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Birmingham, United Kingdom

The University of Birmingham is a red brick university located in the city of Birmingham, United Kingdom. It received its royal charter in 1900 as a successor to Queen's College, Birmingham and Mason Science College . Birmingham was the first red brick university to gain a charter. It is a founding member of both the Russell Group of British research universities and the international network of research universities, Universitas 21.The University of Birmingham was ranked 11th in the UK and 64th in the world by QS World University Rankings. In 2013, Birmingham was named 'University of the Year 2014' in the Times Higher Education awards. Birmingham is also ranked 4th in the UK for Graduate Prospects in The Times and The Sunday Times Good University Guide 2015.The student population includes around 19,000 undergraduate and 9,000 postgraduate students, which is the 11th largest in the UK. The annual income of the institution for 2010–11 was £470.7 million, with an expenditure of £443.7 million.The university is home to the Barber Institute of Fine Arts, housing works by Van Gogh, Picasso and Monet, the Lapworth Museum of Geology, the Cadbury Research Library home to the Mingana Collections of Middle Eastern manuscripts and the Chamberlain Collection, and the Joseph Chamberlain Memorial Clock Tower, which is a prominent landmark visible from many parts of the city. Academics and alumni of the university include former British Prime Ministers Neville Chamberlain, and Stanley Baldwin, and eight Nobel laureates. Wikipedia.


Rickinson A.B.,University of Birmingham
Seminars in Cancer Biology | Year: 2014

Epstein-Barr virus (EBV) is aetiologically linked to a wide range of human tumours. Some arise as accidents of the virus' lifestyle in its natural niche, the B lymphoid system; these include B-lymphoproliferative disease of the immunocompromised, Hodgkin Lymphoma, Burkitt Lymphoma and particular forms of diffuse large B cell lymphoma. Interestingly, HIV infection increases the incidence of each of these B cell malignancies, though by different degrees and for different reasons. Other EBV-associated tumours arise through rare viral entry into unnatural target tissues; these include all cases of nasal T/NK cell lymphoma and of undifferentiated nasopharyngeal carcinoma plus a small but significant subset of gastric carcinomas, a tumour type more generally associated with chronic Helicobacter pylori infection. Understanding EBV's involvement in the pathogenesis of these different malignancies is an important long-term goal. This article focuses on two overlapping, but relatively neglected, areas of research that could contribute to that goal. The first addresses the mechanisms whereby coincident infections with other pathogens increase the risk of EBV-positive malignancies, and takes as its paradigm the actions of holoendemic malaria and HIV infections as co-factors in Burkitt lymphomagenesis. The second widens the argument to include both infectious and non-infectious sources of chronic inflammation in the pathogenesis of EBV-positive tumours such as T/NK cell lymphoma, nasopharyngeal carcinoma and gastric carcinoma. © 2014.


Brockington I.F.,University of Birmingham
Current Psychiatry Reports | Year: 2011

The literature on menstrual psychosis is briefly reviewed in this article. There are about 80 cases with substantial evidence, and about 200 other possible cases. The clinical features are generally those of manic depressive (bipolar) disorder. The diagnosis requires the accurate dating of the onsets of episodes and of menstrual bleeding. Obtaining a baseline of several carefully dated episodes is also important in finding the best way to arrest the periodic illness. Although conventional psychotropic drugs can shorten episodes, they do not prevent recurrences. For this, unconventional treatments appear to be more effective, especially thyroid hormone and clomiphene. Patients with menstrual psychosis usually have abnormal menstruation, such as anovulatory cycles, luteal defects, or periods of amenorrhea. This, and the occurrence of episodes before the menarche, suggests that the interaction between the bipolar diathesis and menstruation is in the hypothalamus. © 2011 Springer Science+Business Media, LLC.


Rodriguez P.,University of Birmingham | Koper M.T.M.,Leiden University
Physical Chemistry Chemical Physics | Year: 2014

This perspective article reviews recent advances in the study of important catalytic reactions on gold electrodes. The paper discusses both oxidation and reduction reactions: the oxidation of carbon monoxide and alcohols as well as the oxygen reduction reaction on gold electrodes and also a brief discussion of other interesting reactions on gold electrodes such as the amine borane oxidation and the CO2 reduction. A common theme in electrocatalysis on gold is the sensitive dependence of various reaction rates on pH and gold surface structure. The electrocatalysis of redox reactions on gold is highly pH dependent, often preferring alkaline media, due to the prominent role of negatively charged reaction intermediates related to the fact that gold does not bind the neutral intermediates strongly enough. Gold also tends to be a selective catalyst, again due to its weak adsorption properties, as on gold the reaction often stops when a difficult bond breaking or making event will be the necessary next step. This journal is © the Partner Organisations 2014.


Ives J.,University of Birmingham
Sociology of Health and Illness | Year: 2014

This article discusses men's transition to first time fatherhood, with a focus on the way they recognise various in-tension moral demands and negotiate an appropriate role for themselves. The findings are taken from a longitudinal study, drawing on elements of grounded theory, comprising a series of face-to-face and telephone interviews with 11 men over a 9-month period from the 12th week of pregnancy to 8 weeks after the birth. The analysis focuses on men's feelings and experience of exclusion and participation, and their response and reaction to that experience. The findings present two descriptive themes, 'on the inside looking in' and 'present but not participating', followed by third theme 'deference and support: a moral response' that exposes the dilemmatic nature of men's experience and explains the participants' apparent acceptance of being less involved. The discussion explores the concept of moral residue, arguing that while deference and support may be an appropriate role for fathers in the perinatal period it may also be a compromise that leads to feelings of uncertainty and frustration, which is a consequence of being in a genuinely dilemmatic situation. © 2014 Foundation for the Sociology of Health & Illness/John wiley & sons Ltd.


Miall C.,University of Birmingham
Current Biology | Year: 2010

How do we learn from errors during complex movement tasks with redundancy? A new study shows that ambiguous mistakes in bimanual movements are corrected by the non-dominant hand, and responsibility for the error is assumed to fall to the effector with a recent history of poor performance. © 2010 Elsevier Ltd..


Daley A.,University of Birmingham
Cochrane database of systematic reviews (Online) | Year: 2011

Evidence suggests that many perimenopausal and early postmenopausal women will experience menopause symptoms, hot flushes being the most common. Symptoms caused by fluctuating levels of oestrogen may be alleviated by HRT but there has been a marked global decline in its use due to concerns about the risks and benefits of HRT; consequently many women are now seeking alternatives. As large numbers of women are choosing not to take HRT, it is increasingly important to identify evidence based lifestyle modification interventions that have potential to reduce vasomotor menopausal symptoms. To examine the effectiveness of any type of exercise intervention in the management of vasomotor menopausal symptoms (hot flushes and night sweats) in perimenopausal and postmenopausal women. Searches of the following electronic bibliographic databases were performed to identify randomised controlled trials (RCTs): Cochrane Menstrual Disorders and Subfertility Group Specialised trials register; Cochrane Library (CENTRAL) (Wiley Internet interface), MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Science Citation Index and Social Science Citation Index (Web of Science), CINAHL (Ovid) and SPORT Discus. Searches included dates up until 16-24 March 2010. RCTs in which any type of exercise intervention were compared no treatment/control or other treatments in the management of menopausal vasomotor symptoms in symptomatic perimenopausal/postmenopausal women. Six studies were deemed eligible for inclusion. Three authors independently extracted data from eligible studies. Three meta-analyses according to comparator the group were performed. In the comparison of exercise versus no treatment/control (three studies), the non-significant effect size Standardised Mean Difference (SMD) for vasomotor symptoms was -0.14 (95% CI: -0.54 to 0.26); SMD was -0.04, -0.25, -0.38. For the analysis of exercise versus HRT (three studies), the non-significant SMD was 0.49 (95% CI: -0.27 to 1.26); SMD across studies was 0.13, 0.19 and 1.52, with all studies favouring HRT. In the comparison of exercise versus yoga (two studies), the non-significant SMD was -0.09 (95%CI:-0.64 to 0.45); SMD was -0.37 and 0.19. All comparisons were based on small samples. One small study reported data that could not be included in the meta-analysis; in this study hot flush scores were significantly lower in the exercise plus soy milk group (83%) than soy milk only group (72%). The existing studies provided insufficient evidence to determine the effectiveness of exercise as a treatment for vasomotor menopausal symptoms, or whether exercise is more effective than HRT or yoga.


Bion J.,University of Birmingham | Rothen H.U.,University of Bern
American Journal of Respiratory and Critical Care Medicine | Year: 2014

The diversity of European culture is reflected in its healthcare training programs. In intensive care medicine (ICM), the differences in national training programs were so marked that it was unlikely that they could produce specialists of equivalent skills. The Competency-Based Training in Intensive Care Medicine in Europe (CoBaTrICE) program was established in 2003 as a Europe-based worldwide collaboration of national training organizations to create core competencies for ICM using consensus methodologies to establish common ground. The group's professional and research ethos created a social identity that facilitated change. The program was easily adaptable to different training structures and incorporated the voice of patients and relatives. The CoBaTrICE program has now been adopted by 15 European countries, with another 12 countries planning to adopt the training program, and is currently available in nine languages, including English. ICMis nowrecognized as a primary specialty in Spain, Switzerland, and the UK. There are still wide variations in structures andprocesses of training in ICM across Europe, although there has been agreement on a set of common program standards. The combination of a common "product specification" for an intensivist, combined with persisting variation in the educational context in which competencies are delivered, provides a rich source of research inquiry. Pedagogic research in ICM could usefully focus on the interplay between educational interventions, healthcare systems and delivery, and patient outcomes, such as including whether competency-based program are associated with lower error rates, whether communication skills training is associated with greater patient and family satisfaction, how multisource feedback might best be used to improve reflective learning and teamworking, or whether increasing the proportion of specialists trained in acute care in the hospital at weekends results in better patient outcomes. Copyright © 2014 by the American Thoracic Society.


Venous thromboembolism (VTE) is a chronic disease, with fatal recurrences occurring in 5% to 9% of patients, yet it is also one of the best examples of preventable disease. Prognostic models that utilise multiple prognostic factors (demographic, clinical and laboratory patient characteristics) in combination to predict individual outcome risk may allow the identification of patients who would benefit from long-term anticoagulation therapy, and conversely those that would benefit from stopping such therapy due to a low risk of recurrence. The study will systematically review the evidence on potential prognostic models for the recurrence of VTE or adverse outcomes following the cessation of therapy, and synthesise and summarise each model's prognostic value. The review has been registered with PROSPERO (CRD42013003494). Articles will be sought from the Cochrane library (CENTRAL, CDSR, DARE, HTA databases), MEDLINE and EMBASE. Trial registers will be searched for ongoing studies, and conference abstracts will be sought. Reference lists and subject experts will be utilised. No restrictions on language of publications will be applied. Studies of any design will be included if they examine, in patients ceasing therapy after at least three months' treatment with an oral anticoagulant therapy, whether more than one factor in combination is associated with the risk of VTE recurrence or another adverse outcome. Study quality will be assessed using appropriate guidelines for prognostic models. Prognostic models will be summarised qualitatively and, if tested in multiple validation studies, their predictive performance will be summarised using a random-effects meta-analysis model to account for any between-study heterogeneity. The results of the review will identify prognostic models for the risk of VTE recurrence or adverse outcome following cessation of therapy for a first unprovoked VTE. These will be informative for clinicians currently treating patients for a first unprovoked VTE and considering whether to stop treatment or not for particular individuals. The conclusions of the review will also inform the potential development of new prognostic models and clinical prediction rules to identify those at high or low risk of VTE recurrence or adverse outcome following a first unprovoked VTE.


Davies P.W.,University of Birmingham
Pure and Applied Chemistry | Year: 2010

Our development of noble-metal-catalyzed reactions that involve the preparation of sulfur ylides directly from alkynes, without employing sacrificial functionality, is reviewed. © 2010 IUPAC.


Schleif F.-M.,University of Birmingham
Neurocomputing | Year: 2015

In supervised learning probabilistic models are attractive to define discriminative models in a rigid mathematical framework. More recently, prototype approaches, known for compact and efficient models, were defined in a probabilistic setting, but are limited to metric vectorial spaces. Here we propose a generalization of the discriminative probabilistic prototype learning algorithm for arbitrary proximity data, widely applicable to a multitude of data analysis tasks. We extend the algorithm to incorporate adaptive distance measures, kernels and non-metric proximities in a full probabilistic framework. © 2014 Elsevier B.V.


Kenyon S.,University of Birmingham
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Premature birth carries substantial neonatal morbidity and mortality. Subclinical infection is associated with preterm rupture of membranes (PROM). Prophylactic maternal antibiotic therapy might lessen infectious morbidity and delay labour, but could suppress labour without treating underlying infection. OBJECTIVES: To evaluate the immediate and long-term effects of administering antibiotics to women with PROM before 37 weeks, on maternal infectious morbidity, neonatal morbidity and mortality, and longer-term childhood development. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (29 April 2010). SELECTION CRITERIA: Randomised controlled trials comparing antibiotic administration with placebo that reported clinically relevant outcomes were included as were trials of different antibiotics. Trials in which no placebo was used were included for the outcome of perinatal death alone. DATA COLLECTION AND ANALYSIS: We extracted data from each report without blinding of either the results or the treatments that women received. We sought unpublished data from a number of authors. MAIN RESULTS: We included 22 trials, involving 6800 women and babies.The use of antibiotics following PROM is associated with statistically significant reductions in chorioamnionitis (average risk ratio (RR) 0.66, 95% confidence interval (CI) 0.46 to 0.96, and a reduction in the numbers of babies born within 48 hours (average RR 0.71, 95% CI 0.58 to 0.87) and seven days of randomisation (average RR 0.79, 95% CI 0.71 to 0.89). The following markers of neonatal morbidity were reduced: neonatal infection (RR 0.67, 95% CI 0.52 to 0.85), use of surfactant (RR 0.83, 95% CI 0.72 to 0.96), oxygen therapy (RR 0.88, 95% CI 0.81 to 0.96), and abnormal cerebral ultrasound scan prior to discharge from hospital (RR 0.81, 95% CI 0.68 to 0.98). Co-amoxiclav was associated with an increased risk of neonatal necrotising enterocolitis (RR 4.72, 95% CI 1.57 to 14.23).One study evaluated the children's health at seven years of age (ORACLE Children Study) and found antibiotics seemed to have little effect on the health of children. AUTHORS' CONCLUSIONS: The decision to prescribe antibiotics for women with PROM is not clearcut. Benefits in some short-term outcomes (prolongation of pregnancy, infection, less abnormal cerebral ultrasound before discharge from hospital) should be balanced against a lack of evidence of benefit for others, including perinatal mortality, and longer term outcomes. If antibiotics are prescribed it is unclear which would be the antibiotic of choice.Co-amoxiclav should be avoided in women at risk of preterm delivery due to increased risk of neonatal necrotising enterocolitis.


Orford J.,University of Birmingham
Addiction | Year: 2012

Aim To provide an overview of gambling and problem gambling in Britain, including historical background, current regulations and the recognition, prevalence and treatment of problem gambling. Methods A new theory, Gambling Restraint Erosion Theory (GRET), is used as a framework for understanding the history of gambling regulation in Britain in the 20th century and evidence about the prevalence of gambling and problem gambling, as well as public attitudes towards gambling, in Britain in the first decade of the 21st century. Findings Restraints on gambling were progressively dismantled as regulation moved from partial prohibition, to tolerance, and then to liberalization by the turn of the millennium. British adult gambling prevalence surveys carried out in 1999/2000, 2006/07 and 2009/10 suggest that the British public is still relatively restrained in its engagement in gambling, and is still suspicious of gambling. There is evidence from the last of those surveys that engagement in some forms of gambling, and the prevalence of problem gambling, have risen, and that attitudes have become less negative towards gambling. Conclusions Restraints which kept British gambling circumscribed, and the prevalence of problem gambling low, may be in the process of being eroded. Meanwhile, an effective public health response to problem gambling is constrained by lack of Department of Health interest and a failure to develop a research and treatment base independent of the gambling industry. © 2012 The Author, Addiction © 2012 Society for the Study of Addiction.


Ross J.D.C.,University of Birmingham
Current Opinion in Infectious Diseases | Year: 2015

Purpose of review: This review explores the potential for nucleic acid contamination with gonorrhoea or chlamydia within healthcare settings, the implications that this has for the transmission of infection and the potential for contamination to cause false positive test results in patients. Recent findings: Contamination with Chlamydia trachomatis and Neisseria gonorrhoeae nucleic acid on hard surfaces and examination equipment is common particularly in areas where urine samples are being taken. The quantity of material which can be detected is low and unlikely to lead to transmission of infection, but does present a potential risk for contamination of patient samples leading to false positive results. Attempts to reduce contamination through cleaning and improved infection control have been unsuccessful. Summary: Clinicians involved in taking specimens for sexually transmitted infections should be aware of the risk of surface contamination, and the potential for specimen contamination. As patients increasingly take their own genital specimens rather than it being done by doctors or nurses, patients need to be given appropriate advice to minimize the risk of contamination. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Kaban A.,University of Birmingham
Journal of Machine Learning Research | Year: 2014

In this paper we provide a new analysis of compressive least squares regression that removes a spurious log N factor from previous bounds, where N is the number of training points. Our new bound has a clear interpretation and reveals meaningful structural properties of the linear regression problem that makes it solvable effectively in a small dimensional random subspace. In addition, the main part of our analysis does not require the compressive matrix to have the Johnson-Lindenstrauss property, or the RIP property. Instead, we only require its entries to be drawn i.i.d. from a 0-mean symmetric distribution with finite first four moments.


Pulse oximetry screening for critical congenital heart defects (CCHDs) is a highly specific, moderately sensitive test which is cost effective, acceptable to both clinical staff and parents and meets the criteria for universal screening. Pulse oximetry screening is gaining considerable worldwide support and last year was added to the recommended uniform screening panel in the USA following endorsement by the Health and Human Services Secretary.There is significant heterogeneity in published screening protocols and it is important to consider all available evidence and also take local factors into account when developing a screening programme, whether it is within an individual hospital, neonatal network or even at a national level.This paper presents available options based both on the published evidence and personal practice experience which will aid those considering the introduction of screening to make the right decisions both from a clinical and financial perspective. © 2012 Elsevier Ltd.


Hirschfield G.M.,University of Birmingham | Siminovitch K.A.,Samuel Lunenfeld Research Institute
Clinical Reviews in Allergy and Immunology | Year: 2015

Primary biliary cirrhosis is characterised by a progressive and destructive lymphocytic cholangitis, targeting small intra-hepatic bile ducts. In association with the histologic liver injury, patients characteristically express highly specific auto-antibodies that recognise a conserved epitope of the pyruvate dehydrogenase complex found on the inner membrane of the mitochondria. Family studies demonstrate a clear increased incidence and prevalence of associated autoimmune diseases; and historically, a clear HLA association with disease has been evident. With the use of a high-throughput whole-genome array technology, significant insights into the non-HLA loci associated with risk for disease development have been made. These studies, which have primarily incorporated genome-wide association screens and targeted analysis of immune genes, have highlighted the integral roles for immune cell development and function in disease risk. This has revealed the IL-12/JAK-STAT signalling pathway as a key etiologic factor. In conjunction with a better understanding of environmental triggers, such work lays the foundation for better disease insights mechanistically and, hopefully, therapeutically. Obstacles to uncovering all the associated genetic risk and the correlation between genotype and phenotype remain to be circumvented, as do better appreciation of the processes that underpin not only disease initiation but also presentation and outcome. © 2014, Springer Science+Business Media New York.


Higgs S.,University of Birmingham
Appetite | Year: 2015

Social norms are implicit codes of conduct that provide a guide to appropriate action. There is ample evidence that social norms about eating have a powerful effect on both food choice and amounts consumed. This review explores the reasons why people follow social eating norms and the factors that moderate norm following. It is proposed that eating norms are followed because they provide information about safe foods and facilitate food sharing. Norms are a powerful influence on behaviour because following (or not following) norms is associated with social judgements. Norm following is more likely when there is uncertainty about what constitutes correct behaviour and when there is greater shared identity with the norm referent group. Social norms may affect food choice and intake by altering self-perceptions and/or by altering the sensory/hedonic evaluation of foods. The same neural systems that mediate the rewarding effects of food itself are likely to reinforce the following of eating norms. © 2014 Elsevier Ltd.


How prominent a role the workhouse played in the lives of older paupers in the nineteenth century is a matter of debate. This article addresses this issue, as well as the difficulty in determining who was classified as old and identifying them within Birmingham workhouse. It argues that Birmingham's institutionalisation rate of older paupers was more akin to London than an average provincial union. Birmingham was one of the few workhouses which provided dedicated facilities for those with disability, labelled 'bedridden wards'. Examination of the inmates within these wards aids our understanding of the development of poor law institutions as providers of care for older people with chronic illness in the twentieth century. © 2013 The Author.


Stone R.J.,University of Birmingham
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

The uptake of virtual simulation technologies in both military and civilian surgical contexts has been both slow and patchy. The failure of the virtual reality community in the 1990s and early 2000s to deliver affordable and accessible training systems stems not only from an obsessive quest to develop the 'ultimate' in so-called 'immersive' hardware solutions, from head-mounted displays to large-scale projection theatres, but also from a comprehensive lack of attention to the needs of the end users. While many still perceive the science of simulation to be defined by technological advances, such as computing power, specialized graphics hardware, advanced interactive controllers, displays and so on, the true science underpinning simulation-the science that helps to guarantee the transfer of skills from the simulated to the real-is that of human factors, a well-established discipline that focuses on the abilities and limitations of the end user when designing interactive systems, as opposed to the more commercially explicit components of technology. Based on three surgical simulation case studies, the importance of a human factors approach to the design of appropriate simulation content and interactive hardware for medical simulation is illustrated. The studies demonstrate that it is unnecessary to pursue real-world fidelity in all instances in order to achieve psychological fidelity- the degree to which the simulated tasks reproduce and foster knowledge, skills and behaviours that can be reliably transferred to real-world training applications. © 2011 The Royal Society.


Daniels J.P.,University of Birmingham
Current Opinion in Obstetrics and Gynecology | Year: 2013

PURPOSE OF REVIEW: Long-term data from the studies of various endometrial ablation techniques are beginning to emerge. This review appraises the current literature on endometrial ablation for heavy menstrual bleeding, with particular emphasis on second-generation techniques, and their effectiveness, rates of repeat and further interventions and adverse events occurring 1 year or more after the procedure. RECENT FINDINGS: Second-generation, nonhysteroscopic techniques are marginally superior to hysteroscopic approaches, in terms of amenorrhoea, refractory menorrhagia and satisfaction rates. Hysterectomy rates are around 20% at 2 years, with a further 3-5% having repeat ablations. Bipolar radiofrequency and microwave ablation give rise to higher amenorrhoea rates than thermal balloon ablation, and are less likely to require repeat or further intervention. SUMMARY: Endometrial ablation is a well tolerated and effective procedure for the treatment of heavy menstrual bleeding. Second-generation techniques provide greater benefit than hysteroscopic techniques, with shorter procedural times and the possibility of outpatient treatment. Chronic pelvic pain frequently resolves after ablation, but can also develop de novo. Pregnancy outcomes are poor and continuing contraception is recommended. © 2013 Wolters Kluwer Health / Lippincott Williams & Wilkins.


Sloman A.,University of Birmingham
International Journal of Machine Consciousness | Year: 2010

This paper extends three decades of work arguing that researchers who discuss consciousness should not restrict themselves only to (adult) human minds, but should study (and attempt to model) many kinds of minds, natural and artificial, thereby contributing to our understanding of the space containing all of them. We need to study what they do or can do, how they can do it, and how the natural ones can be emulated in synthetic minds. That requires: (a) understanding sets of requirements that are met by different sorts of minds, i.e. the niches that they occupy, (b) understanding the space of possible designs, and (c) understanding complex and varied relationships between requirements and designs. Attempts to model or explain any particular phenomenon, such as vision, emotion, learning, language use, or consciousness lead to muddle and confusion unless they are placed in that broader context. A methodology for making progress is summarised and a novel requirement proposed for a theory of how human minds work: the theory should support a single generic design for a learning, developing system that, in addition to meeting familiar requirements, should be capable of developing different and opposed philosophical viewpoints about consciousness, and the so-called hard problem. In other words, we need a common explanation for the mental machinations of mysterians, materialists, functionalists, identity theorists, and those who regard all such theories as attempting to answer incoherent questions. No designs proposed so far come close. © 2010 World Scientific Publishing Company.


Lip G.Y.H.,University of Birmingham
Journal of Thrombosis and Haemostasis | Year: 2013

The objective of this article is to provide a commentary on the recommendations for stroke prevention from the 2012 focused update of the European Society of Cardiology guidelines on the management of atrial fibrillation and the evidence (or lack of it) supporting these recommendations. These guidelines strongly advocate a major clinical practice shift towards initially focusing on the identification of 'truly low risk' patients who do not need any antithrombotic therapy. After this initial decision-making step, effective stroke prevention - that is, oral anticoagulation therapy (whether as well-controlled adjusted dose warfarin or with one of the novel oral anticoagulants) - could be offered to patients with atrial fibrillation with ≥ 1 stroke risk factors. The 2012 focused update guideline also provides additional guidance on advances in stroke and bleeding risk assessment that are evident since publication of the 2010 guideline, as well as recommendations on the use of the novel oral anticoagulants and the left atrial appendage occlusion devices that have been increasingly used in European clinical practice over the last 2 years. © 2013 International Society on Thrombosis and Haemostasis.


Fowler T.,University of Birmingham | Zammit S.,University of Cardiff | Owen M.J.,University of Cardiff | Rasmussen F.,Karolinska Institutet
Archives of General Psychiatry | Year: 2012

Context: The strong association between lower IQ and risk for psychosis has led to the suggestion that the search for genes influencing cognition may provide a useful strategy for examining the genetic origins of psychosis. However, research in this area has generally used designs in which twin pairs are selected by case status and with assessment of IQ after the onset of psychosis rather than longitudinal population-based samples. Objective: To examine the relationship and shared genetic origin between premorbid IQ and psychotic disorders in a longitudinal population-based cohort. Design: Genetically informative longitudinal study. Setting: Population-based cohort in Sweden. Participants: Individuals were identified from the populationbased Swedish Multi-Generation Register and consisted of male sibling (n=369 960), monozygotic twin (n=1986), and dizygotic twin (n=2253) pairs born between January 1951 and December 1976. Their IQs were measured during compulsory military conscription. Main Outcome Measure: Individuals having a subsequent diagnosis of psychosis were identified via the Swedish National Hospital Discharge Register. Results: Heritability estimates for IQ and psychosis were similar to previous estimates, approximately 69% and 56%, respectively. However, the phenotypic correlation between IQ and psychosis was only-0.11, of which 91% was due to shared genetic influences. The proportion of genetic variance for psychosis shared with that for IQwas approximately 7%. Conclusions: Using IQ as a phenotype to identify genes that have an important role in the genetic origin of schizophrenia is unlikely to be a successful strategy. The low correlation seen in this study between premorbid IQ and psychosis vs the higher correlations reported in the literature with postmorbid IQ suggests the correlation between these phenotypes has more to do with the influence that the onset of psychosis has on cognitive functioning than with shared genetic origin. © 2012 American Medical Association.


Stowe R.,University of Birmingham
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: One of the complications of long-term treatment of Parkinson's disease (PD) with levodopa is the development of motor complications. Generally, when motor complications develop, clinicians add in an additional drug (to the levodopa regimen) from one of three other classes of anti-Parkinsonian treatments (dopamine agonists, catechol-O-methyl transferase inhibitors (COMTIs) or monoamine oxidase type B inhibitors (MAOBIs)). However, despite trials having shown that these drugs are beneficial compared to placebo, it remains unclear as to the best way to treat patients experiencing motor complications and whether one class of drug is more effective than another. OBJECTIVES: This meta-analysis aims to assess more reliably the benefits and risks of the three classes of drugs (dopamine agonists, COMTIs and MAOBIs) currently used as adjuvant treatment to levodopa in PD patients suffering from motor complications. The three drug classes were compared with the aim of determining whether one class of drug provides better symptomatic control than another. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, PubMed, LILACS and Web of Science, plus major journals in the field, abstract books, conference proceedings and reference lists of retrieved publications. SELECTION CRITERIA: Randomised trials comparing an orally administered dopamine agonist, COMTI or MAOBI versus placebo, both on a background of levodopa therapy, in PD patients experiencing motor complications. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data on off-time, levodopa dose, motor complications, side-effects, treatment concordance, clinician-rated disability, mortality, quality of life and health economic data. MAIN RESULTS: Forty-four eligible trials, involving 8436 participants were identified. Compared to placebo, adjuvant therapy significantly reduced off-time (-1.05 hours/day, 95% confidence interval (CI) -1.19 to -0.90; P<0.00001), the required levodopa dose (-55.65 mg/day, CI -62.67 to -48.62; P<0.00001) and improved UPDRS scores (UPDRS ADL score: -1.31 points, CI -1.62 to -0.99; P<0.00001; UPDRS motor score: -2.84 points, CI -3.36 to -2.32; P<0.00001; UPDRS total score: -3.26 points, CI -4.52 to -2.00; P<0.00001). However, dyskinesia (odds ratio (OR) 2.50, CI 2.21 to 2.84; P<0.00001) and side-effects including constipation (OR 3.19, CI 2.17 to 4.68; P<0.00001), dizziness (OR 1.57, CI 1.30 to 1.90; P<0.00001), dry mouth (OR 2.33, CI 1.22 to 4.47; P=0.01), hallucinations (OR 2.16, CI 1.70 to 2.74; P<0.00001), hypotension (OR 1.47, CI 1.18 to 1.83; P=0.0007), insomnia (OR 1.38, CI 1.09 to 1.74; P=0.007), nausea (OR 1.78, CI 1.53 to 2.07; P<0.00001), somnolence (OR 1.87, CI 1.40 to 2.51; P<0.0001) and vomiting (OR 2.56, CI 1.67 to 3.93; P<0.0001) were all increased with adjuvant therapy.Indirect comparisons of the three drug classes suggested that dopamine agonists were more efficacious in reducing off-time (dopamine agonist: -1.54 hours/day; COMTI: -0.83 hours/day; MAOBI: -0.93 hours/day; test for heterogeneity between drug classes P=0.0003) and levodopa dose (dopamine agonist: -116 mg/day; COMTI: -52 mg/day; MAOBI: -29 mg/day; test for heterogeneity between drug classes P<0.00001). UPDRS scores also improved more with dopamine agonists than with COMTI or MAOBI (UPDRS total scores - dopamine agonist: -10.01 points versus COMTI: -1.46 points versus MAOBI: -2.20 points; test for heterogeneity between drug classes P<0.00001), although more dyskinesia were seen with dopamine agonists (OR 2.70) and COMTI (OR 2.50) than with MAOBI (OR 0.94) (test for heterogeneity between drug classes P=0.009). Although the increase in the overall incidence of side-effects was generally more marked with dopamine agonists (OR 1.52) and COMTI (OR 2.0) than with MAOBI (OR 1.32), heterogeneity between drug classes was only of borderline significance (P=0.07). AUTHORS' CONCLUSIONS: Compared to placebo, adjuvant therapy reduces off-time, levodopa dose, and improves UPDRS scores in PD patients who develop motor complications on levodopa therapy. However, this is at the expense of increased dyskinesia and numerous other side-effects. Indirect comparisons suggest that dopamine agonist therapy may be more effective than COMTI and MAOBI therapy, which have comparable efficacy. However, as indirect comparisons should be interpreted with caution, direct head-to-head randomised trials assessing the impact of these different drug classes on overall patient-rated quality of life are needed.


Franklin-Tong N.,University of Birmingham
Current Biology | Year: 2010

Higher plants don't have motile sperm; they rely on pollen tubes to deliver them. Recent research has identified key components involved in pollen tube tip bursting that allow sperm release and fertilization. © 2010 Elsevier Ltd.


Campbell M.J.,Roswell Park Cancer Institute | Turner B.M.,University of Birmingham
Advances in Experimental Medicine and Biology | Year: 2013

In human health and disease the choreographed actions of a wide armory of transcription factors govern the regulated expression of coding and nonprotein coding genes. These actions are central to human health and are evidently aberrant in cancer. Central components of regulated gene expression are a variety of epigenetic mechanisms that include histone modifications. The post-translational modifications of histones are widespread and diverse, and appear to be spatial - temporally regulated in a highly intricate manner. The true functional consequences of these patterns of regulation are still emerging. Correlative evidence supports the idea that these patterns are distorted in malignancy on both a genome-wide and a discrete gene loci level. These patterns of distortion also often reflect the altered expression of the enzymes that control these histone states. Similarly gene expression patterns also appear to reflect a correlation with altered histone modifications at both the candidate loci and genome-wide level. Clarity is emerging in resolving these relationships between histone modification status and gene expression -patterns. For example, altered transcription factor interactions with the key co-activator and co-repressors, which in turn marshal many of the histone-modifying enzymes, may distort regulation of histone modifications at specific gene loci. In turn these aberrant transcriptional processes can trigger other altered epigenetic events such as DNA methylation and underline the aberrant and specific gene expression patterns in cancer. Considered in this manner, altered expression and recruitment of histone-modifying enzymes may underline the distortion to transcriptional responsiveness observed in malignancy. Insight from understanding these processes addresses the challenge of targeted epigenetic therapies in cancer. © 2013 Springer Science+Business Media New York.


Rees N.V.,University of Birmingham
Electrochemistry Communications | Year: 2014

The field of particle impact electrochemistry has grown rapidly in the few years since its development, with discoveries including: detection, characterisation, and quantification of nanoparticles (NPs); solution and surface aggregation of NPs; kinetics of redox reactions of NPs and of species at NPs; and information on surface chemistry of NPs. This mini-review aims to briefly cover the many advances made since the end of 2011. © 2014 Elsevier B.V.


Eggenberger P.,Observatoire de Geneva | Montalban J.,Luniversite Of Liege | Miglio A.,University of Birmingham
Astronomy and Astrophysics | Year: 2012

Context. Recent asteroseismic observations have led to the determination of rotational frequency splittings for ℓ = 1 mixed modes in red giants. Aims. We investigate how these observed splittings can constrain the modelling of the physical processes transporting angular momentum in stellar interiors. Methods. We first compare models including a comprehensive treatment of shellular rotation only, with the rotational splittings observed for the red giant KIC 8366239. We then study how these asteroseismic constraints can give us information about the efficiency of an additional mechanism for the internal transport of angular momentum. This is done by computing rotating models of KIC 8366239 that include a constant viscosity corresponding to this physical process, in addition to the treatment of shellular rotation. Results. We find that models of red giant stars including shellular rotation only predict steep rotation profiles, which are incompatible with the measurements of rotational splittings in the red giant KIC 8366239. Meridional circulation and shear mixing alone are found to produce an insufficient internal coupling so that an additional mechanism for the internal transport of angular momentum is needed during the post-main sequence evolution. We show that the viscosity ν add corresponding to this mechanism is strongly constrained to be ν add = 3 × 10 4 cm 2 s -1 thanks to the observed ratio of the splittings for modes in the wings to those at the centre of the dipole forests. Such a value of viscosity may suggest that the same unknown physical process is at work during the main sequence and the post-main sequence evolution. © 2012 ESO.


