongst others, for the study of variations within the metabolome in many animal, plant and microbial systems. This review discusses the advantages and disadvantages of each technique, putting the current status of the field of metabolomics in context, and providing examples of applications for each technique employed.

Stepped care in psychological therapies: Access, effectiveness and efficiency. Narrative literature review.

Abstract: Background There is a significant gap between the demand for psychological therapy services and the available supply. One proposal to overcome this problem is to increase efficiency of provision through the adoption of briefer ‘minimal interventions’ within stepped care models. Aims To examine the theoretical underpinnings of stepped care, together with the practicalities of the adoption of this system of care. Method Narrative literature review. Results The potential clinical and economic benefits of stepped care are dependent upon underlying assumptions of equivalence in terms of clinical outcomes, efficiency in terms of resource use and costs, and acceptability of ‘ minimal interventions’ to patients and therapists. Illustrative studies of these issues are considered. Conclusions Although psychological services might benefit from the adoption of the stepped care model, a substantial research agenda needs to be fulfilled before a judgement can be made as to whether stepped care might be an efficient method of delivering psychological services.

Smoking and fracture risk: a meta-analysis

Abstract: Smoking is widely considered a risk factor for future fracture. The aim of this study was to quantify this risk on an international basis and to explore the relationship of this risk with age, sex and bone mineral density (BMD). We studied 59,232 men and women (74% female) from ten prospective cohorts comprising EVOS/EPOS, DOES, CaMos, Rochester, Sheffield, Rotterdam, Kuopio, Hiroshima and two cohorts from Gothenburg. Cohorts were followed for a total of 250,000 person-years. The effect of current or past smoking, on the risk of any fracture, any osteoporotic fracture and hip fracture alone was examined using a Poisson model for each sex from each cohort. Covariates examined were age, sex and BMD. The results of the different studies were merged using the weighted beta-coefficients. Current smoking was associated with a significantly increased risk of any fracture compared to non-smokers (RR=1.25; 95% Confidence Interval (CI)=1.15-1.36). Risk ratio (RR) was adjusted marginally downward when account was taken of BMD, but it remained significantly increased (RR=1.13). For an osteoporotic fracture, the risk was marginally higher (RR=1.29; 95% CI=1.13-1.28). The highest risk was observed for hip fracture (RR=1.84; 95% CI=1.52-2.22), but this was also somewhat lower after adjustment for BMD (RR=1.60; 95% CI=1.27-2.02). Risk ratios were significantly higher in men than in women for all fractures and for osteoporotic fractures, but not for hip fracture. Low BMD accounted for only 23% of the smoking-related risk of hip fracture. Adjustment for body mass index had a small downward effect on risk for all fracture outcomes. For osteoporotic fracture, the risk ratio increased with age, but decreased with age for hip fracture. A smoking history was associated with a significantly increased risk of fracture compared with individuals with no smoking history, but the risk ratios were lower than for current smoking. We conclude that a history of smoking results in fracture risk that is substantially greater than that explained by measurement of BMD. Its validation on an international basis permits the use of this risk factor in case finding strategies.

Psoriasis: epidemiology, clinical features, and quality of life

Abstract: Psoriasis is a common chronic, recurrent, immune mediated disease of the skin and joints. It can have a significant negative impact on the physical, emotional, and, psychosocial wellbeing of affected patients. Psoriasis is found worldwide but the prevalence varies among different ethnic groups. It has a strong genetic component but environmental factors such as infections can play an important role in the presentation of disease. There are several clinical cutaneous manifestations of psoriasis but most commonly the disease presents as chronic, symmetrical, erythematous, scaling papules and plaques. The epidemiology, clinical features, and impact on quality of life of psoriasis are reviewed.