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Bristol, United Kingdom

The University of Bristol is a red brick research university located in Bristol, United Kingdom. It received its Royal Charter in 1909, and its predecessor institution, University College, Bristol, had been in existence since 1876.Bristol has been ranked 29th by the QS World University Rankings, and is ranked amongst the top ten of UK universities by QS, THE, and ARWU. A highly selective institution, it has an average of 14 applicants for each undergraduate place.Bristol is organised into six academic faculties composed of multiple schools and departments running over 200 undergraduate courses situated in the Clifton area along with three of its nine halls of residence. The other six halls are located in Stoke Bishop, an outer city suburb located 1.8 miles away. The University had a total income of £459.2 million in 2012/13, of which £120.1 million was from research grants and contracts. It is the largest independent employer in Bristol.Current academics include 21 Fellows of the Academy of Medical science, 13 Fellows of the British Academy, 13 Fellows of the Royal Academy of Engineering and 40 Fellows of the Royal Society.Bristol is a member of the Russell Group of research-intensive British universities, the European-wide Coimbra Group and the Worldwide Universities Network, of which the University's Vice-Chancellor Eric Thomas was chairman from 2005 to 2007. In addition, the University holds an Erasmus Charter, sending more than 500 students per year to partner institutions in Europe. Wikipedia.


Shales C.,University of Bristol
Veterinary surgery : VS : the official journal of the American College of Veterinary Surgeons | Year: 2010

To (1) identify prognostic indicators for stability after stabilization of sacroiliac luxation with screws inserted in lag fashion and (2) report dorsoventral dimensions of the sacrum in cats. Multicenter retrospective study. Cats (n=40) with sacroiliac luxation. Case records and radiographs of cats presented at the Queen's Veterinary School Hospital Cambridge and the Royal Veterinary College Hatfield for screw fixation of sacroiliac luxation were reviewed. Dorsoventral dimensions of 15 feline cadaveric sacral bodies were measured to identify the appropriate implant size for use in fixation with screws inserted in lag fashion. Of 40 cats, 13 had left, 14 right, and 13 bilateral sacroiliac luxations. Of 48 screws analyzed, 42 (87.5%) were placed within the sacral body or exited ventrally and 6 (12.5%) were considered malpositioned. Screw purchase within the sacrum was statistically different between unstable and stable repairs (P=.001). Using confidence intervals for screw length within the sacrum and effect on stability, the lowest screw depth that contained 95% of the screws that did not loosen was approximately 60% of the sacral width. Mean dorsoventral sacral dimension at its narrowest point was 5.9+/-1.14 mm. There was no significant difference in the incidence of implant loosening between those luxations that were 100% reduced and those that were <100% reduced (P=.7837). Screw purchase within the feline sacrum of at least 60% of the sacral width significantly reduces the risk of loosening. Screw placement to a depth of 60% of the width of the feline sacrum is recommended.


After a period of relative senescence in the field of vascular smooth muscle cell (VSMC) research with particular regards to atherosclerosis, the last few years has witnessed a resurgence, with extensive research re-assessing potential molecular mechanisms and pathways that modulate VSMC behaviour within the atherosclerotic-prone vessel wall and the atherosclerotic plaque itself. Attention has focussed on the pathological contribution of VSMC in plaque calcification; systemic and local mediators such as inflammatory molecules and lipoproteins; autocrine and paracrine regulators which affect cell-cell and cell to matrix contacts alongside cytoskeletal changes. In this brief focused review, recent insights that have been gained into how a myriad of recently identified factors can influence the pathological behaviour of VSMC and their subsequent contribution to atherosclerotic plaque development and progression has been discussed. An overriding theme is the mechanisms involved in the alterations of VSMC function during atherosclerosis. © The Author 2014.


Phillipson O.T.,University of Bristol
Neurobiology of Aging | Year: 2014

The aging risk factor for Parkinson's disease is described in terms of specific disease markers including mitochondrial and gene dysfunctions relevant to energy metabolism. This review details evidence for the ability of nutritional agents to manage these aging risk factors. The combination of alpha lipoic acid, acetyl- l-carnitine, coenzyme Q10, and melatonin supports energy metabolism via carbohydrate and fatty acid utilization, assists electron transport and adenosine triphosphate synthesis, counters oxidative and nitrosative stress, and raises defenses against protein misfolding, inflammatory stimuli, iron, and other endogenous or xenobiotic toxins. These effects are supported by gene expression via the antioxidant response element (ARE; Keap/Nrf2 pathway), and by peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha), a transcription coactivator, which regulates gene expression for energy metabolism and mitochondrial biogenesis, and maintains the structural integrity of mitochondria. The effectiveness and synergies of the combination against disease risks are discussed in relation to gene action, dopamine cell loss, and the accumulation and spread of pathology via misfolded alpha-synuclein. In addition there are potential synergies to support a neurorestorative role via glial derived neurotrophic factor expression. © 2014 The Author.


Correlative evidence has often suggested that the lunisolar tidal force, to which the Sun contributes 30 % and the Moon 60 % of the combined gravitational acceleration, regulates a number of features of plant growth upon Earth. The time scales of the effects studied have ranged from the lunar day, with a period of approx. 24.8 h, to longer, monthly or seasonal variations. We review evidence for a lunar involvement with plant growth. In particular, we describe experimental observations which indicate a putative lunar-based relationship with the rate of elongation of roots of Arabidopsis thaliana maintained in constant light. The evidence suggests that there may be continuous modulation of root elongation growth by the lunisolar tidal force. In order to provide further supportive evidence for a more general hypothesis of a lunisolar regulation of growth, we highlight similarly suggestive evidence from the time courses of (a) bean leaf movements obtained from kymographic observations; (b) dilatation cycles of tree stems obtained from dendrograms; and (c) the diurnal changes of wood-water relationships in a living tree obtained by reflectometry. At present, the evidence for a lunar or a lunisolar influence on root growth or, indeed, on any other plant system, is correlative, and therefore circumstantial. Although it is not possible to alter the lunisolar gravitational force experienced by living organisms on Earth, it is possible to predict how this putative lunisolar influence will vary at times in the near future. This may offer ways of testing predictions about possible Moon-plant relationships. As for a hypothesis about how the three-body system of Earth-Sun-Moon could interact with biological systems to produce a specific growth response, this remains a challenge for the future. Plant growth responses are mainly brought about by differential movement of water across protoplasmic membranes in conjunction with water movement in the super-symplasm. It may be in this realm of water movements, or even in the physical forms which water adopts within cells, that the lunisolar tidal force has an impact upon living growth systems.


Nakagawa F.,University College London | May M.,University of Bristol | Phillips A.,University College London
Current Opinion in Infectious Diseases | Year: 2013

Purpose of Review: The life expectancy of people living with HIV has dramatically increased since effective antiretroviral therapy has been available, and still continues to improve. Here, we review the latest literature on estimates of life expectancy and consider the implications for future research. Recent Findings: With timely diagnosis, access to a variety of current drugs and good lifelong adherence, people with recently acquired infections can expect to have a life expectancy which is nearly the same as that of HIV-negative individuals. Modelling studies suggest that life expectancy could improve further if there were increased uptake of HIV testing, better antiretroviral regimens and treatment strategies, and the adoption of healthier lifestyles by those living with HIV. In particular, earlier diagnosis is one of the most important factors associated with better life expectancy. A consequence of improved survival is the increasing number of people with HIV who are aged over 50 years old, and further research into the impact of ageing on HIV-positive people will therefore become crucial. The development of age-specific HIV treatment and management guidelines is now called for. Summary: Analyses on cohort studies and mathematical modelling studies have been used to estimate life expectancy of those with HIV, providing useful insights of importance to individuals and healthcare planning. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Allogrooming occurs in a wide range of species and can serve both hygienic and social functions.While the latter have long been thought to be underpinned by reductions in tension for recipients, recent work has suggested that donors may also benefit in this way. Here, I show that, in cooperatively breeding green woodhoopoes Phoeniculus purpureus, involvement in allogrooming is followed by a reduction in self-grooming by both recipients and donors, but that the former exhibit a greater decrease. Moreover, I demonstrate for the first time that the dominance status of the allogrooming participant is important, with subordinate group members reducing subsequent self-grooming to a greater extent than the dominant pair. If avian self-directed behaviour reflects current distress levels in the same way as found in various primates, my results would indicate that allogrooming benefits are not confined to mammals, and would have important implications both for accurate assessments of the true costs and benefits of affiliative behaviour and for our understanding of the evolution of sociality. © 2011 The Royal Society.


Wolf M.,Leibniz Institute of Freshwater Ecology and Inland Fisheries | McNamara J.M.,University of Bristol
American Naturalist | Year: 2012

Personality differences can be found in a wide range of species across the animal kingdom, but why natural selection gave rise to such differences remains an open question. Frequency-dependent selection is a potent mechanism explaining variation; it does not explain, however, the other two key features associated with personalities, consistency and correlations. Using the hawk-dove game and a frequency-dependent foraging game as examples, we here show that this changes fundamentally whenever one takes into account the physiological architecture underlying behavior (e.g., metabolism). We find that the inclusion of physiology changes the evolutionary predictions concerning consistency and correlations: while selection gives rise to inconsistent individuals and stochastically fluctuating behavioral correlations in scenarios that neglect physiology, we find high levels of behavioral consistency and tight and stable trait correlations in scenarios that incorporate physiology. The coevolution of behavioral and physiological traits also gives rise to adaptive physiological differences that are systematically associated with behavioral differences. As well as providing a framework for understanding behavioral consistency and behavioral correlations, our work thus also provides an explanation for systematic physiological differences within populations, a phenomenon that appears to exist in a wide range of species but that, up to now, has been poorly understood. © 2012 by The University of Chicago.


Ying Y.,University of Exeter | Li P.,University of Bristol
Journal of Machine Learning Research | Year: 2012

The main theme of this paper is to develop a novel eigenvalue optimization framework for learning a Mahalanobis metric. Within this context, we introduce a novel metric learning approach called DML-eig which is shown to be equivalent to a well-known eigenvalue optimization problem called minimizing the maximal eigenvalue of a symmetric matrix (Overton, 1988; Lewis and Overton, 1996). Moreover, we formulate LMNN (Weinberger et al., 2005), one of the state-of-the-art metric learning methods, as a similar eigenvalue optimization problem. This novel framework not only provides new insights into metric learning but also opens new avenues to the design of efficient metric learning algorithms. Indeed, first-order algorithms are developed for DML-eig and LMNN which only need the computation of the largest eigenvector of a matrix per iteration. Their convergence characteristics are rigorously established. Various experiments on benchmark data sets show the competitive performance of our new approaches. In addition, we report an encouraging result on a difficult and challenging face verification data set called Labeled Faces in the Wild (LFW). © 2012 Yiming Ying and Peng Li.


Wiesner K.,University of Bristol
Chaos | Year: 2010

Nature intrinsically computes. It has been suggested that the entire universe is a computer, in particular, a quantum computer. To corroborate this idea we require tools to quantify the information processing. Here we review a theoretical framework for quantifying information processing in a quantum dynamical system. So-called intrinsic quantum computation combines tools from dynamical systems theory, information theory, quantum mechanics, and computation theory. We will review how far the framework has been developed and what some of the main open questions are. On the basis of this framework we discuss upper and lower bounds for intrinsic information storage in a quantum dynamical system. © 2010 American Institute of Physics.


There is ongoing debate regarding the shape of life-course trajectories in mental health. Many argue the relationship is U-shaped, with mental health declining with age to mid-life, then improving. However, I argue that these models are beset by the age-period-cohort (APC) identification problem, whereby age, cohort and year of measurement are exactly collinear and their effects cannot be meaningfully separated. This means an apparent life-course effect could be explained by cohorts. This paper critiques two sets of literature: the substantive literature regarding life-course trajectories in mental health, and the methodological literature that claims erroneously to have 'solved' the APC identification problem statistically (e.g. using Yang and Land's Hierarchical APC-HAPC-model). I then use a variant of the HAPC model, making strong but justified assumptions that allow the modelling of life-course trajectories in mental health (measured by the General Health Questionnaire) net of any cohort effects, using data from the British Household Panel Survey, 1991-2008. The model additionally employs a complex multilevel structure that allows the relative importance of spatial (households, local authority districts) and temporal (periods, cohorts) levels to be assessed. Mental health is found to increase throughout the life-course; this slows at mid-life before worsening again into old age, but there is no evidence of a U-shape - I argue that such findings result from confounding with cohort processes (whereby more recent cohorts have generally worse mental health). Other covariates were also evaluated; income, smoking, education, social class, urbanity, ethnicity, gender and marriage were all related to mental health, with the latter two in particular affecting life-course and cohort trajectories. The paper shows the importance of understanding APC in life-course research generally, and mental health research in particular. © 2014 Elsevier Ltd.


Devadason R.,University of Bristol
Urban Studies | Year: 2010

Cosmopolitanism has been described as the cultural habitus of globalisation. It is therefore, albeit defined somewhat loosely, often associated with ethnically diverse, global cities. This paper considers the extent to which London engenders cosmopolitan values amongst its residents. It draws on survey data from the LOCAL MULTIDEM study of minorities' political participation to address these themes. The analysis examines perceptions of respect, belonging and geographical imaginaries-amongst established minorities and the ethnic majority-in north London. It is argued that cosmopolitan ethics are transformative and dialectical and, critically, cannot remain the preserve of the privileged in multi-ethnic neighbourhoods. The analysis presented demonstrates that a sense of belonging and cosmopolitan imaginaries are not evenly accessed by different ethnic groups; notably, that Bangladeshi Londoners who are born and bred in the city are less likely to appropriate these discourses than Caribbean, Indian or White residents. ©2010 Urban Studies Journal Limited.


Williams D.,Durham University | Jarrold C.,University of Bristol
Autism Research | Year: 2013

Across studies, analysis of performance on classic measures of executive functioning (EF) among individuals with autism spectrum disorder (ASD) suggests that people with this disorder may be impaired only when tasks are experimenter-administered, but not when the same tasks are computer-administered. This would imply that the underlying cause of apparent executive dysfunction in ASD is a diminished ability to engage with another person/comprehend what another person expects, rather than a diminution of the control processes that typically underpin EF task performance. However, this suggestion is limited because, to our knowledge, no study has directly compared the equivalence of computer-administered and standard experimenter-administered versions of EF tasks that have been presented in counterbalanced order among a common sample of individuals with ASD. In the current study, 21 children with ASD and 22 age- and intelligence quotient (IQ)-matched comparison participants completed, in counterbalanced order, computerised and manual versions of both a planning task and a cognitive flexibility/set-shifting task. Contrary to expectation, results indicated that participants with ASD were equally impaired in terms of the key dependent variable on standard and computerised versions of both tasks. Practically, these results suggest that computer-administered and experimenter-administered versions of planning and set-shifting tasks are equivalent among individuals with ASD and can be used interchangeably in studies of EF among this population. Theoretically, these results challenge the notion that poor performance on EF tasks among school-aged children with ASD is only the result of a limited ability to engage with a human experimenter/comprehend socially presented rules. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.


Marks D.I.,University of Bristol
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2010

Acute lymphoblastic leukemia (ALL) in adults is a rare disease. The results of therapy remain unsatisfactory, and progress has been relatively slow. This article will focus on curative therapy in patients aged 30 to 60 years, but will also discuss the management of elderly patients with ALL. Recent large trials have increased our knowledge of the factors that determine outcome, and have clarified the role of blood and marrow transplantation in the management of this disease. These trials have also highlighted the major issues we need to focus on if we are to improve outcomes. This article describes the results of chemotherapy and blood and marrow transplantation for Philadelphia chromosome negative and positive adult ALL in the "older" adult patient, but also critically examines the major controversies and suggests how they might be resolved. The role of allografting in adult ALL is comprehensively discussed. Results of recent studies on T-cell ALL and reduced-intensity allografting are reviewed. A better understanding of the biology of the disease (including gene profiling) may allow individualization of therapy and, in time, targeted therapy.


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

BACKGROUND: Cardiac rehabilitation is an important component of recovery from coronary events but uptake and adherence to such programmes are below the recommended levels. This aim is to update a previous non-Cochrane systematic review which examined interventions that may potentially improve cardiac patient uptake and adherence in rehabilitation or its components and concluded that there is insufficient evidence to make specific recommendations. OBJECTIVES: To determine the effects of interventions to increase patient uptake of, and adherence to, cardiac rehabilitation. SEARCH STRATEGY: A previous systematic review identified studies published prior to June 2001. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 4 2007), MEDLINE (2001 to January 2008), EMBASE (2001 to January 2008), CINAHL (2001 to January 2008), PsycINFO (2001 to January 2008), Web of Science: ISI Proceedings (2001 to April 2008), and NHS Centre for Reviews and Dissemination (CRD) databases (Health Technology Assessment (HTA) and Database of Abstracts of Reviews of Effects (DARE)) from 2001 to January 2008. Reference lists of identified systematic reviews and randomised control trials (RCTs) were also checked for additional studies. SELECTION CRITERIA: Adults with myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, heart failure, angina, or coronary heart disease eligible for cardiac rehabilitation and randomised or quasi-randomised trials of interventions to increase uptake or adherence to cardiac rehabilitation or any of its component parts. Only studies reporting a measure of adherence were included. DATA COLLECTION AND ANALYSIS: Titles and abstracts of all identified references were screened for eligibility by two reviewers independently and full papers of potentially relevant trials were obtained and checked. Included studies were assessed for risk of bias by two reviewers. MAIN RESULTS: Ten studies were identified, three of interventions to improve uptake of cardiac rehabilitation and seven of interventions to increase adherence. Meta-analysis was not possible due to multiple sources of heterogeneity. All three interventions targeting uptake of cardiac rehabilitation were effective. Two of seven studies intended to increase adherence had a significant effect. Only one study reported the non-significant effects of the intervention on cardiovascular risk factors and no studies reported data on mortality, morbidities, costs or health care resource utilisation. AUTHORS' CONCLUSIONS: There is some evidence to suggest that interventions to increase the uptake of cardiac rehabilitation can be effective. Few practice recommendations for increasing adherence to cardiac rehabilitation can be made at this time. Interventions targeting patient identified barriers may increase the likelihood of success. Further high quality research is needed.


Tadic V.B.,University of Bristol
IEEE Transactions on Information Theory | Year: 2010

This paper considers the asymptotic properties of the recursive maximum-likelihood estimator for hidden Markov models. The paper is focused on the analytic properties of the asymptotic log-likelihood and on the point-convergence and convergence rate of the recursive maximum-likelihood estimator. Using the principle of analytic continuation, the analyticity of the asymptotic log-likelihood is shown for analytically parameterized hidden Markov models. Relying on this fact and some results from differential geometry (Lojasiewicz inequality), the almost sure point convergence of the recursive maximum-likelihood algorithm is demonstrated, and relatively tight bounds on the convergence rate are derived. As opposed to the existing result on the asymptotic behavior of maximum-likelihood estimation in hidden Markov models, the results of this paper are obtained without assuming that the log-likelihood function has an isolated maximum at which the Hessian is strictly negative definite. © 2006 IEEE.


McNeill A.,University of Nottingham | Munafo M.R.,University of Bristol
Journal of Psychopharmacology | Year: 2013

If current trends in smoking prevalence continue, even with the implementation of enhanced tobacco control measures, millions of smokers will continue to fall ill and die as a direct result of their smoking. Many of these will be from the most deprived groups in society-smoking continues to be one of the strongest drivers of health inequalities. The personal costs of this morbidity and mortality, as well as costs to business and the economy, are unequalled and will therefore remain high for several decades to come. However, there is an addition to the tobacco control armoury that could have a marked impact on public health, but it requires radical action to be taken. This would be to embrace harm reduction, but this approach is as controversial in the case of tobacco as it is in the case of illicit drugs from where it derives. However, harm reduction remains the Cinderella of the three major strategies for reducing smoking-related harm, the others being prevention and cessation. Here we make the case that harm reduction has an important role to play in reducing the health burden of tobacco use. © The Author(s) 2013.


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.


De Bie T.,University of Bristol
Proceedings of the ACM SIGKDD International Conference on Knowledge Discovery and Data Mining | Year: 2011

We formalize the data mining process as a process of information exchange, defined by the following key components. The data miner's state of mind is modeled as a probability distribution, called the background distribution, which represents the uncertainty and misconceptions the data miner has about the data. This model initially incorporates any prior (possibly incorrect) beliefs a data miner has about the data. During the data mining process, properties of the data (to which we refer as patterns) are revealed to the data miner, either in batch, one by one, or even interactively. This acquisition of information in the data mining process is formalized by updates to the background distribution to account for the presence of the found patterns. The proposed framework can be motivated using concepts from information theory and game theory. Understanding it from this perspective, it is easy to see how it can be extended to more sophisticated settings, e.g. where patterns are probabilistic functions of the data (thus allowing one to account for noise and errors in the data mining process, and allowing one to study data mining techniques based on subsampling the data). The framework then models the data mining process using concepts from information geometry, and I-projections in particular. The framework can be used to help in designing new data mining algorithms that maximize the efficiency of the information exchange from the algorithm to the data miner. Copyright 2011 ACM.


Hill J.G.,University of Sheffield | Legon A.C.,University of Bristol
Physical Chemistry Chemical Physics | Year: 2015

Benchmark quality structures and interaction energies have been produced using explicitly correlated coupled cluster methods for a systematic series of hydrogen and halogen bonded complexes: B⋯HCCH, B⋯HCl and B⋯ClF, with six different Lewis bases B. Excellent agreement with experimental structures is observed, verifying the method used to deduce the equilibrium deviation from collinearity of the intermolecular bond via rotational spectroscopy. This level of agreement also suggests that the chosen theoretical method can be employed when experimental equilibrium data are not available. The application of symmetry adapted perturbation theory reveals differences in the underlying mechanisms of interaction for hydrogen and halogen bonding, providing insights into the differences in non-linearity. In the halogen bonding case it is shown that the dispersion term is approximately equal to the overall interaction energy, highlighting the importance of choosing the correct theoretical method for this type of interaction. © the Owner Societies 2015.


The mechanisms by which ischemic preconditioning (IP) inhibits mitochondrial permeability transition pore opening and, hence, ischemia-reperfusion injury remain unclear. Here we investigate whether and how mitochondria-bound hexokinase 2 (mtHK2) may exert part of the cardioprotective effects of IP. Control and IP Langendorff-perfused rat hearts were subject to ischemia and reperfusion with measurement of hemodynamic function and infarct size. Outer mitochondrial membrane (OMM) permeabilization after ischemia was determined by measuring rates of respiration and H2O2 production in the presence and absence of added cytochrome c in isolated mitochondria and permeabilized fibers. IP prevented OMM permeabilization during ischemia and reduced the loss of mtHK2, but not Bcl-xL, observed in control ischemic hearts. By contrast, treatment of permeabilized fibers with glucose-6-phosphate at pH 6.3 induced mtHK2 loss without OMM permeabilization. However, metabolic pretreatments of the perfused heart chosen to modulate glucose-6-phosphate and intracellular pHi revealed a strong inverse correlation between end-ischemic mtHK2 content and infarct size after reperfusion. Loss of mtHK2 was also associated with reduced rates of creatine phosphate generation during the early phase of reperfusion. This could be mimicked in permeabilized fibers after mtHK2 dissociation. We propose that loss of mtHK2 during ischemia destabilizes mitochondrial contact sites, which, when accompanied by degradation of Bcl-xL, induces OMM permeabilization and cytochrome c loss. This stimulates reactive oxygen species production and mitochondrial permeability transition pore opening on reperfusion, leading to infarction. Consequently, inhibition of mtHK2 loss during ischemia could be an important mechanism responsible for the cardioprotection mediated by IP and other pretreatments.