Information on ethnicity is commonly used by health services and researchers to plan services, ensure equality of access, and for epidemiological studies. In common with other important demographic and clinical data it is often incompletely recorded. This paper presents a method for imputing missing data on the ethnicity of cancer patients, developed for a regional cancer registry in the UK. Routine records from cancer screening services, name recognition software (Nam Pehchan and Onomap), 2001 national Census data, and multiple imputation were used to predict the ethnicity of the 23% of cases that were still missing following linkage with self-reported ethnicity from inpatient hospital records. The name recognition software were good predictors of ethnicity for South Asian cancer cases when compared with data on ethnicity derived from hospital inpatient records, especially when combined (sensitivity 90.5%; specificity 99.9%; PPV 93.3%). Onomap was a poor predictor of ethnicity for other minority ethnic groups (sensitivity 4.4% for Black cases and 0.0% for Chinese/Other ethnic groups). Area-based data derived from the national Census was also a poor predictor non-White ethnicity (sensitivity: South Asian 7.4%; Black 2.3%; Chinese/Other 0.0%; Mixed 0.0%). Currently, neither method for assigning individuals to an ethnic group (name recognition and ethnic distribution of area of residence) performs well across all ethnic groups. We recommend further development of name recognition applications and the identification of additional methods for predicting ethnicity to improve their precision and accuracy for comparisons of health outcomes. However, real improvements can only come from better recording of ethnicity by health services.


Diquattro N.E.,University of California at Davis | Sawaki R.,University of Birmingham | Geng J.J.,University of California at Davis
Cerebral Cortex | Year: 2014

The most prevalent neurobiological theory of attentional control posits 2 distinct brain networks: The dorsal and ventral attention networks. The role of the dorsal attentional network in top-down attentional control is well established, but there is less evidence for the putative role of the ventral attentional network in initiating stimulusdriven reorienting. Here, we used functional magnetic resonance imaging and dynamic causal modeling (DCM) to test the role of the ventral and dorsal networks in attentional reorienting during instances of attentional capture by a target-colored distracter. In the region of interest analyses, we found that frontal eye field (FEF) was selectively activated by conditions where attention was reoriented (i.e. to spatial cues and target-colored distracters). In contrast, temporoparietal junction (TPJ) responded positively to all stimulus conditions. The DCM results indicated that FEF received sensory inputs earlier than TPJ, and that only the connection from FEF to TPJ was modulated by the appearance of the target-colored distracter. The results provide novel empirical evidence against the idea that TPJ generates stimulus-driven reorientations of attention. We conclude that our results are incompatible with existing theories of TPJ involvement in the stimulus-driven reorientation of attention and discuss alternative explanations such as contextual updating. © The Author 2013. Published by Oxford University Press.


Adams M.J.,University of Birmingham
Journal of the Royal Society, Interface / the Royal Society | Year: 2013

Many aspects of both grip function and tactile perception depend on complex frictional interactions occurring in the contact zone of the finger pad, which is the subject of the current review. While it is well established that friction plays a crucial role in grip function, its exact contribution for discriminatory touch involving the sliding of a finger pad is more elusive. For texture discrimination, it is clear that vibrotaction plays an important role in the discriminatory mechanisms. Among other factors, friction impacts the nature of the vibrations generated by the relative movement of the fingertip skin against a probed object. Friction also has a major influence on the perceived tactile pleasantness of a surface. The contact mechanics of a finger pad is governed by the fingerprint ridges and the sweat that is exuded from pores located on these ridges. Counterintuitively, the coefficient of friction can increase by an order of magnitude in a period of tens of seconds when in contact with an impermeably smooth surface, such as glass. In contrast, the value will decrease for a porous surface, such as paper. The increase in friction is attributed to an occlusion mechanism and can be described by first-order kinetics. Surprisingly, the sensitivity of the coefficient of friction to the normal load and sliding velocity is comparatively of second order, yet these dependencies provide the main basis of theoretical models which, to-date, largely ignore the time evolution of the frictional dynamics. One well-known effect on taction is the possibility of inducing stick-slip if the friction decreases with increasing sliding velocity. Moreover, the initial slip of a finger pad occurs by the propagation of an annulus of failure from the perimeter of the contact zone and this phenomenon could be important in tactile perception and grip function.


Sim J.,Keele University | Dawson A.,University of Birmingham
American Journal of Public Health | Year: 2012

We argue that cluster-randomized trials are an important methodology, essential to the evaluation of many public health interventions. However, in the case of at least some cluster-randomized trials, it is not possible, or is incompatible with the aims of the study, to obtain individual informed consent. This should not necessarily be seen as an impediment to ethical approval, providing that sufficient justification is given for this omission. Wefurtherarguethat itshould be the institutional review board's task to evaluatewhether the protocol is sufficiently justified to proceed without consent and that this is preferable to any reliance on community consent or other means of proxy consent.


Liu F.,City University of Hong Kong | Liang Z.,City University of Hong Kong | Li J.,University of Birmingham
Physical Review Letters | Year: 2013

We introduce a field transformation method for wave manipulation based on completely reciprocal and passive materials. While coordinate transformations in transformation optics (TO) change the size and shape of an object, field transformations give us direct control on the impedance and polarization signature of an object. Using our approach, a new type of perfect conductor can be realized to completely convert between transverse electric and transverse magnetic polarizations at any incidence angles and a perfect magnetic conductor of arbitrary shape can be mimicked by using anisotropic materials. The approach can be further combined with TO to enhance existing TO devices. For example, a dielectric cylinder can become completely transparent for both polarizations using bianisotropic materials. © 2013 American Physical Society.


Wang Q.X.,University of Birmingham
Physics of Fluids | Year: 2013

This paper is concerned with the bubble dynamics of underwater explosion in a compressible liquid flow whose Mach number, based on characteristic liquid velocities, is O(10-1). We will study this phenomenon based on weakly compressible theory using the method of matched asymptotic expansions. As a result, the inner flow near the bubble to second order is described by Laplace's equation with the compressible effects appearing only in the far field condition. The problem can thus be modelled approximately using the boundary integral method. Validations are performed against the Keller equation for spherical bubbles and available experimental data for "small-charge" explosions for non-spherical bubbles under the action of buoyancy. The computation traces jet impact, the transition of the bubble from a singly connected to a doubly connected form, and the recombining of a doubly connected to a singly connected form, and the further repeated transitions. The computational result of the bubble shapes correlates well with experimental data to the end of the second oscillation. The first collapse, which we call the "principal collapse," is the most severe in terms of energy loss. The damping of the bubble oscillation is alleviated by the buoyancy effects and reduced with the buoyancy parameter. © 2013 AIP Publishing LLC.


Franklyn J.A.,University of Birmingham
Clinical Endocrinology | Year: 2013

Mild thyroid dysfunction is common, and more prevalent than overt hyper- and hypothyroidism. Subclinical (mild) thyroid dysfunction is a biochemical entity characterized by an abnormality of serum TSH associated with normal serum thyroid hormone concentrations. Subclinical hyperthyroidism is thus defined as low or suppressed serum TSH with normal serum-free T4 and T3, while subclinical hypothyroidism is defined as raised serum TSH with normal circulating T4. These biochemical abnormalities are part of the much wider spectrum of thyroid dysfunction which includes overt hyperthyroidism and overt hypothyroidism, but by no means always indicate underlying thyroid disease. There is much debate about the significance of mild abnormalities of thyroid function in terms of symptoms and potential associations with long-term morbidity and mortality and hence much debate about whether to screen for these abnormalities, and, once identified, whether to treat or monitor, and if so, how? Our knowledge base has increased significantly in recent years, principally because studies of large cohorts have begun to define the epidemiology and associations of mild thyroid dysfunction (including short-term and long-term outcomes) and a small but increasing number of randomized-controlled intervention studies have been reported. There is, however, much to learn about these disorders and, given their prevalence, their impact on health. © 2012 Blackwell Publishing Ltd.


Stockley R.A.,Queen Elizabeth Hospital Birmingham | Turner A.M.,University of Birmingham
Trends in Molecular Medicine | Year: 2014

The recognition of α-1-antitrypsin deficiency, its function, and its role in predisposition to the development of severe emphysema was a watershed in our understanding of the pathophysiology of the condition. This led to the concept and development of intravenous replacement therapy used worldwide to protect against lung damage induced by neutrophil elastase. Nevertheless, much remained unknown about the deficiency and its impact, although in recent years the genetic and clinical variations in manifestation have provided new insights into assessing impact, efficacy of therapy, and development of new therapeutic strategies, including gene therapy, and outcome measures, such as biomarkers and computed tomography. The current article reviews this progress over the preceding 50 years. © 2013 Elsevier Ltd.


Sorahan T.,University of Birmingham
International Journal of Environmental Research and Public Health | Year: 2015

A previous publication of 57,311 pesticide applicators enrolled in the US Agricultural Health Study (AHS) produced disparate findings in relation to multiple myeloma risks in the period 1993–2001 and ever-use of glyphosate (32 cases of multiple myeloma in the full dataset of 54,315 applicators without adjustment for other variables: rate ratio (RR) 1.1, 95% confidence interval (CI) 0.5 to 2.4; 22 cases of multiple myeloma in restricted dataset of 40,719 applicators with adjustment for other variables: RR 2.6, 95% CI 0.7 to 9.4). It seemed important to determine which result should be preferred. RRs for exposed and non-exposed subjects were calculated using Poisson regression; subjects with missing data were not excluded from the main analyses. Using the full dataset adjusted for age and gender the analysis produced a RR of 1.12 (95% CI 0.50 to 2.49) for ever-use of glyphosate. Additional adjustment for lifestyle factors and use of ten other pesticides had little effect (RR 1.24, 95% CI 0.52 to 2.94). There were no statistically significant trends for multiple myeloma risks in relation to reported cumulative days (or intensity weighted days) of glyphosate use. The doubling of risk reported previously arose from the use of an unrepresentative restricted dataset and analyses of the full dataset provides no convincing evidence in the AHS for a link between multiple myeloma risk and glyphosate use. © 2015 by the authors; licensee MDPI, Basel, Switzerland.


Turner B.M.,University of Birmingham
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2014

The nucleosome core particle is the first stage of DNA packaging in virtually all eukaryotes. It both organises nuclear DNA and protects it from adventitious binding of transcription factors and the consequent deregulation of gene expression. Both properties are essential to allow the genome expansion characteristic of complex eukaryotes. The nucleosome is a flexible structure in vivo, allowing selective relaxation of its intrinsically inhibitory effects in response to external signals. Structural changes are brought about by dedicated remodelling enzymes and by posttranslational modifications of the core histones.Histone modifications occasionally alter nucleosome structure directly, but their more usual roles are to act as receptors on the nucleosome surface that are recognised by specific protein domains. The bound proteins, in turn, affect nucleosome structure and function. This strategy enormously expands the signalling capacity of the nucleosome and its ability to influence both the initiation and elongation stages of transcription. The enzymes responsible for placing and removing histone modifications, and the modification-binding proteins themselves, are ubiquitous, numerous and conserved amongst eukaryotes. Like the nucleosome, they date back to the earliest eukaryotes and may have played integral and essential roles in eukaryotic evolution. The present properties and epigenetic functions of the nucleosome reflect its evolutionary past and the selective pressures to which it has responded and can be better understood in this context. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function. © 2014 Elsevier B.V.


Grimwade D.,Kings College London | Freeman S.D.,University of Birmingham
Blood | Year: 2014

The past 40 years have witnessed major advances in defining the cytogenetic aberrations, mutational landscape, epigenetic profiles, and expression changes underlying hematological malignancies. Although it has become apparent that acute myeloid leukemia (AML) is highly heterogeneous at the molecular level, the standard framework for risk stratification guiding transplant practice in this disease remains largely based on pretreatment assessment of cytogenetics and a limited panel of molecular genetic markers, coupled with morphological assessment of bone marrow (BM) blast percentage after induction. However, application of more objective methodology such as multiparameter flow cytometry (MFC) has highlighted the limitations of morphology for reliable determination of remission status. Moreover, there is a growing body of evidence that detection of subclinical levels of leukemia (ie, minimal residual disease, MRD) using MFC or molecular-based approaches provides powerful independent prognostic information. Consequently, there is increasing interest in the use of MRD detection to provide early end points in clinical trials and to inform patient management. However, implementation of MRD assessment into clinical practice remains a major challenge, hampered by differences in the assays and preferred analytical methods employed between routine laboratories. Although this should be addressed through adoption of standardized assays with external quality control, it is clear that the molecular heterogeneity of AML coupled with increasing understanding of its clonal architecture dictates that a "one size fits all" approach to MRD detection in this disease is not feasible. However, with the range of platforms now available, there is considerable scope to realistically track treatment response in every patient. © 2014 by The American Society of Hematology.


Muller F.,University of Birmingham | Tora L.,French Institute of Health and Medical Research | Tora L.,Nanyang Technological University
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2014

One of the key events in eukaryotic gene regulation and consequent transcription is the assembly of general transcription factors and RNA polymerase II into a functional pre-initiation complex at core promoters. An emerging view of complexity arising from a variety of promoter associated DNA motifs, their binding factors and recent discoveries in characterising promoter associated chromatin properties brings an old question back into the limelight: how is a promoter defined? In addition to position-dependent DNA sequence motifs, accumulating evidence suggests that several parallel acting mechanisms are involved in orchestrating a pattern marked by the state of chromatin and general transcription factor binding in preparation for defining transcription start sites. In this review we attempt to summarise these promoter features and discuss the available evidence pointing at their interactions in defining transcription initiation in developmental contexts. This article is part of a Special Issue entitled: Chromatin and epigenetic regulation of animal development. © 2013 Elsevier B.V.


Vinen W.F.,University of Birmingham
Journal of Low Temperature Physics | Year: 2010

The paper is, for the most part, a review, written in its original form for an International Workshop on Vortices, Superfluid Dynamics, and Quantum Turbulence, held in Lammi, Finland, in 2010. Achievements are reviewed, and a strong emphasis is placed on problems that are either unsolved or still the subject of active discussion. These problems often call for more powerful experimental techniques, including local probes and actual visualization of the turbulent motion. Special emphasis is placed on recent progress in the development of visualization. © Springer Science+Business Media, LLC 2010.


Millar R.,University of Birmingham
Journal of Health, Organisation and Management | Year: 2012

Purpose: The purpose of this paper is to reflect on social enterprise as an organisational form in health organisation and management. Design/methodology/approach: The paper presents a critique of the underlying assumptions associated with social enterprise in the context of English health and social care. Findings: The rise of social enterprise models of service provision reflects increasingly hybrid organisational forms and functions entering the health and social care market. Whilst at one level this hybridity increases the diversity of service providers promoting innovative and responsive services, the paper argues that further inspection of the assumptions associated with social enterprise reveal an organisational form that is symbolic of isomorphic processes pushing healthcare organisations toward greater levels of homogeneity, based on market-based standardisation and practices. Social enterprise forms part of isomorphic processes moving healthcare organisation and management towards market "norms". Originality/value: In line with the aim of the "New Perspectives section", the paper aims to present a provocative perspective about developments in health and social care, as a spur to further debate and research in this area. © Emerald Group Publishing Limited.


Liu F.,University of Birmingham | Liu F.,City University of Hong Kong | Li J.,City University of Hong Kong
Physical Review Letters | Year: 2015

By considering gauge transformations on the macroscopic Maxwell's equations, a two-dimensional gauge field, with its pseudomagnetic field in the real space, is identified as tilted anisotropy in the constitutive parameters. We show that the optical spin Hall effect with broadband response and one-way edge states become possible simply by using anisotropic media. The proposed gauge field also allows us to obtain unidirectional propagation for a particular pseudospin based on the Aharonov-Bohm effect. Our approach will be useful in spoof magneto-optics with arbitrary magnetic fields mimicked by metamaterials with subwavelength unit cells. It also serves as a generic way to design polarization-dependent devices. © 2015 American Physical Society.


Williams I.,University of Birmingham
Health Services Management Research | Year: 2011

There is no single intervention that will trigger or ensure innovation in health care, as the interaction between the innovation and the context of its introduction is necessarily complex and variable. Although academic attention has recently turned to the role of organizations in promoting and embedding innovation, this literature remains light on prescription, and tends to ignore the issue of substitution and disengagement. Innovation needs to be adapted as well as adopted into organizational contexts and receptive climates for innovation can only be developed incrementally over time. This paper identifies recommendations for increasing the readiness of health-care organizations for innovation. Key organizational strategies for embedding innovation include: development of incentives; sophisticated knowledge management; interfunctional and interorganizational coordination and collaboration; and development of an innovation infrastructure. More attention is required to substitution and disengagement of interventions and practices (exnovation) in the current economic climate.


Lip G.Y.H.,University of Birmingham
Journal of Thrombosis and Haemostasis | Year: 2011

Atrial fibrillation (AF) is the commonest sustained cardiac rhythm disorder, which is associated with a substantial risk of mortality and morbidity arising from stroke and thromboembolism. Extensive epidemiological evidence and robust data from clinical trials have shown that stroke and thromboembolism in AF can be prevented by oral anticoagulation (OAC). Despite this evidence and guidelines, appropriate thromboprophylaxis is still suboptimal, and this is partly due to the only OAC agent being available is the vitamin K antagonist class of drugs (e.g. warfarin) that has many limitations and disadvantages. With the availability of new OAC agents that avoid the disutility of the vitamin K antagonists, it is hoped that greater use of OAC would allow more effective thromboprophylaxis and have a great impact on preventing strokes related to AF. Additionally, stroke risk assessments need to evolve such that they are better at identifying the 'truly low risk' subjects who do not need antithrombotic therapy, whilst all other patients with ≥1 stroke risk factors can be considered for OAC. The availability of comprehensive stroke and bleeding risk assessments would enable us to make informed decisions in everyday clinical practice. The aim of the review article is to provide a state-of-the-art overview of the clinical epidemiology of stroke in AF, stroke (and bleeding) risk assessments and the current provision of thromboprophylaxis for patients with AF. © 2011 International Society on Thrombosis and Haemostasis.


Buckley C.D.,University of Birmingham
Immunology Letters | Year: 2011

One of the most important but as yet unanswered questions in inflammation research is not why inflammation occurs (we all get episodes of self limiting inflammation during the course of our lives) but why it does not resolve. Current models of inflammation stress the role of antigen-specific lymphocyte responses and attempt to address the causative agent. However, recent studies have begun to challenge the primacy of the leukocyte and have instead focused on an extended immune system in which stromal cells, such as fibroblasts play a role in the persistence of the inflammatory lesion. In this review I will illustrate how fibroblasts help regulate the switch from acute resolving to chronic persistent inflammation and provide positional memory during inflammatory responses. In chronic inflammation the normal physiological process of the removal of unwanted inflammatory effector cells becomes disordered, leading to the accumulation of leucocytes within lymphoid aggregates that resemble those seen in lymphoid tissue. I will describe how fibroblasts provide survival and retention signals for leukocytes leading to their inappropriate and persistent accumulation within inflamed tissue. © 2011 Elsevier B.V.


Vezirgiannidou S.-E.,University of Birmingham
Environmental Politics | Year: 2013

How have different ways of framing climate change influenced the policy-making process in the United States? Frames related to energy security and green growth/economy have been most prominent in the agenda of the Obama administration and the Democratic Party. Pairing climate change with other concerns is thought to increase support from constituencies not traditionally concerned with environmental problems and to overcome debates over science. However, the way in which these two frames have been presented allows for other concerns to override climate considerations, and eventually the climate message loses its potency. Support for climate legislation is more likely to increase through more tailored messages that re-emphasise the effects of climate change. © 2013 Copyright Taylor & Francis.


Lip G.Y.H.,University of Birmingham
Nature Reviews Cardiology | Year: 2011

Atrial fibrillation (AF) is a major cause of stroke and thromboembolism, resulting in substantial morbidity and mortality. For the majority of patients with AF, aspirin has a limited role in stroke prevention, being an inferior strategy and not necessarily safer than the anticoagulant warfarin, especially in the elderly. Novel oral anticoagulant drugs, such as oral direct thrombin inhibitors and oral factor Xa inhibitors, might further diminish the role of aspirin for stroke prevention in AF. Nonetheless, aspirin use should continue in the early stages following presentation of a patient with AF and acute coronary syndrome, and after stenting, in combination with oral anticoagulant drugs and clopidogrel, as appropriate. Notably, aspirin combined with clopidogrel shows only modest benefit in stroke prevention compared with aspirin monotherapy in patients with AF who refuse oral anticoagulant drugs (including warfarin), or in those individuals who have difficulties in anticoagulation monitoring, and can be used where bleeding risk is not excessive. © 2011 Macmillan Publishers Limited. All rights reserved.


Auchus R.J.,University of Michigan | Arlt W.,University of Birmingham
Journal of Clinical Endocrinology and Metabolism | Year: 2013

The most common form of congenital adrenal hyperplasia is steroid 21-hydroxylase deficiency (21OHD). When the nonclassical (mild) form is included, 21OHD is the most common genetic disease in human beings. With the advent of pharmaceutical preparation of glucocorticoids starting inthe1960s and newborn screening starting in the 1990s, the majority of children with 21OHD are reaching adulthood, which has yielded a cohort of patients with, in essence, a new disease. Only recently have some data emerged from cohorts of adults with 21OHD, and in some centers, experience with the management of these patients is growing. These patients suffer from poor health, infertility, characteristic tumors in the adrenal glands and gonads, and consequences of chronic glucocorticoid therapy. Their care is fragmented and inconsistent, and many stop taking their medications out of frustration. Internal medicine residents and endocrinology fellows receive little training in their care, which further discourages their seeking medical attention. Adults with 21OHD have a different physiology from patients with Addison's disease or other androgenexcess states, and their needs are different than those of young children with 21OHD. Consequently, their care requires unorthodox treatment and monitoring strategies foreign to most endocrine practitioners. Our goal for this article is to review their physiology, complications, and needs in order to develop rational and effective treatment and monitoring strategies. Copyright © 2013 by The Endocrine Society.


Background: There is a developing literature into Anger Management interventions for people with intellectual disability. While initial reports suggest that these interventions are effective there are few evaluations examining what aspects of the therapeutic process contribute to effectiveness. Method: Individuals with an intellectual disability and anger control difficulties who were referred to community psychology services were allocated to either experienced clinical psychologists or a less experienced assistant psychologist who followed the same intervention framework. Results: Significant reductions in self-reported anger intensity were reported; however, the group who were treated by more experienced therapists reported more change and more individuals reported clinically significant change. Conclusions: While effective change was reported by both groups, these results suggest that clinical experience and training may be an important variable in determining the magnitude of change. This has implications for the design of intellectual disability mental health services. Copyright © British Association for Behavioural and Cognitive Psychotherapies 2012.


The last couple of decades have seen an extraordinary transformation in our knowledge and understanding of the multifarious biological roles of inositol phospholipids. Herein, I briefly consider two topics. The first is the role that recently acquired biochemical and genomic information - especially from archaeons - has played in illuminating the possible evolutionary origins of the biological employment of inositol in lipids, and some questions that these studies raise about the 'classical' biosynthetic route to phosphatidylinositol. The second is the growing recognition of the importance in eukaryotic cells of phosphatidylinositol 3,5-bisphosphate. Phosphatidylinositol 3,5-bisphosphate only entered our phosphoinositide consciousness quite recently, but it is speedily gathering a plethora of roles in diverse cellular processes and diseases thereof. These include: control of endolysosomal vesicular trafficking and of the activity of ion channels and pumps in the endolysosomal compartment; control of constitutive and stimulated protein traffic to and from plasma membrane subdomains; control of the nutrient and stress-sensing target of rapamycin complex 1 pathway (TORC1); and regulation of key genes in some central metabolic pathways. I consider two topics. First, did inositol phospholipids originate in an archaeal ancestor of eukaryotes, and is their unexpected biosynthesis therein really unique? Second, what are the regulatory roles of PtdIns(3,5)P2 in eukaryotes? These seem to include influence over endolysosomal vesicular trafficking and ion homeostasis, plasma membrane protein trafficking, the TORC1 pathway and gene expression in central carbohydrate pathways. © 2013 FEBS.


Robinson S.,University of Birmingham
Health Economics | Year: 2011

Economic analysis is increasingly being employed in formal resource allocation decision-making processes in health care. As a consequence, the methods employed by economic analysts are increasingly subject to close scrutiny. One such area of methodology concerns the instruments used to elicit preferences for various health states for use in the construction of quality-adjusted life years. There are a number of techniques which may be used to elicit preferences and different techniques produce different results. The objective of this study was to explore the test-retest reliability of two techniques: Time Trade Off (TTO) and Person Trade Off (PTO) valuations were collected by a general population postal survey. A total of 798 respondents returned questionnaires. The intra class correlation coefficients ranged from 0.40 to 0.88 for TTO and, -0.17 to 0.82 for PTO, with the majority of coefficients being >0.50. The reliability coefficients varied between techniques and health states, with the TTO technique tending to produce higher coefficients. While the reliability results for TTO were generally positive, the reliability results for PTO are less clear. Copyright © 2010 John Wiley & Sons, Ltd.


Boelaert K.,University of Birmingham
Nature Reviews Endocrinology | Year: 2013

Thyroid dysfunction is common in the general population, and mild or subclinical forms can be present in more than 10% of individuals aged >80 years. The diagnosis of abnormal thyroid hormone concentrations in people aged >60 years poses a challenge, as the clinical presentation of thyroid dysfunction is usually nonspecific, and ageing is associated with a number of physiological changes that can affect thyroid function test results. Furthermore, the presence of acute or chronic nonthyroidal illnesses and the use of medications that interfere with thyroid function tests are common confounders in the determination of thyroid status in the elderly. Early diagnosis and treatment of overt thyroid dysfunction is crucial in this population in view of the marked effects of abnormal circulating thyroid hormone levels on a number of organ systems, including the heart, the skeleton and the neurological system. The clinical significance of mild thyroid overactivity and underactivity remains uncertain, and the need for treatment of subclinical thyroid dysfunction is much debated. A number of large epidemiological studies have identified associations between mild thyroid dysfunction and short-term as well as long-term adverse outcomes, and a small but increasing number of randomized controlled intervention studies have been reported. Guidelines recommend treatment of thyroid dysfunction on the basis of the degree of abnormal serum TSH concentrations, patient age and associated comorbidities. This Review describes the current evidence on the prevalence, diagnosis, management and long-term consequences of thyroid dysfunction in the elderly.


McGrath E.E.,University of Birmingham
Journal of Thoracic Oncology | Year: 2011

Bone metastases play an important role in the morbidity and mortality of patients with malignant disease. Despite therapeutic advances in the treatment of solid organ malignancy such as lung cancer, less development on metastasis interventions has been forthcoming. More recent research has focused on molecular pathway manipulation in the prevention and treatment of metastatic bone disease and associated complications such as bone pain and hypercalcemia. The osteoprotegerin/receptor activator of nuclear factor-κβ ligand/receptor activator of nuclear factor-κβ pathway, which is physiologically involved in bone turnover, has been of considerable interest, and recent promising data have been revealed. In this study, we describe this molecular pathway in terms of its natural physiological function, manipulation for therapeutic benefit, and recent clinical trial results. Copyright © 2011 by the International Association for the Study of Lung.


Evans H.E.,University of Birmingham
Surface and Coatings Technology | Year: 2011

The spallation of thermal barrier coatings can be life-limiting but its prediction has proven to be a difficult problem. The final spallation event can often occur by buckling and is driven by the release of strain energy within the ceramic top coat and within the underlying thermally-grown oxide (TGO) layer if the delamination interface is at the TGO/bond-coat interface. Prior to this event, substantial sub-critical damage must develop at one or both of the TGO interfaces. It is argued in this paper that it is only the strain energy within the TGO produced during cooling that contributes significantly to this damage development and not that within the top coat. A critical strain energy within the TGO layer is suggested as a possible pragmatic method of predicting spallation. A critical assessment of proposed mechanisms which implicate bond coat oxidation in the failure process is also undertaken in the paper. Attention is given to: the role of phase changes in the bond coat; the influence of the mechanical constraint imposed by the top coat on the mechanical stability of the bond coat interface; the effect of the growth of the TGO on a non-planar interface on stress development; the importance of localised Al depletion in nucleating a fast-growing non-protective TGO. © 2011 Elsevier B.V.


McGorry P.,University of Melbourne | Bates T.,Headstrong The National Center for Youth Mental Health | Birchwood M.,University of Birmingham
British Journal of Psychiatry | Year: 2013

Despite the evidence showing that young people aged 12-25 years have the highest incidence and prevalence of mental illness across the lifespan, and bear a disproportionate share of the burden of disease associated with mental disorder, their access to mental health services is the poorest of all age groups. A major factor contributing to this poor access is the current design of our mental healthcare system, which is manifestly inadequate for the unique developmental and cultural needs of our young people. If we are to reduce the impact of mental disorder on this most vulnerable population group, transformational change and service redesign is necessary. Here, we present three recent and rapidly evolving service structures from Australia, Ireland and the UK that have each worked within their respective healthcare contexts to reorient existing services to provide youth-specific, evidence-based mental healthcare that is both accessible and acceptable to young people.


Ginty A.T.,University of Birmingham
International Journal of Psychophysiology | Year: 2013

This paper brings together two largely distinct areas: biological responses to acute psychological stress and biological responses to reward. Research has associated blunted biological responses to acute psychological stress with a range of adverse health and behavioral outcomes; a separate line of research relates deficient biological reactions to reward with similar outcomes. This paper argues that both manifestations of blunting reflect a more general failure in biological responding to active challenges in life that require intact motivational and emotional processing systems. © 2013.


El-Tawil A.M.,University of Birmingham
International Journal of Colorectal Disease | Year: 2010

Epidemiological studies provide strong evidence to confirm the correlation between cigarette smoking and inflammatory bowel diseases. This relationship is proved to be positive in Crohn's disease and negative in ulcerative colitis. What in smoking alters the course of inflammatory bowel diseases is still a mystery. Different smoking parts have different and may be opponent actions. Smoking has dual effects. Some of its activities are, sometimes, constructive as they are working in an antagonistic manner to the mechanism of the disease, such as reducing rectal blood flow and accordingly less recruitments of inflammatory mediators to the area of inflammation, enhancement of mucosal production, and consequently, strengthening the membranes, and inhibition of pro-inflammatory mediators' liberation and activity in subjects with ulcerative colitis. Yet the outcome of smoking actions may be affected by the existence of other cofactors. Odd factors, such as shortage of zinc in subjects with Crohn's disease, may facilitate liberation of pro-inflammatory mediators and their activities and accordingly exacerbates symptoms. © 2010 Springer-Verlag.


Cuthbert M.O.,University of Birmingham
Water Resources Research | Year: 2010

An analytical solution to a linearized Boussinesq equation is extended to develop an expression for groundwater drainage using estimations of aquifer parameters. This is then used to develop an improved water table fluctuation (WTF) technique for estimating groundwater recharge. The resulting method extends the standard WTF technique by making it applicable, as long as aquifer properties for the area are relatively well known, in areas with smoothly varying water tables and is not reliant on precipitation data. The method is validated against numerical simulations and a case study from a catchment where recharge is "known" a priori using other means. The approach may also be inverted to provide initial estimates of aquifer parameters in areas where recharge can be reliably estimated by other methods. Copyright 2010 by the American Geophysical Union.


Rajabally Y.A.,University of Birmingham
Muscle and Nerve | Year: 2015

Immunoglobulins are an effective but expensive treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Although the goal is to improve function, use of functional scales to monitor therapy is not widespread. Limited recent evidence suggests that doses lower than those used traditionally may be as effective. There are no proven correlations of effective dose with weight, disease severity, or duration. The clinical course of CIDP is heterogeneous and includes monophasic forms and complete remissions. Careful monitoring of immunoglobulin use is necessary to avoid overtreatment. Definitive evidence for immunoglobulin superiority over steroids is lacking. Although latest trial evidence favors immunoglobulins over steroids, the latter may result in higher remission rates and longer remission periods. This article addresses the appropriateness of first-line, high-dose immunoglobulin treatment for CIDP and reviews important clinical questions regarding the need for long-term therapy protocols, adequate monitoring, treatment withdrawal, and consideration of corticosteroids as an alternative to immunoglobulin therapy. Muscle Nerve 51:657-661, 2015 © 2015 Wiley Periodicals, Inc. 51 5 May 2015 10.1002/mus.24554 Issues & Opinions Issues & Opinions © 2015 Wiley Periodicals, Inc..


Campbell J.,University of Birmingham
Metallurgical and Materials Transactions A: Physical Metallurgy and Materials Science | Year: 2014

John Campbell describes how thermal treatment of the liquid alloy appears to affect the structure of the subsequently solidified alloy. He attributes the refinement of Si particles to the heredity of the melt structure, the action of the superheating being to dissolve Si-Si atomic clusters. The refinement of the iron-rich phases, particularly the β-Fe phase, Al5FeSi, is attributed partly to an increased cooling rate and partly to the transformation of γ to α-alumina clusters which are less good initiation sites for β-Fe.


Ward T.,Victoria University of Wellington | Beech A.R.,University of Birmingham
Psychology, Crime and Law | Year: 2015

While the quality of empirical research on risk predication, assessment and management in the sexual offending field has been of a high standard, relatively little attention has been paid to theoretical issues related to risk and its conceptualisation. In this paper, we develop alternative ways of understanding dynamic risk factors and their utility in theory construction and case formulation. We would stress that this work is of a preliminary nature but believe that it is crucial that standard clinical and research practices are critically challenged from time to time, and their underlying theoretical assumptions evaluated. Our aim is to encourage researchers and practitioners to look at the issue of dynamic risk factors from a different viewpoint; one that we hope can help move the sex offender field forward. © 2014, © 2014 Taylor & Francis.


Wilson M.,University of Birmingham
Magnetic resonance in medicine : official journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine | Year: 2011

Totally Automatic Robust Quantitation in NMR (TARQUIN), a new method for the fully automatic analysis of short echo time in vivo (1)H Magnetic resonance spectroscopy is presented. Analysis is performed in the time domain using non-negative least squares, and a new method for applying soft constraints to signal amplitudes is used to improve fitting stability. Initial point truncation and Hankel singular value decomposition water removal are used to reduce baseline interference. Three methods were used to test performance. First, metabolite concentrations from six healthy volunteers at 3 T were compared with LCModel™. Second, a Monte-Carlo simulation was performed and results were compared with LCModel™ to test the accuracy of the new method. Finally, the new algorithm was applied to 1956 spectra, acquired clinically at 1.5 T, to test robustness to noisy, abnormal, artifactual, and poorly shimmed spectra. Discrepancies of less than approximately 20% were found between the main metabolite concentrations determined by TARQUIN and LCModel™ from healthy volunteer data. The Monte-Carlo simulation revealed that errors in metabolite concentration estimates were comparable with LCModel™. TARQUIN analyses were also found to be robust to clinical data of variable quality. In conclusion, TARQUIN has been shown to be an accurate and robust algorithm for the analysis of magnetic resonance spectroscopy data making it suitable for use in a clinical setting. © 2010 Wiley-Liss, Inc.


