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Manchester, United Kingdom

The University of Manchester is a large research university situated in the city of Manchester, England. Manchester University, as it is commonly known, is a public university formed in 2004 by the merger of the University of Manchester Institute of Science and Technology and the Victoria University of Manchester . Manchester is a member of the worldwide Universities Research Association group, the Russell Group of British research universities and the N8 Group. The University of Manchester is regarded as a "red brick university", and was a product of the civic university movement of the late 19th century. It formed a constituent part of the federal Victoria University between 1880, when it received its royal charter, and 1903-1904, when it was dissolved.The main campus is south of Manchester city centre on Oxford Road. In 2012, the university had around 39,000 students and 10,400 staff, making it the largest single-site university in the United Kingdom. The University of Manchester had an income of £827 million in 2012–13, of which £200 million was from research grants and contracts.In the 2008 Research Assessment Exercise, Manchester came third in terms of research power and eighth for grade point average quality when including specialist institutions. More students try to gain entry to the University of Manchester than to any other university in the country, with more than 60,000 applications for undergraduate courses. According to the 2012 Highfliers Report, Manchester is the most targeted university by the Top 100 Graduate Employers.The University of Manchester is ranked 30th in the world by QS World University Rankings. In the 2014 Academic Ranking of World Universities, Manchester is ranked 38th in the world and 5th in the UK. It is ranked 52nd in the world and 12th in Europe in the 2014 Times Higher Education World University Rankings.The university owns and operates major cultural assets such as the Manchester Museum, Whitworth Art Gallery, John Rylands Library and Jodrell Bank Observatory which includes the Grade I listed Lovell Telescope.The University of Manchester has 25 Nobel laureates among its past and present students and staff, the fourth-highest number of any single university in the United Kingdom. Four Nobel laureates are currently among its staff – more than any other British university. Wikipedia.

Seddon T.,University of Manchester
International Journal of Drug Policy | Year: 2014

The recent emergence of vibrant markets in 'new psychoactive substances' or 'legal highs' has posed significant new challenges for drug policy. These partly concern what to do about them but the speed and complexity of change has also raised difficulties for how policy responses should be developed. Existing drug policy systems appear too slow and cumbersome to keep up with the pace of change, remaining locked in large part within 'old' ways of thinking that centre almost exclusively around the deployment (or not) of the criminal law and its related enforcement apparatus. In this paper, it is argued that we need to rethink the problem through the lens of regulation, in order to learn lessons from other sectors where more agile responses to changing markets and business innovation have often proved possible. By examining examples drawn from these other areas, an alternative policy-making framework can be developed, involving a more flexible mix of state regulation, civil society action and private law mechanisms. This new approach is founded on a recognition of the networked and polycentric character of effective market governance in an era of global regulatory capitalism. © 2014 Elsevier B.V.

Chan S.-W.,University of Manchester
Frontiers in Microbiology | Year: 2014

Hepatitis C virus (HCV) is a single-stranded, positive-sense RNA virus of clinical importance. The virus establishes a chronic infection and can progress from chronic hepatitis, steatosis to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The mechanisms of viral persistence and pathogenesis are poorly understood. Recently the unfolded protein response (UPR), a cellular homeostatic response to endoplasmic reticulum (ER) stress, has emerged to be a major contributing factor in many human diseases. It is also evident that viruses interact with the host UPR in many different ways and the outcome could be pro-viral, anti-viral or pathogenic, depending on the particular type of infection. Here we present evidence for the elicitation of chronic ER stress in HCV infection. We analyze the UPR signaling pathways involved in HCV infection, the various levels of UPR regulation by different viral proteins and finally, we propose several mechanisms by which the virus provokes the UPR. © 2014 Chan.

Plack C.J.,University of Manchester
Current Biology | Year: 2010

A recent study suggests that musical consonance is based on harmonicity, a preference that reflects the central role of harmonicity in auditory perception. © 2010 Elsevier Ltd. All rights reserved.

Finney N.,University of Manchester
Transactions of the Institute of British Geographers | Year: 2011

This paper is situated at the confluence of two emerging areas of research: a lifecourse approach in internal migration studies and in geography more broadly and studies of sub-populations within lifecourse research. The paper aims to better understand the complexities of ethnic group migration in Britain, in particular why young adults of some ethnic groups are more residentially mobile than others. The paper draws on theories of norms of transition to adulthood. UK Census microdata of migration within Britain by age and ethnic group are used. The paper shows ethnic similarities: internal migration patterns that are distinct in young adulthood compared with other ages and many common characteristics of residential mobility. However, there are also differences between ethnic groups in levels of internal migration and in how young adult life events are associated with migration. In particular, partnership brings increased residential mobility for White British young adults but reduced mobility for South Asian young adults with females in both cases being the 'partnership movers'. Being a student increases residential mobility for White British and Chinese young adults but reduces mobility for young adults from Black and South Asian ethnic groups (particularly for females in the Pakistani ethnic group). This raises issues of access to higher education. The paper concludes that a lifecourse perspective provides an understanding of ethnic differences in internal migration that were previously lacking from 'segregation' perspectives. © 2011 The Author. Transactions of the Institute of British Geographers © 2011 Royal Geographical Society (with the Institute of British Geographers).

Bayat A.,University of Manchester
Plastic and Reconstructive Surgery | Year: 2010

Background: Skin scars have a unique impact on patients' lives. Quantification with disease-specific patient-reported outcome measures is essential for assessing disease severity. This study aimed to develop and validate the first scar-specific patient-reported outcome measure. Methods: Instrument content was derived from qualitative interviews with scar patients. Quotes were identified from transcripts for use as instrument items. This draft measure was field tested in cognitive debriefing interviews. The final instrument was determined using Rasch analysis in a large-scale validation survey. Results: Five hundred sixty-seven potential items were extracted from interviews (n = 34 patients; 24 women; mean age, 35.7 years). Patients primarily reported physical symptoms and impacts on quality of life. Consequently, a symptom scale (16 items) and quality-of-life scale (36 items) were created. Cognitive debriefing (n = 16 patients; 10 women; mean age, 32.8 years) indicated the draft measure was relevant, clear, and practical. Two quality-of-life items, considered too extreme by patients, were deleted. Ten quality-of-life and three symptom items were removed as a result of the validation survey (n = 103 patients; 69 women; mean age, 35.5 years). Final Rasch analysis confirmed two unidimensional scales (p > 0.05) with good internal consistency (0.85 for the symptom scale and 0.93 for the quality-of-life scale). Reproducibility was adequate for the symptom scale (0.83) and good for the quality-of-life scale (0.89). Conclusions: The Patient-Reported Impact of Scars Measure is the first scientifically rigorous, scar-specific, patient-reported outcome measure. It has two unidimensional scales with good psychometric and scaling properties. It is well accepted by patients and easy to use, and should prove valuable for assessing scar disease severity in clinical trials and in general and specialty clinics. Copyright © 2010 by the American Society of Plastic Surgeons.

Holland C.,University of Manchester
Expert Review of Anticancer Therapy | Year: 2011

Endometrial cancers are the most common gynecological malignancies in developed countries. Surgery is the main treatment modality but radiotherapy and, increasingly, chemotherapy are used to treat women with advanced disease and those at high risk of recurrence. Although the treatment of endometrial cancer is becoming increasingly evidence based, there remains a lack of consensus in several aspects of management. These include issues related to the type and extent of surgery and the role of adjuvant treatments as well as more conservative treatment options for younger women. This article discusses these unresolved issues, the current evidence in these areas, and highlights where current research is attempting to answer some of the outstanding questions. © 2011 Expert Reviews Ltd.

Derby B.,University of Manchester
Annual Review of Materials Research | Year: 2010

Inkjet printing is viewed as a versatile manufacturing tool for applications in materials fabrication in addition to its traditional role in graphics output and marking. The unifying feature in all these applications is the dispensing and precise positioning of very small volumes of fluid (1-100 picoliters) on a substrate before transformation to a solid. The application of inkjet printing to the fabrication of structures for structural or functional materials applications requires an understanding as to how the physical processes that operate during inkjet printing interact with the properties of the fluid precursors used. Here we review the current state of understanding of the mechanisms of drop formation and how this defines the fluid properties that are required for a given liquid to be printable. The interactions between individual drops and the substrate as well as between adjacent drops are important in defining the resolution and accuracy of printed objects. Pattern resolution is limited by the extent to which a liquid drop spreads on a substrate and how spreading changes with the overlap of adjacent drops to form continuous features. There are clearly defined upper and lower bounds to the width of a printed continuous line, which can be defined in terms of materials and process variables. Finer-resolution features can be achieved through appropriate patterning and structuring of the substrate prior to printing, which is essential if polymeric semiconducting devices are to be fabricated. Low advancing and receding contact angles promote printed line stability but are also more prone to solute segregation or "coffee staining" on drying. © 2010 by Annual Reviews. All rights reserved.

Howard B.A.,The Institute of Cancer Research | Lu P.,University of Manchester
Seminars in Cell and Developmental Biology | Year: 2014

The stroma, which is composed of supporting cells and connective tissue, comprises a large component of the local microenvironment of many epithelial cell types, and influences several fundamental aspects of cell behaviour through both tissue interactions and niche regulation. The significance of the stroma in development and disease has been increasingly recognised. Whereas normal stroma is essential for various developmental processes during vertebrate organogenesis, it can be deregulated and become abnormal, which in turn can initiate or promote a disease process, including cancer. The mouse mammary gland has emerged in recent years as an excellent model system for understanding stromal function in both developmental and cancer biology. Here, we take a systematic approach and focus on the dynamic interactions that the stroma engages with the epithelium during mammary specification, cell differentiation, and branching morphogenesis of both the embryonic and postnatal development of the mammary gland. Similar stromal-epithelial interactions underlie the aetiology of breast cancer, making targeting the cancer stroma an increasingly important and promising therapeutic strategy to pursue for breast cancer treatment. © 2014 Elsevier Ltd.

Fitzpatrick J.L.,University of Manchester | Lupold S.,Syracuse University
Molecular Human Reproduction | Year: 2014

Sperm experience intense and varied selection that dramatically impacts the evolution of sperm quality. Selection acts to ensure that sperm are fertilization-competent and able to overcome the many challenges experienced on theirway towards eggs.However, simply being able to fertilize an egg is not enough to ensure male fertility in most species. Owing to the prevalence of female multiple mating throughout the animal kingdom, successful fertilization requires sperm to outcompete rival sperm. In addition, females can actively influence sperm quality, storage or utilization to influence male fertility. This review provides an overview of how these selective forces influence the evolution of sperm quality. After exploring the link between sperm traits and male fertility,we examine how post-mating competition between rival ejaculates influences the evolution of sperm quality.We then describe how complex genetic, social and sexual interactions influence sperm quality, focusing on the importance of seminal fluid and interactions between sperm and the female's reproductive tract. In light of the complexities of selection on sperm traits, greater use of multivariate approaches that incorporate male-male, sperm-sperm and sperm-female interactions to study sperm quality will enhance our understanding of how selection acts on sperm traits and factors influencing male fertility. Because the metric of male reproductive success-fertilization-is the same across the animal kingdom, we argue that information about sperm evolution gained from nonhuman animals has enormous potential to further our understanding of the factors that impact human fertility. © The Author 2014.

Layfield R.A.,University of Manchester
Organometallics | Year: 2014

Single-molecule magnets (SMMs) display slow relaxation of the magnetization, purely of molecular origin, in the absence of an applied magnetic field. This review summarizes the important role played by organometallic chemistry in the recent development of SMMs. The broad applicability of organometallic synthesis has led to a series of organometallic SMMs containing transition metals, lanthanides, or actinides, with several examples accounting for some of the most fascinating low-temperature magnetism. The review has two main aims. The first aim is to provide organometallic chemists with an introduction to one of the most exciting areas of modern molecular magnetism and, in particular, to highlight how organometallic chemistry has allowed the field to evolve in new directions. The second aim is more of a clarion call: organometallic chemistry still has hugely underexploited potential in the development of single-molecule magnets, and it is reasonable to expect that different synthetic approaches will lead to new and unusual magnetic phenomena. By using this review as an entry point for studying the literature in more detail, hopefully more organometallic chemists will consider directing their synthetic repertoire toward the design and realization of new, and possibly improved, single-molecule magnets. © 2014 American Chemical Society.

Braithwaite R.J.,University of Manchester
Cryosphere | Year: 2015

Translated into modern terminology, Kurowski suggested in 1891 that the equilibrium line altitude (ELA) of a glacier is equal to the mean altitude of the glacier when the whole glacier is in balance between accumulation and ablation. Kurowski's method has been widely misunderstood, partly due to inappropriate use of statistical terminology by later workers, and has only been tested by Braithwaite and Müller in a 1980 paper (for 32 glaciers). I now compare Kurowski's mean altitude with balanced-budget ELA calculated for 103 present-day glaciers with measured surface mass-balance data. Kurowski's mean altitude is significantly higher (at 95 % level) than balanced-budget ELA for 19 outlet and 42 valley glaciers, but not significantly higher for 34 mountain glaciers. The error in Kurowski mean altitude as a predictor of balanced-budget ELA might be due to generally lower balance gradients in accumulation areas compared with ablation areas for many glaciers, as suggested by several workers, but some glaciers have higher gradients, presumably due to precipitation increase with altitude. The relatively close agreement between balanced-budget ELA and mean altitude for mountain glaciers (mean error-8 m with standard deviation 59 m) may reflect smaller altitude ranges for these glaciers such that there is less room for effects of different balance gradients to manifest themselves. © 2015 Author(s).

Sansom R.S.,University of Manchester
Systematic Biology | Year: 2015

The utility of fossils in evolutionary contexts is dependent on their accurate placement in phylogenetic frameworks, yet intrinsic and widespread missing data make this problematic. The complex taphonomic processes occurring during fossilization can make it difficult to distinguish absence from non-preservation, especially in the case of exceptionally preserved soft-tissue fossils: is a particular morphological character (e.g., appendage, tentacle, or nerve) missing from a fossil because it was never there (phylogenetic absence), or just happened to not be preserved (taphonomic loss)? Missing data have not been tested in the context of interpretation of non-present anatomy nor in the context of directional shifts and biases in affinity. Here, complete taxa, both simulated and empirical, are subjected to data loss through the replacement of present entries (1s) with either missing (?s) or absent (0s) entries. Both cause taxa to drift down trees, from their original position, toward the root. Absolute thresholds at which downshift is significant are extremely low for introduced absences (two entries replaced, 6% of present characters). The opposite threshold in empirical fossil taxa is also found to be low; two absent entries replaced with presences causes fossil taxa to drift up trees. As such, only a few instances of non-preserved characters interpreted as absences will cause fossil organisms to be erroneously interpreted as more primitive than they were in life. This observed sensitivity to coding non-present morphology presents a problem for all evolutionary studies that attempt to use fossils to reconstruct rates of evolution or unlock sequences of morphological change. Stem-ward slippage, whereby fossilization processes cause organisms to appear artificially primitive, appears to be a ubiquitous and problematic phenomenon inherent to missing data, even when no decay biases exist. Absent characters therefore require explicit justification and taphonomic frameworks to support their interpretation. © The Author(s) 2014. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.

Bolton-Maggs P.H.B.,University of Manchester | Cohen H.,University College London
British Journal of Haematology | Year: 2013

The Serious Hazards of Transfusion (SHOT) UK confidential haemovigilance reporting scheme began in 1996. Over the 16 years of reporting, the evidence gathered has prompted changes in transfusion practice from the selection and management of donors to changes in hospital practice, particularly better education and training. However, half or more reports relate to errors in the transfusion process despite the introduction of several measures to improve practice. Transfusion in the UK is very safe: 2·9 million components were issued in 2012, and very few deaths are related to transfusion. The risk of death from transfusion as estimated from SHOT data in 2012 is 1 in 322 580 components issued and for major morbidity, 1 in 21 413 components issued; the risk of transfusion-transmitted infection is much lower. Acute transfusion reactions and transfusion-associated circulatory overload carry the highest risk for morbidity and death. The high rate of participation in SHOT by National Health Service organizations, 99·5%, is encouraging. Despite the very useful information gained about transfusion reactions, the main risks remain human factors. The recommendations on reduction of errors through a 'back to basics' approach from the first annual SHOT report remain absolutely relevant today. © 2013 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Nonaka D.,Christie Hospital | Nonaka D.,University of Manchester
American Journal of Surgical Pathology | Year: 2012

Distinguishing between lung adenocarcinoma and squamous cell carcinoma is becoming increasingly important, given the different treatment regimens available. Although histologic subdivision between the two is generally not difficult in differentiated tumors, it can be challenging in poorly differentiated tumors and may require a panel of immunohistochemistry stains. The p63 gene encodes two different N-termini (TA and ΔN). ΔNp63 is selectively expressed in squamous cell carcinoma, whereas TAp63 is not restricted only to it. 4A4, a widely used anti-p63 antibody, identifies both isoforms and is expressed in about 15% of adenocarcinomas, and, although generally focal, its expression can be diffuse. In this study, a total of 150 lung adenocarcinomas and 50 squamous cell carcinomas were immunostained by antibodies for p63 (4A4), ΔNp63 (p40), and TTF-1 (8G7G3/1). Twenty-seven adenocarcinomas (18%) were positive for p63 to a variable extent, with diffuse reaction being seen in 13 tumors (8.7%). p63 expression was seen in all subtypes of adenocarcinomas, except for the mucinous type. p40 was negative in all adenocarcinomas. All squamous cell carcinomas were diffusely positive for both p63 and p40. Four of 27 p63-positive adenocarcinomas were negative for TTF-1. p63 expression is not uncommonly seen in adenocarcinomas, whereas ΔNp63 (p40) expression is specific for squamous cell carcinoma, with sensitivity comparable to that of p63 expression. Presence of p63-positive cells in poorly differentiated lung adenocarcinoma may be erroneously interpreted as evidence of squamous cell differentiation. p40 appears to be a more reliable marker for squamous cell carcinoma. © 2012 by Lippincott Williams & Wilkins.

Eden T.,University of Manchester
Cancer Treatment Reviews | Year: 2010

The acute leukaemias account for about 30% of all malignancy seen in childhood across the Western world. A peak incidence of precursor B cell ALL has emerged as socio-economic conditions have improved in countries worldwide. From twin studies and the use of neonatal blood spots it has been possible to back track the first initiating genetic events within critical haemopoietic cells to foetal development in utero for most precursor B cell ALL and some cases of AML. These events may occur as part of normal foetal development. Whether other factors (environmental or constitutional) are involved to increase the chance of these first genetic changes happening is unclear. For some leukaemias (e.g. infant MLL positive ALL) the first event appears adequate to create a malignant clone but for the majority of ALL and AML further 'genetic' changes are required, probably postnatal. Many environmental factors have been proposed as causative for leukaemia but only ionising irradiation and certain chemicals, e.g. benzene and cytotoxics (alkylators and topoisomerase II inhibitors) have been confirmed and then principally for acute myeloid leukaemia. It appears increasingly likely that delayed, dysregulated responses to 'common' infectious agents play a major part in the conversion of pre-leukaemic clones into overt precursor B cell ALL, the most common form of childhood leukaemia. Constitutional polymorphic alleleic variants in immune response genes (especially the HLA Class II proteins) and cytokines may play a role in determining the type of immune response.High penetrance germ-line mutations are involved in only about 5% of childhood leukaemias (more in AML than ALL). There is little evidence to support any role of viral transformation in causation, unlike in animals. Other environmental factors for which some evidence exists include non-ionising electromagnetic radiation and electric fields, although their mode of action in leukaemogenesis remains unclear. There is no single cause for childhood leukaemia and for most individuals a combination of factors appears to be necessary; all involving gene-environment interactions. To date few clear preventative measures have emerged, except the complete avoidance of first trimester X-rays in pregnancy; a healthy diet with adequate oral folic acid intake both preconception and early in pregnancy; and the early exposure of children to other children outside the home to facilitate stimulation and maturation of the natural immune system. Here then are clear echoes of the " hygiene hypothesis" regarding the initiation of allergies, autoimmune disease and type I diabetes mellitus in children and young people. © 2010.

Pisco A.O.,University of Manchester
Nature communications | Year: 2013

The development of drug resistance, the prime cause of failure in cancer therapy, is commonly explained by the selection of resistant mutant cancer cells. However, dynamic non-genetic heterogeneity of clonal cell populations continuously produces metastable phenotypic variants (persisters), some of which represent stem-like states that confer resistance. Even without genetic mutations, Darwinian selection can expand these resistant variants, which would explain the invariably rapid emergence of stem-like resistant cells. Here, by using quantitative measurements and modelling, we show that appearance of multidrug resistance in HL60 leukemic cells following treatment with vincristine is not explained by Darwinian selection but by Lamarckian induction. Single-cell longitudinal monitoring confirms the induction of multidrug resistance in individual cells. Associated transcriptome changes indicate a lasting stress response consistent with a drug-induced switch between high-dimensional cancer attractors. Resistance induction correlates with Wnt pathway upregulation and is suppressed by β-catenin knockdown, revealing a new opportunity for early therapeutic intervention against the development of drug resistance.

Horsley A.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2012

Chronic pulmonary infection is one of the hallmarks of lung disease in cystic fibrosis. Infections dominated by organisms of the Burkholderia cepacia complex, a group of at least 17 closely-related species of gram-negative bacteria, are particularly difficult to treat. These infections may be associated with a fulminant necrotising pneumonia, and are greatly feared by patients. Burkholderia cepacia bacteria are innately resistant to many common antibiotics and able to acquire resistance against many more. Since strict patient segregation was introduced to cystic fibrosis medical care, the incidence of the more virulent epidemic strains has fallen, and new infections are more likely to be with environmentally-acquired strains which seem to exhibit less virulence. Nonetheless, exacerbations of respiratory symptoms require effective therapy directed against the dominant bacterial species. Although evidence-based guidelines exist for the treatment of respiratory exacerbations involving Pseudomonas aeruginosa, the most common chronic infection in cystic fibrosis, these cannot be directly extended to Burkholderia cepacia complex infections. The aim of this review is to assess the available trial evidence for choice and application of treatments for Burkholderia cepacia complex infections. To assess the effectiveness and safety of different antibiotic regimens in people with cystic fibrosis experiencing an exacerbation, who are chronically infected with organisms of the Burkholderia cepacia complex. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews.Date of latest search: 29 November 2011. Randomised and quasi-randomised controlled trials of treatments for exacerbations of pulmonary symptoms in cystic fibrosis patients chronically infected with organisms of the Burkholderia cepacia complex. No relevant trials were identified. No trials were included in this review. Burkholderia cepacia complex infections present a significant challenge for cystic fibrosis clinicians and patients alike. The incidence is likely to increase as the cystic fibrosis population ages and the problem of how to manage and treat these infections becomes more important. There is a lack of trial evidence to guide decision making and no conclusions can be drawn from this review about the optimal antibiotic regimens for cystic fibrosis patients with chronic Burkholderia cepacia complex infections. Clinicians must continue to assess each patient individually, taking into account in vitro antibiotic susceptibility data, previous clinical responses and their own experience. There is a clear need for multi-centre randomised clinical trials to assess the effectiveness of different antibiotic regimens in cystic fibrosis patients infected with organisms of the Burkholderia cepacia complex.

Lavender T.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2012

Caesarean section rates are progressively rising in many parts of the world. One suggested reason is increasing requests by women for caesarean section in the absence of clear medical indications, such as placenta praevia, HIV infection, contracted pelvis and, arguably, breech presentation or previous caesarean section. The reported benefits of planned caesarean section include greater safety for the baby, less pelvic floor trauma for the mother, avoidance of labour pain and convenience. The potential disadvantages, from observational studies, include increased risk of major morbidity or mortality for the mother, adverse psychological sequelae, and problems in subsequent pregnancies, including uterine scar rupture and a greater risk of stillbirth and neonatal morbidity. The differences in neonatal physiology following vaginal and caesarean births are thought to have implications for the infant, with caesarean section potentially increasing the risk of compromised health in both the short and the long term. An unbiased assessment of advantages and disadvantages would assist discussion of what has become a contentious issue in modern obstetrics. To assess, from randomised trials, the effects on perinatal and maternal morbidity and mortality, and on maternal psychological morbidity, of planned caesarean delivery versus planned vaginal birth in women with no clear clinical indication for caesarean section. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2012) and reference lists of relevant studies. All comparisons of intention to perform caesarean section and intention for women to give birth vaginally; random allocation to treatment and control groups; adequate allocation concealment; women at term with single fetuses with cephalic presentations and no clear medical indication for caesarean section. We identified no studies that met the inclusion criteria. There were no included trials. There is no evidence from randomised controlled trials, upon which to base any practice recommendations regarding planned caesarean section for non-medical reasons at term. In the absence of trial data, there is an urgent need for a systematic review of observational studies and a synthesis of qualitative data to better assess the short- and long-term effects of caesarean section and vaginal birth.

Ethnic disparities in UK mental healthcare persist despite decades of policy and practice initiatives to eradicate them. Inequalities in access, care and outcomes are most evident among people of Black Caribbean origin. However, much of this evidence is derived from clinical practice and research among men with serious mental illness. Lack of evidence about common mental health issues in Black British Caribbean women is an important omission as reducing inequalities in mental healthcare and providing effective interventions require improved understanding of aetiology, epidemiology, symptom profile and ways of coping. In this paper, I explore the conundrum of apparently low levels of perinatal depression among Black British Caribbean women despite significant levels of psychosocial risk and against the backdrop of high prevalence of diagnosed mental illness among Black British Caribbean men. I posit that the intersections of ethnicity, gender and spirituality might provide at least a partial explanation for apparent underdiagnosis in this group of women. Understanding Black British Caribbean women's mental health needs, coping styles, help-seeking strategies and their relationship with formal systems of care has important ramifications for research, policy and practice aimed at reducing mental health disparities in the context of the UK's equity-based healthcare system. © 2013 Copyright Taylor and Francis Group, LLC.

This paper proposes extending Urban Political Ecology's (UPE) ideas about the urbanisation of nature in order to include the geographical imprints of expanding, global metabolic flows of matter, energy and capital. It does so through the analysis of Huasco, a small agricultural village in northern Chile that has been overburdened with massive energy undertakings aimed at powering the operations of mines that supply raw materials to international markets. Like the sewage and technological networks that feed the life of cities, the paper argues that Huasco-as a metabolic vehicle of planetary urbanisation-has also been hidden from view, and thus the fetishisation of urban infrastructural networks initially theorised by UPE, has been ratcheted-up to the global level by the mediating powers of neoliberalising capitalism. Just as the socio-material arrangements that facilitate the smooth functioning of the modern city and household are riddled with glitches and exclusions, the paper suggests that globally up-scaled infrastructures reveal even larger contradictions that put into jeopardy the very premises upon which the ongoing commodification of nature is grounded. © 2015 The Author.

Mabbott S.,University of Manchester
The Analyst | Year: 2013

Deposition of silver onto British 2p coins has been demonstrated as an efficient and cost effective approach to producing substrates capable of promoting surface enhanced Raman scattering (SERS). Silver application to the copper coins is undemanding taking just 20 s, and results in the formation of multiple hierarchial dendritic structures. To demonstrate that the silver deposition sites were capable of SERS the highly fluorescent Rhodamine 6G (R6G) probe was used. Analyses indicated that Raman enhancement only occurs at the silver deposition sites and not from the roughened copper surface. The robustness of the substrate in the identification and discrimination of illegal and legal drugs of abuse was then explored. Application of the drugs to the substrates was carried out using spotting and soaking methodologies. Whilst little or no SERS spectra of the drugs were generated upon spotting, soaking of the substrate in a methanolic solution of the drugs yielded a vast amount of spectral information. Excellent reproducibility of the SERS method and classification of three of the drugs, 4-methylmethcathinone (mephedrone), 5,6-methylenedioxy-2-aminoindane (MDAI) and 3,4-methylenedioxy-N-methylamphetamine (MDMA) were demonstrated using principal components analysis and partial least squares.

The purpose of this study is to develop a droplet-based microfluidic device capable of monitoring drug precipitation upon a shift from gastric pH (pH 1.5) to intestinal pH (pH 6.5-7.0). The extent of precipitation occurring in droplets over time was measured using a novel on-chip laser scattering technique specifically developed for this study. The precipitation of ketoconazole, a poorly water-soluble basic drug, was investigated under different concentrations and pH values. It has been shown that the drug precipitates rapidly under supersaturation. Two water-soluble aqueous polymers, namely, polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose (HPMC) have been evaluated as precipitation inhibitors. HPMC was shown to be the most potent precipitation inhibitor. It is envisaged that the microfluidic pH-shift method developed in this study would form a proof-of-concept study, towards the development of a high throughput method for screening pharmaceutical excipients/precipitation inhibitors.

Temple I.P.,University of Manchester
Heart rhythm : the official journal of the Heart Rhythm Society | Year: 2013

The structure and functioning of the atrioventricular (AV) node has remained mysterious owing to its high degree of complexity. In this review article, we integrate advances in knowledge regarding connexin expression in the AV node. Complex patterning of 4 different connexin isoforms with single channel conductances ranging from ultralow to high explains the dual pathway electrophysiology of the AV node, the presence of 2 nodal extensions, longitudinal dissociation in the penetrating bundle, and, most importantly, how the AV node maintains slow conduction between the atria and the ventricles. It is shown that the complex patterning of connexins is the consequence of the embryonic development of the cardiac conduction system. Finally, it is argued that connexin dysregulation may be responsible for AV node dysfunction. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Allan V.J.,University of Manchester
EMBO Journal | Year: 2016

Post-translational modifications of tubulin, such as the removal of the C-terminal tyrosine of α-tubulin, have long been proposed to influence the ability of microtubule motors to walk along the microtubule surface. This hypothesis has now been tested for cytoplasmic dynein-1 (dynein), revealing that active dynein-dynactin-adaptor complexes prefer to start moving on tyrosinated microtubules. This choice is governed by the p150 subunit of dynactin. Once moving, however, dynein is not choosy about whether the microtubule is tyrosinated or not. Microtubule tyrosination at the C-terminus of α-tubulin allows for robust initiation of mammalian dynein-dynactin processivity, but tyrosination is dispensable once dynein is motile. © 2016 The Author.

Prokop K.A.,Johns Hopkins University | De Visser S.P.,University of Manchester | Goldberg D.P.,Johns Hopkins University
Angewandte Chemie - International Edition | Year: 2010

Chemical equation presented Runaway reactivity: A manganese(V)-oxo porphyrinoid complex displays an unprecedented increase in reaction rate for a hydrogen-atom abstraction upon addition of anionic axial ligands (X=F - and CN-; see scheme). Density functional theory calculations are in excellent agreement with experiment, and provide insight into the origins of these remarkable axial ligand effects. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Marin-Franch I.,Indiana University | Foster D.H.,University of Manchester
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2013

The colors present in an image of a scene provide information about its constituent elements. But the amount of information depends on the imaging conditions and on how information is calculated. This work had two aims. The first was to derive explicitly estimators of the information available and the information retrieved from the color values at each point in images of a scene under different illuminations. The second was to apply these estimators to simulations of images obtained with five sets of sensors used in digital cameras and with the cone photoreceptors of the human eye. Estimates were obtained for 50 hyperspectral images of natural scenes under daylight illuminants with correlated color temperatures 4,000, 6,500, and 25,000 K. Depending on the sensor set, the mean estimated information available across images with the largest illumination difference varied from 15.5 to 18.0 bits and the mean estimated information retrieved after optimal linear processing varied from 13.2 to 15.5 bits (each about 85 percent of the corresponding information available). With the best sensor set, 390 percent more points could be identified per scene than with the worst. Capturing scene information from image colors depends crucially on the choice of camera sensors. © 1979-2012 IEEE.

Valle J.W.,University of Manchester
Annals of Oncology | Year: 2010

The prognosis for advanced/inoperable biliary tract cancer is poor and the management of biliary obstruction and sepsis remains the cornerstone of best supportive care (BSC). Many phase II studies have reported some activity of chemotherapy, usually involving one or more of a fluoropyrimidine, a platinum agent and gemcitabine. No adequately powered study has shown conclusively a benefit for chemotherapy compared with BSC alone although three small randomized studies have suggested an improved survival. Results from the randomized phase III ABC-02 study demonstrated a survival advantage of cisplatin and gemcitabine doublet-chemotherapy over gemcitabine monotherapy {median survival of 11.7 compared with 8.1 months, hazard ratio (HR), 0.64 [95% confidence interval (CI) 0.52 to 0.80]; log rank P < 0.001} as well as a significantly longer progression-free survival [median 8 compared with 5 months; HR 0.63 (95% CI 0.51 to 0.77); log rank P < 0.001]. A similar magnitude of benefit was seen in Japanese patients in a second study using the same treatment regimens (the BT-22 study). Ongoing studies are underway evaluating other chemotherapy regimens in first-line although attention is turning to the addition of targeted therapies; these will be reviewed. Pivotal to success in this process is both the identification of appropriate targets across this heterogeneous group of malignancies (e.g. EGFR, VEGF, MEK inhibition, amongst others) and collaboration between investigators to deliver relevant, timely and adequately powered studies. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Coulthard P.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Sutures, staples and adhesive tapes are the traditional methods of wound closure, whilst tissue adhesives have entered clinical practice more recently. Closure of wounds with sutures enables meticulous closure, but they may show tissue reactivity and can require removal. Tissue adhesives offer the advantages of no risk of needlestick injury and no requirement to remove sutures later. Tissue adhesives have been used primarily in emergency rooms but this review looks at the use of tissue adhesives in the operating room where surgeons are increasingly using these for the closure of surgical skin incisions. OBJECTIVES: To determine the relative effects of various tissue adhesives and conventional skin closure techniques on the healing of surgical wounds. SEARCH STRATEGY: For this update we searched the Cochrane Wounds Group Specialised Register (Searched 17/11/09); The Cochrane Central Register of Controlled Trials (CENTRAL) - The Cochrane Library Issue 4 2009; Ovid MEDLINE - 1950 to November Week 1 2009; Ovid EMBASE - 1980 to 2009 Week 46; EBSCO CINAHL - 1982 to 17 November 20098. No date or language restrictions were applied. SELECTION CRITERIA: Only randomised controlled clinical trials were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Screening of eligible studies and data extraction were conducted independently and in triplicate whilst assessment of the methodological quality of the trials was conducted independently and in duplicate. Results were expressed as random effects models using mean difference for continuous outcomes and relative risks with 95% confidence intervals for dichotomous outcomes. Heterogeneity was investigated including both clinical and methodological factors. MAIN RESULTS: This update identified an additional six trials resulting in a total of fourteen RCTs (1152 patients) which met the inclusion criteria. Sutures were significantly better than tissue adhesives for minimising dehiscence (10 trials). Sutures were also found to be significantly faster to use. For all other analyses of infection, patient and operator satisfaction and cost there was no significant difference between sutures and tissue adhesives. No differences were found between tissue adhesives and tapes (2 trials) for minimising dehiscence, infection, patients assessment of cosmetic appearance, patient satisfaction or surgeon satisfaction. However a statistically significant difference in favour of using tape was found for surgeons' assessment of cosmetic appearance (mean difference 13, 95% CI 5 to 21). Tapes were also demonstrated to be significantly faster to use than tissue adhesives as were staples (1 trial). No other outcome measures were analysed in this group. One trial compared tissue adhesives with a variety of methods of wound closure and found both patients and clinicians were significantly more satisfied with the alternative closure methods than the adhesives. In this same trial tissue adhesives were significantly less time consuming to use. For the remaining outcomes of dehiscence and infection no difference was observed between groups. This trial also compared high viscosity with low viscosity adhesives and found that high viscosity adhesives were less time consuming to use than low viscosity tissue adhesives. For all other outcomes of dehiscence, infection, patient satisfaction and operator satisfaction there was no statistically significant difference between high and low viscosity adhesives. AUTHORS' CONCLUSIONS: Sutures were significantly better than tissue adhesives for minimising dehiscence and were found to be significantly faster to use. Although surgeons may consider the use of tissue adhesives as an alternative to other methods of surgical site closure in the operating theatre they must be aware that adhesives may take more time to apply and that if higher tension is needed upon an incision, sutures may minimise dehiscence. There is a need for more well designed randomised controlled trials comparing tissue adhesives and alternative methods of closure. These trials should include people whose health may interfere with wound healing and surgical sites of high tension.