Russell C.A.,University of Bristol
Angewandte Chemie - International Edition | Year: 2010

Two P or not two P? This bastardization of a well-known Shakespearean phrase is used to highlight recent work that shows that irradiation of white phosphorus produces diphosphorus, P 2 (see scheme), which may be reacted in situ in a double Diels-Alder reaction to give cage diphosphines. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Gregory S.,University of Bristol
Journal of Statistical Mechanics: Theory and Experiment | Year: 2011

Networks commonly exhibit a community structure, whereby groups of vertices are more densely connected to each other than to other vertices. Often these communities overlap, such that each vertex may occur in more than one community. However, two distinct types of overlapping are possible: crisp (where each vertex belongs fully to each community of which it is a member) and fuzzy (where each vertex belongs to each community to a different extent). We investigate the effects of the fuzziness of community overlap. We find that it has a strong effect on the performance of community detection methods: some algorithms perform better with fuzzy overlapping while others favour crisp overlapping. We also evaluate the performance of some algorithms that recover the belonging coefficients when the overlap is fuzzy. Finally, we investigate whether real networks contain fuzzy or crisp overlapping. © 2011 IOP Publishing Ltd.


Oba Y.,University of Missouri | Sarva S.T.,University of Missouri | Dias S.,University of Bristol
Thorax | Year: 2016

Background: The place of long-acting β agonist/long-acting muscarinic antagonist (LABA/LAMA) combinations in stable patients with COPD is not well defined. The purpose of this study was to systematically review the efficacy and safety of LABA/LAMA combinations. Methods: Several databases and manufacturers' websites were searched for relevant clinical trials. Randomised control trials, at least 12 weeks duration, comparing a LABA/LAMA combination with placebo and/or monotherapy were included. The data were pooled using a network as well as a traditional direct comparison meta-analysis. Results: Twenty-three trials with a total of 27 172 patients were included in the analysis. LABA/LAMA combinations were associated with a greater improvement in lung function, St. George's Respiratory Questionnaire (SGRQ) score, and Transitional Dyspnoea Index (TDI) than monotherapies. LABA/LAMA combinations were associated with a significantly greater proportion of SGRQ and TDI responders than monotherapies (OR 1.23 (95% credible interval (CrI) 1.06-1.39), OR 1.34 (95% CrI 1.19-1.50) versus LABAs and OR 1.24 (95% CrI 1.11-1.36), OR 1.31 (95% CrI 1.18-1.46) versus LAMAs, respectively) and fewer moderate-to-severe exacerbations compared with LABAs (HR 0.82 (95% CrI 0.73-0.93)), but not when compared with LAMAs (HR 0.92 (95% CrI 0.84-1.00)). There were no statistically significant differences associated with LABA/LAMA combinations compared with monotherapies in safety outcomes as well as in severe exacerbations. Conclusions: The combination therapy was the most effective strategy in improving lung function, quality of life, symptom scores and moderate-to-severe exacerbation rates, and had similar effects on safety outcomes and severe exacerbations as compared with monotherapies. © 2016, BMJ Publishing Group. All rights reserved.


Hall J.R.,University of Bristol
Proceedings. Biological sciences / The Royal Society | Year: 2013

Nearly all research on camouflage has investigated its effectiveness for concealing stationary objects. However, animals have to move, and patterns that only work when the subject is static will heavily constrain behaviour. We investigated the effects of different camouflages on the three stages of predation-detection, identification and capture-in a computer-based task with humans. An initial experiment tested seven camouflage strategies on static stimuli. In line with previous literature, background-matching and disruptive patterns were found to be most successful. Experiment 2 showed that if stimuli move, an isolated moving object on a stationary background cannot avoid detection or capture regardless of the type of camouflage. Experiment 3 used an identification task and showed that while camouflage is unable to slow detection or capture, camouflaged targets are harder to identify than uncamouflaged targets when similar background objects are present. The specific details of the camouflage patterns have little impact on this effect. If one has to move, camouflage cannot impede detection; but if one is surrounded by similar targets (e.g. other animals in a herd, or moving background distractors), then camouflage can slow identification. Despite previous assumptions, motion does not entirely 'break' camouflage.


Lindsay D.M.,University of Reading | McArthur D.,University of Bristol
Chemical Communications | Year: 2010

Chiral N-heterocyclic carbene-borane complexes have been synthesised, and have been shown to reduce ketones with Lewis acid promotion. Chiral N-heterocyclic carbene-borane and -diorganoborane complexes can reduce ketones with enantioselectivities up to 75% and 85% ee, respectively. © The Royal Society of Chemistry.


Clark E.M.,University of Bristol
Current Osteoporosis Reports | Year: 2014

Fractures in otherwise healthy children are important because they are common, impact on daily activity, and may identify those who may have an increased fracture risk as adults. This review covers the descriptive epidemiology of fractures in healthy children (aged 0-16) and provides an overview of what is known about the child-related determinants of fractures, dividing associations into those that are potentially modifiable and those that are not. Maternal-related influences during pregnancy have not been covered, nor have determinants related to the injury such as trauma level, landing surface, injury type, the physical environment, or societal impacts. Age, gender, low bone mass, and exposure to injury are the child-related determinants of fractures with the highest quality research showing a convincing association. © 2014 Springer Science+Business Media.


Lepora N.F.,University of Bristol
IEEE Transactions on Haptics | Year: 2016

This study provides a synthetic viewpoint that compares, contrasts, and draws commonalities for biomimetic perception over a range of tactile sensors and tactile stimuli. Biomimetic active perception is formulated from three principles: (i) evidence accumulation based on leading models of perceptual decision making; (ii) action selection with an evidence-based policy, here based on overt focal attention; and (iii) sensory encoding of evidence based on neural coding. Two experiments with each of three biomimetic tactile sensors are considered: the iCub (capacitive) fingertip, the TacTip (optical) tactile sensor, and BIOTACT whiskers. For each sensor, one experiment considers a similar task (perception of shape and location) and the other a different tactile perception task. In all experiments, active perception with a biomimetic action selection policy based on focal attention outperforms passive perception with static or random action selection. The active perception also consistently reaches superresolved accuracy (hyperacuity) finer than the spacing between tactile elements. Biomimetic active touch thus offers a common approach for biomimetic tactile sensors to accurately and robustly characterize and explore non-trivial, uncertain environments analogous to how animals perceive the natural world. © 2016 IEEE.


The authors of the World Health Organization Semen Analysis Manual are to be congratulated on producing a new edition; it is an essential tool to disseminate good practice in andrology. However, the tests described have poor prognostic power to predict a man's fertility and show little about the underlying causes of sub-fertility. This commentary urges a revival of research into the diagnosis of male fertility. It suggests that fertility should be regarded as a continuum and that the artificial binary division between fertile and infertile should be abandoned. Models to predict a sub-fertile couple's chance of conception in a year should be developed on the basis of prospective data. These models would allow for sophisticated decision making about management. The future lies in the identification of tests to detect underlying pathologies open to specific treatment. Leads such as oxidative stress, defects in the intracellular regulation and the developing field of proteomics should be explored. © 2010 AJA, SIMM & SJTU.


McNamara J.M.,University of Bristol | Leimar O.,University of Stockholm
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

In applying game theory to problems in biology, differences between individuals are often ignored. In particular, when analysing the evolution of cooperation it is often implicitly assumed that ignoring variation will produce predictions that approximate the solution when differences are included. This need not be true. As we demonstrate, differences are not innocuous noise, but can fundamentally change the nature of a game. Even small amounts ofvariability can stabilize cooperation by, for example, maintaining the need to deal with cheaters. Differences promote the need to learn about others in an interaction, leading to contingent behaviour that can reduce conflict, and to negotiated outcomes that may or may not be more cooperative than unconditional actions. Once there are mechanisms such as mutation and environmental influences that maintain variation within populations, whether cooperation evolves may depend on the variation in the cooperativeness trait. Variation means that it may be worth taking a chance that a partner is cooperative by being cooperative. When there are markets, so that individuals can break off interactions to seek a better partner, variation promotes choosiness and hence penalizes those uncooperative individuals, who are rejected. Variation promotes the need to monitor the previous behaviour of others, and once this social sensitivity exists, the need to maintain a good reputation can promote cooperation. © 2010 The Royal Society.


Birchley G.,University of Bristol
Journal of Medical Ethics | Year: 2016

A growing number of bioethics papers endorse the harm threshold when judging whether to override parental decisions. Among other claims, these papers argue that the harm threshold is easily understood by lay and professional audiences and correctly conforms to societal expectations of parents in regard to their children. English law contains a harm threshold which mediates the use of the best interests test in cases where a child may be removed from her parents. Using Diekema's seminal paper as an example, this paper explores the proposed workings of the harm threshold. I use examples from the practical use of the harm threshold in English law to argue that the harm threshold is an inadequate answer to the indeterminacy of the best interests test. I detail two criticisms: First, the harm standard has evaluative overtones and judges are loath to employ it where parental behaviour is misguided but they wish to treat parents sympathetically. Thus, by focusing only on 'substandard' parenting, harm is problematic where the parental attempts to benefit their child are misguided or wrong, such as in disputes about withdrawal of medical treatment. Second, when harm is used in genuine dilemmas, court judgments offer different answers to similar cases. This level of indeterminacy suggests that, in practice, the operation of the harm threshold would be indistinguishable from best interests. Since indeterminacy appears to be the greatest problem in elucidating what is best, bioethicists should concentrate on discovering the values that inform best interests.


Gibson M.A.,University of Bristol | Gurmu E.,Addis Ababa Institute of Technology
Proceedings of the National Academy of Sciences of the United States of America | Year: 2011

Intergenerational transfer of wealth has been proposed as playing a pivotal role in the evolution of human sibling relationships. Sibling rivalry is assumed to be more marked when offspring compete for limited heritable resources, which are crucial for reproductive success (e.g., land and livestock); whereas in the absence of heritable wealth, related siblings may cooperate. To date, comparative studies undertaken to support this evolutionary assumption have been confounded by other socioecological factors, which vary across populations, e.g., food sharing and intergroup conflict. In this article we explore effects of sibling competition and cooperation for agricultural resources, marriage, and reproduction in one contemporary Ethiopian agropastoralist society. Here recent changes in land tenure policy, altering transfers of land from parents to offspring, present a unique framework to test the importance of intergenerational transfers of wealth in driving sibling competition, while controlling for socioeconomic biases. In households where land is inherited, the number of elder brothers reduces a man's agricultural productivity, marriage, and reproductive success, as resources diminish and competition increases with each additional sibling. Where land is not inherited (for males receiving land directly from the government and all females) older siblings do not have a competitive effect and in some instances may be beneficial. This study has wider implications for the evolution of human family sizes. Recent changes in wealth transfers, which have driven sibling competition, may be contributing to an increased desire for smaller family sizes.


A few dinosaurs are inferred to have undergone an ontogenetic shift from quadrupedal-to-bipedal posture, or vice versa, based on skeletal allometry. The basal ceratopsian Psittacosaurus lujiatunensis is considered to have been mainly bipedal as an adult. Here we infer a postural shift in this species based on a novel combination of limb measurements and histological data. The forelimb is strongly negatively allometric relative to the hindlimb, and patterns of vascular canal orientation provide evidence that growth of the hindlimb was particularly rapid during the middle part of ontogeny. Histology also makes it possible to determine the ontogenetic ages of individual specimens, showing that the forelimb-to-hindlimb ratio changed rapidly during the first or second year of life and thereafter decreased gradually. Occurrence of an ontogenetic shift from quadrupedality to bipedality was evidently widespread in dinosaurs, and may even represent the ancestral condition for the entire group.


Bridle J.R.,University of Bristol
Proceedings. Biological sciences / The Royal Society | Year: 2014

Generalist species and phenotypes are expected to perform best under rapid environmental change. In contrast to this view that generalists will inherit the Earth, we find that increased use of a single host plant is associated with the recent climate-driven range expansion of the UK brown argus butterfly. Field assays of female host plant preference across the UK reveal a diversity of adaptations to host plants in long-established parts of the range, whereas butterflies in recently colonized areas are more specialized, consistently preferring to lay eggs on one host plant species that is geographically widespread throughout the region of expansion, despite being locally rare. By common-garden rearing of females' offspring, we also show an increase in dispersal propensity associated with the colonization of new sites. Range expansion is therefore associated with an increase in the spatial scale of adaptation as dispersive specialists selectively spread into new regions. Major restructuring of patterns of local adaptation is likely to occur across many taxa with climate change, as lineages suited to regional colonization rather than local success emerge and expand.


Blockley D.,University of Bristol
Mechanical Systems and Signal Processing | Year: 2013

Two assumptions, commonly made in risk and reliability studies, have a long history. The first is that uncertainty is either aleatoric or epistemic. The second is that standard probability theory is sufficient to express uncertainty. The purposes of this paper are to provide a conceptual analysis of uncertainty and to compare Bayesian approaches with interval approaches with an example relevant to research on climate change. The analysis reveals that the categorisation of uncertainty as either aleatoric or epistemic is unsatisfactory for practical decision making. It is argued that uncertainty emerges from three conceptually distinctive and orthogonal attributes FIR i.e., fuzziness, incompleteness (epistemic) and randomness (aleatory). Characterisations of uncertainty, such as ambiguity, dubiety and conflict, are complex mixes of interactions in an FIR space. To manage future risks in complex systems it will be important to recognise the extent to which we 'don't know' about possible unintended and unwanted consequences or unknown-unknowns. In this way we may be more alert to unexpected hazards. The Bayesian approach is compared with an interval probability approach to show one way in which conflict due to incomplete information can be managed. © 2012 Elsevier Ltd.


Adams J.C.,University of Bristol
Expert Review of Molecular Diagnostics | Year: 2015

Fascin-1 is a filamentous actin-binding protein that crosslinks actin microfilaments into tight, parallel bundles. These bundles are important for the extension of microspikes, filopodia and invadopodia from cell surfaces and for the functionality of these protrusions in cell migration and/or dynamic sensing of the local microenvironment. Fascin-1 is absent in normal colonic epithelium, but its upregulation in colorectal adenomas and adenocarcinomas and its correlation with an aggressive clinical course has piqued the interest of many laboratories with research interests in cancer metastasis. This report summarizes current knowledge of the molecular interactions of fascin-1 in relation to its activities and mechanisms of upregulation in colorectal carcinoma cells. The status and key questions surrounding investigations of fascin-1 as a novel, early prognostic biomarker in colorectal cancer are discussed. Ongoing pre-clinical research into new migration inhibitory and anti-metastatic compounds that alter the actin cytoskeleton, and the goal of targeting fascin-1, is also discussed. © 2015 Informa UK, Ltd.


Gotte J.B.,Max Planck Institute for the Physics of Complex Systems | Dennis M.R.,University of Bristol
Optics Letters | Year: 2013

The magnitudes of beam shifts (Goos-Hänchen and Imbert-Fedorov, spatial and angular) are greatly enhanced when a reflected light beam is postselected by an analyzer, by analogy with superweak measurements in quantum theory. Particularly strong enhancements can be expected close to angles at which no light is transmitted for fixed initial and final polarizations. We derive a formula for the angular and spatial shifts at such angles (which includes the Brewster angle), and we show that their maximum size is limited by higher-order terms from the reflection coefficients occurring in the Artmann shift formula. © 2013 Optical Society of America.


Biosynthetic genes for the prenylated xanthone shamixanthone have been identified in the Aspergillus nidulans genome; based on assignment of putative functions from sequence analyses and selected gene deletions, a pathway was proposed leading from the anthraquinone emodin via the benzophenone carboxylic acid monodictyphenone and the xanthone emericellin to shamixanthone. Several aspects of this proposed pathway are inconsistent with previously identified biosynthetic intermediates: the anthraquinone chrysophanol and the benzophenone aldehyde derivatives arugosins F and A/B, isotopic labelling studies and chemical precedents. A new pathway is presented that provides a full rationale for the results of the gene deletion studies and reconciles them with previous biosynthetic results, and is in accord with established chemical and biosynthetic mechanisms. The importance of interpreting genetic information in terms of established biosynthetic events is discussed. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Szczelkun M.D.,University of Bristol
Advances in Experimental Medicine and Biology | Year: 2013

On the basis of the familial name, a "helicase" might be expected to have an enzymatic activity that unwinds duplex polynucleotides to form single strands. A more encompassing taxonomy that captures alternative enzymatic roles has defined helicases as a sub-class of molecular motors that move directionally and processively along nucleic acids, the so-called "translocases". However, even this definition may be limiting in capturing the full scope of helicase mechanism and activity. Discussed here is another, alternative view of helicases - as machines which couple NTP-binding and hydrolysis to changes in protein conformation to resolve stable nucleoprotein assembly states. This "molecular switch" role differs from the classical view of helicases as molecular motors in that only a single catalytic NTPase cycle may be involved. This is illustrated using results obtained with the DEAD-box family of RNA helicases and with a model bacterial system, the ATP-dependent Type III restriction-modification enzymes. Further examples are discussed and illustrate the wide-ranging examples of molecular switches in genome metabolism. © 2013 Springer Science+Business Media New York.


Brunstrom J.M.,University of Bristol
International Journal of Obesity | Year: 2014

It is widely accepted that meal size is governed by psychological and physiological processes that generate fullness towards the end of a meal. However, observations of natural eating behaviour suggest that this preoccupation with within-meal events may be misplaced and that the role of immediate post-ingestive feedback (for example, gastric stretch) has been overstated. This review considers the proposition that the locus of control is more likely to be expressed in decisions about portion size, before a meal begins. Consistent with this idea, we have discovered that people are extremely adept at estimating the 'expected satiety' and 'expected satiation' of different foods. These expectations are learned over time and they are highly correlated with the number of calories that end up on our plate. Indeed, across a range of foods, the large variation in expected satiety/satiation may be a more important determinant of meal size than relatively subtle differences in palatability. Building on related advances, it would also appear that memory for portion size has an important role in generating satiety after a meal has been consumed. Together, these findings expose the importance of planning and episodic memory in the control of appetite and food intake in humans. © 2014 Macmillan Publishers Limited All rights reserved.


Vertesi T.,Hungarian Academy of Sciences | Pironio S.,University of Geneva | Brunner N.,University of Bristol
Physical Review Letters | Year: 2010

We show that the detection efficiencies required for closing the detection loophole in Bell tests can be significantly lowered using quantum systems of dimension larger than two. We introduce a series of asymmetric Bell tests for which an efficiency arbitrarily close to 1/N can be tolerated using N-dimensional systems, and a symmetric Bell test for which the efficiency can be lowered down to 61.8% using four-dimensional systems. Experimental perspectives for our schemes look promising considering recent progress in atom-photon entanglement and in photon hyperentanglement. © 2010 The American Physical Society.


Hart E.C.J.,University of Bristol | Charkoudian N.,U.S. Army
Physiology | Year: 2014

Sex and age have important influences on sympathetic neural control of blood pressure in humans. Young women are relatively protected against risk of hypertension due to greater peripheral vasodilator influences compared with young men and older people. This protective effect is lost at menopause. Older men and women have higher sympathetic nerve activity and tighter coupling between SNA and blood pressure, contributing to the increased risk of hypertension with aging. © 2014 Int. Union Physiol. Sci./Am. Physiol. Soc.


Orr-Ewing A.J.,University of Bristol
Journal of Chemical Physics | Year: 2014

Bimolecular reactions in the gas phase exhibit rich and varied dynamical behaviour, but whether a profound knowledge of the mechanisms of isolated reactive collisions can usefully inform our understanding of reactions in liquid solutions remains an open question. The fluctuating environment in a liquid may significantly alter the motions of the reacting particles and the flow of energy into the reaction products after a transition state has been crossed. Recent experimental and computational studies of exothermic reactions of CN radicals with organic molecules indicate that many features of the gas-phase dynamics are retained in solution. However, observed differences may also provide information on the ways in which a solvent modifies fundamental chemical mechanisms. This perspective examines progress in the use of time-resolved infra-red spectroscopy to study reaction dynamics in liquids, discusses how existing theories can guide the interpretation of experimental data, and suggests future challenges for this field of research. © 2014 AIP Publishing LLC.


Brunstrom J.M.,University of Bristol
Proceedings of the Nutrition Society | Year: 2011

Unlike energy expenditure, energy intake occurs during discrete events: snacks and meals. The prevailing view is that meal size is governed by physiological and psychological events that promote satiation towards the end of a meal. This review explores an alternative and perhaps controversial proposition. Specifically that satiation plays a secondary role, and that meal size (kJ) is controlled by decisions about portion size, before a meal begins. Recently, techniques have been developed that enable us to quantify 'expected satiation' and 'expected satiety' (respectively, the fullness and the respite from hunger that foods are expected to confer). When compared on a kJ-for-kJ basis, these expectations differ markedly across foods. Moreover, in self-selected meals, these measures are remarkably good predictors of the energy content of food that ends up on our plate, even more important than palatability. Expected satiation and expected satiety are influenced by the physical characteristics of a food (e.g. perceived volume). However, they are also learned. Indeed, there is now mounting evidence for 'expected-satiation drift', a general tendency for a food to have higher expected satiation as it increases in familiarity. Together, these findings show that important elements of control (discrimination and learning/adaptation) are clearly evident in plans around portion size. Since most meals are eaten in their entirety, understanding the nature of these controls should be given high priority. © The Author 2011.


Henderson A.J.,University of Bristol | Warner J.O.,Imperial College London
Seminars in Fetal and Neonatal Medicine | Year: 2012

There is convincing evidence that asthma has its origins in early life. We review the epidemiological and biological evidence for fetal exposures that may have a causal role in asthma development. However, those factors that provoke asthma exacerbations are not necessarily the same as those associated with disease induction. Epidemiological studies have identified many potential exposures linked to asthma but these do not confirm causality and have not been replicated by experiment. Asthma is a heterogeneous disease and there are developmental influences on at least two pathways, airway structure and airway inflammation. The fetus is not immunologically naive and intrauterine exposures can act directly to invoke immunological sensitisation leading postnatally to airway inflammation. Other potential mechanisms include indirect effects on airway and lung growth through fetal nutrition and epigenetic modifications of DNA expression by environmental exposures. Identifying the causal factors will provide the targets for interventions to prevent disease. © 2012 Elsevier Ltd.


Al-Safi S.W.,University of Cambridge | Short A.J.,University of Bristol
Physical Review Letters | Year: 2013

Many-party correlations between measurement outcomes in general probabilistic theories are given by conditional probability distributions obeying the nonsignaling condition. We show that any such distribution can be obtained from classical or quantum theory by relaxing positivity constraints on either the mixed state shared by the parties or the local functions that generate measurement outcomes. Our results apply to generic nonsignaling correlations, but in particular they yield two distinct quasiclassical models for quantum correlations. © 2013 American Physical Society.


Walker A.M.,University of Bristol
Physics of the Earth and Planetary Interiors | Year: 2012

The full elastic constants tensors of diopside (CaMgSi 2O 6) and jadeite (NaAlSi 2O 6) have been calculated using a planewave and pseudopotentials based implementation of density functional theory within the generalised gradient approximation at pressures between 0 and 20GPa. Both minerals stiffen over this pressure range with the isotropic average bulk moduli increasing by ∼50% and the shear moduli by ∼20%. However, in detail the behaviour of the individual elastic constants varies and this drives changes in the anisotropy. Overall, and in contrast to predictions based on the extrapolation of calculations based on inter-atomic potential models, the elastic anisotropy of diopside decreases with increasing pressure. The elastic anisotropy of jadeite increases slightly at low pressure, exhibits a maximum at around 10GPa and then begins to slowly decrease. Despite the small changes in the total and maximum anisotropy, the shear-wave anisotropy for certain propagation directions vary dramatically with pressure. For example, the anisotropy experienced by a shear-wave propagating in the [010] direction in diopside doubles between 5 and 15GPa. © 2011 Elsevier B.V.


Yu S.,Sun Yat Sen University | Yu S.,University of Bristol
Optics Express | Year: 2015

Ultra-short- and short-reach optical interconnects are the new high growth applications for optical communications. High capacity density, high spectral efficiency, low cost, low power consumption, and fast configurability are some of the key requirements for potential optical transmission technology candidates. Based on recent progress in orbital angular momentum multiplexed optical transmission and optical device technologies, this paper discusses the potentials and challenges of using orbital angular momentum multiplexing in optical interconnect applications scenarios to meet above requirements. © 2015 Optical Society of America.