Sabiiti W.,St Georges, University of London | May R.C.,University of Birmingham
Future Microbiology | Year: 2012

Brain infection by the fungus Cryptococcus neoformans results in inflammation of the meninges and brain parenchyma, a condition known as meningoencephalitis. One million people are estimated to suffer cryptococcal meningitis globally and >60% of these cases die within 3 months of diagnosis. Humans are believed to contract infection by inhalation of spores or dried yeast cells, which subsequently colonize the lung tissue. In the lungs, cryptococci may be cleared by the lung phagocytes, stay latent, cause pulmonary infection and/or disseminate to other body parts, preferentially the brain, culminating in cryptococcal meningoencephalitis. In this review, we discuss the pathogenesis of C. neoformans from the environment to the brain, the current understanding of the mechanisms of cryptococcal transmission into the brain and cryptococcal meningitis. We also give an insight into future cryptococcosis research and the development of novel therapies. © 2012 Future Medicine Ltd.


De la Croix A.,Erasmus Medical Center | Skelton J.,University of Birmingham
Medical Education | Year: 2013

Context Institutional interactions are often asymmetrical in that the professional has more control over the conversation. It is difficult to say who the professional is in simulated consultations between simulated patients (SPs) and medical students because these feature a real (educational) institutional context and a simulated (medical) institutional context. This study describes this asymmetry and makes educational recommendations based on the description. Methods One hundred assessed conversations between SPs and Year3 students were transcribed and analysed using discourse analysis (DA). We aimed to find linguistic patterns in predefined parts of the conversations (questions, topic initiations, openings, closings) that might suggest conversational dominance. Results The SP is conversationally more dominant, despite performing the role of the patient, in that he or she asks more direct questions, is more likely to initiate topics, is more likely not to follow topic changes by students, and closes the consultation. The student is likely to follow topics initiated by the SP and to seek permission to pre-close the consultation. Conclusions The apparently greater dominance of the SP indicates that the simulated consultation differs from the doctor-patient consultation in certain key aspects. It is in that sense unrealistic. We argue, however, that 'realism' ought not to be a goal of simulated consultation and that what matters is that such consultations are sufficiently realistic for their educational purpose. We discuss the educational implications that follow from this. © 2013 Blackwell Publishing Ltd.


Sorahan T.,University of Birmingham
Occupational Medicine | Year: 2012

Background: The effects of magnetic field exposure on cancer risks remains unclear. Aims: To examine cancer incidence among a cohort of UK electricity generation and transmission workers. Methods: Cancer morbidity experienced by a cohort of 81 842 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1973-2008. All employees had worked for at least 6 months with some employment between 1973 and 1982. Standardized registration ratios (SRRs) were calculated on the basis of national rates. Results: Overall cancer morbidity was slightly below expectation in males and females. Significant excesses were found in male workers for mesothelioma (Observed [Obs] 504, SRR 331), skin cancer (non-melanoma) (Obs 3187, SRR 107) and prostate cancer (Obs 2684, SRR 107) and in female workers for cancer of the small intestine (Obs 10, SRR 306) and nasal cancer (Obs 9, SRR 474). Brain cancers were close to expectation in males and below expectation in females. Leukaemia incidence (all types) was slightly below expectation in males and females. More detailed analyses showed import ant contrasts for mesothelioma and leukaemia. Conclusions: The clear occupational excess of mesothelioma was not matched by a corresponding excess of lung cancer, and the level of asbestos-induced lung cancer in this industry must be low. Leukaemia risks declined with period from hire; confident interpretation of this finding is not possible. The excesses of cancers of the nasal cavities and small intestine are probably not occupational, though the excess of skin cancer may be due to outdoor work. © The Author 2012. Published by Oxford University Press on behalf of the Society of Occupational Medicine.


Kourtzi Z.,University of Birmingham
Vision Research | Year: 2010

Successful actions and interactions in the complex environments we inhabit entail making fast and optimal perceptual decisions. Extracting the key features from our sensory experiences and deciding how to interpret them is a computationally challenging task that is far from understood. Accumulating evidence suggests that the brain may solve this challenge by combining sensory information and previous knowledge about the environment acquired through evolution, development, and everyday experience. Here, we review the role of visual learning and experience-dependent plasticity in shaping decisions. We propose that learning plays an important role in translating sensory experiences to decisions and actions by shaping neural representations across cortical circuits in a task-dependent manner. © 2009 Elsevier Ltd.


Landini G.,University of Birmingham
Journal of Microscopy | Year: 2010

Summary: Fractal geometry, developed by B. Mandelbrot, has provided new key concepts necessary to the understanding and quantification of some aspects of pattern and shape randomness, irregularity, complexity and self-similarity. In the field of microscopy, fractals have profound implications in relation to the effects of magnification and scaling on morphology and to the methodological approaches necessary to measure self-similar structures. In this article are reviewed the fundamental concepts on which fractal geometry is based, their relevance to the microscopy field as well as a number of technical details that can help improving the robustness of morphological analyses when applied to microscopy problems. © 2010 The Author Journal of Microscopy © 2010 The Royal Microscopical Society.


Jeukendrup A.E.,University of Birmingham
Journal of Sports Sciences | Year: 2011

Endurance sports are increasing in popularity and athletes at all levels are looking for ways to optimize their performance by training and nutrition. For endurance exercise lasting 30 min or more, the most likely contributors to fatigue are dehydration and carbohydrate depletion, whereas gastrointestinal problems, hyperthermia, and hyponatraemia can reduce endurance exercise performance and are potentially health threatening, especially in longer events (>4 h). Although high muscle glycogen concentrations at the start may be beneficial for endurance exercise, this does not necessarily have to be achieved by the traditional supercompensation protocol. An individualized nutritional strategy can be developed that aims to deliver carbohydrate to the working muscle at a rate that is dependent on the absolute exercise intensity as well as the duration of the event. Endurance athletes should attempt to minimize dehydration and limit body mass losses through sweating to 2-3% of body mass. Gastrointestinal problems occur frequently, especially in long-distance races. Problems seem to be highly individual and perhaps genetically determined but may also be related to the intake of highly concentrated carbohydrate solutions, hyperosmotic drinks, as well as the intake of fibre, fat, and protein. Hyponatraemia has occasionally been reported, especially among slower competitors with very high intakes of water or other low sodium drinks. Here I provide a comprehensive overview of recent research findings and suggest several new guidelines for the endurance athlete on the basis of this. These guidelines are more detailed and allow a more individualized approach. © 2011 Taylor and Francis Group, LLC.


Crist J.V.,Kings College London | Grunfeld E.A.,University of Birmingham
Psycho-Oncology | Year: 2013

Objective Fear of cancer recurrence (FCR) is a significant psychological problem for cancer survivors. Some survivors experience FCR, which is both persistent and highly distressing. The aim of this systematic review was to identify the key factors associated with fear of recurrence among cancer patients. Methods A comprehensive literature search using keywords was performed with three databases, followed by an organic search to identify additional relevant articles. Included studies had a quantitative methodology presenting empirical findings focussed on adult cancer patients. A methodological quality assessment was performed for each study, and the strength of evidence was defined by the consistency of results. Results Forty-three studies met the inclusion criteria and are presented in this review. The most consistent predictor of elevated FCR was younger age. There was strong evidence for an association between physical symptoms and fear of cancer recurrence. Additional factors moderately associated with increased FCR included treatment type, low optimism, family stressors and fewer significant others. Inconsistent evidence was found for socio-demographic factors. Conclusions Fear of cancer recurrence is a complex issue influenced by a multitude of factors, including demographic, clinical and psychological factors. However, some studies have reported contradictory evidence, and FCR has been measured using a range of scales, which can hamper comparison across studies. Further research is needed to clarify inconsistencies in the current published research. Copyright © 2012 John Wiley & Sons, Ltd.


Zlatanou A.,University of Birmingham
Oncogene | Year: 2015

Rad18 functions at the cross-roads of three different DNA damage response (DDR) pathways involved in protecting stressed replication forks: homologous recombination repair, DNA inter-strand cross-link repair and DNA damage tolerance. Although Rad18 serves to facilitate replication of damaged genomes by promoting translesion synthesis (TLS), this comes at a cost of potentially error-prone lesion bypass. In contrast, loss of Rad18-dependent TLS potentiates the collapse of stalled forks and leads to incomplete genome replication. Given the pivotal nature with which Rad18 governs the fine balance between replication fidelity and genome stability, Rad18 levels and activity have a major impact on genomic integrity. Here, we identify the de-ubiquitylating enzyme USP7 as a critical regulator of Rad18 protein levels. Loss of USP7 destabilizes Rad18 and compromises UV-induced PCNA mono-ubiquitylation and Pol η recruitment to stalled replication forks. USP7-depleted cells also fail to elongate nascent daughter strand DNA following UV irradiation and show reduced DNA damage tolerance. We demonstrate that USP7 associates with Rad18 directly via a consensus USP7-binding motif and can disassemble Rad18-dependent poly-ubiquitin chains both in vitro and in vivo. Taken together, these observations identify USP7 as a novel component of the cellular DDR involved in preserving the genome stability.Oncogene advance online publication, 11 May 2015; doi:10.1038/onc.2015.149. © 2015 Macmillan Publishers Limited


Saidi Y.,University of Birmingham | Finka A.,University of Lausanne | Goloubinoff P.,University of Lausanne
New Phytologist | Year: 2011

An accurate assessment of the rising ambient temperature by plant cells is crucial for the timely activation of various molecular defences before the appearance of heat damage. Recent findings have allowed a better understanding of the early cellular events that take place at the beginning of mild temperature rise, to timely express heat-shock proteins (HSPs), which will, in turn, confer thermotolerance to the plant. Here, we discuss the key components of the heat signalling pathway and suggest a model in which a primary sensory role is carried out by the plasma membrane and various secondary messengers, such as Ca 2+ ions, nitric oxide (NO) and hydrogen peroxide (H 2O 2). We also describe the role of downstream components, such as calmodulins, mitogen-activated protein kinases and Hsp90, in the activation of heat-shock transcription factors (HSFs). The data gathered for land plants suggest that, following temperature elevation, the heat signal is probably transduced by several pathways that will, however, coalesce into the final activation of HSFs, the expression of HSPs and the onset of cellular thermotolerance. © 2010 The Authors. New Phytologist © 2010 New Phytologist Trust.


Ham C.,University of Birmingham
Health Economics, Policy and Law | Year: 2010

The purpose of this paper is to describe the characteristics of the high-performing chronic care system and the four implementation strategies needed to achieve such a system. The paper starts with a description of the Chronic Care Model and summarises evidence on its impact. This is followed by a review of international evidence on gaps in the quality of chronic care. These gaps suggest that, useful and influential as the Chronic Care Model is, more is needed to help health care decision makers bring about the reorientation required to meet the needs of populations in which chronic diseases predominate. The second half of the paper therefore sets out the ten characteristics and four implementation strategies required to achieve a high-performing chronic care system. In doing so, it provides practical guidance to policy makers and health care leaders on the most promising strategies for improving the provision of chronic care, drawing on evidence from the experience of England, New Zealand and USA. Copyright © Cambridge University Press 2009.


Mannion R.,University of Birmingham
British Medical Bulletin | Year: 2011

The latest NHS reforms in England will require all general practices to become members of general practitioner (GP) consortia. These organisations will have responsibility for commissioning the majority of health care for their local populations. This article reviews the history and evidence on impact of the previous models of GP commissioning that have been introduced in the NHS with the aim of distilling key lessons for the design, implementation and evaluation of the latest reforms. GP commissioning has the potential to generate a variety of benefits for the NHS and patients, including lowering elective and non-elective referrals, reducing waiting times, improved coordination of primary and community support services and better financial risk management. GP commissioning has also the potential to reduce patient satisfaction, increase inequalities between geographical areas and may generate substantial management and transaction costs. The GP community will need to display strong directive leadership as well as nurture a culture of collaboration and group camaraderie among practices if the GP consortia model of commissioning is to deliver the desired improvements in quality and performance. The implementation of the new GP consortia model of commissioning needs to be monitored and evaluated to ensure that the benefits are maximized and any unintended and dysfunctional effects mitigated. © 2011 The Author.


Myin-Germeys I.,Maastricht University | Birchwood M.,University of Birmingham | Kwapil T.,University of North Carolina at Greensboro
Schizophrenia Bulletin | Year: 2011

The current article discusses how momentary assessment may fundamentally contribute to identifying environmental risk factors and symptom patterns, as well as provide new opportunities for treatment. A new prototype device, the "PsyMate," was specifically developed to implement momentary assessment in clinical practice. It was shown that self-monitoring of both positive and negative psychotic symptoms (a) is feasible, (b) provides a much more detailed and fine-grained picture of symptoms, and (c) reveals patterns of behavior that may be relevant for treatment. Furthermore, the PsyMate could be instrumental for real-time and real-world delivery of psychological interventions. With PsyMate, patients can become active partners in the therapeutic process, resulting in greater patient ownership and empowerment as well as understanding of their symptoms and the environment. © The Author 2011. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.


Pallen M.J.,University of Birmingham
Trends in Microbiology | Year: 2011

The scientific community is comfortable with recognising mitochondria as organelles that happen to be descendants of bacteria. Here, I playfully explore the arguments for and against a phylogenetic fundamentalism that states that mitochondria are bacteria and should be given their own taxonomic family, the Mitochondriaceae. I also explore the consequences of recognizing mitochondria as bacteria for our understanding of the systemic responsetotrauma and for the prospects of creating transgenic mitochondria. © 2010 Elsevier Ltd.


Barton P.,University of Birmingham
Health Economics | Year: 2011

Aim: To explore what happens to the expected value of perfect information (EVPI) as an increasingly large number of decision options is considered. Methods: A stylised model of screening for a hypothetical cancer. The model was used to test different possible ages for 'once in a lifetime' screening under a variety of assumptions about model parameter uncertainty. Initial model runs only considered screening at ages which are multiples of 16 years, then multiples of 8 years were allowed, then 4 years, etc. Results: Effects of more refined choice sets on the cost-effectiveness acceptability frontier (CEAF) and EVPI are shown. The CEAF collapses to zero for threshold incremental cost-effectiveness ratios at which screening at some age is preferred to no screening, while the EVPI stabilises at a non-zero figure. Conclusions: The CEAF is likely to be highly dependent on the choice of options when these are a selection from a very large set of possible options. In contrast, the EVPI can be reasonably approximated by a model with a slightly limited choice set. Copyright © 2010 John Wiley & Sons, Ltd.


Shikhmurzaev Y.D.,University of Birmingham
European Physical Journal: Special Topics | Year: 2011

Some aspects of research into the dynamic wetting phenomenon are discussed where multidisciplinarity of the dynamic wetting community becomes a hindrance rather than an advantage. An instance of this is when the accumulated knowledge is cast into mathematical models that mix conceptual frameworks inherent in different levels of description. An attempt is made to establish some common reference points for the modelling and outline a research programme that utilizes the already obtained results and the complementary expertise of several sectors of the research community. © 2011 EDP Sciences and Springer.


Corujeira Gallo S.,CSIRO | Dong H.,University of Birmingham
Scripta Materialia | Year: 2012

Low-temperature active-screen plasma nitriding is an effective surface engineering technology to improve the wear and corrosion resistance of austenitic stainless steel through the formation of expanded austenite. The material sputtered from the active screen and redeposited on the specimens has been suggested to play an important role in the nitriding mechanism involved. This paper reports a patterned deposition layer, which is in correlation with the grain orientation of polycrystalline specimens. This has provided new insights into the nitriding mechanism. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Fraise A.,University of Birmingham
Journal of Hospital Infection | Year: 2011

Clostridium difficile has been recognised for some time as a pathogen which can contaminate the environment and which is associated with secondary spread via this route. Unfortunately many of the disinfectants currently used in healthcare environments are inactive against this organism. For example, alcohol-containing hand rubs do not have sporicidal activity and some quaternary ammonium compounds and detergents may even encourage sporulation. European standards have been developed to allow a standardised methodology for testing the efficacy of disinfectants, but no European standard exists for testing products against C. difficile in medical environments. Most laboratories use an adapted version of EN 13704 which was designed for food, domestic and industrial applications. It is important when testing a disinfectant that it is tested under dirty as well as clean conditions and that the disinfectant is adequately neutralised. Some of the currently available biocides have good activity against C. difficile although relatively long contact times are sometimes required and this may not accurately reflect in-use practises. Other agents have very little activity against C. difficile even after a contact time of 1 h. It has to be recognised that testing activity against C. difficile is technically very challenging and therefore there can be large interlaboratory variations in results. When interpreting data, it is essential to scrutinise the methodology used in detail. © 2010 The Hospital Infection Society.


Lip G.Y.H.,University of Birmingham
European Heart Journal | Year: 2013

Decision making with regard to thromboprophylaxis should be based upon the absolute risks of stroke/thromboembolism and bleeding and the net clinical benefit for a given patient. As a consequence, a crucial part of atrial fibrillation (AF) management requires the appropriate use of thromboprophylaxis, and the assessment of stroke as well as bleeding risk can help inform management decisions by clinicians. The objective of this review article is to provide an overview of stroke and bleeding risk assessment in AF. There would be particular emphasis on when, how, and why to use these risk stratification schemes, with a specific focus on the CHADS2 [congestive heart failure, hypertension, age, diabetes, stroke (doubled)], CHA2DS 2-VASc [congestive heart failure or left ventricular dysfunction, hypertension, age ≥75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65-74 and sex category (female)], and HAS-BLED [hypertension (i.e. uncontrolled blood pressure), abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR (if on warfarin), elderly (e.g. age >65, frail condition), drugs (e.g. aspirin, NSAIDs)/alcohol concomitantly] risk scores. © 2012 Published on behalf of the European Society of Cardiology. All rights reserved.


Lip G.Y.H.,University of Birmingham
Clinical Cardiology | Year: 2012

Stroke prevention with appropriate thromboprophylaxis still remains central to the management of atrial fibrillation (AF). Nonetheless, stroke risk in AF is not homogeneous, but despite stroke risk in AF being a continuum, prior stroke risk stratification schema have been used to 'artificially' categorise patients into low, moderate and high risk stroke strata, so that the patients at highest risk can be identified for warfarin therapy. Data from recent large cohort studies show that by being more inclusive, rather than exclusive, of common stroke risk factors in the assessment of the risk for stroke and thromboembolism in AF patients, we can be so much better in assessing stroke risk, and in optimising thromboprophylaxis with the resultant reduction in stroke and mortality. Thus, there has been a recent paradigm shift towards getting better at identifying the 'truly low risk' patients with AF who do not even need antithrombotic therapy, whilst those with one or more stroke risk factors can be treated with oral anticoagulation, whether as well-controlled warfarin or one or the new oral anticoagulant drugs. The new European guidelines on AF have evolved to deemphasise the artificial low/moderate/high risk strata (as they were not very predictive of thromboembolism, anyway) and stressed a risk factor based approach (within the CHA 2DS 2-VASc score) given that stroke risk is a continuum. Those categorised as 'low risk' using the CHA 2DS 2-VASc score are 'truly low risk' for thromboembolism, and the CHA 2DS 2-VASc score performs as good as-and possibly better- than the CHADS 2 score in predicting those at 'high risk'. Indeed, those patients with a CHA 2DS 2-VASc score = 0 are 'truly low risk' so that no antithrombotic therapy is preferred, whilst in those with a CHA 2DS 2-VASc score of 1 or more, oral anticoagulation is recommended or preferred. Given that guidelines should be applicable for >80% of the time, for >80% of the patients, this stroke risk assessment approach covers the majority of the patients we commonly seen in everyday clinical practice, and considers the common stroke risk factors seen in these patients. The European guidelines also do stress that antithrombotic therapy is necessary in all patients with AF unless they are age <65 years and truly low risk. Indeed, some patients with 'female gender' only as a single risk factor (but still CHA 2DS 2-VASc score of 1, due to gender) do not need anticoagulation, especially if they fulfil the criterion of "age <65 and lone AF, and very low risk". In the European and Canadian guidelines, bleeding risk assessment is also emphasised, and the simple validated HAS-BLED score is recommended. A HAS-BLED score of ≥3 represents a sufficiently high risk such that caution and/or regular review of a patient is needed. It also makes the clinician think of correctable common bleeding risk factors, and the availability of such a score allows an informed assessment of bleeding risk in AF patients, when antithrombotic therapy is being initiated. © 2012 Wiley Periodicals, Inc.


McGrath E.E.,University of Birmingham
Journal of Thoracic Oncology | Year: 2011

Tumor necrosis factor-related apoptosis-inducing ligand is a type II membrane-bound protein whose C-terminal extracellular domain shows clear homology to other tumor necrosis factor family members. It is constitutively expressed on macrophages, T cells, natural killer cells, and dendritic cells and selectively kills transformed cells leaving most of the normal cells alone. This selectivity has led to great interest in it use as a therapeutic agent for the treatment of malignancy. In this review, this critical pathway is described, highlighting its mechanistic manipulation for therapeutic benefit and the recent phase I and II trials in lung cancer that have been performed or are currently ongoing are also discussed. Copyright © 2011 by the International Association for the Study of Lung Cancer.


Gunther U.L.,University of Birmingham
Topics in current chemistry | Year: 2013

Nuclear magnetic resonance (NMR) spectroscopy is a broadly used analytical method with major applications in chemistry, biochemistry and medicine. Key applications include structural analysis of small molecules, metabolites, larger biomolecules such as proteins, RNA and DNA, and applications in material science. Magnetic resonance imaging (MRI), which is based on the same physical principles, is extensively used in medical diagnostics and represents the most widespread application of NMR. However, NMR is fundamentally limited in sensitivity and this has always restricted its applicability. Hyperpolarization techniques such as dynamic nuclear polarization (DNP) have become a major field of research and development because they hold the promise of increasing the sensitivity of NMR by several orders of magnitude. Such sensitivity enhancements could significantly broaden NMR applications, combining its unique structural information with much higher sensitivity. Unfortunately, there is no single implementation of DNP that would be suitable for a broader range of typical NMR applications. Experimental conditions often circumscribe areas of possible applications. Nevertheless, recent developments point towards experimental protocols providing solutions for specific applications of NMR. This review summarizes the concepts behind DNP in the light of recent developments and potential applications.


Lovick T.A.,University of Birmingham
Brazilian Journal of Medical and Biological Research | Year: 2012

The female brain operates in a constantly changing chemical milieu caused by cyclical changes in gonadal hormones during the estrous cycle (menstrual cycle in women). Such hormones are highly lipophilic and pass readily from the plasma to the brain where they can influence neuronal function. It is becoming clear that the rapid reduction in peripheral circulating progesterone, which occurs during the late diestrous phase of the cycle, can trigger a withdrawal-like response, in which changes in GABAa receptor expression render hyper-responsive certain brain areas involved in processing responses to stressful stimuli. The periaqueductal gray matter (PAG) is recognised as an important region for integrating anxiety/defence responses. Withdrawal from progesterone, via actions of its neuroactive metabolite allopregnanolone, triggers up-regulation of extrasynaptic GABAa receptors on GABAergic neurons in the PAG. As a consequence, ongoing GABAergic tone on the output cells decreases, leading to an increase in functional excitability of the circuitry and enhanced responsiveness to stressful stimuli during the late diestrous phase. These changes during late diestrus could be prevented by short-term neurosteroid administration, timed to produce a more gradual fall in the peripheral concentration of allopregnanolone than the rapid decrease that occurs naturally, thus removing the trigger for the central withdrawal response.


Zhao Y.-B.,University of Birmingham
IEEE Transactions on Signal Processing | Year: 2013

Recently, the worse-case analysis, probabilistic analysis and empirical justification have been employed to address the fundamental question: When does ℓ1-minimization find the sparsest solution to an underdetermined linear system? In this paper, a deterministic analysis, rooted in the classic linear programming theory, is carried out to further address this question. We first identify a necessary and sufficient condition for the uniqueness of least ℓ1-norm solutions to linear systems. From this condition, we deduce that a sparsest solution coincides with the unique least ℓ1-norm solution to a linear system if and only if the so-called range space property (RSP) holds at this solution. This yields a broad understanding of the relationship between ℓ0-and ℓ1-minimization problems. Our analysis indicates that the RSP truly lies at the heart of the relationship between these two problems. Through RSP-based analysis, several important questions in this field can be largely addressed. For instance, how to efficiently interpret the gap between the current theory and the actual numerical performance of ℓ1- minimization by a deterministic analysis, and if a linear system has multiple sparsest solutions, when does ℓ1-minimization guarantee to find one of them? Moreover, new matrix properties (such as the RSP of order K and the Weak-RSP of order K) are introduced in this paper, and a new theory for sparse signal recovery based on the RSP of order K is established. © 2013 IEEE.


Simpkins N.S.,University of Birmingham
Chemical Communications | Year: 2013

The polycyclic polyprenylated acylphloroglucinol (PPAP) family of natural products includes important compounds with notable biological activities, such as garsubellin A, hyperforin and clusianone. The synthesis of these complex, bridged, highly oxidized and substituted systems presents a formidable challenge to synthetic chemists. This feature article describes how the use of unconventional bridgehead substitution chemistry has enabled the synthesis of these natural products and their analogues. © 2013 The Royal Society of Chemistry.


Cehovin L.,University of Ljubljana | Kristan M.,University of Ljubljana | Leonardis A.,University of Ljubljana | Leonardis A.,University of Birmingham
IEEE Transactions on Pattern Analysis and Machine Intelligence | Year: 2013

This paper addresses the problem of tracking objects which undergo rapid and significant appearance changes. We propose a novel coupled-layer visual model that combines the target's global and local appearance by interlacing two layers. The local layer in this model is a set of local patches that geometrically constrain the changes in the target's appearance. This layer probabilistically adapts to the target's geometric deformation, while its structure is updated by removing and adding the local patches. The addition of these patches is constrained by the global layer that probabilistically models the target's global visual properties, such as color, shape, and apparent local motion. The global visual properties are updated during tracking using the stable patches from the local layer. By this coupled constraint paradigm between the adaptation of the global and the local layer, we achieve a more robust tracking through significant appearance changes. We experimentally compare our tracker to 11 state-of-the-art trackers. The experimental results on challenging sequences confirm that our tracker outperforms the related trackers in many cases by having a smaller failure rate as well as better accuracy. Furthermore, the parameter analysis shows that our tracker is stable over a range of parameter values. © 1979-2012 IEEE.


Ewer A.K.,University of Birmingham
Current Opinion in Cardiology | Year: 2013

PURPOSE OF REVIEW: The concept of using pulse oximetry as a screening method to detect undiagnosed critical congenital heart defects (CCHD) in asymptomatic newborns was first explored over 10 years ago. A number of studies were subsequently reported, which initially involved relatively small numbers of patients, low prevalence of CCHD and heterogeneous methodology. As a consequence, the majority of clinicians felt the case for routine pulse oximetry screening had not been proven. RECENT FINDINGS: In the last 3 years, four European studies reporting the test accuracy of routine pulse oximetry screening, and involving over 150 000 babies, have strengthened the argument. A systematic review and meta-analysis of almost 230 000 screened babies has also recently been published which reported high specificity, moderate sensitivity and a low false-positive rate. In addition, acceptability to parents and staff, cost-effectiveness and feasibility of implementing screening outside the research context have also been reported. SUMMARY: Pulse oximetry screening is a highly specific, moderately sensitive test, which is acceptable to parents and staff, likely to be cost-effective and fulfils the criteria for universal screening. Routine screening for CCHD using pulse oximetry is being increasingly supported and was added to the recommended uniform screening panel in the USA in 2011. Copyright © 2013 Lippincott Williams & Wilkins.


Calvert M.,University of Birmingham | Blazeby J.,University of Bristol | Altman D.G.,University of Oxford | Revicki D.A.,United Biosource Corporation | And 2 more authors.
JAMA - Journal of the American Medical Association | Year: 2013

The CONSORT (Consolidated Standards of Reporting Trials) Statement aims to improve the reporting of randomized controlled trials (RCTs); however, it lacks guidance on the reporting of patient-reported outcomes (PROs), which are often inadequately reported in trials, thus limiting the value of these data. In this article, we describe the development of the CONSORT PRO extension based on the methodological framework for guideline development proposed by the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network. Five CONSORT PRO checklist items are recommended for RCTs in which PROs are primary or important secondary end points. These recommendations urge that the PROs be identified as a primary or secondary outcome in the abstract, that a description of the hypothesis of the PROs and relevant domains be provided (ie, if a multidimensional PRO tool has been used), that evidence of the PRO instrument's validity and reliability be provided or cited, that the statistical approaches for dealing with missing data be explicitly stated, and that PRO-specific limitations of study findings and generalizability of results to other populations and clinical practice be discussed. Examples and an updated CONSORT flow diagram with PRO items are provided. It is recommended that the CONSORT PRO guidance supplement the standard CONSORT guidelines for reporting RCTs with PROs as primary or secondary outcomes. Improved reporting of PRO data should facilitate robust interpretation of the results from RCTs and inform patient care. ©2013 American Medical Association. All rights reserved.


Nunan F.,Implementation of a Fisheries Management Plan | Nunan F.,University of Birmingham
Fish and Fisheries | Year: 2014

Fisheries policies often pursue multiple objectives, which may, in some instances, be in conflict or competition with each other. It may not be possible, for example, to create or maintain employment and generate increasing volumes of revenue for government whilst also sustaining stocks and biodiversity. Two approaches to fisheries management, one focused on capturing wealth and limiting access and the other on maintaining access for employment and providing community development and welfare, present contrasting policy advice, with different points of emphases and objectives. This article examines the case of Lake Victoria, where the three main commercial fisheries are seen to contribute to different objectives for the lake's fisheries. Insights from the debate between wealth-based and welfare-based approaches to fisheries management provide a framework for the analysis of fisheries policy and practice on the lake. From the analysis, it is concluded that whilst there is much rhetoric in support of a wealth-based approach, this has not been followed through in implementation, reflecting the lack of political support for new taxation and limiting access. The welfare functions of the fisheries are significant, but could be substantially strengthened through greater investment in the provision of services to fisheries communities. The approaches are not mutually exclusive, but pursuing wealth-based management must support livelihoods, employment and development, as well as fisheries management objectives. Without the incorporation of welfare objectives, fisheries policies will not be politically accepted or fully implemented, suggesting the need for a balance between wealth and welfare objectives and measures. © 2013 John Wiley & Sons Ltd.


Barnett A.H.,University of Birmingham
Core Evidence | Year: 2011

Lixisenatide is a once-daily glucagon-like peptide 1 (GLP-1) receptor agonist mimicking several favorable actions of endogenous GLP-1 that result in improved glycemic control with little or no hypoglycemia and weight loss. Phase II trials have shown that lixisenatide 20 μg once daily restores first-phase insulin release in patients with type 2 diabetes and improves the second-phase insulin response. Administered once or twice daily for 4 weeks, it significantly reduced postprandial and fasting blood glucose levels, and glycosylated hemoglobin (HbA1c). The efficacy and safety of lixisenatide once daily is being assessed in the GETGOAL Phase III clinical trial program. Results have shown beneficial effects on HbA1c compared with placebo in combination with commonly used antidiabetes agents, with no increased risk of hypoglycemia and with beneficial weight reduction. Adverse effects were similar to those observed for available GLP-1 receptor agonists, the most frequent being gastrointestinal. Both GLP-1 receptor agonists and long-acting insulin analogs have demonstrated protective effects on beta cells in preclinical studies. This, along with the pronounced effect of lixisenatide on postprandial plasma glucose, provides a rationale for combining it with long-acting basal insulin analogs, in the hope that the additive effects on glycemic control combined with a potential benefit on islet cells may lead to a new treatment approach to control blood glucose better and prevent long-term complications in patients with type 2 diabetes. © 2011 Barnett, publisher and licensee Dove Medical Press Ltd.


Jones A.W.,University of Birmingham
Journal of the American Society for Mass Spectrometry | Year: 2012

The radical ion chemistry of a suite of S-nitrosopeptides has been investigated. Doubly and triply-protonated ions of peptides NYCGLPGEYWLGNDK, NYCGLPGEYWLGNDR, NYCGLPGERWLGNDR, NACGAPGEKWAGNDK, NYCGLPGEKYLGNDK, NYGLPGCEKWYGNDK and NYGLPGEKWYGCNDK were subjected to electron capture dissociation (ECD), and collision-induced dissociation (CID). The peptide sequences were selected such that the effect of the site of S-nitrosylation, the nature and position of the basic amino acid residues, and the nature of the other amino acid side chains, could be interrogated. The ECD mass spectra were dominated by a peak corresponding to loss of (•)NO from the charge-reduced precursor, which can be explained by a modified Utah-Washington mechanism. Some backbone fragmentation in which the nitrosyl modification was preserved was also observed in the ECD of some peptides. Molecular dynamics simulations of peptide ion structure suggest that the ECD behavior was dependent on the surface accessibility of the protonated residue. CID of the S-nitrosylated peptides resulted in homolysis of the S-N bond to form a long-lived radical with loss of (•)NO. The radical peptide ions were isolated and subjected to ECD and CID. ECD of the radical peptide ions provided an interesting comparison to ECD of the unmodified peptides. The dominant process was electron capture without further dissociation (ECnoD). CID of the radical peptide ions resulted in cysteine, leucine, and asparagine side chain losses, and radical-induced backbone fragmentation at tryptophan, tyrosine, and asparagine residues, in addition to charge-directed backbone fragmentation.


Bowman S.J.,University of Birmingham
Current Pharmaceutical Biotechnology | Year: 2012

Primary Sjögren's Syndrome (PSS) is characterized by dryness of the eyes and mouth due to lymphocytic infiltration of secretory exocrine glands. As well as disabling dryness, patients commonly have fatigue and arthralgia and an associated reduction in quality of life. The condition principally affects adult women and is relatively common - approximately 1:1000 to 1:250 adult women are estimated to have the condition in European/North American studies. Current therapy is principally symptomatic with the use of artificial tears and oral gels, pastilles and sprays. Medications to stimulate residual glandular secretion can be helpful for appropriate individuals. A proportion of patients also develop extraglandular features such as skin vasculitis, or lung, neurological, haematological or other systemic involvement. Conventional general immunosuppressive therapies such as corticosteroids or disease-modifying drugs, have been used in some patients with these clinical features. Biologic therapies specifically directed against molecules involved in disease pathogenesis represent a potentially more effective approach to therapeutic intervention in rheumatic diseases including PSS. The greatest experience in PSS is with rituximab, an anti-B-cell monoclonal antibody already in use for the treatment of B-cell lymphoma and rheumatoid arthritis. A randomised placebo controlled study is currently recruiting in France and a further study is planned in the UK. This review discusses the utility of biologic therapies in PSS, potential challenges for their use, the available data on rituximab and the potential role for other biologic therapies currently in development, or in clinical trials, in other autoimmune conditions. © 2012 Bentham Science Publishers.