Ding Z.,University of Manchester
IEEE Transactions on Automatic Control | Year: 2013

This technical note deals with consensus output regulation of network connected multi-agent systems. Every agent or subsystem is a nonlinear system in the output feedback form with relative degree one, but subsystems may have different dynamics in terms of different nonlinear functions and even different system orders. The subsystem dynamics are influenced by state variables generated from an exosystem. The outputs of the subsystems are required to follow a desired trajectory which is a function of the exosystem state. Only some subsystems have access to the desired trajectory, and the other subsystems will have to rely on the exchange of information through the network. In this technical note, a consensus control design is proposed to ensure that the outputs of all the subsystems converge to the same desired output trajectory by exploiting the internal model design strategy. The proposed control design only uses the relative outputs of the subsystems, and does not require the estimation of subsystem state variables. © 2013 IEEE.

Death C.,University of Manchester
Environmental Politics | Year: 2016

Whilst the ‘green state debate’ has primarily focused on a narrow range of usual suspects in the developed world, the debate can be enriched and challenged by considering more diverse cases. Viewing African states from a green state perspective invites empirical reassessment of the geographical scope of the concept, and introduces a new set of conceptual questions about the political significance of transitions in environmental governance. Ecological modernisation theory has largely neglected African states because it is assumed that African states are weak, failing, or failed, and that environmentalism is a post-materialist phenomenon. Whilst both assumptions can be challenged empirically, a biopolitical perspective on the African environmental state, drawing on the work of Michel Foucault, can both position African state development within a longer-term context and challenge some assumptions of ecological modernisation. Examples from Egypt, South Africa, and the Kavango-Zambezi Trans-frontier Conservation Area highlight underestimated continuities in environmental state practices. The international and transnational drivers of the green state in Africa are emphasised, as well as the political dangers of a green ‘state building’ project. © 2015 Taylor & Francis.

Abdelkader A.M.,University of Manchester
Journal of the European Ceramic Society | Year: 2016

The unique combination of electrical, mechanical and chemical properties of MAX phase ceramics makes them attractive for energy and structural industrial applications. Here, an inexpensive and simple electrochemical deoxidation process is used to produce high quality, homogeneous micron-size particles of one of the most widely studied MAX phases, Cr2AlC. The process used cathode precursors made of cheap and available oxides of both chromium and aluminum and applied a constant potential difference in molten NaCl-CaCl2 as the electrolyte. It was found that the reduction mechanism took an unusual pathway through the formation of sub-stoichiometric oxides and oxycarbide phases that did not necessarily involve reactions between the cathode and the electrolyte. The Cr2AlC powder produced could be easily pressed into a monolithic bulk that have 4.8±0.8GPa hardness and showed excellent oxidation resistance at temperatures below 1100°C. The method is quite generally applicable to the preparation of other MAX phases. Implications are drawn considering the industrial scale-up of this method for the low-cost production of MAX ceramics. © 2015.

Exposure to a variety of toxins and/or infectious agents leads to disease, degeneration and death, often characterised by circumstances in which cells or tissues do not merely die and cease to function but may be more or less entirely obliterated. It is then legitimate to ask the question as to whether, despite the many kinds of agent involved, there may be at least some unifying mechanisms of such cell death and destruction. I summarise the evidence that in a great many cases, one underlying mechanism, providing major stresses of this type, entails continuing and autocatalytic production (based on positive feedback mechanisms) of hydroxyl radicals via Fenton chemistry involving poorly liganded iron, leading to cell death via apoptosis (probably including via pathways induced by changes in the NF-κB system). While every pathway is in some sense connected to every other one, I highlight the literature evidence suggesting that the degenerative effects of many diseases and toxicological insults converge on iron dysregulation. This highlights specifically the role of iron metabolism, and the detailed speciation of iron, in chemical and other toxicology, and has significant implications for the use of iron chelating substances (probably in partnership with appropriate anti-oxidants) as nutritional or therapeutic agents in inhibiting both the progression of these mainly degenerative diseases and the sequelae of both chronic and acute toxin exposure. The complexity of biochemical networks, especially those involving autocatalytic behaviour and positive feedbacks, means that multiple interventions (e.g. of iron chelators plus antioxidants) are likely to prove most effective. A variety of systems biology approaches, that I summarise, can predict both the mechanisms involved in these cell death pathways and the optimal sites of action for nutritional or pharmacological interventions. © 2010 The Author(s).

Yang W.,University of Manchester
Measurement Science and Technology | Year: 2010

Electrical capacitance tomography (ECT) has been developed since the late 1980s for visualization and measurement of a permittivity distribution in a cross section using a multi-electrode capacitance sensor. While the hardware and image reconstruction algorithms for ECT have been published extensively and the topics have been reviewed, few papers have been published to discuss ECT sensors and the design issues, which are crucial for a specific application. This paper will briefly discuss the principles of ECT sensors, but mostly will address key issues for ECT sensor design, with reference to some existing ECT sensors as a good understanding of the key issues would help optimization of the design of ECT sensors. The key issues to be discussed include the number and length of electrodes, the use of external and internal electrodes, implications of wall thickness, earthed screens (including the outer screen, axial end screens and radial screens), driven guard electrodes, dealing with high temperature and high pressure, twin planes for velocity measurement by cross correlation and limitations in sensor diameter. While conventional ECT sensors are circular with the electrodes in a single plane or in twin planes, some non-conventional ECT sensors, such as square, conical and 3D sensors, will also be discussed. As a practical guidance, the procedure to fabricate an ECT sensor will be given. In the end are summary and discussion on future challenges, including re-engineering of ECT sensors. © 2010 IOP Publishing Ltd.

Dasgupta P.,University of Cambridge | Dasgupta P.,University of Manchester
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

In this paper, I formalize the idea of sustainable development in terms of intergenerational wellbeing. I then sketch an argument that has recently been put forward formally to demonstrate that intergenerational well-being increases over time if and only if a comprehensive measure of wealth per capita increases. The measure of wealth includes not only manufactured capital, knowledge and human capital (education and health), but also natural capital (e.g. ecosystems). I show that a country's comprehensive wealth per capita can decline even while gross domestic product (GDP) per capita increases and the UN Human Development Index records an improvement. I then use some rough and ready data from the world's poorest countries and regions to show that during the period 1970-2000 wealth per capita declined in South Asia and sub-Saharan Africa, even though the Human Development Index (HDI) showed an improvement everywhere and GDP per capita increased in all places (except in sub-Saharan Africa, where there was a slight decline). I conclude that, as none of the development indicators currently in use is able to reveal whether development has been, or is expected to be, sustainable, national statistical offices and international organizations should now routinely estimate the (comprehensive) wealth of nations. © 2010 The Royal Society.

Friedle S.,Massachusetts Institute of Technology | Reisner E.,Massachusetts Institute of Technology | Reisner E.,University of Manchester | Lippard S.J.,Massachusetts Institute of Technology
Chemical Society Reviews | Year: 2010

This tutorial review describes recent progress in modeling the active sites of carboxylate-rich non-heme diiron enzymes that activate dioxygen to carry out several key reactions in Nature. The chemistry of soluble methane monooxygenase, which catalyzes the selective oxidation of methane to methanol, is of particular interest for (bio)technological applications. Novel synthetic diiron complexes that mimic structural, and, to a lesser extent, functional features of these diiron enzymes are discussed. The chemistry of the enzymes is also briefly summarized. A particular focus of this review is on models that mimic characteristics of the diiron systems that were previously not emphasized, including systems that contain (i) aqua ligands, (ii) different substrates tethered to the ligand framework, (iii) dendrimers attached to carboxylates to mimic the protein environment, (iv) two N-donors in a syn-orientation with respect to the iron-iron vector, and (v) a N-rich ligand environment capable of accessing oxygenated high-valent diiron intermediates. © 2010 The Royal Society of Chemistry.

Turner N.J.,University of Manchester
Current Opinion in Chemical Biology | Year: 2011

Ammonia lyases catalyse the reversible addition of ammonia to cinnamic acid (1: R = H) and p-hydroxycinnamic (1: R = OH) to generate l-phenylalanine (2: R = H) and l-tyrosine (2: R = OH) respectively (Figure 1a). Both phenylalanine ammonia lyase (PAL) and tyrosine ammonia lyase (TAL) are widely distributed in plants, fungi and prokaryotes. Recently there has been interest in the use of these enzymes for the synthesis of a broader range of l-arylalanines. Aminomutases catalyse a related reaction, namely the interconversion of α-amino acids to β-amino acids (Figure 1b). In the case of l-phenylalanine, this reaction is catalysed by phenylalanine aminomutase (PAM) and proceeds stereospecifically via the intermediate cinnamic acid to generate β-Phe 3. Ammonia lyases and aminomutases are related in sequence and structure and share the same active site cofactor 4-methylideneimidazole-5-one (MIO). There is currently interest in the possibility of using these biocatalysts to prepare a wide range of enantiomerically pure l-configured α-amino and β-amino acids. Recent reviews have focused on the mechanism of these MIO containing enzymes. The aim of this review is to review recent progress in the application of ammonia lyase and aminomutase enzymes to prepare enantiomerically pure α-amino and β-amino acids. © 2010 Elsevier Ltd.

Phillipson C.,University of Manchester
Ageing and Society | Year: 2015

Research on minority ethnic ageing remains a neglected area within mainstream race and ethnicity studies as well as that of social gerontology. This paper examines the background and reasons for this, arguing that a focus on minority ethnic issues provides a reminder of the complexity of the lifecourse, and of the diversity of ageing as a cultural, economic and social construction. The discussion reviews definitions of ethnicity and their relevance to work in social gerontology. The paper provides an account of early studies of minority ethnic ageing, identifying the strengths and limitations of this research. Later work is then considered, notably that focusing on issues connected with the rise of transnational communities and the changing character of neighbourhoods in urban environments. The paper argues that developing research on minority ethnic ageing has become especially important for understanding the impact of globalisation on re-defining communities, relationships and identities, within and beyond nation states. Globalisation, it is suggested, can be seen as a product of the movement of ethnic groups; equally, ethnic groups are themselves transformed by the possibilities created by global change. The paper concludes with a number of suggestions for embedding work on ethnicity within research in social gerontology. Copyright © Cambridge University Press 2014.

Neil Charman W.,University of Manchester
Ophthalmic and Physiological Optics | Year: 2011

Evidence for a possible role for the peripheral retina in the control of refractive development is discussed, together with Howland's suggestion (Paper presented at the 13th International Myopia Conference, Tubingen, Germany, July 26-29, 2010) that signals to generate appropriate growth might be derived from ocular oblique astigmatism. The dependence of this, or similar peripheral mechanisms, on exposure to a uniform field of near-zero dioptric vergence is emphasized: this is required to ensure a consistent relationship between the astigmatic image fields and the retina. This condition is satisfied by typical outdoor environments. In contrast, indoor environments are likely to be unfavourable to peripherally-based emmetropization, since dioptric stimuli may vary widely across the visual field. This is particularly the case when short working distances or markedly asymmetric head postures with respect to the visual task are adopted. © 2011 The College of Optometrists.

Kell D.B.,University of Manchester | Pretorius E.,University of Pretoria
Metallomics | Year: 2014

Serum ferritin presents a paradox, as the iron storage protein ferritin is not synthesised in serum yet is to be found there. Serum ferritin is also a well known inflammatory marker, but it is unclear whether serum ferritin reflects or causes inflammation, or whether it is involved in an inflammatory cycle. We argue here that serum ferritin arises from damaged cells, and is thus a marker of cellular damage. The protein in serum ferritin is considered benign, but it has lost (i.e. dumped) most of its normal complement of iron which when unliganded is highly toxic. The facts that serum ferritin levels can correlate with both disease and with body iron stores are thus expected on simple chemical kinetic grounds. Serum ferritin levels also correlate with other phenotypic readouts such as erythrocyte morphology. Overall, this systems approach serves to explain a number of apparent paradoxes of serum ferritin, including (i) why it correlates with biomarkers of cell damage, (ii) why it correlates with biomarkers of hydroxyl radical formation (and oxidative stress) and (iii) therefore why it correlates with the presence and/or severity of numerous diseases. This leads to suggestions for how one might exploit the corollaries of the recognition that serum ferritin levels mainly represent a consequence of cell stress and damage. © 2014 The Royal Society of Chemistry.

Vijayaraghavan A.,University of Manchester
Journal of Materials Chemistry | Year: 2012

This highlight explores the applications of single walled carbon nanotubes (SWCNTs) sorted according to chirality, diameter or metallicity in electronics, optoelectronics and sensors. In nearly all applications of individual SWCNT devices, sorting provides a new dimension of functionality and significant improvements in performance. Such devices have been made possible because SWCNTs can now be sorted using methods such as density-gradient ultracentrifugation or selective polymer wrapping and assembled using scalable bottom-up assembly methods such as dielectrophoresis. © 2012 The Royal Society of Chemistry.

O'Flaherty M.,University of Liverpool | Buchan I.,University of Manchester | Capewell S.,University of Liverpool
Heart | Year: 2013

Developed countries have enjoyed substantial falls in cardiovascular disease (CVD) mortality. However, low and middle income countries are drowning in a rising tide of CVD and other non-communicable diseases. Current and future trends in CVD mortality will therefore require increasing attention in the 21st century. The success of clinical cardiology in providing evidence-based cost-effective treatments should be celebrated. However, the growing understanding of CVD mortality trends highlights the crucial role of tobacco, diet, alcohol and inactivity as key drivers. Pro-active public health approaches focused on 'upstream' population-wide policies are increasingly recognised as being potentially powerful, rapid, equitable and cost-saving. However, the future political challenges could be substantial.

Chandola T.,University of Manchester
Public Health | Year: 2012

Urban populations around the world face increasingly common health problems. This is partly because of common spatial and socio-economic factors that result in substantial inequalities in health among urban populations. Spatial methods can now map out dimensions of urban living, such as the segregation of poor communities as a result of population concentration of poverty in deprived neighbourhoods. Even in rich countries such as the UK, separate from the health disadvantages of living in a poor neighbourhood, if you live in a neighbourhood that is surrounded by deprivation, you have a higher risk of mortality. However, neighbourhood deprivation is not synonymous with poor social capital. Some communities can be resilient to the health-damaging aspects of living in a poor neighbourhood if they have access to social support and other social ties. © 2012 The Royal Society for Public Health.

Gouk P.,University of Manchester
Progress in Brain Research | Year: 2015

In 1749, the London physician Richard Brocklesby (1722-1797) published his Reflections on Antient [sic] and Modern Musick, an essay that not only sought to compare these practices in terms of their effects, but also to gather evidence supporting the use of music in treating mania and other mental diseases. As might be expected, Brocklesby's discussion of music therapy has already received attention by authors looking back to the origins of this practice, not least because he offers an account of a successful musical cure that took place in his own time (Rorke, 2001). My chapter, however, seeks to broaden the discussion of the Reflections, in order to show how Brocklesby's projected musical cures fit into his larger worldview, one that was influenced as much by Plato and other ancient philosophers as it was by modern thinkers such as Isaac Newton and his followers. Brocklesby's argument was essentially that music acted as a link between the mind and body and therefore could restore their intrinsic harmony, a connection that was mediated by the animal spirits, which also served as the vehicle of the passions. The movements and proportions of music could arouse or quell the passions by their effect on these (imaginary) spirits, which flowed through the nerves and brain and acted as the agent for the mind or soul. I show how his account of music in antiquity led him to reflect on the way that music was perceived and responded to in his own time, both as a stimulus to mental and bodily action, and as a source of esthetic pleasure through the cultivation of musical taste. © 2015 Elsevier B.V.

Mughal M.Z.,University of Manchester
Current Osteoporosis Reports | Year: 2011

Rickets is disorder of a growing child arising from disorders that result in impaired apoptosis of hypertrophic cells and mineralization of the growth plate. Rickets due to nutritional causes remains an important global problem. The factors responsible for resurgence of rickets among dark-skinned infants living in developed countries include the following: residence in northern or southern latitudes, voluntary avoidance of exposure to solar ultraviolet B radiation, maternal vitamin D deficiency during pregnancy, and prolonged breastfeeding without provision of vitamin D supplements. Fibroblast growth factor 23 (FGF23), secreted by osteocytes, is an important regulator of serum phosphate and 1,25(OH) 2D 3 levels. Hypophosphatemic rickets resulting from increased synthesis or under-catabolism of FGF23 is reviewed. © 2011 Springer Science+Business Media, LLC.

Douglas I.,University of Manchester
Current Opinion in Environmental Sustainability | Year: 2012

The ecology of cities assesses the health and well-being benefits of urban greenspace, vegetated areas and water bodies. Ecology in cities examines how the characteristics of the urban landscape mosaic, and various parts of it, affect human health and well-being. Human consumption and behaviour in one urban area can affect the health and well-being of people in other, such as through export of waste and trans-boundary emissions and pollutant flows. Environmental, economic, technological, social and individual risk factors and impacts affect urban populations at four urban ecosystem scales: patches within the urban mosaic, built-up areas, urban regions and the global scale. Increasing urban built-up area sizes lead to more severe heat island effects, particularly for people with inadequate cooling living in buildings that retain heat. Urban people benefit in varied ways from everyday contact with nature, but some urban greeenspaces create both health benefits and health hazards. Cultural or social contrasts in responses to urban nature and greenspaces vary. Despite a general consensus that a healthy urban ecosystem can improve human health and well-being, a large part of the global urban population in low latitude, low income cities, the poorest urban dwellers are likely to suffer from contact with many aspects of nature. © 2012 Elsevier B.V.

Howell S.J.,University of Manchester
Current Opinion in Obstetrics and Gynecology | Year: 2013

Purpose of Review: Recent advances in the genomic analysis of breast cancers show promise in better defining endocrine sensitive subtypes. In addition, several key trials have recently reported results that better define the optimal sequence of endocrine agents and approaches to overcome endocrine resistance. Recent Findings: In clinical practice 'luminal' breast cancer is commonly used interchangeably with estrogen receptor positivity by immunohistochemistry. Genomic analysis better defines this subgroup of tumours but also highlights the complexity of the genetic landscape. These advances are discussed, along with pivotal data from contemporary clinical trials of endocrine therapy, the treatment modality most relevant to the 'luminal' subgroup. The review focuses on data from trials in advanced breast cancer. Four studies (FIRST, FACT, SWOG S0226 and SoFEA) have recently reported and improved our understanding of the optimal sequence of endocrine agents, in particular the estrogen receptor downregulator fulvestrant. The TAMRAD and BOLERO2 trials reported significant improvements in outcome with tamoxifen and exemestane, respectively, when these standard agents were combined with the mammalian target of rapamycin inhibitor everolimus. Summary: Overall these data represent significant advances for women with metastatic breast cancer that will be translated into the early breast cancer setting in the near future. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Merigo J.M.,University of Barcelona | Merigo J.M.,University of Manchester | Gil-Lafuente A.M.,University of Barcelona
Information Sciences | Year: 2013

The induced 2-tuple linguistic generalized ordered weighted averaging (2-TILGOWA) operator is presented. This new aggregation operator extends previous approaches by using generalized means, order-inducing variables in the reordering of the arguments and linguistic information represented with the 2-tuple linguistic approach. Its main advantage is that it includes a wide range of linguistic aggregation operators. Thus, its analyses can be seen from different perspectives and we obtain a much more complete picture of the situation considered and are able to select the alternative that best fits with our interests or beliefs. We further generalize the 2-TILGOWA by using quasi-arithmetic means and Choquet integrals. The result is the Quasi-2-TILOWA operator and the 2-tuple linguistic induced quasi-arithmetic Choquet integral aggregation. We conclude this paper by analysing the applicability of this new approach in a multi-person linguistic decision-making problem concerning product management. © 2013 Elsevier Inc. All rights reserved.

Kitas G.D.,Dudley Group of Hospitals NHS Foundation Trust | Kitas G.D.,University of Manchester | Gabrie S.E.,Mayo Medical School
Annals of the Rheumatic Diseases | Year: 2011

Rheumatoid arthritis is associated with an increased risk for cardiovascular events, such as myocardial infarction and stroke. Epidemiological evidence suggests that classic cardiovascular risk factors, such as hypertension, dyslipidaemia, insulin resistance and body composition alterations are important but not sufficient to explain all of the excess risk. High-grade systemic inflammation and its interplay with classic risk factors may also contribute. Some associations between classic risk factors and cardiovascular risk in people with rheumatoid arthritis appear counterintuitive but may be explained on the basis of biological alterations. More research is necessary to uncover the exact mechanisms responsible for this phenomenon, develop accurate systems used to identify patients at high risk, design and assess prevention strategies specific to this population of patients.

Derby B.,University of Manchester
Journal of the European Ceramic Society | Year: 2011

Inkjet printing is a powerful microfabrication tool that has been applied to the manufacture of ceramic components. To successfully fabricate ceramic objects a number of conditions must be satisfied concerning fluid properties and drop placement accuracy. It has been proposed that fluids are printable within the bounds 1 < Z< 10 (where Z is the inverse of the Ohnesorge number) and these limits are shown to be consistent with ceramic suspensions delivered by piezoelectric drop-on-demand inkjet printers. The physical processes that occur during drop impact and spreading are reviewed and these are shown to define the minimum feature size attainable for a given printed drop diameter. Finally the defects that can occur during the drying of printed drops are reviewed (coffee staining) and mechanisms and methodologies to reduce this phenomenon are discussed. © 2011 Elsevier Ltd.

Das A.,University of Alabama | Bhupal Dev P.S.,University of Manchester | Okada N.,University of Alabama
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

Seesaw models with a small lepton number breaking can naturally accommodate electroweak-scale pseudo-Dirac neutrinos with a sizable mixing with the active neutrinos, while satisfying the light neutrino oscillation data. Due to the smallness of the lepton number breaking parameter, the 'smoking gun' collider signature of same-sign dileptons is suppressed, and the heavy neutrinos in these models would manifest at the LHC dominantly through lepton number conserving trilepton final states. Using the recent CMS results for anomalous production of multilepton events at the s=8TeV LHC with an integrated luminosity of 19.5fb -1, we derive direct upper bounds on the light-heavy neutrino mixing parameter as a function of the heavy Dirac neutrino mass. These limits extend the collider sensitivity to higher heavy neutrino masses up to about 500 GeV. In the lower mass range, our limits are comparable to the existing indirect constraints derived from Higgs and electroweak precision data. © 2014 Elsevier B.V.

Dupre S.M.,University of Manchester
Neuroendocrinology | Year: 2011

In mammals, the nocturnal melatonin signal is well established as a key hormonal indicator of seasonal changes in day-length, providing the brain with an internal representation of the external photoperiod. The pars tuberalis (PT) of the pituitary gland is the major site of expression of the G-coupled receptor MT1 in the brain and is considered as the main site of integration of the photoperiodic melatonin signal. Recent studies have revealed how the photoperiodic melatonin signal is encoded and conveyed by the PT to the brain and the pituitary, but much remains to be resolved. The development of new animal models and techniques such as cDNA arrays or high throughput sequencing has recently shed the light onto the regulatory networks that might be involved. This review considers the current understanding of the mechanisms driving photoperiodism in the mammalian PT with a particular focus on the seasonal prolactin secretion. Copyright © 2011 S. Karger AG, Basel.

Shokri N.,University of Manchester
Physics of Fluids | Year: 2014

Understanding the physics ofwater evaporation from saline porous media is important in many natural and engineering applications such as durability of building materials and preservation of monuments, water quality, and mineral-fluid interactions. We applied synchrotron x-ray micro-tomography to investigate the pore-scale dynamics of dissolved salt distribution in a three dimensional drying saline porous media using a cylindrical plastic column (15 mm in height and 8 mm in diameter) packed with sand particles saturated with CaI2 solution (5% concentration by mass) with a spatial and temporal resolution of 12 μm and 30 min, respectively. Every time the drying sand column was set to be imaged, two different images were recorded using distinct synchrotron x-rays energies immediately above and below the K-edge value of Iodine. Taking the difference between pixel gray values enabled us to delineate the spatial and temporal distribution of CaI2 concentration at pore scale. Results indicate that during early stages of evaporation, air preferentially invades large pores at the surface while finer pores remain saturated and connected to the wet zone at bottom via capillary-induced liquid flow acting as evaporating spots. Consequently, the salt concentration increases preferentially in finer pores where evaporation occurs. Higher salt concentration was observed close to the evaporating surface indicating a convection-driven process. The obtained salt profiles were used to evaluate the numerical solution of the convection-diffusion equation (CDE). Results show that the macro-scale CDE could capture the overall trend of the measured salt profiles but fail to produce the exact slope of the profiles. Our results shed new insight on the physics of salt transport and its complex dynamics in drying porous media and establish synchrotron x-ray tomography as an effective tool to investigate the dynamics of salt transport in porous media at high spatial and temporal resolution. © 2014 AIP Publishing LLC.

Briggs T.A.,University of Manchester
Arthritis Research and Therapy | Year: 2013

A growing body of literature has demonstrated that the multifunctional glycoprotein osteopontin (OPN), has a role in type I interferon (IFN) production and may be involved in systemic lupus erythematosus (SLE) pathogenesis. A recent report has provided further support for this, demonstrating an association between raised baseline circulating plasma osteopontin (cOPN) levels and IFN, and an elevation in cOPN prior to the onset of both increased cumulative disease and end-organ damage. These associations were most marked in paediatric SLE, implying that cOPN may be a useful biomarker of disease activity in childhood lupus. © 2013 BioMed Central Ltd.

Moore M.A.,University of Manchester
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

The one-dimensional long-range Ising spin glass provides useful insights into the properties of finite-dimensional spin glasses with short-range interactions. The defect energy renormalization-group equations derived for it by Kotliar, Anderson, and Stein have been reexamined and a new fixed point has been found. The fixed points which have previously been studied are found to be inappropriate. It is shown that the renormalization-group equations themselves directly imply that that the spin-glass phase is replica symmetric, in agreement with droplet model expectations, when the range exponent σ lies between the upper and lower critical values. © 2010 The American Physical Society.

Custovic A.,University of Manchester
Clinical and Experimental Allergy | Year: 2015

The role of allergen exposure in the development of allergic disease has been a matter of considerable debate, and our understanding of the importance of allergens has evolved over the last 25 years. Several observational and primary prevention studies have investigated these relationships, and different studies reported inconsistent, and sometimes opposite findings. It has to be emphasized that a clear understanding of how aeroallergen exposure occurs, and accurate and reproducible measurement of exposure are essential prerequisites for understanding the role of exposure. However, our current understanding of how we get exposed to allergens is not based on solid evidence, but on a number of assumptions, and we urgently need to develop better proxy measures (or indices) of exposure. In addition, the relative importance of the timing of exposure (e.g. early compared to exposure in later life) is unknown. It is also unclear which route of exposure is the most relevant (e.g. inhaled vs. oral vs. transcutaneous). Available data suggest that the dose-response relationship between allergen exposure and allergic disease may differ between different allergens, dose ranges and exposure patterns, and these relationships may further differ between different populations and geographical areas. It is increasingly clear that childhood asthma and atopy are not single phenotypes, and it is likely that allergen exposure has different effect on distinct subgroups under the umbrella terms of 'sensitization' and 'asthma'. Susceptibility to allergen exposure, other environmental exposures and their interactions may also differ between individuals with different genetic predispositions. However, the precise nature of these complex relationships is unclear. We need a holistic approach offered by systems biology, with integration of information on the standardized and reliable measures of exposures (including allergens and other relevant exposures) with genetic and biological data to fully understand the role of allergens in the development of allergic disease. © 2014 John Wiley & Sons Ltd.

Renehan A.G.,University of Manchester
Diabetologia | Year: 2012

A number of observational studies have linked insulin glargine (A21Gly,B31Arg,B32Arg human insulin) with a putative increased cancer risk, particularly breast cancer, but many of these 'first generation' studies had study design and analysis flaws, and were inconclusive. A small number of 'second generation' studies are now emerging in which the applied pharmaco-epidemiological principles are more robust. For example, when Ruitar and colleagues (Diabetologia DOI:10.1007/s00125-011- 2312-4) focused specifically on breast cancer rather than all incident cancer risk, they were able to show a positive association with insulin glargine for breast cancer although there was no association with all incident cancer risk. A list of preferred qualities for pharmaco-epidemiological studies is presented. © 2011 Springer-Verlag.

McKeown N.B.,University of Cardiff | Budd P.M.,University of Manchester
Macromolecules | Year: 2010

The past decade has seen the development of microporous materials (i.e., materials containing pores of dimensions <2 nm) derived wholly from organic components. Here we review this nascent area with a particular emphasis on amorphous polymers that possess intrinsic microporosity (IM), which is defined as microporosity that arises directly from the shape and rigidity of component macromolecules. Although IM can be readily identified within soluble non-network polymers and oligomers, for network polymers it is harder to differentiate IM from template effects that are responsible for the microporosity within hyper-cross-linked networks. The numerous examples of microporous polymers assembled from rigid monomers by the formation of rigid linking groups are surveyed and their IM assessed. The potential applications of these materials are highlighted. © 2010 American Chemical Society.

Perks H.,University of Manchester
Journal of Product Innovation Management | Year: 2012

This empirical paper presents the results of a detailed case-study investigation of co-creation in radical service innovation. The rationale for the paper is that detailed interventions must be tracked to offer a realistic account of how co-creation occurs. This provides a strong empirical contribution to the emerging body of scholars developing the co-creation paradigm, predominantly characterized by conceptual advances in service-dominant logic. Our focus is on radical service innovation, which is disruptive in the sector. The overall aim of the paper is to unravel the nature of microlevel processes of co-creation in radical service innovation. The study adopts sequential analysis to examine co-creation. Patterns of sequences of actions and interactions associated with 40 incremental developments, involving multiple actors, are investigated. These co-created innovative developments underpin the emergence of a radical telematics-based motor insurance service. The findings suggest that the co-creation path is not simple or uni-faceted, and the paper unravels the nature of complex patterns of activities and interactions, Our in-depth systematic analysis illuminates a combination approach with two main patterns of sequences: one dominated by ad-hoc and enduring independent innovation activities by network actors and one dominated by lead-firm innovation and interaction activity. The findings advance knowledge of the way co-creation occurs in radical service innovation. The study results suggest that managerial attention be placed to, first, finding ways to induce independent innovative behavior from network partners and, second, to the development of interaction mechanisms to foster sharing and visualization of such innovation advances. © 2012 Product Development & Management Association.

Caldwell J.L.,University of Manchester
Circulation Research | Year: 2014

RATIONALE:: Transverse (t-) tubules regulate cardiac excitation contraction coupling and exhibit inter-chamber and inter-species differences in expression. In cardiac disease t-tubule loss occurs and affects the systolic calcium transient. However, the mechanisms controlling t-tubule maintenance and whether these factors differ between species, cardiac chambers and in a disease setting remain unclear.OBJECTIVE:: To determine the role of the BAR domain protein amphiphysin II (AmpII) in regulating t-tubule maintenance and the systolic calcium transient.METHODS AND RESULTS:: T-tubule density was assessed by di-4-ANEPPS, FM4-64 or WGA staining using confocal microscopy. In rat, ferret and sheep hearts t-tubule density and AmpII protein levels were lower in the atrium than the ventricle. Heart failure was induced in sheep using right ventricular tachypacing and ferrets by ascending aortic coarctation. In both heart failure models, AmpII protein and t-tubule density were decreased in the ventricles. In the sheep, atrial t-tubules were also lost in heart failure and AmpII levels decreased. Conversely junctophilin 2 levels did not show inter-chamber differences in the rat and ferret nor did they change in heart failure in the sheep or ferret. Αdditionally, in rat atrial and sheep heart failure atrial cells where t-tubules were absent, junctophilin 2 had sarcomeric intracellular distribution. Small interfering RNA induced knockdown of AmpII protein reduced t-tubule density, calcium transient amplitude and the synchrony of the systolic calcium transient.CONCLUSIONS:: AmpII is intricately involved in t-tubule maintenance. Reducing AmpII protein decreases t-tubule density, reduces the amplitude and increases the heterogeneity of the systolic calcium transient. © 2014 American Heart Association, Inc.

Crow Y.J.,University of Manchester
Annals of the New York Academy of Sciences | Year: 2011

The concept of grouping Mendelian disorders associated with an upregulation of type I interferon is not currently recognized in the medical literature. Here, we argue that such a concept has scientific validity and clinical utility. Specifically, we discuss a group of conditions, including Aicardi-Goutières syndrome, spondyloenchondrodysplasia, and cases of systemic lupus erythematosus with complement deficiency, in which an upregulation of type I interferons is apparently central to their pathogenesis. We believe that these diseases can usefully be considered to represent a novel set of inborn errors of immunity, and that the recognition of such diseases as type I interferonopathies will have significance in the development and use of targeted therapies. © 2011 New York Academy of Sciences.

Saunders B.R.,University of Manchester
Journal of Colloid and Interface Science | Year: 2012

Hybrid polymer/nanoparticle solar cells have a light harvesting layer composed of semiconducting inorganic nanoparticles and a semiconducting conjugated polymer. They have potential to give high power conversion efficiencies (PCE). However, the PCE values reported for these solar cells are not currently as high as anticipated. This article reviews the main methods currently used for preparing hybrid polymer/nanoparticle solar cells from the colloid perspective. PCE data for the period of 2005-2011 are presented for hybrid polymer/nanoparticle solar cells and compared to those from polymer/fullerene cells. The key reasons for the relatively low PCE values for hybrid polymer/nanoparticle solar cells are uncontrolled aggregation and residual insulating ligands at the nanoparticle surface. Two hybrid polymer/nanoparticle systems studied at Manchester are considered in which the onset of aggregation and its affect on composite film morphology were studied from the colloidal perspective. It is concluded that step-change approaches are required to increase the PCEs of hybrid polymer/nanoparticle solar cells and move them toward the 10% value required for widespread commercialisation. A range of nanoparticles that have potential for application in possible longer term terawatt solar energy production are discussed. © 2011 Elsevier Inc.

Baron M.,University of Manchester
Seminars in Cell and Developmental Biology | Year: 2012

It is well established that Notch signalling is activated in response to ligand binding through a series of proteolytic cleavages that release the Notch intracellular domain, allowing it to translocate to the nucleus to regulate downstream target gene expression. However there is still much to learn about the mechanisms that can bring about these proteolytic events in the numerous physiological contexts in which signal activation occurs. A number of studies have suggested that endocytosis of Notch contributes to the signal activation process, but the molecular details are unclear and controversial. There is conflicting data as to whether endocytosis of the receptor is essential for ligand-induced signalling or supplements it. Other studies have revealed that Notch can be activated in the endosomal pathway, independently of its ligands, through the activity of Deltex, a Ring-domain Ubiquitin ligase that binds to the Notch intracellular domain. However, it is unclear how the Deltex-activation mechanism relates to that of ligand-induced signalling, or to ectopic Notch signalling brought about by disruption of ESCRT complexes that affect multivesicular body formation. This review will address these issues and argue that the data are best reconciled by proposing distinct activation mechanisms in different cellular locations that contribute to the cellular pool of the soluble Notch intracellular domain. The resulting signalling network may provide developmental robustness to environmental and genetic variation. © 2012 Elsevier Ltd.