Cunningham J.A.,University of Bristol
Proceedings. Biological sciences / The Royal Society | Year: 2012

The Ediacaran Doushantuo biota has yielded fossils that include the oldest widely accepted record of the animal evolutionary lineage, as well as specimens with alleged bilaterian affinity. However, these systematic interpretations are contingent on the presence of key biological structures that have been reinterpreted by some workers as artefacts of diagenetic mineralization. On the basis of chemistry and crystallographic fabric, we characterize and discriminate phases of mineralization that reflect: (i) replication of original biological structure, and (ii) void-filling diagenetic mineralization. The results indicate that all fossils from the Doushantuo assemblage preserve a complex mélange of mineral phases, even where subcellular anatomy appears to be preserved. The findings allow these phases to be distinguished in more controversial fossils, facilitating a critical re-evaluation of the Doushantuo fossil assemblage and its implications as an archive of Ediacaran animal diversity. We find that putative subcellular structures exhibit fabrics consistent with preservation of original morphology. Cells in later developmental stages are not in original configuration and are therefore uninformative concerning gastrulation. Key structures used to identify Doushantuo bilaterians can be dismissed as late diagenetic artefacts. Therefore, when diagenetic mineralization is considered, there is no convincing evidence for bilaterians in the Doushantuo assemblage.


Satchell S.C.,University of Bristol
Kidney International | Year: 2012

The effects of diabetes on glomerular structure and particularly that of the glomerular capillary wall have been extensively documented. By correlation with clinical measurements, Weil and colleagues provide important insights into the functional significance of glomerular structural changes in type 2 diabetes. Podocyte detachment correlates with albumin-to-creatinine ratio, but less strongly than does loss of endothelial fenestrations, which also correlates with reduced glomerular filtration rate. The role of the glomerular endothelium in diabetic nephropathy demands further scrutiny. © 2012 International Society of Nephrology.


Churchill R.,University of Bristol
The Cochrane database of systematic reviews | Year: 2013

So-called 'third wave' cognitive and behavioural therapies represent a new generation of psychological therapies that are increasingly being used in the treatment of psychological problems. However, the effectiveness and acceptability of third-wave cognitive and behavioural therapy (CBT) approaches as treatment for acute depression remain unclear. 1. To examine the effects of all third wave CBT approaches compared with treatment as usual/waiting list/attention placebo/psychological placebo control conditions for acute depression.2. To examine the effects of different third wave CBT approaches (ACT, compassionate mind training, functional analytic psychotherapy, dialectical behaviour therapy, MBCT, extended behavioural activation and metacognitive therapy) compared with treatment as usual/waiting list/attention placebo/psychological placebo control conditions for acute depression.3. To examine the effects of all third wave CBT approaches compared with different types of comparators (treatment as usual, no treatment, waiting list, attention placebo, psychological placebo) for acute depression. We searched the Cochrane Depression Anxiety and Neurosis Group Trials Specialised Register (CCDANCTR to 01/01/12), which includes relevant randomised controlled trials from The Cochrane Library (all years), EMBASE, (1974-), MEDLINE (1950-) and PsycINFO (1967-). We also searched CINAHL (May 2010) and PSYNDEX (June 2010) and reference lists of the included studies and relevant reviews for additional published and unpublished studies. An updated search of CCDANCTR restricted to search terms relevant to third wave CBT therapies was conducted in March 2013 (CCDANCTR to 01/02/13). Randomised controlled trials that compared third wave CBT therapies with control conditions for acute depression in adults. Two review authors independently identified studies, assessed trial quality and extracted data. Study authors were contacted for additional information when required. We rated the quality of evidence using GRADE methods. Four small studies (224 participants) were included in the review. Little information was provided about the process of allocating participants to groups. None of the studies used independent outcome assessors, and evidence suggested researcher allegiance towards the active treatments. The four studies examined a diversity of third wave CBT approaches (extended behavioural activation, acceptance and commitment therapy and competitive memory training) and control conditions. None of the studies conducted follow-up assessments. The results showed a significant difference in clinical response rates in favour of third wave CBT when compared with treatment as usual (TAU) conditions (three studies, 170 participants, risk ratio (RR) 0.51, 95% confidence interval (CI) 0.27 to 0.95; very low quality). No significant difference in treatment acceptability based on dropout rates was found between third wave CBT approaches and TAU (four studies, 224 participants, RR 1.01, 95% CI 0.08 to 12.30; very low quality). Both analyses showed substantial statistical heterogeneity. Very low quality evidence suggests that third wave CBT approaches appear to be more effective than treatment as usual in the treatment of acute depression. The very small number of available studies and the diverse types of interventions and control comparators, together with methodological limitations, limit the ability to draw any conclusions on their effect in the short term or over a longer term. The increasing popularity of third wave CBT approaches in clinical practice underscores the importance of completing further studies of third wave CBT approaches in the treatment of acute depression, on a short- and long-term basis, to provide evidence of their effectiveness to policy-makers, clinicians and users of services.


Adams J.C.,University of Bristol
Cold Spring Harbor perspectives in biology | Year: 2011

Thrombospondins are evolutionarily conserved, calcium-binding glycoproteins that undergo transient or longer-term interactions with other extracellular matrix components. They share properties with other matrix molecules, cytokines, adaptor proteins, and chaperones, modulate the organization of collagen fibrils, and bind and localize an array of growth factors or proteases. At cell surfaces, interactions with an array of receptors activate cell-dependent signaling and phenotypic outcomes. Through these dynamic, pleiotropic, and context-dependent pathways, mammalian thrombospondins contribute to wound healing and angiogenesis, vessel wall biology, connective tissue organization, and synaptogenesis. We overview the domain organization and structure of thrombospondins, key features of their evolution, and their cell biology. We discuss their roles in vivo, associations with human disease, and ongoing translational applications. In many respects, we are only beginning to appreciate the important roles of these proteins in physiology and pathology.


Nicholls S.M.,University of Bristol
Investigative ophthalmology & visual science | Year: 2012

The purpose of our study is to develop a pre-clinical model of corneal graft rejection in the semi-inbred NIH minipig as a model of human rejection. NIH minipigs received corneal allografts with MHC and minor mismatches, or minor mismatches alone. Clinical rejection was monitored, and major subsets of leukocytes and ingress of vessels were quantified post-mortem by automated digital methods. Spectratypes of recipient T-cell receptor β-subunit variable region (TRβV) were analyzed. The capacity of pig corneal endothelial cells to proliferate in vivo was assessed. Autografts (n = 5) and SLA(cc) to SLA(cc) allografts (minor mismatches, n = 5) were not rejected. Median graft survival of SLA(dd) and SLA(bb) allografts in SLA(cc) strain recipients (major and minor mismatches) was 57 (n = 10) and 67 (n = 6) days, respectively. Rejected grafts did not recover clarity in vivo, and corneal endothelial cells did not proliferate in organ culture after cryo-injury. There were significantly more leukocytes in clinically rejected versus accepted grafts (P < 0.0001) and in transplanted versus contralateral eyes (P < 0.0001). Numbers of T-cells were significantly greater in clinically accepted grafts versus autografts and in rejected grafts versus accepted (P < 0.005 for most subsets). There were significant differences in TRβV spectratype between graft groups in cornea, but not in draining lymph node or blood (P < 0.05). The NIH minipig offers a robust model of human rejection suitable for immunological or therapeutic studies. In particular, there is limited capacity for corneal endothelial repair in vivo, and histological evidence suggests that allosensitization of the recipient may develop in the absence of clinical rejection.


Yang T.H.,National University of Singapore | Navascues M.,University of Bristol
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

Self-testing is a device-independent approach to estimate the state and measurement operators without the need to assume the dimension of our quantum system. In this paper, we show that one can self-test black boxes into any pure entangled two-qubit state by performing simple Bell-type experiments. The approach makes use of only one family of Bell inequalities with two inputs and two outputs. Furthermore, we outline the sufficient conditions for one to self-test any dimensional bipartite entangled state. All these methods are robust to small but inevitable experimental errors. © 2013 American Physical Society.


Weavers H.,University of Cambridge | Weavers H.,University of Bristol | Skaer H.,University of Cambridge
Developmental Cell | Year: 2013

Tissue morphogenesis involves both the sculpting of tissue shape and the positioning of tissues relative toone another in the body. Using the renal tubules of Drosophila, we show that a specific distal tubule cell regulates both tissue architecture and position in the body cavity. Focusing on the anterior tubules, we demonstrate that tip cells make transient contacts with alary muscles at abdominal segment boundaries, moving progressively forward as convergentextension movements lengthen the tubule. Tip cellanchorage antagonizes forward-directed, TGF-β-guided tubule elongation, thereby ensuring the looped morphology characteristic of renal tubules from worms to humans. Distinctive tip cell exploratory behavior, adhesion, and basement membrane clearing underlie target recognition and dynamic interactions. Defects in these features obliterate tip cell anchorage, producing misshapen and misplaced tubules with impaired physiological function. © 2013 The Authors.


Leinhardt Z.M.,University of Bristol | Stewart S.T.,Harvard University
Astrophysical Journal | Year: 2012

Collisions are the core agent of planet formation. In this work, we derive an analytic description of the dynamical outcome for any collision between gravity-dominated bodies. We conduct high-resolution simulations of collisions between planetesimals; the results are used to isolate the effects of different impact parameters on collision outcome. During growth from planetesimals to planets, collision outcomes span multiple regimes: cratering, merging, disruption, super-catastrophic disruption, and hit-and-run events. We derive equations (scaling laws) to demarcate the transition between collision regimes and to describe the size and velocity distributions of the post-collision bodies. The scaling laws are used to calculate maps of collision outcomes as a function of mass ratio, impact angle, and impact velocity, and we discuss the implications of the probability of each collision regime during planet formation. Collision outcomes are described in terms of the impact conditions and the catastrophic disruption criteria, Q*RD - the specific energy required to disperse half the total colliding mass. All planet formation and collisional evolution studies have assumed that catastrophic disruption follows pure energy scaling; however, we find that catastrophic disruption follows nearly pure momentum scaling. As a result, Q*RD is strongly dependent on the impact velocity and projectile-to-target mass ratio in addition to the total mass and impact angle. To account for the impact angle, we derive the interacting mass fraction of the projectile; the outcome of a collision is dependent on the kinetic energy of the interacting mass rather than the kinetic energy of the total mass. We also introduce a new material parameter, c*, that defines the catastrophic disruption criteria between equal-mass bodies in units of the specific gravitational binding energy. For a diverse range of planetesimal compositions and internal structures, c* has a value of 5± 2; whereas for strengthless planets, we find c* = 1.9 ±0.3. We refer to the catastrophic disruption criteria for equal-mass bodies as the principal disruption curve, which is used as the reference value in the calculation of Q*RD for any collision scenario. The analytic collision model presented in this work will significantly improve the physics of collisions in numerical simulations of planet formation and collisional evolution. © 2012. The American Astronomical Society. All rights reserved.


Stewart S.T.,Harvard University | Leinhardt Z.M.,University of Bristol
Astrophysical Journal | Year: 2012

Numerical simulations of the stochastic end stage of planet formation typically begin with a population of embryos and planetesimals that grow into planets by merging. We analyzed the impact parameters of collisions leading to the growth of terrestrial planets from recent N-body simulations that assumed perfect merging and calculated more realistic outcomes using a new analytic collision physics model. We find that collision outcomes are diverse and span all possible regimes: hit-and-run, merging, partial accretion, partial erosion, and catastrophic disruption. The primary outcomes of giant impacts between planetary embryos are approximately evenly split between partial accretion, graze-and-merge, and hit-and-run events. To explore the cumulative effects of more realistic collision outcomes, we modeled the growth of individual planets with a Monte Carlo technique using the distribution of impact parameters from N-body simulations. We find that fewer planets reached masses >0.7 M Earth using the collision physics model compared to simulations that assumed every collision results in perfect merging. For final planets with masses >0.7 M Earth, 60% are enriched in their core-to-mantle mass fraction by >10% compared to the initial embryo composition. Fragmentation during planet formation produces significant debris (15% of the final mass) and occurs primarily by erosion of the smaller body in partial accretion and hit-and-run events. In partial accretion events, the target body grows by preferentially accreting the iron core of the projectile and the escaping fragments are derived primarily from the silicate mantles of both bodies. Thus, the bulk composition of a planet can evolve via stochastic giant impacts. © 2012. The American Astronomical Society. All rights reserved..


Muller M.P.,Perimeter Institute for Theoretical Physics | Masanes L.,University of Bristol
New Journal of Physics | Year: 2013

It is sometimes pointed out as a curiosity that the state space of quantum two-level systems, i.e. the qubit, and actual physical space are both three-dimensional and Euclidean. In this paper, we suggest an information-theoretic analysis of this relationship, by proving a particular mathematical result: suppose that physics takes place in d spatial dimensions, and that some events happen probabilistically (not assuming quantum theory in any way). Furthermore, suppose there are systems that carry 'minimal amounts of direction information', interacting via some continuous reversible time evolution. We prove that this uniquely determines spatial dimension d = 3 and quantum theory on two qubits (including entanglement and unitary time evolution), and that it allows observers to infer local spatial geometry from probability measurements. © IOP Publishing and Deutsche Physikalische Gesellschaft.


Dennis M.R.,University of Bristol
Optics Letters | Year: 2011

A new classification of circular polarization C points in three-dimensional polarization ellipse fields is proposed. The classification type depends on the out-of-plane variation of the polarization ellipse axis, in particular, whether the ellipse axes are in the plane of circular polarization one or three times. A minimal set of parameters for this classification is derived and discussed in the context of the familiar in-plane C point classification into lemon, star, and monstar types. This new geometric classification is related to the Möbius index of polarization singularities recently introduced by Freund. © 2011 Optical Society of America.


Meech R.,University of Bristol
Wiley Interdisciplinary Reviews: Membrane Transport and Signaling | Year: 2012

The low numbers of hydrogen ions in physiological solutions encouraged the assumption that H+ currents flowing through conductive pathways would be so small as to be unmeasurable even if theoretically possible. Evidence for an H+-based action potential in the luminescent dinoflagellate Noctiluca and for an H+-conducting channel created by the secretions of the bacterium Bacillus brevis, did little to alter this perception. The clear demonstration of H+ conduction in molluscan neurons might have provided the breakthrough but the new pathway was without an easily demonstrable function, and escaped general attention. Indeed the extreme measures that must be taken to successfully isolate H+ currents meant that it was some years before proton channels were identified in mammalian cells. However, with the general availability of patch-clamp techniques and evidence for an important role in mammalian neutrophils, the stage was set for a series of structure/function studies with the potential to make the proton channel the best understood channel of all. In addition, widespread genomic searches have established that proton channels play important roles in processes ranging from fertilization of the human ovum to the progression of breast cancer. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Whitelaw A.,University of Bristol | Aquilina K.,Frenchay Hospital
Archives of Disease in Childhood: Fetal and Neonatal Edition | Year: 2012

Intraventricular haemorrhage and posthaemorrhagic ventricular dilatation remain an important challenge in the management of prematurity and are associated with significant permanent morbidity. Progressive ventricular dilatation causes white matter injury by pressure, distortion, free radical injury and inflammation. Therapeutic interventions include serial lumbar punctures, only useful when the ventricles remain in communication with the lumbar subarachnoid space, and repeated aspiration through a ventricular access device. Reduction of cerebrospinal fluid production by acetazolamide and frusemide in a large multicentre randomised trial showed a worse outcome in the treated arm. A trial of drainage, irrigation and fibrinolytic therapy did not demonstrate a reduced need for permanent cerebrospinal fluid diversion, but did show a significant reduction in severe cognitive disability at two years. Ventriculoperitoneal shunting is indicated when the ventricles continue to enlarge at a body weight of around 2.5 kg and cerebrospinal fluid protein levels are below 1.5 g /L. This review summarises current concepts on the pathophysiology and management of post-haemorrhagic ventricular dilatation, underlining clinical challenges and ongoing research. Although the percentage of small preterm infants developing intraventricular haemorrhage (IVH) has been greatly reduced in the last three decades, increased survival of very immature infants has meant that large IVH with subsequent posthaemorrhagic ventricular dilatation is still a serious unsolved problem.


Bright J.A.,University of Bristol
Journal of Paleontology | Year: 2014

Finite element analysis (FEA) is a powerful quantitative tool that models mechanical performance in virtual reconstructions of complex structures, such as animal skeletons. The unique potential of FEA to elucidate the function, performance, and ecological roles of extinct taxa is an alluring prospect to paleontologists, and the technique has gained significant attention over recent years. However, as with all modeling approaches, FE models are highly sensitive to the information that is used to construct them. Given the imperfect quality of the fossil record, paleontologists are unlikely to ever know precisely which numbers to feed into their models, and it is therefore imperative that we understand how variation in FEA inputs directly affects FEA results. This is achieved through sensitivity and validation studies, which assess how inputs influence outputs, and compare these outputs to experimental data obtained from extant species. Although these studies are restricted largely to primates at present, they highlight both the power and the limitations of FEA. Reassuringly, FE models seem capable of reliably reproducing patterns of stresses and strains even with limited input data, but the magnitudes of these outputs are often in error. Paleontologists are therefore cautioned not to over-interpret their results. Crucially, validations show that without knowledge of skeletal material properties, which are unknowable from fossilized tissues, absolute performance values such as breaking stresses cannot be accurately determined. The true power of paleontological FEA therefore lies in the ability to manipulate virtual representations of morphology, to make relative comparisons between models, and to quantitatively assess how evolutionary changes of shape result in functional adaptations. Copyright © 2014, The Paleontological Society.


Benton M.J.,University of Bristol
Palaeontology | Year: 2015

A key question in palaeontology is whether the fossil record taken at face value is adequate to represent true patterns of diversity through time. Some methods of assessing data quality have depended on the commonly observed covariation of palaeodiversity and fossiliferous formation counts through time, based on the assumption that the count of formations containing fossils, to a greater or lesser extent, drives diversity; but what if diversity drives formations? Close study of two fossil records, early tetrapods (Devonian-Jurassic) and dinosaurs, shows how the relationship between new taxa and new fossiliferous formations varies through research time. Initially, each new find represents a new fossiliferous formation and discovery follows the 'bonanza' model (fossils drive formations). In unexplored parts of the world, new taxa are identified frequently in new regions/formations. Only after time, in well-explored continents such as Europe and North America, does collecting style switch to a mix of exploration for new formations and re-sampling of known fossiliferous formations. Data are most striking for dinosaurs, where the Triassic-Jurassic record largely comprises finds from Europe and North America, where new formation discoveries reached their half-life in 1914. This contrasts with the Cretaceous, which is dominated by rapidly rising discoveries from regions outside Europe and North America and the formation half-life for these 'new' lands is 1986, showing that 50% of new Cretaceous dinosaur-bearing formations were identified only in the past 30 years. The relationship between dinosaur-bearing formations and palaeodiversity then combines three signals in variable amounts, reflecting the original diversity (relative abundances of particular taxa in different formations), redundancy (new fossiliferous formations accruing because of new fossil finds) and sampling (intensity of exploration for new fossiliferous formations, and of search within already-sampled formations). For fossil vertebrates at least, formation counts of various kinds are poor predictors of sampling, missing, for example, the bonanza samples of Lagerstätten such as the Yixian Formation in China: thousands of specimens, dozens of species, but counted as one formation. These observations suggest that formation count cannot be regarded as an unbiased metric of sampling. © The Palaeontological Association.


OBJECTIVE: The aim of this study was to describe the efficacy of pamidronate therapy on disease activity in children with chronic non-bacterial osteitis (CNO) using whole body MRI (WB-MRI).METHODS: Clinical assessment and WB-MRI were obtained in 11 children before and after 1 year of pamidronate therapy using a 1.5 T MRI scanner and short tau inversion recovery sequences. The images were reported by a paediatric radiologist.RESULTS: WB-MRI identified 75 lesions in 11 patients; 16 of these lesions had not been detected by clinical examination. Follow-up MRI after 1 year of pamidronate showed complete resolution of inflammation in 45 lesions, moderate improvement in 10 lesions and no change in 20 lesions. Two new lesions developed while on treatment.CONCLUSION: WB-MRI allows a more accurate assessment of the disease extent in CNO than clinical examination alone and is useful in the objective measurement of treatment efficacy. Pamidronate appears to be an effective treatment in children with CNO unresponsive to NSAIDs. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.


The role of both autologous (autoSCT) and allogeneic stem cell transplantation (alloSCT) in the management of mantle cell lymphoma (MCL) remains to be clarified. We conducted a consensus project using the RAND-modified Delphi consensus procedure to provide guidance on how SCT should be used in MCL. With regard to autoSCT, there was consensus in support of: autoSCT is the standard first-line consolidation therapy; induction therapy should include high-dose cytarabine and Rituximab; complete or partial remission should be achieved before autoSCT; Rituximab maintenance following autoSCT is not indicated; and omission of autoSCT in 'low-risk' patients is not indicated. No consensus could be reached regarding: autoSCT in the treatment of relapsed disease following non-transplant therapy; the value of positron emission tomography scanning and minimal residual disease (MRD) monitoring; in vivo purging with Rituximab; total body irradiation conditioning for autoSCT; and preemptive Rituximab after autoSCT. For alloSCT, consensus was reached in support of: alloSCT should be considered for patients relapsing after autoSCT; reduced intensity conditioning regimens should be used; allogeneic immunotherapy should be used for MRD eradication after alloSCT; and there is a lack of prognostic criteria to guide the use of alloSCT as first-line consolidation. No consensus was reached regarding the role of alloSCT for relapsed disease following non-transplant therapy.Leukemia advance online publication, 29 August 2014; doi:10.1038/leu.2014.223.


Dodd J.W.,University of Bristol
Alzheimer's Research and Therapy | Year: 2015

Almost 40 million people currently live with dementia but this is estimated to double over the next 20 years; despite this, research identifying modifiable risk factors is scarce. There is increasing evidence that cognitive impairment is more frequent in those with chronic lung disease than those without. Chronic obstructive pulmonary disease affects 210 million people, with cognitive impairment present in 60% of certain populations. Co-morbid cognitive dysfunction also appears to impact on important outcomes such as quality of life, hospitalisation and survival. This review summarises the evidence of an association between cognition, impaired lung function and obstructive lung disease. It goes on to examine the contribution of neuro-imaging to our understanding of the underlying pathophysiology. While the mechanisms of brain pathology and cognitive impairment are likely to be complex and multi-factorial, there is evidence to suggest a key role for occult cerebrovascular damage independent of traditional vascular risk factors, including smoking. © 2015 Dodd; licensee BioMed Central.


Eggers J.,University of Bristol
Physics of Fluids | Year: 2014

We consider the breakup of a fluid thread, neglecting the effect of the outside fluid (or air). After breakup, the solution of the fluid equations consists of two threads, receding rapidly from the point of breakup. We show that the bulk of each thread is described by a similarity solution of slender geometry (which we call the thread solution), but which breaks down near the tip. Near the tip of the thread the thread solution can be matched to a solution of Stokes' equation, which consists of a finger of constant spatial radius, rounded at the end. Very close to breakup, the thread solution balances inertia, viscosity, and surface tension (Navier-Stokes case). If however the fluid viscosity is large (as measured by the dimensionless Ohnesorge number), some time after breakup the thread solution consists of a balance of surface tension and viscosity only (Stokes case), and the thread profile can be described analytically. © 2014 AIP Publishing LLC.