Quested E.,University of Birmingham
Journal of dance medicine & science : official publication of the International Association for Dance Medicine & Science | Year: 2011

Limited research has considered the social-environmental and motivational processes predictive of self evaluations and body-related concerns. Evidence suggests that low self-esteem, poor body evaluations, and associated anxieties are particularly prevalent among the student dance population. Grounded in self-determination theory (SDT), this study examined the relationships among perceptions of autonomy support, motivation regulations, and self-evaluations of body-related concerns in the context of vocational dance. Three hundred and ninety-two dancers completed questionnaires regarding their perceptions of autonomy support in their dance school, reasons for engaging in dance, self-esteem, social physique anxiety (SPA), and body dissatisfaction. Structural equation modeling analyses revealed that perceived autonomy support predicted intrinsic motivation (+) and amotivation (-). Extrinsic regulation positively predicted SPA. Amotivation mediated the associations between perceptions of autonomy support and dancers' self-esteem, SPA, and body dissatisfaction. The utility of SDT in understanding predictors of self-worth, physical evaluations, and associated concerns was supported. Moreover, this study provides preliminary evidence supporting the applicability of SDT in dance contexts.


Jeukendrup A.,Gatorade Sports Science Institute | Jeukendrup A.,University of Birmingham
Sports Medicine | Year: 2014

There have been significant changes in the understanding of the role of carbohydrates during endurance exercise in recent years, which allows for more specific and more personalized advice with regard to carbohydrate ingestion during exercise. The new proposed guidelines take into account the duration (and intensity) of exercise and advice is not restricted to the amount of carbohydrate; it also gives direction with respect to the type of carbohydrate. Studies have shown that during exercise lasting approximately 1 h in duration, a mouth rinse or small amounts of carbohydrate can result in a performance benefit. A single carbohydrate source can be oxidized at rates up to approximately 60 g/h and this is the recommendation for exercise that is more prolonged (2-3 h). For ultra-endurance events, the recommendation is higher at approximately 90 g/h. Carbohydrate ingested at such high ingestion rates must be a multiple transportable carbohydrates to allow high oxidation rates and prevent the accumulation of carbohydrate in the intestine. The source of the carbohydrate may be a liquid, semisolid, or solid, and the recommendations may need to be adjusted downward when the absolute exercise intensity is low and thus carbohydrate oxidation rates are also low. Carbohydrate intake advice is independent of body weight as well as training status. Therefore, although these guidelines apply to most athletes, they are highly dependent on the type and duration of activity. These new guidelines may replace the generic existing guidelines for carbohydrate intake during endurance exercise. © The Author(s) 2014.


Batchelor H.K.,University of Birmingham | Fotaki N.,University of Bath | Klein S.,University of Greifswald
Advanced Drug Delivery Reviews | Year: 2014

The complex process of oral drug absorption is influenced by a host of drug and formulation properties as well as their interaction with the gastrointestinal environment in terms of drug solubility, dissolution, permeability and pre-systemic metabolism. For adult dosage forms the use of biopharmaceutical tools to aid in the design and development of medicinal products is well documented. This review considers current literature evidence to guide development of bespoke paediatric biopharmaceutics tools and reviews current understanding surrounding extrapolation of adult methodology into a paediatric population. Clinical testing and the use of in silico models were also reviewed. The results demonstrate that further work is required to adequately characterise the paediatric gastrointestinal tract to ensure that biopharmaceutics tools are appropriate to predict performance within this population. The most vulnerable group was found to be neonates and infants up to 6. months where differences from adults were greatest. © 2013.


Clifford C.,University of Birmingham
European Journal of Cancer Care | Year: 2011

cancer of the vulva Cancer of the vulva is a rare condition that has been subject to limited research with a paucity of studies into the impact of this disease. Although the physical effects may readily be described, little is known about the psychological, emotional and social impact of this condition. To increase insights, a qualitative research study was undertaken to explore the experiences of women with vulval cancer living in the UK. An interpretive phenomenological approach based on the work of Heidegger and Van Manen was used to frame the study in which 13 women under 50 years of age were interviewed between 6 months and 5 years after their surgery. Data were analysed using framework analysis described by Ritchie and Spencer. This article describes the concept of aloneness which emerged from the data. This includes consideration of the women's sense of isolation due to the geographical distance between the woman's home and the hospital, and a sense of separation as they described their loss of sexual function and ability to enjoy the sexual relationship they had previously, following the onset of their symptoms of vulval cancer and subsequent treatment. The women's sense of aloneness was also manifest in their perception that there was a lack of knowledge and understanding about this condition both in their social world and the healthcare system in which they received treatment. © 2011 Blackwell Publishing Ltd.


Li G.,University of Birmingham
Nature Physics | Year: 2016

The translational Doppler effect of electromagnetic and sound waves has been successfully applied in measurements of the speed and direction of vehicles, astronomical objects and blood flow in human bodies, and for the Global Positioning System. The Doppler effect plays a key role for some important quantum phenomena such as the broadened emission spectra of atoms and has benefited cooling and trapping of atoms with laser light. Despite numerous successful applications of the translational Doppler effect, it fails to measure the rotation frequency of a spinning object when the probing wave propagates along its rotation axis. This constraint was circumvented by deploying the angular momentum of electromagnetic waves—the so-called rotational Doppler effect. Here, we report on the demonstration of rotational Doppler shift in nonlinear optics. The Doppler frequency shift is determined for the second harmonic generation of a circularly polarized beam passing through a spinning nonlinear optical crystal with three-fold rotational symmetry. We find that the second harmonic generation signal with circular polarization opposite to that of the fundamental beam experiences a Doppler shift of three times the rotation frequency of the optical crystal. This demonstration is of fundamental significance in nonlinear optics, as it provides us with insight into the interaction of light with moving media in the nonlinear optical regime. © 2016 Nature Publishing Group


Thomas G.N.,University of Birmingham
Current diabetes reviews | Year: 2010

Diabetes is reaching epidemic proportions. High risk groups, such as those older individuals or with glucose intolerance have been shown to exhibit a high risk of developing diabetes. We aimed to systematically identify and evaluate those studies that have investigated the impact of lifestyle interventions on the prevention of the development of incident Type 2 diabetes in those with glucose intolerance. Non-pharmacological lifestyle interventions, including manipulation of dietary intakes and physical activity levels are the main approaches taken to reduce the onset of diabetes in high risk groups, such as those with glucose intolerance. Intensive use of each of these lifestyle interventions have been shown to halve the risk of incident diabetes, although less intensive interventions appear to be less effective. Lifestyle modification is a useful weapon in the armoury of preventing the onset of diabetes, which is essential to reduce the associated increased risk of morbidity and mortality that might otherwise overwhelm health care systems in both developed and developing countries.


Sloan P.A.,University of Birmingham
Journal of Physics Condensed Matter | Year: 2010

Time-resolved scanning tunnelling microscopy (STM) and its application in molecular science are reviewed. STM can image individual atoms and molecules and thus is able to observe the results of molecular processes such as diffusion, desorption, configuration switching, bond-breaking and chemistry, on the atomic scale. This review will introduce time-resolved STM, its experimental limitations and implementations with particular emphasis on thermally activated and tunnelling current induced molecular processes. It will briefly examine the push towards ultrafast imaging. In general, results achieved by time-resolved STM demonstrate the necessity of both space and time resolution for fully characterizing molecular processes on the atomic scale. © 2010 IOP Publishing Ltd.


Blanch R.J.,University of Birmingham
Investigative ophthalmology & visual science | Year: 2012

Retinal injury is a common cause of profound and intractable loss of vision. Clinical outcomes are poor in both open and closed globe injuries because cell death, scarring, and a failure of tissue and axon regeneration are not ameliorated by current treatments. Much animal research is directed at understanding and modifying these pathologies, although results have yet to translate into clinical practice. Axotomy-induced retinal ganglion cell (RGC) death in mammals can be effectively reduced and axon regeneration enhanced over the short term. After retinal injury in mammals, the retinal pigment epithelium (RPE) and retinal glia either regenerate lost RPE and neuroretinal cells or form nonfunctional scars. An understanding of the mechanisms underlying injury responses is critical to the successful development of therapeutic strategies to promote ocular repair.


Turner J.E.,University of Birmingham
Medicine and science in sports and exercise | Year: 2011

The purpose of this study was to examine the short- and long-term (up to 1 month) effects of an ultraendurance running event on redox homeostasis. Markers of oxidative stress and antioxidant capacity in peripheral blood were assessed after a single-stage 233-km (143 miles) running event. Samples were collected from nine men (mean±SD: age=46.1±5.3 yr, body mass index=24.9±2.3 kg·m -2, maximal oxygen uptake=56.3±3.3 mL·kg -1·min -1). Peripheral blood mononuclear cells were assayed for nonspecific DNA damage (frank strand breaks) and damage to DNA caused specifically by oxidative stress (formamidopyrimidine DNA glycosylase-dependent damage). Protein carbonylation and lipid peroxidation were assessed in plasma. Reduced glutathione (GSH) was measured in whole blood. Peripheral blood mononuclear cell frank strand breaks were elevated above baseline at 24 h after the race (P<0.001). Formamidopyrimidine DNA glycosylase-dependent oxidative DNA damage was increased immediately after the race (P<0.05). Protein carbonylation remained elevated for 7 d after the race (P<0.04), whereas lipid peroxidation was increased for 24 h (P<0.05) and fell below baseline 28 d later (P<0.05). GSH, a measure of antioxidant capacity, also showed a biphasic response, increasing by one-third after the race (P<0.01) and falling to two-thirds of baseline levels 24 h later (P<0.001). GSH remained depleted to approximately one-third of prerace values 28 d after the race (P<0.01). Ultraendurance exercise causes oxidative stress, which persists for one calendar month depending on the specific biomarker examined. These results suggest that ultraendurance events are associated with a prolonged period of reduced protection against oxidative stress.


Alexandre D.,University of Birmingham
Nuclear Physics A | Year: 2014

Multi-strange baryons are of particular interest in the understanding of particle production mechanisms, as their high strangeness content makes them susceptible to changes in the hadrochemistry of the colliding systems. In ALICE, these hyperons are reconstructed via the detection of their weak decay products, which are identified through their measured ionisation losses and momenta in the Time Projection Chamber. The production rates of charged Ξ and Ω baryons in proton-proton (pp), proton-lead (p-Pb) and lead-lead (Pb-Pb) collisions are reported as a function of pT. A direct comparison in the hyperon-to-pion ratios between the three collision systems is made as a function of event charged-particle multiplicity. The recently measured production rates in p-Pb interactions reveal an enhancement with increasing event multiplicity, consistent with a hierarchy dependent on the strangeness content of the hyperons. These results are discussed in the context of chemical equilibrium predictions, taking into account the extracted temperature parameter from a thermal model fit to the hadron yields in Pb-Pb data. © 2014 CERN.


Loman N.J.,University of Birmingham | Quinlan A.R.,University of Virginia
Bioinformatics | Year: 2014

Motivation: Nanopore sequencing may be the next disruptive technology in genomics, owing to its ability to detect single DNA molecules without prior amplification, lack of reliance on expensive optical components, and the ability to sequence long fragments. The MinION™ from Oxford Nanopore Technologies (ONT) is the first nanopore sequencer to be commercialized and is now available to early-access users. The MinION™ is a USB-connected, portable nanopore sequencer that permits real-time analysis of streaming event data. Currently, the research community lacks a standardized toolkit for the analysis of nanopore datasets. Results: We introduce poretools, a flexible toolkit for exploring datasets generated by nanopore sequencing devices from MinION™ for the purposes of quality control and downstream analysis. Poretools operates directly on the native FAST5 (an application of the HDF5 standard) file format produced by ONT and provides a wealth of format conversion utilities and data exploration and visualization tools. © The Author 2014. Published by Oxford University Press.


Edlin R.,University of Birmingham
Health technology assessment (Winchester, England) | Year: 2010

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of azacitidine (aza) compared with conventional care regimes (CCR) for higher risk patients with myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML), based on the evidence submission from the manufacturer to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The patient outcomes governing relative effectiveness and cost-effectiveness were defined as overall survival, time to progression (TTP) to AML, adverse events and health-related quality of life (HRQoL). The clinical evidence was derived from an open-label randomised controlled trial referred to as study AZA-001. It compared aza with CCR in 358 patients with higher risk MDS, CMML and AML 20-30% blasts. The outcomes reported in AZA-001 included overall survival, TTP to AML and adverse events. No HRQoL results were reported; however, outcomes likely to impact on HRQoL were provided. The results showed that: the median overall survival was 24.5 months on aza, compared with 15.0 months in the CCR group (p = 0.0001); the response rates were low (complete remission 17% aza versus 8% CCR); the median time to transformation to AML was greater in the aza group (17.8 versus 11.5 months; p < 0.0001); and of patients who were red blood cell (RBC) transfusion-dependent at baseline, 45% of those on aza became RBC transfusion-independent during the treatment period, compared with 11.8% in the CCR group (p < 0.0001). The ERG reran the submission's search strategies after some modifications incorporating minor improvements. The ERG analysed the submitted economic model (model 1) and identified a number of inconsistencies and errors within the model. The manufacturer submitted a revised model for analysis by the ERG. Using the issues identified in the earlier analysis, the ERG conducted those repairs to the revised model that were feasible within time constraints. The ERG ran this version in probabilistic sensitivity analyses to generate cost-effectiveness acceptability frontiers. The results of these exploratory analyses indicated that: for standard-dose chemotherapy (SDC)-treated patients, of six treatment options available, best supportive care (BSC) was likely the most cost-effective option up to a threshold of 51,000 pounds/quality-adjusted life-year (QALY) [beyond 51,000 pounds/QALY, aza + low-dose chemotherapy (LDC) became cost-effective]; for LDC-treated patients, of four options available, BSC was again the most cost-effective option up to a willingness-to-pay threshold of 51,000 pounds/QALY (aza + LDC became cost-effective after 51,000 pounds/QALY); for BSC-treated patients, aza + BSC became cost-effective relative to BSC at a threshold of about 52,000 pounds/QALY. The ERG considers these results exploratory and considers that they should be viewed with caution. The AZA-001 study showed that, compared with CCR, those MDS patients receiving aza had prolonged median survival, had delayed progression to AML, had reduced dependence on transfusions and had a small improvement in response rate. Given the general paucity of economic modelling work in MDS and the limitations of the submitted industry model there is an evident need for an independent cost-effectiveness analysis of aza in MDS. At the time of writing, the guidance appraisal consultation document issued by NICE on 4 March 2010 states that azacitidine is not recommended as a treatment option for people not eligible for haemopoietic stem cell transplantation with the the following conditions: intermediate-2 and high-risk MDS according to the International Prognostic Scoring System, CMML with 10-29% marrow blasts without myeloproliferative disorder, or with AML with 20-30% blasts and multilineage dysplasia, according to World Health Organization classification.


Cytomegalovirus infection is very common and leads to the generation of a very strong humoral and cellular immune response that is maintained for life and appears necessary to control viral replication. This leads to marked alterations in the composition of the immune cell repertoire and epidemiological evidence shows that this can be associated with increased levels of morbidity and mortality in the elderly. The immune response appears to be triggered by frequent episodes of subclinical viral reactivation and the predominant effect is of the accumulation of large numbers of cytotoxic cells. These observations suggest that mechanisms that could serve to control the expansion of this immune response could have significant potential in improving the health of elderly donors. © 2010.


Taylor G.,University of Birmingham
BMJ (Clinical research ed.) | Year: 2014

To investigate change in mental health after smoking cessation compared with continuing to smoke. Systematic review and meta-analysis of observational studies. Web of Science, Cochrane Central Register of Controlled Trials, Medline, Embase, and PsycINFO for relevant studies from inception to April 2012. Reference lists of included studies were hand searched, and authors were contacted when insufficient data were reported. Longitudinal studies of adults that assessed mental health before smoking cessation and at least six weeks after cessation or baseline in healthy and clinical populations. 26 studies that assessed mental health with questionnaires designed to measure anxiety, depression, mixed anxiety and depression, psychological quality of life, positive affect, and stress were included. Follow-up mental health scores were measured between seven weeks and nine years after baseline. Anxiety, depression, mixed anxiety and depression, and stress significantly decreased between baseline and follow-up in quitters compared with continuing smokers: the standardised mean differences (95% confidence intervals) were anxiety -0.37 (95% confidence interval -0.70 to -0.03); depression -0.25 (-0.37 to -0.12); mixed anxiety and depression -0.31 (-0.47 to -0.14); stress -0.27 (-0.40 to -0.13). Both psychological quality of life and positive affect significantly increased between baseline and follow-up in quitters compared with continuing smokers 0.22 (0.09 to 0.36) and 0.40 (0.09 to 0.71), respectively). There was no evidence that the effect size differed between the general population and populations with physical or psychiatric disorders. Smoking cessation is associated with reduced depression, anxiety, and stress and improved positive mood and quality of life compared with continuing to smoke. The effect size seems as large for those with psychiatric disorders as those without. The effect sizes are equal or larger than those of antidepressant treatment for mood and anxiety disorders.


Reynolds R.F.,University of Birmingham
Gait and Posture | Year: 2010

Standing sway can be reduced simply by conscious effort but the extent to which this ability changes with stance conditions is unknown. Here, the influence of stance width and vision upon the ability to voluntarily reduce sway was investigated. 14 subjects were asked to stand either relaxed or still. Three stance conditions (wide/narrow/tandem) were compared, with eyes open or closed. When standing still, subjects successfully reduced body sway by up to 24% (root mean square of lateral trunk velocity), primarily by attenuating their peak sway frequency (0.2-0.4 Hz). Standing still was associated with a mean increase in ankle muscle co-contraction, but the extent of this increase did not correlate with the ability to reduce sway for individual subjects. Within each stance condition, subjects who swayed more when relaxed also displayed the greatest scope for sway reduction when asked to stand still. However, the opposite trend was observed across conditions: as relaxed sway increased, the capacity for sway reduction was reduced. Hence, voluntary control was lowest during tandem stance and greatest with feet apart, an effect augmented by eye closure. The results show that the degree to which sway can be voluntarily modified is not fixed, but reflects the difficulty of the standing task. © 2009 Elsevier B.V. All rights reserved.


Kendall K.,University of Birmingham
International Journal of Applied Ceramic Technology | Year: 2010

The benefits of microtubular solid oxide fuel cells (SOFCs) are addressed, including increased power density, rapid start-up, and cycling performance. Several international developments are discussed, especially small portable applications, which demand fast start and multiple cycles. Extrusion is the main method for making microtubular SOFCs because improved structure and properties can result from better mixing of the component particles and coextrusion can integrate several cell components in one process step. When the tubes are <3 mm in diameter, it is shown that the power density and thermal shock resistance are much increased, with start-up in a few seconds rather than hours for planar designs, as demonstrated in a single-cell hand-held system running on butane. The problems of cycling, both thermal and redox, are then considered in detail. Thermal cycling degradation follows a fatigue curve whereas redox damage is linear with the number of cycles. New results are presented on thermal and redox cycling performance. © 2009 The American Ceramic Society.


Connock M.,University of Birmingham
Health technology assessment (Winchester, England) | Year: 2010

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of certolizumab pegol (CZP) for adults with active rheumatoid arthritis (RA) that have not responded adequately to treatment with conventional disease modifying anti-rheumatic drugs (DMARDs) including methotrexate (MTX), in accordance with the licensed indication, based upon the evidence submission from the manufacturer to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The outcome measures included American College of Rheumatology (ACR) 20, 50 and 70 response rates and quality of life measures after 3 months and 6 months of treatment. The ERG examined the submission's search strategies and considered they appeared comprehensive and that it was unlikely that relevant studies would have been missed. Only English language studies were considered in the submission and non-English language studies relevant to the decision problem may possibly have been ignored. The ERG analysed the first submitted economic model so as to itemise in detail clarification points that were brought to the attention of the manufacturer. In response the manufacturer submitted a modified cost-effectiveness analysis. The ERG undertook further analysis of this second model and other additional submitted evidence. The clinical evidence was derived from two multicentre blinded randomised controlled trials (RCTs) comparing CZP + MTX to placebo + MTX (the RAPID 1 and RAPID 2 trials). RAPID 1 lasted 52 weeks with 982 patients and RAPID 2 24 weeks with 619 patients. Evidence for clinical effectiveness of CZP in mono-therapy came from the 24-week FAST4WARD trial with 220 patients that compared CZP (400 mg every 4 weeks) versus placebo. The three key RCTs demonstrated statistically significant superiority of CZP + MTX versus placebo + MTX and of CZP versus placebo with respect to a variety of outcomes including ACR 20, ACR 50 and ACR 70 measures and quality of life measures at 3 and 6 months. On the basis of results from the indirect comparison meta-analyses, the manufacturer suggested that CZP may be at least as effective as other 'biological' DMARD (bDMARD) comparators and, in a few ACR measures at 3 and 6 months, more effective. CZP is an effective therapy for adult RA patients whose disease has failed to respond adequately to cDMARDs including MTX or who are intolerant of MTX. The cost-effectiveness of CZP relative to other bDMARDs is unclear because the economic modelling undertaken may have ignored relevant effectiveness data and potential differences between trial populations, and so may have included effectiveness results that were biased in favour of CZP; underestimated uncertainty in the relative effectiveness of compared DMARDs; and ignored the potential influence of differences between bDMARDs with regard to adverse events and their related costs and health impacts. The NICE guidance issued in October 2009 states that: the Committee is minded not to recommend certolizumab pegol as a treatment option for people with RA; and the Committee recommends that NICE asks the manufacturer of CZP for more information on the clinical effectiveness and cost-effectiveness of CZP for the treatment of people with RA. On receipt of this information and details of a patient access scheme NICE issued final guidance recommending CZP, under certain criteria, as a treatment option for people with RA.


Jones S.,University of Birmingham | Rappoport J.Z.,Northwestern University
International Journal of Biochemistry and Cell Biology | Year: 2014

Epidermal growth factor (EGF) receptor (EGFR) signalling regulates diverse cellular functions, promoting cell proliferation, differentiation, migration, cell growth and survival. EGFR signalling is critical during embryogenesis, in particular in epithelial development, and disruption of the EGFR gene results in epithelial immaturity and perinatal death. EGFR signalling also functions during wound healing responses through accelerating wound re-epithelialisation, inducing cell migration, proliferation and angiogenesis. Upregulation of EGFR signalling is often observed in carcinomas and has been shown to promote uncontrolled cell proliferation and metastasis. Therefore aberrant EGFR signalling is a common target for anticancer therapies. Various reports indicate that EGFR signalling primarily occurs at the plasma membrane and EGFR degradation following endocytosis greatly attenuates signalling. Other studies argue that EGFR internalisation is essential for complete activation of downstream signalling cascades and that endosomes can serve as signalling platforms. The aim of this review is to discuss current understanding of intersection between EGFR signalling and trafficking. © 2014 Elsevier Ltd.


Toke D.,University of Birmingham
Environmental Politics | Year: 2011

Ecological modernisation (EM) theory has involved a debate about the relative importance of concentrating on incorporating technological change into mainstream industry and, on the other hand, developing 'reflexive' capacities for debate involving social movements (SMs). However, such discussions may obscure the need to study the involvement of SMs in the development and deployment of 'ecological' technologies themselves. This issue is investigated through an analysis of renewable energy, principally wind power. SM involvement in eco-technological development and implementation may be understated by EM theory. © 2011 Taylor & Francis.


Prediction of transcription factor binding sites is an important challenge in genome analysis. The advent of next generation genome sequencing technologies makes the development of effective computational approaches particularly imperative. We have developed a novel training-based methodology intended for prokaryotic transcription factor binding site prediction. Our methodology extends existing models by taking into account base interdependencies between neighbouring positions using conditional probabilities and includes genomic background weighting. This has been tested against other existing and novel methodologies including position-specific weight matrices, first-order Hidden Markov Models and joint probability models. We have also tested the use of gapped and ungapped alignments and the inclusion or exclusion of background weighting. We show that our best method enhances binding site prediction for all of the 22 Escherichia coli transcription factors with at least 20 known binding sites, with many showing substantial improvements. We highlight the advantage of using block alignments of binding sites over gapped alignments to capture neighbouring position interdependencies. We also show that combining these methods with ChIP-on-chip data has the potential to further improve binding site prediction. Finally we have developed the ungapped likelihood under positional background platform: a user friendly website that gives access to the prediction method devised in this work.


Leyva F.,University of Birmingham
Journal of Cardiovascular Magnetic Resonance | Year: 2010

Cardiac resynchronization therapy (CRT) is an established treatment for patients with symptomatic heart failure, severely impaired left ventricular (LV) systolic dysfunction and a wide (> 120 ms) complex. As with any other treatment, the response to CRT is variable. The degree of pre-implant mechanical dyssynchrony, scar burden and scar localization to the vicinity of the LV pacing stimulus are known to influence response and outcome. In addition to its recognized role in the assessment of LV structure and function as well as myocardial scar, cardiovascular magnetic resonance (CMR) can be used to quantify global and regional LV dyssynchrony. This review focuses on the role of CMR in the assessment of patients undergoing CRT, with emphasis on risk stratification and LV lead deployment. © 2010 Leyva; licensee BioMed Central Ltd.


Hemming K.,University of Birmingham
Cochrane database of systematic reviews (Online) | Year: 2013

Epilepsy is a common neurological condition which affects between 0.5% and 1% of the population. Approximately 30% of people with epilepsy do not respond to treatment with currently available drugs. The majority of these people have partial epilepsy. Vigabatrin is an antiepileptic drug licensed for use in the treatment of refractory epilepsy. No major side effects associated with the use of vigabatrin were detected by initial randomised controlled trials of the drug. However, longer-term observational studies have subsequently identified that its use is associated with asymptomatic visual field constriction. The objective of this review was to synthesise evidence from short-term, randomised, placebo-controlled trials of vigabatrin. We summarised the effects of vigabatrin on seizures and short-term side effects when used as an add-on treatment for people with drug-resistant partial epilepsy. A review of longer-term observational studies and estimates of proportions of patients developing visual field constrictions is currently being undertaken and results will be cited in this review in due course. We searched the Cochrane Epilepsy Group Specialised Register (12 October 2012), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 9), MEDLINE (1946 to October week 1, 2012) and reference lists of articles. We also contacted the manufacturers of vigabatrin (Hoechst Marion Roussel). We included randomised, double-blind, placebo-controlled, fully published trials of vigabatrin in people with drug-resistant partial epilepsy. Two review authors assessed trials for inclusion and extracted data. Primary analysis was by intention-to-treat (ITT). Outcomes evaluated included 50% or greater reduction in seizure frequency, treatment withdrawal and side effects observable in the short term. Results are presented on the risk ratio (RR) scale with 95% or 99% confidence intervals (CI). Eleven suitable trials that tested vigabatrin doses between 1000 mg and 6000 mg were identified and included in the analysis. There were 982 observations on 747 patients in the primary ITT analysis of treatment efficacy. Patients treated with vigabatrin were significantly more likely to obtain a 50% or greater reduction in seizure frequency compared with those treated with placebo (RR 2.58, 95% CI 1.87 to 3.57). Those treated with vigabatrin were also significantly more likely to have treatment withdrawn (RR 2.49, 95% CI 1.05 to 5.88), and were more likely to experience a number of side effects, significantly so for fatigue or drowsiness. There was some evidence of small study effect bias, with smaller studies tending to report greater estimates of RR than larger studies. It is possible, therefore, that the actual RR of obtaining 50% reduction in seizure frequency is less than that obtained by a meta-analysis of fully published studies. This review of randomised controlled trials showed that vigabatrin can reduce seizure frequency in people with drug-resistant partial epilepsy. Short-term follow-up of patients showed that some side effects were associated with its use. Further analysis of longer-term observational studies is required to evaluate how likely patients are to develop visual field defects and whether such side effects are associated with dose and duration of drug use.


Derbyshire S.W.G.,University of Birmingham
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2010

The majority of commentary on foetal pain has looked at the maturation of neural pathways to decide a lower age limit for foetal pain. This approach is sensible because there must be a minimal necessary neural development that makes pain possible. Very broadly, it is generally agreed that the minimal necessary neural pathways for pain are in place by 24 weeks gestation. Arguments remain, however, as to the possibility of foetal pain before or after 24 weeks. Some argue that the foetus can feel pain earlier than 24 weeks because pain can be supported by subcortical structures. Others argue that the foetus cannot feel pain at any stage because it is maintained in a state of sedation in the womb and lacks further neural and conceptual development necessary for pain. Much of this argument rests on the definition of terms such as 'wakefulness' and 'pain'. If a behavioural and neural reaction to a noxious stimulus is considered sufficient for pain, then pain is possible from 24 weeks and probably much earlier. If a conceptual subjectivity is considered necessary for pain, however, then pain is not possible at any gestational age. Regardless of how pain is defined, it is clear that pain for conceptual beings is qualitatively different than pain for non-conceptual beings. It is therefore a mistake to draw an equivalence between foetal pain and pain in the older infant or adult. © 2010 Elsevier Ltd.


Tomlinson C.L.,University of Birmingham
The Cochrane database of systematic reviews | Year: 2013

Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. Physiotherapy aims to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety, and well-being, thereby enhancing quality of life. To assess the effectiveness of physiotherapy intervention compared with no intervention in patients with PD. We identified relevant trials by conducting electronic searches of numerous literature databases (e.g. MEDLINE, EMBASE) and trial registers, and by handsearching major journals, abstract books, conference proceedings, and reference lists of retrieved publications. The literature search included trials published up to the end of January 2012. Randomised controlled trials of physiotherapy intervention versus no physiotherapy intervention in patients with PD. Two review authors independently extracted data from each article. We used standard meta-analysis methods to assess the effectiveness of physiotherapy intervention compared with no physiotherapy intervention. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance, and martial arts. We used tests for heterogeneity to assess for differences in treatment effect across these different physiotherapy interventions. We identified 39 trials with 1827 participants. We considered the trials to be at a mixed risk of bias as the result of unreported allocation concealment and probable detection bias. Compared with no intervention, physiotherapy significantly improved the gait outcomes of speed (mean difference 0.04 m/s, 95% confidence interval (CI) 0.02 to 0.06, P = 0.0002); two- or six-minute walk test (13.37 m, 95% CI 0.55 to 26.20, P = 0.04) and Freezing of Gait questionnaire (-1.41, 95% CI -2.63 to -0.19, P = 0.02); functional mobility and balance outcomes of Timed Up & Go test (-0.63 s, 95% CI -1.05 to -0.21, P = 0.003), Functional Reach Test (2.16 cm, 95% CI 0.89 to 3.43, P = 0.0008), and Berg Balance Scale (3.71 points, 95% CI 2.30 to 5.11, P < 0.00001); and clinician-rated disability using the Unified Parkinson's Disease Rating Scale (UPDRS) (total -6.15 points, 95% CI-8.57 to -3.73, P < 0.00001; activities of daily living: -1.36, 95% CI -2.41 to -0.30, P = 0.01; and motor: -5.01, 95% CI -6.30 to -3.72, P < 0.00001). No difference between arms was noted in falls (Falls Efficacy Scale: -1.91 points, 95% CI -4.76 to 0.94, P = 0.19) or patient-rated quality of life (PDQ-39 Summary Index: -0.38 points, 95% CI -2.58 to 1.81, P = 0.73). One study reported that adverse events were rare; no other studies reported data on this outcome. Indirect comparisons of the different physiotherapy interventions revealed no evidence that the treatment effect differed across physiotherapy interventions for any of the outcomes assessed. Benefit for physiotherapy was found in most outcomes over the short term (i.e. < 3 months) but was significant only for speed, two- or six-minute walk test, Freezing of Gait questionnaire, Timed Up & Go, Functional Reach Test, Berg Balance Scale, and clinician-rated UPDRS. Most of the observed differences between treatments were small. However, for some outcomes (e.g. speed, Berg Balance Scale, UPDRS), the differences observed were at, or approaching, what are considered minimal clinically important changes. These benefits should be interpreted with caution because the quality of most of the included trials was not high. Variation in measurements of outcome between studies meant that our analyses include a small proportion of the participants recruited.This review illustrates that a wide range of approaches are employed by physiotherapists to treat patients with PD. However, no evidence of differences in treatment effect was noted between the different types of physiotherapy interventions being used, although this was based on indirect comparisons. A consensus menu of 'best practice' physiotherapy is needed, as are large, well-designed randomised controlled trials undertaken to demonstrate the longer-term efficacy and cost-effectiveness of 'best practice' physiotherapy in PD.


Egginton S.,University of Birmingham
Acta physiologica (Oxford, England) | Year: 2011

(1) Angiogenesis (growth of new capillaries from an existing capillary bed) may result from a mismatch in microvascular supply and metabolic demand (metabolic error signal). Krogh examined the distribution and number of capillaries to explore the correlation between O(2) delivery and O(2) consumption. Subsequently, the heterogeneity in angiogenic response within a muscle has been shown to reflect either differences in fibre type composition or mechanical load. However, local control leads to targetted angiogenesis in the vicinity of glycolytic fibre types following muscle stimulation, or oxidative fibres following endurance training, while heterogeneity of capillary spacing is maintained during ontogenetic growth. (2) Despite limited microscopy resolution and lack of specific markers, Krogh's interest in the structure of the capillary wall paved the way for understanding the mechanisms of capillary growth. Angiogenesis may be influenced by the response of perivascular or stromal cells (fibroblasts, macrophages and pericytes) to altered activity, likely acting as a source for chemical signals modulating capillary growth such as vascular endothelial growth factor. In addition, haemodynamic factors such as shear stress and muscle stretch play a significant role in adaptive remodelling of the microcirculation. (3) Most indices of capillarity are highly dependent on fibre size, resulting in possible bias because of scaling. To examine the consequences of capillary distribution, it is therefore helpful to quantify the area of tissue supplied by individual capillaries. This allows the spatial limitations inherent in most models of tissue oxygenation to be overcome generating an alternative approach to Krogh's tissue cylinder, the capillary domain, to improve descriptions of intracellular oxygen diffusion. © 2010 The Author. Acta Physiologica © 2010 Scandinavian Physiological Society.