In this paper, we describe the use of iTRAQ (isobaric Tags for Relative and Absolute Quantitation) tags for comparison of protein expression levels between multiple samples. These tags label all peptides in a protein digest before labeled samples are pooled, fractionated and analyzed using mass spectrometry (MS). As the tags are isobaric, the intensity of each peak is the sum of the intensity of this peptide from all samples, providing a moderate enhancement in sensitivity. On peptide fragmentation, amino-acid sequence ions also show this summed intensity, providing a sensitivity enhancement. However, the distinct distribution of isotopes in the tags is such that, on further fragmentation, a tag-specific reporter ion is released. The relative intensities of these ions represent the relative amount of peptide in the analytes. Integration of the relative quantification data for the peptides allows relative quantification of the protein. This protocol discusses the rationale behind design, optimization and performance of experiments, comparing protein samples using iTRAQ chemistries combined with strong cation exchange chromatographic fractionation and MS.

Cobb M.,University of Manchester
Cell | Year: 2013

In 1953, Watson and Crick not only described the double-helix structure of DNA, but also embraced the idea that genes contained a code that expresses information and thereby changed our view of life. This article traces how these ideas entered biological thinking and highlights the connections between different branches of science at the time, exploring the power of metaphor in science. © 2013 Elsevier Inc.

Sellick C.A.,University of Manchester
Nature protocols | Year: 2011

Metabolite profiling of industrially important suspension-cultured mammalian cells is being increasingly used for rational improvement of bioprocesses. This requires the generation of global metabolite profiles that cover a broad range of metabolites and that are representative of the cells at the time of sampling. The protocol described here is a validated method for recovery of physiologically relevant amounts of key metabolites from suspension-cultured mammalian cells. The method is a two-step process consisting of initial quenching of the cells (to stop cellular metabolism and allow isolation of the cells) followed by extraction of the metabolites. The cells are quenched in 60% methanol supplemented with 0.85% (wt/vol) ammonium bicarbonate at -40 °C. Metabolites are then extracted from the quenched cells using two 100% methanol extractions followed by a single water extraction. Metabolite samples generated using this protocol are amenable to analysis by mass spectrometry-based techniques (e.g., gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry), NMR spectroscopy and enzymatic assays.

Ding Z.,University of Manchester
IET Control Theory and Applications | Year: 2011

In this study, differential stability is introduced for non-linear systems, and this concept is further exploited in reduced-order observer design for non-linear systems with non-linearities of unmeasured state variables, a more general class of non-linear systems than the systems with linear observer errors. It has been shown that if the dynamics of unmeasured state variables under a state transformation is differentially stable, a reduced-order observer can be designed to produce asymptotically convergent estimates of the unmeasured state variables. A systematic design method is then introduced for a class of multi-output non-linear systems. For such a system, a non-linear term of the unmeasured state variables enter the system through a coupling matrix. It is found that a reduced-order observer can be designed if the linear part with the coupling matrix as the input matrix has no unstable invariant zeros. A further exploitation is presented for a class of single-output non-linear systems with non-linearity of unmeasured state variables. In this case, the coupling vector is allowed to be a vector field which depends on the system output. © 2011 The Institution of Engineering and Technology.

This inter-disciplinary theory-building paper is motivated by the debate on grand societal challenges and by calls in the innovation studies literature for frameworks that offer a better understanding of the co-evolution of industries and their economic, political, cultural, and social environments. In response to these debates, the paper develops a new triple embeddedness framework (TEF), which conceptualizes firms-in-industries as embedded in two external (economic and socio-political) environments and in an industry regime which mediates strategic actions towards the external environments. The TEF's theoretical logic draws on the adaptation-selection debate, which suggests that the co-evolution phenomenon can be approached from two angles. With regard to (population-level) selection theories, which highlight pressures on industries from external environments, the TEF accommodates insights from evolutionary economics, neo-institutional theory, and economic sociology. With regard to (firm-level) adaptation theories, the TEF accommodates insights from externally-oriented strategy schools (economic positioning strategy, innovation strategy, corporate political strategy, discursive strategy, issue management) and internally-oriented strategy approaches (linked to knowledge/capabilities and cognition/sensemaking). The combination of insights produces a multi-dimensional framework with bi-directional interactions between firms-in-industries and their environments. Implications for the grand challenge agenda are discussed in a separate section and illustrated with examples. © 2013 Elsevier B.V. All rights reserved.

Donnachie A.,University of Manchester | Landshoff P.V.,University of Cambridge
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2013

It is shown that pp and pp- data, including those from the TOTEM experiment, agree well with Regge theory. © 2013 Elsevier B.V.

Browne L.E.,University of Manchester
Wiley Interdisciplinary Reviews: Membrane Transport and Signaling | Year: 2012

P2X receptors are trimeric ion channels that open in response to extracellular ATP. The publication of the first X-ray structure of a closed P2X receptor has confirmed many of the functional experiments carried out since the mid-1990s and provides a point of reference for the molecular dissection of P2X receptor function. These co-ordinates shed light on the ATP binding sites housed in the extracellular domain, the contacts between subunits, the pathways for ion access, and the cation-selective pore that spans the cell membrane. They also provide a template for structure-based design of much needed pharmacological agents to act on a receptor superfamily whose physiological roles extend from synaptic transmission to inflammation and control of programmed cell death. Interpretation of functional data in the context of this closed P2X receptor structure reveals structural rearrangements in the transmembrane pore and extracellular domain. Here the current understanding of the molecular structure of P2X receptors is reviewed. This review will be of relevance to those interested in the mechanisms that underlie the molecular operation of P2X receptors, and other ion channels gated by diffusible ligands (pentameric Cys-loop receptors, tetrameric glutamate receptors), as well as trimeric ion channels that are distantly related to P2X receptors (acid-sensing ion channels and the epithelial sodium channel). © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..

Palmier-Claus J.,University of Manchester
Psychiatry research | Year: 2013

Suicide risk is high in early psychosis. Recent research has suggested that mood variability may be associated with levels of suicidal thoughts and behaviour. This has not been investigated in individuals during and following a first or second episode of non-affective psychosis. Repeated-measures data over 18 months from a large randomised controlled trial for cognitive behaviour therapy (N=309) were analysed using latent growth curve modelling, whereby both the variability and the level of depression, anxiety and guilt were entered as predictors of suicidality. The variability of depression, but not guilt and anxiety, predicted the course of suicidality even when controlling for a large range of potential confounders. The level of depression, anxiety and guilt for each participant also strongly predicted the development of suicidality. The findings support the theory that variability in depression may contribute to the formation of suicidal ideation and related behaviour. More variable depression may be harder to predict and intervene against, and therefore increase the likelihood that suicidality escalates. The levels of emotions may also be an important determinant. This has implications for the treatment and assessment of suicidality in early psychosis. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Woodcock L.V.,University of Manchester
Journal of Physical Chemistry B | Year: 2012

A state of random close packing (RCP) of spheres is found to have a thermodynamic status and a fundamental role in the description of liquid-state equilibria. The RCP limiting amorphous ground state, with reproducible density and well-characterized structure, is obtained by well-defined irreversible and reversible processes. The limiting packing fraction yRCP = 0.6366 ± 0.0005 (Buffons constant within the uncertainty), and a residual entropy per sphere δS(RCP-FCC) ≃ kB (Boltzmanns constant). Since the Mayer virial expansion does not represent dense fluid equations-of-state for densities exceeding the available-volume percolation transition (ρpa), we infer that a RCP state belongs to the same thermodynamic phase as prepercolation equilibrium dense hard-sphere fluid and likewise for hard-core fluids with attractive forces. Monte Carlo (MC) calculation of the liquid-state coexistence properties of square-well (SW) attractive spheres, together with existing MC results for liquid-vapor coexistence in the SW fluid, support this conclusion. Further findings for liquid-vapor coexistence limits are reported. The extremely weak second-order available-volume percolation transition of the hard-sphere fluid is strengthened by square-well perturbation as temperature is reduced. At the critical temperature, this transition becomes first order, whereupon a liquid at the percolation density coexists in thermodynamic equilibrium with its vapor at a lower density. The critical coexisting vapor density relates to the extended-volume bonded cluster percolation transition ρ pe(λ) defined for given well width (λ). Taking experimental liquid argon data as an example, it can be seen that the thermodynamic description of the coexistence limits, found here for square-well fluids, applies to real liquids. © 2012 American Chemical Society.

Ibrahim M.A.A.,University of Manchester | Ibrahim M.A.A.,Minia University
Journal of Physical Chemistry B | Year: 2012

A recently published study on halogen bonding in casein kinase 2 (CK2)-inhibitor complexes claimed that the halogen-bond-corrected PM6 semiempirical method (PM6-DH2X) describes the halogen bonding properties correctly, whereas the AMBER empirical potential fails. The current study employs our positive extra-point (PEP) approach for halogen bonding, in which the σ-hole on the halogen atom is represented by an extra point of charge. The performance of the two methods in describing halogen bonding in halobenzene•••Lewis base and CK2-inhibitor complexes was reassessed. Compared to basis set superposition error- (BSSE-) corrected MP2/aug-cc-pVDZ (with PP functions on the Br and I atoms) data, the AMBER force field described the halogen bonding in halobenzene•••Lewis base complexes slightly better than the PM6-DH2X method. Fifteen polyhalogenated benzimidazole inhibitors (taken from a study of Dobeš et al.) complexed to CK2 protein were studied. The binding energies were calculated using the molecular mechanical-generalized Born surface area (MM-GBSA) approach. Compared to the corresponding experimental data, the AMBER force field yielded much better results than the PM6-DH2X method. Finally, the performance of both methods in describing C-X•••π-system and C- X•••H-O/C interactions was examined. A comparison with MP2 data revealed that the PM6-DH2X method failed to describe them, whereas the AMBER force field performed well. © 2012 American Chemical Society.

O'Connor J.P.B.,University of Manchester | Jayson G.C.,Paterson Institute for Cancer Research
Clinical Cancer Research | Year: 2012

The management of solid tumors has been transformed by the advent of VEGF pathway inhibitors. Early clinical evaluation of these drugs has used pharmacodynamic biomarkers derived from advanced imaging such as dynamic MRI, computed tomography (CT), and ultrasound to establish proof of principle. We have reviewed published studies that used these imaging techniques to determine whether the same biomarkers relate to survival in renal, hepatocellular, and brain tumors in patients treated with VEGF inhibitors. Data show that in renal cancer, pretreatment measurements of Ktrans and early pharmacodynamic reduction in tumor enhancement and density have prognostic significance in patients treated with VEGF inhibitors. A weaker, but significant, relationship is seen with subtle early size change (10% in one dimension) and survival. Data from high-grade glioma suggest that pretreatment fractional blood volume and Ktrans were prognostic of overall survival. However, lack of control data with other therapies prevents assessment of the predictive nature of these biomarkers, and such studies are urgently required. ©2012 AACR.

Normal pregnancy is associated with the presence of circulating placental microvesicles (MVs). Increased MV shedding and altered immune activation are seen in patients with preeclampsia, suggesting that placental MVs may play a role in the pathophysiology of this disease. Therefore, the aim of this study was to investigate the activation of peripheral blood mononuclear cells (PBMCs) by MVs shed by first-trimester, normal term, and preeclamptic term placenta. First-trimester and preeclamptic term, but not normal term, placental-derived MVs activated PBMCs, as evidenced by elevated IL1B. Significant changes were also seen with several other cytokines and chemokines, and in general when compared to normal term MVs, preeclamptic MVs induced a greater pro-inflammatory response in PBMCs. Pretreatment of PBMCs with first-trimester or normal term placental MVs resulted in a dampened IL1B response to a subsequent lipopolysaccharide (LPS) challenge. In contrast, treatment of PBMCs with preeclamptic term placental MVs exacerbated the LPS response. This was also the case for several other cytokines and chemokines. These studies suggest that placental MVs can modulate basal peripheral immune cell activation and responsiveness to LPS during normal pregnancy, and that in preeclampsia this effect is exacerbated.

Herholz K.,University of Manchester
Biomarkers in Medicine | Year: 2012

PET with the glucose analog FDG as a tracer is a mature and increasingly available clinical imaging technique that can improve the diagnostic accuracy for Alzheimers disease, which is of particular value at an early stage of the disease when clinical symptoms are still mild and nonspecific. It can also monitor progression of Alzheimers disease, and the findings are closely related to clinical symptoms. FDG PET, therefore, could also potentially be used as an imaging biomarker for selection of patients and assessment of outcome in clinical trials. Several published intervention studies indicate a good correspondence between clinical outcome and FDG PET findings, but study designs and methods used for data analysis vary widely. Recent developments towards standardization of largely user-independent methods for quantification of regional metabolic impairment on FDG PET scans will allow a new generation of studies that could provide the required evidence for full qualification of FDG PET as an imaging biomarker in clinical trials. © 2012 Future Medicine Ltd.

Bensasson D.,University of Manchester
BMC Evolutionary Biology | Year: 2011

Background: Although their role in cell division is essential, centromeres evolve rapidly in animals, plants and yeasts. Unlike the complex centromeres of plants and aminals, the point centromeres of Saccharomcyes yeasts can be readily sequenced to distinguish amongst the possible explanations for fast centromere evolution. Results: Using DNA sequences of all 16 centromeres from 34 strains of Saccharomyces cerevisiae and population genomic data from Saccharomyces paradoxus, I show that centromeres in both species evolve 3 times more rapidly even than selectively unconstrained DNA. Exceptionally high levels of polymorphism seen in multiple yeast populations suggest that rapid centromere evolution does not result from the repeated selective sweeps expected under meiotic drive. I further show that there is little evidence for crossing-over or gene conversion within centromeres, although there is clear evidence for recombination in their immediate vicinity. Finally I show that the mutation spectrum at centromeres is consistent with the pattern of spontaneous mutation elsewhere in the genome. Conclusions: These results indicate that rapid centromere evolution is a common phenomenon in yeast species. Furthermore, these results suggest that rapid centromere evolution does not result from the mutagenic effect of gene conversion, but from a generalised increase in the mutation rate, perhaps arising from the unusual chromatin structure at centromeres in yeast and other eukaryotes. © 2011Bensasson; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2. 0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Dowker J.S.,University of Manchester
Classical and Quantum Gravity | Year: 2011

A piston is introduced into a spherical lune Casimir cavity turning it into two adjacent lunes separated by the (hemispherical) piston. On the basis of zeta-function regularization, the vacuum energy of the arrangement is finite for conformal propagation in spacetime. For even spheres this energy is independent of the angle of the lune. For odd dimensions it is shown that for all Neumann, or all Dirichlet, boundary conditions the piston is repelled or attracted by the nearest wall if d = 3, 7, ... or if d = 1, 5, ... , respectively. For hybrid N-D conditions these requirements are switched. If a mass is added, divergences arise which render the model suspect. The analysis, however, is relatively straightforward and involves the Barnes zeta function. The extension to finite temperatures is made and it is shown that for the 3, 7, ... series of odd spheres, the repulsion by the walls continues but that, above a certain temperature, the free energy acquires two minima symmetrically placed about the midpoint. © 2011 IOP Publishing Ltd.

Novoselov K.S.,University of Manchester
Reviews of Modern Physics | Year: 2011

Much like the world described in Abbott's Flatland, graphene is a two-dimensional object. And, as "Flatland" is "a romance of many dimensions," graphene is much more than just a flat crystal. It possesses a number of unusual properties which are often unique or superior to those in other materials. In this brief lecture I would like to explain the reason for my (and many other people's) fascination with this material, and invite the reader to share some of the excitement I've experienced while researching it. © 2011 American Physical Society.

Mullin T.,University of Manchester
Annual Review of Fluid Mechanics | Year: 2011

In his landmark paper of 1883, Reynolds addressed the question of why the fluid motion along a pipe changes from a laminar to a turbulent state at modest flow rates. His discoveries have remained a focus of hydrodynamic stability for the intervening 125 years, and the central puzzle of why the transition takes place at all remains unresolved. It is an enigma as all theoretical and numerical evidence suggests that the base state of fully developed flow, Hagen-Poiseuille flow, is linearly stable. The transition to turbulence is abrupt, mysterious, and largely dependent on the quality of the facility used in any experimental investigation. It is therefore not an example of transition via a sequence of instabilities or bifurcations in which considerable success has been achieved over the same period. Despite wide-ranging research activity that has uncovered many important pieces of the jigsaw, the central puzzle remains unresolved. The purpose of this review is to bring together the available experimental evidence and attempt to extract a set of accepted facts about this important problem. © 2011 by Annual Reviews. All rights reserved.

Logothetis N.K.,University of Manchester
Current Opinion in Neurobiology | Year: 2015

Brains are dynamic systems, consisting of huge number of massively interconnected elementary components. The activity of these components results in an initial condition-sensitive evolution of network states through highly non-linear, probabilistic interactions. The dynamics of such systems cannot be described merely by studying the behavior of their components; instead their study benefits from employing multimodal methods. Neural-Event-Triggered (NET) fMRI is a novel method allowing identification of events that can be used to examine multi-structure activity in the brain. First results offered insights into the networks that might be involved in memory consolidation. On-going work examines the physiological underpinnings of the up and down modulation of metabolic activity, mapped with this methodology. © 2014.

During Drosophila development, translational control plays a crucial role in regulating gene expression, and is particularly important during pre-patterning of the maturing oocyte. A critical step in translation initiation is the binding of the eukaryotic translation initiation factor 4E (eIF4E) to the mRNA cap structure, which ultimately leads to recruitment of the ribosome. d4EHP is a translational repressor that prevents translation initiation by out-competing eIF4E on the cap structure for a subset of mRNAs. However, only two examples of mRNAs subject to d4EHP translation repression in Drosophila are known. Here we show that the belle (bel) mRNA is translationally repressed by the d4EHP protein in the Drosophila ovary. Consistent with this regulation, d4EHP overexpression in the ovary phenocopies the bel mutant. We also provide evidence that the Bel protein binds to eIF4E and may itself function as a translation repressor protein, with bruno as a potential target for Bel repression in the oocyte. Bruno is known to repress the mRNA of the key oocyte axis determinant oskar (osk) during oogenesis, and we find that an increase in the level of Bruno protein in bel mutant ovaries is associated with a reduction in Osk protein. Overall, our data suggest that a translational regulatory network exists in which consecutive translational repression events act to correctly pattern the Drosophila oocyte.

Lavender T.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Telephone communication is increasingly being accepted as a useful form of support within health care. There is some evidence that telephone support may be of benefit in specific areas of maternity care such as to support breastfeeding and for women at risk of depression. There is a plethora of telephone-based interventions currently being used in maternity care. It is therefore timely to examine which interventions may be of benefit, which are ineffective, and which may be harmful. To assess the effects of telephone support during pregnancy and the first six weeks post birth, compared with routine care, on maternal and infant outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (23 January 2013) and reference lists of all retrieved studies. We included randomised controlled trials, comparing telephone support with routine care or with another supportive intervention aimed at pregnant women and women in the first six weeks post birth. Three review authors independently assessed studies identified by the search strategy, carried out data extraction and assessed risk of bias. Data were entered by one review author and checked by a second. Where necessary, we contacted trial authors for further information on methods or results. We have included data from 27 randomised trials involving 12,256 women. All of the trials examined telephone support versus usual care (no additional telephone support). We did not identify any trials comparing different modes of telephone support (for example, text messaging versus one-to-one calls). All but one of the trials were carried out in high-resource settings. The majority of studies examined support provided via telephone conversations between women and health professionals although a small number of trials included telephone support from peers. In two trials women received automated text messages. Many of the interventions aimed to address specific health problems and collected data on behavioural outcomes such as smoking cessation and relapse (seven trials) or breastfeeding continuation (seven trials). Other studies examined support interventions aimed at women at high risk of postnatal depression (two trials) or preterm birth (two trials); the rest of the interventions were designed to offer women more general support and advice.For most of our pre-specified outcomes few studies contributed data, and many of the results described in the review are based on findings from only one or two studies. Overall, results were inconsistent and inconclusive although there was some evidence that telephone support may be a promising intervention. Results suggest that telephone support may increase women's overall satisfaction with their care during pregnancy and the postnatal period, although results for both periods were derived from only two studies. There was no consistent evidence confirming that telephone support reduces maternal anxiety during pregnancy or after the birth of the baby, although results on anxiety outcomes were not easy to interpret as data were collected at different time points using a variety of measurement tools. There was evidence from two trials that women at high risk of depression who received support had lower mean depression scores in the postnatal period, although there was no clear evidence that women who received support were less likely to have a diagnosis of depression. Results from trials offering breastfeeding telephone support were also inconsistent, although the evidence suggests that telephone support may increase the duration of breastfeeding. There was no strong evidence that women receiving telephone support were less likely to be smoking at the end of pregnancy or during the postnatal period.For infant outcomes, such as preterm birth and infant birthweight, overall, there was little evidence. Where evidence was available, there were no clear differences between groups. Results from two trials suggest that babies whose mothers received support may have been less likely to have been admitted to a neonatal intensive care unit (NICU), although it is not easy to understand the mechanisms underpinning this finding. Despite some encouraging findings, there is insufficient evidence to recommend routine telephone support for women accessing maternity services, as the evidence from included trials is neither strong nor consistent. Although benefits were found in terms of reduced depression scores, breastfeeding duration and increased overall satisfaction, the current trials do not provide strong enough evidence to warrant investment in resources.

Furness S.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Xerostomia is the subjective sensation of dry mouth. Common causes of xerostomia include adverse effects of many commonly prescribed medications, disease (e.g. Sjogren's Syndrome) and radiotherapy outcomes or where different scales were used to assess an outcome, we calculated standardised mean differences (SMD) together with 95% CIs. We attempted to extract data on adverse effects of interventions. Where data were missing or unclear we attempted to contact study authors to obtain further information. There were nine studies (total 366 participants randomised) included in this review of non-pharmacological interventions for dry mouth which were divided into three comparisons. Eight studies were assessed at high risk of bias in at least one domain and the remaining study was at unclear risk of bias.Five small studies (total 153 participants, with dry mouth following radiotherapy treatment) compared acupuncture with placebo. Four were assessed at high risk and one at unclear risk of bias. Two trials reported outcome data for dry mouth in a form suitable for meta-analysis. The pooled estimate of these two trials (70 participants, low quality evidence) showed no difference between acupuncture and control in dry mouth symptoms (SMD -0.34, 95% CI -0.81 to 0.14, P value 0.17, I(2) = 39%) with the confidence intervals including both a possible reduction or a possible increase in dry mouth symptoms. Acupuncture was associated with more adverse effects (tiny bruises and tiredness which were mild and temporary). There was a very small increase in unstimulated whole saliva (UWS) at the end of 4 to 6 weeks of treatment (three trials, 71 participants, low quality evidence) (MD 0.02 ml/minute, 95% CI 0 to 0.04, P value 0.04, I(2) = 57%), and this benefit persisted at the 12-month follow-up evaluation (two trials, 54 participants, low quality evidence) (UWS, MD 0.06 ml/minute, 95% CI 0.01 to 0.11, P value 0.03, I(2) = 10%). For the outcome of stimulated whole saliva (SWS, three trials, 71 participants, low quality evidence) there was a benefit favouring acupuncture (MD 0.19 ml/minute, 95% CI 0.07 to 0.31, P value 0.002, I(2) = 1%) an effect which also persisted at the 12-month follow-up evaluation (SWS MD 0.28 ml/minute, 95% CI 0.09 to 0.47, P value 0.004, I(2) = 0%) (two trials, 54 participants, low quality evidence).Two small studies, both at high risk of bias, compared the use of an electrostimulation device with a placebo device in participants with Sjögren's Syndrome (total 101 participants). A further study, also at high risk of bias, compared acupuncture-like electrostimulation of different sets of points in participants who had previously been treated with radiotherapy. None of these studies reported the outcome of dry mouth. There was no difference between electrostimulation and placebo in the outcomes of UWS or SWS at the end of the 4-week treatment period in the one study (very low that provided data for these outcomes. No adverse effects were reported.A single study at high risk of bias, compared the stimulatory effect of powered versus manual toothbrushing and found no difference for the outcomes of UWS or SWS. There is low quality evidence that acupuncture is no different from placebo acupuncture with regard to dry mouth symptoms, which is the most important outcome. This may be because there were insufficient participants included in the two trials to show a possible effect or it may be that there was some benefit due to 'placebo' acupuncture which could have biased the effect to the null. There is insufficient evidence to determine the effects of electrostimulation devices on dry mouth symptoms. It is well known that dry mouth symptoms may be problematic even when saliva production is increased, yet only two of the trials that evaluated acupuncture reported dry mouth symptoms, a worrying reporting bias. There is some low quality evidence that acupuncture results in a small increase in saliva production in patients with dry mouth following radiotherapy.There is insufficient evidence to determine the effects of electrostimulation devices on dry mouth symptoms or saliva production in patients with Sjögren's Syndrome. Reported adverse effects of acupuncture are mild and of short duration, and there were no reported adverse effects from electrostimulation.

Smyth R.M.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Intentional artificial rupture of the amniotic membranes during labour, sometimes called amniotomy or 'breaking of the waters', is one of the most commonly performed procedures in modern obstetric and midwifery practice. The primary aim of amniotomy is to speed up contractions and, therefore, shorten the length of labour. However, there are concerns regarding unintended adverse effects on the woman and baby. To determine the effectiveness and safety of amniotomy alone for routinely shortening all labours that start spontaneously. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 April 2013). Randomised controlled trials comparing amniotomy alone versus intention to preserve the membranes. We excluded quasi-randomised trials. Two review authors assessed identified studies for inclusion, assessed risk of bias and extracted data. Primary analysis was by intention-to-treat. We have included 15 studies in this updated review, involving 5583 women. Amniotomy alone versus intention to preserve the membranes (no amniotomy) for spontaneous labour There was no clear statistically significant difference between women in the amniotomy and control groups in length of the first stage of labour (mean difference (MD) -20.43 minutes, 95% confidence interval (CI) -95.93 to 55.06), caesarean section (risk ratio (RR) 1.27, 95% CI 0.99 to 1.63), maternal satisfaction with childbirth experience (MD -1.10, 95% CI -7.15 to 4.95) or Apgar score less than seven at five minutes (RR 0.53, 95% CI 0.28 to 1.00). There was no consistency between trials regarding the timing of amniotomy during labour in terms of cervical dilatation. Amniotomy alone versus intention to preserve the membranes (no amniotomy) for spontaneous labours that have become prolonged There was no clear statistically significant difference between women in the amniotomy and control group in caesarean section (RR 0.95, 95% CI 0.15 to 6.08), maternal satisfaction with childbirth experience (MD 22.00, 95% CI 2.74 to 41.26) or Apgar score less than seven at five minutes (RR 2.86, 95% CI 0.12 to 66.11). On the basis of the findings of this review, we cannot recommend that amniotomy should be introduced routinely as part of standard labour management and care. We recommend that the evidence presented in this review should be made available to women offered an amniotomy and may be useful as a foundation for discussion and any resulting decisions made between women and their caregivers.

Furber C.M.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2013

Being obese and pregnant is associated with substantial risks for the mother and her child. Current weight management guidance for obese pregnant women is limited. The latest recommendations suggest that obese pregnant women should gain between 5.0 and 9.1 kg during the pregnancy period, and weight loss is discouraged. However, observational studies indicate that some obese pregnant women, especially those who are heavier, lose weight during pregnancy. Furthermore, some obese pregnant women may intentionally lose weight. The safety of weight loss when pregnant and obese is not substantiated; some observational studies suggest that risks associated with weight loss such as pre-eclampsia are improved, but others indicate that the incidence of small- for-gestational infants are increased. It is important to evaluate interventions that are designed to reduce weight in obese pregnant women so that the safety of weight loss during this period can be established. To evaluate the effectiveness of interventions that reduce weight in obese pregnant women. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2012) and contacted experts in the field. Randomised controlled trials, 'quasi-random' studies and cluster-randomised trials comparing a weight-loss intervention with routine care or more than one weight loss intervention. Cross-over trials were not eligible for inclusion. We identified no studies that met the inclusion criteria for this review. There were no included trials. There are no trials designed to reduce weight in obese pregnant women. Until the safety of weight loss in obese pregnant women can be established, there can be no practice recommendations for these women to intentionally lose weight during the pregnancy period. Further study is required to explore the potential benefits, or harm, of weight loss in pregnancy when obese before weight loss interventions in pregnancy can be designed. Qualitative research is also required to explore dietary habits of obese pregnant women, especially those who are morbidly obese.

North R.A.,University of Manchester | Jarvis M.F.,Abbvie Inc.
Molecular Pharmacology | Year: 2013

The study of P2X receptors has long been handicapped by a poverty of small-molecule tools that serve as selective agonists and antagonists. There has been progress, particularly in the past 10 years, as cell-based high-throughput screening methods were applied, together with large chemical libraries. This has delivered some drug-like molecules in several chemical classes that selectively target P2X1, P2X3, or P2X7 receptors. Some of these are, or have been, in clinical trials for rheumatoid arthritis, pain, and cough. Current preclinical research programs are studying P2X receptor involvement in pain, inflammation, osteoporosis, multiple sclerosis, spinal cord injury, and bladder dysfunction. The determination of the atomic structure of P2X receptors in closed and open (ATP-bound) states by X-ray crystallography is now allowing new approaches by molecular modeling. This is supported by a large body of previous work using mutagenesis and functional expression, and is now being supplemented by molecular dynamic simulations and in silico ligand docking. These approaches should lead to P2X receptors soon taking their place alongside other ion channel proteins as therapeutically important drug targets. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.

Bolton-Maggs P.H.,University of Manchester
Pediatric Blood and Cancer | Year: 2013

The rare inherited coagulation disorders (RICD) are uncommon and thus not well-defined in terms of severity or management. Inheritance is autosomal; in some of these disorders in the heterozygote state affected individuals may be mildly symptomatic. Severe deficiencies are more common in association with consanguinity. Factor X and factor XIII deficiency have the most severe manifestations, while factor XI deficiency is the least severe. Factor VII and factor XI deficiencies show a poor relationship between the factor level and bleeding risk. Unlike hemophilia, women are equally affected by these RICD and can have problems related to menstruation and childbirth. © 2012 Wiley Periodicals, Inc.

De Visser S.P.,University of Manchester
Journal of Physical Chemistry B | Year: 2011

One of the most basic equations of state describing nonideal gases and liquids is the van der Waals equation of state, and as a consequence, it is generally taught in most first year undergraduate chemistry courses. In this work, we show that the constants a and b in the van der Waals equation of state are linearly proportional to the polarizability volume of the molecules in a gas or liquid. Using this information, a new thermodynamic one-parameter equation of state is derived that contains experimentally measurable variables and physics constants only. This is the first equation of state apart from the Ideal Gas Law that contains experimentally measurable variables and physics constants only, and as such, it may be a very useful and practical equation for the description of dilute gases and liquids. The modified van der Waals equation of state describes pV as the sum of repulsive and attractive intermolecular interaction energies that are represented by an exponential repulsion function between the electron clouds of the molecules and a London dispersion component, respectively. The newly derived equation of state is tested against experimental data for several gas and liquid examples, and the agreement is satisfactory. The description of the equation of state as a one-parameter function also has implications on other thermodynamic functions, such as critical parameters, virial coefficients, and isothermal compressibilities. Using our modified van der Waals equation of state, we show that all of these properties are a function of the molecular polarizability volume. Correlations of experimental data confirm the derived proportionalities. © 2011 American Chemical Society.

Millar C.B.,University of Manchester
Biochemical Journal | Year: 2013

Chromatin acts as an organizer and indexer of genomic DNA and is a highly dynamic and regulated structure with properties directly related to its constituent parts. Histone variants are abundant components of chromatin that replace canonical histones in a subset of nucleosomes, thereby altering nucleosomal characteristics. The present review focuses on the H2A variant histones, summarizing current knowledge of how H2A variants can introduce chemical and functional heterogeneity into chromatin, the positions that nucleosomes containing H2A variants occupy in eukaryotic genomes, and the regulation of these localization patterns. © The Authors Journal compilation © 2013 Biochemical Society.

Guinea F.,CSIC - Institute of Materials Science | Katsnelson M.I.,Radboud University Nijmegen | Geim A.K.,University of Manchester
Nature Physics | Year: 2010

Among many remarkable qualities of graphene, its electronic properties attract particular interest owing to the chiral character of the charge carriers, which leads to such unusual phenomena as metallic conductivity in the limit of no carriers and the half-integer quantum Hall effect observable even at room temperature. Because graphene is only one atom thick, it is also amenable to external influences, including mechanical deformation. The latter offers a tempting prospect of controlling graphenes properties by strain and, recently, several reports have examined graphene under uniaxial deformation. Although the strain can induce additional Raman features, no significant changes in graphenes band structure have been either observed or expected for realistic strains of up to ∼15% (refs9, 10, 11). Here we show that a designed strain aligned along three main crystallographic directions induces strong gauge fields that effectively act as a uniform magnetic field exceeding 10 T. For a finite doping, the quantizing field results in an insulating bulk and a pair of countercirculating edge states, similar to the case of a topological insulator. We suggest realistic ways of creating this quantum state and observing the pseudomagnetic quantum Hall effect. We also show that strained superlattices can be used to open significant energy gaps in graphenes electronic spectrum. © 2010 Macmillan Publishers Limited. All rights reserved.

Dowker J.S.,University of Manchester
Journal of Physics A: Mathematical and Theoretical | Year: 2010

The coefficient of the log term in the entanglement entropy associated with hyperspherical surfaces in flat spacetime is shown to equal the conformal anomaly by conformally transforming Euclideanized spacetime to a sphere and using already existing formulae for the relevant heat-kernel coefficients after cyclic factoring. The result follows from the fact that the conformal anomaly on this lune has an extremum at the ordinary sphere limit. A proof is given. Agreement with a recent evaluation of the coefficient is found. © 2010 IOP Publishing Ltd.

Battye R.A.,University of Manchester | Pearson J.A.,Durham University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

The evolution of perturbations is a crucial part of the phenomenology of the dark sector cosmology. We advocate parametrizing these perturbations using equations of state for the entropy perturbation and the anisotropic stress. For small perturbations, these equations of state will be linear in the density, velocity and metric perturbations, and in principle these can be related back to the field content of the underlying model allowing for confrontation with observations. We illustrate our point by constructing gauge-invariant entropy perturbations for theories where the dark sector Lagrangian is a general function of a scalar field, its first and second derivatives, and the metric and its first derivative, L=L(,∂μ, ∂μ∂ν,gμν, ∂αgμν). As an example, we show how to apply this approach to the case of models of kinetic gravity braiding. © 2013 American Physical Society.

Tee K.L.,University of Manchester | Wong T.S.,University of Sheffield
Biotechnology Advances | Year: 2013

Genetic diversity creation is a core technology in directed evolution where a high quality mutant library is crucial to its success. Owing to its importance, the technology in genetic diversity creation has seen rapid development over the years and its application has diversified into other fields of scientific research. The advances in molecular cloning and mutagenesis since 2008 were reviewed. Specifically, new cloning techniques were classified based on their principles of complementary overhangs, homologous sequences, overlapping PCR and megaprimers and the advantages, drawbacks and performances of these methods were highlighted. New mutagenesis methods developed for random mutagenesis, focused mutagenesis and DNA recombination were surveyed. The technical requirements of these methods and the mutational spectra were compared and discussed with references to commonly used techniques. The trends of mutant library preparation were summarised. Challenges in genetic diversity creation were discussed with emphases on creating "smart" libraries, controlling the mutagenesis spectrum and specific challenges in each group of mutagenesis methods. An outline of the wider applications of genetic diversity creation includes genome engineering, viral evolution, metagenomics and a study of protein functions. The review ends with an outlook for genetic diversity creation and the prospective developments that can have future impact in this field. © 2013 The Authors.