Hargreaves J.R.,London School of Hygiene and Tropical Medicine | Howe L.D.,University of Bristol
AIDS | Year: 2010

Objective: HIV prevalence trends suggest that the epidemic is stable or declining in many sub-Saharan African countries. However, trends might differ between socioeconomic groups. Educational attainment is a common measure of socioeconomic position in HIV datasets from Africa. Several studies have shown higher HIV prevalence among more educated groups, but this may change over time. We describe changes in HIV prevalence by educational attainment in Tanzania from 2003 to 2007. DESIGN AND Methods: Analysis of data from two large, nationally representative HIV prevalence surveys conducted among adults aged 15-49 years in Tanzania in 2003-2004 (10 934 participants) and 2007-2008 (15 542 participants). We explored whether changes in HIV prevalence differed between groups with different levels of educational attainment after adjustment for potential confounding factors (sex, age, urban/rural residence and household wealth). Results: Changes in HIV prevalence differed by educational attainment level (interaction test P value = 0.07). HIV prevalence was stable among those with no education (adjusted odds ratio 2007-2008 vs. 2003-2004 1.03, 95% confidence interval 0.72-1.47), whereas showing a small but borderline significant decline among those with primary education (adjusted odds ratio 0.85, 95% confidence interval 0.69-1.03) and a larger statistically significant decline among those with secondary education (adjusted odds ratio 0.53, 95% confidence interval 0.34-0.84). Discussion: Prevalent HIV infections are now concentrating among those with the lowest levels of education in Tanzania. Although HIV-related mortality, migration and cohort effects might contribute to this, different HIV incidence by educational level between the surveys provides the most likely explanation. Urgent measures to improve HIV prevention among those with limited education and of low socioeconomic position are necessary in Tanzania. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Bates D.O.,University of Bristol
Biochemical Society Transactions | Year: 2011

PET (pre-eclamptic toxaemia), characterized by pregnancy-related hypertension and proteinuria, due to widespread endothelial dysfunction, is a primary cause of maternal morbidity. Altered circulating factors, particularly the VEGF (vascular endothelial growth factor) family of proteins and their receptors, are thought to be key contributors to this disease. Plasma from patients with PET induces numerous cellular and physiological changes in endothelial cells, indicating the presence of a circulating imbalance of the normal plasma constituents. These have been narrowed down to macromolecules of the VEGF family of proteins and receptors. It has been shown that responses of endothelial cells in intact vessels to plasma from patients with pre-eclampsia is VEGF-dependent. It has recently been shown that this may be specific to the VEGF 165b isoform, and blocked by addition of recombinant human PlGF (placental growth factor). Taken together with results that show that sVEGFR1 (soluble VEGF receptor 1) levels are insufficient to bind VEGF-A in human plasma from patients with pre-eclampsia, and that other circulating macromolecules bind, but do not inactivate, VEGF-A, this suggests that novel hypotheses involving altered bioavailability of VEGF isoforms resulting from reduced or bound PlGF, or increased sVEGFR1 increasing biological activity of circulating plasma, could be tested. This suggests that knowing how to alter the balance of VEGF family members could prevent endothelial activation, and potentially some symptoms, of pre-eclampsia. ©The Authors Journal compilation ©2011 Biochemical Society.


Jeffrey M.R.,University of Bristol
Physica D: Nonlinear Phenomena | Year: 2014

Sharp switches in behaviour, like impacts, stick-slip motion, or electrical relays, can be modelled by differential equations with discontinuities. A discontinuity approximates fine details of a switching process that lie beyond a bulk empirical model. The theory of piecewise-smooth dynamics describes what happens assuming we can solve the system of equations across its discontinuity. What this typically neglects is that effects which are vanishingly small outside the discontinuity can have an arbitrarily large effect at the discontinuity itself. Here we show that such behaviour can be incorporated within the standard theory through nonlinear terms, and these introduce multiple sliding modes. We show that the nonlinear terms persist in more precise models, for example when the discontinuity is smoothed out. The nonlinear sliding can be eliminated, however, if the model contains an irremovable level of unknown error, which provides a criterion for systems to obey the standard Filippov laws for sliding dynamics at a discontinuity. © 2014 Elsevier B.V. All rights reserved.


Navascues M.,University of Bristol | de la Torre G.,ICFO - Institute of Photonic Sciences | Vertesi T.,Hungarian Academy of Sciences
Physical Review X | Year: 2014

The future progress of semi-device-independent quantum information science depends crucially on our ability to bound the strength of the nonlocal correlations achievable with finite-dimensional quantum resources. In this work, we characterize quantum nonlocality under local dimension constraints via a complete hierarchy of semidefinite programming relaxations. In the bipartite case, we find that the first level of the hierarchy returns nontrivial bounds in all cases considered, allowing us to study nonlocality scenarios with four measurement settings on one side and twelve on the other in a normal desktop. In the tripartite case, we apply the hierarchy to derive a Bell-type inequality that can only be violated when each of the three parties has local dimension greater than 2, hence certifying three-dimensional tripartite entanglement in a device-independent way. Finally, we show how the new method can be trivially modified to detect nonseparable measurements in two-qubit scenarios.


Dettmann C.P.,University of Bristol
Communications in Theoretical Physics | Year: 2014

The Lorentz gas, a point particle making mirror-like reflections from an extended collection of scatterers, has been a useful model of deterministic diffusion and related statistical properties for over a century. This survey summarises recent results, including periodic and aperiodic models, finite and infinite horizon, external fields, smooth or polygonal obstacles, and in the Boltzmann - Grad limit. New results are given for several moving particles and for obstacles with flat points. Finally, a variety of applications are presented. © 2014 Chinese Physical Society and IOP Publishing Ltd.


Context: Several single-nucleotide polymorphisms (SNPs) have been reliably associated with areal bone mineral density (aBMD) in genome-wide association studies of mostly older subjects. Objective: We aimed to test those SNPs for an association with peripheral quantitative computed tomography (pQCT) bone measures in two young cohorts. Design and Study Participants: We genotyped nine SNPs from the most promising aBMD candidates in a cohort of 15-yr-olds [in the Avon Longitudinal Study of Parents and Children (ALSPAC)] and carried out association analysis with several tibial pQCT measures to determine whether these candidates were important during adolescent growth and which particular skeletal parameters each of the candidates were acting upon. We also carried out a metaanalysis of the SNPs for association with cortical bone mineral density (BMDC) in ALSPAC and a similar male-only study (Gothenburg Osteoporosis and Obesity Determinants). Results: In the ALSPAC cohort, we found a significant association between RANK SNP (rs3018362) and BMDC but not any of the other pQCT bone measures. In the metaanalysis, we found the OPG SNP (rs4355801) and the RANK SNP (rs3018362) to be significantly associated with BMDC. We also found suggestive evidence of an association between the MARK3 SNP (rs2010281) and BMDC but with a direction of effect opposite to that previously reported. Conclusion: The association of genes from the RANK/RANKL/OPG pathway and BMDC provides new insight into how this system might affect the skeleton, confirming it to be associated with volumetric cortical bone density but observing no relationship with bone size. Copyright © 2010 by The Endocrine Society.


Eggers J.,University of Bristol
Physics of Fluids | Year: 2014

When a liquid containing a dilute solution of long, flexible polymers breaks up under the action of surface tension, it forms long threads of nearly uniform thickness. However, at a thickness in the order of microns, the thread becomes unstable to the formation of a non-uniform "blistering" pattern: tiny drops separated by threads of highly concentrated polymer solution.We show that standardmodels for the coupling between stress and polymer concentration lead to a linear instability, which exhibits very strong transient growth of the free surface perturbation. A high concentration of polymer remains in the thread part of the structure. © 2014 AIP Publishing LLC.


Brereton R.G.,University of Bristol
Journal of Chemometrics | Year: 2011

The principles of one-class classifiers are introduced, together with the distinctions between one-class/multiclass, soft/hard, conjoint/disjoint and modelling/discriminatory methods. The methods are illustrated using case studies, namely from nuclear magnetic resonance metabolomic profiling, thermal analysis of polymers and simulations. Two main groups of classifier are described, namely statistically based distance metrics from centroids (Euclidean distance and quadratic discriminant analysis) and support vector domain description (SVDD). The statistical basis of the D statistic and its relationship with the F statistic, χ2, normal distribution and T2 is discussed. The SVDD D value is described. Methods for assessing the distance of residuals to disjoint principal component models (Q statistic) and their combination with distance-based methods to give the G statistic are outlined. © 2011 John Wiley & Sons, Ltd.


Cornell S.E.,University of Bristol
Environmental Pollution | Year: 2011

The organic component of atmospheric reactive nitrogen plays a role in biogeochemical cycles, climate and ecosystems. Although its deposition has long been known to be quantitatively significant, it is not routinely assessed in deposition studies and monitoring programmes. Excluding this fraction, typically 25-35%, introduces significant uncertainty in the determination of nitrogen deposition, with implications for the critical loads approach. The last decade of rainwater studies substantially expands the worldwide dataset, giving enough global coverage for specific hypotheses to be considered about the distribution, composition, sources and effects of organic-nitrogen deposition. This data collation and meta-analysis highlights knowledge gaps, suggesting where data-gathering efforts and process studies should be focused. New analytical techniques allow long-standing conjectures about the nature and sources of organic N to be investigated, with tantalising indications of the interplay between natural and anthropogenic sources, and between the nitrogen and carbon cycles. © 2010 Published by Elsevier Ltd.


Rees C.A.,University of Bristol
Archives of Disease in Childhood | Year: 2014

The autonomic nervous system (ANS) has been strikingly neglected in Western medicine. Despite its profound importance for regulation, adjustment and coordination of body systems, it lacks priority in training and practice and receives scant attention in numerous major textbooks. The ANS is integral to manifestations of illness, underlying familiar physical and psychological symptoms. When ANS activity is itself dysfunctional, usual indicators of acute illness may prove deceptive. Recognising the relevance of the ANS can involve seeing the familiar through fresh eyes, challenging assumptions in clinical assessment and in approaches to practice. Its importance extends from physical and psychological wellbeing to parenting and safeguarding, public services and the functioning of society. Exploration of its role in conditions ranging from neurological, gastrointestinal and connective tissue disorders, diabetes and chronic fatigue syndrome, to autism, behavioural and mental health difficulties may open therapeutic avenues. The ANS offers a mechanism for so-called functional illnesses and illustrates the importance of recognising that 'stress' takes many forms, physical, psychological and environmental, desirable and otherwise. Evidence of intrauterine and post-natal programming of ANS reactivity suggests that neonatal care and safeguarding practice may offer preventive opportunity, as may greater understanding of epigenetic change of ANS activity through, for example, accidental or psychological trauma or infection. The aim of this article is to accelerate recognition of the importance of the ANS throughout paediatrics, and of the potential physical and psychological cost of neglecting it.


Cox R.,Leibniz University of Hanover | Cox R.,University of Bristol
Natural Product Reports | Year: 2014

Oxidative rearrangements are key reactions during the biosyntheses of many secondary metabolites in fungi. This review highlights the most important examples of these reactions and aims to draw together key mechanistic themes to allow a better understanding and future exploitation of this key class of fungal catalysts. © 2014 the Partner Organisations.


Simpson T.J.,University of Bristol
Natural Product Reports | Year: 2014

This Viewpoint article provides a personal viewpoint of research in the area of fungal polyketide biosynthesis. It spans the period from the first applications and subsequent development of modern stable-isotope labelling methods, the isolation, sequencing and expression of PKS genes, biochemical and structural characterisation of PKS domains, fungal genome sequencing, through to genetic engineering of whole pathways. This article forms part of a "trilogy" of related Viewpoints from three close contemporaries who have been privileged to share in these developments since their outset over forty years ago and to enjoy both professional and personal interactions throughout that time. © 2014 the Partner Organisations.


Rands S.A.,University of Bristol
Interface Focus | Year: 2012

The arms race between brood parasites and their hosts has led to many different host behaviours for avoiding parasitism. Some of these behaviours are social, and require the presence of conspecifics to work effectively: in response to alarm calls, some species engage in mobbing behaviour where neighbours join nest tenants in attacking and repelling an invading brood parasite. There are risks involved for the neighbours, but it has been demonstrated that social mobbing allows individuals to learn about the presence of brood parasites in the environment, suggesting that social learning is occurring. Here, I consider whether using social signals to alert naive individuals to the presence of brood parasites is a suitable strategy, compared with sitting tight on the nest in response to the signal (which should reduce the chances of being parasitized). I also compare the efficiency of these strategies with the case where individuals fail to change behaviour in response a brood parasite. Using an individual-based simulation model, I demonstrate that both mobbing and sitting tight are effective strategies in response to a signal, and that mobbing is more effective when the chances of being parasitized increase. These results are discussed and compared with known host-brood parasite relationships. © 2012 The Royal Society.


Lawson D.J.,University of Bristol | Falush D.,Max Planck Institute for Evolutionary Anthropology
Annual Review of Genomics and Human Genetics | Year: 2012

A large number of algorithms have been developed to classify individuals into discrete populations using genetic data. Recent results show that the information used by both model-based clustering methods and principal components analysis can be summarized by a matrix of pairwise similarity measures between individuals. Similarity matrices have been constructed in a number of ways, usually treating markers as independent but differing in the weighting given to polymorphisms of different frequencies. Additionally, methods are now being developed that take linkage into account. We review several such matrices and evaluate their information content. A two-stage approach for population identification is to first construct a similarity matrix and then perform clustering. We review a range of common clustering algorithms and evaluate their performance through a simulation study. The clustering step can be performed either on the matrix or by first using a dimension-reduction technique; we find that the latter approach substantially improves the performance of most algorithms. Based on these results, we describe the population structure signal contained in each similarity matrix and find that accounting for linkage leads to significant improvements for sequence data. We also perform a comparison on real data, where we find that population genetics models outperform generic clustering approaches, particularly with regard to robustness for features such as relatedness between individuals. © 2012 by Annual Reviews. All rights reserved.


Wiggins S.,University of Bristol
Microfluidics and Nanofluidics | Year: 2011

We consider an Eulerian predictor of optimal mixing appropriate for steady, three-dimensional channel flow of the type that is commonly used in a variety of microfluidic mixing applications. This Eulerian indicator is applied to a kinematic model of the channel flow that allows one to control the flow structure of the secondary flows and the number of distinct secondary flows. The cases of two and three distinct secondary flows are considered and the Eulerian indicator predicts the optimal flow structure in the two secondary flow case and in the three secondary flow case that result in the best mixing. Moreover, it is shown that the case of three secondary flows mixes "optimally" (i.e., faster and more completely) than the case of two secondary flows. An explanation of this difference is given in terms of the Eulerian flow structure. © 2010 US Government.


McNamara J.M.,University of Bristol | Dall S.R.X.,University of Exeter
Ecology Letters | Year: 2011

Ostensibly, it makes sense in a changeable world to condition behaviour and development on information when it is available. Nevertheless, unconditional behavioural and life history strategies are widespread. Here, we show how intergenerational effects can limit the evolutionary value of responding to reliable environmental cues, and thus favour the evolutionary persistence of otherwise paradoxical unconditional strategies. While cue-ignoring genotypes do poorly in the wrong environments, in the right environment they will leave many copies of themselves, which will themselves leave many copies, and so on, leading genotypes to accumulate in habitats in which they do well. We call this 'The Multiplier Effect'. We explore the consequences of the multiplier effect by focussing on the ecologically important phenomenon of natal philopatry. We model the environment as a large number of temporally varying breeding sites connected by natal dispersal between sites. Our aim is to identify which aspects of an environment promote the multiplier effect. We show, if sites remain connected through some background level of 'accidental' dispersal, unconditional natal philopatry can evolve even when there is density dependence (with its accompanying kin competition effects), and cues that are only mildly erroneous. Thus, the multiplier effect may underpin the evolution and maintenance of unconditional strategies such as natal philopatry in many biological systems. © 2011 Blackwell Publishing Ltd/CNRS.


Halestrap A.P.,University of Bristol
IUBMB Life | Year: 2012

Monocarboxylate transporters (MCTs) catalyze the proton-linked transport of monocarboxylates such as L-lactate, pyruvate, and the ketone bodies across the plasma membrane. There are four isoforms, MCTs 1-4, which are known to perform this function in mammals, each with distinct substrate and inhibitor affinities. They are part of the larger SLC16 family of solute carriers, also known as the MCT family, which has 14 members in total, all sharing conserved sequence motifs. The family includes a high-affinity thyroid hormone transporter (MCT8), an aromatic amino acid transporter (T-type amino acid transporter 1/MCT10), and eight orphan members yet to be characterized. MCTs were predicted to have 12 transmembrane helices (TMs) with intracellular C- and N-termini and a large intracellular loop between TMs 6 and 7, and this was confirmed by labeling studies and proteolytic digestion. Site-directed mutagenesis has identified key residues required for catalysis and inhibitor binding and enabled the development of a molecular model of MCT1 in both inward and outward facing conformations. This suggests a likely mechanism for the translocation cycle. Although MCT family members are not themselves glycosylated, MCTs1-4 require association with a glycosylated ancillary protein, either basigin or embigin, for their correct translocation to the plasma membrane. These ancillary proteins have a single transmembrane domain and two to three extracellular immunoglobulin domains. They must remain closely associated with MCTs1-4 to maintain transporter activity. MCT1, MCT3, and MCT4 bind preferentially to basigin and MCT2 to embigin. The choice of binding partner does not affect substrate specificity or kinetics but can influence inhibitor specificity. © 2011 IUBMB.


Cullen P.J.,University of Bristol | Korswagen H.C.,University Utrecht
Nature Cell Biology | Year: 2012

Sorting nexins are a large family of evolutionarily conserved phosphoinositide-binding proteins that have fundamental roles in orchestrating cargo sorting through the membranous maze that is the endosomal network. One ancient group of complexes that contain sorting nexins is the retromer. Here we discuss how retromer complexes regulate endosomal sorting, and describe how this is generating exciting new insight into the central role played by endosomal sorting in development and homeostasis of normal tissues.


Newby A.C.,University of Bristol
Vascular Pharmacology | Year: 2012

The matrix metalloproteinases (MMPs) are 23 secreted or cell surface proteases that act together and with other protease classes to turn over the extracellular matrix, cleave cell surface proteins and alter the function of many secreted bioactive molecules. In the vasculature MMPs influence the migration proliferation and apoptosis of vascular smooth muscle, endothelial cells and inflammatory cells, thereby affecting intima formation, atherosclerosis and aneurysms, as substantiated in clinical and mouse knockout and transgenic studies. Prominent counterbalancing roles for MMPs in tissue destruction and repair emerge from these experiments. Naturally occurring tissue inhibitors of MMPs (TIMPs), pleiotropic mediators such as tetracyclines, chemically-synthesised small molecular weight MMP inhibitors (MMPis) and inhibitory antibodies have all shown effects in animal models of vascular disease but only doxycycline has been evaluated extensively in patients. A limitation of broad specificity MMPis is that they prevent both matrix degradation and tissue repair functions of different MMPs. Hence MMPis with more restricted specificity have been developed and recent studies in models of atherosclerosis accurately replicate the phenotypes of the corresponding gene knockouts. This review documents the established actions of MMPs and their inhibitors in vascular pathologies and considers the prospects for translating these findings into new treatments. © 2012 Elsevier Inc.


Mosher D.F.,University of Wisconsin - Madison | Adams J.C.,University of Bristol
Matrix Biology | Year: 2012

The thrombospondins are a family of secreted, oligomeric glycoproteins that interact with cell surfaces, multiple components of the extracellular matrix, growth factors and proteases. These interactions underlie complex roles in cell interactions and tissue homeostasis in animals. Thrombospondins have been grouped functionally with SPARCs, tenascins and CCN proteins as adhesion-modulating or matricellular components of the extracellular milieu. Although all these multi-domain proteins share various commonalities of domains, the grouping is not based on structural homologies. Instead, the terms emphasise the general observations that these proteins do not form large-scale ECM structures, yet act at cell surfaces and function in coordination with the structural ECM and associated extracellular proteins. The designation of adhesion-modulation thus depends on observed tissue and cell culture ECM distributions and on experimentally identified functional properties. To date, the evolutionary relationships of these proteins have not been critically compared: yet, knowledge of their evolutionary histories is clearly relevant to any consideration of functional similarities. In this article, we survey briefly the structural and functional knowledge of these protein families, consider the evolution of each family, and outline a perspective on their functional roles. © 2012 International Society of Matrix Biology.


Lessells C.M.,Netherlands Institute of Ecology | McNamara J.M.,University of Bristol
Proceedings of the Royal Society B: Biological Sciences | Year: 2012

Understanding the evolution of parental care is complicated by the occurrence of evolutionary conflicts of interest within the family, variation in the quality and state of family members, and repeated bouts of investment in a family of offspring. As a result, family members are expected to negotiate over care. We present a model for the resolution of sexual conflict in which parents negotiate over repeated bouts of care. Negotiation is mediated by parents deciding at the start of each bout how much care to give on the basis of the state (mass) of offspring, which reflects the amount of care previously received. The evolutionarily stable pattern of care depends on whether the parents care together for the whole family, or each cares alone for part of the divided family. When they care together, they provide less care in the first bout, more in the last bout, and less care overall, resulting in lower parental and offspring fitness. Our results emphasize that negotiation over parental care may occur as a means of avoiding exploitation owing to sexual conflict, even in the absence of variation in the quality of either sex of parent, and lead to a reduction in fitness. © 2011 The Royal Society.


Marx F.G.,University of Bristol
Proceedings of the Royal Society B: Biological Sciences | Year: 2012

The validity of biological explanations of patterns of palaeodiversity has been called into question owing to an apparent correlation of diversity with the amount of sedimentary rock preserved. However, this claim has largely been based on comprehensive estimates of global marine Phanerozoic diversity, thus raising the question of whether a similar bias applies to the records of smaller, well-defined taxonomic groups. Here, new data on European Caenozoic marine sedimentary rock outcrop area are presented and compared with European occurrences of three groups of marine mammals (cetaceans, pinnipedimorphs and sirenians). Limited evidence was found for a correlation of outcrop area with marine mammal palaeodiversity. In addition, similar patterns were identified in the cetacean and pinnipedimorph diversity data. This may point to the preservation of a genuine biological signal not overwhelmed by geological biases in the marine mammal diversity data, and opens the door to further analyses of both marine mammal evolution and geological bias in other small and well-defined groups of taxa. © 2008 The Royal Society.


Booth P.J.,University of Bristol
Current Opinion in Structural Biology | Year: 2012

Knowledge of the transition state is key to understanding a reaction mechanism. This vital information has been lacking for integral membrane protein folding, but now recent advances have given insight into the structure of their folding transition state. This progress has arisen through the successful translation of a classical protein engineering method, φ value analysis, from water-soluble proteins to the hydrophobic, membrane-embedded protein class. This review covers the transition state for the folding of α helical membrane proteins. Helix formation in the transition state correlates with sequence position and the order of transmembrane insertion into the cell membrane, showing that in vitro measurements, in entirely different conditions to natural membranes, may reflect the cellular situation. © 2012 Elsevier Ltd.


White M.F.,University of St. Andrews | Dillingham M.S.,University of Bristol
Current Opinion in Structural Biology | Year: 2012

Several unexpected reports of iron-sulphur clusters in nucleic acid binding proteins have recently appeared in the literature. Once thought to be relatively rare in these systems, iron-sulphur clusters are now known to be essential components of diverse nucleic acid processing machinery including glycosylases, primases, helicases, nucleases, transcription factors, RNA polymerases and RNA methyltransferases. In many cases, the function of the cluster is poorly understood and crystal structures of these iron-sulphur enzymes reveal little in common between them. In this article, we review the recent developments in the field and discuss to what extent there might exist common mechanistic roles for iron-sulphur clusters in nucleic acid enzymes. © 2011 Elsevier Ltd.