Jackson J.B.,University of Birmingham
Biochimica et Biophysica Acta - Bioenergetics | Year: 2012

Proton-translocating transhydrogenase is found in the inner membranes of animal mitochondria, and in the cytoplasmic membranes of many bacteria. It catalyses hydride transfer from NADH to NADP+ coupled to inward proton translocation. Evidence is reviewed suggesting the enzyme operates by a binding-change mechanism. Experiments with Escherichia coli transhydrogenase indicate the enzyme is driven between open and occluded states by protonation and deprotonation reactions associated with proton translocation. In the open states NADP+/NADPH can rapidly associate with, or dissociate from, the enzyme, and hydride transfer is prevented. In the occluded states bound NADP+/NADPH cannot dissociate, and hydride transfer is allowed. Crystal structures of a complex of the nucleotide-binding components of Rhodospirillum rubrum transhydrogenase show how hydride transfer is enabled and disabled at appropriate steps in catalysis, and how release of NADP +/NADPH is restricted in the occluded state. Thermodynamic and kinetic studies indicate that the equilibrium constant for hydride transfer on the enzyme is elevated as a consequence of the tight binding of NADPH relative to NADP+. The protonation site in the translocation pathway must face the outside if NADP+ is bound, the inside if NADPH is bound. Chemical shift changes detected by NMR may show where alterations in protein conformation resulting from NADP+ reduction are initiated. © 2012 Elsevier B.V. All rights reserved.


Parker R.,University of Birmingham
Clinics in Liver Disease | Year: 2014

A transjugular intrahepatic portosystemic shunt (TIPS) is an expandable metal stent inserted via the jugular vein that creates a shunt from the portal vein to the systemic circulation via an artificial communication through the liver. It is used to treat complications of portal hypertension. In addition to rescue treatment in variceal bleeding, TIPS can play an important role in prevention of rebleeding. TIPS can improve symptoms if medical treatment of ascites or hepatic hydrothrorax has failed, but may not improve survival. Selected cases of Budd-Chiari syndrome improve with TIPS. This article discusses the indications, evidence, and complications of TIPS. © 2014 Elsevier Inc.


Armstrong M.J.,University of Birmingham | Adams L.A.,University of Western Australia | Canbay A.,University of Duisburg - Essen | Syn W.-K.,Institute of Hepatology
Hepatology | Year: 2014

Nonalcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease, and is strongly associated with the metabolic syndrome. In the last decade, it has become apparent that the clinical burden of NAFLD is not restricted to liver-related morbidity or mortality, and the majority of deaths in NAFLD patients are related to cardiovascular disease (CVD) and cancer. These findings have fuelled concerns that NAFLD may be a new, and added risk factor for extrahepatic diseases such as CVD, chronic kidney disease (CKD), colorectal cancer, endocrinopathies (including type 2 diabetes mellitus [T2DM] and thyroid dysfunction), and osteoporosis. In this review we critically appraise key studies on NAFLD-associated extrahepatic disease. There was marked heterogeneity between studies in study design (cross-sectional versus prospective; sample size; presence/absence of well-defined controls), population (ethnic diversity; community-based versus hospital-based cohorts), and method of NAFLD diagnosis (liver enzymes versus imaging versus biopsy). Taking this into account, the cumulative evidence to date suggests that individuals with NAFLD (specifically, nonalcoholic steatohepatitis) harbor an increased and independent risk of developing CVD, T2DM, CKD, and colorectal neoplasms. We propose future studies are necessary to better understand these risks, and suggest an example of a screening strategy. (Hepatology 2014;59:1174-1197) © 2014 by the American Association for the Study of Liver Diseases.


Lovering A.L.,University of Birmingham | Safadi S.S.,University of British Columbia | Strynadka N.C.J.,University of British Columbia
Annual Review of Biochemistry | Year: 2012

The peptidoglycan biosynthetic pathway is a critical process in the bacterial cell and is exploited as a target for the design of antibiotics. This pathway culminates in the production of the peptidoglycan layer, which is composed of polymerized glycan chains with cross-linked peptide substituents. This layer forms the major structural component of the protective barrier known as the cell wall. Disruption in the assembly of the peptidoglycan layer causes a weakened cell wall and subsequent bacterial lysis. With bacteria responsible for both properly functioning human health (probiotic strains) and potentially serious illness (pathogenic strains), a delicate balance is necessary during clinical intervention. Recent research has furthered our understanding of the precise molecular structures, mechanisms of action, and functional interactions involved in peptidoglycan biosynthesis. This research is helping guide our understanding of how to capitalize on peptidoglycan-based therapeutics and, at a more fundamental level, of the complex machinery that creates this critical barrier for bacterial survival. © 2012 by Annual Reviews. All rights reserved.


Winer J.B.,University of Birmingham
Journal of Neuroimmunology | Year: 2011

Numerous clinical subtypes of Guillain-Barré syndrome have been described over the century since the original description of the syndrome. These variants of Guillain-Barré syndrome are discussed and their immunological pathogenesis reviewed. © 2010 Elsevier B.V.


Bowery N.G.,University of Birmingham
Advances in Pharmacology | Year: 2010

This chapter forms an introduction to the subsequent chapters in this volume which highlight the significance and potential therapeutic application of GABAB receptors. It is now 30 years since the GABAB site was first described in mammalian tissue. Since then much has emerged about its physiological role in the mammalian nervous system and its relationship to other neurotransmitter receptors. It appears to function at pre- and postsynaptic locations as both an auto- and a hetero-receptor where its activation modulates the membrane conductance of Ca2+ and K+. The receptor is G-protein coupled and was the first to be shown to exist, possibly in multiple forms, as a heterodimer. The primary agonist for the receptor is baclofen and this continues to be used therapeutically as a centrally active muscle relaxant. Other potential applications for agonists are suggested and positive allosteric modulators may provide an alternative and more effective approach. One application of an agonist, for which there are strong positive clinical data, is in gastroesophageal reflux disease where the receptor target is outside the brain. Antagonists of the GABAB receptor may also have therapeutic applications such as in cognitive deficits, affective disorders, and absence seizures but robust clinical evidence remains to be demonstrated. Each of these applications is also discussed in the chapters that follow. © 2010 Elsevier Inc.


Kenyon S.,University of Birmingham
The Cochrane database of systematic reviews | Year: 2013

A major cause of failure to achieve spontaneous vaginal birth is delay in labour due to presumed inefficient uterine action. Oxytocin is given to increase contractions and high-dose regimens may potentially increase the number of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the uterus, there is a possibility of increased adverse events. To compare starting dose and increment dose of oxytocin for augmentation for women delayed in labour to determine whether augmentation by high-dose regimens of oxytocin improves labour outcomes and to examine the effect on both maternal/neonatal outcomes and women's birth experiences. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. We included all randomised and quasi-randomised controlled trials for women in delayed labour requiring augmentation by oxytocin comparing high-dose regimens (defined as starting dose and increment of equal to or more than 4 mU per minute) with low-dose regimens (defined as starting dose and an increment of less than 4 mU per minute). Increase interval: between 15 and 40 minutes. The separation of low- and high-dose regimens is based on an arbitrary decision. Four review authors undertook assessment of trial eligibility, risk of bias, and data extraction independently. We included four studies involving 644 pregnant women. Three studies were randomised controlled trials and one trial was a quasi-randomised study. A higher dose of oxytocin was associated with a significant reduction in length of labour reported from one trial (mean difference (MD) -3.50 hours; 95% confidence interval (CI) -6.38 to -0.62; one trial, 40 women). There was a decrease in the rate of caesarean section (risk ratio (RR) 0.62; 95% CI 0.44 to 0.86 four trials, 644 women) and an increase in the rate of spontaneous vaginal birth in the high-dose group (RR 1.35; 95% CI 1.13 to 1.62, three trials, 444 women), although for both of these outcomes there were inconsistencies between studies in the size of effect. When we carried out sensitivity analysis (temporarily removing a study at high risk of bias) the differences between groups were no longer statistically significantThere were no significant differences between high- and low-dose regimens for instrumental vaginal birth, epidural analgesia, hyperstimulation, postpartum haemorrhage, chorioamnionitis or women's perceptions of experiences. For neonatal outcomes, there was no significant difference between groups for Apgar scores, umbilical cord pH, admission to special care baby unit, or neonatal mortality. The following outcomes were not evaluated in the included studies: perinatal mortality, uterine rupture, abnormal cardiotocography, women's pyrexia, dystocia and neonatal neurological morbidity. Higher-dose regimens of oxytocin (4 mU per minute or more) were associated with a reduction in the length of labour and in caesarean section, and an increase in spontaneous vaginal birth. However, there is insufficient evidence to recommend that high-dose regimens are advised routinely for women with delay in the first stage of labour. Further research should evaluate the effect of high-dose regimens of oxytocin for women delayed in labour and should include maternal and neonatal outcomes as well as the effects on women.


van der Horst D.,University of Birmingham
Applied Geography | Year: 2011

Many governments are now offering incentive payments to private land owners to adapt their management of the land in such a way as to safeguard or enhance ecosystem service provision. These payments are offered to individual land owners, whose decisions may be influenced by economic rationality, but also other factors. Understanding factors such as social capital and neighbourhood networks is particularly relevant as these can help to create local patterns of high and coordinated uptake. This is important because the delivery of many ecosystem services depends on spatial patterns of interventions at the landscape scale, i.e. at spatial scales of multiple farms. To date little empirical work has been carried out to estimate the extent and relative importance of local land owner networks on entry into ecosystem services payment schemes. This study demonstrates a method to detect possible relationships between farm locations and the time of adoption. Based on Thorsten Hagerstrand's model of innovation diffusion as a spatio-temporal process, a simulation approach is used to detect spatio-temporal clustering in the uptake of a case study ESP scheme, the Environmentally Sensitive Area (ESA) scheme in Scotland. The analysis reveals clear spatio-temporal uptake patterns at different spatial scales and in different types of rural spaces. It is argued that these findings have relevance for local adaptation of policies, both to liaise more effectively with sections of the farming community, and to achieve better uptake patterns at the landscape scale. © 2010 Elsevier Ltd.


Cooper M.S.,University of Birmingham
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2011

Pregnancy and lactation are associated with profound changes in calcium physiology. This can make interpretation of biochemical tests difficult during these times. Diseases of bone and calcium metabolism are uncommon during pregnancy but can be severe when they occur. These conditions are complicated by the need for dual consideration for the maternal and foetal health. These conditions are also much less well studied than related conditions that occur outside of pregnancy resulting in a reduction in evidence for and confidence in recommendations relating to management. This chapter will review the changes in calcium physiology that occur with pregnancy and lactation, describe the disorders of calcium and parathyroid physiology that can occur and outline the most appropriate way to manage these conditions. © 2011 Elsevier Ltd. All rights reserved.


Smith W.R.,University of Birmingham
Journal of Fluid Mechanics | Year: 2010

Large-amplitude oscillations of incompressible viscous drops are studied at small capillary number. On the long viscous time scale, a formal perturbation scheme is developed to determine original modulation equations. These two ordinary differential equations comprise the averaged condition for conservation of energy and the averaged projection of the Navier-Stokes equations onto the vorticity vector. The modulation equations are applied to the free decay of axisymmetric oblate-prolate spheroid oscillations. On the long time scale, only the modulation equation for energy is required. In this example, the results compare well with linear viscous theory, weakly nonlinear inviscid theory and experimental observations. The new results show that previous experimental observations and numerical simulations are all manifestations of a single-valued relationship between dimensionless decay rate and amplitude. Moreover, if the amplitude of the oscillations does not exceed 30% of the drop radius, this decay rate may be approximated by a quadratic. The new results also show that, when the amplitude of the oscillations exceeds 20% of the drop radius, fluid in the inviscid bulk of the drop is undergoing abrupt changes in its acceleration in comparison to the acceleration during small-amplitude deformations. © 2010 Cambridge University Press.


Mouhot J.-F.,University of Birmingham
Climatic Change | Year: 2011

The first part of the paper demonstrates the connection between the abolition of slavery and the Industrial Revolution: steam power changed the perception of labour; new techniques facilitated diffusion of pro-abolition pamphlets; fewer threats to basic existence resulting from industrial advances fostered sensibilities and moral standards toward abolitionism; and, through industrial development, the North grasped victory in the American Civil War. The second part presents similarities between societies in the past that have used slave labour and those in the present that use fossil fuels. It argues that slaves and fossil-fuelled machines play(ed) similar economic and social roles: both slave societies and developed countries externalise(d) labour and both slaves and modern machines free(d) their owners from daily chores. Consequently, we are as dependent on fossil fuels as slave societies were dependent on bonded labour. It also suggests that, in differing ways, suffering resulting (directly) from slavery and (indirectly) from the excessive burning of fossil fuels are now morally comparable. When we emit carbon dioxide at a rate that exceeds what the ecosystem can absorb, when we deplete non-renewable resources, we indirectly cause suffering to other human beings. Similarly, cheap oil facilitates imports of goods from countries with little social protection and hence help externalise oppression. The conclusion draws on the lessons which may be learned by Climate Change campaigners from the campaigns to abolish slavery: environmental apathy can be opposed effectively if we learn from what worked in the fight against this inhuman institution. © 2010 Springer Science+Business Media B.V.


Acute coronary artery obstruction at the time of device implantation is a recognized, albeit rare, complication of TAVI and is most frequently managed by emergency percutaneous intervention. This complication usually manifests with circulatory collapse due to compromising left ventricular ischemia and is most often observed immediately following valve deployment in the catheter laboratory or in theater. Immediate circulatory support is often necessary. We describe the first report of delayed left main stem obstruction 3.5 hours after successful deployment of a 26 mm Edwards SAPIEN XT valve via transfemoral implantation, with sudden development of circulatory collapse on the ward. Circulatory support was rapidly and effectively instituted with an automated non-invasive cardiac massage device, AutoPulse, that delivers continuous chest compressions. Successful emergency percutaneous intervention was then undertaken to the left main stem to displace a calcified nodule during automated external cardiac massage with the AutoPulse.


Anderson M.C.,University of Cambridge | Hanslmayr S.,University of Birmingham | Hanslmayr S.,University of Konstanz
Trends in Cognitive Sciences | Year: 2014

Not all memories are equally welcome in awareness. People limit the time they spend thinking about unpleasant experiences, a process that begins during encoding, but that continues when cues later remind someone of the memory. Here, we review the emerging behavioural and neuroimaging evidence that suppressing awareness of an unwelcome memory, at encoding or retrieval, is achieved by inhibitory control processes mediated by the lateral prefrontal cortex. These mechanisms interact with neural structures that represent experiences in memory, disrupting traces that support retention. Thus, mechanisms engaged to regulate momentary awareness introduce lasting biases in which experiences remain accessible. We argue that theories of forgetting that neglect the motivated control of awareness omit a powerful force shaping the retention of our past. © 2014 The Authors.


Evans J.,University of Manchester | Jones P.,University of Birmingham
Applied Geography | Year: 2011

Social scientists have begun engaging with participants 'on the move' in a variety of ways. This paper presents the results of a pilot study, which deployed a qualitative GIS technique to analyse the effectiveness of walked interviews in capturing data relating to people's understanding of place. We give an account of the walking interview exploring two issues: the relationship between what people say and where they say it; and qualitative and quantitative differences between data generated by walking and sedentary interviews. Our results indicate that the data generated through walking interviews are profoundly informed by the landscapes in which they take place, emphasising the importance of environmental features in shaping discussions. We also demonstrate a measureable difference between walking and sedentary techniques in the production of rich place narratives both in terms of their quantity and spatial specificity to the study area. The paper concludes by acknowledging that a technocentric analysis of place runs the risk of emphasising locational above humanistic elements, but argues that, done sensitively, a qualitative GIS approach offers great potential for engaging planners and policy makers with the importance of local connections to place. © 2010 Elsevier Ltd.


Cai X.-M.,University of Birmingham
Boundary-Layer Meteorology | Year: 2012

We develop a large-eddy simulation (LES) model based on a meteorological numerical model for a real scale street-canyon flow with rough building facets heated by a given temperature. The model is applied to a canyon with the aspect ratio of unity for two idealized heating scenarios: (1) the roof and the entire upstream wall are heated, named as 'assisting cases', and (2) the roof and the entire downstream wall are heated, named as 'opposing cases'. These facets were heated up to 15 K above the air temperature. A wall function for temperature is proposed for a rough facet with an assumption that the thermal roughness length, z 0T, is much smaller than the aerodynamic roughness length, z 0. It is demonstrated that the sensible heat flux and canyon-air temperature are significantly influenced by the near-facet process that is parametrized by z 0T as the primary factor; other processes such as in-canyon mixing and roof-level exchange are secondary. This new finding strongly suggests that it is vital to choose an appropriate value of z 0T in a numerical simulation of street-canyon flows with the facet-air exchange processes of heat or any scalar. The finding also raises an awareness of the demand for carefully designed laboratory or field experiments of quantifying z 0T values for various urban surfaces. For the opposing cases, an unsteady penetrating narrow updraft zone appears occasionally along the heated wall and this feature is consistent field observations. The unique result indicates the superior capability of LES. The results of this study can be used to guide the parametrization of turbulent processes inside the urban canopy layer. © 2011 Springer Science+Business Media B.V.


Reynolds R.F.,University of Birmingham
Journal of Physiology | Year: 2011

The effects of electrical vestibular stimulation upon movement and perception suggest two evoked sensations: head roll and inter-aural linear acceleration. The head roll vector causes walking subjects to turn in a direction dependent on head pitch, requiring generation of torque around a vertical axis. Here the effect of vestibular stimulation upon vertical torque (T z) was investigated during quiet stance. With the head tilted forward, square-wave stimuli applied to the mastoid processes evoked a polarity-specific T z response accompanied by trunk yaw. Stochastic vestibular stimulation (SVS) was used to investigate the effect of head pitch with greater precision; the SVS-T z cross-correlation displayed a modulation pattern consistent with the head roll vector and this was also reflected by changes in coherence at 2-3 Hz. However, a separate response at 7-8 Hz was unaffected by head pitch. Head translation (rather than rotation) had no effect upon this high frequency response either, suggesting it is not caused by a sense of body rotation induced by an inter-aural acceleration vector offset from the body. Instead, high coherence between medio-lateral shear force and T z at the same frequency range suggests it is caused by mechanical coupling to evoked medio-lateral sway. Consistent with this explanation, the 7-8 Hz response was attenuated by 90 deg head roll or yaw, both of which uncouple the inter-aural axis from the medio-lateral sway axis. These results demonstrate two vertical torque responses to electrical vestibular stimulation in standing subjects. The high frequency response can be attributed to mechanical coupling to evoked medio-lateral sway. The low frequency response is consistent with a reaction to a sensation of head roll, and provides a novel method for investigating proprioceptive-vestibular interactions during stance. © 2011 The Author. Journal compilation © 2011 The Physiological Society.


Prescott T.J.,University of Sheffield | Diamond M.E.,International School for Advanced Studies | Wing A.M.,University of Birmingham
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

Active sensing systems are purposive and information-seeking sensory systems. Active sensing usually entails sensor movement, but more fundamentally, it involves control of the sensor apparatus, in whatever manner best suits the task, so as to maximize information gain. In animals, active sensing is perhaps most evident in the modality of touch. In this theme issue, we look at active touch across a broad range of species from insects, terrestrial and marine mammals, through to humans. In addition to analysing natural touch, we also consider how engineering is beginning to exploit physical analogues of these biological systems so as to endow robots with rich tactile sensing capabilities. The different contributions show not only the varieties of active touch-antennae, whiskers and fingertips-but also their commonalities. They explore how active touch sensing has evolved in different animal lineages, how it serves to provide rapid and reliable cues for controlling ongoing behaviour, and even how it can disintegrate when our brains begin to fail. They demonstrate that research on active touch offers a means both to understand this essential and primary sensory modality, and to investigate how animals, including man, combine movement with sensing so as to make sense of, and act effectively in, the world. © 2011 The Royal Society.


Lim H.S.,University of Birmingham
PACE - Pacing and Clinical Electrophysiology | Year: 2012

Contemporary devices include sophisticated algorithms specifically designed to minimize ventricular pacing, with the intention of limiting the patient's exposure to potentially deleterious effects of right ventricular pacing. The added complexity and adverse effects (some potentially life-threatening) associated with the use of these algorithms are often under-appreciated. The operational features, efficacy, and the potential adverse effects associated with one of these algorithms to minimize ventricular pacing-the Managed Ventricular Pacing™ algorithm-are reviewed to guide the appropriate prescription of this therapy. (PACE 2012;35:1528-1536) ©2012, The Author. Journal compilation ©2012 Wiley Periodicals, Inc.


Freer M.,University of Birmingham | Fynbo H.O.U.,University of Aarhus
Progress in Particle and Nuclear Physics | Year: 2014

The 7.65 MeV, Jπ=0+, second excited state in 12C is known as the Hoyle-state after Fred Hoyle. In the 1950s Hoyle proposed the existence of the state in order to account for the stellar abundance of carbon. Aside from its key role in the synthesis of the elements it is believed to possess a rather unusual structure, where the dominant degrees of freedom are those of α-particle clusters rather than nucleons. An understanding of the properties of the Hoyle state, for example its radius and excitations, has been the focus of a major experimental activity. Similarly, unravelling precisely why a cluster state should arise at precisely the right energy to promote synthesis of carbon has been a central theoretical challenge. To a significant extent, the Hoyle-state has become a cornerstone for state-of-the-art nuclear theory. This review examines the present status of both theory and experiment and indicates directions for future developments to resolve some of the remaining open questions. © 2014 Published by Elsevier B.V. All rights reserved.


In recent years there has been a wealth of literature arguing the need for empirical and interdisciplinary approaches to bioethics, based on the premise that an empirically informed ethical analysis is more grounded, contextually sensitive and therefore more relevant to clinical practice than an 'abstract' philosophical analysis. Bioethics has (arguably) always been an interdisciplinary field, and the rise of 'empirical' (bio)ethics need not be seen as an attempt to give a new name to the longstanding practice of interdisciplinary collaboration, but can perhaps best be understood as a substantive attempt to engage with the nature of that interdisciplinarity and to articulate the relationship between the many different disciplines (some of them empirical) that contribute to the field. It can also be described as an endeavour to explain how different disciplinary approaches can be integrated to effectively answer normative questions in bioethics, and fundamental to that endeavour is the need to think about how a robust methodology can be articulated that successfully marries apparently divergent epistemological and metaethical perspectives with method. This paper proposes 'Reflexive Bioethics' (RB) as a methodology for interdisciplinary and empirical bioethics, which utilizes a method of 'Reflexive Balancing' (RBL). RBL has been developed in response to criticisms of various forms of reflective equilibrium, and is built upon a pragmatic characterization of Bioethics and a 'quasi-moral foundationalism', which allows RBL to avoid some of the difficulties associated with RE and yet retain the flexible egalitarianism that makes it intuitively appealing to many. © 2013 John Wiley & Sons Ltd.


Farley A.C.,University of Birmingham
Cochrane database of systematic reviews (Online) | Year: 2012

Most people who stop smoking gain weight. There are some interventions that have been designed to reduce weight gain when stopping smoking. Some smoking cessation interventions may also limit weight gain although their effect on weight has not been reviewed. To systematically review the effect of: (1) Interventions targeting post-cessation weight gain on weight change and smoking cessation.(2) Interventions designed to aid smoking cessation that may also plausibly affect weight on post-cessation weight change. Part 1 - We searched the Cochrane Tobacco Addiction Group's Specialized Register and CENTRAL in September 2011.Part 2 - In addition we searched the included studies in the following "parent" Cochrane reviews: nicotine replacement therapy (NRT), antidepressants, nicotine receptor partial agonists, cannabinoid type 1 receptor antagonists and exercise interventions for smoking cessation published in Issue 9, 2011 of the Cochrane Library. Part 1 - We included trials of interventions that were targeted at post-cessation weight gain and had measured weight at any follow up point and/or smoking cessation six or more months after quit day.Part 2 - We included trials that had been included in the selected parent Cochrane reviews if they had reported weight gain at any time point. We extracted data on baseline characteristics of the study population, intervention, outcome and study quality. Change in weight was expressed as difference in weight change from baseline to follow up between trial arms and was reported in abstinent smokers only. Abstinence from smoking was expressed as a risk ratio (RR). We used the most rigorous definition of abstinence available in each trial. Where appropriate, we performed meta-analysis using the inverse variance method for weight and Mantel-Haenszel method for smoking using a fixed-effect model. Part 1: Some pharmacological interventions tested for limiting post cessation weight gain (PCWG) resulted in a significant reduction in WG at the end of treatment (dexfenfluramine (Mean difference (MD) -2.50 kg, 95% confidence interval (CI) -2.98 to -2.02, 1 study), phenylpropanolamine (MD -0.50 kg, 95% CI -0.80 to -0.20, N=3), naltrexone (MD -0.78 kg, 95% CI -1.52 to -0.05, N=2). There was no evidence that treatment reduced weight at 6 or 12 months (m). No pharmacological intervention significantly affected smoking cessation rates.Weight management education only was associated with no reduction in PCWG at end of treatment (6 or 12m). However these interventions significantly reduced abstinence at 12m (Risk ratio (RR) 0.66, 95% CI 0.48 to 0.90, N=2). Personalised weight management support reduced PCWG at 12m (MD -2.58 kg, 95% CI -5.11 to -0.05, N=2) and was not associated with a significant reduction of abstinence at 12m (RR 0.74, 95% CI 0.39 to 1.43, N=2). A very low calorie diet (VLCD) significantly reduced PCWG at end of treatment (MD -3.70 kg, 95% CI -4.82 to -2.58, N=1), but not significantly so at 12m (MD -1.30 kg, 95% CI -3.49 to 0.89, N=1). The VLCD increased chances of abstinence at 12m (RR 1.73, 95% CI 1.10 to 2.73, N=1). There was no evidence that cognitive behavioural therapy to allay concern about weight gain (CBT) reduced PCWG, but there was some evidence of increased PCWG at 6m (MD 0.74, 95% CI 0.24 to 1.24). It was associated with improved abstinence at 6m (RR 1.83, 95% CI 1.07 to 3.13, N=2) but not at 12m (RR 1.25, 95% CI 0.83 to 1.86, N=2). However, there was significant statistical heterogeneity.Part 2: We found no evidence that exercise interventions significantly reduced PCWG at end of treatment (MD -0.25 kg, 95% CI -0.78 to 0.29, N=4) however a significant reduction was found at 12m (MD -2.07 kg, 95% CI -3.78 to -0.36, N=3).Both bupropion and fluoxetine limited PCWG at the end of treatment (bupropion MD -1.12 kg, 95% CI -1.47 to -0.77, N=7) (fluoxetine MD -0.99 kg, 95% CI -1.36 to -0.61, N=2). There was no evidence that the effect persisted at 6m (bupropion MD -0.58 kg, 95% CI -2.16 to 1.00, N=4), (fluoxetine MD -0.01 kg, 95% CI -1.11 to 1.10, N=2) or 12m (bupropion MD -0.38 kg, 95% CI -2.00 to 1.24, N=4). There were no data on WG at 12m for fluoxetine.Overall, treatment with NRT attenuated PCWG at the end of treatment (MD -0.69 kg, 95% CI -0.88 to -0.51, N=19), with no strong evidence that the effect differed for the different forms of NRT. There was evidence of significant statistical heterogeneity caused by one study which reported a 4.3 kg reduction in PCWG due to NRT. With this study removed, the difference in weight change at end of treatment was -0.45 kg (95% CI -0.66 to -0.27, N=18). There was no evidence of an effect on PCWG at 12m (MD -0.42 kg, 95% CI -0.92 to 0.08, N=15).We found evidence that varenicline significantly reduced PCWG at end of treatment (MD -0.41 kg, 95% CI -0.63 to -0.19, N=11), but this effect was not maintained at 6 or 12m. Three studies compared the effect of bupropion to varenicline. Participants taking bupropion gained significantly less weight at the end of treatment (-0.51 kg (95% CI -0.93 to -0.09 kg), N=3). Direct comparison showed no significant difference in PCWG between varenicline and NRT. Although some pharmacotherapies tested to limit PCWG show evidence of short-term success, other problems with them and the lack of data on long-term efficacy limits their use. Weight management education only, is not effective and may reduce abstinence. Personalised weight management support may be effective and not reduce abstinence, but there are too few data to be sure. One study showed a VLCD increased abstinence but did not prevent WG in the longer term. CBT to accept WG did not limit PCWG and may not promote abstinence in the long term. Exercise interventions significantly reduced weight in the long term, but not the short term. More studies are needed to clarify whether this is an effect of treatment or a chance finding. Bupropion, fluoxetine, NRT and varenicline reduce PCWG while using the medication. Although this effect was not maintained one year after stopping smoking, the evidence is insufficient to exclude a modest long-term effect. The data are not sufficient to make strong clinical recommendations for effective programmes to prevent weight gain after cessation.


The small ubiquitin-like modifier (SUMO) proteins have been implicated in the pathology of a number of diseases, including neurodegenerative diseases. The conjugation machinery for SUMOylation consists of a number of proteins which are redox sensitive. Here, under oxidative stress (100 μM hydrogen peroxide), antioxidant (100 μM ascorbate) or control conditions 169 proteins were identified by electospray ionisation fourier transform ion cyclotron resonance mass spectrometry. The majority of these proteins (70%) were found to contain SUMOylation consensus sequences. From the remaining proteins a small number (12%) were found to contain possible SUMO interacting motifs. The proteins identified included DNA and RNA binding proteins, structural proteins and proteasomal proteins. Several of the proteins identified under oxidative stress conditions had previously been identified as SUMOylated proteins, thus validating the method presented.


Arman M.,University of Birmingham | Krauel K.,Universitatsmedizin Greifswald
Journal of Thrombosis and Haemostasis | Year: 2015

Beyond their prominent role in hemostasis and thrombosis, platelets are increasingly recognized as having immunologic functions. Supporting this, human platelets express FcγRIIA (CD32a), a low-affinity Fc receptor (FcR) for the constant region of IgG that recognizes immune complexes (ICs) and IgG-opsonized cells with high avidity. In leukocytes, FcγRIIA engagement initiates strong effector functions that are key for immune and inflammatory responses, including cytokine release, antibody-dependent cell-mediated killing of pathogens, and internalization of ICs. However, the physiologic relevance of platelet-expressed FcγRIIA has received little attention in previous reviews on FcRs. This article summarizes and discusses the available information on human platelet FcγRIIA. The importance of this receptor in heparin-induced thrombocytopenia, a prothrombotic adverse drug effect, is well documented. However, studies demonstrating platelet activation by IgG-opsonized bacteria point to the physiologic relevance of platelet FcγRIIA in immunity. In this context, platelet activation and secretion may facilitate both a direct antimicrobial function of platelets and crosstalk with other immune cells. Additionally, a role for platelet FcγRIIA in IgG-independent hemostasis and physiologic thrombosis, by means of amplifying integrin αIIbβ3 outside-in signaling, has also been proposed. Nonetheless, the thrombotic complications found in some infective and autoimmune diseases may result from unbalanced FcγRIIA-mediated platelet aggregation. Moreover, FcγRIIA is not expressed in mice, and thrombocytopenia and/or thrombotic events found after drug administration can only be recapitulated by the use of human FcγRIIA-transgenic mice. Altogether, the available data support a functional role for platelet FcγRIIA in health and disease, and emphasize the need for further investigation of this receptor. © 2015 International Society on Thrombosis and Haemostasis.


Vickers S.,University of Birmingham
Fuzzy Sets and Systems | Year: 2010

Höhle has identified fuzzy sets, valued in a frame (complete Heyting algebra) Ω, with certain sheaves over Ω: the subsheaves of constant sheaves. More general sheaves can be got as quotients of the fuzzy sets. His principal approach to sheaves over Ω, and topos-theoretic constructions on them, is via complete Ω-valued sets. In this paper we show how the geometric fragment of those constructions can be described in a natural "stalkwise" manner, provided one works also with incomplete Ω-valued sets. Our exposition examines in detail the interactions between different technical expressions of the notion of sheaf, and highlights a conceptual view of sheaf as "continuous set-valued map". © 2009 Elsevier B.V. All rights reserved.


Sutton M.,University of Manchester | Nikolova S.,University of Manchester | Boaden R.,University of Manchester | Lester H.,University of Birmingham | And 2 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Pay-for-performance programs are being adopted internationally despite little evidence that they improve patient outcomes. In 2008, a program called Advancing Quality, based on the Hospital Quality Incentive Demonstration in the United States, was introduced in all National Health Service (NHS) hospitals in the northwest region of England (population, 6.8 million). METHODS: We analyzed 30-day in-hospital mortality among 134,435 patients admitted for pneumonia, heart failure, or acute myocardial infarction to 24 hospitals covered by the pay-for-performance program. We used difference-in-differences regression analysis to compare mortality 18 months before and 18 months after the introduction of the program with mortality in two comparators: 722,139 patients admitted for the same three conditions to the 132 other hospitals in England and 241,009 patients admitted for six other conditions to both groups of hospitals. RESULTS: Risk-adjusted, absolute mortality for the conditions included in the pay-for-performance program decreased significantly, with an absolute reduction of 1.3 percentage points (95% confidence interval [CI], 0.4 to 2.1; P = 0.006) and a relative reduction of 6%, equivalent to 890 fewer deaths (95% CI, 260 to 1500) during the 18-month period. The largest reduction, for pneumonia, was significant (1.9 percentage points; 95% CI, 0.9 to 3.0; P<0.001), with nonsignificant reductions for acute myocardial infarction (0.6 percentage points; 95% CI, -0.4 to 1.7; P = 0.23) and heart failure (0.6 percentage points; 95% CI, -0.6 to 1.8; P = 0.30). CONCLUSIONS: The introduction of pay for performance in all NHS hospitals in one region of England was associated with a clinically significant reduction in mortality. As compared with a similar U.S. program, the U.K. program had larger bonuses and a greater investment by hospitals in quality-improvement activities. Further research is needed on how implementation of pay-for-performance programs influences their effects. Copyright © 2012 Massachusetts Medical Society.