Spector L.G.,University of Minnesota | Birch J.,University of Manchester
Pediatric Blood and Cancer | Year: 2012

Few causes of hepatoblastoma have been conclusively identified, mainly due to the extreme rarity of the disease. Inherited conditions including Familial Adenomatous Polyposis and Beckwith-Wiedemann Syndrome dramatically raise risk of hepatoblastoma but account for few cases overall. A small number of case-control studies investigating risk factors for sporadic hepatoblastoma have been conducted to date. Although most of these studies feature fewer than 200 cases, several clues have emerged. Most notably there is a roughly 20-fold increased risk of hepatoblastoma among children with very low birth weight (<1,500g) and a doubling of risk among those with moderately low birth weight (1,500-2,500g). A modicum of evidence points to a possible role of parental tobacco use prior to or during pregnancy in the causation of hepatoblastoma as well. © 2012 Wiley Periodicals, Inc.

Potgieter M.,University of Pretoria | Bester J.,University of Pretoria | Kell D.B.,University of Manchester | Pretorius E.,University of Pretoria
FEMS Microbiology Reviews | Year: 2015

Blood in healthy organisms is seen as a 'sterile' environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. 'Non-culturability', reflected by discrepancies between plate counts and total counts, is commonplace in environmental microbiology. It is overcome by improved culturing methods, and we asked how common this would be in blood. A number of recent, sequence-based and ultramicroscopic studies have uncovered an authentic blood microbiome in a number of non-communicable diseases. The chief origin of these microbes is the gut microbiome (especially when it shifts composition to a pathogenic state, known as 'dysbiosis'). Another source is microbes translocated from the oral cavity. 'Dysbiosis' is also used to describe translocation of cells into blood or other tissues. To avoid ambiguity, we here use the term 'atopobiosis' for microbes that appear in places other than their normal location. Atopobiosis may contribute to the dynamics of a variety of inflammatory diseases. Overall, it seems that many more chronic, non-communicable, inflammatory diseases may have a microbial component than are presently considered, and may be treatable using bactericidal antibiotics or vaccines. © FEMS 2015.

Dumville J.C.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Foot ulcers in people with diabetes are a prevalent and serious global health issue. Dressings form a key part of ulcer treatment, with clinicians and patients having many different types to choose from including hydrogel dressings. A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use. To assess the effects of hydrogel wound dressings compared with alternative dressings or none on the healing of foot ulcers in people with diabetes. For this first update, in April 2013, we searched the following databases the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions based on language or date of publication. Published or unpublished randomised controlled trials (RCTs) that have compared the effects on ulcer healing of hydrogel with alternative wound dressings or no dressing in the treatment of foot ulcers in people with diabetes. Two review authors independently performed study selection, risk of bias assessment and data extraction. We included five studies (446 participants) in this review. Meta analysis of three studies comparing hydrogel dressings with basic wound contract dressings found significantly greater healing with hydrogel: risk ratio (RR) 1.80, 95% confidence interval (CI) 1.27 to 2.56. The three pooled studies had different follow-up times (12 weeks, 16 weeks and 20 weeks) and also evaluated ulcers of different severities (grade 3 and 4; grade 2 and grade unspecified). One study compared a hydrogel dressing with larval therapy and found no statistically significant difference in the number of ulcers healed and another found no statistically significant difference in healing between hydrogel and platelet-derived growth factor. There was also no statistically significant difference in number of healed ulcers between two different brands of hydrogel dressing. All included studies were small and at unclear risk of bias and there was some clinical heterogeneity with studies including different ulcer grades. No included studies compared hydrogel with other advanced wound dressings. There is some evidence to suggest that hydrogel dressings are more effective in healing (lower grade) diabetic foot ulcers than basic wound contact dressings however this finding is uncertain due to risk of bias in the original studies. There is currently no research evidence to suggest that hydrogel is more effective than larval therapy or platelet-derived growth factors in healing diabetic foot ulcers, nor that one brand of hydrogel is more effective than another in ulcer healing. No RCTs comparing hydrogel dressings with other advanced dressing types were found.

Dumville J.C.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Foot ulcers in people with diabetes are a prevalent and serious global health issue. Wound dressings are regarded as important components of ulcer treatment, with clinicians and patients having many different types to choose from including hydrocolloid dressings. There is a range of different hydrocolloids available including fibrous-hydrocolloid and hydrocolloid (matrix) dressings. A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use. To compare the effects of hydrocolloid wound dressings with no dressing or alternative dressings on the healing of foot ulcers in people with diabetes. For this first update, in April 2013, we searched the following databases the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions based on language or date of publication. Published or unpublished randomised controlled trials (RCTs) that have compared the effects on ulcer healing of hydrocolloid with alternative wound treatments in the treatment of foot ulcers in people with diabetes. Two review authors independently performed study selection, risk of bias assessment and data extraction. We included five studies (535 participants) in the review: these compared hydrocolloids with basic wound contact dressings, foam dressings, alginate dressings and a topical treatment. Meta-analysis of two studies indicated no statistically significant difference in ulcer healing between fibrous-hydrocolloids and basic wound contact dressings: risk ratio 1.01 (95% CI 0.74 to 1.38). One of these studies found that a basic wound contact dressing was more cost-effective than a fibrous-hydrocolloid dressing. One study compared a hydrocolloid-matrix dressing with a foam dressing and found no statistically significant difference in the number of ulcers healed. There was no statistically significant difference in healing between an antimicrobial (silver) fibrous-hydrocolloid dressing and standard alginate dressing; an antimicrobial dressing (iodine-impregnated) and a standard fibrous hydrocolloid dressing or a standard fibrous hydrocolloid dressing and a topical cream containing plant extracts. Currently there is no research evidence to suggest that any type of hydrocolloid wound dressing is more effective in healing diabetic foot ulcers than other types of dressing or a topical cream containing plant extracts. Decision makers may wish to consider aspects such as dressing cost and the wound management properties offered by each dressing type e.g. exudate management.

Hackl E.V.,University of Manchester
Biopolymers | Year: 2014

Natively unfolded (intrinsically disordered (ID) proteins) have been attracting an increasing attention due to their involvement in many regulatory processes. Natively unfolded proteins can fold upon binding to their metabolic partners. Coupled folding and binding events usually involve only relatively short motifs (binding motifs). These binding motifs which are able to fold should have an increased propensity to form a secondary structure. The aim of the present work was to probe the conformation of the intrinsically disordered protein 4E-BP1 in the native and partly folded states by limited proteolysis and to reveal regions with a high propensity to form an ordered structure. Trifuoroethanol (TFE) in low concentrations (up to 15 vol%) was applied to increase the helical population of protein regions with a high intrinsic propensity to fold. When forming helical structures, these regions lose mobility and become more protected from proteases than random/unfolded protein regions. Limited proteolysis followed by mass spectrometry analysis allows identification of the regions with decreased mobility in TFE solutions. Trypsin and V8 proteases were used to perform limited proteolysis of the 4E-BP1 protein in buffer and in solutions with low TFE concentrations at 37°C and at elevated temperatures (42 and 50°C). Comparison of the results obtained with the previously established 4E-BP1 structure and the binding motif illustrates the ability of limited proteolysis in the presence of a folding assistant (TFE) to map the regions with high and low propensities to form a secondary structure revealing potential binding motifs inside the intrinsically disordered protein. Copyright © 2013 Wiley Periodicals, Inc.

Dumville J.C.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Foot ulcers in people with diabetes are a prevalent and serious global health issue. Dressings form a key part of ulcer treatment, with clinicians and patients having many different types to choose from. A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use. The review aimed to evaluate the effects of foam wound dressings on the healing of foot ulcers in people with diabetes. For this first update we searched the following databases the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL in April 2013. There were no restrictions based on language or date of publication. Published or unpublished randomised controlled trials (RCTs) that evaluated the effects on ulcer healing of one or more foam wound dressings in the treatment of foot ulcers in people with diabetes. Two review authors independently performed study selection, risk of bias assessment and data extraction. We included six studies (157 participants) in this review. Meta analysis of two studies indicated that foam dressings do not promote the healing of diabetic foot ulcers compared with basic wound contact dressings (RR 2.03, 95%CI 0.91 to 4.55). Pooled data from two studies comparing foam and alginate dressing found no statistically significant difference in ulcer healing (RR 1.50, 95% CI 0.92 to 2.44). There was no statistically significant difference in the number of diabetic foot ulcers healed when foam dressings were compared with hydrocolloid (matrix) dressings. All included studies were small and/or had limited follow-up times. Currently there is no research evidence to suggest that foam wound dressings are more effective in healing foot ulcers in people with diabetes than other types of dressing however all trials in this field are very small. Decision makers may wish to consider aspects such as dressing cost and the wound management properties offered by each dressing type e.g. exudate management.

Smith A.J.,University of Manchester
Physiology (Bethesda, Md.) | Year: 2011

14-3-3 proteins regulate the function and subcellular sorting of membrane proteins. Often, 14-3-3 binding to client proteins requires phosphorylation of the client, but the relevant kinase is unknown in most cases. We summarize current progress in identifying kinases that target membrane proteins with 14-3-3 binding sites and discuss the molecular mechanisms of 14-3-3 action. One of the kinases involved is Akt/PKB, which has recently been shown to activate the 14-3-3-dependent switch in a number of client membrane proteins.

Dumville J.C.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Foot ulcers in people with diabetes mellitus are a common and serious global health issue. Dressings form a key part of ulcer treatment, with clinicians and patients having many different types to choose from including alginate dressings. A clear and current overview of current evidence is required to facilitate decision-making regarding dressing use. To compare the effects of alginate wound dressings with no wound dressing or alternative dressings on the healing of foot ulcers in people with diabetes mellitus. For this first update, in April 2013, we searched the following databases the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. There were no restrictions based on language or date of publication. Published or unpublished randomised controlled trials (RCTs) that have compared the effects on ulcer healing of alginate dressings with alternative wound dressings or no dressing in the treatment of foot ulcers in people with diabetes. Two review authors independently performed study selection, risk of bias assessment and data extraction. We included six studies (375 participants) in this review; these compared alginate dressings with basic wound contact dressings, foam dressings and a silver-containing, fibrous-hydrocolloid dressing. Meta analysis of two studies found no statistically significant difference between alginate dressings and basic wound contact dressings: risk ratio (RR) 1.09 (95% CI 0.66 to 1.80). Pooled data from two studies comparing alginate dressings with foam dressings found no statistically significant difference in ulcer healing (RR 0.67, 95% CI 0.41 to 1.08). There was no statistically significant difference in the number of diabetic foot ulcers healed when an anti-microbial (silver) hydrocolloid dressing was compared with a standard alginate dressing (RR 1.40, 95% CI 0.79 to 2.47). All studies had short follow-up times (six to 12 weeks), and small sample sizes. Currently there is no research evidence to suggest that alginate wound dressings are more effective in healing foot ulcers in people with diabetes than other types of dressing however many trials in this field are very small. Decision makers may wish to consider aspects such as dressing cost and the wound management properties offered by each dressing type e.g. exudate management.

Bowen A.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Unilateral spatial neglect causes difficulty attending to one side of space. Various rehabilitation interventions have been used but evidence of their benefit is lacking. To assess whether cognitive rehabilitation improves functional independence, neglect (as measured using standardised assessments), destination on discharge, falls, balance, depression/anxiety and quality of life in stroke patients with neglect measured immediately post-intervention and at longer-term follow-up; and to determine which types of interventions are effective and whether cognitive rehabilitation is more effective than standard care or an attention control. We searched the Cochrane Stroke Group Trials Register (last searched June 2012), MEDLINE (1966 to June 2011), EMBASE (1980 to June 2011), CINAHL (1983 to June 2011), PsycINFO (1974 to June 2011), UK National Research Register (June 2011). We handsearched relevant these subgroups (I2 > 40%) when we pooled standardised neglect assessment data, limiting the ability to draw generalised trials of cognitive rehabilitation for neglect. However, future studies need to have appropriate high quality methodological design and reporting, to examine persisting effects of treatment and to include an attention control comparator.

McLeod D.,University of Manchester
Acta Ophthalmologica | Year: 2010

The volume of cells that a length of capillary supplies with O2 is called a Krogh cylinder. This geometric 'tissue unit' was named after the Danish zoophysiologist and Nobel laureate August Krogh who made important discoveries in the fields of external and internal respiration in the first half of the last century. Krogh's ideas concerning tissue O2 distribution can be extrapolated to retinal oxygenation by larger vessels (including arterioles, arteries and even veins) and by vessel groups within higher-order 'microvascular units' (including the choroid). During retinal development, for example, the difference in pO2 levels within arteries and capillaries determines Krogh cylinders of different radius and establishes the periarterial capillary-free zone of His. The O2 supply to the venous end of a tissue unit may be compromised during periods of reduced perfusion, increased O2 consumption or hypoxaemia, resulting in an 'anoxic corner' of the Krogh cylinder. A funnel of hypometabolic (and therefore hypoxia-tolerant) cells will likely intervene between the necrotic cells and unaffected cells located closer to the O2 source. Macular perivenular whitening heralds anoxic corners and/or hypoxic funnels owing to hypoperfusion within second-order microvascular units. In eyes with extensive retinal capillary closure from diabetes, Krogh cylinders surround the medium-sized arteries and veins that form arteriovenous shunts while traversing the midperipheral retina. These isolated tissue units incorporate an outer sheath of hypoxic cells within which vascular endothelial growth factor is upregulated. This 'angiogenic sheath' expands following retinal detachment; it corresponds to the hypoxia-tolerant funnel within capillary-based tissue units and to the cerebral penumbra after stroke. Journal compilation © 2010 Acta Ophthalmol.

Bastia T.,University of Manchester
Environment and Planning A | Year: 2011

Feminist geographies of migration are often based on the assumption that migration brings about social change, potentially disrupting patriarchal structures and bringing about new spaces where gender relations can be renegotiated and reconfigured. On the basis of multisited research conducted with migrants from the same community of origin in Bolivia, I analyse how gender, class, and ethnicity are renegotiated through internal and cross-border migration. A transnational, multi- scalar, multisited, and intersectional approach is applied to the study of social change through migration, with the aim of investigating whether labour migration provides avenues for greater gender equality. At the individual level there are certainly indications that women achieve greater indepen- dence through migration. However, the multiscalar and intersectional analysis suggests that women trade 'gender gains' for upward social mobility in the class hierarchy. By doing so, they also contribute to the reproduction of patriarchal social relations. © 2011 Pion Ltd and its Licensors.

Buckley M.,University of Manchester
Proceedings of the Royal Society B: Biological Sciences | Year: 2015

Since the late eighteenth century, fossils of bizarre extinct creatures have been described from the Americas, revealing a previously unimagined chapter in the history of mammals. The most bizarre of these are the ‘native’ South American ungulates thought to represent a group of mammals that evolved in relative isolation on South America, but with an uncertain affinity to any particular placental lineage. Many authors have considered them descended from Laurasian ‘condylarths’, which also includes the probable ancestors of perissodactyls and artiodactyls, whereas others have placed them either closer to the uniquely South American xenarthrans (anteaters, armadillos and sloths) or the basal afrotherians (e.g. elephants and hyraxes). These hypotheses have been debated owing to conflicting morphological characteristics and the hitherto inability to retrieve molecular information. Of the ‘native’ South American mammals, only the toxodonts and litopterns persisted until the Late Pleistocene–Early Holocene. Owing to known difficulties in retrieving ancient DNA (aDNA) from specimens from warm climates, this research presents a molecular phylogeny for both Macrauchenia patachonica (Litopterna) and Toxodon platensis (Notoungulata) recovered using proteomics-based (liquid chromatography–tandem mass spectrometry) sequencing analyses of bone collagen. The results place both taxa in a clade that is monophyletic with the perissodactyls, which today are represented by horses, rhinoceroses and tapirs. © 2015 The Authors.

Reeves M.,University of Manchester
Environment and Planning D: Society and Space | Year: 2011

This paper proceeds from a moment of impromptu border-fixing in the wake of an intercommunal conflict, to explore the everyday spatialisation of the state in a rural region of Central Asia. Drawing on ethnography from the Kyrgyzstan -Uzbekistan border, it contributes to a growing concern to understand how the state is rendered integral' in everyday life. Rather than focusing on the enactments and justificatory statements of state officials, the paper explores instead the diffuse but passionate work of borderland dwellers in policing the state edge in a context of political upheaval. Territory' in this reading is not just an a priori attribute of the state, nor only the product of official imaginings and interventions, but the site, too, of everyday practical and symbolic work, a vehicle for claims making and the means of performative enactments of belonging and difference. The paper calls for greater attention to the ordinary affects' that are elicited by borders and boundedness and the need to bring discussions of territoriality into conversation with a literature on the affective life of the state. Doing so, it argues, will both enrich our understanding of everyday state formation and give us greater purchase on the role of events in rupturing and reconfiguring state space. © 2011 Pion Ltd and its Licensors.

Dev P.S.B.,University of Manchester | Dev P.S.B.,TU Munich | Mohapatra R.N.,University of Maryland University College
Physical Review Letters | Year: 2015

We show that the excess events observed in a number of recent LHC resonance searches can be simultaneously explained within a nonsupersymmetric left-right inverse seesaw model for neutrino masses with WR mass around 1.9 TeV. The minimal particle content that leads to gauge coupling unification in this model predicts gR≃0.51 at the TeV scale, which is consistent with data. The extra color singlet, SU(2)-triplet fermions required for unification can be interpreted as the dark matter of the Universe. Future measurements of the ratio of same-sign to opposite-sign dilepton events can provide a way to distinguish this scenario from the canonical cases of type-I and inverse seesaw, i.e., provide a measure of the relative magnitudes of the Dirac and Majorana masses of the right-handed neutrinos in the SU(2)R doublet of the left-right symmetric model. © 2015 American Physical Society. © 2015 American Physical Society.

Helliwell J.R.,University of Manchester
Crystallography Reviews | Year: 2010

The colouration of the lobster shell, famously known from its colour change on cooking, derives from a complicated mix of astaxanthin carotenoid molecules and several proteins in complex. Crystals of various components have been known for many years but the breakthrough in structure determination came from the use of synchrotron radiation 'softer X-rays' of wavelength 2Å, thereby targeting the increase in the sulphur anomalous scattering and the xenon LI absorption edge. One structure of the gene-group of proteins was thus solved and this could be used for molecular replacement solution of the β-crustacyanin dimer complex in spite of a very high solvent content of ∼80%. The crystal structure of the α-crustacyanin complex of eight β-crustacyanins still eludes us but electron microscopy (EM) structure determination would be a way forward. At present, the molecular tuning parameters causing the 100 nm bathochromic shift of the β-crustacyanin are at least known from our work and have already stimulated considerable further research in theoretical and carotenoid chemistry. The protonation state of two critically placed histidines is of keen interest here, as well as the proximity of the two astaxanthins bound to the β-crustacyanin protein. There are wider biological implications too, including the colours of rare lobsters, where site-specific amino acid changes could be a cause and much molecular biology for colour tuning would be possible. A colour-based heat sensor could also be designed. Nutraceuticals based on the health giving properties of astaxanthin are also of keen interest. The mimicking of the colour change solely with carotenoids is being sought supported by our structural crystallography results of unbound carotenoids. Public interest has been especially strong not least because 'the' question: 'Why does a lobster change colour on cooking?' is known to nearly everyone. Notably, popular science-summary articles have been published in magazines. We will soon be entering a new era of ultra-bright X-ray Free Electron Lasers (XFELs) and the possibility of single molecule protein structure determination; the α-crustacyanin complex of eight β-crustacyanins would provide a test of the new methods and cross-comparison with EM. The comparisons of amino acid sequences of other crustacea colouration proteins with that of β-crustacyanin provide 3D 'homology models' and allow species and evolution comparisons. This topical review provides a summary of recent work and likely future research goals. © 2010 Taylor & Francis.

Wilson J.,University of Manchester
Environment and Planning D: Society and Space | Year: 2011

In the work of Henri Lefebvre the new town is frequently referred to as a social text' in which the nature of capitalist modernity can be deciphered with unusual clarity. This paper locates Lefebvre's seminal Notes on the new town" within his broader political and philosophical project and employs it as the theoretical basis for a critique of the Rural Cities, a series of new towns currently being constructed in Chiapas, Mexico, in which the region's peasant population is being relocated. Drawing on fieldwork conducted in Chiapas, I argue that the Rural Cities constitute a strategy for the imposition of capitalist social relations and the administration of everyday life by the state based on a technocratic rationality that erases the cultural practices of the region's indigenous and peasant population. I then discuss the numerous contradictions that are emerging through the implementation of the Rural Cities and conclude by contrasting them to the Zapatista caracoles. The caracoles, I suggest, constitute an alternative transformation of everyday life in Chiapas, which resonates with Lefebvre's vision of a revolutionary romanticism". © 2011 Pion Ltd and its Licensors.

Kaika M.,University of Manchester
Environment and Planning D: Society and Space | Year: 2011

In this contribution I sketch a framework for interpreting the parallel process of banalisation of old and proliferation of new 'iconic' corporate architecture as the Janus-faced manifestation of a qualitative shift in the relationship between capital and architecture. Highlighting the change from place-bound, place-loyal urban elites to footloose transnational elites, I argue that after the 1970s the need to develop a new set of building specifications and use values to accommodate the requirements of a new urban economy was matched by an equally pressing need to institute a new set of symbolic values for a new generation of elites. Drawing upon Castoriadis's work, I conceptualise architecture as the narrativisation of the desires of elites during a given era, and as a key component in instituting a society's radical imaginary during moments of change. Within this framework, I argue that despite their common commitment to spectacular design, there are a number of significant differences between contemporary and earlier corporate 'icons'. Discerning the distinct symbolic, material, and social role of contemporary corporate buildings, I challenge their identification as 'iconic' architecture and place them instead under a new category, which I term 'autistic architecture'. © 2011 Pion Ltd and its Licensors.

Brocklehurst P.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Methods of remuneration have been linked with the professional behaviour of primary care physicians. In dentistry, this can be exacerbated as clinicians operate their practices as businesses and take the full financial risk of the provision of services. The main methods for remunerating primary care dentists include fee-for-service, fixed salary and capitation payments. The aim of this review was to determine the impact that these remuneration mechanisms have upon primary care dentists' behaviour. To evaluate the effects of different methods of remuneration on the level and mix of activities provided by primary care dentists and the impact this has on patient outcomes. We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 7, 2013); MEDLINE (Ovid) (1947 to 11 June 2013); EMBASE (Ovid) (1947 to 11 June 2013); EconLit (1969 to 11 June 2013); the NHS Economic Evaluation Database (EED) (11 June 2013); and the Health Economic Evaluations Database (HEED) (11 June 2013). We conducted cited reference searches for the included studies in ISI Web of Knowledge; searched grey literature sources; handsearched selected journals; and contacted authors of relevant studies. Primary care dentists were defined as clinicians that deliver routine or mainstream dental care in a primary care environment. We included randomised controlled trials (RCTs), non-randomised controlled clinical trials (NRCTs), controlled before-after (CBA) studies and interrupted time series (ITS) studies. The methods of remuneration that we considered were: fee-for-service, fixed salary and capitation payments. Primary outcome measures were: measures of clinical activity; volume of clinical activity undertaken; time taken and clinical session length, or both; clinician type utilised; measures of health service utilisation; access and attendance as a proportion of the population; re-attendance rates; recall frequency; levels of oral health inequalities; non-attendance rates; healthcare costs; measures of patient outcomes; disease reduction; health maintenance; and patient satisfaction. We also considered measures of practice profitability/income and any reported unintended effects of the included methods of remuneration. Three of the review authors (PRB, JP, AMG) independently reviewed titles and abstracts and resolved disagreements by discussion. The same three review authors undertook data extraction and assessed the quality of the evidence from all the studies that met the selection criteria, according to Cochrane Collaboration procedures. Two cluster-RCTs, with data from 503 dental practices, representing 821 dentists and 4771 patients, met the selection criteria. We judged the risk of bias to be high for both studies and the overall quality of the evidence was low/very low for all outcomes, as assessed using the GRADE approach.One study used a factorial design to investigate the impact of fee-for-service and an educational intervention on the placement of fissure sealants in permanent molar teeth. The authors reported a statistically significant increase in clinical activity in the arm that was incentivised with a fee-for-service payment. However, the study was conducted in the four most deprived areas of Scotland, so the applicability of the findings to other settings may be limited. The study did not report data on measures of health service utilisation or measures of patient outcomes.The second study used a parallel group design undertaken over a three-year period to compare the impact of capitation payments with fee-for-service payments on primary care dentists' clinical activity. The study reported on measures of clinical activity (mean percentage of children receiving active preventive advice, health service utilisation (mean number of visits), patient outcomes (mean number of filled teeth, mean percentage of children having one or more teeth extracted and the mean number of decayed teeth) and healthcare costs (mean expenditure). Teeth were restored at a later stage in the disease process in the capitation system and the clinicians tended to see their patients less frequently and tended to carry out fewer fillings and extractions, but also tended to give more preventive advice.There was insufficient information regarding the cost-effectiveness of the different remuneration methods. Financial incentives within remuneration systems may produce changes to clinical activity undertaken by primary care dentists. However, the number of included studies is limited and the quality of the evidence from the two included studies was low/very low for all outcomes. Further experimental research in this area is highly recommended given the potential impact of financial incentives on clinical activity, and particular attention should be paid to the impact this has on patient outcomes.

Brocklehurst P.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Oral cancer is an important global healthcare problem, its incidence is increasing and late-stage presentation is common. Screening programmes have been introduced for a number of major cancers and have proved effective in their early detection. Given the high morbidity and mortality rates associated with oral cancer, there is a need to determine the effectiveness of a screening programme for this disease, either as a targeted, opportunistic or population-based measure. Evidence exists from modelled data that a visual oral examination of high-risk individuals may be a cost-effective screening strategy and the development and use of adjunctive aids and biomarkers is becoming increasingly common. To assess the effectiveness of current screening methods in decreasing oral cancer mortality. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 22 July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 6), MEDLINE via OVID (1946 to 22 July 2013), EMBASE via OVID (1980 to 22 July 2013) and CANCERLIT via PubMed (1950 to 22 July 2013). There were no restrictions on language in the search of the electronic databases. Randomised controlled trials (RCTs) of screening for oral cancer or potentially malignant disorders using visual examination, toluidine blue, fluorescence imaging or brush biopsy. Two review authors screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias independently and in duplicate. We used mean differences (MDs) and 95% confidence intervals (CIs) for continuous data and risk ratios (RRs) with 95% CIs for dichotomous data. Meta-analyses would have been undertaken using a random-effects model if the number of studies had exceeded a minimum of three. Study authors were contacted where possible and where deemed necessary for missing information. A total of 3239 citations were identified through the searches. Only one RCT, with 15-year follow-up met the inclusion criteria (n = 13 clusters: 191,873 participants). There was no statistically significant difference in the oral cancer mortality rates for the screened group (15.4/100,000 person-years) and the control group (17.1/100,000 person-years), with a RR of 0.88 (95% CI 0.69 to 1.12). A 24% reduction in mortality was reported between the screening group (30/100,000 person-years) and the control group (39.0/100,000) for high-risk individuals who used tobacco or alcohol or both, which was statistically significant (RR 0.76; 95% CI 0.60 to 0.97). No statistically significant differences were found for incidence rates. A statistically significant reduction in the number of individuals diagnosed with stage III or worse oral cancer was found for those in the screening group (RR 0.81; 95% CI 0.70 to 0.93). No harms were reported. The study was assessed as at high risk of bias. There is evidence that a visual examination as part of a population-based screening programme reduces the mortality rate of oral cancer in high-risk individuals. In addition, there is a stage shift and improvement in survival rates across the population as a whole. However, the evidence is limited to one study, which has a high risk of bias and did not account for the effect of cluster randomisation in the analysis. There was no evidence to support the use of adjunctive technologies like toluidine blue, brush biopsy or fluorescence imaging as a screening tool to reduce oral cancer mortality. Further RCTs are recommended to assess the efficacy and cost-effectiveness of a visual examination as part of a population-based screening programme in low, middle and high-income countries.

Walsh T.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

The early detection and excision of potentially malignant disorders (PMD) of the lip and oral cavity that require intervention may reduce malignant transformations (though will not totally eliminate malignancy occurring), or if malignancy is detected during surveillance, there is some evidence that appropriate treatment may improve survival rates. To 51%. Three studies were judged to be at low risk of bias overall; two were judged to be at high risk of bias resulting from the flow and timing domain; and for five studies the overall risk of bias was judged as unclear resulting from insufficient information to form a judgement for at least one of the four quality assessment domains. Applicability was of low concern overall for two studies; high concern overall for three studies due to high risk population, and unclear overall applicability for five studies. Estimates of sensitivity for MSE (two studies, 34,819 participants) were 0.18 (95% CI 0.13 to 0.24) and 0.33 (95% CI 0.10 to 0.65); specificity for MSE was 1.00 (95% CI 1.00 to 1.00) and 0.54 (95% CI 0.37 to 0.69). One study (7975 participants) directly compared COE with COE plus vital rinsing in a randomised controlled trial. This study found a higher detection rate for oral cavity cancer in the conventional oral examination plus vital rinsing adjunct trial arm. The prevalence of the target condition both between and within index tests varied considerably. For COE estimates of sensitivity over the range of prevalence levels varied widely. Observed estimates of specificity were more homogeneous. Index tests at a prevalence reported in the population (between 1% and 5%) were better at correctly classifying the absence of PMD or oral cavity cancer in disease-free individuals that classifying the presence in diseased individuals. Incorrectly classifying disease-free individuals as having the disease would have clinical and financial implications following inappropriate referral; incorrectly classifying individuals with the disease as disease-free will mean PMD or oral cavity cancer will only be diagnosed later when the disease will be more severe. General dental practitioners and dental care professionals should remain vigilant for signs of PMD and oral cancer whilst performing routine oral examinations in practice.

Ingleson M.J.,University of Manchester
Topics in Organometallic Chemistry | Year: 2015

The past 5 years has witnessed considerable growth in the field of borocation chemistry with a multitude of new cations containing 2, 3 and 4 coordinate boron centres reported. Perhaps more significant has been the expansion in the synthetic utility of borocations as stoichiometric reagents and catalysts. It is these new applications of borocations that are the primary focus of this article which concentrates on reports from 2009 to the end of June 2014. The correlation between structure and reactivity in these recent studies will be emphasised to aid in the future design of new borocations for specific targeted outcomes. © Springer International Publishing Switzerland 2015.

Worthington H.V.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Many dentists or hygienists provide scaling and polishing for patients at regular intervals, even if those patients are considered to be at low risk of developing periodontal disease. There is debate over the clinical effectiveness and cost effectiveness of 'routine scaling and polishing' and the 'optimal' frequency at which it should be provided for healthy adults.A 'routine scale and polish' treatment is defined as -2% (95% CI -10% to 6%; P value = 0.65), with 40% of the sites in the control group with bleeding. The MD for 12-monthly scale and polish was -1% (95% CI -9% to 7%; P value = 0.82). The body of evidence was assessed as of low quality.- Objective 2: Scale and polish at different time intervals Two studies, both at unclear risk of bias, compared routine scale and polish provided at different time intervals. When comparing six with 12 months there was insufficient evidence to determine a difference for gingivitis at 24 months SMD -0.08 (95% CI -0.27 to 0.10). There were some statistically significant differences in favour of scaling and polishing provided at more frequent intervals, in particular between three and 12 months for the outcome of gingivitis at 24 months, with OHI, MD -0.14 (95% CI -0.23 to -0.05; P value = 0.003) and without OHI MD -0.21 (95% CI -0.30 to -0.12; P value < 0.001) (mean per patient measured on 0-3 scale), based on one study. There was some evidence of a reduction in calculus. This body of evidence was assessed as of low quality.- Objective 3: Scale and polish with and without OHIOne study provided data for the comparison of scale and polish treatment with and without OHI. There was a reduction in gingivitis for the 12-month scale and polish treatment when assessed at 24 months MD -0.14 (95% CI -0.22 to -0.06) in favour of including OHI. There were also significant reductions in plaque for both three and 12-month scale and polish treatments when OHI was included. The body of evidence was once again assessed as of low quality.- Objective 4: Scale and polish provided by a dentist compared with a dental care professionalNo studies were found which compared the effects of routine scaling and polishing provided by a dentist or dental care professional (dental therapist or dental hygienist) on periodontal health. There is insufficient evidence to determine the effects of routine scale and polish treatments. High quality trials conducted in general dental practice settings with sufficiently long follow-up periods (five years or more) are required to address the objectives of this review.

Riley P.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

The frequency with which patients should attend for a dental check-up and the potential effects on oral health of altering recall intervals between check-ups have been the subject of ongoing international debate in recent decades. Although recommendations regarding optimal recall intervals vary between countries and dental healthcare systems, six-monthly dental check-ups have traditionally been advocated by general dental practitioners in many developed countries.This is an update of a Cochrane review first published in 2005, and previously updated in 2007. To determine the beneficial and harmful effects of different fixed recall intervals (for example six months versus 12 months) for the following different types of dental check-up: a) clinical examination only; b) clinical examination plus scale and polish; c) clinical examination plus preventive advice; d) clinical examination plus preventive advice plus scale and polish.To determine the relative beneficial and harmful effects between any of these different types of dental check-up at the same fixed recall interval.To compare the beneficial and harmful effects of recall intervals based on clinicians' assessment of patients' disease risk with fixed recall intervals.To compare the beneficial and harmful effects of no recall interval/patient driven attendance (which may be symptomatic) with fixed recall intervals. The following electronic databases were searched: the Cochrane Oral Health Group's Trials Register (to 27 September 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE via OVID (1946 to 27 September 2013) and EMBASE via OVID (1980 to 27 September 2013). We searched the US National Institutes of Health Trials Register (http://clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (http://www.who.int/ictrp/en/) for ongoing trials. Reference lists from relevant articles were scanned and the authors of some papers were contacted to identify further trials and obtain additional information. We did not apply any restrictions regarding language or date of publication when searching the electronic databases. We included randomised controlled trials (RCTs) assessing the effects of different dental recall intervals. Two review authors independently assessed the search results against the inclusion criteria of the review, extracted data and carried out risk of bias assessment. We contacted study authors for clarification or further information where necessary and feasible. If we had found more than one study with similar comparisons reporting the same outcomes, we would have combined the studies in a meta-analysis using a random-effects model if there were at least four studies, or a fixed-effect model if there were less than four studies. We expressed the estimate of effect as mean difference with 95% confidence intervals (CIs) for continuous outcomes. We would have used risk ratios with 95% CI for any dichotomous outcomes. We included one study that analysed 185 participants. The study compared the effects of a clinical examination every 12 months with a clinical examination every 24 months on the outcomes of caries (decayed, missing, filled surfaces (dmfs/DMFS) increment) and economic cost outcomes (total time used per person). As the study was at high risk of bias, had a small sample size and only included low-risk participants, we rated the quality of the body of evidence for these outcomes as very low.For three to five-year olds with primary teeth, the mean difference (MD) in dmfs increment was -0.90 (95% CI -1.96 to 0.16) in favour of 12-month recall. For 16 to 20-year olds with permanent teeth, the MD in DMFS increment was -0.86 (95% CI -1.75 to 0.03) also in favour of 12-month recall. There is insufficient evidence to determine whether 12 or 24-month recall with clinical examination results in better caries outcomes.For three to five-year olds with primary teeth, the MD in time used by each participant was 10 minutes (95% CI -6.7 to 26.7) in favour of 24-month recall. For 16 to 20-year olds with permanent teeth, the MD was 23.7 minutes (95% CI 4.12 to 43.28) also in favour of 24-month recall. This single study at high risk of bias represents insufficient evidence to determine whether 12 or 24-month recall with clinical examination results in better time/cost outcomes. There is a very low quality body of evidence from one RCT which is insufficient to draw any conclusions regarding the potential beneficial and harmful effects of altering the recall interval between dental check-ups. There is no evidence to support or refute the practice of encouraging patients to attend for dental check-ups at six-monthly intervals. It is important that high quality RCTs are conducted for the outcomes listed in this review in order to address the objectives of this review.