The estimation of bite force and bite performance in fossil and extinct animals is a challenging subject in palaeontology and is highly dependent on the reconstruction of the cranial myology. Furthermore, the morphology and arrangement of the adductor muscles considerably affect feeding processes and mastication and thus also have important dietary and ecological ramifications. However, in the past, the reconstruction of the (cranial) muscles was restricted to the identification of muscle attachment sites or simplified computer models. This study presents a detailed reconstruction of the adductor musculature of the Cretaceous therizinosaur Erlikosaurus andrewsi based on a stepwise and iterative approach. The detailed, three-dimensional models of the individual muscles allow for more accurate measurements of the muscle properties (length, cross-section, attachment angle and volume), from which muscle and bite force estimates are calculated. Bite force estimations are found to be the lowest at the tip of the snout (43-65 N) and respectively higher at the first (59-88 N) and last tooth (90-134 N) position. Nevertheless, bite forces are comparatively low for E. andrewsi, both in actual numbers as well as in comparison with other theropod dinosaurs. The results further indicate that the low bite performance was mainly used for leaf-stripping and plant cropping, rather than active mastication or chewing processes. Muscle and thus bite force in E. andrewsi (and most likely all therizinosaurs) is considerably constrained by the cranial anatomy and declines in derived taxa of this clade. This trend is reflected in the changes of dietary preferences from carnivory to herbivory in therizinosaurs. © 2012 The Author Journal of Anatomy © 2012 Anatomical Society.


Harvey J.N.,University of Bristol
Wiley Interdisciplinary Reviews: Computational Molecular Science | Year: 2014

Many chemical reactions involve one or more changes in the total electronic spin of the reacting system as part of one or more elementary steps. Computational and theoretical methods that can be used to understand such reaction steps are described, and a number of recent examples are highlighted. A particularly strong focus is given to general rules that govern multistep reactions of this type. The two most important rules are (1) that spin-state change without change in atom connectivity, or spin crossover, is facile and rapid, at least when it is exothermic; and (2) that reactions involving spin-state change and changes in atom connectivity tend to prefer stepwise mechanisms in which spin crossover steps alternate with spin-allowed bond-making and breaking steps. © 2013 John Wiley & Sons, Ltd.


Howard-Jones P.A.,University of Bristol
Nature Reviews Neuroscience | Year: 2014

For several decades, myths about the brain-neuromyths-have persisted in schools and colleges, often being used to justify ineffective approaches to teaching. Many of these myths are biased distortions of scientific fact. Cultural conditions, such as differences in terminology and language, have contributed to a 'gap' between neuroscience and education that has shielded these distortions from scrutiny. In recent years, scientific communications across this gap have increased, although the messages are often distorted by the same conditions and biases as those responsible for neuromyths. In the future, the establishment of a new field of inquiry that is dedicated to bridging neuroscience and education may help to inform and to improve these communications. © 2015 Macmillan Publishers Limited.


Radiation pressure is associated with the momentum of light, and it plays a crucial role in a variety of physical systems. It is usually assumed that both the optical momentum and the radiation-pressure force are naturally aligned with the propagation direction of light, given by its wavevector. Here we report the direct observation of an extraordinary optical momentum and force directed perpendicular to the wavevector, and proportional to the optical spin (degree of circular polarization). Such an optical force was recently predicted for evanescent waves and other structured fields. It can be associated with the ’spin-momentum’ part of the Poynting vector, introduced by Belinfante in field theory 75 years ago. We measure this unusual transverse momentum using a femtonewton-resolution nano-cantilever immersed in an evanescent optical field above the total internal reflecting glass surface. Furthermore, the measured transverse force exhibits another polarization-dependent contribution determined by the imaginary part of the complex Poynting vector. By revealing new types of optical forces in structured fields, our findings revisit fundamental momentum properties of light and enrich optomechanics. © 2016 Nature Publishing Group


Churchill A.,University of Bristol | Graw J.,Helmholtz Center Munich
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2011

Cataracts (opacities of the lens) are frequent in the elderly, but rare in paediatric practice. Congenital cataracts (in industrialized countries) are mainly caused by mutations affecting lens development. Much of our knowledge about the underlying mechanisms of cataractogenesis has come from the genetic analysis of affected families: there are contributions from genes coding for transcription factors (such as FoxE3, Maf, Pitx3) and structural proteins such as crystallins or connexins. In addition, there are contributions from enzymes affecting sugar pathways (particularly the galactose pathway) and from a quite unexpected area: axon guidance molecules like ephrins and their receptors. Cataractous mouse lenses can be identified easily by visual inspection, and a remarkable number of mutant lines have now been characterized. Generally, most of the mouse mutants show a similar phenotype to their human counterparts; however, there are some remarkable differences. It should be noted that many mutations affect genes that are expressed not only in the lens, but also in tissues and organs outside the eye. There is increasing evidence for pleiotropic effects of these genes, and increasing consideration that cataracts may act as early and readily detectable biomarkers for a number of systemic syndromes. © 2011 The Royal Society.


Okasha S.,University of Bristol
Interface Focus | Year: 2012

The concept of emergence and the related notion of 'downward causation' have arisen in numerous branches of science, and have also been extensively discussed in philosophy. Here, I examine emergence and downward causation in relation to evolutionary biology. I focus on the old, but ongoing discussion in evolutionary biology over the 'levels of selection' question: which level(s) of the biological hierarchy natural selection acts at, e.g. the gene, individual, group or species level? The concept of emergence has arisen in the levels-of-selection literature as a putative way of distinguishing between 'true' selection at a higher level from cases where selection acts solely at the lower level but has effects that percolate up the biological hierarchy, generating the appearance of higher level selection. At first blush, this problem seems to share a common structure with debates about emergence in other areas, but closer examination shows that it turns on issues that are sui generis to biology. © 2011 The Royal Society.


Skrzypczyk P.,ICFO - Institute of Photonic Sciences | Navascues M.,University of Bristol | Cavalcanti D.,ICFO - Institute of Photonic Sciences
Physical Review Letters | Year: 2014

Einstein-Podolsky-Rosen steering is a form of bipartite quantum correlation that is intermediate between entanglement and Bell nonlocality. It allows for entanglement certification when the measurements performed by one of the parties are not characterized (or are untrusted) and has applications in quantum key distribution. Despite its foundational and applied importance, Einstein-Podolsky-Rosen steering lacks a quantitative assessment. Here we propose a way of quantifying this phenomenon and use it to study the steerability of several quantum states. In particular, we show that every pure entangled state is maximally steerable and the projector onto the antisymmetric subspace is maximally steerable for all dimensions; we provide a new example of one-way steering and give strong support that states with positive-partial transposition are not steerable. © 2014 American Physical Society.


Helffrich G.,University of Bristol
Earth and Planetary Science Letters | Year: 2014

A variety of studies of the Earth's outer core report wave speeds near the top of the core slightly lower than reference models for core properties. One interpretation of the slower wavespeed profile is that it could represent a change in the core's light element concentration with depth in the core. I explore the consequences of this idea by interpreting the velocity profile as arising from diffusion gradients imposed in the outer core by various mechanisms. In order to estimate relative diffusion rates for light elements in liquid iron I also examine theories for transport properties of high pressure metallic liquids that are based on hard-sphere models. From the seismic wavespeed profile, an effective diffusivity may be obtained, which ranges from 0.1 to 10 × 10 -7 m2s -1 depending on the particular boundary condition or initial condition chosen. The upper bound of the range is higher than expected from high pressure experiments and models of diffusivity in liquid metals for all elements except H. The lower bound is within the uncertainty of theoretical predictions and experimental determinations given the range of expected outer core temperatures if diffusion involves low Z elements. Plausible agreement arises from a class of models that represent diffusion out of a compositionally different layer existing from the time of the formation of the Earth. If the wavespeed profile in the core is diffusive in nature, the data suggest that it is an original feature of the core. © 2014 Elsevier B.V.


Sumner S.,University of Bristol
Molecular Ecology | Year: 2014

Insect societies dominate the natural world: They mould landscapes, sculpt habitats, pollinate plants, sow seeds and control pests. The secret to their success lies in the evolution of queen (reproductive) and worker (provisioner and carer) castes (Oster & Wilson). A major problem in evolutionary biology is explaining the evolution of insect castes, particularly the workers (Darwin). Next-generation sequencing technologies now make it possible to understand how genomic material is born, lost and reorganized in the evolution of alternative phenotypes. Such analyses are revealing a general role for novel (e.g. taxonomically restricted) genes in phenotypic innovations across the animal kingdom (Chen et al.). In this issue of molecular ecology, Feldmeyer et al. () provide overwhelming evidence for the importance of novel genes in caste evolution in an ant. Feldmeyer et al.'s study is important and exciting because it cements the role of genomic novelty, as well as conservation, firmly into the molecular jigsaw of social evolution. Evolution is eclectic in its exploitation of both old and new genomic material to generate replicated phenotypic innovations across the tree of life. © 2013 John Wiley & Sons Ltd.


Verdon J.P.,University of Bristol
Environmental Research Letters | Year: 2014

The link between subsurface fluid injection and induced seismicity has gained recent significance with an increase in earthquakes associated with the disposal of oilfield waste fluids. There are obvious similarities between wastewater reinjection and proposed CO2 storage (CCS) operations. However, as well as the seismic hazard, induced seismicity during CCS operations poses additional risks, because an induced event located above the target reservoir could compromise the hydraulic integrity of the caprock. In this paper we re-examine case examples where earthquakes have been induced by wastewater injection into deep aquifers in the light of proposed future CCS operations. In particular we consider possible controls on event magnitudes, and look at the spatial distributions of events. We find that the majority of events are located below the target reservoirs. This is an encouraging observation from the perspective of caprock integrity, although it presents a challenge in terms of pre-injection characterization of deep-lying faults several kilometres below the target zone. We observe that 99% of events are found within 20 km of injection wells, suggesting a minimum radius for geomechanical characterization and monitoring. We conclude by making recommendations for modelling and monitoring strategies to be followed prior to and during commercial-scale deployment of CO2 storage projects. © 2014 IOP Publishing Ltd.


The Land-surface Processes and eXchanges Dynamic Global Vegetation Model (LPX-DGVM, one of several developments of the Lund-Potsdam-Jena (LPJ) model) is evaluated in terms of its interception component and used to simulate trends in 20th century global relative throughfall from natural vegetation. Mean global annual runoff is estimated to have been reduced by 163±19km3year-1 between 1901 and 2006 as a result of biophysical changes controlling throughfall generation. Widespread decreases in relative throughfall of up to -1% are evident between the periods 1901-1953 and 1954-2006, while changes of up to -15% are shown in parts of North America and East Asia. Areas of simulated decrease in relative throughfall often lie in close proximity to areas of increase, reflecting the effects of vegetation shifts. It is shown that simulated global absolute throughfall has generally increased (because of increasing precipitation) during the studied period, but the curtailing of runoff caused by decreased relative throughfall (as a result of increased fractional plant coverage and possible vegetation shifts) has caused a slight exacerbation of water stress in some regions (including parts of East Asia, North America and the tropics) and increased water supplies in others (for example, other parts of the tropics and northern Russia). This study offers an initial insight into an often overlooked product of climate-induced vegetation changes and attempts to quantify how these responses may contribute to influencing the global freshwater budget and global water resources. © 2012 John Wiley & Sons, Ltd.


Lautenschlager S.,University of Bristol
Palaontologische Zeitschrift | Year: 2014

During the last decade, three-dimensional, digital models have become increasingly important in geosciences and in particular in palaeontological research. Although significant advances in hard- and software technology have facilitated the acquisition and creation of such models, the presentation of three-dimensional data is still greatly handicapped by the traditionally two-dimensional means of publication. The ability to integrate three-dimensional (3D) models, which can be interactively manipulated, into portable document format (PDF) documents not only considerably improves their accessibility, but also represents an innovative, but so far neglected, approach for the presentation and communication of digital data. This article introduces and illustrates a comprehensive workflow for the creation of 3D PDFs, incorporating different techniques and methodological steps, and using both commercial and freely available software resources. Advantages and disadvantages of each method are discussed, and are accompanied by selected examples of digital models. These examples encompass different methods of data acquisition (computed tomography, synchrotron radiation X-ray tomographic microscopy, photogrammetry) and span a wide range of sizes and taxonomic groups. To the best of the author's knowledge, this article represents the first application of 3D PDF technology fully integrated into a scientific publication in palaeontology or even geosciences, and not restricted to supplementary material. It provides the reader with extended visual information and facilitates the dissemination of data. As both authors and readers benefit greatly from their usage, it is argued that 3D PDFs should become an accepted standard in palaeontological publications of three-dimensional models. © 2013 Springer-Verlag Berlin Heidelberg.


We set out a generalized linear model framework for the synthesis of data from randomized controlled trials. A common model is described, taking the form of a linear regression for both fixed and random effects synthesis, which can be implemented with normal, binomial, Poisson, and multinomial data. The familiar logistic model for meta-analysis with binomial data is a generalized linear model with a logit link function, which is appropriate for probability outcomes. The same linear regression framework can be applied to continuous outcomes, rate models, competing risks, or ordered category outcomes by using other link functions, such as identity, log, complementary log-log, and probit link functions. The common core model for the linear predictor can be applied to pairwise meta-analysis, indirect comparisons, synthesis of multiarm trials, and mixed treatment comparisons, also known as network meta-analysis, without distinction. We take a Bayesian approach to estimation and provide WinBUGS program code for a Bayesian analysis using Markov chain Monte Carlo simulation. An advantage of this approach is that it is straightforward to extend to shared parameter models where different randomized controlled trials report outcomes in different formats but from a common underlying model. Use of the generalized linear model framework allows us to present a unified account of how models can be compared using the deviance information criterion and how goodness of fit can be assessed using the residual deviance. The approach is illustrated through a range of worked examples for commonly encountered evidence formats.


Azarpeyvand M.,University of Bristol
Journal of the Acoustical Society of America | Year: 2014

The mechanism of generating backward dragging forces on objects standing in the path of a single, translationally invariant, symmetric acoustic Bessel beam is studied. This paper aims to provide mechanical and structural conditions for the emergence of negative axial forces based on the elastodynamic response of acoustically penetrable objects and beam's nonparaxiality parameter. An extensive numerical study has been performed for various liquid and solid elastic cases to illustrate the validity of the proposed eigenfrequency-based conditions. Results have revealed the existence of a complex but interpretable link between the emergence of negative radiation forces on spheres illuminated by zero-order Bessel beams and the eigenfrequencies of the particle. Considerable progress has been made in elucidating these relationships, which may lead to the development of predictable and robust single-beam acoustic handling devices. © 2014 Acoustical Society of America.


Saleem M.A.,University of Bristol
Pediatric Nephrology | Year: 2012

Steroid-resistant nephrotic syndrome (SRNS), also termed focal segmental glomerulosclerosis (FSGS), is one of the most difficult conditions for the nephrologist to manage, particularly when the disease recurs post-transplantation. This syndrome is extremely interesting from the biological perspective as the non-genetic form is most likely caused by an as yet unknown disorder of the circulating plasma. This elusive 'plasma factor' has been the focus of researchers for several decades. Many hypotheses have been proposed and tested, but none have yet passed the test of clinical utility. However, the search appears to be narrowing, facilitated by landmark discoveries in the molecular properties of the glomerular filtration barrier, as well as by improved experimental tools. In the therapeutic/clinical setting, the targeting of specific molecules in treatments has improved, of which one example is treatment with specific monoclonal antibodies. In this context, our report on the effects of tumor necrosis factor-alpha (TNF-α) on podocytes is instructive as it demonstrates that this cytokine can have directly deleterious effects on podocytes in vivo and that this effect can be targeted clinically, potentially halting or reversing the disease process. As with all thought-provoking research, this result raises several interesting questions. Is TNF-α the elusive 'plasma factor' or is it one of several? Does it directly affect the glomerular filtration barrier, or does it modulate the immune response? And could this technique be used as a cell-based assay for disease activity? Our report adds another potential candidate to the growing list of candidates that need to be tested in a wider population of well-phenotyped patients with SRNS. © 2012 IPNA.


Burd C.,Yale University | Cullen P.J.,University of Bristol
Cold Spring Harbor Perspectives in Biology | Year: 2014

The endosomal network comprises an interconnected network of membranous compartments whose primary function is to receive, dissociate, and sort cargo that originates fromthe plasma membrane and the biosynthetic pathway. A major challenge in cell biology is to achieve a thorough molecular description of howthis network operates, and in so doing, how defects contribute to the etiology and pathology of human disease.We discuss the increasing body of evidence that implicates an ancient evolutionary conserved complex, termed "retromer," as a master conductor in the complex orchestration of multiple cargo-sorting events within the endosomal network. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.


Hamilton W.,University of Bristol
British Journal of General Practice | Year: 2010

Around a quarter of those in the developed world die of cancer. Most cancers present to primary care with symptoms, even when there is a screening test for the particular cancer. However, the symptoms of cancer are also symptoms of benign disease, and the GP has to judge whether cancer is a possible explanation. Very little research examined this process until relatively recently. This review paper examines the process of primary care diagnosis, especially the selection of patients for rapid investigation. It concentrates on the four commonest UK cancers: breast, lung, colon, and prostate as these have been the subject of most recent studies. ©British Journal of General Practice 2010.


Crawley E.,University of Bristol
QJM : monthly journal of the Association of Physicians | Year: 2013

Chronic fatigue syndrome (CFS) is relatively common and disabling. Over 8000 patients attend adult services each year, yet little is known about the outcome of patients attending NHS services. Investigate the outcome of patients with CFS and what factors predict outcome. Longitudinal patient cohort. We used data from six CFS/ME (myalgic encephalomyelitis) specialist services to measure changes in fatigue (Chalder Fatigue Scale), physical function (SF-36), anxiety and depression (Hospital Anxiety and Depression Scale) and pain (visual analogue pain rating scale) between clinical assessment and 8-20 months of follow-up. We used multivariable linear regression to investigate baseline factors associated with outcomes at follow-up. Results: Baseline data obtained at clinical assessment were available for 1643 patients, of whom 834 (51%) had complete follow-up data. There were improvements in fatigue [mean difference from assessment to outcome: -6.8; 95% confidence interval (CI) -7.4 to -6.2; P < 0.001]; physical function (4.4; 95% CI 3.0-5.8; P < 0.001), anxiety (-0.6; 95% CI -0.9 to -0.3; P < 0.001), depression (-1.6; 95% CI -1.9 to -1.4; P < 0.001) and pain (-5.3; 95% CI -7.0 to -3.6; P < 0.001). Worse fatigue, physical function and pain at clinical assessment predicted a worse outcome for fatigue at follow-up. Older age, increased pain and physical function at assessment were associated with poorer physical function at follow-up. Patients who attend NHS specialist CFS/ME services can expect similar improvements in fatigue, anxiety and depression to participants receiving cognitive behavioural therapy and graded exercise therapy in a recent trial, but are likely to experience less improvement in physical function. Outcomes were predicted by fatigue, disability and pain at assessment.


Foster D.,University of Bristol | Manton N.S.,University of Cambridge
Nuclear Physics B | Year: 2015

Classically spinning B = 1 Skyrmions can be regarded as approximations to nucleons with quantised spin. Here, we investigate nucleon-nucleon scattering through numerical collisions of spinning Skyrmions. We identify the dineutron/diproton and dibaryon short-lived resonance states, and also the stable deuteron state. Our simulations lead to predictions for the polarisation states occurring in right angle scattering. © 2015 The Authors.


Henson J.,University of Bristol
Physical Review Letters | Year: 2015

Recently, many simple principles have been proposed that can explain quantum limitations on possible sets of experimental probabilities in nonlocality and contextuality experiments. However, few implications between these principles are known. Here it is shown that the lack of irreducible third-order interference (a generalization of the idea that no probabilistic interference remains unaccounted for once we have taken into account interference between pairs of slits in a n-sit experiment) implies the principle known as the E principle or consistent exclusivity (that, if each pair of a set of experimental outcomes are exclusive alternatives in some measurement, then their probabilities are consistent with the existence of a further measurement in which they are all exclusive). This is a step towards a more unified understanding of quantum nonlocality and contextuality, which promises to allow derivations of important results from minimal, easily grasped assumptions. As one example, this result implies that lack of third-order interference bounds violation of the Clauser-Horne-Shimony-Holt-Bell inequality to 2.883. © 2015 American Physical Society.


By reducing energy density, low-energy sweeteners (LES) might be expected to reduce energy intake (EI) and body weight (BW). To assess the totality of the evidence testing the null hypothesis that LES exposure (versus sugars or unsweetened alternatives) has no effect on EI or BW, we conducted a systematic review of relevant studies in animals and humans consuming LES with ad libitum access to food energy. In 62 of 90 animal studies exposure to LES did not affect or decreased BW. Of 28 reporting increased BW, 19 compared LES with glucose exposure using a specific ‘learning’ paradigm. Twelve prospective cohort studies in humans reported inconsistent associations between LES use and body mass index (−0.002 kg m- 2 per year, 95% confidence interval (CI) −0.009 to 0.005). Meta-analysis of short-term randomized controlled trials (129 comparisons) showed reduced total EI for LES versus sugar-sweetened food or beverage consumption before an ad libitum meal (−94 kcal, 95% CI −122 to −66), with no difference versus water (−2 kcal, 95% CI −30 to 26). This was consistent with EI results from sustained intervention randomized controlled trials (10 comparisons). Meta-analysis of sustained intervention randomized controlled trials (4 weeks to 40 months) showed that consumption of LES versus sugar led to relatively reduced BW (nine comparisons; −1.35 kg, 95% CI –2.28 to −0.42), and a similar relative reduction in BW versus water (three comparisons; −1.24 kg, 95% CI –2.22 to −0.26). Most animal studies did not mimic LES consumption by humans, and reverse causation may influence the results of prospective cohort studies. The preponderance of evidence from all human randomized controlled trials indicates that LES do not increase EI or BW, whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water.International Journal of Obesity advance online publication, 10 November 2015; doi:10.1038/ijo.2015.177. © 2015 Macmillan Publishers Limited


Berry M.V.,University of Bristol
Contemporary Physics | Year: 2015

Optical phenomena visible to everyone have been central to the development of, and abundantly illustrate, important concepts in science and mathematics. The phenomena considered from this viewpoint are rainbows, sparkling reflections on water, mirages, green flashes, earthlight on the moon, glories, daylight, crystals and the squint moon. And the concepts involved include refraction, caustics (focal singularities of ray optics), wave interference, numerical experiments, mathematical asymptotics, dispersion, complex angular momentum (Regge poles), polarisation singularities, Hamilton’s conical intersections of eigenvalues (‘Dirac points’), geometric phases and visual illusions. © 2014, Taylor & Francis.


Bird A.,University of Bristol
Preventive Medicine | Year: 2011

Objective: This article outlines an epistemological framework for understanding how Hill's criteria may aid us in establishing a causal hypothesis (A causes B) in an observational study. Method: We consider Hill's criteria in turn with respect to their ability or otherwise to exclude alternative hypotheses (B causes A; there is a common cause of A and B; there is no causal connection between A and B). Results: We may classify Hill's criteria according to which of the alternative hypotheses they are able to exclude, and also on the basis of whether they relate to (a) evidence from within observational study or (b) evidence independent of that study. It is noted that no criterion is able to exclude the common cause hypothesis in a systematic way. Conclusion: Observational studies are typically weaker than experimental studies, since the latter can systematically exclude competing hypotheses, whereas observational studies lack a systematic way of ruling out the common cause hypothesis. © 2011 Elsevier Inc.