Lindson-Hawley N.,University of Birmingham
Cochrane database of systematic reviews (Online) | Year: 2012

The standard way to stop smoking is to quit abruptly on a designated quit day. A number of smokers have tried unsuccessfully to quit this way. Reducing smoking before quitting could be an alternative approach to cessation. Before this method is adopted it is important to determine whether it is at least as successful as abrupt quitting. 1. To compare the success of reducing smoking to quit and abrupt quitting interventions. 2. To compare adverse events between arms in studies that used pharmacotherapy to aid reduction. We searched the Cochrane Tobacco Addiction Review Group specialised register using topic specific terms. The register contains reports of trials of tobacco addiction interventions identified from searches of MEDLINE, EMBASE and PsycInfo. We also searched reference lists of relevant papers and contacted authors of ongoing trials. Date of most recent search: July 2012. We included randomized controlled trials (RCTs) that recruited adults who wanted to quit smoking. Studies included at least one condition which instructed participants to reduce their smoking and then quit and one condition which instructed participants to quit abruptly. The outcome measure was abstinence from smoking after at least six months follow-up. We pooled the included trials using a Mantel-Haenszel fixed-effect model. Trials were split for two sub-group analyses: pharmacotherapy vs no pharmacotherapy, self help therapy vs behavioural support. Adverse events were summarised as a narrative. It was not possible to compare them quantitatively as there was variation in the nature and depth of reporting across studies. Ten studies were relevant for inclusion, with a total of 3760 participants included in the meta-analysis. Three of these studies used pharmacotherapy as part of the interventions. Five studies included behavioural support in the intervention, four included self-help therapy, and the remaining study had arms which included behavioural support and arms which included self-help therapy. Neither reduction or abrupt quitting had superior abstinence rates when all the studies were combined in the main analysis (RR= 0.94, 95% CI= 0.79 to 1.13), whether pharmacotherapy was used (RR= 0.87, 95% CI= 0.65 to 1.22), or not (RR= 0.97, 95% CI= 0.78 to 1.21), whether studies included behavioural support (RR= 0.87, 95% CI= 0.64 to 1.17) or self-help therapy (RR= 0.98, 95% CI= 0.78 to1.23). We were unable to draw conclusions about the difference in adverse events between interventions, however recent studies suggest that pre-quit NRT does not increase adverse events. Reducing cigarettes smoked before quit day and quitting abruptly, with no prior reduction, produced comparable quit rates, therefore patients can be given the choice to quit in either of these ways. Reduction interventions can be carried out using self-help materials or aided by behavioural support, and can be carried out with the aid of pre-quit NRT. Further research needs to investigate which method of reduction before quitting is the most effective, and which categories of smokers benefit the most from each method, to inform future policy and intervention development.


Gupta J.K.,University of Birmingham
Cochrane database of systematic reviews (Online) | Year: 2012

Uterine fibroids cause heavy prolonged bleeding, pain, pressure symptoms and subfertility. The traditional method of treatment has been surgery as medical therapies have not proven effective. Uterine artery embolization (UAE) has been reported to be an effective and safe alternative to treat fibroids in women not desiring future fertility. There is a significant body of evidence based on case controlled studies and case reports. This is an update of the review previously published in 2006. To review the benefits and risks of uterine artery embolization (UAE) versus other medical or surgical interventions for symptomatic uterine fibroids. We searched the Cochrane Menstrual Disorders & Subfertility Group Trials register (searched November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, 4th Quarter 2011), MEDLINE (1950 to November 2011) and EMBASE (January 1980 to November 2011). We also contacted authors of eligible RCTs for unpublished data. Randomised controlled trials (RCTs) of UAE versus any medical or surgical therapy for symptomatic uterine fibroids. Two of the authors (AS and JKG) assessed the trials and extracted the data independently. Five RCTs were included in this review. Three trials compared UAE with abdominal hysterectomy in 291 women. A fourth trial included 157 women and compared UAE with surgery (43 hysterectomies and 8 myomectomies). The fifth trial included 121 women and compared UAE with myomectomy in women wishing to preserve fertility.There was moderately good evidence that there is no significant difference between UAE and surgery in patient satisfaction rates at two years (OR 0.69, 0.40 to 1.21, 516 women, 5 trials) nor at five years (OR 0.90, 95% CI 0.45 to 1.80, 295 women, 2 trials). There was very low level evidence suggesting that myomectomy may be associated with better fertility outcomes than UAE, but this analysis was restricted to the limited cohort of women (n=66) who tried to conceive in the single study of UAE versus myomectomy (live birth: OR 0.33, 95% CI 0.11 to 1.00; pregnancy: OR 0.29, 95% CI 0.10 to 0.85). There was no significant difference between the two interventions in the rate of major complications. Compared to surgery, UAE significantly reduced the length of the procedure, length of hospital stay and time to resumption of routine activities and also decreased the likelihood of needing a blood transfusion. However, UAE was associated with higher rates of minor short term and long term complications, more unscheduled readmissions after discharge and an increased surgical reintervention rate. This increase in the surgical reintervention rate may balance out the initial cost advantage of UAE (reinterventions within 2 years: OR 5.64, 95% CI 2.92 to 10.90, 486 women, 4 trials; within 5 years: OR 5.79, 95% CI 2.65 to 12.65. 289 women, 2 trials). There was no significant difference in ovarian failure rates at long term follow-up. UAE appears to have an overall patient satisfaction rate similar to hysterectomy and myomectomy and offers an advantage with regards to a shorter hospital stay and a quicker return to routine activities. However, UAE is associated with a higher rate of minor complications and an increased likelihood of requiring surgical intervention within two to five years of the initial procedure. There is very low level evidence suggesting that myomectomy may be associated with better fertility outcomes than UAE, but more research is needed.


Daniels J.P.,University of Birmingham
BMJ (Clinical research ed.) | Year: 2012

To determine the relative effectiveness of second generation ablation techniques in the treatment of heavy menstrual bleeding. Network meta-analysis on the primary outcome measures of amenorrhoea, heavy bleeding, and patients' dissatisfaction with treatment. Nineteen randomised controlled trials (involving 3287 women) were identified through electronic searches of the Cochrane Library, Medline, Embase and PsycINFO databases from inception to April 2011. The reference lists of known relevant articles were searched for further articles. Two reviewers independently selected articles without language restrictions. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials involving second generation endometrial destruction techniques for women with heavy menstrual bleeding unresponsive to medical treatment. Of the three most commonly used techniques, network meta-analysis showed that bipolar radiofrequency and microwave ablation resulted in higher rates of amenorrhoea than thermal balloon ablation at around 12 months (odds ratio 2.51, 95% confidence interval 1.53 to 4.12, P<0.001; and 1.66, 1.01 to 2.71, P=0.05, respectively), but there was no evidence of a convincing difference between the three techniques in the number of women dissatisfied with treatment or still experiencing heavy bleeding. Compared with bipolar radio frequency and microwave devices, an increased number of women still experienced heavy bleeding after free fluid ablation (2.19, 1.07 to 4.50, P=0.03; and 2.91, 1.23 to 6.88, P=0.02, respectively). Compared with radio frequency ablation, free fluid ablation was associated with reduced rates of amenorrhoea (0.36, 0.19 to 0.67, P=0.004) and increased rates of dissatisfaction (4.79, 1.07 to 21.5, P=0.04). Of the less commonly used devices, endometrial laser intrauterine thermotherapy was associated with increased rates of amenorrhoea compared with all the other devices, while cryoablation led to a reduced rate compared with bipolar radio frequency and microwave. Bipolar radio frequency and microwave ablative devices are more effective than thermal balloon and free fluid ablation in the treatment of heavy menstrual bleeding with second generation endometrial ablation devices.


PURPOSE OF REVIEW: To outline what is known about collaborative work between the main stakeholders in mental health and psychiatry (professionals, patients or service users and family members). To learn from recent practice what are the main areas of joint work, what is working well, what are the key issues and problems and what has been learned from doing it. RECENT FINDINGS: Service users and family members are valued in education and training. Service users as peer support workers have helped patients recover, and methods of participatory research can bring new insights. There is a need to support and build an evidence base for these new ways of working. SUMMARY: The run-down of institutions, the new paradigm of recovery and human rights laws have led to increased joint working in the field of law and policy, research, education and training, service provision and coercion. Joint working challenges the old ways of knowledge creation and practices such as coercive treatment. More work is needed to build on what is being learned and move to genuine equality and partnership. © 2012 Wolters Kluwer Health | Lippincott Williams &Wilkins.


Walker G.,Lancaster University | Day R.,University of Birmingham
Energy Policy | Year: 2012

Bringing attention to fuel poverty as a distinct manifestation of social inequality has asserted the place of affordable warmth in the profile of contemporary rights and entitlements. As such, fuel poverty can be understood as an expression of injustice, involving the compromised ability to access energy services and thereby to secure a healthful living environment. In this paper, we consider how fuel poverty may be aligned to various alternative concepts of social and environmental justice. Whilst recognising that fuel poverty is fundamentally a complex problem of distributive injustice, we argue that other understandings of injustice are also implicated and play important roles in producing and sustaining inequalities in access to affordable warmth. Addressing fuel poverty has to involve seeking justice in terms of the cultural and political recognition of vulnerable and marginalised social groups and pursuing procedural justice through opening up involvement and influence in decision-making processes. We make this argument both in theoretical terms, and through considering the experience of fuel poverty advocacy and policy development in the UK. Opportunities for future action may be illuminated through such interconnected justice framings as wider awareness of energy, climate and poverty issues emerge. © 2012 Elsevier Ltd.


Freise A.,University of Birmingham | Strain K.,University of Glasgow
Living Reviews in Relativity | Year: 2010

Several km-scale gravitational-wave detectors have been constructed world wide. These instruments combine a number of advanced technologies to push the limits of precision length measurement. The core devices are laser interferometers of a new kind; developed from the classical Michelson topology these interferometers integrate additional optical elements, which significantly change the properties of the optical system. Much of the design and analysis of these laser interferometers can be performed using well-known classical optical techniques, however, the complex optical layouts provide a new challenge. In this review we give a textbook-style introduction to the optical science required for the understanding of modern gravitational wave detectors, as well as other high-precision laser interferometers. In addition, we provide a number of examples for a freely available interferometer simulation software and encourage the reader to use these examples to gain hands-on experience with the discussed optical methods.


Recent contributions to the de novo design of metalloproteins based on coiled coils and helical bundles are described herein, with examples covering mononuclear, multinuclear, and metallo-porphyrin sites, as well as membrane soluble designs. Important progress is being made in the field with a diverse range of functionalities, sometimes beyond those found in biology, being successfully engineered into these simplified scaffolds and represents an exciting prospect for the future. © 2016 Elsevier Ltd.


Muller M.,University of Birmingham
Geography Compass | Year: 2015

Assemblage thinking and actor-network theory (ANT) have been at the forefront of a paradigm shift that sees space and agency as the result of associating humans and non-humans to form precarious wholes. This shift offers ways of rethinking the relations between power, politics and space from a more processual, socio-material perspective. After sketching and comparing the concepts of the assemblage and the actor-network, this paper reviews the current scholarship in human geography which clusters around the four themes of deterritorialisation/reterritorialisation; power; materials, objects and technologies; and topological space. Looking towards the future, it suggests that assemblage thinking and ANT would benefit from exploring links with other social theories, arguing for a more sustained engagement with issues of language and power, and affect and the body. © 2014 John Wiley & Sons Ltd.


Baker C.,University of Birmingham
Journal of Wind Engineering and Industrial Aerodynamics | Year: 2013

High winds have a number of different effects on the design and operation of trains, the most important being the need to design trains that will not blow over in high winds. The current European design methodology is contained within a draft CEN code of practice (. CEN, 2009). In this paper the author will argue that there are inconsistencies and inadequacies in the approach adopted in that document, particularly in the levels of complexity of the different components and in the uncertainties that are involved. This leads to a proposal for a revised methodology that is more consistent in terms of the complexity of its components and can be used for train authorisation and route risk analysis. In particular the paper addresses the following issues:. •The development of simple correlations for train overturning moment coefficient as a function of yaw angle.•The use of a simplified model of the train overturning phenomenon, which takes into account "real" effects (such as vehicle suspension, curvature, admittance effects and track roughness), through second order correction factors.•The calibration of this model using previously published data obtained using more complex methodologies.•The application of this methodology to risk based assessments for use in train authorisation and route risk analysis.•The consideration of the uncertainty chain throughout the calculation process.Emerging out of this work, the concept arises of a simple parameter referred to as the characteristic velocity, which combines train geometry and aerodynamic effects and can be used as an indication of train safety in high cross winds. © 2013 Elsevier Ltd.


Reston T.J.,University of Birmingham | Ranero C.R.,CSIC - Institute of Marine Sciences
Geochemistry, Geophysics, Geosystems | Year: 2011

Seismic images of Cretaceous slow spreading crust from the eastern Central Atlantic provide new constraints on the process of seafloor spreading and the importance of detachment faulting. The seismic depth sections image detachment faults that appear to have exhumed footwall massifs of similar geometry to massifs of plutonic and mantle rocks mapped at the present Mid-Atlantic Ridge. The detachments are consistent with the structure and microearthquakes of the Mid-Atlantic Ridge at 26°N, with the footwall rotation inferred from paleomagnetic data and with numerical modeling of oceanic detachments. Other seismically imaged detachments have similar dimensions and geometry, but are covered by a layer of small fault blocks. The detachment types differ in whether or not the fault locks up in the subsurface, probably controlled by the fault strength, the elastic thickness, and whether the exhumed footwall is partly covered by basalts. Toward the segment middle, decreasing mantle serpentinization, decreasing elastic thickness, and thicker median valley basalts all increase the likelihood that the fault locks up, and a new fault propagates upwards from the still active root zone, transferring a slice of the hanging wall to the footwall, to be rafted with the footwall out of the median valley. As a result an oceanic detachment fault, exhuming the footwall at a segment end to form an oceanic core complex, may disappear laterally beneath rafted blocks; detachment faulting may be more widespread at slow spreading ridges than interpreted from seafloor mapping. Copyright 2011 by the American Geophysical Union.


Screening for congenital heart defects (CHDs) relies on antenatal ultrasound and postnatal clinical examination; however, life-threatening defects often go undetected. To determine the accuracy, acceptability and cost-effectiveness of pulse oximetry as a screening test for CHDs in newborn infants. A test accuracy study determined the accuracy of pulse oximetry. Acceptability of testing to parents was evaluated through a questionnaire, and to staff through focus groups. A decision-analytic model was constructed to assess cost-effectiveness. Six UK maternity units. These were 20,055 asymptomatic newborns at ≥ 35 weeks' gestation, their mothers and health-care staff. Pulse oximetry was performed prior to discharge from hospital and the results of this index test were compared with a composite reference standard (echocardiography, clinical follow-up and follow-up through interrogation of clinical databases). Detection of major CHDs - defined as causing death or requiring invasive intervention up to 12 months of age (subdivided into critical CHDs causing death or intervention before 28 days, and serious CHDs causing death or intervention between 1 and 12 months of age); acceptability of testing to parents and staff; and the cost-effectiveness in terms of cost per timely diagnosis. Fifty-three of the 20,055 babies screened had a major CHD (24 critical and 29 serious), a prevalence of 2.6 per 1000 live births. Pulse oximetry had a sensitivity of 75.0% [95% confidence interval (CI) 53.3% to 90.2%] for critical cases and 49.1% (95% CI 35.1% to 63.2%) for all major CHDs. When 23 cases were excluded, in which a CHD was already suspected following antenatal ultrasound, pulse oximetry had a sensitivity of 58.3% (95% CI 27.7% to 84.8%) for critical cases (12 babies) and 28.6% (95% CI 14.6% to 46.3%) for all major CHDs (35 babies). False-positive (FP) results occurred in 1 in 119 babies (0.84%) without major CHDs (specificity 99.2%, 95% CI 99.0% to 99.3%). However, of the 169 FPs, there were six cases of significant but not major CHDs and 40 cases of respiratory or infective illness requiring medical intervention. The prevalence of major CHDs in babies with normal pulse oximetry was 1.4 (95% CI 0.9 to 2.0) per 1000 live births, as 27 babies with major CHDs (6 critical and 21 serious) were missed. Parent and staff participants were predominantly satisfied with screening, perceiving it as an important test to detect ill babies. There was no evidence that mothers given FP results were more anxious after participating than those given true-negative results, although they were less satisfied with the test. White British/Irish mothers were more likely to participate in the study, and were less anxious and more satisfied than those of other ethnicities. The incremental cost-effectiveness ratio of pulse oximetry plus clinical examination compared with examination alone is approximately £24,900 per timely diagnosis in a population in which antenatal screening for CHDs already exists. Pulse oximetry is a simple, safe, feasible test that is acceptable to parents and staff and adds value to existing screening. It is likely to identify cases of critical CHDs that would otherwise go undetected. It is also likely to be cost-effective given current acceptable thresholds. The detection of other pathologies, such as significant CHDs and respiratory and infective illnesses, is an additional advantage. Other pulse oximetry techniques, such as perfusion index, may enhance detection of aortic obstructive lesions. The National Institute for Health Research Health Technology programme. © Queen's Printer and Controller of HMSO 2012.


Haycraft E.,Loughborough University | Blissett J.,University of Birmingham
Journal of Nutrition Education and Behavior | Year: 2012

Objective: This study aimed to identify predictors of controlling feeding practices in both mothers and fathers of young children. Design: Cross-sectional, questionnaire design. Setting: Nursery schools within the United Kingdom recruited participants. Participants: Ninety-six mothers and fathers comprising 48 mother-father pairs of male and female children aged 2 to 5 years. Main Outcome Measures: Parents' child feeding practices, eating psychopathology, general mental health symptomology, and their children's eating behaviors and temperament. Analysis: Preliminary correlations; stepwise regressions. Results: Maternal controlling feeding was predicted by children's eating behaviors (emotional over- and undereating), child temperament (sociability), and maternal general mental health symptoms. Paternal reports of children's eating behaviors (slow eating and emotional undereating) were the only significant predictors of fathers' controlling feeding practices. Conclusions and Implications: Mothers' and fathers' feeding practices seem to be better linked to child characteristics than to the presence of eating psychopathology symptoms. Children's emotional eating predicted all 3 controlling feeding practices in mothers and warrants further study to elucidate the causal nature of this relationship. © 2012 Society for Nutrition Education and Behavior.


Lock R.,University of Birmingham
Journal of Biological Education | Year: 2014

Between 1963 and 2009, there have been 13 published studies offering empirical evidence on biology fieldwork in schools and colleges in the UK. This paper considers the evidence from these studies relating to work with 16-19 year old students undertaking academic study beyond the compulsory years of schooling; advanced ('A') level. It analyses data concerning the amount and type of fieldwork experience students were offered and the factors that influence opportunity for such study. A multi-method approach is used, involving historical research, content and critical analysis as well as secondary analysis, in order to explore: (1) whether there has been a reduction in the fieldwork opportunities offered to 16-19 year olds, as has been claimed by Government and national bodies such as Parliament, the British Ecological Society (BES) and the Field Studies Council (FSC); and (2) the factors affecting the provision of biology fieldwork in the UK. The findings suggest that fieldwork provision in biology is declining and that eight factors have contributed to this decline. The paper concludes by identifying the implications for researchers, policy formers and those responsible for pre-service teacher training.


Allen K.,University of Birmingham
Social Science and Medicine | Year: 2011

This paper aims to explore the management of a rare chromosome disorder, Prader-Willi syndrome (PWS), within families. It is particularly concerned with developing an understanding of the management of diet and other everyday practices affecting the body. People with PWS tend to experience poor muscle tone combined with food obsession. The level of control over diet needed to prevent obesity and related health complications is often lacking as individuals also experience various forms of learning disability, autistic spectrum disorders and behavioural problems. The findings are based on data from twenty qualitative case studies of English families with a young person with PWS. Analysis of management strategies highlights the centrality of embodied agency in shaping everyday practices and interactions. The significance and influence of biology within this process is particularly evident, as people with the genetic condition PWS experience embodiment and emotion in distinct ways and differently from non-PWS family members in the research sample. Focusing on the multidimensional nature of processes surrounding body management, the paper highlights three key management practices and explores how these practices are influenced by people with PWS and interpreted by family members. Three key practices are identified as: restricting access to food, keeping occupied, and use of routine. The study represents the first UK empirical sociological study of PWS and primarily adds an insight of family management of PWS to a medically dominated literature around the disorder. The findings can sensitise health and social care professionals to some potential issues for families managing PWS, and guide and develop appropriate interventions to support young people with PWS and their carers. © 2010 Elsevier Ltd.


This paper suggests that many of the pressing dilemmas of bioethics are global and structural in nature. Accordingly, global ethical frameworks are required which recognize the ethically significant factors of all global actors. To this end, ethical frameworks must recognize the rights and interests of both individuals and groups (and the interrelation of these). The paper suggests that the current dominant bioethical framework is inadequate to this task as it is over-individualist and therefore unable to give significant weight to the ethical demands of groups (and by extension communal and public goods). It will explore this theme by considering the inadequacy of informed consent (the 'global standard' of bioethics) to address two pressing global bioethical issues: medical tourism and population genetics. Using these examples it will show why consent is inadequate to address all the significant features of these ethical dilemmas. Four key failures will be explored, namely,• That the rights and interests of those related (and therefore affected) are neglected;• That consent fails to take account of the context and commitments of individuals which may constitute inducement and coercion;• That consent alone does not have the ethical weight to negate exploitation or make an unjust action just ('the fallacy of sufficiency');• That consent is a single one-off act which is inappropriate for the types of decision being made. It will conclude by suggesting that more appropriate models are emerging, particularly in population genetics, which can supplement consent. © 2010 Blackwell Publishing Ltd.


Foster P.A.,University of Birmingham
International Journal of Colorectal Disease | Year: 2013

Aim: The role of oestrogen metabolism and action in colorectal cancer (CRC) is controversial. An extensive review of the current literature, encompassing epidemiological evidence, systemic and peripheral oestrogen concentrations, 17β-hydroxysteroid dehydrogenase (17β-HSD) and aromatase in CRC, steroid sulphatase (STS)/oestrone sulphotransferase (EST) and in vitro and in vivo genomic effects was therefore undertaken. Methods: A literature search (key words: colorectal cancer, oestrogen, oestrogen receptor, 17β-HSD, STS, organic anion transporter) was performed using Embase, Medline, and Pubmed and papers were evaluated on scientific relevance on an individual basis. Results: Epidemiological data highlights that premenopausal women, or postmenopausal women taking hormone replacement therapy, are significantly less likely than males to develop CRC. This implies that oestrogen signalling is most likely involved in CRC physiology and aetiology. Little is known about oestrogen metabolism in the colon. However, the expression of 17β-HSD, STS, and EST, enzymes involved in oestrogen metabolism, have shown prognostic significance. Evidence also suggests that protective effects are modulated through oestrogen receptor beta, although which metabolite of oestrogen, oestradiol (E 2) or oestrone (E1), is more active remains undefined. To complicate matters, the changes in the peripheral ratios of these enzymes, oestrogens and receptors most likely influences CRC progression. Conclusion: Epidemiological evidence, now supported by in vitro and in vivo studies, strongly associates oestrogen action and metabolism with CRC. Initially protective against CRC, once developed, results suggests that oestrogens increase proliferation. Consequently, hormone-ablation therapy, already successful against breast and prostate cancer, may be effective against CRC. © 2013 Springer-Verlag Berlin Heidelberg.


Krachler A.M.,University of Birmingham | Orth K.,Southwestern Medical Center
Virulence | Year: 2013

Bacterial infections are a major cause of morbidity and mortality worldwide and are increasingly problematic to treat due to the rise in antibiotic-resistant strains. it becomes more and more challenging to develop new antimicrobials that are able to withstand the ever-increasing repertoire of bacterial resistance mechanisms. This necessitates the development of alternative approaches to prevent and treat bacterial infections. One of the first steps during bacterial infection is adhesion of the pathogen to host cells. A pathogen's ability to colonize and invade host tissues strictly depends on this process. Thus, interference with adhesion (anti-adhesion therapy) is an efficient way to prevent or treat bacterial infections. As a basis to present different strategies to interfere with pathogen adhesion, this review briefly introduces general concepts of bacterial attachment to host cells. we further discuss advantages and disadvantages of anti-adhesion treatments and issues that are in need of improvement so as to make anti-adhesion compounds a more broadly applicable alternative to conventional antimicrobials. © 2013 Landes Bioscience.


Needham C.,University of Birmingham
BMC Health Services Research | Year: 2013

Background: The article explores the implications of personal budgets within English social care services, which position the individual as market actor. Rooting the research in the broader personalization agenda, the study looks at the limitations of the market in relation to individual purchase of private goods (e.g. home care), in the pooling of funds to purchase group services and in the provision of public goods such as building-based services. Method. The article takes a multi-method approach, combining an interpretive focus on the framing of the personal budget-holder by advocates of personalization with national evaluation data, and data from a small survey of day centre workers. Results: The article identifies three framings of the individual budget-holder articulated by advocates of personalization. The first is that personal budget-holders will be empowered market actors, commissioning the services they need. The second is that budget-holders will pool resources with others to purchase group services in order to broaden the range of options available to them. The third is that services which cannot be disaggregated into individual or group budgets - such as day centres - are not valued by service users. The article looks at the evaluation data on these three claims in turn. It identifies four limitations to the capacity of people to purchase care goods on an individual basis: lack of transparency in allocating budgets, complexity in managing a budget, excessive auditing of spending and lack of responsiveness from the provider market. Pooling of budgets to purchase collective services is found to be underdeveloped, and hampered by the complexity which is a broader limitation on personal budgets. Day centres are found to be closing not in response to commissioning decisions by individual budget-holders but because of decommissioning by local authorities, minimising the scope for individuals to express a preference for this type of care. The survey highlights patterns of day centre closure, rising fees for attendance and reduced eligibility, and the underdevelopment of mechanisms to facilitate commissioning of new collective spaces. Conclusions: The paper concludes that the transition to personal budgets - in the context of the accompanying financial crisis in local authorities - has led to inadequate attention to the potential for an undersupply of collective and public goods. The loss of day centre provision will be felt by personal budget holders but also by self-funders and people in residential accommodation who may no longer be eligible for, or able to afford, to access shared spaces. Local authorities are actively taking on the role of decommissioners without sufficient responsiveness to how and what individuals want them to commission. © 2013 Needham; licensee BioMed Central Ltd.


Gale N.,University of Birmingham | Sultan H.,Sandwell Primary Care Trust
Health and Place | Year: 2013

A theoretical understanding of why some people with chronic obstructive pulmonary disorder (COPD) experienced 'peace of mind' when a new telehealth service was introduced into a community respiratory service (CRS) is presented in this article. This is based on analysis of in-depth, qualitative, situated interviews with COPD patients who were receiving the service. Telehealth brought peace of mind through two mechanisms: legitimising contact with health professionals and increased patient confidence in the management of their condition. When the home is the primary health space, the introduction of telehealth can modify emotional and bodily experiences to an extent that is significant for people with COPD. The process by which technology can provide 'peace of mind' to people with long term conditions should be taken into account when designing or commissioning a service. © 2013 Elsevier Ltd.


Johnston I.,University of Birmingham | Williams B.,Whitehead Institute For Biomedical Research
Cell Systems | Year: 2016

Since their endosymbiotic origin, mitochondria have lost most of their genes. Although many selective mechanisms underlying the evolution of mitochondrial genomes have been proposed, a data-driven exploration of these hypotheses is lacking, and a quantitatively supported consensus remains absent. We developed HyperTraPS, a methodology coupling stochastic modeling with Bayesian inference, to identify the ordering of evolutionary events and suggest their causes. Using 2015 complete mitochondrial genomes, we inferred evolutionary trajectories of mtDNA gene loss across the eukaryotic tree of life. We find that proteins comprising the structural cores of the electron transport chain are preferentially encoded within mitochondrial genomes across eukaryotes. A combination of high GC content and high protein hydrophobicity is required to explain patterns of mtDNA gene retention; a model that accounts for these selective pressures can also predict the success of artificial gene transfer experiments in vivo. This work provides a general method for data-driven inference of the ordering of evolutionary and progressive events, here identifying the distinct features shaping mitochondrial genomes of present-day species. A generalizable stochastic modeling and inference approach is developed to characterize the patterns of mtDNA gene loss throughout evolutionary history and to perform a data-driven comparison of the highly debated hypotheses regarding the forces underlying mtDNA evolution. © 2016 Elsevier Inc.


MacLennan C.A.,Novartis | MacLennan C.A.,University of Birmingham
Seminars in Immunology | Year: 2013

Low-income countries typically lag behind industrialised nations, where the introduction of new vaccines is commonly tailored to the pressures of the commercial market. Happily in recent years this paradigm has started to change with the introduction of a univalent meningococcal A conjugate vaccine that is specifically targeted for the prevention of epidemic meningitis in Africa. The declaration of the 2010s as a New Decade of Vaccines, together with Millennium Development Goals 4 and 5, provide a strong mandate for a new approach to the development of vaccines for low-income countries, so that there has never been a more exciting time to work in this field. This review considers the opportunities and challenges of developing these new vaccines in the context of innovations in vaccinology, the need to induce protective immunity in the populations at risk and the requirement for strong partnership between the countries that will use these vaccines and different elements of the vaccine industry. © 2013 The Author.


Speake C.,University of Birmingham | Quinn T.,International Bureau of Weights and Measures in Sevres
Physics Today | Year: 2014

Three decades of careful experimentation have painted a surprisingly hazy picture of the constant governing the most familiar force on Earth.


Jackson D.,MRC Biostatistics Unit | Riley R.,University of Birmingham | White I.R.,MRC Biostatistics Unit
Statistics in Medicine | Year: 2011

The multivariate random effects model is a generalization of the standard univariate model. Multivariate meta-analysis is becoming more commonly used and the techniques and related computer software, although continually under development, are now in place. In order to raise awareness of the multivariate methods, and discuss their advantages and disadvantages, we organized a one day 'Multivariate meta-analysis' event at the Royal Statistical Society. In addition to disseminating the most recent developments, we also received an abundance of comments, concerns, insights, critiques and encouragement. This article provides a balanced account of the day's discourse. By giving others the opportunity to respond to our assessment, we hope to ensure that the various view points and opinions are aired before multivariate meta-analysis simply becomes another widely used de facto method without any proper consideration of it by the medical statistics community. We describe the areas of application that multivariate meta-analysis has found, the methods available, the difficulties typically encountered and the arguments for and against the multivariate methods, using four representative but contrasting examples. We conclude that the multivariate methods can be useful, and in particular can provide estimates with better statistical properties, but also that these benefits come at the price of making more assumptions which do not result in better inference in every case. Although there is evidence that multivariate meta-analysis has considerable potential, it must be even more carefully applied than its univariate counterpart in practice. © 2011 John Wiley & Sons, Ltd.


Booth D.A.,University of Birmingham
Trends in Food Science and Technology | Year: 2014

Advance in food science depends on measuring the factors in human perception that influence eaters' activities with branded products. Assessed samples must include at least two levels of a sensed material characteristic (e.g. sucrose) or conceptual marketing attribute (e.g. "low fat"), minimally confounded by other features. Each feature needs to be measured for its effect on the individual's objective achievement of choosing among the samples for a familiar context of use. These influences interact, consciously and unconsciously. This theory of how a mind works has generated a wide range of scientifically illuminating and commercially practical examples, illustrated in this review. © 2013 Elsevier Ltd.


Li Z.,Henan Polytechnic University | Thomas C.,University of Birmingham
Trends in Food Science and Technology | Year: 2014

Fresh fruits are very susceptible to mechanical damage during harvesting, packaging and transport, which can result in a substantial reduction in quality. Ideally, such damage would be minimized through improved understanding of the mechanisms. If damage occurs, economic losses might be minimized by grading affected fruits, based on the severity of damage, into those that need more than minimal further processing and those that do not. In either case, an objective and quantitative evaluation of the degree of mechanical damage is required. However, this is still far from being realized and remains an important challenge of past and proposed research in food safety.This review concerns the quantitative evaluation of mechanical damage to fresh fruits. Firstly, the sources of damage to fresh fruits during mechanical handling are summarized. The mechanisms are described in detail. Existing quantitative assessments characterizing surface and internal mechanical damage and its prediction are then reviewed. Finally, future research directions are discussed. The main challenge in evaluating mechanical damage to fresh fruit objectively is to develop a method to assess accurately the extent of internal damage to fruits caused by excessive external forces. © 2013 Elsevier Ltd.


Hayward S.A.L.,University of Birmingham
Current Opinion in Insect Science | Year: 2014

Omic technologies have revolutionised how environmental physiologists investigate stress response pathways. To date, however, omic screens typically constitute simple presence/absence correlations, and fall short of explaining mechanism. Disentangling function necessitates hypothesis-driven manipulation of selected molecular signals, and a systems level view will only come from more detailed tissue-specific and time series sampling. The increasing accessibility of omic applications means that species can be selected based on Krogh principles, but focus also needs to be given to core models where multi-platform approaches can be combined to provide a deeper understanding. This review highlights recent technological and intellectual advances in the application of omics to understanding insect stress adaptation, and sets out how to address remaining knowledge gaps. © 2014 Elsevier Inc. All rights reserved.


Gough C.,University of Birmingham
Journal of the Acoustical Society of America | Year: 2015

As the first step toward developing a generic model for the acoustically radiating vibrational modes of the violin and related instruments, the modes of both freely supported and edge-constrained top and back plates have been investigated as functions of shape, arching height, elastic anisotropy, the f-holes and associated island area, thickness graduations, and the additional boundary constraints of the ribs, soundpost, and bass-bar present in the assembled instrument. Comsol shell structure finite element software has been used as a quasi-experimental tool, with physical and geometric properties varied smoothly, often over several orders of magnitude, allowing the development of the plate modes to be followed continuously from those of an initially square plate to those of doubly-arched, guitar-shaped, orthotropic plates and their dependence on all the above factors. © 2015 Acoustical Society of America.


Gough C.E.,University of Birmingham
Journal of the Acoustical Society of America | Year: 2015

A generic physical model for the vibro-acoustic modes of the violin is described treating the body shell as a shallow, thin-walled, guitar-shaped, box structure with doubly arched top and back plates. comsol finite element, shell structure, software is used to identify and understand the vibrational modes of a simply modeled violin. This identifies the relationship between the freely supported plate modes when coupled together by the ribs and the modes of the assembled body shell. Such coupling results in a relatively small number of eigenmodes or component shell modes, of which a single volume-changing breathing mode is shown to be responsible for almost all the sound radiated in the monopole signature mode regime below ∼1 kHz for the violin, whether directly or by excitation of the Helmholtz f-hole resonance. The computations describe the influence on such modes of material properties, arching, plate thickness, elastic anisotropy, f-holes cut into the top plate, the bass-bar, coupling to internal air modes, the rigid neck-fingerboard assembly, and, most importantly, the soundpost. Because the shell modes are largely determined by the symmetry of the guitar-shaped body, the model is applicable to all instruments of the violin family. © 2015 Acoustical Society of America.