Riley P.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

Periodontal disease and dental caries are highly prevalent oral diseases that can lead to pain and discomfort, oral hygiene and aesthetic problems, and eventually tooth loss, all of which can be the development of periodontitis (attachment loss) (RR 0.92, 95% CI 0.67 to 1.27, one study, 480 participants, low-quality evidence). Caries After 24 to 36 months of use, triclosan/copolymer toothpaste slightly reduced coronal caries when using the decayed and filled surfaces (DFS) index (MD -0.16, 95% CI -0.31 to -0.02, four studies, 9692 participants, high-quality evidence). The control group mean was 3.44, representing a 5% reduction in coronal caries. After 36 months of use, triclosan/copolymer toothpaste probably reduced root caries (MD -0.31, 95% CI -0.39 to -0.23, one study, 1357 participants, moderate-quality evidence). Calculus After six months of use, triclosan/copolymer toothpaste may have reduced the mean total calculus per participant by 2.12 mm (MD -2.12 mm, 95% CI -3.39 to -0.84, two studies, 415 participants, low-quality evidence). The control group mean was 14.61 mm, representing a 15% reduction in calculus. Adverse effects There were no data available for meta-analysis regarding adverse effects, but 22 studies (73%) reported that there were no adverse effects caused by either the experimental or control toothpaste.There was considerable heterogeneity present in the meta-analyses for plaque, gingivitis and calculus. Plaque and gingivitis showed such consistent results that it did not affect our conclusions, but the reader may wish to interpret the results with more caution. There was moderate-quality evidence showing that toothpastes containing triclosan/copolymer, in addition to fluoride, reduced plaque, gingival inflammation and gingival bleeding when compared with fluoride toothpastes without triclosan/copolymer. These reductions may or may not be clinically important, and are evident regardless of initial plaque and gingivitis levels, or whether a baseline oral prophylaxis had taken place or not. High-quality evidence showed that triclosan/copolymer toothpastes lead to a small reduction in coronal caries. There was weaker evidence to show that triclosan/copolymer toothpastes may have reduced root caries and calculus, but insufficient evidence to show whether or not they prevented periodontitis. There do not appear to be any serious safety concerns regarding the use of triclosan/copolymer toothpastes in studies up to three years in duration.

Esposito M.,University of Manchester
The Cochrane database of systematic reviews | Year: 2013

To minimise the risk of implant failures after their placement, dental implants are kept load-free for 3 to 8 months to establish osseointegration (conventional loading). It would be beneficial if the healing period could be shortened without jeopardising implant success. Nowadays implants are loaded early and even immediately and it would be useful to know whether there is a difference in success rates between immediately and early loaded implants compared with conventionally loaded implants. To evaluate the effects of (1) immediate (within 1 week), early (between 1 week and 2 months), and conventional (after 2 months) loading of osseointegrated implants; (2) immediate occlusal versus non-occlusal loading and early occlusal versus non-occlusal loading; (3) direct loading versus progressive loading immediately, early and conventionally. The following electronic databases were searched: the Cochrane Oral Health Group's Trials Register (to 8 June 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2012, Issue 4), MEDLINE via OVID (1946 to 8 June 2012) and EMBASE via OVID (1980 to 8 June 2012). Authors of identified trials were contacted to find unpublished randomised controlled trials (RCTs). There were no restrictions regarding language or date of publication. All RCTs of root-form osseointegrated dental implants, having a follow-up of 4 months to 1 year, comparing the same implant type immediately, early or conventionally loaded, occlusally or non-occlusally loaded, or progressively loaded or not. Outcome measures were: prosthesis and implant failures and radiographic marginal bone level changes. Data were independently extracted, in duplicate, by at least two review authors. Trial authors were contacted for missing information. Risk of bias was assessed for each trial by at least two review authors, and data were extracted independently, and in duplicate. Results were combined using fixed-effect models with mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI). A summary of findings table of the main findings was constructed. Forty-five RCTs were identified and, from these, 26 trials including a total of 1217 participants and 2120 implants were included. Three trials were at low risk of bias, 12 were at high risk of bias and for the remaining 11 the risk of bias was unclear. In nine of the included studies there were no prosthetic failures within the first year, with no implant failures in 7 studies and the mean rate of implant failure in all 26 trials was a low 2.5%. From 15 RCTs comparing immediate with convential loading there was no evidence of a difference in either prosthesis failure (RR 1.87; 95% CI 0.70 to 5.01; 8 trials) or implant failure (RR 1.65; 95% CI 0.68 to 3.98; 10 trials) in the first year, but there is some evidence of a small reduction in bone loss favouring immediate loading (MD -0.10 mm; 95% CI -0.20 to -0.01; P = 0.03; 9 trials), with some heterogeneity (Tau2 = 0.01; Chi2 = 14.37, df = 8 (P = 0.07); I2 = 44%). However, this very small difference may not be clinically important. From three RCTs which compared early loading with conventional loading, there is insufficient evidence to determine whether or not there is a clinically important difference in prosthesis failure, implant failure or bone loss. Six RCTs compared immediate and early loading and found insufficient evidence to determine whether or not there is a clinically important difference in prosthesis failure, implant failure or bone loss. From the two trials which compared occlusal loading with non-occlusal loading there is insufficient evidence to determine whether there is a clinically important difference in the outcomes of prosthesis failure, implant failure or bone loss. We did not identify any trials which evaluated progressive loading of implants. Overall there was no convincing evidence of a clinically important difference in prosthesis failure, implant failure, or bone loss associated with different loading times of implants. More well-designed RCTs are needed and should be reported according to the CONSORT guidelines (www.consort-statement.org/).

Pavitt G.D.,University of Manchester
Cold Spring Harbor perspectives in biology | Year: 2012

Homeostasis of the protein-folding environment in the endoplasmic reticulum (ER) is maintained by signal transduction pathways that collectively constitute an unfolded protein response (UPR). These affect bulk protein synthesis and thereby the levels of ER stress, but also culminate in regulated expression of specific mRNAs, such as that encoding the transcription factor ATF4. Mechanisms linking eukaryotic initiation factor 2 (eIF2) phosphorylation to control of unfolded protein load in the ER were elucidated more than 10 years ago, but recent work has highlighted the diversity of processes that impinge on eIF2 activity and revealed that there are multiple mechanisms by which changes in eIF2 activity can modulate the translation of individual mRNAs. In addition, the potential for affecting this step of translation initiation pharmacologically is becoming clearer. Furthermore, it is now clear that another strand of the UPR, controlled by the endoribonuclease inositol-requiring enzyme 1 (IRE1), also affects rates of protein synthesis in stressed cells and that its effector function, mediated by the transcription factor X-box-binding protein 1 (XBP1), is subject to important mRNA-specific translational regulation. These new insights into the convergence of translational control and the UPR will be reviewed here.

In public debates about the volume of food that is currently wasted by UK households, there exists a tendency to blame the consumer or individualise responsibilities for affecting change. Drawing on ethnographic examples, this article explores the dynamics of domestic food practices and considers their consequences in terms of waste. Discussions are structured around the following themes: (1) feeding the family; (2) eating 'properly'; (3) the materiality of 'proper' food and its intersections with the socio-temporal demands of everyday life and (4) anxieties surrounding food safety and storage. Particular attention is paid to the role of public health interventions in shaping the contexts through which food is at risk of wastage. Taken together, I argue that household food waste cannot be conceptualised as a problem of individual consumer behaviour and suggest that policies and interventions might usefully be targeted at the social and material conditions in which food is provisioned. © 2011 Copyright Taylor and Francis Group, LLC.

Esposito M.,University of Manchester
European journal of oral implantology | Year: 2010

CONFLICT-OF-INTEREST STATEMENT: Marco Esposito, Pietro Felice and Paul Coulthard are among the authors of four of the included trials, however, they were not involved in the quality assessment of these trials. This review is based on a Cochrane systematic review entitled 'Interventions for replacing missing teeth: augmentation procedures of the maxillary sinus' published in The Cochrane Library (see http:// www.cochrane.org/ for information). Cochrane systematic reviews are regularly updated to include new research and in response to comments and criticisms from readers. If you wish to comment on this review, please send your comments to the Cochrane website or to Marco Esposito. The Cochrane Library should be consulted for the most recent version of the review. The results of a Cochrane Review can be interpreted differently, depending on people's perspectives and circumstances. Please consider the conclusions presented carefully. They are the opinions of the review authors, and are not necessarily shared by the Cochrane Collaboration. BACKGROUND: Insufficient bone volume is a common problem encountered in the rehabilitation of the edentulous posterior maxillae with implant supported prostheses. Bone volume is limited by the presence of the maxillary sinus together with loss of alveolar bone height. Sinus lift procedures increase bone volume by augmenting the sinus cavity with autogenous bone and/or commercially available biomaterials. OBJECTIVES: To test whether and when augmentation of the maxillary sinus is necessary and which are the most effective augmentation techniques for rehabilitating patients with implant-supported prostheses. SEARCH METHODS: The Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE were searched. Several dental journals were hand searched. The bibliographies of review articles were checked, and personal references were searched. More than 55 implant manufacturing companies were also contacted. The last electronic search was conducted on 7th January 2010. SELECTION CRITERIA: Randomised controlled trials (RCTs) of different techniques and materials for augmenting the maxillary sinus for rehabilitation with dental implants reporting the outcome of implant therapy at least to abutment connection. DATA COLLECTION AND ANALYSIS: Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted independently and in duplicate. Authors were contacted for any missing information. Results were expressed as random-effects models using mean differences for continuous outcomes and odds ratios for dichotomous outcomes with 95% confidence intervals. The statistical unit of the analysis was the patient. RESULTS: Ten RCTs out of 29 potentially eligible trials were suitable for inclusion. One trial including 15 patients, evaluated whether 5-mm-long implants with a diameter of 6 mm could be an alternative to sinus lift in bone having a residual height of 4 to 6 mm. Nine trials with 235 patients compared different sinus lift techniques and, of these, four trials (114 patients) evaluated the efficacy of platelet-rich plasma (PRP). Since different techniques were evaluated in different trials, only two meta-analyses evaluating the efficacy of PRP could be performed for implant failures (two trials) and complications (three trials). No statistically significant difference was observed for any of the evaluated interventions. CONCLUSIONS: Conclusions are based on few trials, usually underpowered, having short follow-ups, and often judged to be at high risk of bias, therefore they should be viewed as preliminary and interpreted with great caution. It is still unclear when sinus lift procedures are needed. Short implants (5 mm) can be successfully loaded in maxillary bone with a residual height of 4 to 6 mm, but their long-term prognosis is unknown. Elevating the sinus lining in the presence of 1 to 5 mm of residual bone height without the addition of a bone graft may be sufficient to regenerate new bone to allow rehabilitation with implant-supported prostheses. Bone substitutes might be successfully used as replacements for autogenous bone. If the residual alveolar bone height is 3 to 6 mm, a crestal approach to lifting the sinus lining and placing 8 mm implants may lead to less complications than a lateral window approach and placing implants at least 10 mm long. PRP treatment does not seem to improve the clinical outcome of sinus lift procedures with autogenous bone or bone substitutes.

Severe mental illness is a serious and potentially life changing set of conditions. This paper describes and analyses patient characteristics and service usage over one year of a representative cohort of people with a diagnosis of severe mental illness across England, including contacts with primary and secondary care and continuity of care. Data were collected from primary care patient notes (n = 1150) by trained nurses from 64 practices in England, covering all service contacts from 1(st) April 2008 to 31st March 2009. The estimated national rate of patients seen only in primary care in the period was 31.1% (95% C.I. 27.2% to 35.3%) and the rates of schizophrenia and bipolar disorder were 56.8% (95% C.I. 52.3% to 61.2%) and 37.9% (95% C.I. 33.7% to 42.2%). In total, patients had 7,961 consultations within primary care and 1,993 contacts with mental health services (20% of the total). Unemployed individuals diagnosed more recently were more likely to have contact with secondary care. Of those seen in secondary care, 61% had at most two secondary care contacts in the period. Median annual consultation rates with GPs were lower than have been reported for previous years and were only slightly above the general population. Relational continuity in primary care was poor for 21% of patients (Modified Modified Continuity Index = <0.5), and for almost a third of new referrals to mental health services the primary care record contained no information on the referral outcome. Primary care is centrally involved in the care of people with serious mental illness, but primary care and cross-boundary continuity is poor for a substantial proportion. Research is needed to determine the impact of poor continuity on patient outcomes, and above all, the impact of new collaborative ways of working at the primary/secondary care interface.

Fedotov S.,University of Manchester
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2010

The main aim of the paper is to incorporate the nonlinear kinetic term into non-Markovian transport equations described by a continuous time random walk (CTRW) with nonexponential waiting time distributions. We consider three different CTRW models with reactions. We derive nonlinear Master equations for the mesoscopic density of reacting particles corresponding to CTRW with arbitrary jump and waiting time distributions. We apply these equations to the problem of front propagation in the reaction-transport systems with Kolmogorov-Petrovskii-Piskunov kinetics and anomalous diffusion. We have found an explicit expression for the speed of a propagating front in the case of subdiffusive transport. © 2010 The American Physical Society.

Heintzen C.,University of Manchester
Wiley Interdisciplinary Reviews: Membrane Transport and Signaling | Year: 2012

Light is both an energy source and a carrier of information. Changes in light intensity, direction, quality, spectral composition, and the metronomic predictability of the Earths' light-dark cycles carry vital information about the environment. Photoreceptors have evolved that sense these characteristics of light and trigger cellular signaling processes that control physiology, development, and behavior and enable organisms to develop a sense of space and time. In plants and fungi the photoreceptive rhodopsins, light oxygen voltage proteins, phytochromes and cryptochromes sense changes in and facilitate the adaptation to the light environment. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mac Ginty R.,University of Manchester
Evaluation and Program Planning | Year: 2013

Many of the approaches to measuring peace favoured by international organisations, INGOs and donor governments are deficient. Their level of analysis is often too broad or too narrow, and their aggregated statistical format often means that they represent the conflict-affected area in ways that are meaningless to local communities. This article takes the form of a proposal for a new generation of locally organised indicators that are based in everyday life. These indicators are inspired by practice from sustainable development in which indicators are crowd sourced. There is the potential for these to become 'indicators. +' or part of a conflict transformation exercise as communities think about what peace might look like and how it could be realised. The article advocates a form of participatory action research that would be able to pick up the textured 'hidden transcript' found in many deeply divided societies and could allow for better targeted peacebuilding and development assistance. © 2012 Elsevier Ltd.

Tesfaye S.,Diabetes Research Unit | Boulton A.J.M.,University of Manchester | Dickenson A.H.,University College London
Diabetes Care | Year: 2013

Although a number of the diabetic neuropathies may result in painful symptomatology, this review focuses on the most common: chronic sensorimotor distal symmetrical polyneuropathy (DSPN). It is estimated that 15-20% of diabetic patients may have painful DSPN, but not all of these will require therapy. In practice, the diagnosis of DSPN is a clinical one, whereas for longitudinal studies and clinical trials, quantitative sensory testing and electrophysiological assessment are usually necessary. A number of simple numeric rating scales are available to assess the frequency and severity of neuropathic pain. Although the exact pathophysiological processes that result in diabetic neuropathic pain remain enigmatic, both peripheral and central mechanisms have been implicated, and extend from altered channel function in peripheral nerve through enhanced spinal processing and changes in many higher centers. A number of pharmacological agents have proven efficacy in painful DSPN, but all are prone to side effects, and none impact the underlying pathophysiological abnormalities because they are only symptomatic therapy. The two first-line therapies approved by regulatory authorities for painful neuropathy are duloxetine and pregabalin. a-Lipoic acid, an antioxidant and pathogenic therapy, has evidence of efficacy but is not licensed in the U.S. and several European countries. All patients with DSPN are at increased risk of foot ulceration and require foot care, education, and if possible, regular podiatry assessment. © 2013 by the American Diabetes Association.

Crow Y.J.,University of Manchester
Handbook of Clinical Neurology | Year: 2013

Aicardi-Goutières syndrome (AGS) is a genetically determined encephalopathy demonstrating phenotypic overlap both with the sequelae of congenital infection and with systemic lupus erythematosus (SLE). Recent molecular advances have revealed that AGS can be caused by mutations in any one of five genes, most commonly on a recessive basis but occasionally as a dominant trait. Like AGS, SLE is associated with a perturbation of type I interferon metabolism. Interestingly then, heterozygous mutations in the AGS1 gene TREX1, and the AGS5 gene SAMHD1, underlie a cutaneous subtype of SLE called familial chilblain lupus, and mutations in TREX1 represent the single most common cause of monogenic SLE identified to date. Evidence is emerging to show that the nucleases defective in AGS are involved in removing endogenously produced nucleic acid species, and that a failure of this removal results in activation of the immune system. This hypothesis explains the phenotypic overlap of AGS with congenital infection and some aspects of SLE, where an equivalent type I interferon-mediated innate immune response is triggered by viral and self nucleic acids respectively. These studies beg urgent questions about the development and use of immunosuppressive therapies in AGS and related phenotypes. © 2013 Elsevier B.V.

Glaus P.,University of Manchester | Honkela A.,Aalto University | Rattray M.,University of Sheffield
Bioinformatics | Year: 2012

Motivation: High-throughput sequencing enables expression analysis at the level of individual transcripts. The analysis of transcriptome expression levels and differential expression (DE) estimation requires a probabilistic approach to properly account for ambiguity caused by shared exons and finite read sampling as well as the intrinsic biological variance of transcript expression. Results: We present Bayesian inference of transcripts from sequencing data (BitSeq), a Bayesian approach for estimation of transcript expression level from RNA-seq experiments. Inferred relative expression is represented by Markov chain Monte Carlo samples from the posterior probability distribution of a generative model of the read data. We propose a novel method for DE analysis across replicates which propagates uncertainty from the sample-level model while modelling biological variance using an expression-level-dependent prior. We demonstrate the advantages of our method using simulated data as well as an RNA-seq dataset with technical and biological replication for both studied conditions. © The Author(s) 2012. Published by Oxford University Press.

Verkhratsky A.,University of Manchester
ASN neuro | Year: 2012

Diseases of the human brain are almost universally attributed to malfunction or loss of nerve cells. However, a considerable amount of work has, during the last decade, expanded our view on the role of astrocytes in CNS (central nervous system), and this analysis suggests that astrocytes contribute to both initiation and propagation of many (if not all) neurological diseases. Astrocytes provide metabolic and trophic support to neurons and oligodendrocytes. Here, we shall endeavour a broad overviewing of the progress in the field and forward the idea that loss of homoeostatic astroglial function leads to an acute loss of neurons in the setting of acute insults such as ischaemia, whereas more subtle dysfunction of astrocytes over periods of months to years contributes to epilepsy and to progressive loss of neurons in neurodegenerative diseases. The majority of therapeutic drugs currently in clinical use target neuronal receptors, channels or transporters. Future therapeutic efforts may benefit by a stronger focus on the supportive homoeostatic functions of astrocytes.

Bresalier M.,University of Manchester
Journal of the History of Medicine and Allied Sciences | Year: 2013

This article explores the decisive role of British military medicine in shaping official approaches to the 1918 influenza pandemic. It contends that British approaches were defined through a system of military pathology, which had been established by the War Office as part of the mobilization of medicine for the First World War. Relying on the bacteriological laboratory for the identification and control of pathogenic agents, military pathology delivered therapeutic and preventive measures against a range of battlefield diseases, and military and civilian authorities trusted that it could do the same with influenza. This article traces how it shaped efforts to establish the etiology of the pandemic and to produce a general influenza vaccine. It highlights the challenges involved in both strategies. Understanding the central role of military pathology helps make sense of the nature, direction, scale, and limitations of medical mobilization against the pandemic in Britain and the authority accorded to specific medical bodies for elaborating and coordinating strategies. Crucially, it demands that we rethink the relationship between the war and pandemic as one about the social organization of medical knowledge and institutions. © 2011 The Author.

A small number of studies have sought to establish that research papers with more funding acknowledgements achieve higher impact and have claimed that such a link exists because research supported by more funding bodies undergoes more peer review. In this paper, a test of this link is made using recently available data from the Web of Science, a source of bibliographic data that now includes funding acknowledgements. The analysis uses 3,596 papers from a single year, 2009, and a single journal, the Journal of Biological Chemistry. Analysis of this data using OLS regression and two ranks tests reveals the link between count of funding acknowledgements and high impact papers to be statistically significant, but weak. It is concluded that count of funding acknowledgements should not be considered a reliable indicator of research impact at this level. Relatedly, indicators based on assumptions that may hold true at one level of analysis may not be appropriate at other levels. © 2012 Akadémiai Kiadó, Budapest, Hungary.

Jankovic V.,University of Manchester
Wiley Interdisciplinary Reviews: Climate Change | Year: 2013

Although the scientific research in the atmospheres of urban space has been long in existence, it has still not found its proper place in the contemporary historical analysis. The historical emphasis on large-scale phenomena and the advent of numerical weather prediction has occluded the scientific relevance and social dimension of investigations into small-scale atmospheric processes. As a result, agricultural, forest, urban, and indoor meteorologies have received relatively little attention to date, as have micro-climatology, turbulence studies, and the air pollution meteorology. This article provides an outline of the historical and contemporary studies of urban weather and climate in Europe and North America. It looks into the origins of the field, the evolution of main topics of research, and the processes of disciplinary institutionalization. The article suggests that a closer inspection of the developments in urban climatology would permit a more representative account of modern atmospheric sciences and provide a more comprehensive understanding of the contemporary concerns over the anthropogenic climate change. © 2013 John Wiley & Sons, Ltd.

Battye R.A.,University of Manchester | Moss A.,University of Nottingham
Physical Review Letters | Year: 2014

We discuss whether massive neutrinos (either active or sterile) can reconcile some of the tensions within cosmological data that have been brought into focus by the recently released Planck data. We point out that a discrepancy is present when comparing the primary CMB and lensing measurements both from the CMB and galaxy lensing data using CFHTLenS, similar to that which arises when comparing CMB measurements and SZ cluster counts. A consistent picture emerges and including a prior for the cluster constraints and BAOs we find that for an active neutrino model with three degenerate neutrinos, Σmν=(0.320±0.081) eV, whereas for a sterile neutrino, in addition to 3 neutrinos with a standard hierarchy and Σmν=0.06 eV, mν,sterileeff=(0.450±0.124) eV and ΔNeff=0.45±0.23. In both cases there is a significant detection of modification to the neutrino sector from the standard model and in the case of the sterile neutrino it is possible to reconcile the BAO and local H0 measurements. However, a caveat to our result is some internal tension between the CMB and lensing and cluster observations, and the masses are in excess of those estimated from the shape of the matter power spectrum from galaxy surveys. © 2014 American Physical Society.

Perry D.M.,University of Manchester
Plastic and reconstructive surgery | Year: 2010

BACKGROUND: Cutaneous scarring is affected by genetic, physiologic, and biochemical factors. These produce a continuum of scar types (i.e., keloid, hypertrophic, atrophic, contracted, and fine line) that can be symptomatic, aesthetically unsatisfactory, psychologically distressing, and functionally restrictive to the affected individual. Accurate scar assessment allows for quantification of scar evolution and management, and is key to evaluating the effectiveness of applied modulating therapies and treatments. Numerous objective instruments exist for the evaluation of different scar characteristics, but no consensus has been reached as to the most appropriate device. This review aims to explore the current range of noninvasive objective assessment tools available for cutaneous skin scarring, with specific emphasis on their application to research trials and clinical practice. METHODS: An extensive search of the literature was completed to assemble comprehensive data surrounding the objective assessment of skin scars by both validation studies and clinical trials. RESULTS: A wide range of tools exist to monitor cutaneous scar physical characteristics. Primarily, there are four parameters explored by these instruments: (1) color, including pigmentation and vascularity (e.g., laser Doppler); (2) surface area (e.g., three-dimensional scanning); (3) height/depth (e.g., ultrasonography); and (4) pliability (e.g., tonometry). Many studies appraise single instruments in specific scar patient groups with subjective comparator tools. CONCLUSIONS: There is no overall valid and reliable noninvasive objective assessment tool for measurement of cutaneous skin scar characteristics. Further studies are warranted that compare multiple, parameter-specific instruments in a single-sample group and across a range of scar types.

Esposito M.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: 'Immediate' implants are placed in dental sockets just after tooth extraction. 'Immediate-delayed' implants are those implants inserted after weeks up to about a couple of months to allow for soft tissue healing. 'Delayed' implants are those placed thereafter in partially or completely healed bone. The potential advantages of immediate implants are that treatment time can be shortened and that bone volumes might be partially maintained thus possibly providing good aesthetic results. The potential disadvantages are an increased risk of infection and failures. After implant placement in postextractive sites, gaps can be present between the implant and the bony walls. It is possible to fill these gaps and to augment bone simultaneously to implant placement. There are many techniques to achieve this but it is unclear when augmentation is needed and which could be the best augmentation technique. OBJECTIVES: To evaluate success, complications, aesthetics and patient satisfaction between 'immediate', 'immediate-delayed' and 'delayed' implants.To evaluate whether and when augmentation procedures are necessary and which is the most effective technique. SEARCH STRATEGY: The Cochrane Oral Health Group's Trials Register (to 2 June 2010), CENTRAL (The Cochrane Library 2010, Issue 2), MEDLINE via OVID (1950 - 2 June 2010) and EMBASE via OVID (1980 - 2 June 2010) were searched. Several dental journals were handsearched. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing immediate, immediate-delayed, and delayed implants, or comparing various bone augmentation procedures around the inserted implants, reporting the outcome of the interventions to at least 1 year after functional loading. DATA COLLECTION AND ANALYSIS: Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted independently and in duplicate. Trial authors were contacted for any missing information. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CIs). The statistical unit of the analysis was the patient. MAIN RESULTS: Fourteen eligible RCTs were identified but only seven trials could be included. Four RCTs evaluated implant placement timing. Two RCTs compared immediate versus delayed implants in 126 patients and found no statistically significant differences. One RCT compared immediate-delayed versus delayed implants in 46 patients. After 2 years patients in the immediate-delayed group perceived the time to functional loading significantly shorter, were more satisfied and independent blinded assessor judged the level of the perimplant marginal mucosa in relation to that of the adjacent teeth as more appropriate (RR = 1.68; 95% CI 1.04 to 2.72). These differences disappeared 5 years after loading but significantly more complications occurred in the immediate-delayed group (RR = 4.20; 95% CI 1.01 to 17.43). One RCT compared immediate with immediately delayed implants in 16 patients for 2 years and found no differences. Three RCTs evaluated different techniques of bone grafting for implants immediately placed in extraction sockets. No statistically significant difference was observed when evaluating whether autogenous bone is needed in postextractive sites (1 trial with 26 patients) or which was the most effective augmentation technique (2 trials with 56 patients). AUTHORS' CONCLUSIONS: There is insufficient evidence to determine possible advantages or disadvantages of immediate, immediate-delayed or delayed implants, therefore these preliminary conclusions are based on few underpowered trials often judged to be at high risk of bias. There is a suggestion that immediate and immediate-delayed implants may be at higher risks of implant failures and complications than delayed implants on the other hand the aesthetic outcome might be better when placing implants just after teeth extraction. There is not enough reliable evidence supporting or refuting the need for augmentation procedures at immediate implants placed in fresh extraction sockets or whether any of the augmentation techniques is superior to the others.

Humphreys G.F.,University of Manchester | Gennari S.P.,University of York
NeuroImage | Year: 2014

Despite much interest in language production and comprehension mechanisms, little is known about the relationship between the two. Previous research suggests that linguistic knowledge is shared across these tasks and that the left inferior frontal gyrus (LIFG) may be commonly recruited. However, it remains unclear the extent to which production and comprehension share competition mechanisms. Here we investigate this issue and specifically examine competition in determining the event roles in a sentence (agent or affected participant). We used both behavioral and fMRI methods and compared the reading and production of high- and low-competition sentences, specifically targeting LIFG. We found that activity in pars opercularis (PO), independently identified by a competition-driven localizer, was modulated by competition in both tasks. Psychophysiological interaction analyses seeded in PO revealed task-specific networks: In comprehension, PO only interacted with the posterior temporal lobe, whereas in production, it interacted with a large network including hippocampal, posterior temporal, medial frontal and subcortical structures. Production and comprehension therefore recruit partially distinct functional networks but share competitive processes within fronto-temporal regions. We argue that these common regions store long-term linguistic associations and compute their higher-order contingencies, but competition in production ignites a larger neural network implementing planning, as required by task demands. © 2013.

Roberts C.,University of Manchester
Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine | Year: 2011

A major potential confound in axial 3D dynamic contrast-enhanced magnetic resonance imaging studies is the blood inflow effect; therefore, the choice of slice location for arterial input function measurement within the imaging volume must be considered carefully. The objective of this study was to use computer simulations, flow phantom, and in vivo studies to describe and understand the effect of blood inflow on the measurement of the arterial input function. All experiments were done at 1.5 T using a typical 3D dynamic contrast-enhanced magnetic resonance imaging sequence, and arterial input functions were extracted for each slice in the imaging volume. We simulated a set of arterial input functions based on the same imaging parameters and accounted for blood inflow and radiofrequency field inhomogeneities. Measured arterial input functions along the vessel length from both in vivo and the flow phantom agreed with simulated arterial input functions and show large overestimations in the arterial input function in the first 30 mm of the vessel, whereas arterial input functions measured more centrally achieve accurate contrast agent concentrations. Use of inflow-affected arterial input functions in tracer kinetic modeling shows potential errors of up to 80% in tissue microvascular parameters. These errors emphasize the importance of careful placement of the arterial input function definition location to avoid the effects of blood inflow. © 2010 Wiley-Liss, Inc.

De Vries F.T.,University of Manchester | Shade A.,Yale University
Frontiers in Microbiology | Year: 2013

Soil microbial communities are intricately linked to ecosystem functioning because they play important roles in carbon and nitrogen cycling. Still, we know little about how soil microbial communities will be affected by disturbances expected with climate change. This is a significant gap in understanding, as the stability of microbial communities, defined as a community's ability to resist and recover from disturbances, likely has consequences for ecosystem function. Here, we propose a framework for predicting a community's response to climate change, based on specific functional traits present in the community, the relative dominance of r- and K-strategists, and the soil environment. We hypothesize that the relative abundance of r- and K-strategists will inform about a community's resistance and resilience to climate change associated disturbances. We also propose that other factors specific to soils, such as moisture content and the presence of plants, may enhance a community's resilience. For example, recent evidence suggests microbial grazers, resource availability, and plant roots each impact on microbial community stability. We explore these hypotheses by offering three vignettes of published data that we re-analyzed. Our results show that community measures of the relative abundance of r- and K-strategists, as well as environmental properties like resource availability and the abundance and diversity of higher trophic levels, can contribute to explaining the response of microbial community composition to climate change-related disturbances. However, further investigation and experimental validation is necessary to directly test these hypotheses across a wide range of soil ecosystems. © 2013 de Vries and Shade.

Herrick A.L.,University of Manchester
Current Opinion in Rheumatology | Year: 2011

Purpose of review: The present review gives an update of the current management of Raynaud's phenomenon and its ischaemic complications (digital ulceration and critical ischaemia) and discusses possible further developments in the next 5-10 years. New approaches to therapy are being driven by increased understanding of pathophysiology and by increased international networking of clinicians and scientists, facilitating clinical trials. Recent findings: Key points include phosphodiesterase inhibitors most likely confer benefit, although clinical trials have given somewhat conflicting results, and have been short-term; a new topical, easy-to-use glyceryl trinitrate preparation has been shown to improve Raynaud's Condition Score; the endothelin-1 receptor antagonist bosentan has now been shown to reduce the number of new systemic sclerosis (SSc)-related digital ulcers in two multinational clinical trials; and although statin therapy is likely to confer benefit in SSc-related Raynaud's phenomenon, further research is required to confirm this. Summary: New therapeutic approaches in patients who do not respond to more traditionally used vasodilators include phosphodiesterase inhibitors and (for those with recurrent SScrelated digital ulcers) endothelin-1 receptor antagonism. Several other potential new therapies are being researched. Optimal management of digital ulceration is multidisciplinary including tissue viability and (sometimes) surgical input. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Sutherland J.D.,University of Manchester
Cold Spring Harbor perspectives in biology | Year: 2010

It has normally been assumed that ribonucleotides arose on the early Earth through a process in which ribose, the nucleobases, and phosphate became conjoined. However, under plausible prebiotic conditions, condensation of nucleobases with ribose to give beta-ribonucleosides is fraught with difficulties. The reaction with purine nucleobases is low-yielding and the reaction with the canonical pyrimidine nucleobases does not work at all. The reasons for these difficulties are considered and an alternative high-yielding synthesis of pyrimidine nucleotides is discussed. Fitting the new synthesis to a plausible geochemical scenario is a remaining challenge but the prospects appear good. Discovery of an improved method of purine synthesis, and an efficient means of stringing activated nucleotides together, will provide underpinning support to those theories that posit a central role for RNA in the origins of life.

Tournier C.,University of Manchester
Genes and Cancer | Year: 2013

c-Jun NH2-terminal kinase (JNK) was discovered almost 20 years ago as the protein kinase responsible for phosphorylating c-Jun at Ser-63 and Ser-73. These sites had previously been demonstrated to be essential for the stimulation of c-Jun activity and for cooperation with Ha-ras in oncogenic transformation. This led to the idea that JNK was a positive regulator of cellular transformation. However, the analysis of jnk gene deletion in various mouse models of cancer has produced conflicting findings, with some studies supporting the pro-oncogenic function of JNK and others providing evidence that JNK acts as a tumor suppressor. This review will discuss how these unexpected findings have increased our understanding of the role of JNK signaling in cancer and have provided a source of new working hypotheses. © The Author(s) 2013.

Loudon A.S.I.,University of Manchester
Current Biology | Year: 2012

A recent study suggests that circadian clocks may have evolved at the time of the Great Oxidation Event 2.5 billion years ago in order to drive detoxification of reactive oxygen species. © 2012 Elsevier Ltd.

Keevil B.G.,University of Manchester
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2013

Liquid chromatography tandem mass spectrometry (LC-MS/MS) is increasingly becoming the method of choice for steroid hormone measurements due to small sample volumes, fast analysis times and improved specificity compared to immunoassays. Achievement of demanding analytical targets for steroid analysis is now becoming possible because of improvements in sample preparation technology, liquid chromatography column technology and mass spectrometer design. The most popular sample treatment strategies comprise protein precipitation (PP), solid-phase extraction (SLE) and liquid-liquid extraction (LLE). Modern liquid chromatography columns can ensure the adequate separation of isobaric compounds e.g. 21 Deoxycortisol, 11 Deoxycortisol and Corticosterone. The most appropriate method may be chosen to improve assay sensitivity by reducing matrix effects (LLE, SPE) or simplicity and speed (PP). Specific examples of some clinically important steroids including oestradiol, aldosterone, renin, serum cortisol, salivary cortisol and salivary testosterone will be described. © 2013 Elsevier Ltd. All rights reserved.