Fritz S.P.,University of Bristol
Synlett | Year: 2012

(A) Synthesis of Mitomycin K: One of the first applications was the use of diphenylvinylsulfonium triflate (1) in the epoxy-annulation reaction towards mitomycin K, by Kim and Jimenez.1 In this case, a substituted indole aldehyde was treated with 1, using sodium hydride as base, to afford an intermediate ylide, which underwent epoxide formation. (B) Epoxy-Annulation Reactions: This methodology was further extended to the synthesis of five- and six-membered epoxides or aziridine fused heterocyles.2 An enantioselective variant, using a chiral vinylsulfonium salt, was also reported. (C) Synthesis of 4,5-Epoxytetrahydropyrans: Ley and co-workers3 applied the same method to the synthesis of 4,5-epoxytetrahydropyrans, achieving high diastereoselectivity. Additionally, their work compared the difference in reactivity of 1 to the equivalent vinylphosphonium salt, which could be used to form the corresponding olefin in high yield. (D) Synthesis of Six-Membered Heterocycles: In 2008 Aggarwal and co-workers4 discovered that reactions of vinyl sulfonium salt 1, with 1,2-aminoalcohols/thiols or 1,2-diamines, in the presence of base led to morpholines, thiomorpholines and piperazines. This methodology was later expanded to the in situ generation of 1 from 25 and the use of easier-to-cleave sulfinamide protecting groups6, instead of sulfonamides. (E) Synthesis of Oxazino[4,3-a]indoles: Chen et al.7 later expanded this methodology to the synthesis of biologically important oxazino[4,3-a]indoles using KOH as base. (F) Synthesis of N-Aryloxazolidin-2-ones: Xie and co-workers8 developed a novel tandem reaction with vinyl sulfonium triflate 1 to transform tert-butyl carbamates into N-aryloxazolidin- 2-ones. (G) Synthesis of Pyrrolidin-2-ones: Xie et al.9 later expanded their method to the synthesis of pharmacologically important five-membered pyrrolidin-2-ones, using the acidic b-C-H bond for nucleophilic attack of vinyl sulfonium salt 1. They were able to expand this method to a large variety of N-protecting groups and electron-withdrawing substituents. They also discovered that reaction of an amide with 1 leads to formation of aminoethanol esters. (H) Synthesis of Imidazolinium Salts: McGarrigle et al.10 applied in situ generated 1 towards the synthesis of imidazolinium salts, an important class of NHC-precursors. This was also possible as a one-pot procedure from easily available starting materials. (I) Synthesis of N-Vinyloxazolidinones: Yar et al.11 later demonstrated the synthesis of N-vinyloxazolidinones from N-Cbz protected aminoalcohols. Tandem mass spectrometry was used to investigate the mechanism of this reaction, in which an intermediate alkoxide acts as a base to effect an intramolecular E2 elimination prior to attack at the Cbz protecting group. © Thieme Stuttgart · New York.


Inoue J.,University College London | Donoghue P.C.J.,University of Bristol | Yang Z.,University College London
Systematic Biology | Year: 2010

Bayesian inference provides a powerful framework for integrating different sources of information (in particular, molecules and fossils) to derive estimates of species divergence times. Indeed, it is currently the only framework that can adequately account for uncertainties in fossil calibrations. We use 2 Bayesian Markov chain Monte Carlo programs, MULTIDIVTIME and MCMCTREE, to analyze 3 empirical datasets to estimate divergence times in amphibians, actinopterygians, and felids. We evaluate the impact of various factors, including the priors on rates and times, fossil calibrations, substitution model, the violation of the molecular clock and the rate-drift model, and the exact and approximate likelihood calculation. Assuming the molecular clock caused seriously biased time estimates when the clock is violated, but 2 different rate-drift models produced similar estimates. The prior on times, which incorporates fossil-calibration information, had the greatest impact on posterior time estimation. In particular, the strategies used by the 2 programs to incorporate minimum-and maximum-age bounds led to very different time priors and were responsible for large differences in posterior time estimates in a previous study. The results highlight the critical importance of fossil calibrations to molecular dating and the need for probabilistic modeling of fossil depositions, preservations, and sampling to provide statistical summaries of information in the fossil record concerning species divergence times.


Masuda N.,University of Bristol
New Journal of Physics | Year: 2015

In many political elections, the electorate appears to be a composite of partisan and independent voters. Given that partisans are not likely to convert to a different party, an important goal for a political party could be to mobilize independent voters toward the party with the help of strong leadership, mass media, partisans, and the effects of peer-to-peer influence. Based on the exact solution of classical voter model dynamics in the presence of perfectly partisan voters (i.e., zealots), we propose a computational method that uses pinning control strategy to maximize the share of a party in a social network of independent voters. The party, corresponding to the controller or zealots, optimizes the nodes to be controlled given the information about the connectivity of independent voters and the set of nodes that the opposing party controls.Weshow that controlling hubs is generally a good strategy, but the optimized strategy is even better. The superiority of the optimized strategy is particularly eminent when the independent voters are connected as directed (rather than undirected) networks. ©2015 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft


Ring-opening polymerization of a wide variety of strained organometallic rings has allowed the preparation of a variety of new metallopolymers over the past decade or so. The most developed class of materials, polyferrocenylsilanes, has been shown to exhibit interesting properties and a variety of applications as "soft" materials and their study has also led to the discovery of remarkable self-assembly phenomena. This article provides a brief review of some selected recent advances in this interesting area with a focus on the work in the authors group and with their collaborators. © 2010 Published by Elsevier B.V.


Fenton A.,University of Liverpool | Viney M.E.,University of Bristol | Lello J.,University of Cardiff
Ecology Letters | Year: 2010

There is great interest in the occurrence and consequences of interspecific interactions among co-infecting parasites. However, the extent to which interactions occur is unknown, because there are no validated methods for their detection. We developed a model that generated abundance data for two interacting macroparasite (e.g., helminth) species, and challenged the data with various approaches to determine whether they could detect the underlying interactions. Current approaches performed poorly - either suggesting there was no interaction when, in reality, there was a strong interaction occurring, or inferring the presence of an interaction when there was none. We suggest the novel application of a generalized linear mixed modelling (GLMM)-based approach, which we show to be more reliable than current approaches, even when infection rates of both parasites are correlated (e.g., via a shared transmission route). We suggest that the lack of clarity regarding the presence or absence of interactions in natural systems may be largely attributed to the unreliable nature of existing methods for detecting them. However, application of the GLMM approach may provide a more robust method of detection for these potentially important interspecific interactions from ecological data. © 2010 Blackwell Publishing Ltd/CNRS.


Smith G.D.,University of Bristol
International Journal of Epidemiology | Year: 2011

Epidemiologists aim to identify modifiable causes of disease, this often being a prerequisite for the application of epidemiological findings in public health programmes, health service planning and clinical medicine. Despite successes in identifying causes, it is often claimed that there are missing additional causes for even reasonably well-understood conditions such as lung cancer and coronary heart disease. Several lines of evidence suggest that largely chance events, from the biographical down to the sub-cellular, contribute an important stochastic element to disease risk that is not epidemiologically tractable at the individual level. Epigenetic influences provide a fashionable contemporary explanation for such seemingly random processes. Chance events-such as a particular lifelong smoker living unharmed to 100 years-are averaged out at the group level. As a consequence population-level differences (for example, secular trends or differences between administrative areas) can be entirely explicable by causal factors that appear to account for only a small proportion of individual-level risk. In public health terms, a modifiable cause of the large majority of cases of a disease may have been identified, with a wild goose chase continuing in an attempt to discipline the random nature of the world with respect to which particular individuals will succumb. The quest for personalized medicine is a contemporary manifestation of this dream. An evolutionary explanation of why randomness exists in the development of organisms has long been articulated, in terms of offering a survival advantage in changing environments. Further, the basic notion that what is near-random at one level may be almost entirely predictable at a higher level is an emergent property of many systems, from particle physics to the social sciences. These considerations suggest that epidemiological approaches will remain fruitful as we enter the decade of the epigenome. Published by Oxford University Press on behalf of the International Epidemiological Association. © The Author 2011; all rights reserved.


Oltean S.,University of Bristol | Bates D.O.,University of Nottingham
Oncogene | Year: 2014

The immense majority of genes are alternatively spliced and there are many isoforms specifically associated with cancer progression and metastasis. The splicing pattern of specific isoforms of numerous genes is altered as cells move through the oncogenic process of gaining proliferative capacity, acquiring angiogenic, invasive, antiapoptotic and survival properties, becoming free from growth factor dependence and growth suppression, altering their metabolism to cope with hypoxia, enabling them to acquire mechanisms of immune escape, and as they move through the epithelial-mesenchymal and mesenchymal-epithelial transitions and metastasis. Each of the 'hallmarks of cancer' is associated with a switch in splicing, towards a more aggressive invasive cancer phenotype. The choice of isoforms is regulated by several factors (signaling molecules, kinases, splicing factors) currently being identified systematically by a number of high-throughput, independent and unbiased methodologies. Splicing factors are de-regulated in cancer, and in some cases are themselves oncogenes or pseudo-oncogenes and can contribute to positive feedback loops driving cancer progression. Tumour progression may therefore be associated with a coordinated splicing control, meaning that there is the potential for a relatively small number of splice factors or their regulators to drive multiple oncogenic processes. The understanding of how splicing contributes to the various phenotypic traits acquired by tumours as they progress and metastasise, and in particular how alternative splicing is coordinated, can and is leading to the development of a new class of anticancer therapeutics-the alternative-splicing inhibitors.


Heatherley S.V.,University of Bristol
Nutritional Neuroscience | Year: 2011

As a psychostimulant, caffeine is thought to reduce road accidents by keeping drivers alert and wakeful. Studies have found that caffeine can improve performance on vigilance tasks and in driving simulators under normal sleeping conditions and after sleep restriction or deprivation. However, there is increasing evidence that these beneficial effects of caffeine are due to withdrawal reversal. Studies comparing the effects of caffeine versus placebo on driving performance have tested habitual caffeine consumers deprived of caffeine from the evening before the test day. The conclusion from this review is, therefore, that improvements in driving performance and alertness after caffeine are likely to represent withdrawal reversal rather than a net beneficial effect of caffeine. Further research using designs that control for caffeine withdrawal are necessary and, accordingly, advice given to the public on use of caffeine as an antidote to tiredness and impaired performance should be reviewed. © W.S. Maney & Son Ltd. 2011.


Egro F.M.,University of Bristol
Journal of Molecular Endocrinology | Year: 2013

A series of studies have reported a constant global rise in the incidence of type 1 diabetes. Epidemiological and immunological studies have demonstrated that environmental factors may influence the pathogenesis, leading to a cell-mediated pancreatic β-cell destruction associated with humoral immunity. The search for the triggering factor(s) has been going on for the past century, and yet they are still unknown. This review provides an overview of some of the most well-known theories found in the literature: hygiene, viral, vitamin D deficiency, breast milk and cow's milk hypotheses. Although the hygiene hypothesis appears to be the most promising, positive evidence from animal, human and epidemiological studies precludes us from completely discarding any of the other hypotheses. Moreover, due to contrasting evidence in the literature, a single factor is unlikely to cause an increase in the incidence of diabetes all over the world, which suggests that a multifactorial process might be involved. Although the immunological mechanisms are still unclear, there seems to be some overlap between the various hypotheses. It is thought that the emphasis should be shifted from a single to a multifactorial process and that perhaps the 'balance shift' model should be considered as a possible explanation for the rise in the incidence of type 1 diabetes. © 2013 Society for Endocrinology.


Blockley D.I.,University of Bristol
Civil Engineering and Environmental Systems | Year: 2010

The purpose of the paper is to outline the particular interpretation of systems thinking developed at the University of Bristol over the last 30 years. The importance of process and uncertainty are central themes. Put at its simplest, systems thinking is joined-up thinking. It is getting the right information (what) to the right people (who) at the right time (when) for the right purpose (why) in the right form (where) and in the right way (how). The three ideas at the heart of delivering systems thinking are thinking in layers, thinking in connected loops and thinking about new processes. Everything has life cycle and hence is a process - but one that is set in the context of a system containing other connected processes - some at higher and some at lower levels of definition. All processes have attributes that are characterised using why, how, who, what, where, when. There is a need to integrate hard and soft systems. This requires us to be very clear about the meaning and usage of the terms subjective and objective when we argue that engineering judgement is both valid and important. It is argued that truth is to knowledge as the inverse of risk is to action. The three attributes of uncertainty are stated as FIR - fuzziness, incompleteness and randomness. Robustness and its inverse, vulnerability, are crucial, though often ignored. Systems thinking is not simply an engineering approach; rather it is a philosophy for solving many practical problems such as joined-up government, social work, dealing with climate change and terrorism. Finally it is argued that our journey to 2030 requires us to adopt an evolutionary observational approach using systems thinking. © 2010 Taylor & Francis.


Gregory S.,University of Bristol
New Journal of Physics | Year: 2010

We propose an algorithm for finding overlapping community structure in very large networks. The algorithm is based on the label propagation technique of Raghavan, Albert and Kumara, but is able to detect communities that overlap. Like the original algorithm, vertices have labels that propagate between neighbouring vertices so that members of a community reach a consensus on their community membership. Our main contribution is to extend the label and propagation step to include information about more than one community: each vertex can now belong to up to v communities, where v is the parameter of the algorithm. Our algorithm can also handle weighted and bipartite networks. Tests on an independently designed set of benchmarks, and on real networks, show the algorithm to be highly effective in recovering overlapping communities. It is also very fast and can process very large and dense networks in a short time. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.


Inconsistency can be thought of as a conflict between "direct" evidence on a comparison between treatments B and C and "indirect" evidence gained from AC and AB trials. Like heterogeneity, inconsistency is caused by effect modifiers and specifically by an imbalance in the distribution of effect modifiers in the direct and indirect evidence. Defining inconsistency as a property of loops of evidence, the relation between inconsistency and heterogeneity and the difficulties created by multiarm trials are described. We set out an approach to assessing consistency in 3-treatment triangular networks and in larger circuit structures, its extension to certain special structures in which independent tests for inconsistencies can be created, and describe methods suitable for more complex networks. Sample WinBUGS code is given in an appendix. Steps that can be taken to minimize the risk of drawing incorrect conclusions from indirect comparisons and network meta-analysis are the same steps that will minimize heterogeneity in pairwise meta-analysis. Empirical indicators that can provide reassurance and the question of how to respond to inconsistency are also discussed.


Carel H.H.,University of Bristol
Theoretical Medicine and Bioethics | Year: 2013

In this article, I propose that illness is philosophically revealing and can be used to explore human experience. I suggest that illness is a limit case of embodied experience. By pushing embodied experience to its limit, illness sheds light on normal experience, revealing its ordinary and thus overlooked structure. Illness produces a distancing effect, which allows us to observe normal human behavior and cognition via their pathological counterpart. I suggest that these characteristics warrant illness a philosophical role that has not been articulated. Illness can be used as a philosophical tool for the study of normally tacit aspects of human existence. I argue that illness itself can be integral to philosophical method, insofar as it facilitates a distancing from everyday practices. This method relies on pathological or limit cases to illuminate normally overlooked aspects of human perception and action. I offer Merleau-Ponty's analysis of the case of Schneider as an example of this method. © 2013 Springer Science+Business Media Dordrecht.


Research demonstrates that mental illness is not a major cause of violence yet assumptions about a link and concern about the risks posed by mentally disordered people has resulted in the predominance of a public safety role for mental health services (Munro and Rumgay 2000). In consequence, screening, classifying and monitoring individuals considered to pose a potential risk to others due to their potential for violence has become a key responsibility. The purpose of healthcare screening is to identify a disease or condition, or its associated risk factors, to provide treatment or encourage preventative action on the part of 'at risk' individuals. Mental health screening differs since neither a disease entity nor a causal model to link mental disorder and violence exist (Leitner et al. 2006). Mental health service users are typically marginalised and screening may occur without their consent, knowledge or involvement. They may also disagree that they have the condition in question, i.e. a propensity to violence. The expectation upon professionals to promote service user involve-ment in care and treatment sits uneasily with these processes. This paper reviews the ongoing but unsuccessful efforts to develop effective screening for violence amongst people defined as mentally disordered and explores the implications for mental health services in the light of this evidence. It also considers the continuing lack of service user involvement in risk assessment. First however, the paper considers correlates for violence since screening depends for its efficacy upon risk factors thought to be positively associated with the condition of concern © 2010 Taylor & Francis.


Bortolami E.,University of Bristol
Journal of feline medicine and surgery | Year: 2012

This randomised, blinded, cross-over study investigated the ease of oral transmucosal administration of two formulations of buprenorphine using glucose as a control in 12 cats. The cats received three treatments: buprenorphine multi-dose, buprenorphine and the equivalent volume of glucose 5%. Ease of treatment administration, observation of swallowing, changes in pupil size, sedation, salivation, vomiting, behaviour and food intake were assessed. The data were analysed using MLwiN and multi-level modelling. Ease of administration of buprenorphine multi-dose was statistically different from glucose (P <0.001), and the administration of all treatments became easier over the study periods. Swallowing was not statistically different between groups (P >0.05). Mydriasis was evident after the administration of both formulations of buprenorphine. Sedation, salivation, vomiting, behavioural changes or in-appetence were not observed after any treatment. Cats tolerated oral transmucosal administration of glucose better than buprenorphine multi-dose, while buprenorphine administration was tolerated as well as glucose.


Kerswell R.R.,University of Bristol | Pringle C.C.T.,Coventry University | Willis A.P.,University of Sheffield
Reports on Progress in Physics | Year: 2014

This article introduces and reviews recent work using a simple optimization technique for analysing the nonlinear stability of a state in a dynamical system. The technique can be used to identify the most efficient way to disturb a system such that it transits from one stable state to another. The key idea is introduced within the framework of a finite-dimensional set of ordinary differential equations (ODEs) and then illustrated for a very simple system of two ODEs which possesses bistability. Then the transition to turbulence problem in fluid mechanics is used to show how the technique can be formulated for a spatially-extended system described by a set of partial differential equations (the well-known Navier-Stokes equations). Within that context, the optimization technique bridges the gap between (linear) optimal perturbation theory and the (nonlinear) dynamical systems approach to fluid flows. The fact that the technique has now been recently shown to work in this very high dimensional setting augurs well for its utility in other physical systems. © 2014 IOP Publishing Ltd.


Cashman K.V.,University of Bristol | Giordano G.,Third University of Rome
Journal of Volcanology and Geothermal Research | Year: 2014

Large caldera-forming eruptions have long been a focus of both petrological and volcanological studies; petrologists have used the eruptive products to probe conditions of magma storage (and thus processes that drive magma evolution), while volcanologists have used them to study the conditions under which large volumes of magma are transported to, and emplaced on, the Earth's surface. Traditionally, both groups have worked on the assumption that eruptible magma is stored within a single long-lived melt body. Over the past decade, however, advances in analytical techniques have provided new views of magma storage regions, many of which provide evidence of multiple melt lenses feeding a single eruption, and/or rapid pre-eruptive assembly of large volumes of melt. These new petrological views of magmatic systems have not yet been fully integrated into volcanological perspectives of caldera-forming eruptions. Here we explore the implications of complex magma reservoir configurations for eruption dynamics and caldera formation. We first examine mafic systems, where stacked-sill models have long been invoked but which rarely produce explosive eruptions. An exception is the 2010 eruption of Eyjafjallajökull volcano, Iceland, where seismic and petrologic data show that multiple sills at different depths fed a multi-phase (explosive and effusive) eruption. Extension of this concept to larger mafic caldera-forming systems suggests a mechanism to explain many of their unusual features, including their protracted explosivity, spatially variable compositions and pronounced intra-eruptive pauses. We then review studies of more common intermediate and silicic caldera-forming systems to examine inferred conditions of magma storage, time scales of melt accumulation, eruption triggers, eruption dynamics and caldera collapse. By compiling data from large and small, and crystal-rich and crystal-poor, events, we compare eruptions that are well explained by simple evacuation of a zoned magma chamber (termed the Standard Model by Gualda and Ghiorso, 2013) to eruptions that are better explained by tapping multiple, rather than single, melt lenses stored within a largely crystalline mush (which we term complex magma reservoirs). We then discuss the implications of magma storage within complex, rather than simple, reservoirs for identifying magmatic systems with the potential to produce large eruptions, and for monitoring eruption progress under conditions where successive melt lenses may be tapped. We conclude that emerging views of complex magma reservoir configurations provide exciting opportunities for re-examining volcanological concepts of caldera-forming systems. © 2014 Elsevier B.V.


McInerney J.O.,National University of Ireland, Maynooth | O'Connell M.J.,Dublin City University | Pisani D.,University of Bristol
Nature Reviews Microbiology | Year: 2014

The origin of the eukaryotic cell, which is known as eukaryogenesis, has puzzled scientists for more than 100 years, and many hypotheses have been proposed. Recent analyses of new data enable the safe elimination of some of these hypotheses, whereas support for other hypotheses has increased. In this Opinion article, we evaluate the available theories for their compatibility with empirical observations and conclude that cellular life consists of two primary, paraphyletic prokaryotic groups and one secondary, monophyletic group that has symbiogenic origins-the eukaryotes. © 2014 Macmillan Publishers Limited. All rights reserved.


Thoresen M.,University of Bristol
Seminars in Fetal and Neonatal Medicine | Year: 2010

For infants with perinatal hypoxia-ischaemia, the ability to give an accurate prognosis at different ages enables the clinician to make decisions on the continuation of management, and also assists in discussions regarding further treatment and prognosis with parents and families. This review suggests which outcome markers are still valid, which need new 'cut-off values' and which can no longer be used in cooled infants. The main focus is on convenient bedside technologies such as the amplitude-integrated electroencephalogram that can be easily applied in routine clinical practice. © 2010 Elsevier Ltd.


Satchell S.,University of Bristol
Nature Reviews Nephrology | Year: 2013

The unique permeability characteristics of the glomerular capillary wall depend on its three-layer structure, consisting of endothelial cells, the basement membrane and podocytes. These components form the glomerular filtration barrier (GFB). That albuminuria may occur in the absence of changes in podocyte foot processes suggests that GFB components other than podocytes have essential roles in albumin handling. The endothelium forms the first part of the GFB and is characterized by fenestrations - transcellular holes that are filled with endothelial glycocalyx, a hydrated mesh principally comprised of proteoglycans. The glycocalyx and adsorbed plasma constituents form the endothelial surface layer (ESL). Human and animal studies have shown that the glomerular ESL restricts macromolecule passage and ensures that plasma albumin is largely excluded from the GFB. The glomerular endothelium is also likely to indirectly influence glomerular albumin handling by modifying podocyte behaviour. These modifications may occur physiologically through soluble mediators and/or pathologically through increased exposure of podocytes to plasma components as a consequence of ESL dysfunction. The importance of the glomerular endothelium and ESL in albumin handling also sheds light on the relationship between albuminuria and vascular disease. The therapeutic potential that this relationship offers will become evident with better understanding of the structure, composition and regulation of the glycocalyx. © 2013 Macmillan Publishers Limited. All rights reserved.


Suleiman M.S.,University of Bristol
Perfusion | Year: 2011

Cardioplegic arrest and cardiopulmonary bypass are key triggers of myocardial injury during aortic valve surgery. Cardioplegic ischaemic arrest is associated with disruption to metabolic and ionic homeostasis in cardiomyocytes. These changes predispose the heart to reperfusion injury caused by elevated intracellular reactive oxygen species and calcium. Cardiopulmonary bypass is associated with an inflammatory response that can generate systemic oxidative stress which, in turn, provokes further damage to the heart. Techniques of myocardial protection are routinely applied to all hearts, irrespective of their pathology, although different cardiomypathies respond differently to ischaemia and reperfusion injury. In particular, the efficacy of cardioprotective interventions used to protect the hypertrophic heart in patients with aortic valve disease remains controversial. This review will describe key cellular changes in hypertrophy, response to ischaemia and reperfusion and cardioplegic arrest and highlight the importance of optimising cardioprotective strategies to suit hypertrophic hearts.


Viney M.,University of Bristol
Proceedings. Biological sciences / The Royal Society | Year: 2013

In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise and that noise may be adaptive. For example, gene networks can generate bistable states resulting in phenotypic diversity and switching among individual cells of a genotype, which may be a bet hedging strategy. Here, we review the sources of noise in gene expression, the extent to which noise in biological systems may be adaptive and suggest that applying evolutionary rigour to the study of noise is necessary to fully understand organismal phenotypes.