Densham R.M.,University of Birmingham
Nature Structural and Molecular Biology | Year: 2016

The opposing activities of 53BP1 and BRCA1 influence pathway choice in DNA double-strand-break repair. How BRCA1 counteracts the inhibitory effect of 53BP1 on DNA resection and homologous recombination is unknown. Here we identify the site of BRCA1–BARD1 required for priming ubiquitin transfer from E2∼ubiquitin and demonstrate that BRCA1–BARD1's ubiquitin ligase activity is required for repositioning 53BP1 on damaged chromatin. We confirm H2A ubiquitination by BRCA1–BARD1 and show that an H2A-ubiquitin fusion protein promotes DNA resection and repair in BARD1-deficient cells. BRCA1–BARD1's function in homologous recombination requires the chromatin remodeler SMARCAD1. SMARCAD1 binding to H2A-ubiquitin and optimal localization to sites of damage and activity in DNA repair requires its ubiquitin-binding CUE domains. SMARCAD1 is required for 53BP1 repositioning, and the need for SMARCAD1 in olaparib or camptothecin resistance is alleviated by 53BP1 loss. Thus, BRCA1–BARD1 ligase activity and subsequent SMARCAD1-dependent chromatin remodeling are critical regulators of DNA repair. © 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Martin G.R.,University of Birmingham
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

Birds show interspecific variation both in the size of the fields of individual eyes and in the ways that these fields are brought together to produce the total visual field. Variation is found in the dimensions of all main parameters: binocular region, cyclopean field and blind areas. There is a phylogenetic signal with respect to maximum width of the binocular field in that passerine species have significantly broader field widths than non-passerines; broadest fields are found among crows (Corvidae). Among non-passerines, visual fields show considerable variation within families and even within some genera. It is argued that (i) the main drivers of differences in visual fields are associated with perceptual challenges that arise through different modes of foraging, and (ii) the primary function of binocularity in birds lies in the control of bill position rather than in the control of locomotion. The informational function of binocular vision does not lie in binocularity per se (two eyes receiving slightly different information simultaneously about the same objects from which higher-order depth information is extracted), but in the contralateral projection of the visual field of each eye. Contralateral projection ensures that each eye receives information from a symmetrically expanding optic flow-field from which direction of travel and time to contact targets can be extracted, particularly with respect to the control of bill position. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Background:We report the findings of a feasibility study using information technology to search electronic primary care records and to identify patients with possible colorectal cancer.Methods:An algorithm to flag up patients meeting National Institute for Health and Care Excellence (NICE) urgent referral criteria for suspected colorectal cancer was developed and incorporated into clinical audit software. This periodically flagged up such patients aged 60 to 79 years. General practitioners (GPs) reviewed flagged-up patients and decided on further clinical management. We report the numbers of patients identified and the numbers that GPs judged to need further review, investigations or referral to secondary care and the final diagnoses.Results:Between January 2012 and March 2014, 19 580 records of patients aged 60 to 79 years were searched in 20 UK general practices, flagging up 809 patients who met urgent referral criteria. The majority of the patients had microcytic anaemia (236 (29%)) or rectal bleeding (205 (25%)). A total of 274 (34%) patients needed further clinical review of their records; 199 (73%) of these were invited for GP consultation, and 116 attended, of whom 42 were referred to secondary care. Colon cancer was diagnosed in 10 out of 809 (1.2%) flagged-up patients and polyps in a further 28 out of 809 (3.5%).Conclusions:It is technically possible to identify patients with colorectal cancer by searching electronic patient records.British Journal of Cancer advance online publication, 3 March 2015; doi:10.1038/bjc.2015.45 www.bjcancer.com. © 2015 Cancer Research UK


Hart A.,University of Birmingham
Journal of Petroleum Exploration and Production Technology | Year: 2014

Heavy crude oil and bitumen resources are more than double the conventional light oil reserves worldwide. Heavy crude oil and bitumen production is on average twice as capital and energy intensive as the production of conventional oil. This is because of their extremely low mobility due to high viscosity at reservoir conditions alongside the presence of undesirable components such as asphaltenes, heavy metals and sulphur making it more challenging to produce, transport as well as refine. It is well know that pipelines are the most convenient means of transporting crude oil from the producing field to the refinery. However, moving heavy crude oil and bitumen is extremely challenging because of their inability to flow freely. As such, without prior reduction in the heavy crude oil and bitumen viscosity, transportation via pipeline is difficult. This is because of the huge energy (i.e. high pumping power) required to overcome the high-pressure drop in the pipeline due to their high viscosity at reservoir conditions. To reduce this high-pressure drop and cost of transportation, several technologies have been proposed to improve the flow properties of the heavy crude oil and bitumen through pipelines. In this study, different technologies are reviewed and the advantages and disadvantages of each technology are highlighted with the view that the review will provide direction for improvement and development of novel technologies for bitumen and heavy oil transportation via pipelines. © 2013, The Author(s).


Mollan S.P.,University of Birmingham
The Cochrane database of systematic reviews | Year: 2014

Giant cell arteritis (GCA) is a common inflammatory condition that affects medium and large-sized arteries and can cause sudden, permanent blindness. At present there is no alternative to early treatment with high-dose corticosteroids as the recommended standard management. Corticosteroid-induced side effects can develop and further disease-related ischaemic complications can still occur. Alternative and adjunctive therapies are sought. Aspirin has been shown to have effects on the immune-mediated inflammation in GCA, hence it may reduce damage caused in the arterial wall. To assess the safety and effectiveness of low-dose aspirin, as an adjunctive, in the treatment of giant cell arteritis (GCA). We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2013, Issue 12), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to January 2014), EMBASE (January 1980 to January 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to January 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the US Food and Drugs Administration (FDA) web site (www.fda.gov). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 24 January 2014. We planned to include only randomised controlled trials (RCTs) comparing outcomes of GCA with and without concurrent adjunctive use of low-dose aspirin. Two authors independently assessed the search results for trials identified by the electronic searches. No trials met our inclusion criteria, therefore we undertook no assessment of risk of bias or meta-analysis. We found no RCTs that met the inclusion criteria. There is currently no evidence from RCTs to determine the safety and efficacy of low-dose aspirin as an adjunctive treatment in GCA. Clinicians who are considering the use of low-dose aspirin as an adjunctive treatment in GCA must also recognise the established haemorraghic risks associated with aspirin, especially in the context of concurrent treatment with corticosteroids. There is a clear need for effectiveness trials to guide the management of this life-threatening condition.


Britton M.M.,University of Birmingham
ChemPhysChem | Year: 2014

The development of improved energy-storage devices, as well as corrosion prevention and metal-electrofinishing technologies, requires knowledge of local composition and transport behaviour in electrolytes near bulk metals, in situ and in real time. It remains a challenge to acquire such data and new analytical methods are required. Recent work shows that magnetic resonance imaging (MRI) is able to map concentration gradients and visualise electrochemical processes in electrochemical cells containing bulk metals. This recent work, along with the challenges, and solutions, associated with MRI of these electrochemical cells are reviewed. Caught on film: Magnetic resonance imaging (MRI) is common in medical research and, more recently, is being applied to visualize chemical composition, molecular transport, and physical environment in engineering and materials research. Researchers are now starting to use these techniques to investigate electrochemical devices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Lip G.Y.H.,University of Birmingham
Expert Review of Cardiovascular Therapy | Year: 2014

Atrial fibrillation (AF) results in a substantial risk of mortality and morbidity from stroke and thromboembolism, and thus, a cornerstone of AF management requires appropriate and effective stroke prevention, which is oral anticoagulation. In the last decade, substantial changes in the landscape of stroke prevention in AF are evident. New knowledge has led to improved treatment options and guidelines have evolved. For example, stroke and bleeding risk assessment has now focused on use of the validated CHA2DS2-VASc and HAS-BLED scores, respectively to make clinical decisions. An important clinical practice shift is the initial identification of 'low-risk' patients, that is, CHA2DS2-VASc score = 0 (male) or 1 (females), who do not need any antithrombotic therapy. Subsequent to this step OAC can be offered to patients with ≥1 stroke risk factors. More recently, the SAMe-TT2R2 score has been proposed to aid decision-making, by using simple clinical variables by identifying those AF patients likely to do well on warfarin (SAMe-TT2R2 score 0-1) or those more likely to have poor anticoagulation control (SAMe-TT2R2 score >2), where a non-vitamin K antagonist oral anticoagulant may be a better option. © Informa UK, Ltd.


Fisher J.P.,University of Birmingham
Experimental Physiology | Year: 2014

New findings: What is the topic of this review? The autonomic nervous system plays a key role in bringing about the cardiovascular responses to exercise necessitated by the increased metabolic requirements of the active skeletal muscle. The complex interaction of central and peripheral neural control mechanisms evokes a decrease in parasympathetic activity and an increase sympathetic activity to the heart during exercise. What advances does it highlight? This review presents some of the recent insights provided by human studies into the role of mechanically and metabolically sensitive skeletal muscle afferents in the regulation of cardiac autonomic control during exercise. The autonomic responses to exercise are orchestrated by the interactions of several central and peripheral neural mechanisms. This report focuses on the role of peripheral feedback from skeletal muscle afferents in the autonomic control of the heart during exercise in humans. Heart rate responses to passive calf stretch are abolished with cardiac parasympathetic blockade, indicating that the activation of mechanically sensitive skeletal muscle afferents (muscle mechanoreceptors) can inhibit cardiac parasympathetic activity and is likely to contribute to the increase in heart rate at the onset of exercise. Recent experiments show that the partial restriction of blood flow to the exercising skeletal muscles, to augment the activation of metabolically sensitive skeletal muscle afferents (muscle metaboreceptors) in humans, evokes an increase in heart rate that is attenuated with β1-adrenergic blockade, thus suggesting that this response is principally mediated via an increase in cardiac sympathetic activity. Heart rate remains at resting levels during isolated activation of muscle metaboreceptors with postexercise ischaemia following hand grip, unless cardiac parasympathetic activity is inhibited, whereupon a sympathetically mediated increase in heart rate is unmasked. During postexercise ischaemia following leg cycling exercise, heart rate appears to remain elevated due to withdrawal of parasympathetic tone and/or the activation of sympathetic activity to the heart. Although the importance of skeletal muscle afferent feedback to the autonomic control of the heart during exercise is incontrovertible, the complexity of cardiac sympathetic-parasympathetic interactions and the absence of direct intraneural recordings in humans mean that it remains incompletely understood. © 2013 The Author. Experimental Physiology © 2013 The Physiological Society.


Lip G.Y.H.,University of Birmingham | Haguenoer K.,University of Tours | Saint-Etienne C.,University of Tours | Fauchier L.,University of Tours
Chest | Year: 2014

BACKGROUND: The efficacy and safety of anticoagulation with use of vitamin K antagonists (VKAs) is highly dependent on the quality of anticoagulation control as reflected by the average time in a therapeutic range of 2.0 to 3.0. A clinical dilemma is trying to predict which anticoagulation-naive patients with atrial fibrillation (AF) would do well on a VKA (with a time in therapeutic range > 70%) and which are less likely to do well on a VKA but could be managed with novel oral anticoagulants.METHODS: The cohort comprised 8,120 patients, among whom 4,637 patients were receiving VKA. We investigated whether the SAMe-TT2R2(sex female, age, 60 years, medical history [more than two comorbidities], treatment [interacting drugs, eg, amiodarone for rhythm control] tobacco use [doubled], race [doubled]) score could discriminate among patients with AF who were likely to have a labile international normalized ratio (INR) during follow-up as well as stroke/thromboembolism (TE), clinically relevant bleeding (defined as severe bleeding and as Bleeding Academic Research Consortium [BARC]-defined major bleeding), and death while being treated with a VKA.RESULTS: During a mean follow-up of 1,016 ± 1,108 days, there was a significant increase in risk of severe bleeding events (risk ratio [RR], 1.38; 95% CI, 1.12-2.68; P 5 .002) and a significant increase in risk of major BARC bleeding (RR, 1.77; 95% CI, 1.29-2.44; P = .0005) in patients with AF with a high SAMe-TT 2 R 2 score (> 2). Increasing SAMe-TT 2 R 2 score was associated with an increasing risk of labile INR ( P 5 .004), stroke/TE (P = .007), severe bleeding (P < .0001), major BARC bleeding (P < .0001), and death (P = .002) at follow-up. Among the patients taking VKAs, the SAMe-TT 2 R 2 score was predictive of labile INR (C statistic approximately 0.58) as well as of stroke/TE, severe bleeding, major BARC bleeding, and death (C statistic, 0.54-0.57 for events), reflecting the suboptimal time in therapeutic range in such patients. This was not the case for patients who were not taking VKAs.CONCLUSIONS: We demonstrate that the SAMe-TT2R2score was predictive for an increasing risk of stroke/TE, severe bleeding, major BARC bleeding, and death, reflecting poor anticoagulation control (and labile INRs) among patients with AF given VKAs. © 2014 AMERICAN COLLEGE OF CHEST PHYSICIANS.


Del Pozzo W.,National Institute for Subatomic Physics | Del Pozzo W.,University of Birmingham
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

The advanced worldwide network of gravitational waves (GW) observatories is scheduled to begin operations within the current decade. Thanks to their improved sensitivity, they promise to yield a number of detections and thus to open new observational windows for astronomy and astrophysics. Among the scientific goals that should be achieved, there is the independent measurement of the value of the cosmological parameters, hence an independent test of the current cosmological paradigm. Because of the importance of such a task, a number of studies have evaluated the capabilities of GW telescopes in this respect. However, since GW do not yield information about the source redshift, different groups have made different assumptions regarding the means through which the GW redshift can be obtained. These different assumptions imply also different methodologies to solve this inference problem. This work presents a formalism based on Bayesian inference developed to facilitate the inclusion of all assumptions and prior information about a GW source within a single data analysis framework. This approach guarantees the minimization of information loss and the possibility of including naturally event-specific knowledge (such as the sky position for a gamma ray burst-GW coincident observation) in the analysis. The workings of the method are applied to a specific example, loosely designed along the lines of the method proposed by Schutz in 1986, in which one uses information from wide-field galaxy surveys as prior information for the location of a GW source. I show that combining the results from few tens of observations from a network of advanced interferometers will constrain the Hubble constant H 0 to an accuracy of ∼4%-5% at 95% confidence. © 2012 American Physical Society.


Sinden N.J.,University of Birmingham | Stockley R.A.,Adapt Inc
European Respiratory Journal | Year: 2013

Chronic obstructive pulmonary disease (COPD) is associated with tissue damage believed to result from an imbalance between serine proteinases and their inhibitors. Although the role of neutrophil elastase (NE) has been studied, it is likely that other proteinases play a role. The importance of proteinase 3 (PR3) has not been established, as specific substrates have only recently been available. We studied clinically stable subjects with either alpha-1-antitrypsin (A1AT) deficiency or usual COPD with chronic bronchitis. Sol phase sputum was analysed for PR3 activity and concentration, NE activity and concentration, concentrations of airway inhibitors (A1AT, secretory leukoproteinase inhibitor and elafin) and markers of neutrophilic inflammation. 12 patients were also studied during exacerbations. PR3 activity was present in most sputum samples and greater than NE activity (which was largely undetectable) in both subject groups (A1AT deficiency median PR3 128 nM, interquartile range (IQR) 33-558 nM; NE 0 nM, IQR 0-0 nM; p=0.0043; COPD PR3 22 nM, IQR 0-103 nM; NE 0 nM, IQR 0-0 nM; p=0.015). PR3 activity was greater during exacerbations than in the stable state (p=0.037) and correlated with markers of neutrophilic inflammation. The regular identification of PR3 activity in sputum from stable subjects with A1AT deficiency or usual COPD suggests it may play a greater role in the pathophysiology than previously thought. Copyright©ERS 2013.


Jackson D.,Institute of Public Health | Riley R.D.,University of Birmingham
Statistics in Medicine | Year: 2014

Making inferences about the average treatment effect using the random effects model for meta-analysis is problematic in the common situation where there is a small number of studies. This is because estimates of the between-study variance are not precise enough to accurately apply the conventional methods for testing and deriving a confidence interval for the average effect. We have found that a refined method for univariate meta-analysis, which applies a scaling factor to the estimated effects' standard error, provides more accurate inference. We explain how to extend this method to the multivariate scenario and show that our proposal for refined multivariate meta-analysis and meta-regression can provide more accurate inferences than the more conventional approach. We explain how our proposed approach can be implemented using standard output from multivariate meta-analysis software packages and apply our methodology to two real examples. © 2013 John Wiley & Sons, Ltd.


Wilkins L.,University of Birmingham
Investigative ophthalmology & visual science | Year: 2013

A driving simulator was used to examine the relationship between motion perception and driving performance. Although motion perception test scores have been shown to be related to driving safety, it is not clear which combination of tests are the best predictors and whether motion perception training can improve driving performance. In experiment 1, 60 younger drivers (22.4 ± 2.5 years) completed three motion perception tests (2-dimensional [2D] motion-defined letter [MDL] identification, 3D motion in depth sensitivity [MID], and dynamic visual acuity [DVA]) followed by two driving tests (emergency braking [EB] and hazard perception [HP]). In experiment 2, 20 drivers (21.6 ± 2.1 years) completed 6 weeks of motion perception training (using the MDL, MID, and DVA tests), while 20 control drivers (22.0 ± 2.7 years) completed an online driving safety course. The EB performance was measured before and after training. In experiment 1, MDL (r = 0.34) and MID (r = 0.46) significantly correlated with EB score. The change in DVA score as a function of target speed (i.e., "velocity susceptibility") was correlated most strongly with HP score (r = -0.61). In experiment 2, the motion perception training group had a significant decrease in brake reaction time on the EB test from pre- to posttreatment, while there was no significant change for the control group: t(38) = 2.24, P = 0.03. Tests of 3D motion perception are the best predictor of EB, while DVA velocity susceptibility is the best predictor of hazard perception. Motion perception training appears to result in faster braking responses.


This paper presents the first large-eddy simulation (LES) study of transfer and dispersion of a scalar released from a rough urban facet, either the street surface, the upstream-wall, or the downstream-wall, under the thermo-dynamical conditions of either the upstream-wall or the downstream-wall, plus the roof, heated by solar radiation. The boundary condition of a constant value is adopted for the scalars on the rough urban facets and a wall function is proposed for the scalars.The LES results demonstrate that dispersion inside the street canyon possesses distinctive characteristics for two conditions: the assisting condition in which the thermal-driven flow has the same direction as that of the wind-driven vortex and the opposing condition in which the thermal-driven flow has the opposite direction as that of the wind-driven vortex. For the street-released scalar under the opposing condition, the concentration fluctuations relative to the mean concentration can reach 50% and in general they are much larger than those for the assisting cases which are in the range of 25-30%. The exchange velocity of a scalar between the street canyon air and the urban boundary layer (UBL), wCB(c), is one order of magnitude larger than the exchange velocity between a facet and the urban boundary layer, UBL, w0B(c), indicating quantitatively that the resistance to the transfer of a facet-released scalar is dominated by the near-facet processes. As the temperature difference between the wall and the UBL, Δ. T, increases, the total resistance to street canyon ventilation becomes more dominated by the near-facet resistance. The assisting conditions are favourable to ventilating the scalars from both walls, whereas the opposing conditions are only favourable to the ventilation of the downstream-wall released scalar. In the range of Δ. T tested in this study, the exchange velocity, wCB(c), linearly increases with Δ. T and can be well parameterised. For the assisting cases, the advective (or dispersive) flux dominates the turbulent flux in most part of the canyon and the partition between the two alters dramatically across the roof level with turbulent processes dominating above the roof level. This study also suggests that for the street-released scalar, the resistance between the bottom canyon and the upper canyon is significant compared with the one between the upper canyon and the UBL. It is therefore necessary to adopt a two-box model in order to reasonably model such a case. The results of this study provide the guidance of improving the parameterisation schemes of transfer and dispersion for street canyons which currently do not consider the influence of wall heating. © 2012 Elsevier Ltd.


Moran D.,University of Birmingham
Environment and Planning D: Society and Space | Year: 2013

Geography, as a disciplinary lens, brings a valuable perspective to the study of the carceral, and carceral geography's concern for the spatial could provide a new explanatory perspective to the consideration of some accepted tenets within criminology, whilst at the same time offering a productive and useful 'grounding' of contemporary geographies of emotion and affect. In the context of hyperincarceration and the carceral continuum of recidivism and repeated reimprisonment, this paper considers the long-observed relationship between prison visitation and reduced recidivism, posits prison visiting rooms as underresearched carceral spaces, and develops theoretical and methodological innovations which nuance the understanding of prison visiting.


Morel T.,University of Liege | Miglio A.,University of Birmingham
Monthly Notices of the Royal Astronomical Society: Letters | Year: 2012

The frequency of maximum oscillation power measured in dwarfs and giants exhibiting solar-like pulsations provides a precise, and potentially accurate, inference of the stellar surface gravity. An extensive comparison for about 40 well-studied pulsating stars with gravities derived using classical methods (ionization balance, pressure-sensitive spectral features or location with respect to evolutionary tracks) supports the validity of this technique and reveals an overall remarkable agreement with mean differences not exceeding 0.05dex (although with a dispersion of up to ∼0.2dex). It is argued that interpolation in theoretical isochrones may be the most precise way of estimating the gravity by traditional means in nearby dwarfs. Attention is drawn to the usefulness of seismic targets as benchmarks in the context of large-scale surveys. © 2011 The Authors Monthly Notices of the Royal Astronomical Society © 2011 RAS.


Pollet B.G.,University of the Western Cape | Staffell I.,Imperial College London | Shang J.L.,University of Birmingham
Electrochimica Acta | Year: 2012

Decarbonising transport is proving to be one of today's major challenges for the global automotive industry due to many factors such as the increase in greenhouse gas and particulate emissions affecting not only the climate but also humans, the increase in pollution, rapid oil depletion, issues with energy security and dependency from foreign sources and population growth. For more than a century, our society has been dependent upon oil, and major breakthroughs in low- and ultra-low carbon technologies and vehicles are urgently required. This review paper highlights the current status of hybrid, battery and fuel cell electric vehicles from an electrochemical and market point of view. The review paper also discusses the advantages and disadvantages of using each technology in the automotive industry and the impact of these technologies on consumers. © 2012 Elsevier Ltd.


Meads C.,Brunel University | Moore D.,University of Birmingham
BMC Public Health | Year: 2013

Background: The UK Parliamentary Enquiry and USA Institute of Medicine state that lesbians may be at a higher risk of breast cancer but there is insufficient information. Lesbians and bisexual (LB) women have behavioural risk-factors at higher rates compared to heterosexuals such as increased alcohol intake and higher stress levels. Conversely, breast cancer rates are higher in more affluent women yet income levels in LB women are relatively low. This systematic review investigated all evidence on whether there is, or likely to be, higher rates of breast cancer in LB women. Methods. Cochrane library (CDSR, CENTRAL, HTA, DARE, NHSEED), MEDLINE, EMBASE, PsychINFO, CAB abstracts, Web of Science (SCI, SSCI), SIGLE and Social Care Online databases were searched to October 2013. Unpublished research and specific lesbian, gay and bisexual websites were checked, as were citation lists of relevant papers. Included were studies in LB populations reporting breast cancer incidence or prevalence rates, risk model results or risk-factor estimates. Inclusions, data-extraction and quality assessment were by two reviewers with disagreements resolved by discussion. Results: Searches found 198 references. No incidence rates were found. Nine studies gave prevalence estimates - two showed higher, four showed no differences, one showed mixed results depending on definitions, one had no comparison group and one gave no sample size. All studies were small with poor methodological and/or reporting quality. One incidence modelling study suggested a higher rate. Four risk modelling studies were found, one Rosner-Colditz and three Gail models. Three suggested higher and one lower rate in LB compared to heterosexual women. Six risk-factor estimates suggested higher risk and one no difference between LB and heterosexual women. Conclusions: The only realistic way to establish rates in LB women would be to collect sexual orientation within routine statistics, including cancer registry data, or from large cohort studies. © 2013 Meads and Moore; licensee BioMed Central Ltd.


Day R.,University of Birmingham
Energy Policy | Year: 2015

This paper is a commentary on the theme of this special issue, low carbon thermal technologies and older age, and the Conditioning Demand project. Drawing on the project findings, I discuss some key aspects of ageing that are relevant to the roll-out of low carbon technologies in domestic settings in ageing, developed societies. These include biological, cognitive, institutional and social dimensions. I conclude with some suggestions for ways of working to maximise the potential benefits of low carbon thermal technologies for older people. © 2014 Elsevier Ltd.


Aging is frequently characterized by the accumulation of altered proteins and dysfunctional mitochondria. This review discusses possible causes of these effects, their interdependence and the impact of energy metabolism on proteostasis, especially formation and elimination of altered proteins. It is suggested NAD+ to some degree regulates formation of aberrant proteins and generation of oxygen free-radicals and reactive oxygen species (ROS), because when NAD+ is limiting, glycolytic triose phosphates spontaneously decompose into methylglyoxal (MG), a highly deleterious glycating agent and ROS inducer. That NAD+ has stimulatory effects on stress protein expression and autophagy, while mitochondria regenerate NAD+ from NADH, further integrates energy metabolism into proteostasis. It is suggested that, as altered proteins can deleteriously interact with mitochondria, changes in synthesis, or elimination, of cytosolic error-proteins will affect mitochondrial activity. It is also suggested that functional mitochondria are essentially antiaging agents, while their dysfunction or inactivity accelerate ROS formation and aging. These proposals may also help explain the oxygen paradox that while ROS may be causal to aging, increased mitochondrial activity (i.e., oxygen utilization) suppresses aging and much associated pathology. Increased synthesis of glutathione, humanin, and mitochondrial chaperone proteins are other additional consequences of increased mitogenesis and which would help ensure proteostasis.


The move from “paraphilias” to “paraphilic disorders,” where only the latter constitute mental disorders, has been hailed as a major change to the conception of non-normative sexualities in DSM-5. However, this is a claim that has been criticized by numerous activists and doctors working for removal of all diagnoses of so-called sexual disorders from the APA’s manual. This article, written from a critical humanities, queer theory-inflected perspective, examines the historical and ideological grounds underlying the inclusion of the newly branded “paraphilic disorders” in DSM-5. It argues that the diagnosis does nothing to overturn the conservative and utilitarian view of sexuality as genitally oriented and for reproduction that has colored sexological and psychiatric history. It suggests that despite homosexuality no longer being classed as a disorder, an implicit heteronormativity continues to define psychiatric perceptions of sexuality. In sum, this article proposes that (1) the production of the field of psychiatric knowledge concerning “perversion”/“sexual deviation”/“paraphilia”/“paraphilic disorder” is more ideological than properly scientific; (2) the “normophilic” bias of the DSM is a bias in favor of heteronormativity and reproduction; and (3) some sexual practices are valued above others, regardless of claims that the presence of a paraphilic practice itself is no longer a criterion for a diagnosis of mental disorder. © 2015, Springer Science+Business Media New York.


The paper by Shaffer, McManama, Swank, Williams & Durgin (2014) uses correlations between palm-board and verbal estimates of geographical slant to argue against dissociation of the two measures. This paper reports the correlations between the verbal, visual and palm-board measures of geographical slant used by Proffitt and co-workers as a counterpoint to the analyses presented by Shaffer and colleagues. The data are for slant perception of staircases in a station (N= 269), a shopping mall (N= 229) and a civic square (N= 109). In all three studies, modest correlations between the palm-board matches and the verbal reports were obtained. Multiple-regression analyses of potential contributors to verbal reports, however, indicated no unique association between verbal and palm-board measures. Data from three further studies (combined N= 528) also show no evidence of any relationship. Shared method variance between visual and palm-board matches could account for the modest association between palm-boards and verbal reports. © 2014.


Stockley R.A.,University of Birmingham
Expert Opinion on Emerging Drugs | Year: 2010

Importance of the field: Alpha-1-antitrypsin (A1AT) deficiency is a common genetic condition that predisposes individuals to the development of chronic obstructive pulmonary disease (COPD) as a direct result of damage caused to the lung by proteolytic enzymes released by migrating neutrophils. The lack of A1AT fails to control these enzymes and in the most common genetic deficiency (Pi Z) is due to accumulation of A1AT in the liver as a result of polymer formation. There is no specific treatment for COPD but understanding the pathophysiology of the disease in A1AT deficiency has led to strategies being used or developed to prevent the lung and liver disease. These strategies may have benefits beyond A1AT deficiency. Areas covered in this review: The review covers the history of discovery of the nature and role of A1AT deficiency with particular emphasis on the pathophysiology of the lung disease. Evidence for the role of current therapies is provided together with data of preliminary or experimental strategies that are under development. What the reader will gain: The reader will gain insight into the role of proteinases in the pathophysiology of COPD with particular reference to A1AT deficiency, which is the only human model of the disease. Current evidence of the efficacy of augmentation is provided together with new ways of readdressing the balance between neutrophil proteinases and natural or synthetic inhibitors or repairing lung damage. Take home message: A1AT deficiency is a good model to investigate the role of inflammation and proteolytic enzymes in the pathophysiology of COPD. Augmentation therapy is expensive but restores the deficiency to normal and current evidence suggests this ameliorates progression of the disease. Understanding the mechanisms involved has led to the development of newer strategies to protect the lung and liver from the development of disease but efficacy and safety concerns require careful introduction of these strategies. Although the condition is relatively common in the Northern hemisphere, the ability to deliver conventional Phase III clinical trials with lung physiology as the primary outcome will be limited by the sensitivity of the tests and number of patients required. © 2010 Informa UK, Ltd.


Dawson A.J.,University of Birmingham
Journal of Medical Ethics | Year: 2015

Good medical ethics needs to look more to the resources of public health ethics and use more societal, population or community values and perspectives, rather than defaulting to the individualistic values that currently dominate discussion. In this paper I argue that we can use the recent response to Ebola as an example of a major failure of the global community in three ways. First, the focus has been on the treatment of individuals rather than seeing that the priority ought to be public health measures. Second, the advisory committee on experimental interventions set up by the WHO has focused on ethical issues related to individuals and their guidance has been unclear. Third, the Ebola issue can be seen as a symptom of a massive failure of the global community to take sufficient notice of global injustice.


Freeman S.D.,University of Birmingham
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

Older patients with acute myeloid leukemia (AML) have a high relapse rate after standard chemotherapy. We investigated whether measuring chemotherapy sensitivity by multiparameter flow cytometric minimal residual disease (MFC-MRD) detection has prognostic value in patients older than age 60 years or is simply a surrogate for known age-related risk factors. Eight hundred ninety-two unselected patients treated intensively in the United Kingdom National Cancer Research Institute AML16 Trial were assessed prospectively for MFC-MRD during treatment. Eight hundred thirty-three patients had leukemia-associated immunophenotypes (LAIPs) identified by pretreatment screening. Four hundred twenty-seven patients entered complete remission (CR) after one or two courses (designated C1 and C2, respectively) and were MFC-MRD assessable by LAIP detection in CR bone marrow for at least one of these time points. MRD positivity was defined as residual disease detectable by LAIP. MFC-MRD negativity, which was achieved in 51% of patients after C1 (n = 286) and 64% of patients after C2 (n = 279), conferred significantly better 3-year survival from CR (C1: 42% v 26% in MRD-positive patients, P < .001; C2: 38% v 18%, respectively; P < .001) and reduced relapse (C1: 71% v 83% in MRD-positive patients, P < .001; C2: 79% v 91%, respectively; P < .001), with higher risk of early relapse in MRD-positive patients (median time to relapse, 8.5 v 17.1 months, respectively). In multivariable analysis, MRD status at the post-C1 time point independently predicted survival, identifying a subgroup of intermediate-risk patients with particularly poor outcome. However, survival benefit from gemtuzumab ozogamicin was not associated with MFC-MRD chemotherapy sensitivity. Early assessment of treatment response using flow cytometry provides powerful independent prognostic information in older adults with AML, lending support to the incorporation of MRD detection to refine risk stratification and inform clinical trial design in this challenging group of patients.


Knott J.,University of Birmingham
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2015

This paper describes characteristics of transgranular cleavage fracture in structural steel, viewed at different size-scales. Initially, consideration is given to structures and the service duty to which they are exposed at the macroscale, highlighting failure by plastic collapse and failure by brittle fracture. This is followed by sections describing the use of fracture mechanics and materials testing in carryingout assessments of structural integrity. Attention then focuses on the microscale, explaining how values of the local fracture stress in notched bars or of fracture toughness in pre-cracked test-pieces are related to features of the microstructure: carbide thicknesses in wrought material; the sizes of oxide/silicate inclusions in weld metals. Effects of a microstructure that is 'heterogeneous' at the mesoscale are treated briefly, with respect to the extraction of test-pieces from thick sections and to extrapolations of data to low failure probabilities. The values of local fracture stress may be used to infer a local 'work-of-fracture' that is found experimentally to be a few times greater than that of two free surfaces. Reasons for this are discussed in the conclusion section on nano-scale events. It is suggested that, ahead of a sharp crack, it is necessary to increase the compliance by a cooperative movement of atoms (involving extra work) to allow the crack-tip bond to displace sufficiently for the energy of attraction between the atoms to reduce to zero. © 2015 The Author(s) Published by the Royal Society. All rights reserved.


Overton T.W.,University of Birmingham
Drug Discovery Today | Year: 2014

The production of recombinant proteins is crucial for both the development of new protein drugs and the structural determination of drug targets. As such, recombinant protein production has a major role in drug development. Bacterial hosts are commonly used for the production of recombinant proteins, accounting for approximately 30% of current biopharmaceuticals on the market. In this review, I introduce fundamental concepts in recombinant protein production in bacteria, from drug development to production scales. Recombinant protein production processes can often fail, but how can this failure be minimised to rapidly deliver maximum yields of high-quality protein and so accelerate drug discovery? © 2013 Elsevier Ltd.


PURPOSE OF REVIEW: A broad range of organizational issues can have an impact on client outcomes in residential services for people with intellectual disabilities, and staff psychological factors are increasingly being recognized as important. This review explores some of the recent literature on staff attitudes, attributions, well being and other factors that may impact on outcomes for residents. RECENT FINDINGS: Staff beliefs are associated with the relationship between challenging behaviour and burnout experienced by staff; resident outcomes such as placement breakdown may also be influenced by staff attributions. There is also a body of evidence emerging that suggests staff psychological factors may influence the quality of physical healthcare received by people with intellectual disabilities. SUMMARY: Sufficient evidence exists to suggest that clinicians should routinely consider assessing and evaluating staff psychological factors in clinical interventions in order to assess their potential impact on client care. Further research is required, particularly, to evaluate the specific impact of staff psychological factors on resident outcome. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Baranoff E.,University of Birmingham | Curchod B.F.E.,Stanford University
Dalton Transactions | Year: 2015

FIrpic is the most investigated bis-cyclometallated iridium complex in particular in the context of organic light emitting diodes (OLEDs) because of its attractive sky-blue emission, high emission efficiency, and suitable energy levels. In this Perspective we review the synthesis, structural characterisations, and key properties of this emitter. We also survey the theoretical studies and summarise a series of selected monochromatic electroluminescent devices using FIrpic as the emitting dopant. Finally we highlight important shortcomings of FIrpic as an emitter for OLEDs. Despite the large body of work dedicated to this material, it is manifest that the understanding of photophysical and electrochemical processes are only broadly understood mainly because of the different environment in which these properties are measured, i.e., isolated molecules in solvent vs. device. © 2015 The Royal Society of Chemistry.