Owen L.A.,University of Cincinnati | Dortch J.M.,University of Manchester
Quaternary Science Reviews | Year: 2014

Much effort has been made in recent years to define the timing and extent of Quaternary glaciation throughout the Himalayan-Tibetan orogen. These studies are challenging because of the logistical and political inaccessibility of the region, and the inherent problems associated with the application of numerical dating techniques. Nevertheless, the studies are providing abundant evidence for significant glacial advances throughout the last several glacial cycles and are beginning to accurately define the extent and timing of glaciation in selected regions. Studies are showing that Himalayan-Tibetan glaciers in arid regions during the last glacial cycle reached their maximum extent early in the cycle and that global Last Glacial Maximum glacier advances were significantly less extensive. However, along the more monsoonal-influenced Greater Himalaya, there is increasing evidence to suggest that glaciation was more extensive later in the last glacial cycle, but this has yet to be fully assessed. In addition, the new studies are showing that throughout most Himalayan-Tibetan regions, significant glacier advances occurred during the Lateglacial and early Holocene, with minor advances in some regions during the mid-Holocene. The still relatively poor chronological control in the Himalayan-Tibetan orogen, however, makes it difficult to construct correlations across the region, and with regions elsewhere in the world. This in turn makes it hard to assess the relative importance of the different climatic mechanisms that force glaciation across the Himalayan-Tibetan orogen, and to quantify paleoclimate change in this high altitude subtropical region. The Lateglacial and Holocene glacial records, however, are particularly well preserved in several Himalayan-Tibetan regions. Glacial successions such as these have the greatest potential to be examined in detail using newly developing numerical dating, and geomorphic and sedimentologic methods to derive high-resolution terrestrial records of glaciation that will help in paleoclimatic reconstruction for high altitude subtropical regions. © 2013 Elsevier Ltd.

Jennings W.,University of Manchester
Construction Management and Economics | Year: 2012

The systematic under-estimation of costs in budgeting for large-scale projects raises the vexing question of why there are such incongruities between the projections made at initial stages and the eventual outturn cost. As a first step to understanding the sources of such budgeting overruns in the context of the Olympics, this research note outlines how the costs of the London 2012 Olympic Games were under-estimated in a series of budget forecasts, identifying sources of error and categorizing these according to the effects on budgeting of: (1) inattention to risk inside government; (2) biases in decision-making in the evaluation and use of information; and (3) uncertainty in project management and administration. These factors are accentuated through the planning and budgeting context, as estimates at different stages of the process serve alternative purposes and entail varying levels of knowledge and scrutiny. © 2012 Copyright Taylor and Francis Group, LLC.

Hoyle D.C.,University of Manchester
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2011

For many learning problems, estimates of the inverse population covariance are required and often obtained by inverting the sample covariance matrix. Increasingly for modern scientific data sets, the number of sample points is less than the number of features and so the sample covariance is not invertible. In such circumstances, the Moore-Penrose pseudo-inverse sample covariance matrix, constructed from the eigenvectors corresponding to nonzero sample covariance eigenvalues, is often used as an approximation to the inverse population covariance matrix. The reconstruction error of the pseudo-inverse sample covariance matrix in estimating the true inverse covariance can be quantified via the Frobenius norm of the difference between the two. The reconstruction error is dominated by the smallest nonzero sample covariance eigenvalues and diverges as the sample size becomes comparable to the number of features. For high-dimensional data, we use random matrix theory techniques and results to study the reconstruction error for a wide class of population covariance matrices. We also show how bagging and random subspace methods can result in a reduction in the reconstruction error and can be combined to improve the accuracy of classifiers that utilize the pseudo-inverse sample covariance matrix. We test our analysis on both simulated and benchmark data sets. © 2011 IEEE.

Deakin J.F.W.,University of Manchester
Journal of Psychopharmacology | Year: 2013

In this brief reflection I outline how Fred Graeff and I came to integrate our ideas and findings concerning the behavioural functions of serotonin (5-HT) over 20 years ago in '5-HT and mechanisms of defence', reproduced in this volume (pp. 000-000). The principal insight was that different 5-HT pathways mediate distinct adaptive responses to aversive events of different types. It emerged from a number of strands in neuropsychopharmacology: the functional implications of the still-fresh images of monoamine neuroanatomy of the 1970s; the ethological differentiation of behavioural responses to proximal and distal threats; and the seemingly contradictory effects of 5-HT drugs in unconditioned, Pavlovian and instrumental paradigms of reward and aversion. The article has been cited over 600 times and continues to be cited. The evidence was mainly from the animal literature but included some experimental psychopharmacological tests in humans. Some more recent and notable human corroborations are highlighted in this perspective. © The Author(s) 2013.

Harris J.,University of Manchester
Bioethics | Year: 2011

This paper identifies human enhancement as one of the most significant areas of bioethical interest in the last twenty years. It discusses in more detail one area, namely moral enhancement, which is generating significant contemporary interest. The author argues that so far from being susceptible to new forms of high tech manipulation, either genetic, chemical, surgical or neurological, the only reliable methods of moral enhancement, either now or for the foreseeable future, are either those that have been in human and animal use for millennia, namely socialization, education and parental supervision or those high tech methods that are general in their application. By that is meant those forms of cognitive enhancement that operate across a wide range of cognitive abilities and do not target specifically 'ethical' capacities. The paper analyses the work of some of the leading contemporary advocates of moral enhancement and finds that in so far as they identify moral qualities or moral emotions for enhancement they have little prospect of success. © 2010 Blackwell Publishing Ltd.

Skeoch S.,University of Manchester | Bruce I.N.,NIHR Manchester Musculoskeletal Biomedical Research Unit
Nature Reviews Rheumatology | Year: 2015

Rheumatoid arthritis (RA) has long been associated with increased cardiovascular risk, but despite substantial improvements in disease management, mortality remains high. Atherosclerosis is more prevalent in RA than in the general population, and atherosclerotic lesions progress at a faster rate and might be more prone to rupture, causing clinical events. Cells and cytokines implicated in RA pathogenesis are also involved in the development and progression of atherosclerosis, which is generally recognized as an inflammatory condition. The two diseases also share genetic and environmental risk factors, which suggests that patients who develop RA might also be predisposed to developing cardiovascular disease. In RA, inflammation and atherosclerosis are closely linked. Inflammation mediates its effects on atherosclerosis both through modulation of traditional risk factors and by directly affecting the vessel wall. Treatments such as TNF inhibitors might have a beneficial effect on cardiovascular risk. However, whether this benefit is attributable to effective control of inflammation or whether targeting specific cytokines, implicated in atherosclerosis, provides additional risk reduction is unclear. Further knowledge of the predictors of cardiovascular risk, the effects of early control of inflammation and of drug-specific effects are likely to improve the recognition and management of cardiovascular risk in patients with RA. © 2015 Macmillan Publishers Limited.

Dierking I.,University of Manchester
Materials | Year: 2014

The polymer stabilized state of ferroelectric liquid crystals (FLC) is reviewed; and the effect of a dispersed polymer network in an FLC outlined and discussed. All fundamental material aspects are demonstrated; such as director tilt angle; spontaneous polarization; response time and viscosity; as well as the dielectric modes. It was found that the data can largely be explained by assuming an elastic interaction between the polymer network strands and the liquid crystal molecules. The elastic interaction parameter was determined; and increases linearly with increasing polymer concentration. © 2014 by the authors.

Dursun T.,ASELSAN Inc. | Soutis C.,University of Manchester
Materials and Design | Year: 2014

Aluminium alloys have been the primary material for the structural parts of aircraft for more than 80. years because of their well known performance, well established design methods, manufacturing and reliable inspection techniques. Nearly for a decade composites have started to be used more widely in large commercial jet airliners for the fuselage, wing as well as other structural components in place of aluminium alloys due their high specific properties, reduced weight, fatigue performance and corrosion resistance. Although the increased use of composite materials reduced the role of aluminium up to some extent, high strength aluminium alloys remain important in airframe construction. Aluminium is a relatively low cost, light weight metal that can be heat treated and loaded to relatively high level of stresses, and it is one of the most easily produced of the high performance materials, which results in lower manufacturing and maintenance costs. There have been important recent advances in aluminium aircraft alloys that can effectively compete with modern composite materials. This study covers latest developments in enhanced mechanical properties of aluminium alloys, and high performance joining techniques. The mechanical properties on newly developed 2000, 7000 series aluminium alloys and new generation Al-Li alloys are compared with the traditional aluminium alloys. The advantages and disadvantages of the joining methods, laser beam welding and friction stir welding, are also discussed. © 2013 Elsevier Ltd.

Klingenberg C.P.,University of Manchester
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

Although most studies on integration and modularity have focused on variation among individuals within populations or species, this is not the only level of variation for which integration and modularity exist. Multiple levels of biological variation originate from distinct sources: genetic variation, phenotypic plasticity resulting from environmental heterogeneity, fluctuating asymmetry from random developmental variation and, at the interpopulation or interspecific levels, evolutionary change. The processes that produce variation at all these levels can impart integration or modularity on the covariance structure among morphological traits. In turn, studies of the patterns of integration and modularity can inform about the underlying processes. In particular, the methods of geometric morphometrics offer many advantages for such studies because they can characterize the patterns of morphological variation in great detail and maintain the anatomical context of the structures under study. This paper reviews biological concepts and analytical methods for characterizing patterns of variation and for comparing across levels. Because research comparing patterns across level has only just begun, there are relatively few results, generalizations are difficult and many biological and statistical questions remain unanswered. Nevertheless, it is clear that research using this approach can take advantage of an abundance of new possibilities that are so far largely unexplored. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Vickerman J.C.,University of Manchester
Analyst | Year: 2011

The possibility of exploiting the analytical power of mass spectrometry to image the chemistry of biological and similarly complex materials without the use of tags and with good spatial resolution is seductive. The status, strengths, weaknesses and complementarity of the three main techniques are briefly reviewed and assessed. © 2011 The Royal Society of Chemistry.

Insects preserved in copal, the sub-fossilized resin precursor of amber, have potential value in molecular ecological studies of recently-extinct species and of extant species that have never been collected as living specimens. The objective of the work reported in this paper was therefore to determine if ancient DNA is present in insects preserved in copal. We prepared DNA libraries from two stingless bees (Apidae: Meliponini: Trigonisca ameliae) preserved in 'Anthropocene' Colombian copal, dated to 'post-Bomb' and 10,612±62 cal yr BP, respectively, and obtained sequence reads using the GS Junior 454 System. Read numbers were low, but were significantly higher for DNA extracts prepared from crushed insects compared with extracts obtained by a non-destructive method. The younger specimen yielded sequence reads up to 535 nucleotides in length, but searches of these sequences against the nucleotide database revealed very few significant matches. None of these hits was to stingless bees though one read of 97 nucleotides aligned with two non-contiguous segments of the mitochondrial cytochrome oxidase subunit I gene of the East Asia bumblebee Bombus hypocrita. The most significant hit was for 452 nucleotides of a 470-nucleotide read that aligned with part of the genome of the root-nodulating bacterium Bradyrhizobium japonicum. The other significant hits were to proteobacteria and an actinomycete. Searches directed specifically at Apidae nucleotide sequences only gave short and insignificant alignments. All of the reads from the older specimen appeared to be artefacts. We were therefore unable to obtain any convincing evidence for the preservation of ancient DNA in either of the two copal inclusions that we studied, and conclude that DNA is not preserved in this type of material. Our results raise further doubts about claims of DNA extraction from fossil insects in amber, many millions of years older than copal.

Woolf A.S.,University of Manchester | Davies J.A.,University of Edinburgh
Journal of the American Society of Nephrology | Year: 2013

The mammalian ureter contains two main cell types: a multilayered water-tight epithelium called the urothelium, surrounded by smooth muscle layers that, by generating proximal to distal peristaltic waves, pump urine fromthe renal pelvis toward the urinary bladder. Here, we review the cellular mechanisms involved in the development of these tissues, and themolecules that control the process.We consider the relevance of these biologic findings for understanding the pathogenesis of human ureter malformations. Copyright © 2013 by the American Society of Nephrology.

Woollams A.M.,University of Manchester
Neuropsychologia | Year: 2015

The degree to which a word's meaning evokes a mental image exerts an influence on performance across a variety of conceptual and linguistic tasks. In normal healthy participants, this effect takes the form of an advantage for high over low imageability words. Consideration of the influence of imageability on performance of patients with semantic dementia can provide information concerning its cognitive and neural bases. Semantic dementia patients show deficits in conceptual processing tasks, and an associated enhancement of the advantage for high over low imageability words. Semantic dementia patients also show deficits in linguistic processing tasks, including reading aloud words with inconsistent spelling-sound correspondences. This study provides the first systematic exploration of the influence of imageability on semantic dementia patients' reading aloud performance. Over 10 cases, the imageability effect seen for inconsistent words was actually reversed in reaction times, with faster performance for low than high imageability items. The same reversal was observed for inconsistent words when the frequency of legitimate alternative reading of components errors was considered, and this reversed effect grew larger with increasing semantic impairment. This result is interpreted in terms of the development of stronger connections along the direct pathway between spelling and sound for low than high imageability items that are then revealed under diminished semantic activation. This interpretation emphasises the interaction between form and meaning that occurs throughout learning in connectionist models. © 2015 Elsevier Ltd.

Bouzarovski S.,University of Manchester
Wiley Interdisciplinary Reviews: Energy and Environment | Year: 2014

Energy poverty can be seen as situation in which a household lacks a socially and materially necessitated level of energy services in the home. In the context of the European Union (EU), its causes and consequences largely coincide with those of the more narrowly defined notion of 'fuel poverty', which has attracted a significant amount of public attention, scientific research, and state policy in Ireland and the UK. Outside of these two countries, however, EU energy poverty scholarship, debates, and policies are embryonic. From the limited amount of research that has been published to date, it is possible to conclude that the condition is predicated upon high energy prices, low household incomes, inefficient buildings and appliances, and specific households energy needs. It is particularly widespread in Eastern, Central, and Southern Europe, where it tends to affect groups who are already vulnerable to income poverty. Recent years have seen a conceptual shift in the mainstream theorization of domestic energy deprivation, onto more complex and nuanced issues of household needs, built environment flexibility, and social resilience. © 2013 John Wiley & Sons, Ltd.

Dada J.O.,University of Manchester
Renewable and Sustainable Energy Reviews | Year: 2014

The poor state of electricity supply system in Nigeria is threatening the welfare and security of life and properties of millions of individuals with adverse economic consequences for the country. The inadequacy of the national grid, especially the inability of the electricity generation capacity to match increasing demand in the country has led to increasing agitation for increased penetration of renewable energy sources (RESs) into the electricity supply mix. While great attention has been focused on the potential of RESs for electricity generation in the country, little or no attention has been given to the application of Smart/Micro-Grid (SM-G) technologies to the ageing Nigeria grid infrastructures and electrification of the rural areas. The aim of this paper is to bring into focus the benefits and challenges of enabling SM-G in the electricity supply system in Nigeria. SM-G will bring benefits to the electricity stakeholders in form of improvements in reliability, efficiency, economics, environment, security and safety. The paper gives an overview and reviews the current state of the electricity supply system in the country. It discusses the SM-G concepts and associated technologies, and highlights how they can help address the electricity problems in the country. The challenges of applying these concepts in Nigeria context are also discussed. Enabling SM-G in the country will not only lead to improvement in the quality, efficiency and reliability of the electricity grid, but also promote the provision of electricity supply to the remote rural areas using RESs. © 2014 Elsevier Ltd.

Kendall A.C.,University of Manchester
Journal of Investigative Dermatology | Year: 2015

The skin produces bioactive lipids that participate in physiological and pathological states, including homeostasis, induction, propagation, and resolution of inflammation. However, comprehension of the cutaneous lipid complement, and contribution to differing roles of the epidermal and dermal compartments, remains incomplete. We assessed the profiles of eicosanoids, endocannabinoids, N-acyl ethanolamides, and sphingolipids, in human dermis, epidermis, and suction blister fluid. We identified 18 prostanoids, 12 hydroxy-fatty acids, 9 endocannabinoids and N-acyl ethanolamides, and 21 non-hydroxylated ceramides and sphingoid bases, several demonstrating significantly different expression in the tissues assayed. The array of dermal and epidermal fatty acids was reflected in the lipid mediators produced, whereas similarities between lipid profiles in blister fluid and epidermis indicated a primarily epidermal origin of suction blister fluid. Supplementation with omega-3 fatty acids ex vivo showed that their action is mediated through perturbation of existing species and formation of other anti-inflammatory lipids. These findings demonstrate the diversity of lipid mediators involved in maintaining tissue homeostasis in resting skin and hint at their contribution to signaling, cross-support, and functions of different skin compartments. Profiling lipid mediators in biopsies and suction blister fluid can support studies investigating cutaneous inflammatory responses, dietary manipulation, and skin diseases lacking biomarkers and therapeutic targets.Journal of Investigative Dermatology advance online publication, 12 March 2015; doi:10.1038/jid.2015.41. © 2015 The Society for Investigative Dermatology, Inc

Klingenberg C.P.,University of Manchester | Marugan-Lobon J.,Autonomous University of Madrid
Systematic Biology | Year: 2013

Quantifying integration and modularity of evolutionary changes in morphometric traits is crucial for understanding how organismal shapes evolve. For this purpose, comparative studies are necessary, which need to take into account the phylogenetic structure of interspecific data. This study applies several of the standard tools of geometric morphometrics, which mostly have been used in intraspecific studies, in the new context of analyzing integration and modularity based on comparative data. Morphometric methods such as principal component analysis, multivariate regression, partial least squares, and modularity tests can be applied to phylogenetically independent contrasts of shape data.We illustrate this approach in an analysis of cranial evolution in 160 species from all orders of birds. Mapping the shape information onto the phylogeny indicates that there is a significant phylogenetic signal in skull shape. Multivariate regression of independent contrasts of shape on independent contrasts of size reveals clear evolutionary allometry. Regardless of whether or not a correction for allometry is used, evolutionary integration between the face and braincase is strong, and tests reject the hypothesis that the face and braincase are separate evolutionarymodules. These analyses can easily be applied to other taxa and can be combined with other morphometric tools to address a wide range of questions about evolutionary patterns and processes. [Aves;comparativemethods; independent contrasts;morphological integration; partial least squares; Procrustes superimposition; shape; skull.] © The Author(s) 2013.

Goble C.,University of Manchester
IEEE Internet Computing | Year: 2014

Modern scientific research isn't possible without software. However, its vital role is often overlooked by funders, universities, assessment committees, and even the research community itself. This is a serious issue that needs urgent attention. This article raises a number of points concerning quality, code review, and openness; development practices and training in scientific computing; career recognition of research software engineers; and sustainability models for funding scientific software. We must get software recognized to be the first-class experimental scientific instrument that it is and get 'better software for better research.' © 1997-2012 IEEE.

Zheng Y.-Z.,Xian University of Science and Technology | Zhou G.-J.,Xian University of Science and Technology | Zheng Z.,Xian University of Science and Technology | Zheng Z.,University of Arizona | Winpenny R.E.P.,University of Manchester
Chemical Society Reviews | Year: 2014

There has been a rapid expansion in the use of molecular magnets for both low- and ultra low-temperature cooling applications in recent years, and here we review the chemical variation and magnetothermal properties of reported molecular coolers, structuring the review by structural dimensions, metal-ions involved and ligands employed. This review provides an overview of the developments in designing better low-temperature magnetic refrigerants, and includes description of new 3D-materials that, in some ways, out-perform traditional magnetic coolants. Thus, this review should serve as both a tutorial for many newcomers and a summary of progress for researchers who are active in the field. © 2014 The Royal Society of Chemistry.

Mancarella P.,University of Manchester
Energy | Year: 2014

MES (multi-energy systems) whereby electricity, heat, cooling, fuels, transport, and so on optimally interact with each other at various levels (for instance, within a district, city or region) represent an important opportunity to increase technical, economic and environmental performance relative to "classical" energy systems whose sectors are treated "separately" or "independently". This performance improvement can take place at both the operational and the planning stage. While such systems and in particular systems with distributed generation of multiple energy vectors (DMG (distributed multi-generation)) can be a key option to decarbonize the energy sector, the approaches needed to model and relevant tools to analyze them are often of great complexity. Likewise, it is not straightforward to identify performance metrics that are capable to properly capture costs and benefits that are relating to various types of MES according to different criteria. The aim of this invited paper is thus to provide the reader with a comprehensive and critical overview of the latest models and assessment techniques that are currently available to analyze MES and in particular DMG systems, including for instance concepts such as energy hubs, microgrids, and VPPs (virtual power plants), as well as various approaches and criteria for energy, environmental, and techno-economic assessment. © 2013 Elsevier Ltd.

Cobb M.,University of Manchester
Current Biology | Year: 2014

Seventy years ago, Oswald Avery and his colleagues from the Rockefeller Institute published the first evidence that genes are made of DNA. Their discovery was received with a mixture of enthusiasm, suspicion and perplexity. In this article, I trace the reasons for these different responses, and show how we need to revise our usual explanations of what finally convinced everyone that the Avery group was right. © 2014 Elsevier Ltd.

Nelson B.J.,ETH Zurich | Peyer K.E.,University of Manchester
ACS Nano | Year: 2014

Essentially all experimental investigations of swimming micro- and nanorobots have focused on swimming in homogeneous Newtonian liquids. In this issue of ACS Nano, Schamel et al. investigate the actuation of "nanopropellers" in a viscoelastic biological gel that illustrates the importance of the size of the nanostructure relative to the gel mesh size. In this Perspective, we shed further light on the swimming performance of larger microrobots swimming in heterogeneous liquids. One of the interesting results of our work is that earlier findings on the swimming performance of motile bacteria in heterogeneous liquids agree, in principle, with our results. We also discuss future research directions that should be pursued in this fascinating interdisciplinary field. © 2014 American Chemical Society.

Fetal growth restriction (FGR) is defined as the inability of a fetus to achieve its genetic growth potential and is associated with a significantly increased risk of morbidity and mortality. Clinically, FGR is diagnosed as a fetus falling below the 5(th) centile of customised growth charts. Sildenafil citrate (SC, Viagra™), a potent and selective phosphodiesterase-5 inhibitor, corrects ex vivo placental vascular dysfunction in FGR, demonstrating potential as a therapy for this condition. However, many FGR cases present without an abnormal vascular phenotype, as assessed by Doppler measures of uterine/umbilical artery blood flow velocity. Thus, we hypothesized that SC would not increase fetal growth in a mouse model of FGR, the placental-specific Igf2 knockout mouse, which has altered placental exchange capacity but normal placental blood flow. Fetal weights were increased (by 8%) in P0 mice following maternal SC treatment (0.4 mg/ml) via drinking water. There was also a trend towards increased placental weight in treated P0 mice (P = 0.056). Additionally, 75% of the P0 fetal weights were below the 5(th) centile, the criterion used to define human FGR, of the non-treated WT fetal weights; this was reduced to 51% when dams were treated with SC. Umbilical artery and vein blood flow velocity measures confirmed the lack of an abnormal vascular phenotype in the P0 mouse; and were unaffected by SC treatment. (14)C-methylaminoisobutyric acid transfer (measured to assess effects on placental nutrient transporter activity) per g placenta was unaffected by SC, versus untreated, though total transfer was increased, commensurate with the trend towards larger placentas in this group. These data suggest that SC may improve fetal growth even in the absence of an abnormal placental blood flow, potentially affording use in multiple sub-populations of individuals presenting with FGR.

Ceh-Pavia E.,University of Manchester
International journal of molecular sciences | Year: 2013

Correct and timely folding is critical to the function of all proteins. The importance of this is illustrated in the biogenesis of the mitochondrial intermembrane space (IMS) "small Tim" proteins. Biogenesis of the small Tim proteins is regulated by dedicated systems or pathways, beginning with synthesis in the cytosol and ending with assembly of individually folded proteins into functional complexes in the mitochondrial IMS. The process is mostly centered on regulating the redox states of the conserved cysteine residues: oxidative folding is crucial for protein function in the IMS, but oxidized (disulfide bonded) proteins cannot be imported into mitochondria. How the redox-sensitive small Tim precursor proteins are maintained in a reduced, import-competent form in the cytosol is not well understood. Recent studies suggest that zinc and the cytosolic thioredoxin system play a role in the biogenesis of these proteins. In the IMS, the mitochondrial import and assembly (MIA) pathway catalyzes both import into the IMS and oxidative folding of the small Tim proteins. Finally, assembly of the small Tim complexes is a multistep process driven by electrostatic and hydrophobic interactions; however, the chaperone function of the complex might require destabilization of these interactions to accommodate the substrate. Here, we review how folding of the small Tim proteins is regulated during their biogenesis, from maintenance of the unfolded precursors in the cytosol, to their import, oxidative folding, complex assembly and function in the IMS.

Falkingham P.L.,University of Manchester
Palaeontologia Electronica | Year: 2012

The 3D digitisation of palaeontological resources is of tremendous use to the field, providing the means to archive, analyse, and visualise specimens that would otherwise be too large to handle, too valuable to destructively sample, or simply in a different geographic location. Digitisation of a specimen to produce a 3D digital model often requires the use of expensive laser scanning equipment or proprietary digital reconstruction software, making the technique inaccessible to many workers. Presented here is a guide for producing high resolution 3D models from photographs, using freely available open-source software. To demonstrate the accuracy and flexibility of the approach, a number of examples are given, including a small trilobite (~0.04 m), a large mounted elephant skeleton (~3 m), and a very large fossil tree root system (~6 m), illustrating that the method is equally applicable to specimens or even outcrops of all sizes. The digital files of the models produced in this paper are included. The results demonstrate that production of digital models from specimens for research or archival purposes is available to anyone, and it is hoped that an increased use of digitisation techniques will facilitate research and encourage collaboration and dissemination of digital data. © Palaeontological Association February 2012.

Ding Z.,University of Manchester
IEEE Transactions on Industrial Electronics | Year: 2015

This paper deals with consensus disturbance rejection of network-connected dynamic systems using disturbance observers. The control objective of consensus disturbance rejection is to achieve a common state trajectory for the network-connected subsystems that are under deterministic disturbances. The difference from the existing disturbance rejection methods is that only the relative state information is used for disturbance rejection, and as a consequence of using the relative state information, only the part of the disturbances that affect the common trajectories will be rejected. The conditions for designing disturbance observers for consensus control are identified for networked-connected multiagent systems. Certain features of the individual subsystems are analyzed for possible implementation of disturbance-observer-based rejection, and the disturbance observers are designed based on the relative state information obtained from the neighboring subsystems under different network connections. When the network connectivity is available for the disturbance observer design, consensus disturbance rejection is achieved for a directed network with a spanning tree. A fully distributed consensus disturbance rejection design is presented for an undirected network with the use of adaptive parameters for the estimation of the unknown network connectivity. Disturbance observers are also proposed for disturbance rejection in the leader-follower consensus control. © 1982-2012 IEEE.

Bower P.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2011

The prevalence of mental health and psychosocial problems in primary care is high. Counselling is a potential treatment for these patients, but there is a lack of consensus over the effectiveness of this treatment in primary care. To assess the effectiveness and cost effectiveness of counselling for patients with mental health and psychosocial problems in primary care. To update the review, the following electronic databases were searched: the Cochrane Collaboration Depression, Anxiety and Neurosis (CCDAN) trials registers (to December 2010), MEDLINE, EMBASE, PsycINFO and the Cochrane Central Register of Controlled Trials (to May 2011). Randomised controlled trials of counselling for mental health and psychosocial problems in primary care. Data were extracted using a standardised data extraction sheet by two reviewers. Trials were rated for quality by two reviewers using Cochrane risk of bias criteria, to assess the extent to which their design and conduct were likely to have prevented systematic error. Continuous measures of outcome were combined using standardised mean differences. An overall effect size was calculated for each outcome with 95% confidence intervals (CI). Continuous data from different measuring instruments were transformed into a standard effect size by dividing mean values by standard deviations. Sensitivity analyses were undertaken to test the robustness of the results. Economic analyses were summarised in narrative form. There was no assessment of adverse events. Nine trials were included in the review, involving 1384 randomised participants. Studies varied in risk of bias, although two studies were identified as being at high risk of selection bias because of problems with concealment of allocation. All studies were from primary care in the United Kingdom and thus comparability was high. The analysis found significantly greater clinical effectiveness in the counselling group compared with usual care in terms of mental health outcomes in the short-term (standardised mean difference -0.28, 95% CI -0.43 to -0.13, n = 772, 6 trials) but not in the long-term (standardised mean difference -0.09, 95% CI -0.27 to 0.10, n = 475, 4 trials), nor on measures of social function (standardised mean difference -0.09, 95% CI -0.29 to 0.11, n = 386, 3 trials). Levels of satisfaction with counselling were high. There was some evidence that the overall costs of counselling and usual care were similar. There were limited comparisons between counselling and other psychological therapies, medication, or other psychosocial interventions. Counselling is associated with significantly greater clinical effectiveness in short-term mental health outcomes compared to usual care, but provides no additional advantages in the long-term. Participants were satisfied with counselling. Although some types of health care utilisation may be reduced, counselling does not seem to reduce overall healthcare costs. The generalisability of these findings to settings outside the United Kingdom is unclear.

Charman W.N.,University of Manchester
Ophthalmic and Physiological Optics | Year: 2014

Purpose: To outline the refractive problems associated with presbyopia and to review the basis and relative merits of currently-available methods for their correction, with detailed consideration of spectacle and contact lens approaches. Contents: In the developed world, most of the present population will spend roughly half their lives as presbyopes. The well-known presbyopic changes with age in amplitude of accommodation and required near addition are briefly reviewed, together with the less widely acknowledged slow drifts that occur in distance refraction. The desirability of restoring to presbyopes clear vision for objects at any distance, ideally corresponding to vergences within the range of at least 0 to -5 D, in any viewing direction, is stressed. A general outline is given of possible corrective methods. Methods which satisfy the needs of a 50 year-old may not be suitable for the 80 year-old. Corrections may involve both fixed- and variable-focus lens systems, and surgical methods which modify the optics of the cornea, replace the crystalline lens with different fixed optics, or attempt to at least partially restore active accommodation. Some more recent methods of spectacle and contact lens correction are described in more detail. Particular attention is given to recent commercially-developed spectacles in which the corrective power can be varied actively by either mechanical (liquid-filled deformable lenses or Alvarez lenses) or electrical (liquid crystal lenses) means to allow objects at different distances to be seen clearly. Contact lens corrections show less progress and are still preferred only by a minority of older patients, most of whom are early presbyopes. Summary: The rising proportion of presbyopes in the population, covering an age span of around 40 years, represents both a problem for those concerned with giving their patients the best vision possible at both far and near viewing distances and a commercial opportunity. Traditional single-vision distance and near, bifocal, and progressive spectacle lens solutions, together with contact lens modalities for presbyopic correction, are being challenged by a variety of new approaches. It remains to be seen whether the latter will receive wide acceptance in practice. © 2013 The College of Optometrists.

Crow Y.J.,French Institute of Health and Medical Research | Crow Y.J.,University of Paris Pantheon Sorbonne | Crow Y.J.,University of Manchester
Current Opinion in Immunology | Year: 2015

The concept of grouping Mendelian disorders associated with an up-regulation of type I interferon has only recently been suggested. Here we discuss the progress being made in the delineation and understanding of this novel set of inborn errors of immunity, the human type I interferonopathies. © 2014 Elsevier Ltd.

Regarded as one solution to the problem of how to enable older people to retain their independence, extra-care housing, where each resident has their own self-contained dwelling and access to communal facilities and to care, has received extensive funding in recent years. Implicit in the concept of specialist housing is the notion of 'special' occupants, imagined older people. Adopting a socio-technical approach, this paper considers how ideas about ageing inform those aspects of extra-care-housing-design that relate to thermal comfort. The paper draws on semi-structured interviews with 13 people involved in the design, development and management of UK-based extra-care housing. Participants characterised imagined occupants as vulnerable to cold, at risk from fuel poverty and liable to be burned by hot surfaces or fall from high windows. These user representations were reportedly inscribed into the design of extra-care housing schemes through the inclusion of building features such as communal heating, under-floor heating, restricted window opening and heated corridors. The utilisation of stereotypical user representations of older people raises questions, given that older people's thermal comfort needs can be highly diverse. The paper explores the implications for energy demand. © 2015 The Author.

Crow Y.J.,French Institute of Health and Medical Research | Crow Y.J.,University of Paris Pantheon Sorbonne | Crow Y.J.,University of Manchester | Manel N.,University Pierre and Marie Curie | Manel N.,French Institute of Health and Medical Research
Nature Reviews Immunology | Year: 2015

Dissection of the genetic basis of Aicardi-Goutières syndrome has highlighted a fundamental link between nucleic acid metabolism, innate immune sensors and type I interferon induction. This had led to the concept of the human interferonopathies as a broader set of Mendelian disorders in which a constitutive upregulation of type I interferon activity directly relates to disease pathology. Here, we discuss the molecular and cellular basis of the interferonopathies, their categorization, future treatment strategies and the insights they provide into normal physiology. © 2015 Macmillan Publishers Limited.

Aplin J.D.,University of Manchester
International Journal of Developmental Biology | Year: 2010

The common gestational pathologies are placental and developmental in origin. However, much remains to be learned about the key events of morphogenesis and growth in the placenta. Metabolic settings established early in both the fetus and placenta define their capacity to respond to later challenges, as well as the quality of the response. Placental growth is exponential in the first trimester and involves coordinated events in trophoblast and mesenchyme, with early cell segregation events having a strong influence on growth potential. One of these is the differentiation of progenitor cytotrophoblasts into villous intermediate cells programmed to fuse with the syncytium, or, alternatively, into extravillous migratory cells that transform the maternal vascular supply. In the latter case, contact with decidual extracellular matrix stimulates differentiation, and therefore this decision is influenced by the number of contact sites at the placental periphery, which in turn is a function of branching in the villous tree. The villous trophoblast bilayer is the primary barrier between maternal and fetal tissues. The maternal-facing layer is syncytial and post-mitotic: this limits traffic of pathogens to the fetus and chimaerism arising by shedding of (non-proliferative) syncytial elements into maternal circulation. Conventional cell culture models fail to replicate this critical vectorial relationship. Tissue explants can overcome the problem to some extent, and have been used to show that turnover of trophoblast in the villous environment is regulated by signals from both fetal and maternal tissues. Maternally delivered insulin-like growth factors stimulate growth and might be therapeutically useful when endogenous growth pathways falter. © 2009 UBC Press.

Bardgett R.D.,University of Manchester | Van Der Putten W.H.,Netherlands Institute of Ecology | Van Der Putten W.H.,Wageningen University
Nature | Year: 2014

Evidence is mounting that the immense diversity of microorganisms and animals that live belowground contributes significantly to shaping aboveground biodiversity and the functioning of terrestrial ecosystems. Our understanding of how this belowground biodiversity is distributed, and how it regulates the structure and functioning of terrestrial ecosystems, is rapidly growing. Evidence also points to soil biodiversity as having a key role in determining the ecological and evolutionary responses of terrestrial ecosystems to current and future environmental change. Here we review recent progress and propose avenues for further research in this field. © 2014 Macmillan Publishers Limited. All rights reserved.

Nordqvist P.,University of Manchester
Culture, Health and Sexuality | Year: 2012

Donor conception challenges conventional kinship idioms: the involvement of a gamete donor culturally raises questions about parentage and also the meaning of genetic heritage. Although there is now a growing body of literature exploring how people resorting to donor conception negotiate kinship and connectedness, this predominantly focuses on heterosexual couples. Little is yet known about how lesbian couples navigate these processes. This paper builds on a qualitative interview study comprising 25 lesbian couples in England and Wales with experiences of pursuing donor conception in the context of their couple relationship to explore how these couples negotiate the contribution of the donor. It explores how couples negotiate meanings of parenthood, genetic origins and the bodily process of conception. The paper argues that lesbian couples negotiate parental identities, biogenetic relationships and also the meaning of conception by disassembling and reassembling the meaning of kinship, parenthood, creation, origin and originator. Findings suggest that lesbian couples weave together old and new understandings of relatedness in complex patterns and that this enables them to assert authority as parents. © 2012 Copyright Crown Copyright.