Leimar O.,University of Stockholm | McNamara J.M.,University of Bristol
American Naturalist | Year: 2015

An organism's phenotype can be influenced by maternal cues and directly perceived environmental cues, as well as by its genotype at polymorphic loci, which can be interpreted as a genetic cue. In fluctuating environments, natural selection favors organisms that efficiently integrate different sources of information about the likely success of phenotypic alternatives. In such situations, it can be beneficial to pass on maternal cues that offspring can respond to. A maternal cue could be based on environmental cues directly perceived by the mother but also partly on cues that were passed on by the grandmother. We have used a mathematical model to investigate how the passing of maternal cues and the integration of different sources of information evolve in response to qualitatively different kinds of temporal and spatial environmental fluctuations. The model shows that the passing of maternal cues and the transgenerational integration of sources of information readily evolve. Factors such as the degree of temporal autocorrelation, the predictive accuracy of different environmental cues, and the level of gene flow strongly influence the expression of adaptive maternal cues and the relative weights given to different sources of information. We outline the main features of the relation between the characteristics of environmental fluctuations and the adaptive systems of phenotype determination and compare these predictions with empirical studies on cue integration. © 2015 by The University of Chicago.


Hall E.J.,University of Bristol
Veterinary Clinics of North America - Small Animal Practice | Year: 2011

Antibiotic-responsive diarrhea (ARD) is an idiopathic syndrome causing chronic diarrhea in young, large-breed dogs. Why antibiotics are effective in controlling diarrhea is not understood, and whether small intestinal bacterial numbers are truly increased is now doubted, but previous focus on the condition being small intestinal bacterial overgrowth has hampered the understanding of this condition. The name ARD simply defines the condition, and studies are now looking at the interaction of small intestinal bacteria and the mucosa to try to understand why it occurs. © 2011 Elsevier Inc.


Vinther J.,University of Bristol | Stein M.,Copenhagen University | Longrich N.R.,University of Bath | Harper D.A.T.,Durham University
Nature | Year: 2014

Large, actively swimming suspension feeders evolved several times in Earth's history, arising independently from groups as diverse as sharks, rays and stemteleost fishes1, and in mysticete whales2. However, animals occupying this niche have not been identified fromthe early Palaeozoic era. Anomalocarids, a group of stem arthropods that were the largest nektonic animals of the Cambrian and Ordovician periods, are generally thought to have been apex predators3-5. Here we describe new material from Tamisiocaris borealis6, an anomalocarid fromthe EarlyCambrian (Series 2) Sirius Passet Fauna of North Greenland, and propose that its frontal appendage is specialized for suspension feeding. The appendage bears long, slender and equally spaced ventral spines furnished with dense rows of long and fine auxiliary spines. This suggests that T. borealiswas a microphagous suspension feeder, using its appendages for sweep-net capture of food items down to 0.5mm, within the size range of mesozooplankton such as copepods. Our observations demonstrate that large, nektonic suspension feeders first evolvedduring theCambrian explosion, as part of an adaptive radiation of anomalocarids. The presence of nektonic suspension feeders intheEarlyCambrian, togetherwith evidence for a diverse pelagic community containing phytoplankton7,8 andmesozooplankton7,9,10, indicate the existence of a complex pelagic ecosystem11 supported by high primary productivity and nutrient flux12,13. Cambrian pelagic ecosystems seem to have been more modern than previously believed. © 2014 Macmillan Publishers Limited.


McLatchie L.M.,University of Surrey | Fry C.H.,University of Bristol
BJU International | Year: 2015

Objectives To quantify the amount of ATP released from freshly isolated bladder urothelial cells, study its control by intracellular and extracellular calcium and identify the pathways responsible for its release. Materials and Methods Urothelial cells were isolated from male guinea-pig urinary bladders and stimulated to release ATP by imposition of drag forces by repeated pipetting. ATP was measured using a luciferin-luciferase assay and the effects of modifying internal and external calcium concentration and blockers of potential release pathways studied. Results Freshly isolated guinea-pig urothelial cells released ATP at a mean (sem) rate of 1.9 (0.1) pmoles/mm2 cell membrane, corresponding to about 700 pmoles/g of tissue, and about half [49 (6)%, n = 9) of the available cell ATP. This release was reduced to a mean (sem) of 0.46 (0.08) pmoles/mm2 (160 pmoles/g) with 1.8 mm external calcium, and was increased about two-fold by increasing intracellular calcium. The release from umbrella cells was not significantly different from a mixed intermediate and basal cell population, suggesting that all three groups of cells release a similar amount of ATP per unit area. ATP release was reduced by ≈50% by agents that block pannexin and connexin hemichannels. It is suggested that the remainder may involve vesicular release. Conclusions A significant fraction of cellular ATP is released from isolated urothelial cells by imposing drag forces that cause minimal loss of cell viability. This release involves multiple release pathways, including hemichannels and vesicular release. © 2014 BJU International.


Houston A.I.,University of Bristol
Trends in Ecology and Evolution | Year: 2011

Many birds and mammals forage under water and have to return to the surface to breathe. Models of optimal diving attempt to explain the behaviour of such animals in terms of selection for successful foraging given the constraints imposed by physiology. Several recent papers have questioned the accuracy of both the assumptions and the predictions of these models. Here, I provide a critical review of these papers, arguing that they misrepresent both the models and the data. As a result, they focus on inappropriate tests. I use the debate to suggest various new models and to explore the general relationship between theory and data in behavioural ecology. In particular, I consider the merits of qualitative and quantitative predictions. © 2011 Elsevier Ltd.


Bastow I.D.,University of Bristol | Keir D.,University of Leeds | Keir D.,University of Southampton
Nature Geoscience | Year: 2011

Continental breakup and the transition to seafloor spreading is characterized by extensional faulting, thinning of the lithosphere and, at magmatic margins, voluminous intrusive and extrusive magmatism. It is difficult to discriminate between different mechanisms of extension and magmatism at ancient continental margins because the continent-ocean transition is buried beneath thick layers of volcanic and sedimentary rocks and the tectonic activity that characterized breakup has ceased. Instead, the timing of these mechanisms is inferred from theoretical models or from the geological record preserved at the fully developed, ancient rifted margins. Ongoing rifting in Ethiopia offers a unique opportunity to address these problems because it exposes subaerially the transition between continental rifting towards the south and seafloor spreading further northward. Here we synthesize constraints on the spatial and temporal evolution of magmatism and extension in Ethiopia. We show that although intrusion of magma maintains crustal thickness during the early stages of the continent-ocean transition, subsidence of the margin below sea level, and eruption of voluminous basalt flows, is initiated by late-stage thinning of the heavily intruded, weakened plate just before the onset of seafloor spreading. We thus conclude that faulting, stretching and magma intrusion are each important, but at different times during breakup. © 2011 Macmillan Publishers Limited. All rights reserved.


Marx F.G.,University of Otago | Marx F.G.,University of Bristol | Uhen M.D.,George Mason University
Science | Year: 2010

Modern cetaceans, a poster child of evolution, play an important role in the ocean ecosystem as apex predators and nutrient distributors, as well as evolutionary "stepping stones" for the deep sea biota. Recent discussions on the impact of climate change and marine exploitation on current cetacean populations may benefit from insights into what factors have influenced cetacean diversity in the past. Previous studies suggested that the rise of diatoms as dominant marine primary producers and global temperature change were key factors in the evolution of modern whales. Based on a comprehensive diversity data set, we show that much of observed cetacean paleodiversity can indeed be explained by diatom diversity in conjunction with variations in climate as indicated by oxygen stable isotope records (δ18O).


Munafo M.R.,University of Bristol
Addiction | Year: 2016

Commentary to: Should academic journals publish e-cigarette research linked to tobacco companies? © 2016 Society for the Study of Addiction.


A vertebral centrum belonging to a dyrosaurid, a marine crocodilian recovered from the late Paleocene of Niger, bears a large ovoid and deep puncture on its lateral flank. This mark is identified as a wound inflicted by the bite of another crocodilian. Although the wound shows evidence of healing, the vertebral centrum has been severely damaged and deformed. It provides a rare direct evidence of the aggressive interactions taking place between these now extinct marine reptiles, the largest known marine predators of their time before the rise of the archeocetes. © 2013 SEPM (Society for Sedimentary Geology).


Antcliffe J.B.,University of Bristol
Palaeontology | Year: 2013

Elevated concentrations of an organic compound, 24-isopropylcholestane, found in the Precambrian Huqf Supergroup of Oman may provide the oldest known sponge 'fossil'. This evidence is of critical importance for a properly balanced understanding of the origin of animals. Several different pelagophyte (Class Pelagophyceae part of the Stramenopiles within the Chromaveolata) algae are also capable of producing these exact compounds, and may similarly have done so in deep time. Modern marine algae are also reported to produce structural isomers that are compositionally identical to the sponge marker; they do this in copious quantities. Further, 24-isopropylcholestane can be produced by diagenetic alteration of compounds produced in large quantities by algae. It is also possible that contamination by petroleum derived lubricating oil used when coring while extracting these compounds from subsurface layers, has affected the data. All extinct organisms that may have produced this compounds are unavailable for analysis by the modern organic chemist and cannot be eliminated from the list of possible producers of the sponge marker. There are also significant uncertainties regarding the dating of the strata from which these ancient compounds are found. Although the compounds are widely reported as c. 751 Ma, they are younger than 645 Ma. It seems more likely that these compounds represent algal biochemical evolution at a time when algal burial occurred in great quantity with well known coeval algal fossils but no sponge fossils. The macroalgal biomass may have declined during the agronomic revolution at the base of the Cambrian Period owing to processing by metazoans, accounting for the comparative scarcity of these sponge markers in Phanerozoic sediments, after which time sponge spicules and body fossils become evident. © The Palaeontological Association.


Harvey J.N.,University of Bristol
Faraday Discussions | Year: 2010

New ab initio calculations are reported for two typical organic reactions of polar species, the Wittig reaction of the stabilized ylide Ph 3PCHCO 2CH 3 with benzaldehyde, and the Morita-Baylis-Hillman reaction of the Michael acceptor methyl acrylate with benzaldehyde, catalyzed by quinuclidine. The vacuum ab initio data is combined with continuum solvent models in an attempt to predict solution rate constants. The results show (a) that calculations can now be carried out using accurate local correlation methods with large basis sets for systems with over fifty atoms; (b) that many 'standard' computational methods, while qualitatively useful, and known to give accurate results for small molecular systems, can be very inaccurate for large reactive partners; and (c) that predicting rate constants quantitatively is very difficult. © 2010 The Royal Society of Chemistry.


Berry M.V.,University of Bristol
Journal of Physics A: Mathematical and Theoretical | Year: 2012

Propagation into the far field changes initial waves into their Fourier transforms. This implies that the Riemann zeros could be observed experimentally in the radiation pattern generated by an initial wave whose Fourier transform is proportional to the Riemann zeta function on the critical line. Two such waves are examined, generating the Riemann Ξ(t) function (pattern 1) and the function ζ(1/2+it)/(1/2+it) (pattern 2). For pattern 1, the radiation side lobes are probably too weak to allow detection of the zeros, but for pattern 2 the lobes are stronger, suggesting a feasible experiment. © 2012 IOP Publishing Ltd.


Alexander N.A.,University of Bristol
Journal of Sound and Vibration | Year: 2010

Analytical expressions are determined for the nonlinear resonant frequency (or natural frequency) of the fundamental lateral mode of a pile. A pile with a floating toe, with and without pile cap is considered in this paper. The influence of a nonlinear soil spring model that varies with depth and a nonlinear damping model that is strain amplitude dependent is considered. A non-dimensional equation of motion for the system dynamics is derived from an energy based formulation. This equation is a Duffing's type nonlinear differential system that has nonlinear damping. Harmonic balance with numerical continuation is employed to determine the nonlinear resonance curves of the system. Comparison with some experimental results is made. © 2009 Elsevier Ltd. All rights reserved.


Wiggins S.,University of Bristol
Journal of Fluid Mechanics | Year: 2010

In the 1980s the incorporation of ideas from dynamical systems theory into theoretical fluid mechanics, reinforced by elegant experiments, fundamentally changed the way in which we view and analyse Lagrangian transport. The majority of work along these lines was restricted to two-dimensional flows and the generalization of the dynamical systems point of view to fully three-dimensional flows has seen less progress. This situation may now change with the work of Pouransari et al. (J. Fluid Mech., this issue, vol. 654, 2010, pp. 5-34) who study transport in a three-dimensional time-periodic flow and show that completely new types of dynamical systems structures and consequently, coherent structures, form a geometrical template governing transport. © 2010 Cambridge University Press.


Benton M.J.,University of Bristol
Proceedings of the Geologists' Association | Year: 2011

A new jaw from the Middle Triassic (Anisian) Otter Sandstone Formation of Devon confirms the existence of a derived archosaur (avesuchian). Numerous isolated teeth and vertebrae had already suggested the presence of archosaurs in the Otter Sandstone Formation, presumed predators on the fauna of temnospondyls, procolophonids, and rhynchosaurs, but the new fossil is the first to show some diagnostic characters. Other elements in the same block as the jaw, but not necessarily from the same animal, include a possible skull or pelvic bone, a slender long bone, a small tooth (perhaps prolacertiform), and two presumed archosaur dermal scutes. An additional scute is present, as well as the probable distal end of a pubis, perhaps from a large poposauroid archosaur like the Anisian-age Bromsgroveia or Arizonasaurus. The jaw and pubis represent animals of very different sizes, some 0.8. m and 3. m long in estimated body length respectively. © 2010 The Geologists' Association.


Rock outcrop area and number of sedimentary formations have been widely used as sampling proxies in paleodiversity studies and have often been found to correlate with apparent paleodiversity. However, rock exposure area is a better proxy for the amount of sedimentary rock available for study than the widely used measures of outcrop area (i.e., map area) or number of formations. With the use of remote sensing and a geographic information system (GIS), it is possible to quantify rock exposure area accurately on a regional scale. Rock exposure area does not correlate well with either outcrop area or number of sedimentary formations, and the proportion of rock exposed in different areas can vary considerably with proximity to the coast, bedrock age, lithology, land use, and elevation. Therefore, this suggests that the correlation of paleodiversity and rock volume estimates is best explained by a common-cause hypothesis, rather than a geologic sampling bias hypothesis. GIS methods offer an efficient and accurate method of quantifying regional sedimentary rock exposure and may provide a helpful approach to assessing rock record bias on patterns in the fossil record. © 2011 Geological Society of America.


Severn R.T.,University of Bristol
Earthquake Engineering and Structural Dynamics | Year: 2011

The earliest known shaking table, driven by hand-power, was constructed in Japan at the end of the 19th century. At the beginning of the 20th century developments had moved to the Stanford University in the U.S. with the introduction of an electric motor to produce a more refined oscillatory motion in one direction, the response of the testpiece being recorded mechanically by pens on a rotating drum. Major earthquakes in the 1920s prompted renewed interest at Stanford resulting in a uni-directional table moving on rails, activated either by a pendulum striking at one end-the other being resisted by springs-or by a wheel with an eccentric-mass attached to the table. A valuable feature here was that the size of the eccentric mass could be varied as the harmonic motion continued, thereby providing a method of control. In the 1950s, a similar pendulum input was used on a table constructed at the University of California, but instead of rails, it was supported by a group of vertical bars flexible in one direction only, and the 1939-1945 war had resulted in the availability of electrical devices for measuring response. Also, in Italy at this time the use of pendulums was augmented by contra-rotating mass input devices giving better frequency control; arrays of several electrodynamic exciters were also used. In Japan, motion was induced by the release of compressed springs. The idea of producing input by an oil-filled piston was introduced at MIT after the 1933 Long Beach earthquake to a table suspended from above by wires. Two other innovations here were of the greatest significance. First was an analogue device for using an actual earthquake record as input, and the second was control of the motion by an error-driven electrically controlled feedback loop. The development of these ideas into the shaking tables, which we use today, had to wait upon the general development of control engineering during the 1939-1945 war, followed by progressively greater speeds in digital computation. This history ends (c.1985) after the continuation of these advances made possible full 6-DOF control using many oil-filled actuators, but before they became able to give us real-time control with the attendant abilities of multi-support input and the experimental study of inelastic behaviour. © 2010 John Wiley & Sons, Ltd.


Witham F.,University of Bristol
Earth and Planetary Science Letters | Year: 2011

Magmas progressively exsolve volatiles as they ascend towards the Earth's surface, such that their volatile content is a function of pressure. Water and carbon dioxide concentrations measured in melt inclusions from degassing volcanoes rarely coincide with modelled degassing trends. I show that observed melt inclusion trends can be reproduced through mixing of magmas, either during convection within the volcanic conduit, or within a subterranean magma reservoir. No fluxing gas phase or post-entrapment loss of water need be invoked. A permeable network allowing gas transport is still required to avoid fragmentation of magma at shallow depths. © 2010 Elsevier B.V.


Pandit M.K.,University of Delhi | Pocock M.J.O.,University of Bristol | Kunin W.E.,University of Leeds
Journal of Ecology | Year: 2011

1.The factors associated with plant species' endangerment and (conversely) invasiveness are of broad interest due to their potential value in explaining the causes and consequences of population status. While most past work has focussed on ecological variables, recent work suggests that genetic attributes may be strongly associated with plant species status. 2.We collated data on chromosome numbers for 640 endangered species (worldwide) and their 9005 congeners, and for 81 invasive species and their 2356 congeners. We related ploidy (diploid versus polyploid) to endangerment and invasiveness. We also related chromosome number (absolute number and relative to the minimum recorded for the genus) to endangerment and invasiveness with a randomization test, taking the variation of reported chromosome numbers into account. All analyses considered the relatedness of the taxa. 3.We found that endangered plants are disproportionately likely to be diploid and to have lower ploidy ratios, whilst invasive plant species are generally found to have high chromosome counts and to be polyploid. 4.While considering the effect of relatedness, being endangered is c. 8% less likely as ploidy ratio doubles and 14% less likely for polyploids compared with diploids. Being invasive is 12% more likely as chromosome number doubles and 20% more likely for polyploids compared with diploids. There was no significant effect of raw chromosome number on endangerment or of ploidy ratio on invasiveness. 5.Our findings demonstrate the importance of genomic attributes as risk factors of vulnerability to endangerment or invasiveness in higher plant species, and raise interesting questions as to potential causes of the pattern. 6.Synthesis. Our findings generate new hypotheses on plant rarity and invasiveness influenced by genomic attributes and further our understanding of the role of ploidy in rarity and invasiveness in higher plants. The cause of these relationships are potentially complex, requiring further research; ultimately, understanding the mechanistic basis of population status could aid conservation programs seeking to identify potentially endangered or invasive species. © 2011 The Authors. Journal of Ecology © 2011 British Ecological Society.


Many children do not meet physical activity (PA) guidelines. Extracurricular programmes could provide a mechanism to increase the PA levels of primary-school-aged children. Teaching assistants (TAs) are a valuable resource in all UK primary schools and could be trained to delivery after-school PA programmes. The aim of this feasibility study is to examine whether the Action 3:30 PA intervention, which is delivered by TAs, could be effective in increasing the PA of Year 5 and 6 children. A feasibility trial will be conducted in 20 primary schools. Schools will be randomly assigned to intervention or control arms. Intervention schools will receive a 25-hour TA training programme for two TAs, a first-aid certificate course for two TAs; ongoing TA support; 40 one-hour session plans that can be delivered by TAs; Action 3:30 clubs that run twice a week for 20 weeks; and ten sets of parent information sheets that are distributed biweekly.All measures will be assessed at baseline (Time 0), at the end of the intervention period (Time 1) and four months after the intervention has ended (Time 2). As this is a feasibility study, our primary interest is in estimating the recruitment of schools and children, adherence to the intervention, and completeness of data collection for outcomes and costs.As the most likely primary outcome measure in a future definitive trial will be accelerometer-determined minutes of moderate-to-vigorous PA (MVPA) per day, participants will wear accelerometers for five days (including two weekend days). Several psychosocial variables that could act as mediators in a future trial will be assessed via a questionnaire. Process evaluations of the session attendance, perceived enjoyment and perceived exertion will be assessed during the intervention. At the end of the intervention period, qualitative assessments will be conducted to identify how the programme could be improved before proceeding to a larger trial. The goal of the feasibility trial is to assess the potential of this innovative intervention approach and provide all the information necessary to design a cluster randomized controlled trial. ISRCTN, ISRCTN58502739.


Goda K.,University of Bristol
Earthquake Engineering and Structural Dynamics | Year: 2015

The back-to-back application of mainshock records as aftershock is often considered in conducting aftershock incremental dynamic analysis. In such an approach, the characteristics of mainshock records are considered to be similar to those of major aftershock records within the same mainshock-aftershock sequences. The underlying assumption is that the characteristics of selected mainshocks, other than those used for record selection, are not significant in the assessment of structural responses. A case study is set up to investigate the effects of aftershock record selection on the collapse vulnerability assessment. The numerical results for a specific wood-frame structure indicate that the aftershock fragility can be affected by the aftershock record characteristics, particularly response spectral shape. © 2014 John Wiley & Sons, Ltd.


Rougier J.,University of Bristol
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2013

If you seem to be able to do data assimilation with uncertain static parameters then you are probably not working in environmental science. In this field, applications are often characterized by sensitive dependence on initial conditions and attracting sets in the state-space, which, taken together, can be a major challenge to numerical methods, leading to very peaky likelihood functions. Inherently stochastic models and uncertain static parameters increase the challenge. © 2013 The Author(s) Published by the Royal Society.


Bauza A.,University of the Balearic Islands | Mooibroek T.J.,University of Bristol | Frontera A.,University of the Balearic Islands
Angewandte Chemie - International Edition | Year: 2013

The w(hole) picture: A tetrel bond is a directional noncovalent interaction between a covalently bonded atom of Group IV and a negative site, for example, the lone pair of a Lewis base or an anion. It involves a region of positive electrostatic potential (σ hole), and energetically, they are comparable to hydrogen bonds and other σ-hole-based interactions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Jeffrey M.R.,University of Bristol
International Journal of Bifurcation and Chaos | Year: 2016

We investigate the role of hidden terms at switching surfaces in piecewise smooth vector fields. Hidden terms are zero everywhere except at the switching surfaces, but appear when blowing up the switching surface into a switching layer. When discontinuous systems do surprising things, we can often make sense of them by extending our intuition for smooth system to the switching layer. We illustrate the principle here with a few attractors that are hidden inside the switching layer, being evident in the flow, despite not being directly evident in the vector field outside the switching surface. These can occur either at a single switch (where we will introduce hidden terms somewhat artificially to demonstrate the principle), or at the intersection of multiple switches (where hidden terms arise inescapably). A more subtle role of hidden terms is in bifurcations, and we revisit some simple cases from previous literature here, showing that they exhibit degeneracies inside the switching layer, and that the degeneracies can be broken using hidden terms. We illustrate the principle in systems with one or two switches. © 2016 World Scientific Publishing Company.


Day M.J.,University of Bristol
Parasites and Vectors | Year: 2011

The international prominence accorded the 'One Health' concept of co-ordinated activity of those involved in human and animal health is a modern incarnation of a long tradition of comparative medicine, with roots in the ancient civilizations and a golden era during the 19th century explosion of knowledge in the field of infectious disease research. Modern One Health tends to focus on zoonotic pathogens emerging from wildlife and production animal species, but one of the most significant One Health challenges is rabies for which there is a canine reservoir. This review considers the role of small companion animals in One Health and specifically addresses the major vector-borne infectious diseases that are shared by man, dogs and cats. The most significant of these are leishmaniosis, borreliosis, bartonellosis, ehrlichiosis, rickettsiosis and anaplasmosis. The challenges that lie ahead in this field of One Health are discussed, together with the role of the newly formed World Small Animal Veterinary Association One Health Committee. © 2011 Day; licensee BioMed Central Ltd.