Jones C.,University of Birmingham
Cochrane database of systematic reviews (Online) | Year: 2012

Cognitive behavioural therapy (CBT) is now a recommended treatment for people with schizophrenia. This approach helps to link the person's distress and problem behaviours to underlying patterns of thinking. To review the effects of CBT for people with schizophrenia when compared with other psychological therapies. We searched the Cochrane Schizophrenia Group Trials Register (March 2010) which is based on regular searches of CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected all references of the selected articles for further relevant trials, and, where appropriate, contacted authors. All relevant randomised controlled trials (RCTs) of CBT for people with schizophrenia-like illnesses. Studies were reliably selected and assessed for methodological quality. Two review authors, working independently, extracted data. We analysed dichotomous data on an intention-to-treat basis and continuous data with 65% completion rate are presented. Where possible, for dichotomous outcomes, we estimated a risk ratio (RR) with the 95% confidence interval (CI) along with the number needed to treat/harm. Thirty papers described 20 trials. Trials were often small and of limited quality. When CBT was compared with other psychosocial therapies, no difference was found for outcomes relevant to adverse effect/events (2 RCTs, n = 202, RR death 0.57 CI 0.12 to 2.60). Relapse was not reduced over any time period (5 RCTs, n = 183, RR long-term 0.91 CI 0.63 to 1.32) nor was rehospitalisation (5 RCTs, n = 294, RR in longer term 0.86 CI 0.62 to 1.21). Various global mental state measures failed to show difference (4 RCTs, n = 244, RR no important change in mental state 0.84 CI 0.64 to 1.09). More specific measures of mental state failed to show differential effects on positive or negative symptoms of schizophrenia but there may be some longer term effect for affective symptoms (2 RCTs, n = 105, mean difference (MD) Beck Depression Inventory (BDI) -6.21 CI -10.81 to -1.61). Few trials report on social functioning or quality of life. Findings do not convincingly favour either of the interventions (2 RCTs, n = 103, MD Social Functioning Scale (SFS) 1.32 CI -4.90 to 7.54; n = 37, MD EuroQOL -1.86 CI -19.20 to 15.48). For the outcome of leaving the study early, we found no significant advantage when CBT was compared with either non-active control therapies (4 RCTs, n = 433, RR 0.88 CI 0.63 to 1.23) or active therapies (6 RCTs, n = 339, RR 0.75 CI 0.40 to 1.43) Trial-based evidence suggests no clear and convincing advantage for cognitive behavioural therapy over other - and sometime much less sophisticated - therapies for people with schizophrenia.


Barnett A.H.,University of Birmingham
Advances in Therapy | Year: 2011

The dipeptidyl peptidase 4 (DPP-4) inhibitors comprise a promising new class of agent for the management of type 2 diabetes. They possess a range of physiological effects associated with improved glycemic control including stimulation of glucose-dependent insulin secretion and suppression of glucagon secretion, and lower blood glucose levels through different, but potentially complementary, mechanisms to standard oral therapies. Linagliptin is the latest DPP-4 inhibitor to complete pivotal phase 3 trials. The data show that linagliptin provides significant, clinically meaningful and sustained improvements in glycemic control, with an incidence of adverse events similar to placebo and an excellent tolerability profile. In addition, linagliptin has been shown to be weight neutral and, importantly, there was no increased risk of hypoglycemia attributed to linagliptin use in monotherapy or combination therapy with metformin or pioglitazone. A unique characteristic of linagliptin that differentiates it from other members of the class is its primarily nonrenal route of excretion. The linagliptin phase 3 program included several hundred patients with type 2 diabetes and different stages of renal disease and the data suggest that the drug would not need dose adjustment, regardless of the degree of renal impairment. There is a particular need for safe and effective therapeutic agents that can be used when renal function declines. Linagliptin has recently been approved by the US Food and Drug Administration and may find a place in therapy as a treatment option for the significant number of patients in whom metformin and the other DPP-4 inhibitors are either contraindicated or require dose adjustment because of moderate to severe renal impairment. © 2011 Springer Healthcare.


Heiles S.,TU Darmstadt | Johnston R.L.,University of Birmingham
International Journal of Quantum Chemistry | Year: 2013

Over the past decade, there has been a significant growth in the development and application of methods for performing global optimization (GO) of cluster and nanoparticle structures using first-principles electronic structure methods coupled to sophisticated search algorithms. This has in part been driven by the desire to avoid the use of empirical potentials (EPs), especially in cases where no reliable potentials exist to guide the search toward reasonable regions of configuration space. This has been facilitated by improvements in the reliability of the search algorithms, increased efficiency of the electronic structure methods, and the development of faster, multiprocessor high-performance computing architectures. In this review, we give a brief overview of GO algorithms, though concentrating mainly on genetic algorithm and basin hopping techniques, first in combination with EPs. The major part of the review then deals with details of the implementation and application of these search methods to allow exploration for global minimum cluster structures directly using electronic structure methods and, in particular, density functional theory. Example applications are presented, ranging from isolated monometallic and bimetallic clusters to molecular clusters and ligated and surface supported metal clusters. Finally, some possible future developments are highlighted. © 2013 Wiley Periodicals, Inc.


Blann A.D.,University of Birmingham
Thrombosis Research | Year: 2012

The importance of the endothelium is cancer is not disputed. However, equally without doubt is the fact that cancer is a hypercoagulable state. Furthermore, there is evidence that two are linked, and that this link may also be causative in that changes to vascular biology in cancer lead to an increased risk of thrombosis. The objective of this communication is to summarise the evidence that adverse changes to the endothelium, as evidenced by changes in the expression and secretion of different cells, cell particles, and molecules, together lead to an increased risk of thrombosis. This, in turn, provides the basis for the viewpoint that vascular health is valuable and should be protected and maintained, possibly the use of vascular-friendly treatments. © 2012 Elsevier Ltd.


Lund P.,University of Birmingham | Tramonti A.,University of Rome La Sapienza | De Biase D.,University of Rome La Sapienza
FEMS Microbiology Reviews | Year: 2014

As part of their life cycle, neutralophilic bacteria are often exposed to varying environmental stresses, among which fluctuations in pH are the most frequent. In particular, acid environments can be encountered in many situations from fermented food to the gastric compartment of the animal host. Herein, we review the current knowledge of the molecular mechanisms adopted by a range of Gram-positive and Gram-negative bacteria, mostly those affecting human health, for coping with acid stress. Because organic and inorganic acids have deleterious effects on the activity of the biological macromolecules to the point of significantly reducing growth and even threatening their viability, it is not unexpected that neutralophilic bacteria have evolved a number of different protective mechanisms, which provide them with an advantage in otherwise life-threatening conditions. The overall logic of these is to protect the cell from the deleterious effects of a harmful level of protons. Among the most favoured mechanisms are the pumping out of protons, production of ammonia and proton-consuming decarboxylation reactions, as well as modifications of the lipid content in the membrane. Several examples are provided to describe mechanisms adopted to sense the external acidic pH. Particular attention is paid to Escherichia coli extreme acid resistance mechanisms, the activity of which ensure survival and may be directly linked to virulence. © 2014 Federation of European Microbiological Societies.


Britton M.M.,University of Birmingham
Chemical Society Reviews | Year: 2010

Magnetic resonance imaging (MRI) has long been recognized as one of the most important tools in medical diagnosis and research. However, MRI is also well placed to image chemical reactions and processes, determine the concentration of chemical species, and look at how chemistry couples with environmental factors, such as flow and heterogeneous media. This tutorial review will explain how magnetic resonance imaging works, reviewing its application in chemistry and its ability to directly visualise chemical processes. It will give information on what resolution and contrast are possible, and what chemical and physical parameters can be measured. It will provide examples of the use of MRI to study chemical systems, its application in chemical engineering and the identification of contrast agents for non-clinical applications. A number of studies are presented including investigation of chemical conversion and selectivity in fixed-bed reactors, temperature probes for catalyst pellets, ion mobility during tablet dissolution, solvent dynamics and ion transport in Nafion polymers and the formation of chemical waves and patterns. © 2010 The Royal Society of Chemistry.


Antonsich M.,University of Birmingham
Geography Compass | Year: 2010

Belonging is a notion both vaguely defined and ill-theorized. Scholars in various social disciplines often take this notion for granted, as if its meaning is somewhat self-explanatory. Others tend to equate it with the notion of identity, citizenship, or both. By relying on a critical reading of an extensive literature across academic disciplines, this study aims to offer an analytical framework for the study of belonging. I argue that belonging should be analyzed both as a personal, intimate, feeling of being 'at home' in a place (place-belongingness) and as a discursive resource that constructs, claims, justifies, or resists forms of socio-spatial inclusion/exclusion (politics of belonging). The risk of focusing only on one of these two dimensions is to fall in the trap of either a socially de-contextualized individualism or an all-encompassing social(izing) discourse. The open question is whether the increasing cultural and ethnic diversification of contemporary societies can lead to the formation of communities of belonging beyond communities of identity. © 2010 The Author. Journal Compilation © 2010 Blackwell Publishing Ltd.


Approximately 20,000 people have a transient ischemic attack (TIA) and 23,375 have a minor stroke in England each year. Fatigue, psychological and cognitive impairments are well documented post-stroke. Evidence suggests that TIA and minor stroke patients also experience these impairments; however, they are not routinely offered relevant treatment. This systematic review aims to: (1) establish the prevalence of fatigue, anxiety, depression, post-traumatic stress disorder (PTSD) and cognitive impairment following TIA and minor stroke and to investigate the temporal course of these impairments; (2) explore impact on quality of life (QoL), change in emotions and return to work; (3) identify where further research is required and to potentially inform an intervention study. A systematic review of MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane libraries and grey literature between January 1993 and April 2013 will be undertaken. Two reviewers will conduct screening search results, study selection, data extraction and quality assessment. Studies of adult TIA and minor stroke participants containing any of the outcomes of interest; fatigue, anxiety, depression, PTSD or cognitive impairment will be included. Studies at any time period after TIA/minor stroke, including those with any length of follow-up, will be included to investigate the temporal course of impairments. QoL, change in emotions and return to work will also be documented. The proportion of TIA or minor stroke participants experiencing each outcome will be reported.If appropriate, a meta-analysis will pool results of individual outcomes. Studies will be grouped and analyzed according to their follow-up timeframe into short-term (< 3 months after TIA/minor stroke), medium-term (3 to 12 months) and long term (> 12 months). Sub-analysis of studies with a suitable control group will be conducted. Exploratory sub-analysis of memory and attention domains of cognitive impairment will be conducted. The current treatment goal for TIA and minor stroke patients is secondary stroke prevention. If these patients do experience fatigue, psychological or cognitive impairments then this treatment alone is unlikely to be sufficient. The results of this comprehensive review will increase understanding of treatment needs for this patient group, identify where further research is required and potentially inform an intervention trial.


Hauton D.,University of Birmingham
Comparative Biochemistry and Physiology - A Molecular and Integrative Physiology | Year: 2012

Environmental stresses such as hypoxia can alter the development of the fetus that are manifested later in life, but the impact of early maternal hypoxia (MH) on cardiac performance, coronary flow and catecholamine responsiveness in adult offspring is less clear. The effects of exposure to chronic hypoxia (FIO2=0.12) in early intrauterine development (days E1-10) on cardiac performance of the adult offspring were estimated using the Langendorff-perfused rat heart. Cardiac dysfunction is presented as increased end-diastolic volume, with decreased ventricular stiffness in both male and female adult offspring (P<0.01 for both). While developed pressures were preserved in female MH rats, males demonstrated a decrease in systolic function, estimated as peak developed pressure (P<0.01). Challenge with dobutamine (300nM), an adrenergic positive inotrope, increased cardiac work for control rats (P<0.01 for male and female rats) but not in MH-male rats. Coronary flow was reduced (P<0.01) and SERCA2 protein expression increased (2-fold, P<0.05) in female offspring, while eNOS protein levels were increased (2.5-fold, P<0.05) in females. This suggests gender-specific differences in compensatory responses to early MH, with female rats increasing calcium turnover to improve contractility and increasing coronary flow through increased expression of eNOS protein, partially restoring coronary perfusion while male rats show little compensation. © 2012 Elsevier Inc.


Willis B.H.,University of Birmingham | Hyde C.J.,University of Exeter
Journal of Clinical Epidemiology | Year: 2014

Objectives To determine a plausible estimate for a test's performance in a specific setting using a new method for selecting studies. Study Design and Setting It is shown how routine data from practice may be used to define an "applicable region" for studies in receiver operating characteristic space. After qualitative appraisal, studies are selected based on the probability that their study accuracy estimates arose from parameters lying in this applicable region. Three methods for calculating these probabilities are developed and used to tailor the selection of studies for meta-analysis. The Pap test applied to the UK National Health Service (NHS) Cervical Screening Programme provides a case example. Results The meta-analysis for the Pap test included 68 studies, but at most 17 studies were considered applicable to the NHS. For conventional meta-analysis, the sensitivity and specificity (with 95% confidence intervals) were estimated to be 72.8% (65.8, 78.8) and 75.4% (68.1, 81.5) compared with 50.9% (35.8, 66.0) and 98.0% (95.4, 99.1) from tailored meta-analysis using a binomial method for selection. Thus, for a cervical intraepithelial neoplasia (CIN) 1 prevalence of 2.2%, the post-test probability for CIN 1 would increase from 6.2% to 36.6% between the two methods of meta-analysis. Conclusion Tailored meta-analysis provides a method for augmenting study selection based on the study's applicability to a setting. As such, the summary estimate is more likely to be plausible for a setting and could improve diagnostic prediction in practice. © 2014 Elsevier Inc. All rights reserved.


Lip G.Y.H.,University of Aalborg | Lip G.Y.H.,University of Birmingham | Skjoth F.,University of Aalborg | Rasmussen L.H.,University of Aalborg | Larsen T.B.,University of Aalborg
Journal of the American College of Cardiology | Year: 2015

Background Even a single additional stroke risk factor in patients with atrial fibrillation may confer a risk of stroke. However, there is no consensus on how best to treat these patients. Objectives Our objective was to investigate the risk of stroke and bleeding and the impact of antithrombotic therapy among low-risk patients, i.e., with 0 or 1 CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score risk factor. Methods The nationwide cohort for this study was established by linking data from the Danish Civil Registration System, the Danish National Patient Register, and the Danish National Prescription Registry. We studied 39,400 patients discharged with incident nonvalvular atrial fibrillation with 0 or 1 CHA2DS2-VASc risk factor; 23,572 were not treated, 5,353 were initiated on aspirin, and 10,475 were initiated on warfarin. Results Stroke event rates for untreated low-risk patients (CHA2DS2-VASc = 0 [male], 1 [female]) were 0.49 per 100 person-years at 1 year and 0.47 per 100 person-years at full follow-up (intention-to-treat). Bleeding event rates among untreated low-risk patients were 1.08 per 100 person-years at 1 year and 0.97 at full follow-up. The presence of 1 additional stroke risk factor (CHA2DS2-VASc = 1 [male], = 2 [female]) among untreated patients increased the stroke rate at 1 year to 1.55 per 100 person-years, representing a significant 3.01-fold increase. At the 1-year follow-up, bleeding increased 2.35-fold, and death increased 3.12-fold. Conclusions Low-risk patients (CHA2DS2-VASc = 0 [male], 1 [female]) have a truly low risk for stroke and bleeding. With 1 additional stroke risk factor (CHA2DS2-VASc = 1 [male], = 2 [female]), there was a significant increase in event rates (particularly mortality) if nonanticoagulated. © 2015 American College of Cardiology Foundation.


Whitehouse T.,University of Birmingham | Wendon J.,Kings College
Best Practice and Research: Clinical Gastroenterology | Year: 2013

Untreated acute liver failure (ALF) has a poor outcome and so rapid diagnosis and management is vital if the patient is to survive. ALF has such profound and widespread physiological consequences that whenever possible, patients with ALF should be managed in an intensive care unit. Management is to support the physiology and treat the underlying cause. Advice should be sought from a centre capable of performing liver transplantation. Should recovery seem unlikely, liver transplantation is a viable treatment option in some cases. © 2013 Elsevier Ltd. All rights reserved.


Cook J.,University of Birmingham
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2016

The way in which we move influences our ability to perceive, interpret and predict the actions of others. Thus movements play an important role in social cognition. This review article will appraise the literature concerning movement kinematics and motor control in individuals with autism, and will argue that movement differences between typical and autistic individuals may contribute to bilateral difficulties in reciprocal social cognition. © 2016 The Author(s) Published by the Royal Society. All rights reserved.


Bryan R.T.,University of Birmingham
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2015

Cadherins are mediators of cell–cell adhesion in epithelial tissues. E-cadherin is a known tumour suppressor and plays acentral rolein suppressing the invasive phenotype of cancer cells. However, the abnormal expression of N- and P-cadherin (‘cadherin switching’, CS) has been shown topromotea more invasive and malignant phenotype of cancer, with P-cadherin possibly acting as a key mediator of invasion and metastasis in bladder cancer. Cadherins are also implicated in numerous signalling events related to embryonic development, tissue morphogenesis and homeostasis. It is these wide ranging effects and the serious implications of CS that make the cadherin cell adhesion molecules and their related pathways strong candidate targets for the inhibition of cancer progression, including bladder cancer. This review focuses on CS in the context of bladder cancer and in particular the switch to P-cadherin expression, and discusses other related molecules and phenomena, including EpCAM and the development of the cancer stem cell phenotype. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


An intensively melt sheared aluminum alloy was cast to verify the possibility of heterogeneous nucleation of aluminum grains from fine oxide particles. A novel combined technique of serial milling and lifting out using the focused ion beam has detected fine particles at the grain center of aluminum. High resolution analytical electron microscopy shows that oxides can act as substrates for the nucleation of aluminum grains. Based on the observations, the possibility of survival and nucleation potency of the oxide is discussed. © 2013 The Author.


Higgs S.,University of Birmingham
Appetite | Year: 2015

Manipulation of attention during eating has been reported to affect later consumption via changes in meal memory. The aim of the present studies was to examine the robustness of these effects and investigate moderating factors. Across three studies, attention to eating was manipulated via distraction (via a computer game or TV watching) or focusing of attention to eating, and effects on subsequent snack consumption and meal memory were assessed. The participants were predominantly lean, young women students and the designs were between-subjects. Distraction increased later snack intake and this effect was larger when participants were more motivated to engage with the distracter and were offset when the distractor included food-related cues. Attention to eating reduced later snacking and this effect was larger when participants imagined eating from their own perspective than when they imagined eating from a third person perspective. Meal memory was impaired after distraction but focusing on eating did not affect later meal memory, possibly explained by ceiling effects for the memory measure. The pattern of results suggests that attention manipulations during eating have robust effects on later eating and the effect sizes are medium to large. The data are consistent with previous reports and add to the literature by suggesting that type of attention manipulation is important in determining effects on later eating. The results further suggest that attentive eating may be a useful target in interventions to help with appetite control. © 2015 Elsevier Ltd.


Apperly I.A.,University of Birmingham
Quarterly Journal of Experimental Psychology | Year: 2012

Research on "theory of mind" has traditionally focused on a narrow participant group (preschool children) using a narrow range of experimental tasks (most notably, false-belief tasks). Recent work has greatly expanded the age range of human participants tested to include human infants, older children, and adults, has devised new tasks, and has adopted methods from cognitive psychology and neuroscience. However, theoretical work has not kept pace with these changes, with the result that studies using one kind of method or participant group often inherit assumptions about the nature of theory of mind from other research, with little regard for whether these assumptions are appropriate. I argue that three distinct approaches to thinking about theory of mind are already implicit in research practice, and that future work, whether with infants, children, or adults, will benefit from articulating these approaches more clearly and following their different implications for what theory of mind is and how it should be studied. © 2012 Copyright The Experimental Psychology Society.


Jones A.C.,University of Edinburgh | Neely R.K.,University of Birmingham
Quarterly Reviews of Biophysics | Year: 2015

Nearly 50 years since its potential as a fluorescent base analogue was first recognized, 2-aminopurine (2AP) continues to be the most widely used fluorescent probe of DNA structure and the perturbation of that structure by interaction with enzymes and other molecules. In this review, we begin by considering the origin of the dramatic and intriguing difference in photophysical properties between 2AP and its structural isomer, adenine although 2AP differs from the natural base only in the position of the exocyclic amine group, its fluorescence intensity is one thousand times greater. We then discuss the mechanism of interbase quenching of 2AP fluorescence in DNA, which is the basis of its use as a conformational probe but remains imperfectly understood. There are hundreds of examples in the literature of the use of changes in the fluorescence intensity of 2AP as the basis of assays of conformational change however, in this review we will consider in detail only a few intensity-based studies. Our primary aim is to highlight the use of time-resolved fluorescence measurements, and the interpretation of fluorescence decay parameters, to explore the structure and dynamics of DNA. We discuss the salient features of the fluorescence decay of 2AP when incorporated in DNA and review the use of decay measurements in studying duplexes, single strands and other structures. We survey the use of 2AP as a probe of DNA-enzyme interaction and enzyme-induced distortion, focusing particularly on its use to study base flipping and the enhanced mechanistic insights that can be gained by a detailed analysis of the decay parameters, rather than merely monitoring changes in fluorescence intensity. Finally we reflect on the merits and shortcomings of 2AP and the prospects for its wider adoption as a fluorescence-decay-based probe. © 2015 Cambridge University Press.


Newman P.R.,University of Birmingham | Wing M.,University College London | Wing M.,German Electron Synchrotron
Reviews of Modern Physics | Year: 2014

The hadronic final state in electron-proton collisions at HERA has provided a rich testing ground for development of the theory of the strong force, QCD. In this review, over 200 publications from the H1 and ZEUS Collaborations are summarized. Short distance physics, the measurement of processes at high-energy scales, has provided rigorous tests of perturbative QCD and constrained the structure of the proton as well as allowing precise determinations of the strong coupling constant to be made. Nonperturbative or low-energy processes have also been investigated and results on hadronization interpreted together with those from other experiments. Searches for exotic QCD objects, such as pentaquarks, glueballs, and instantons, have been performed. The subject of diffraction has been reinvigorated through its precise measurement, such that it can now be described by perturbative QCD. After discussion of HERA, the H1 and ZEUS detectors, and the techniques used to reconstruct differing hadronic final states, the above subject areas are elaborated on. The major achievements are then condensed further in a final section summarizing what has been learned. © 2014 American Physical Society.


Zastrow M.L.,University of Michigan | Peacock A.F.A.,University of Michigan | Peacock A.F.A.,University of Birmingham | Stuckey J.A.,University of Michigan | Pecoraro V.L.,University of Michigan
Nature Chemistry | Year: 2012

Metal ions are an important part of many natural proteins, providing structural, catalytic and electron transfer functions. Reproducing these functions in a designed protein is the ultimate challenge to our understanding of them. Here, we present an artificial metallohydrolase, which has been shown by X-ray crystallography to contain two different metal ions-a Zn(II) ion, which is important for catalytic activity, and a Hg(II) ion, which provides structural stability. This metallohydrolase displays catalytic activity that compares well with several characteristic reactions of natural enzymes. It catalyses -nitrophenyl acetate (pNPA) hydrolysis with an efficiency only ∼100-fold less than that of human carbonic anhydrase (CA)II and at least 550-fold better than comparable synthetic complexes. Similarly, CO 2 hydration occurs with an efficiency within ∼500-fold of CAII. Although histidine residues in the absence of Zn(II) exhibit pNPA hydrolysis, miniscule apopeptide activity is observed for CO 2 hydration. The kinetic and structural analysis of this first de novo designed hydrolytic metalloenzyme reveals necessary design features for future metalloenzymes containing one or more metals. © 2012 Macmillan Publishers Limited. All rights reserved.


The benefits of aspirin as an anti-platelet agent are well established; however, there has been much debate about the lack of uniformity in the efficacy of aspirin to inhibit platelet function. In some patients, aspirin fails to inhibit platelets even where compliance has been verified, a phenomenon which has been termed "aspirin resistance". These patients may in turn be at a higher risk of future vascular events. The proportion of "resistant" patients identified depends on the type of platelet function test. Therefore, the aim of this systematic review is to determine which, if any, platelet function test has utility in terms of identifying patients with a high risk of vascular events. The review has been registered with PROSPERO (CRD42012002151). Relevant studies will be sought from bibliographic databases. Trials registers will be searched for ongoing studies. Reference lists will be checked and subject experts contacted. There will be no date or language restrictions. Standard reviewing methodology to minimise bias will be employed. Any prospective studies in patients on aspirin therapy and assessing platelet function in relation to relevant clinical outcomes will be included, as will studies reporting prognostic models. Risk of bias assessment will be based on the Quality Assessment of Diagnostic Accuracy Studies guidelines, and suitable criteria for assessing quality of prognostic studies. Data on test accuracy measures, relative risks, odds or hazard ratios will be extracted and meta-analysed, where possible, using a random-effects model to account for between-study heterogeneity. Where appropriate, the causes of heterogeneity will be explored through meta-regression and sub-group or sensitivity analyses. If platelet function testing is demonstrated to have diagnostic/predictive utility in a specific population, the potential for a cost-effectiveness analysis will be considered and, if possible, an economic model constructed. This will be supported by a systematic review of existing economic evaluation studies. The results of the review could indicate if platelet function test(s) could lead to a reliable prediction of the risk of clinically important events in a defined population, and thus support investigations into adjustments to therapy in order to compensate for a predicted poor response to standard aspirin.


Cruise A.M.,University of Birmingham
Classical and Quantum Gravity | Year: 2012

The science case for observing gravitational waves at frequencies in the millihertzkilohertz range using LIGO, VIRGO, GEO600 or LISA is very strong and the first results are expected at these frequencies. However, as gravitational wave astronomy progresses beyond the first detections, other frequency bands may be worth exploring. Early predictions of gravitational wave emission from discrete sources at very much higher frequencies (megahertz and above) have been published and more recent studies of cosmological signals from inflation, KaluzaKlein modes from gravitational interactions in brane worlds and plasma instabilities surrounding violent astrophysical events, are all possible sources. This communication examines current observational possibilities and the detector technology required to make meaningful observations at these frequencies. © 2012 IOP Publishing Ltd.


Kim K.,University of Birmingham
Metallurgical and Materials Transactions A: Physical Metallurgy and Materials Science | Year: 2014

High-temperature oxidation of molten aluminum was investigated by high-resolution electron microscopes in order to determine the possibility of heterogeneous nucleation of aluminum grains on oxide for the grain refinement and structural uniformity of intensively melt-sheared aluminum alloys. High-resolution observations detect initial amorphous phase and gamma-alumina phase and show fine clusters with size of about 150 to 200 nm composed of extremely fine aluminum grains and gamma-alumina or amorphous aluminum oxide. Furthermore, high-resolution lattice images and diffraction patterns show no orientation relationship, although there is a specific orientation between gamma-alumina and aluminum along (111)[110] with high potency of heterogeneous nucleation. The volumetric shrinkage by the transformation of gamma- into alpha-alumina causes the surface oxide films to repeatedly rupture and leads to the creation of channels to the base melt surface for further oxidation of fresh metal. Based on the observations, the mechanism of high-temperature oxidation of molten aluminum and formation of the fine clusters as well as the possibility of the heterogeneous nucleation of aluminum grains are discussed. © 2014 The Minerals, Metals & Materials Society and ASM International.


Sprittles J.E.,University of Oxford | Shikhmurzaev Y.D.,University of Birmingham
Physics of Fluids | Year: 2012

The process of coalescence of two identical liquid drops is simulated numerically in the framework of two essentially different mathematical models, and the results are compared with experimental data on the very early stages of the coalescence process reported recently. The first model tested is the "conventional" one, where it is assumed that coalescence as the formation of a single body of fluid occurs by an instant appearance of a liquid bridge smoothly connecting the two drops, and the subsequent process is the evolution of this single body of fluid driven by capillary forces. The second model under investigation considers coalescence as a process where a section of the free surface becomes trapped between the bulk phases as the drops are pressed against each other, and it is the gradual disappearance of this "internal interface" that leads to the formation of a single body of fluid and the conventional model taking over. Using the full numerical solution of the problem in the framework of each of the two models, we show that the recently reported electrical measurements probing the very early stages of the process are better described by the interface formation/disappearance model. New theory-guided experiments are suggested that would help to further elucidate the details of the coalescence phenomenon. As a by-product of our research, the range of validity of different "scaling laws" advanced as approximate solutions to the problem formulated using the conventional model is established. © 2012 American Institute of Physics.


Jeukendrup A.E.,University of Birmingham
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2010

Purpose of review: Carbohydrate feeding has been shown to be ergogenic, but recently substantial advances have been made in optimizing the guidelines for carbohydrate intake during prolonged exercise. Recent findings: It was found that limitations to carbohydrate oxidation were in the absorptive process most likely because of a saturation of carbohydrate transporters. By using a combination of carbohydrates that use different intestinal transporters for absorption it was shown that carbohydrate delivery and oxidation could be increased. Studies demonstrated increases in exogenous carbohydrate oxidation rates of up to 65% of glucose: fructose compared with glucose only. Exogenous carbohydrate oxidation rates reach values of 1.75 g/min whereas previously it was thought that 1 g/min was the absolute maximum. The increased carbohydrate oxidation with multiple transportable carbohydrates was accompanied by increased fluid delivery and improved oxidation efficiency, and thus the likelihood of gastrointestinal distress may be diminished. Studies also demonstrated reduced fatigue and improved exercise performance with multiple transportable carbohydrates compared with a single carbohydrate. Summary: Multiple transportable carbohydrates, ingested at high rates, can be beneficial during endurance sports in which the duration of exercise is 3 h or more. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Fregonese S.,University of Birmingham
European Urban and Regional Studies | Year: 2013

This special issue of Euro-commentaries tackles the question of what links unprecedented anti-regime uprisings in the MENA (Middle East and North Africa) region, with the largest protests in decades in several European cities. Beyond the specificities of individual cases, uprisings on both sides of the Mediterranean have highlighted strong and often violent collisions between resistance movements and state security. How are these collisions reshaping urban and political geographies in the Mediterranean? The papers presented here explore different aspects of the 2011 protests, and share the view that these are shaped by concerns for social justice, human rights and democracy, which are not a prerogative of the Arab world, but indicate instead more complex geographies. © The Author(s) 2012.


Appleyard L. The geographies of access to enterprise finance: the case of the West Midlands, UK, Regional Studies. Whilst there is a long history of credit rationing to small and medium-sized enterprises (SMEs) in the UK, the financial crisis has seen banks retreat further from lending to viable SMEs due to a reassessment of risk and lack of available capital. In so doing, the credit crunch is thought to be creating new geographies of financial exclusion. This paper explores the financial inclusion of enterprise through community development finance institutions (CDFIs) which provide loan finance to firms at the commercial margins in the West Midlands, UK. The paper concludes that CDFIs could partially address the financial exclusion of enterprise as an additional, alternative source of finance to that of mainstream banks. © 2013 Copyright The Author(s). Published by Routledge.


Drawing upon collaborative planning theory and on the work of Lefebvre and de Certeau, this paper explores the multistage governance arrangements leading to the employment of temporary uses as an instrument for regeneration in a context of economic crisis. It contributes to a thorough understanding of the relations between the power hierarchy and the strategy/tactics developed through a more or less inclusive collaborative process from place-shaping (weak planning) to place-making (masterplanning). By decrypting the different paths that can be taken by the collaborative process, the paper demonstrates how temporary uses on differential spaces shape space from a use value point of view, influence and challenge the distribution of power and enable (temporary) occupants to acquire and sometimes sustain a position in the place-making process. © 2012 Urban Studies Journal Limited.


Bassel G.W.,University of Birmingham
Trends in Plant Science | Year: 2016

The seed to seedling transition in plants is initiated following the termination of seed dormancy. Here, I present a simplified developmental framework describing the events underlying this transition. I discuss putative mechanisms of signal integration and their relation to a global developmental fate switch in seeds within this framework. I delineate the events that occur before and after the flipping of this switch, marking an important distinction between these different developmental states. To end, I propose that the final fate switch resides within the embryo, and is informed by the endosperm in arabidopsis (Arabidopsis thaliana). This framework can serve as a template to focus future research in seed science. Environmental signal integration in seeds is mediated by the relative abundance of the hormones abscisic acid (ABA) and gibberellins (GA). The dynamic regulation of hormone synthesis and degradation is regulated by exogenous cues.An irreversible developmental fate switch underlies the commitment to make the transition from seed to seedling. Both hormone and protein thresholds likely represent components of this switch.Events downstream of the flipping of the switch include the transcriptional induction of GA synthesis and cell wall-modifying gene expression. These act as downstream molecular markers indicating the developmental fate switch has been previously flipped.Current evidence suggests that the final switch resides within the embryo, where the decision to germinate is ultimately reached. © 2016 Elsevier Ltd.


Phillimore J.,University of Birmingham
Housing Studies | Year: 2013

Following two decades of new migration, the EU is now home to the most diverse population ever. Much new migration has occurred into superdiverse escalator areas already experiencing high levels of deprivation. In the UK, housing market renewal areas (HMRA) had a particular challenge to address housing market failure and the high population turnover often associated with new migration while meeting the needs of established residents. Lack of knowledge about the diverse housing needs of residents risked hampering renewal efforts. This paper uses qualitative data collected from a superdiverse sample of settled and new residents located in the Urban Living HMRA in the West Midlands to examine the ways in which they conceptualise home. The paper argues that understanding the ways in which diverse residents conceptualise home and home making, offers potential for policymakers to understand how residents' needs can be met. © 2013 Copyright Taylor and Francis Group, LLC.


Van der Horst D.,University of Birmingham | Vermeylen S.,Lancaster University
Biomass and Bioenergy | Year: 2011

The prospect of biofuels going 'mainstream' has drawn more attention to the social impacts of the production and use of transport biofuels. Since 2007, many media stories have appeared about alleged negative impacts of biofuels, notably the price of food going up or land-grab by plantation developers. These stories stand in stark contrast with the rosy picture painted by some academics involved in the technical development of bioethanol or biodiesel. This paper explores the questions when and why negative social impacts are likely to occur and under what circumstances more positive impacts might be expected. These impacts are discussed for three geographically defined biofuel supply chains; north-north, south-north and south-south. These three systems differ in the spatial scale of production and consumption and with that comes a different distribution of environmental, social and economic impacts. In the case of domestic production and consumption in developed countries, the social impacts are relatively minor and can be mitigated by social policies. Large scale, export-oriented production systems in developing countries could theoretically yield positive social impacts, but this would require on the one hand the tailored design of 'pro-poor' social innovations and interventions on the ground and on the other hand a certification of the supply chain feeding into consumer demand for 'ethical' fuel. The latent existence of this demand might be significant but recent NGO campaigns have severely undermined the ethical credentials of biofuels. It would require a persistent and collaborative effort to restore the brand value of 'green' fuel, an effort which will require better legislation and radically improved monitoring and enforcement practices in countries where the very absence of these has led to, and is still causing, the large scale destruction of habitats that are carbon sinks of global importance. The significant levels of government funding for biofuels stand in strong contrast with the problematic environmental and social governance of international biofuels supply chains. Notwithstanding the 'must tackle climate change' rhetoric by policy makers and in policy documents, this suggests that biofuels policy may be primarily driven by other concerns, especially regarding energy security. We argue that policies that are designed for a rather narrowly defined purpose of 'security of supply', cannot be realistically expected to yield high social or environmental benefits, and certainly not abroad. © 2010 Elsevier Ltd.