We review some recent progress on the characterisation of long-range patterns of word use in language using methods from information theory. In particular, two levels of structure in language are considered. The first level corresponds to the patterns of words usage over different contextual domains. A direct application of information theory to quantify the specificity of words across different sections of a linguistic sequence leads to a measure of semantic information. Moreover, a natural scale emerges that characterises the typical size of semantic structures. Since the information measure is made up of additive contributions from individual words, it is possible to rank the words according to their overall weight in the total information. This allows the extraction of keywords most relevant to the semantic content of the sequence without any prior knowledge of the language. The second level considered is the complex structure of correlations among words in linguistic sequences. The degree of order in language can be quantified by means of the entropy. Reliable estimates of the entropy were obtained from corpora of texts from several linguistic families by means of lossless compression algorithms. The value of the entropy fluctuates across different languages since it depends on linguistic organisation at various levels. However, when a measure of relative entropy that specifically quantifies the degree of word ordering in language is estimated, it presents an almost constant value over all the linguistic families studied. This suggests that the entropy of word ordering is a novel quantitative linguistic universal. © 2013 Elsevier Ltd.

The sustainable product-service system (SPSS) concept highlights that achieving sustainability requires changes in both 'production' and 'consumption'. Nevertheless, attention has focused mainly on 'production'. This paper enriches the SPSS approach with insights from the sociology of consumption and practice theory to provide a deeper understanding of the use of products and services in daily life contexts. The paper advances three key insights related to: a) the internal dynamics of user practices, b) the strength of linkages of practice elements (loose and tight coupling), c) external linkages to other practices. These insights are mobilised to provide a deeper understanding of the uptake and diffusion of innovations such as SPSS. The insights are illustrated with two cases in which interventions designed to stimulate diffusion have had differential success: energy efficient light bulbs and low temperature laundry. Implications for understanding the diffusion of SPSS are discussed. © 2014 The Author.

Felton T.,University of Manchester | Felton T.,University of Liverpool | Troke P.F.,The Old Court | Hope W.W.,University of Liverpool
Clinical Microbiology Reviews | Year: 2014

Understanding the tissue penetration of systemically administered antifungal agents is critical for a proper appreciation of their antifungal efficacy in animals and humans. Both the time course of an antifungal drug and its absolute concentrations within tissues may differ significantly from those observed in the bloodstream. In addition, tissue concentrations must also be interpreted within the context of the pathogenesis of the various invasive fungal infections, which differ significantly. There are major technical obstacles to the estimation of concentrations of antifungal agents in various tissue subcompartments, yet these agents, even those within the same class, may exhibit markedly different tissue distributions. This review explores these issues and provides a summary of tissue concentrations of 11 currently licensed systemic antifungal agents. It also explores the therapeutic implications of their distribution at various sites of infection. © 2014, American Society for Microbiology. All Rights Reserved.

Bond K.,Specialist Service for Affective Disorders | Anderson I.M.,University of Manchester
Bipolar Disorders | Year: 2015

Objectives: Previous reviews have concluded that interventions including psychoeducation are effective in preventing relapse in bipolar disorder, but the efficacy of psychoeducation itself has not been systematically reviewed. Our aim was to evaluate the efficacy of psychoeducation for bipolar disorder in preventing relapse and other outcomes, and to identify factors that relate to clinical outcomes. Methods: We employed the systematic review of randomized controlled trials of psychoeducation in participants with bipolar disorder not in an acute illness episode, compared with treatment-as-usual, and placebo or active interventions. Pooled odds ratios (ORs) for non-relapse into any episode, mania/hypomania, and depression were calculated using an intent-to-treat (ITT) analysis, assigning dropouts to relapse, with a sensitivity analysis in which dropouts were assigned to non-relapse (optimistic ITT). Results: Sixteen studies were included, eight of which provided data on relapse. Although heterogeneity in the data warrants caution, psychoeducation appeared to be effective in preventing any relapse [n = 7; OR: 1.98-2.75; number needed to treat (NNT): 5-7, depending on the method of analysis] and manic/hypomanic relapse (n = 8; OR: 1.68-2.52; NNT: 6-8), but not depressive relapse. Group, but not individually, delivered interventions were effective against both poles of relapse; the duration of follow-up and hours of therapy explained some of the heterogeneity. Psychoeducation improved medication adherence and short-term knowledge about medication. No consistent effects on mood symptoms, quality of life, or functioning were found. Conclusions: Group psychoeducation appears to be effective in preventing relapse in bipolar disorder, with less evidence for individually delivered interventions. Better understanding of mediating mechanisms is needed to optimize efficacy and personalize treatment. © 2015 John Wiley & Sons A/S.

A hexanucleotide (GGGGCC) expansion in C9ORF72 gene is the most common genetic change seen in familial Frontotemporal Lobar Degeneration (FTLD) and familial Motor Neurone Disease (MND). Pathologically, expansion bearers show characteristic p62 positive, TDP-43 negative inclusion bodies within cerebellar and hippocampal neurons which also contain dipeptide repeat proteins (DPR) formed from sense and antisense RAN (repeat associated non ATG-initiated) translation of the expanded repeat region itself. 'Inappropriate' formation, and aggregation, of DPR might therefore confer neurotoxicity and influence clinical phenotype. Consequently, we compared the topographic brain distribution of DPR in 8 patients with Frontotemporal dementia (FTD), 6 with FTD + MND and 7 with MND alone (all 21 patients bearing expansions in C9ORF72) using a polyclonal antibody to poly-GA, and related this to the extent of TDP-43 pathology in key regions of cerebral cortex and hippocampus. There were no significant differences in either the pattern or severity of brain distribution of DPR between FTD, FTD + MND and MND groups, nor was there any relationship between the distribution of DPR and TDP-43 pathologies in expansion bearers. Likewise, there were no significant differences in the extent of TDP-43 pathology between FTLD patients bearing an expansion in C9ORF72 and non-bearers of the expansion. There were no association between the extent of DPR pathology and TMEM106B or APOE genotypes. However, there was a negative correlation between the extent of DPR pathology and age at onset. Present findings therefore suggest that although the presence and topographic distribution of DPR may be of diagnostic relevance in patients bearing expansion in C9ORF72 this has no bearing on the determination of clinical phenotype. Because TDP-43 pathologies are similar in bearers and non-bearers of the expansion, the expansion may act as a major genetic risk factor for FTLD and MND by rendering the brain highly vulnerable to those very same factors which generate FTLD and MND in sporadic disease.

Llewellyn S.,University of Manchester
Behavioral and Brain Sciences | Year: 2013

This article argues that rapid eye movement (REM) dreaming is elaborative encoding for episodic memories. Elaborative encoding in REM can, at least partially, be understood through ancient art of memory (AAOM) principles: visualization, bizarre association, organization, narration, embodiment, and location. These principles render recent memories more distinctive through novel and meaningful association with emotionally salient, remote memories. The AAOM optimizes memory performance, suggesting that its principles may predict aspects of how episodic memory is configured in the brain. Integration and segregation are fundamental organizing principles in the cerebral cortex. Episodic memory networks interconnect profusely within the cortex, creating omnidirectional "landmark" junctions. Memories may be integrated at junctions but segregated along connecting network paths that meet at junctions. Episodic junctions may be instantiated during non-rapid eye movement (NREM) sleep after hippocampal associational function during REM dreams. Hippocampal association involves relating, binding, and integrating episodic memories into a mnemonic compositional whole. This often bizarre, composite image has not been present to the senses; it is not "real" because it hyperassociates several memories. During REM sleep, on the phenomenological level, this composite image is experienced as a dream scene. A dream scene may be instantiated as omnidirectional neocortical junction and retained by the hippocampus as an index. On episodic memory retrieval, an external stimulus (or an internal representation) is matched by the hippocampus against its indices. One or more indices then reference the relevant neocortical junctions from which episodic memories can be retrieved. Episodic junctions reach a processing (rather than conscious) level during normal wake to enable retrieval. If this hypothesis is correct, the stuff of dreams is the stuff of memory. © 2013 Cambridge University Press.

Harris L.K.,University of Manchester
Placenta | Year: 2010

During the first twenty weeks of human pregnancy, extravillous trophoblasts (EVT) colonise the decidua and remodel the uterine spiral arteries as far as the first third of the myometrium. This process leads to an irreversible vasodilatation, ensuring that maximal blood flow is delivered to the materno-fetal interface at an optimal velocity for nutrient exchange. There is accumulating evidence that subtle changes in vascular structure precede EVT colonisation; however, full physiological transformation is only achieved in the presence of trophoblast. This review discusses the mechanisms employed to facilitate arterial dilatation, including recent data regarding the contribution of vascular cell apoptosis, the importance of elastin catabolism and the source of candidate elastases. It also examines how the complex interplay between EVT, endothelial cells, smooth muscle cells and decidual leukocytes (macrophages and uterine natural killer cells) leads to enhanced receptivity to invasion, vascular cell loss and extracellular matrix remodelling. © 2010 Elsevier Ltd. All rights reserved.

Bundred N.,University of Manchester
Cancer Treatment Reviews | Year: 2012

Bone health is an emerging concern in the early breast cancer setting. Current adjuvant therapies, especially hormonal therapies in premenopausal patients (e.g. goserelin) and aromatase inhibitors in postmenopausal patients, have been associated with substantial decreases in bone mineral density that may place patients at risk for fractures. Bisphosphonates-and the recently approved anti-RANKL antibody, denosumab-have both demonstrated activity for the treatment of postmenopausal osteoporosis and cancer treatment-induced bone loss (CTIBL) in breast cancer patients, although neither has received widespread approval specifically for CTIBL. However, some bisphosphonates, especially the nitrogen-containing bisphosphonate zoledronic acid, have also demonstrated clinically meaningful anticancer effects in patients receiving adjuvant hormonal therapy for breast cancer and in other oncology settings. The effects of denosumab on cancer disease outcomes in the adjuvant setting remain to be established. This discrepancy has created a dilemma in terms of how to evaluate the complete benefit:risk profile of bone-health management options in the adjuvant breast cancer setting. This review summarises the current data on the course of cancer in clinical trials of the antiresorptive agents and provides important insight into the relative anticancer potential of the various therapies. © 2012 Elsevier Ltd.

Guttel S.,University of Manchester
GAMM Mitteilungen | Year: 2013

Matrix functions are a central topic of linear algebra, and problems of their numerical approximation appear increasingly often in scientific computing. We review various rational Krylov methods for the computation of large-scale matrix functions. Emphasis is put on the rational Arnoldi method and variants thereof, namely, the extended Krylov subspace method and the shift-and-invert Arnoldi method, but we also discuss the nonorthogonal generalized Leja point (or PAIN) method. The issue of optimal pole selection for rational Krylov methods applied for approximating the resolvent and exponential function, and functions of Markov type, is treated in some detail. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pahle J.,University of Manchester
BMC systems biology | Year: 2012

Stochastic fluctuations in molecular numbers have been in many cases shown to be crucial for the understanding of biochemical systems. However, the systematic study of these fluctuations is severely hindered by the high computational demand of stochastic simulation algorithms. This is particularly problematic when, as is often the case, some or many model parameters are not well known. Here, we propose a solution to this problem, namely a combination of the linear noise approximation with optimisation methods. The linear noise approximation is used to efficiently estimate the covariances of particle numbers in the system. Combining it with optimisation methods in a closed-loop to find extrema of covariances within a possibly high-dimensional parameter space allows us to answer various questions. Examples are, what is the lowest amplitude of stochastic fluctuations possible within given parameter ranges? Or, which specific changes of parameter values lead to the increase of the correlation between certain chemical species? Unlike stochastic simulation methods, this has no requirement for small numbers of molecules and thus can be applied to cases where stochastic simulation is prohibitive. We implemented our strategy in the software COPASI and show its applicability on two different models of mitogen-activated kinases (MAPK) signalling -- one generic model of extracellular signal-regulated kinases (ERK) and one model of signalling via p38 MAPK. Using our method we were able to quickly find local maxima of covariances between particle numbers in the ERK model depending on the activities of phospho-MKKK and its corresponding phosphatase. With the p38 MAPK model our method was able to efficiently find conditions under which the coefficient of variation of the output of the signalling system, namely the particle number of Hsp27, could be minimised. We also investigated correlations between the two parallel signalling branches (MKK3 and MKK6) in this model. Our strategy is a practical method for the efficient investigation of fluctuations in biochemical models even when some or many of the model parameters have not yet been fully characterised.

Pyysalo S.,University of Manchester
BMC bioinformatics | Year: 2012

We present the preparation, resources, results and analysis of three tasks of the BioNLP Shared Task 2011: the main tasks on Infectious Diseases (ID) and Epigenetics and Post-translational Modifications (EPI), and the supporting task on Entity Relations (REL). The two main tasks represent extensions of the event extraction model introduced in the BioNLP Shared Task 2009 (ST'09) to two new areas of biomedical scientific literature, each motivated by the needs of specific biocuration tasks. The ID task concerns the molecular mechanisms of infection, virulence and resistance, focusing in particular on the functions of a class of signaling systems that are ubiquitous in bacteria. The EPI task is dedicated to the extraction of statements regarding chemical modifications of DNA and proteins, with particular emphasis on changes relating to the epigenetic control of gene expression. By contrast to these two application-oriented main tasks, the REL task seeks to support extraction in general by separating challenges relating to part-of relations into a subproblem that can be addressed by independent systems. Seven groups participated in each of the two main tasks and four groups in the supporting task. The participating systems indicated advances in the capability of event extraction methods and demonstrated generalization in many aspects: from abstracts to full texts, from previously considered subdomains to new ones, and from the ST'09 extraction targets to other entities and events. The highest performance achieved in the supporting task REL, 58% F-score, is broadly comparable with levels reported for other relation extraction tasks. For the ID task, the highest-performing system achieved 56% F-score, comparable to the state-of-the-art performance at the established ST'09 task. In the EPI task, the best result was 53% F-score for the full set of extraction targets and 69% F-score for a reduced set of core extraction targets, approaching a level of performance sufficient for user-facing applications. In this study, we extend on previously reported results and perform further analyses of the outputs of the participating systems. We place specific emphasis on aspects of system performance relating to real-world applicability, considering alternate evaluation metrics and performing additional manual analysis of system outputs. We further demonstrate that the strengths of extraction systems can be combined to improve on the performance achieved by any system in isolation. The manually annotated corpora, supporting resources, and evaluation tools for all tasks are available from http://www.bionlp-st.org and the tasks continue as open challenges for all interested parties.

Canoy D.,University of Manchester
Current Atherosclerosis Reports | Year: 2010

Larger waist circumference or waist-hip ratio, as crude indicators of visceral fat mass, are associated with adverse metabolic profile, but their role in predicting future coronary heart disease (CHD) events has been less investigated. Recent epidemiologic findings suggest that these simple and inexpensive measures of abdominal fat distribution predict CHD independently of body mass index, and, to a certain extent, cardiovascular disease risk factors. The magnitude and shape of the association between abdominal adiposity and CHD have been shown to vary with age, gender, and ethnicity. Studies have also suggested that lower body fat is associated with reduced CHD risk, although the clinical relevance for this finding needs further elucidation. Assessing body fat distribution may be useful for improving CHD risk assessment, although more studies are needed to assess consistency in CHD risk predictions across populations. A consensus is also needed to define the clinically relevant cut-off points for waist circumference or waist-hip ratio. © Springer Science+Business Media, LLC 2010.

To evaluate the risk-benefit profile of anti-TNF therapies in PsA and to study the predictors of treatment response and disease remission [disease activity score (DAS)-28 < 2.6]. The study included PsA patients (n = 596) registered with the British Society for Rheumatology Biologics Register (BSRBR). Response was assessed using the European League against Rheumatism (EULAR) improvement criteria. Univariate and multivariate logistic regression models were developed to examine factors associated with EULAR response and disease remission using a range of covariates. Poisson regression was used to calculate incidence rate ratios (IRRs) for serious adverse events (SAEs) vs seronegative RA controls receiving DMARDs, adjusting for age, sex and baseline co-morbidity. At baseline, the mean (s.d.) DAS-28 was 6.4 (5.6). Of the patients, 70.3% were EULAR responders at 12 months. At 6 months, older patients [adjusted odds ratio (OR) 0.97 per year; 95% CI 0.95, 0.99], females (adjusted OR 0.51; 95% CI 0.34, 0.78) and patients on corticosteroids (adjusted OR 0.45; 95% CI 0.28, 0.72) were less likely to achieve a EULAR response. Over 1776.2 person-years of follow-up (median 3.07 per person), the IRR of SAEs compared with controls was not increased (0.9; 95% CI 0.8, 1.3). Anti-TNF therapies have a good response rate in PsA, and have an adverse event profile similar to that seen in a control cohort of patients with seronegative arthritis receiving DMARD therapy.

Warwicker J.,University of Manchester
Proteins: Structure, Function and Bioinformatics | Year: 2011

Modeling charge interactions is important for understanding many aspects of biological structure and function, and continuum methods such as Finite Difference Poisson-Boltzmann (FDPB) are commonly employed. Calculations of pH-dependence have identified separate populations; surface groups that can be modeled with a simple Debye-Hückel (DH) model, and buried groups, with stronger resultant interactions that are dependent on detailed conformation. This observation led to the development of a combined FDPB and DH method for pK a prediction (termed FD/DH). This study reports application of this method to ionizable groups, including engineered buried charges, in staphylococcal nuclease. The data had been made available to interested research groups before publication of mutant structures and/or pK a values. Overall, FD/DH calculations perform as intended with low ΔpK a values for surface groups (RMSD between predicted and experimental pK a values of 0.74), and much larger ΔpK a values for the engineered internal groups, with RMSD = 1.64, where mutant structures were known and RMSD = 1.80, where they were modeled. The weaker resultant interactions of the surface groups are determined mostly by charge-charge interactions. For the buried groups, R 2 for correlation between predicted and measured ΔpK a values is 0.74, despite the high RMSDs. Charge-charge interactions are much less important, with the R 2 value for buried group ΔpK a values increasing to 0.80 when the term describing charge desolvation alone is used. Engineered charge burial delivers a relatively uniform, nonspecific effect, in terms of pK a. How the protein environment adapts in atomic detail to deliver this resultant effect is still an open question. © 2011 Wiley-Liss, Inc.

Brocklehurst S.H.,University of Manchester
Progress in Physical Geography | Year: 2010

The field of tectonic geomorphology is in a state of tension. The widespread availability of high-quality, high-resolution digital topographic data encourages the development of simple morphological 'tools' which can be used to deduce recent tectonic evolution. Meanwhile, process geomorphologists recognize that current models have a significant empirical basis, and lack insight into the underlying physics of erosion processes. Most tectonic geomorphology research is concerned with rivers, but glaciers, debris flows and hillslope processes also play a key role in hypotheses linking climate to tectonics, via surface processes, while submarine geomorphology has barely been investigated in a tectonic context. Studies combining field data collection, exposure, burial and low-temperature thermochronologic dating, digital topographic analysis, laboratory experiments and numerical models are successfully incorporating physics into geomorphic process 'laws', and demonstrating key tectonic geomorphology hypotheses. The approaches required for further progress have been outlined, but many exciting challenges remain. © The Author(s) 2010.

Lin S.S.,Zhejiang University | Lin S.S.,University of Manchester
Journal of Physical Chemistry C | Year: 2012

Two-dimensional (2D) atomic crystals, especially graphene, have received much attention. However, the main shortcoming of graphene is its zero band gap. Silicon carbide, composed of silicon and carbon, is a typical wurtzite compound semiconductor, with more than 250 alloy types. Herein, we give some evidence of the solution exfoliation of 2D SiC nanoflakes with thickness down to 0.5-1.5 nm. Transmission electron microscopy (TEM) and X-ray diffraction characterizations reveal that graphitic (0001)/(0001̄) SiC most possibly has been formed by sonication of wurtzite SiC. Graphene, which is also produced in this process, naturally forms the ultrathin substrate facilitating the TEM characterization of 2D SiC. The mechanism of this exfoliation process should be related to the surface reconstruction of wurtzite SiC into graphitic SiC. Photoluminescence spectra show a strong light-emitting ability and a quantum-confinement-induced emission peak at 373 nm for these ultrathin SiC nanosheets. © 2012 American Chemical Society.

Powney M.J.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2012

Haloperidol, used alone is recommended to help calm situations of aggression with people with psychosis. This drug is widely accessible and may be the only antipsychotic medication available in areas where resources are limited. To investigate whether haloperidol alone, administered orally, intramuscularly or intravenously, is effective treatment for psychosis-induced agitation or aggression. We searched the Cochrane Schizophrenia Group Trials Register (1st June 2011). Randomised controlled  trials (RCTs) involving people exhibiting agitation or aggression (or both) thought to be due to psychosis, allocated rapid use of haloperidol alone (by any route), compared with any other treatment. Outcomes included tranquillisation or asleep by 30 minutes, repeated need for rapid tranquillisation within 24 hours, specific behaviours (threat or injury to others/self), adverse effects. We independently selected and assessed studies for methodological quality and extracted data. 'Summary of findings' tables were produced for each comparison grading the evidence and calculating, where possible and appropriate, a range of absolute effects. We included 32 studies comparing haloperidol with 18 other treatments. Few studies were undertaken in circumstances that reflect real world practice, and, with notable exceptions, most were small and carried considerable risk of bias.Compared with placebo, more people in the haloperidol group were asleep at two hours (2 RCTs, n = 220, risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.95). Dystonia was common (2 RCTs, n = 207, RR 7.49, CI 0.93 to 60.21). Compared with aripiprazole, people in the haloperidol group required fewer injections than those in the aripiprazole group (2 RCTs, n = 473, RR 0.78, CI 0.62 to 0.99). More people in the haloperidol group experienced dystonia (2 RCTs, n = 477, RR 6.63, CI 1.52 to 28.86).Despite three larger trials with ziprasidone (total n = 739), data remain patchy, largely because of poor design and reporting. Compared with zuclopenthixol acetate, more people who received haloperidol required more than three injections (1 RCT, n = 70, RR 2.54, CI 1.19 to 5.46).Three trials (n = 205) compared haloperidol with lorazepam. There were no significant differences between the groups with regard to the number of participants asleep at one hour (1 RCT, n = 60, RR 1.05, CI 0.76 to 1.44). However, by three hours, significantly more people were asleep in the lorazepam group compared with the haloperidol group (1 RCT, n = 66, RR 1.93, CI 1.14 to 3.27). There were no differences in numbers requiring more than one injection (1 RCT, n = 66, RR 1.14, CI 0.91 to 1.43).Haloperidol's adverse effects were not offset by addition of lorazepam (e.g. dystonia 1 RCT, n = 67, RR 8.25, CI 0.46 to 147.45; required antiparkinson medication RR 2.74, CI 0.81 to 9.25). Addition of promethazine was investigated in one larger and better graded trial (n = 316). More people in the haloperidol group were not tranquil or asleep by 20 minutes (RR 1.60, CI 1.18 to 2.16). Significantly more people in the haloperidol alone group experienced one or more adverse effects (RR 11.28, CI 1.47 to 86.35). Acute dystonia for those allocated haloperidol alone was too common for the trial to continue beyond the interim analysis (RR 19.48, CI 1.14 to 331.92). If no other alternative exists, sole use of intramuscular haloperidol could be life-saving. Where additional drugs to offset the adverse effects are available, sole use of haloperidol for the extreme emergency, in situations of coercion, could be considered unethical. Addition of the sedating promethazine has support from better-grade evidence from within randomised trials. Use of an alternative antipsychotic drug is only partially supported by fragmented and poor-grade evidence. Evidence for use of newer generation antipsychotic alternatives is no stronger than that for older drugs. Adding a benzodiazepine to haloperidol does not have strong evidence of benefit and carries a risk of additional harm.After six decades of use for emergency rapid tranquillisation, this is still an area in need of good independent trials relevant to real world practice.

Furness S.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2012

Reduced circulating estrogen levels around the time of the menopause can induce unacceptable symptoms that affect the health and well-being of women. Hormone therapy (both unopposed estrogen and estrogen/progestogen combinations) is an effective treatment for these symptoms, but is associated with risk of harms. Guidelines recommend that hormone therapy be given at the lowest effective dose and treatment should be reviewed regularly. The aim of this review is to identify the minimum dose(s) of progestogen required to be added to estrogen so that the rate of endometrial hyperplasia is not increased compared to placebo. The objective of this review is to assess which hormone therapy regimens provide effective protection against the development of endometrial hyperplasia or carcinoma. We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (searched January 2012), The Cochrane Library (Issue 1, 2012), MEDLINE (1966 to January 2012), EMBASE (1980 to January 2012), Current Contents (1993 to May 2008), Biological Abstracts (1969 to 2008), Social Sciences Index (1980 to May 2008), PsycINFO (1972 to January 2012) and CINAHL (1982 to May 2008). Attempts were made to identify trials from citation lists of reviews and studies retrieved, and drug companies were contacted for unpublished data. Randomised comparisons of unopposed estrogen therapy, combined continuous estrogen-progestogen therapy, sequential estrogen-progestogen therapy with each other or placebo, administered over a minimum period of 12 months. Incidence of endometrial hyperplasia/carcinoma assessed by a biopsy at the end of treatment was a required outcome. Data on adherence to therapy, rates of additional interventions, and withdrawals owing to adverse events were also extracted. In this update, 46 studies were included. Odds ratios (ORs) were calculated for dichotomous outcomes. The small numbers of studies in each comparison and the clinical heterogeneity precluded meta-analysis for many outcomes. Unopposed estrogen is associated with increased risk of endometrial hyperplasia at all doses, and durations of therapy between one and three years. For women with a uterus the risk of endometrial hyperplasia with hormone therapy comprising low-dose estrogen continuously combined with a minimum of 1 mg norethisterone acetate (NETA) or 1.5 mg medroxyprogesterone acetate (MPA) is not significantly different from placebo at two years (1 mg NETA: OR 0.04; 95% confidence interval (CI) 0 to 2.8; 1.5 mg MPA: no hyperplasia events). Hormone therapy for postmenopausal women with an intact uterus should comprise both estrogen and progestogen to reduce the risk of endometrial hyperplasia.

Darling J.,University of Manchester
Environment and Planning A | Year: 2013

The city of Sheffield was the UK's first 'City of Sanctuary', an identification which suggested that the city would act to welcome asylum seekers and refugees through promoting a 'culture of hospitality'. In this paper I seek to interrogate such claims and explore how the promotion of a language of hospitality marks a form of 'moral urbanism' through which the city is linked to specific values and obligations that enable the governmental ordering of responses to asylum. In exploring public statements, media discussions, and interview accounts of asylum in the city, I argue that a normative account of how to live with asylum is articulated, one which establishes expectations of both citizens and noncitizens alike. The paper opens by tracing this narrative construction of Sheffield as a place with a 'welcoming tradition' through a series of high-profile events of refuge and their reiterative embedding in the public imaginary. I then question this account through demonstrating how such moments of welcome are conditioned by logics of acceptability and control, before considering how the governmental entanglements of moral urbanism might be contested through a politics of critique.

Winch G.M.,University of Manchester
International Journal of Project Management | Year: 2013

Why do major projects escalate on schedule and budget? Research from an engineering management perspective has focused the technical failings in project management, but little has been achieved in improving performance. We therefore contribute to theory by posing the question "can a more comprehensive perspective on the escalation phenomenon drawing on organisation theory be developed?" We turn to three contributions to research on major projects which treat project escalation as an organisational process rather than an engineering problem. We suggest each of these contributions - future-perfect strategising, strategic misrepresentation, and escalation of commitment - makes only a partial contribution, but also they can complement each other as elements in a more comprehensive perspective on the escalation phenomenon. The resultant analytic model is applied to the case of the Channel Fixed Link using a hindsight approach to explore the dynamics of escalation using history for generating theory in project management research. © 2013 Elsevier Ltd and IPMA.

Kazmierczak A.,University of Manchester
Landscape and Urban Planning | Year: 2013

The social ties between the residents of urban neighbourhoods are in decline due to changing work patterns, increased mobility and developments in communications. Neighbourhood open spaces, and green spaces in particular, provide opportunities for social interactions that may help the residents to establish recognition and develop relationships. This paper investigates the contribution of local parks to the development of social ties in inner-city neighbourhoods. Combining quantitative methods (questionnaire survey) with a qualitative approach (focus group discussions), the research was carried out in three inner-city neighbourhoods in Greater Manchester, UK, characterised by different levels of material deprivation and ethnic diversity. The social survey explored the associations between the respondents' visits to local parks and the number of friends and acquaintances they had. The findings suggest that local parks may support the development of social ties in inner-city areas. Associations were found between the quality of the parks, the character of visits, and the extent of social ties in the neighbourhood. The study concludes that for inner-city parks to realise their full potential in supporting social interactions and developing social ties, they need to be well-maintained and provide good recreational facilities. The development of social ties was also found to be considerably affected by the characteristics of the individuals and the neighbourhood. © 2012 Elsevier B.V.

Hall S.M.,University of Manchester
Local Environment | Year: 2013

This paper takes a first step in comparing and synthesising the emerging concept of energy justice with extant ethical consumption literatures as two complementary theoretical approaches to ethics and consumption. To date, theories of ethical consumption and energy justice remain somewhat disconnected, so while they have some areas of potential comparability, these have not yet been fleshed out or developed. To address this lacuna, this paper explores areas where research into ethical consumption might be useful for furthering concepts of energy justice. More specifically the discussion draws on the philosophical foundations, the relationship between consumption and development, and the role of transparency and visibility in reconnecting consumption and production practices as the main areas of overlap in these literatures. The conclusion points to some lessons for emerging energy justice literatures that can be drawn from this task of comparison and synthesis. © 2013 Copyright Taylor and Francis Group, LLC.

Vestbo J.,University of Manchester
European Respiratory Review | Year: 2016

A number of scientific questions cannot be tested in a laboratory, clinic or clinical trial setting. In many cases, observational data can be used to test such hypotheses. This article illustrates how epidemiology can contribute and shows the different ways of using observational data through three approaches: 1) prospective cohort study design; 2) time series analysis; and 3) a nested case-control design in pharmacoepidemiology. In a prospective cohort study design, three cohorts were merged to study lung function decline, testing the importance of different trajectories of lung function decline for developing chronic obstructive pulmonary disease (COPD). Using these three well-described cohorts it was documented that maximally attained lung function in early adulthood is as important as excess decline in forced expiratory volume in 1 s for the development of COPD. Time series analysis is used to examine exposures and disease over time. In a recent review of cardiovascular disease some interesting associations, and not least lack of associations, were presented. Assessing effects of drugs in database studies is challenging. In a nested case- control design in a large cohort study, statins were found to reduce the risk of COPD exacerbations. These findings will be discussed. Observational data from large databases, as well as carefully collected data in cohort studies, can be used to test hypotheses that may not be addressed in a traditional experimental setting. © ERS 2016.

Wakeman S.,University of Manchester
British Journal of Criminology | Year: 2014

This article presents an introductory yet critical overview of autoethnographic research in criminological contexts. Drawing on experiences of participant observation with heroin and crack cocaine users and dealers, as a former user and dealer of these drugs myself, the article demonstrates how the domains of fieldwork, biography and the emotions intersect to render clear a progressive account of heroin addiction. However, this is offset against some negative occurrences directly reducible to doing ethnography where biographical congruence exists between the researcher and the researched. Ultimately, it is argued here that an increased consideration of the self - biographically and emotionally - both permits and facilitates the presentation of analytic yet stylized data in the form of what is termed below, 'lyrical criminology'. © The Author 2014.

Bella H.,University of Manchester
Plastic and Reconstructive Surgery | Year: 2011

Background: This study is a clinical characterization of keloid scars in an African population comprising three rural tribes with familial keloids. Site distribution, morphologic features, and other characteristics of the scars were studied to assess whether each tribe had a specific scar phenotype. Methods: Keloid scar clinics were set up at Soba Hospital in Khartoum, Sudan, for patient recruitment and management. In addition, familial keloid cases were recruited from rural tribal populations during field trips. A database including clinical and demographic data and digital photographs of all keloid cases was established. Statistical analysis was conducted using SPSS and SAS software. Results: One hundred eleven individuals with keloid scarring (67 male subjects and 44 female subjects) were recruited. Patients were predominantly from three multigenerational pedigrees (total of 38 nuclear families) afflicted with keloid scars residing in different rural regions of Sudan. Two distinct morphologic phenotypes of keloid scarring were observed. The first phenotype has been designated "superficial spreading" (horizontal) keloid and the second has been designated "raised" (vertical) keloid. Clinically significant features and statistically measurable morphologic parameters were compared among these phenotypes (p = 0.001). Furthermore, linear claw-like extensions of keloid (transgression) were noted to be significantly higher in the superficial spreading keloid phenotype (p = 0.03). Conclusions: There is strong evidence of different phenotypes of keloid scarring. Two distinct phenotypes have been observed, described, and statistically verified. Each tribe demonstrated one particular phenotype, with two being superficial spreading and one being raised. Other significant clinical characteristics have been described. This is of significance in understanding both the clinical basis and the genetic basis of keloid scarring. Copyright © 2011 by the American Society of Plastic Surgeons.

Burden S.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2012

Post-operative management in gastrointestinal (GI) surgery is becoming well established with 'Enhanced Recovery After Surgery' protocols starting 24 hours prior to surgery with carbohydrate loading and early oral or enteral feeding given to patients the first day following surgery. However, whether or not nutritional intervention should be initiated earlier in the preoperative period remains unclear. Poor pre-operative nutritional status has been linked consistently to an increase in post-operative complications and poorer surgical outcome. To review the literature on preoperative nutritional support in patients undergoing gastrointestinal surgery (GI). The searches were initially run in March 2011 and subsequently updated in February 2012. Databases including all EBM Reviews (Cochrane DSR, ACP Journal Club, DARE, CCTR, CMR, HTA and NHSEED) MEDLINE, EMBASE, AMED, British Nursing Index Archive using OvidSP were included and a search was run on each database separately after which duplicates were excluded. The inclusion criteria were randomised controlled trials that evaluated pre-operative nutritional support in GI surgical participants using a nutritional formula delivered by a parenteral, enteral or oral route. The primary outcomes included post-operative complications and length of hospital stay. Two observers screened the abstracts for inclusion in the review and performed data extraction. Bias was assessed for each of the included studies using the bias assessment tables in the Cochrane Software Review Manager (version 5.1, Cochrane Collaboration). The trials were analysed using risk ratios with Mantel-Haenszel in fixed effects methods displayed with heterogeneity. Meta-analyses were undertaken on trials evaluating immune enhancing (IE) nutrition, standard oral supplements, enteral and parenteral nutrition (PN) which were administered pre-operatively.Study characteristics were summarised in tables. Dichotomous and ratio data were entered into meta-analyses for the primary outcomes. These were then summarised in tables with assumed and corresponding risk with relative effect giving 95% confidence intervals. The searches identified 9900 titles and, after excluding duplicates, 6433 titles were initially screened. After the initial title screen, 6266 were excluded. Abstracts were screened for 167 studies and 33 articles were identified as meeting the inclusion criteria, of which 13 were included in the review after an assessment of the complete manuscripts.Seven trials evaluating IE nutrition were included in the review, of which 6 were combined in a meta-analysis. These studies showed a low to moderate level of heterogeneity and significantly reduced total post-operative complications (risk ratio (RR) 0.67 CI 0.53 to 0.84). Three trials evaluating PN were included in a meta-analysis and a significant reduction in post-operative complications was demonstrated (RR 0.64 95% CI 0.46 to 0.87) with low heterogeneity, in predominantly malnourished participants. Two trials evaluating enteral nutrition (RR 0.79, 95% CI 0.56 to 1.10) and 3 trials evaluating standard oral supplements (RR 1.01 95% CI 0.56 to 1.10) were included, neither of which showed any difference in the primary outcomes. There have been significant benefits demonstrated with pre-operative administration of IE nutrition in some high quality trials. However, bias was identified which may limit the generalizability of these results to all GI surgical candidates and the data needs to be placed in context with other recent innovations in surgical management (eg-ERAS). Some unwanted effects have also been reported with components of IE nutrition in critical care patients and it is unknown whether there would be detrimental effects by administering IE nutrition to patients who could require critical care support after their surgery. The studies evaluating PN demonstrated that the provision of PN to predominantly malnourished surgical candidates reduced post-operative complications; however, these data may not be applicable to current clinical practice, not least because they have involved a high degree of 'hyperalimentation'. Trials evaluating enteral or oral nutrition were inconclusive and further studies are required to select GI surgical patients for these nutritional interventions.

Brocklehurst P.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2012

Recurrent aphthous stomatitis (RAS) is the most frequent form of oral ulceration, characterised by recurrent oral mucosal ulceration in an otherwise healthy individual. At its worst RAS can cause significant difficulties in eating and drinking. Treatment is primarily aimed at pain relief and the promotion of healing to reduce the duration of the disease or reduce the rate of recurrence. A variety of topical and systemic therapies have been utilised. To determine the clinical effect of systemic interventions in the reduction of pain associated with RAS, a reduction in episode duration or frequency. We undertook electronic searches of: Cochrane Oral Health Group and PaPaS Trials Registers (to 6 June 2012); CENTRAL via The Cochrane Library (to Issue 4, 2012); MEDLINE via OVID (1950 to 6 June 2012); EMBASE via OVID (1980 to 6 June 2012); CINAHL via EBSCO (1980 to 6 June 2012); and AMED via PubMed (1950 to 6 June 2012). We searched reference lists from relevant articles and contacted the authors of eligible trials to identify further trials and obtain additional information. We included randomised controlled trials (RCTs) in which the primary outcome measures assess a reduction of pain associated with RAS, a reduction in episode duration or a reduction in episode frequency. Trials were not restricted by outcome alone. We also included RCTs of a cross-over design. Two review authors independently extracted data in duplicate. We contacted trial authors for details of randomisation, blindness and withdrawals. We carried out risk of bias assessment on six domains. We followed The Cochrane Collaboration statistical guidelines and risk ratio (RR) values were to be calculated using fixed-effect models (if two or three trials in each meta-analysis) or random-effects models (if four or more trials in each meta-analysis). A total of 25 trials were included, 22 of which were placebo controlled and eight made head-to-head comparisons (five trials had more than two treatment arms). Twenty-one different interventions were assessed. The interventions were grouped into two categories: immunomodulatory/anti-inflammatory and uncertain. Only one study was assessed as being at low risk of bias. There was insufficient evidence to support or refute the use of any intervention. No single treatment was found to be effective and therefore the results remain inconclusive in regard to the best systemic intervention for RAS. This is likely to reflect the poor methodological rigour of trials, and lack of studies for certain drugs, rather than the true effect of the intervention. It is also recognised that in clinical practice, individual drugs appear to work for individual patients and so the interventions are likely to be complex in nature. In addition, it is acknowledged that systemic interventions are often reserved for those patients who have been unresponsive to topical treatments, and therefore may represent a select group of patients.

Archer J.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2012

Common mental health problems, such as depression and anxiety, are estimated to affect up to 15% of the UK population at any one time, and health care systems worldwide need to implement interventions to reduce the impact and burden of these conditions. Collaborative care is a complex intervention based on chronic disease management models that may be effective in the management of these common mental health problems. To assess the effectiveness of collaborative care for patients with depression or anxiety. We searched the following databases to February 2012: The Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDAN) trials registers (CCDANCTR-References and CCDANCTR-Studies) which include relevant randomised controlled trials (RCTs) from MEDLINE (1950 to present), EMBASE (1974 to present), PsycINFO (1967 to present) and the Cochrane Central Register of Controlled Trials (CENTRAL, all years); the World Health Organization (WHO) trials portal (ICTRP); ClinicalTrials.gov; and CINAHL (to November 2010 only). We screened the reference lists of reports of all included studies and published systematic reviews for reports of additional studies. Randomised controlled trials (RCTs) of collaborative care for participants of all ages with depression or anxiety. Two independent researchers extracted data using a standardised data extraction sheet. Two independent researchers made 'Risk of bias' assessments using criteria from The Cochrane Collaboration. We combined continuous measures of outcome using standardised mean differences (SMDs) with 95% confidence intervals (CIs). We combined dichotomous measures using risk ratios (RRs) with 95% CIs. Sensitivity analyses tested the robustness of the results. We included seventy-nine RCTs (including 90 relevant comparisons) involving 24,308 participants in the review. Studies varied in terms of risk of bias.The results of primary analyses demonstrated significantly greater improvement in depression outcomes for adults with depression treated with the collaborative care model in the short-term (SMD -0.34, 95% CI -0.41 to -0.27; RR 1.32, 95% CI 1.22 to 1.43), medium-term (SMD -0.28, 95% CI -0.41 to -0.15; RR 1.31, 95% CI 1.17 to 1.48), and long-term (SMD -0.35, 95% CI -0.46 to -0.24; RR 1.29, 95% CI 1.18 to 1.41). However, these significant benefits were not demonstrated into the very long-term (RR 1.12, 95% CI 0.98 to 1.27).The results also demonstrated significantly greater improvement in anxiety outcomes for adults with anxiety treated with the collaborative care model in the short-term (SMD -0.30, 95% CI -0.44 to -0.17; RR 1.50, 95% CI 1.21 to 1.87), medium-term (SMD -0.33, 95% CI -0.47 to -0.19; RR 1.41, 95% CI 1.18 to 1.69), and long-term (SMD -0.20, 95% CI -0.34 to -0.06; RR 1.26, 95% CI 1.11 to 1.42). No comparisons examined the effects of the intervention on anxiety outcomes in the very long-term.There was evidence of benefit in secondary outcomes including medication use, mental health quality of life, and patient satisfaction, although there was less evidence of benefit in physical quality of life. Collaborative care is associated with significant improvement in depression and anxiety outcomes compared with usual care, and represents a useful addition to clinical pathways for adult patients with depression and anxiety.

Yong S.L.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2012

Adrenal crisis is a life threatening condition which can be induced by stress during surgery in patients with adrenal insufficiency. This may be prevented by perioperative administration of high doses of steroids. There is disagreement on whether supplemental perioperative steroids are required and, when administered, on the amount and frequency of doses. The review was originally published in 2009 and was updated in 2012. To assess whether it is necessary to administer supplemental perioperative steroids in adult patients on maintenance doses of glucocorticoids because of adrenal insufficiency. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2); MEDLINE (1966 to February 2012); EMBASE (1980 to February 2012); LILACS (1982 to May 2012); and the databases of ongoing trials. We handsearched the Journal of Clinical Endocrinology and Metabolism (1982 to 2008), Clinical Endocrinology (1972 to 2008), Surgery (1948 to 1994), Annals of Surgery (1948 to 1994), and Anaesthesia (1948 to 2001). The original search was performed in January 2009. We included randomized controlled trials that compared the use of supplemental perioperative steroids to placebo in adult patients on maintenance doses of steroids and who required surgery. Two review authors independently assessed trial quality and extracted data. Study authors were contacted for missing information. We used mean differences and standard deviations to summarize the data for each group. Two trials involving 37 patients were included. These studies reported that supplemental perioperative steroids were not required during surgery for patients with adrenal insufficiency. Neither study reported any adverse effects or complications in the intervention and control groups. Both studies were graded as having a high risk of bias. Owing to the small number of patients, the results may not be representative. Based on current available evidence, we are unable to support or refute the use of supplemental perioperative steroids for patients with adrenal insufficiency during surgery.

Potter A.,University of Manchester
Journal of Product Innovation Management | Year: 2013

Suppliers are increasingly being involved in interorganizational new product development (NPD) teams. Successful management of this involvement is critical both to the performance of the new product and to meeting the project's goals. Yet the transfer of knowledge between buyer and supplier may be subject to varying degrees of causal ambiguity, potentially limiting the effect of supplier involvement on performance. Understanding the dynamics of causal ambiguity within interorganizational product development is thus an important unanswered empirical question. A theoretical model is developed exploring the effect of supplier involvement practices (supplier involvement orientation, relationship commitment, and involvement depth) on the level of causal ambiguity experienced within interorganizational NPD teams, and the subsequent impact on time to competitor imitation, new product advantage, and project performance. The model also serves as a test of the paradox that causal ambiguity both inhibits imitation by competitors, but adversely affects organizational outcomes. Survey data collected from 119 research and development-intensive manufacturing firms in the United Kingdom largely support these hypotheses. Results from structural equation modeling show that supplier involvement orientation and long-term relationship commitment lower causal ambiguity within interorganizational NPD teams. The results also shed light on the causal ambiguity paradox showing that causal ambiguity during interorganizational NPD decreases both product and project performance, but has no significant effect on time to competitor imitation. Instead, competitor imitation is delayed by the extent to which the firm develops a new product advantage within the market. A product development strategy based upon maintaining interfirm causal ambiguity to delay competitor imitation is thus unlikely to result in a sustainable competitive advantage. Instead, managers are encouraged to undertake supplier involvement practices aimed at minimizing the level of knowledge ambiguity in the NPD project, and in doing so, improve product and project-related performance. © 2013 Product Development & Management Association.

Callaghan M.J.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2012

Patellofemoral pain syndrome refers to the clinical presentation of knee pain related to changes in the patellofemoral joint. Patellofemoral pain syndrome usually has a gradual onset of pain with none of the features associated with other knee diseases or trauma. It is often treated by physiotherapists, who use a variety of techniques including patellar taping. This involves the application of adhesive sports medical tape applied directly to the skin over the patella on the front of the knee. Patients often report an instantaneous improvement in pain and function after the tape is applied, but its longer term effects are uncertain. The objective was to assess the effects, primarily on pain and function, of patellar taping for treating patellofemoral pain syndrome in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, CINAHL, EMBASE, PEDro, SPORTDiscus, AMED, reference lists of articles, trial registers and conference proceedings. All were searched to August 2011. Randomised controlled trials and quasi-randomised controlled trials testing the effects of patellar taping on clinically relevant outcomes, pain and function, in adults with patellofemoral pain syndrome. We excluded studies testing only the immediate effects of tape application. Both review authors independently performed study selection, data extraction and assessment of risk of bias. Trialists were contacted for more information. Data were pooled where possible. Five small heterogeneous randomised controlled trials, all at high risk of performance bias and most at risk of at least one other type of bias, were included. These involved approximately 200 participants with a diagnosis of patellofemoral pain syndrome. All compared taping versus control (no or placebo taping) and all included one or more co-interventions given to both taping and control group participants; this was prescribed exercise in four trials. The intensity and length of treatment was very varied: for example, length of treatment ranged from one week in one trial to three months in another. A meta-analysis of the visual analogue scale (VAS) pain data (scale 0 to 10: worst pain), measured in different ways, from four trials (data from 161 knees), found no statistically or clinically significant difference between taping and non taping in pain at the end of the treatment programmes (mean difference (MD) -0.15; 95% confidence interval (CI) -1.15 to 0.85; random-effects model used given the significant heterogeneity (P < 0.0001)). Data for other outcomes measuring function and activities of daily living were from single trials only and gave contradictory results. The currently available evidence from trials reporting clinically relevant outcomes is low quality and insufficient to draw conclusions on the effects of taping, whether used on its own or as part of a treatment programme. Further research involving large, preferably multi-centre, good quality and well reported randomised controlled trials that measure clinically important outcomes and long-term results is warranted. Before this, consensus is required on the diagnosis of patellofemoral pain syndrome, the standardisation of outcome measurement and an acceptable approach for patellar taping.

Griffiths-Jones S.,University of Manchester
Current Protocols in Bioinformatics | Year: 2010

miRBase is the central repository for microRNA (miRNA) sequence information. miRBase has a role in defining the nomenclature for miRNA genes and assigning names to novel miRNAs for publication in peer-reviewed journals. The online miRBase database is a resource containing all published miRNA sequences, together with textual annotation and links to the primary literature and to other secondary databases. The database provides a variety of methods to query the data, by specific searches of sequences and associated text and literature. All miRBase data are also available for download from the miRBase FTP site. Curr. Protoc. Bioinform. 29:12.9.1-12.9.10. © 2010 by John Wiley & Sons, Inc.

Font-Palma C.,University of Manchester
Energy Conversion and Management | Year: 2012

Environmental implications of the disposal of waste from the poultry industry have created the need for proper waste management. As a result, poultry litter has been proposed as a potential fuel candidate for thermal conversion technologies since it is an available source. This review discusses the recent advances in the physical and chemical characterisation of poultry litter. The focus of this review is on gasification for energy generation and current commercial combustion facilities. Significant advances have been made in the pyrolysis, gasification and combustion investigations with the aim to determine their kinetics. These results are important for modelling work and critical issues for the simulation of poultry litter gasification are discussed. © 2011 Elsevier Ltd. All rights reserved.

Boucher P.,University of Manchester
Energy Policy | Year: 2012

Biofuels have undergone a controversial resurgence in the UK since the turn of the century. The aim of this article is to consider this development in the context of ongoing interactions between the controversy and regulatory and engineering activities. It is found that the discursive space of the controversy has increasingly narrowed around environmental issues, particularly greenhouse gas emissions. The implications for biofuel development are considered in the context of changing regulatory and engineering visions in response to indirect land-use change. Opposition to the third generation biofuels may be softened, but it may be more difficult to justify the cost of holistic regulation of land-use change. © 2011 Elsevier Ltd.

Farrell P.,University of Manchester
School Psychology International | Year: 2010

At a time when, in most countries, the profession of school psychology is experiencing a period of growth and expansion, many problems still remain. The origins of these problems are linked to the historical development of the profession which has provided school psychologists with a unique and distinctive role in administering IQ tests and using the results to make decisions about special educational provision for children with learning difficulties. This article reviews recent research that is heavily critical of the relevance of IQ testing and the associated medical model of working, and then considers some of the barriers which prevent school psychologists from changing their practices. It concludes with suggestions as to how the profession can move forward with confidence, knowing that it can make a distinctive contribution to supporting vulnerable children, schools and communities around the world. © The Author(s) 2010.

Esposito M.,University of Manchester
Cochrane database of systematic reviews (Online) | Year: 2012

One of the key factors for the long-term success of oral implants is the maintenance of healthy tissues around them. Bacterial plaque accumulation induces inflammatory changes in the soft tissues surrounding oral implants and it may lead to their progressive destruction (peri-implantitis) and ultimately to implant failure. Different treatment strategies for peri-implantitis have been suggested, however it is unclear which are the most effective. To identify the most effective interventions for treating peri-implantitis around osseointegrated dental implants. We searched the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE and EMBASE. Handsearching included several dental journals. We checked the bibliographies of the identified randomised controlled trials (RCTs) and relevant review articles for studies outside the handsearched journals. We wrote to authors of all identified RCTs, to more than 55 dental implant manufacturers and an Internet discussion group to find unpublished or ongoing RCTs. No language restrictions were applied. The last electronic search was conducted on 9 June 2011. All RCTs comparing agents or interventions for treating peri-implantitis around dental implants. Screening of eligible studies, assessment of the methodological quality of the trials and data extraction were conducted in duplicate and independently by two review authors. We contacted the authors for missing information. Results were expressed as random-effects models using mean differences for continuous outcomes and risk ratios for dichotomous outcomes with 95% confidence intervals (CI). Heterogeneity was to be investigated including both clinical and methodological factors. Fifteen eligible trials were identified, but six were excluded. The following interventions were compared in the nine included studies: different non-surgical interventions (five trials); adjunctive treatments to non-surgical interventions (one trial); different surgical interventions (two trials); adjunctive treatments to surgical interventions (one trial). Follow-up ranged from 3 months to 4 years. No study was judged to be at low risk of bias.Statistically significant differences were observed in two small single trials judged to be at unclear or high risk of bias. After 4 months, adjunctive local antibiotics to manual debridement in patients who lost at least 50% of the bone around implants showed improved mean probing attachment levels (PAL) of 0.61 mm (95% confidence interval (CI) 0.40 to 0.82) and reduced probing pockets depths (PPD) of 0.59 mm (95% CI 0.39 to 0.79). After 4 years, patients with peri-implant infrabony defects > 3 mm treated with Bio-Oss and resorbable barriers gained 1.4 mm more PAL (95% CI 0.24 to 2.56) and 1.4 mm PPD (95% CI 0.81 to 1.99) than patients treated with a nanocrystalline hydroxyapatite. There is no reliable evidence suggesting which could be the most effective interventions for treating peri-implantitis. This is not to say that currently used interventions are not effective.A single small trial at unclear risk of bias showed the use of local antibiotics in addition to manual subgingival debridement was associated with a 0.6 mm additional improvement for PAL and PPD over a 4-month period in patients affected by severe forms of peri-implantitis. Another small single trial at high risk of bias showed that after 4 years, improved PAL and PPD of about 1.4 mm were obtained when using Bio-Oss with resorbable barriers compared to a nanocrystalline hydroxyapatite in peri-implant infrabony defects. There is no evidence from four trials that the more complex and expensive therapies were more beneficial than the control therapies which basically consisted of simple subgingival mechanical debridement. Follow-up longer than 1 year suggested recurrence of peri-implantitis in up to 100% of the treated cases for some of the tested interventions. As this can be a chronic disease, re-treatment may be necessary. Larger well-designed RCTs with follow-up longer than 1 year are needed.

Garland J.,University of Manchester
Critical Reviews in Oncology/Hematology | Year: 2013

The variety of genes implicated in cancer induction is extensive but paradoxically all cancer cells behave in an identical and highly predictable fashion. This behaviour is closely correlated with a group of cellular morphological criteria termed Anaplasticity which involves increases/changes in: motility; invasion; replication; nuclear and chromosomal fragmentation; structural degradation; and phenotypic fluidity. Anaplasticity is so predictive it is a universal clinical yardstick for assessment and treatment. To understand this paradox, perceived mechanisms of cancer induction are reviewed and a new proposal made, namely that cancer is a diversion of energy required for structural organisation into maximum energy dissipation (entropy) through increased dynamic activities. This process is driven by oncogenic mutations or a variety of other permanent molecular alterations which re-direct "channels" distributing energy dissipation. These are organised along fractal networks (Fractal Entropy) and are not necessarily structure-dependent. "Oncogenic" alterations of any kind create cumulative effects by permanently stabilising parts of the fractal network, resulting in fractured co-ordination and re-direction of entropy into increased dynamic activity, which is the universal hallmark of cancer. The mechanism of Fractal Entropy employs Chaos and Fractal theories and is illustrated with Mandelbrot figures for fractal distributions and Chaos theory for its influence in creating fractal distributions and their behaviours. The proposal is examined in an in vitro heamatopoietic model (IL3 dependent cells) concerning regulation by growth factors of metabolism, apoptosis, oncogenesis and cell dormancy, and suggests new avenues of multi-disciplinary research. © 2013 Elsevier Ireland Ltd.

Wilson J.,University of Manchester
Antipode | Year: 2014

This paper draws on Slavoj Žižek's critique of ideology in seeking to account for the persistence and transformability of the neoliberal project. Against understandings of neoliberalism as a utopian representation projected onto an external reality, I argue that neoliberal ideology operates as a social fantasy, which structures reality itself against the traumatic Real of Capital. The evolution of the neoliberal project should be understood, not as the meticulous manipulation of social reality, but as a series of increasingly desperate attempts to hold the very fabric of reality together. Reconceptualizing neoliberalization as a form of obsessional neurosis can help to explain the relentless persistence of "zombie neoliberalism" and its paradoxical trajectory towards increasingly intensive forms of social engineering. This argument is developed through a critical engagement with the work of the economist Jeffrey Sachs. From shock therapy to the Millennium Villages Project, Sachs's trajectory embodies the characteristics of the neoliberal neurosis. The paper aims to undermine the apparently monolithic power of neoliberalism, by challenging dominant critical representations of the neoliberal project in terms of a hyper-rational governmentality. It also aims to subvert the attempts by Jeffrey Sachs and other neoliberals to reposition themselves as opponents of the Washington Consensus, and as spokesmen of the Occupy movement. The chosen method of attack is more satirical than polemical. Neurotic neoliberals such as Sachs have successfully appropriated ethical objections to neoliberalism in the name of "globalization with a human face". In the present conjuncture, an immanent critique that reveals the internal incoherence of neoliberal ideology, and the hapless floundering of its proponents, is perhaps more effective than a repetition of familiar forms of moral condemnation. An alternative subtitle for this paper might therefore be "Towards a satirical materialism". © 2013 The Author. Antipode © 2013 Antipode Foundation Ltd.

Dental implants are used for replacing missing teeth. Placing dental implants is limited by the presence of adequate bone volume permitting their anchorage. Several bone augmentation procedures have been developed to solve this problem. Zygomatic implants are long screw-shaped implants developed as a partial or complete alternative to bone augmentation procedures for the severely atrophic maxilla. One to three zygomatic implants can be inserted through the posterior alveolar crest passing through the maxillary sinus, or externally to it, to engage the body of the zygomatic bone. A couple of conventional dental implants may also be needed in the frontal region of the maxilla to stabilise the prosthesis. The potential main advantages of zygomatic implants could be that bone grafting may not be needed and a fixed prosthesis could be fitted sooner. Another specific indication for zygomatic implants could be maxillary reconstruction after maxillectomy in cancer patients. To assess the effects of zygomatic implants with and without bone augmenting procedures in comparison with conventional dental implants in augmented bone for the rehabilitation with implant-supported prostheses of severely resorbed maxillae. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 17 June 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 5), MEDLINE via OVID (1946 to 17 June 2013) and EMBASE via OVID (1980 to 17 June 2013). Personal contacts and all known zygomatic implant manufacturers were contacted to identify unpublished trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised controlled trials (RCTs) including participants with severely resorbed maxillae, who could not be rehabilitated with conventional dental implants, treated with zygomatic implants with and without bone grafts versus participants treated with bone augmentation procedures and conventional dental implants, with a follow-up of at least one year in function. Two review authors would have extracted data from eligible studies and assessed their risk of bias independently and in duplicate. The results of included studies were to be combined in meta-analyses using random-effects models where there were more than four studies, and fixed-effect models where there were less than four studies. We would have expressed the estimate of the intervention effect as mean difference for continuous outcomes and risk ratio for dichotomous outcomes, with 95% confidence intervals. Heterogeneity was to be investigated including both clinical and methodological factors. We did not identify any RCTs which were eligible for inclusion in this review. There is a need for RCTs in this area to assess whether zygomatic implants offer some advantages over alternative bone augmentation techniques for treating atrophic maxillae.

Gilliver S.C.,University of Manchester
Journal of Steroid Biochemistry and Molecular Biology | Year: 2010

It is becoming increasingly clear that endogenous sex steroids are key players in a range of inflammatory contexts. Androgens and estrogens have been shown to have a profound influence on the function of inflammatory cells including macrophages and on the secretion and activation of a range of plasma-borne inflammatory mediators. The menopause and polymorphisms in estrogen receptor genes have separately been shown to affect the incidence of a range of inflammatory disorders. Sex steroids themselves have been shown to be protective in certain conditions; harmful in others. This review will summarize their documented effects on inflammatory processes, with particular focus on two areas that have received much recent attention: the antiatherosclerotic properties of estrogens in females and the wound healing effects of sex steroids. © 2009 Elsevier Ltd.

Richtering W.,RWTH Aachen | Saunders B.R.,University of Manchester
Soft Matter | Year: 2014

Gels have made the transition from brittle materials with few potential applications to high performance systems with mechanical properties approaching that of rubber. They have a wide variety of structures and provide the opportunity to tailor these structures to achieve well-controlled properties over a range of length scales. In this review we consider and compare the structures and properties of a range of gels that have been studied in recent years. In comparing these gels we highlight the importance of key structural parameters in defining gel mechanical properties. It is hoped that this article will provide authors who discover new gels a resource that will easily enable them to determine the differences of their new gels to existing gels. This journal is © the Partner Organisations 2014.

Parnell W.J.,University of Manchester
Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2012

A theory is presented showing that cloaking of objects from antiplane elastic waves can be achieved by employing nonlinear elastic pre-stress in a neo-Hookean elastomeric material. This approach would appear to eliminate the requirement of metamaterials with inhomogeneous anisotropic shear moduli and density. Waves in the pre-stressed medium are bent around the cloaked (cavity) region by inducing inhomogeneous stress fields via pre-stress. The equation governing antiplane waves in the pre-stressed medium is equivalent to the antiplane equation in an unstressed medium with inhomogeneous and anisotropic shear modulus and isotropic scalar mass density. Note however that these properties are induced naturally by the pre-stress. As the magnitude of pre-stress can be altered at will, this enables objects of varying size and shape to be cloaked by placing them inside the fluid-filled deformed cavity region. © 2011 The Royal Society.

Darling J.,University of Manchester
Antipode | Year: 2014

This paper explores the ways in which practices of asylum governance serve to depoliticise those seeking asylum in the UK. In critiquing claims over the "post-political" nature of contemporary governance, the paper proposes a focus upon situated practices of depoliticisation which displace those seeking asylum through the production of specific sites of accommodation and specific discourses of risk, security and moralised concern. The paper questions the tendency within "post-political" thought to strip the potential of modes of informal citizenship through arguing that minor acts of resistance are ineffectual and illusory. In response, the paper explores irregular migrant's "acts of citizenship", and suggests that such prosaic acts can be powerful forms of political interruption through which new ways of seeing asylum are constructed. The paper concludes by suggesting that an incremental politics orientated around such acts of interruption is essential to challenge the material, affective and discursive closures of asylum domopolitics. © 2013 The Author. Antipode © 2013 Antipode Foundation Ltd..

Pilaftsis A.,University of Manchester
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2016

Recently, the LHC collaborations, ATLAS and CMS, have announced an excess in the diphoton channel with local significance of about 3σ around an invariant mass distribution of ∼750 GeV, after analyzing new data collected at center-of-mass energies of s=13 TeV. We present a possible physical interpretation of such a signature, within the framework of a minimal UV-complete model with a massive singlet pseudoscalar state a that couples to a new TeV-scale colored vectorlike fermion F, whose hypercharge quantum number is a non-zero integer. The pseudo-scalar state a might be a heavy pseudo-Goldstone boson, such as a heavy axion, which decays into two photons and whose mass lies around the excess region. The mass of the CP-odd state a and its coupling to F may be due to nonperturbative effects, which can break the original Goldstone shift symmetry dynamically. The possible role that the heavy axion a can play in the radiative generation of a seesaw Majorana scale and in the solution to the so-called strong CP problem is briefly discussed. © 2016 American Physical Society.

Pittman J.K.,University of Manchester
Frontiers in Plant Science | Year: 2012

Intracellular pH homeostasis is an essential process in all plant cells. The transport of H+ into intracellular compartments is critical for providing pH regulation. The maintenance of correct luminal pH in the vacuole and in compartments of the secretory/endocytic pathway is important for a variety of cellular functions including protein modification, sorting, and trafficking. It is becoming increasingly evident that coordination between primary H+ pumps, most notably the V-ATPase, and secondary ion/H+ exchangers allows this endomembrane pH maintenance to occur. This article describes some of the recent insights from the studies of plant cation/H+ exchangers and anion/H+ exchangers that demonstrate the fundamental roles of these transporters in pH homeostasis within intracellular compartments. © 2012 Pittman.

Cigarette smokers have greater problems with alcohol than members of the general population, due partly to the influence of smoking on alcohol consumption. The present study was designed to test the ability of implementation intentions to reduce alcohol consumption among cigarette smokers. Sixty-five smokers (37 women, 28 men; age M= 33.77, SD= 9.69) were randomly allocated to an active control condition (n= 31) or were asked to form implementation intentions using a volitional help sheet (n= 34). The outcome measure was subsequent alcohol intake, measured 1-month postbaseline. There was a significant decrease in alcohol consumption in the intervention group but not in the control condition. At the end of the study, alcohol consumption had decreased significantly, by 2.00 standard units (i.e., 16 grams alcohol) per week in the intervention group, but had increased marginally (by 0.46 standard units per week) in the active control condition (d= 0.63). The findings support the efficacy of the volitional help sheet to reduce alcohol consumption among smokers. Further research is needed to refine the volitional help sheet and explore its efficacy among other at-risk groups. © 2014.

Murrell J.,University of Manchester | Board R.,Rosemere Cancer Center
Cancer Treatment Reviews | Year: 2013

The development of brain metastases is common in patients with metastatic melanoma and heralds a particularly poor prognosis. The development of the immunological agent ipilimumab and targeted treatments such as the selective BRAF inhibitor vemurafenib have revolutionised the treatment of metastatic disease. Evidence from clinical trials suggest these drugs may be effective in the treatment of brain metastases from melanoma. However efficacy may be limited by a lack of penetration of the blood brain barrier (BBB) and by multi substrate efflux pumps expressed on the BBB. The role and sequencing of radiotherapy, both whole brain and stereotactic radiotherapy, is yet to be determined but combinations of radiotherapy and systemic therapies may further increase the effects of these drugs on brain metastases. Considering the impact of brain metastases on morbidity and mortality in metastatic melanoma, future research into systemic drug therapy for the treatment of brain metastases and improvements in BBB penetrance should be a priority. © 2013 Elsevier Ltd.

Guppy M.J.,University of Manchester
Human Vaccines and Immunotherapeutics | Year: 2013

Invasive pneumococcal disease continues to be important problem for older adults. Pneumococcal polysaccharide vaccine (PPV 23) has a clinical effectiveness of 43-81%, and following primary vaccination and revaccination, antibody responses last 5-10 y. Hyporesponsiveness to a second dose of vaccine has not been shown to be a significant problem. The use of pneumococcal conjugate vaccines (initially PCV 7; more recently PCV 13) has led to a dramatic fall in the incidence of conjugate vaccine-type invasive pneumococcal disease in children. Because PCV s are immunogenic in older adults, the question has arisen as to whether to also use PCV s in this age group. However, PCV vaccination of children has also reduced the incidence of conjugate vaccine-serotype disease in older adults, and so wherever PCV s are used in children, there is no epidemiological reason to vaccinate older adults with PCV . The cost-effectiveness of PPV for older adults has changed wherever PCV s have been used for children, and this needs to be periodically re-evaluated. © 2013 Landes Bioscience.

Gask L.,University of Manchester
Canadian Journal of Psychiatry | Year: 2013

Objectives: To consider what the barriers are to effective depression education; to understand what attitudes, knowledge, and skills doctors need to acquire, and finally to examine what we currently know about effective ways of training family physicians (FPs) about depression. Methods: A narrative review of the published literature compiled from searching reviews and original articles was conducted using the following key words: education, training, attitudes, depression, and primary care. Further relevant articles were identified from reference lists. Results: The identified barriers are FPs' attitudes and confidence toward recognizing and managing depression, the way in which they conceptualize depression, and the difficulties they face in implementing change in the systems in which they work. We, as educators, can identify what FPs need to know, and this should include novel ways of organizing care. However, of key importance is the need to address how more effective interventions may be provided, recognizing that FPs may be starting from many different points on 3 differing continua of attitude, skills, and knowledge in relation to depression. Conclusions: We have to not only ensure that the content of what we teach is perceived as relevant to primary care but also review exactly how we go about providing it, using methods that will engage and stimulate doctors at differing stages of readiness to acquire new attitudes, skills, and knowledge about depression. However, we still need to find better ways of helping FPs to recognize and acknowledge their educational needs. Further research is also required to thoroughly evaluate these novel approaches to tailoring educational interventions.

Whitehead J.C.,University of Manchester
Pure and Applied Chemistry | Year: 2010

The combination of a nonthermal, atmospheric plasma with a catalyst is investigated as a means of destroying pollutants in waste gas streams. Using the examples of ichloromethane (DCM) and toluene in air streams, it is shown that the destruction of the pollutant can be increased whilst lowering the operating temperature, giving increasing energy efficiency. Unwanted by-products can also be reduced selectively by appropriate choice of catalyst and of the plasma-catalyst configuration. By studying the temperature dependence of plasma catalysis, some ideas can be obtained about the nature of the interaction between plasma and catalyst in the processing. © 2010 IUPAC.

Morano K.A.,University of Houston | Grant C.M.,University of Manchester | Moye-Rowley W.S.,University of Iowa
Genetics | Year: 2012

A common need for microbial cells is the ability to respond to potentially toxic environmental insults. Here we review the progress in understanding the response of the yeast Saccharomyces cerevisiae to two important environmental stresses: heat shock and oxidative stress. Both of these stresses are fundamental challenges that microbes of all types will experience. The study of these environmental stress responses in S. cerevisiae has illuminated many of the features now viewed as central to our understanding of eukaryotic cell biology. Transcriptional activation plays an important role in driving the multifaceted reaction to elevated temperature and levels of reactive oxygen species. Advances provided by the development of whole genome analyses have led to an appreciation of the global reorganization of gene expression and its integration between different stress regimens. While the precise nature of the signal eliciting the heat shock response remains elusive, recent progress in the understanding of induction of the oxidative stress response is summarized here. Although these stress conditions represent ancient challenges to S. cerevisiae and other microbes, much remains to be learned about the mechanisms dedicated to dealing with these environmental parameters. © 2012 by the Genetics Society of America.

Persaud K.C.,University of Manchester
IEEE Sensors Journal | Year: 2012

In this paper, we review olfactory biosensors based on biological components taken from biological olfactory systems. The strategies adopted in this paper include measuring an animal's behavioral response to chemical stimuli, using tissue- or cell-based biosensors, extracting receptor elements and coupling them to various transduction platforms, and creating sensing elements based on receptor proteins or peripheral chemical sensing elements such as odorant-binding proteins. © 2012 IEEE.

Klingenberg C.P.,University of Manchester
Molecular Ecology Resources | Year: 2011

Increasingly, data on shape are analysed in combination with molecular genetic or ecological information, so that tools for geometric morphometric analysis are required. Morphometric studies most often use the arrangements of morphological landmarks as the data source and extract shape information from them by Procrustes superimposition. The MorphoJ software combines this approach with a wide range of methods for shape analysis in different biological contexts. The program offers an integrated and user-friendly environment for standard multivariate analyses such as principal components, discriminant analysis and multivariate regression as well as specialized applications including phylogenetics, quantitative genetics and analyses of modularity in shape data. MorphoJ is written in Java and versions for the Windows, Macintosh and Unix/Linux platforms are freely available from © 2010 Blackwell Publishing Ltd.

Mitchell N.C.,University of Manchester
Journal of Sedimentary Research | Year: 2012

Clinoforms on coasts exposed to ocean waves form from sand exported from the shoreface during extreme wave conditions and deposited where wave action diminishes. Elsewhere, it is shown that during upper 5-percentile wave conditions, wave-induced shear stresses exceed the sediment threshold of motion to below the clinoform rollovers. Experiments and theory suggest that, where bed sediments are agitated by waves, the effect of gravity should move particles down-slope with a flux proportional to the slope. Combined with considerations of continuity, this implies a diffusion of the sediment topography, a property that would explain the smooth seabed morphology found at sandy rollovers where recorded with multibeam sonar. For situations where this gravity effect dominates, a simple analytical expression developed here shows how the rollover curvature should relate to wave properties and to the offshore component of sediment flux. More sharply curved rollovers are expected where waves have short periods or where the sediment flux is large. Relative sediment fluxes were calculated using the model from rollover curvature and wave properties for sites from California, southeast Australia, and Atlantic and Mediterranean Iberia. The relative magnitudes of the fluxes are roughly as would be expected from local physiography and coastal erosion rates. For sandy clinoforms developed under mainly wave influences, the model could be useful for exploring variations within clinoform datasets (e.g., how varied convexity in an area of uniform wave properties reflects varied sediment flux) and for interpreting how varied curvatures of rollovers within seismic stratigraphy reflect how wave climate and flux have varied in the past. Copyright © 2012, SEPM (Society for Sedimentary Geology).

Marco A.,University of Manchester
Briefings in Functional Genomics | Year: 2012

Many aspects of gene regulation are mediated by RNA molecules. However, regulatory RNAs have remained elusive until very recently. At least three types of small regulatory RNAs have been characterized in Drosophila: microRNAs (miRNAs), piwi-interacting RNAs and endogenous siRNAs. A fourth class of regulatory RNAs includes known long non-coding RNAs such