Greer S.,University of Bristol
British Journal of Criminology | Year: 2010

In an article in a recent issue of this journal, Pantazis and Pemberton claim that anti-terrorist laws passed in the United Kingdom in the context of a post-9/11 official political discourse have turned Muslims into a 'suspect community' (Pantazis and Pemberton 2009). Regrettably, this thesis is built on a series of analytical, methodological, conceptual, logical, empirical, evidential and interpretive errors. There is no evidence to support it and a great deal that points in the opposite direction. This reply argues that the 'suspect community' thesis should, therefore, be rejected by social science, public policy and progressive politics in favour of a much more nuanced, multidimensional, accurate and productive account of the relationship between Muslims and the United Kingdom's anti-terrorist laws. © 2010 The Author.


Zakrzewska J.M.,Surgical and Medical science | Coakham H.B.,University of Bristol
Current Opinion in Neurology | Year: 2012

Purpose of Review: A recent Cochrane systematic review of surgical interventions for trigeminal neuralgia found not a single trial of what is becoming the most popular surgical intervention, namely microvascular decompression (MVD). With an increasing number of anticonvulsant drugs it is likely that patients may not be offered a surgical option for management of their trigeminal neuralgia for many years. Recent Findings: Current studies repeat much of what is already in the literature but there is an increasing appreciation of the value of preoperative imaging and the need to be more precise with the diagnosis. The search for prognosticators for good outcomes continues to dominate the literature. Summary: Microvascular decompression in correctly diagnosed patients is probably the most effective therapy. However, high-quality prospective studies of MVD in a population that has been well phenotyped and which is assessed pre and postoperatively using psychometrically tested questions, administered at regular intervals by independent observers, are needed to provide clear evidence of its superiority over medical therapies. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


PRH/HHex (proline-rich homeodomain protein) is a transcription factor that controls cell proliferation and cell differentiation in a variety of tissues. Aberrant subcellular localisation of PRH is associated with breast cancer and thyroid cancer. Further, in blast crisis chronic myeloid leukaemia, and a subset of acute myeloid leukaemias, PRH is aberrantly localised and its activity is downregulated. Here we show that PRH is involved in the regulation of cell migration and cancer cell invasion. We show for the first time that PRH is expressed in prostate cells and that a decrease in PRH protein levels increases the migration of normal prostate epithelial cells. We show that a decrease in PRH protein levels also increases the migration of normal breast epithelial cells. Conversely, PRH overexpression inhibits cell migration and cell invasion by PC3 and DU145 prostate cancer cells and MDA-MB-231 breast cancer cells. Previous work has shown that the transforming growth factor-β co-receptor Endoglin inhibits the migration of prostate and breast cancer cells. Here we show that PRH can bind to the Endoglin promoter in immortalised prostate and breast cells. PRH overexpression in these cells results in increased Endoglin protein expression, whereas PRH knockdown results in decreased Endoglin protein expression. Moreover, we demonstrate that Endoglin overexpression abrogates the increased migration shown by PRH knockdown cells. Our data suggest that PRH controls the migration of multiple epithelial cell lineages in part at least through the direct transcriptional regulation of Endoglin. We discuss these results in terms of the functions of PRH in normal cells and the mislocalisation of PRH seen in multiple cancer cell types.


Colbeck K.L.,University of Bristol
Emotion (Washington, D.C.) | Year: 2012

The present study compares the emotionality of English taboo words in native English speakers and native Chinese speakers who learned English as a second language. Neutral and taboo/sexual words were included in a Rapid Serial Visual Presentation (RSVP) task as to-be-ignored distracters in a short- and long-lag condition. Compared with neutral distracters, taboo/sexual distracters impaired the performance in the short-lag condition only. Of critical note, however, is that the performance of Chinese speakers was less impaired by taboo/sexual distracters. This supports the view that a first language is more emotional than a second language, even when words are processed quickly and automatically. (PsycINFO Database Record (c) 2012 APA, all rights reserved).


Day M.J.,University of Bristol
Journal of Comparative Pathology | Year: 2010

Improvements in veterinary healthcare over recent decades mean that we now have a significant population of geriatric small companion animals. The design of optimum nutritional and vaccination programmes for these aged animals must be underpinned by knowledge of the physiological changes that occur in later life. It is clear that older dogs and cats are affected by the process of immunosenescence and that similar changes occur in these species to those documented in elderly people. The most consistent findings of recent investigations indicate impairment of cell-mediated immune function with age. Senior dogs and cats are generally shown to have reduced blood CD4+ T cells (with imbalance in Th1 versus Th2 functional activity), elevation in the CD8+ subset and reduction in the CD4:CD8 ratio. The ability of blood lymphocytes to respond to stimulation by mitogens decreases, as does the cutaneous delayed type hypersensitivity response. By contrast, there is relative preservation of the ability to mount humoral immune responses. Serum and salivary immunoglobulin (Ig)A production increases and IgG concentration remains unaltered with age. Elderly animals generally have persisting vaccinal antibody titres at protective level and respond to booster vaccination with elevation in titre. Older dogs and cats are able to make primary humoral responses to novel antigens, but the magnitude of these may be reduced relative to titres achieved in younger animals. Fewer investigations have studied the phenomenon of 'inflammageing' (the effect of cumulative antigenic exposure and onset of late life inflammatory disease) in these species. Senior cats have increased production of pro-inflammatory cytokines by blood monocytes, but this effect has not been demonstrated with cells derived from older dogs. Numerous studies have investigated whether canine and feline immunosenescence might be slowed or reversed by dietary supplementation with antioxidants, but no significant research has addressed the need for geriatric vaccination protocols. © 2009 Elsevier Ltd. All rights reserved.


Pieraccini M.,University of Bristol
Ecology and Society | Year: 2013

How does law affect the resilience of common-pool resources? To answer this question this paper adopts an institutionalist perspective on law, arguing that this shares many similarities with the approach of some legal pluralist scholars, i.e., the recognition that a social-ecological system is influenced by a plurality of legal orders having-to borrow Santos terminology-porous qualities. Studying the production and types of relationships between these legal orders can help us in determining whether a system is or is not likely to be resilient. More precisely, if the legal orders interact in a harmonious and dynamic way thanks to bottom-up as well as top-down forces, the system is likely to be resilient. This theoretical hypothesis is tested in a case study, i.e., an alpine common property in northern Italy called Regole d'Ampezzo. It becomes clear that its resilience to various shocks is due to the harmonic integration and adjustments of customary, property, and environmental laws. However, the completeness of this type of analysis is put under discussion when we move from the macro-institutional level to the micro-political one, i.e., to an analysis of intra-community power relations. Drawing on the work of Foucault on the power- subject nexus, the paper attempts to show that in the specific context of the Regole, the harmonic legal pluralist orders operate as a technique of government, perpetuating certain relationships of power between the actors of the common pool resource. At the same time, the relationships of power also contain the possibility of their reversal since, following Foucault, exercising power means acting on the actions of free subjects. The general conclusion is that a legal study of the resilience of common pool resources can benefit from a politicized version of legal pluralism. © 2013 by the author(s).


Reul J.M.H.M.,University of Bristol
Frontiers in Psychiatry | Year: 2014

Strong psychologically stressful events are known to have a long-lasting impact on behavior. The consolidation of such, largely adaptive, behavioral responses to stressful events involves changes in gene expression in limbic brain regions such as the hippocampus and amygdala. However, the underlying molecular mechanisms were until recently unresolved. More than a decade ago, we started to investigate the role of glucocorticoid hormones in signaling and epigenetic mechanisms participating in the effects of stress on gene transcription in hippocampal neurons. We discovered a novel, rapid non-genomic mechanism in which glucocorticoids via glucocorticoid receptors facilitate signaling of the ERK-MAPK signaling pathway to the downstream nuclear kinases MSK1 and Elk-1 in dentate gyrus granule neurons. Activation of this signaling pathway results in serine10 (S10) phosphorylation and lysine14 (K14) acetylation at histone H3 (H3S10p-K14ac), leading to the induction of the immediate-early genes c-Fos and Egr-1. In addition, we found a role of the DNA methylation status of gene promoters. A series of studies showed that these molecular mechanisms play a critical role in the long-lasting consolidation of behavioral responses in the forced swim test and Morris water maze. Furthermore, an important role of GABA was found in controlling the epigenetic and gene transcriptional responses to psychological stress. Thus, psychologically stressful events evoke a long-term impact on behavior through changes in hippocampal function brought about by distinct glutamatergic and glucocorticoid-driven changes in epigenetic regulation of gene transcription, which are modulated by (local) GABAergic interneurons and limbic afferent inputs. These epigenetic processes may play an important role in the etiology of stress-related mental disorders such as major depressive and anxiety disorders like post-traumatic stress disorder. © 2014 Reul.


Thoresen M.,University of Bristol
Journal of Pediatrics | Year: 2011

Three large randomized controlled trials have demonstrated benefits from 3 days of cooling to 33-34°C after perinatal asphyxia. No serious adverse effects were documented. The trials excluded many infants for hypothermia (HT) therapy, including those of age >6 hours and those with prematurity of <36 weeks gestation, abnormal coagulation, persistent pulmonary hypertension, and congenital abnormalities. This article considers whether the foregoing trial exclusion criteria are feasible given current knowledge and evidence. HT affects the validity of some outcome predictors (eg, clinical examination, amplitude-integrated electroencephalography), but not of magnetic resonance imaging. HT is a time-critical emergency treatment after perinatal asphyxia that requires optimal collaboration among local hospitals, transport teams, and cooling centers. © 2011 Mosby Inc. All rights reserved.


Brennan P.,University of Bristol | Keverne E.B.,University of Cambridge
Neuroscience and Biobehavioral Reviews | Year: 2015

Chemosensory systems play vital roles in the lives of most mammals, including the detection and identification of predators, as well as sex and reproductive status and the identification of individual conspecifics. All of these capabilities require a process of recognition involving a combination of innate (kairomonal/pheromonal) and learned responses. Across very different phylogenies, the mechanisms for pheromonal and odour learning have much in common. They are frequently associated with plasticity of GABA-ergic feedback at the initial level of processing the chemosensory information, which enhances its pattern separation capability. Association of odourant features into an odour object primarily involves anterior piriform cortex for non-social odours. However, the medial amygdala appears to be involved in both the recognition of social odours and their association with chemosensory information sensed by the vomeronasal system. Unusually not only the sensory neurons themselves, but also the GABA-ergic interneurons in the olfactory bulb are continually being replaced, with implications for the induction and maintenance of learned chemosensory responses. © 2014.


Matsusaki M.,Osaka University | Case C.P.,University of Bristol | Akashi M.,Osaka University
Advanced Drug Delivery Reviews | Year: 2014

Three-dimensional (3D) tissue constructs consisting of human cells have opened a new avenue for tissue engineering, pharmaceutical and pathophysiological applications, and have great potential to estimate the dynamic pharmacological effects of drug candidates, metastasis processes of cancer cells, and toxicity expression of nano-materials, as a 3D-human tissue model instead of in vivo animal experiments. However, most 3D-cellular constructs are a cell spheroid, which is a heterogeneous aggregation, and thus the reconstruction of the delicate and precise 3D-location of multiple types of cells is almost impossible.In recent years, various novel technologies to develop complex 3D-human tissues including blood and lymph capillary networks have demonstrated that physiological human tissue responses can be replicated in the nano/micro-meter ranges. Here, we provide a brief overview on current 3D-tissue fabrication technologies and their biomedical applications. 3D-human tissue models will be a powerful technique for pathophysiological applications. © 2014 Elsevier B.V.


Hill L.,University of Bristol
Cultural Geographies | Year: 2013

Located at the interface between contemporary archaeology, cultural and historical geography, this essay explores the 'more-than-representational' nature of memory as embodied and haunted by the spectral. Focusing on the post-industrial landscape of the Royal Forest of Dean, I narrate a walk undertaken in November 2008 with local resident, Ron Beard, as we sought to re-trace an old miners' path. Histories of the landscape unfolded as we walked. Yet they also revealed a haunting sense of loss, a fragmented remembering and forgetting that was unsettled by ghosts from the past. For memory is born of strange and uncanny associations, inexplicable connections between times and places that erupt into the present without warning. As such, memory demands new ways of writing; narratives that better cope with our fragile and contingent recollections, disclosing the haunting presence-absence of the spectral in all its shapes, apparitions and phantasms. I begin by pursuing the idea that memory is more-than-representational. I go on to explore the recurrent manifestation of the spectral, which disturbs, displaces and conditions our understanding of space and time, absence and presence. Developing the argument that alternative styles of writing are needed to reveal the true nature of memory and our haunting engagements with the past - while at the same time accepting Wylie's assertion that spectral geographies should themselves be spectral - I consider the work of Walter Benjamin and W.G. Sebald, which, through devices such as literary montage, biography and phantasmagoria, successfully unsettles, disrupts and enlivens. Taking stylistic inspiration from these great writers, the 'Long Path' is narrated in a non-conventional academic style that seeks itself to displace settled orders of space and time, to reveal the revenant trace of the spectre. © The Author(s) 2013.


Kasparov S.,University of Bristol
Cell Metabolism | Year: 2016

The role of lactate in the brain has been controversial. In this issue, Mächler et al. (2015) present data from in vivo experiments suggesting that there is a downward gradient of lactate in the brain. They provide a mechanistic basis for the proposed export of lactate from astrocytes to neurons. © 2016 Elsevier Inc.


Hobson S.A.,University of Bristol
EXS | Year: 2010

The neuropeptide galanin is widely, but not ubiquitously, expressed in the adult nervous system. Its expression is markedly up-regulated in many neuronal tissues after nerve injury or disease. Over the last 10 years, we have demonstrated that the peptide plays a developmental survival role to subsets of neurons in the peripheral and central nervous systems with resulting phenotypic changes in neuropathic pain and cognition. Galanin also appears to play a trophic role to adult sensory neurons following injury, via activation of GalR2, by stimulating neurite outgrowth. Furthermore, galanin also plays a neuroprotective role to the hippocampus following excitotoxic injury, again mediated by activation of GalR2. Most recently, we have shown that galanin expression is markedly up-regulated in multiple sclerosis (MS) lesions and in the experimental autoimmune encephalomyelitis (EAE) model of MS. Over-expression of galanin in transgenic mice abolishes disease in the EAE model, whilst loss-of-function mutations in galanin or GalR2 increase disease severity. In summary, these studies demonstrate that a GalR2 agonist might have clinical utility in a variety of human diseases that affect the nervous system.


Functional explanations of behaviour often propose optimal strategies for organisms to follow. These 'best' strategies could be difficult to perform given biological constraints such as neural architecture and physiological constraints. Instead, simple heuristics or 'rules-of-thumb' that approximate these optimal strategies may instead be performed. From a modelling perspective, rules-of-thumb are also useful tools for considering how group behaviour is shaped by the behaviours of individuals. Using simple rules-of-thumb reduces the complexity of these models, but care needs to be taken to use rules that are biologically relevant. Here, we investigate the similarity between the outputs of a two-player dynamic foraging game (which generated optimal but complex solutions) and a computational simulation of the behaviours of the two members of a foraging pair, who instead followed a rule-of-thumb approximation of the game's output. The original game generated complex results, and we demonstrate here that the simulations following the much-simplified rules-of-thumb also generate complex results, suggesting that the rule-of-thumb was sufficient to make some of the model outcomes unpredictable. There was some agreement between both modelling techniques, but some differences arose - particularly when pair members were not identical in how they gained and lost energy. We argue that exploring how rules-of-thumb perform in comparison to their optimal counterparts is an important exercise for biologically validating the output of agent-based models of group behaviour. © 2011 Sean A. Rands.


Beaumont M.A.,University of Bristol
Annual Review of Ecology, Evolution, and Systematics | Year: 2010

In the past 10years a statistical technique, approximate Bayesian computation (ABC), has been developed that can be used to infer parameters and choose between models in the complicated scenarios that are often considered in the environmental sciences. For example, based on gene sequence and microsatellite data, the method has been used to choose between competing models of human demographic history as well as to infer growth rates, times of divergence, and other parameters. The method fits naturally in the Bayesian inferential framework, and a brief overview is given of the key concepts. Three main approaches to ABC have been developed, and these are described and compared. Although the method arose in population genetics, ABC is increasingly used in other fields, including epidemiology, systems biology, ecology, and agent-based modeling, and many of these applications are briefly described. Copyright © 2010 by Annual Reviews. All rights reserved.


Halestrap A.P.,University of Bristol
Comprehensive Physiology | Year: 2013

Monocarboxylates such as lactate, pyruvate, and the ketone bodies play major roles in metabolism and must be transported across both the plasma membrane and mitochondrial inner membrane. A family of five proton-linked MonoCarboxylate Transporters (MCTs) is involved in the former and the mitochondrial pyruvate carrier (MPC) mediates the latter. In the intestine and kidney, two Sodium-coupled MonoCarboxylate Transporters (SMCTs) provide active transport of monocarboxylates across the apical membrane of the epithelial cells with MCTs on the basolateral membrane transporting the accumulated monocarboxylate into the blood. The kinetics and substrate and inhibitor specificities of MCTs, SMCTs, and the MPC have been well characterized and the molecular identity of the MCTs and SMCTs defined unequivocally. The identity of the MPC is less certain. The MCTs have been extensively studied and the three-dimensional structure of MCT1 has been modeled and a likely catalytic mechanism proposed. MCTs require the binding of a single transmembrane glycoprotein (either embigin or basigin) for activity. Regulation of MCT activity involves both transcriptional and posttranscriptional mechanisms, examples being upregulation of MCT1 by chronic exercise in red muscle (which oxidizes lactate) and in T-lymphocytes upon stimulation. MCT4 has properties that make it especially suited for lactic acid export by glycolytic cells and is upregulated by hypoxia. Some disease states are associated with modulation of plasma membrane and mitochondrial monocarboxylate transport and MCTs are promising drug targets for cancer chemotherapy. They may also be involved in drug uptake from the intestine and subsequent transport across the blood brain barrier. © 2013 American Physiological Society.


Sakamoto M.,University of Bristol
Proceedings of the Royal Society B: Biological Sciences | Year: 2010

Despite the great diversity in theropod craniomandibular morphology, the presence and distribution of biting function types across Theropoda has rarely been assessed. A novel method of biomechanical profiling using mechanical advantage computed for each biting position along the entirety of the tooth row was applied to 41 extinct theropod taxa. Multivariate ordination on the polynomial coefficients of the profiles reveals the distribution of theropod biting performance in function space. In particular, coelophysoids are found to occupy a unique region of function space, while tetanurans have a wide but continuous function space distribution. Further, the underlying phylogenetic structure and evolution of biting performance were investigated using phylogenetic comparative methods. There is a strong phylogenetic signal in ther-opod biomechanical profiles, indicating that evolution of biting performance does not depart from Brownian motion evolution. Reconstructions of ancestral function space occupation conform to this pattern, but phylogenetically unexpected major shifts in function space occupation can be observed at the origins of some clades. However, uncertainties surround ancestor estimates in some of these internal nodes, so inferences on the nature of these evolutionary changes must be viewed with caution. © 2010 The Royal Society.


Soulsbury C.D.,University of Bristol
PLoS ONE | Year: 2010

Background: Testes size is used as a proxy of male intrasexual competition, with larger testes indicative of greater competition. It has been shown that in some taxa, social mating systems reflect variance in testes size, but results are not consistent, and instead it has been suggested that genetic patterns of mating may reflect testes size. However, there are different measures of genetic patterns of mating. Multiple paternity rates are the most widely used measure but are limited to species that produce multi-offspring litters, so, at least for group living species, other measures such as loss of paternity to males outside the social group (extra group paternity) or the proportion of offspring sired by the dominant male (alpha paternity) might be appropriate. This study examines the relationship between testes size and three genetic patterns of mating: multiple paternity, extragroup paternity and alpha paternity. Methodology/Principal Findings: Using data from mammals, phylogenetically corrected general linear models demonstrate that both multiple paternity and alpha paternity, but not extra group paternity, relate to testes size. Testes size is greater in species with high multiple paternity rates, whereas the converse is found for alpha paternity. Additionally, length of mating season, ovulation mode and litter size significantly influenced testes size in one model. Conclusions/Significance:These results demonstrate that patterns of mating (multiple paternity and alpha paternity rates) determined by genetic analysis can provide reliable indicators of male postcopulatory intrasexual competition (testes size), and that other variables (length of mating season, ovulation mode, litter size) may also be important. © 2010 Carl D. Soulsbury.


Bell K.,University of Bristol
Environmental Research Letters | Year: 2015

Can a healthy environment for all social groups be delivered through capitalism via market mechanisms? Or is it the capitalist system, itself, that has been at the root of the environmental and social crises we now face? This letter engages with this ongoing debate by drawing on material from a wider study, 'Achieving Environmental Justice', which examined the extent, form and causes of environmental justice and injustice in a range of countries with varying depths of marketization - United States, South Korea, United Kingdom, Sweden, China, Bolivia and Cuba. The analysis described here focuses on the interview material from this mixed methods study, drawing on over 140 interviews with officials, policy makers, and civil society leaders. The letter argues that there is an apparent propensity for capitalist processes to exacerbate, rather than reduce, environmental problems and inequities though the pursuit of relentless economic growth and profit accumulation. Therefore, we should perhaps let go of efforts to resolve environmental injustice within the constraints of capitalism and, instead, build an alternative economic system that can meet human needs in the context of a harmonious and respectful relationship with nature. © 2015 IOP Publishing Ltd.


Lautenschlager S.,University of Bristol
Proceedings of the Royal Society B: Biological Sciences | Year: 2014

Therizinosaurs are a group of herbivorous theropod dinosaurs from the Cretaceous of North America and Asia, best known for their iconically large and elongate manual claws. However, among Therizinosauria, ungual morphology is highly variable, reflecting a general trend found in derived theropod dinosaurs (Maniraptoriformes). A combined approach of shape analysis to characterize changes in manual ungual morphology across theropods and finite-element analysis to assess the biomechanical properties of different ungual shapes in therizinosaurs reveals a functional diversity related to ungual morphology. While some therizinosaur taxa used their claws in a generalist fashion, other taxa were functionally adapted to use the claws as grasping hooks during foraging. Results further indicate that maniraptoriform dinosaurs deviated from the plesiomorphic theropod ungual morphology resulting in increased functional diversity. This trend parallels modifications of the cranial skeleton in derived theropods in response to dietary adaptation, suggesting that dietary diversification was a major driver for morphological and functional disparity in theropod evolution. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Simpson S.H.,University of Bristol
Journal of Quantitative Spectroscopy and Radiative Transfer | Year: 2014

Beyond the ubiquitous colloidal sphere, optical tweezers are capable of trapping myriad exotic particles with wildly varying geometries and compositions. This simple fact opens up numerous opportunities for micro-manipulation, directed assembly and characterization of novel nanostructures. Furthermore, the mechanical properties of optical tweezers are transformed by their contents. For example, traps capable of measuring, or applying, femto-Newton scale forces with nanometric spatial resolution can be designed. Analogous, if not superior, angular sensitivity can be achieved, enabling the creation of exquisitely sensitive torque wrenches. These capacities, and others, lead to a multitude of novel applications in the meso- and nanosciences. In this article we review experimental and theoretical work on the relationship between particle geometry, composition and trap properties. A range of associated metrological techniques are discussed. © 2014 Elsevier Ltd.


Holtzman B.K.,Lamont Doherty Earth Observatory | Kendall J.-M.,University of Bristol
Geochemistry, Geophysics, Geosystems | Year: 2010

Based on observations in both the laboratory and the Earth, we develop the hypothesis that plate boundaries are lubricated by networks of melt-rich shear zones. Such lubrication would serve to reduce effective strength and focus deformation at plates boundaries. This idea emerges from two sets of observations: (1) stress-driven melt segregation and organization in experimentally deformed mantle rocks and (2) seismic anisotropy patterns as observed at three divergent plate boundaries (the Ethiopian Rift, the Reykjanes Ridge, and the East Pacific Rise). In all three tectonic settings, the magnitude of anisotropy is greatest at the probable locations of the lithosphere- asthenosphere boundary within the plate boundary ("marginal LAB"). Seismic anisotropy in the upper mantle is controlled by the lattice preferred orientation (LPO) of predominant olivine and the alignment of melt structures. The observed patterns of anisotropy are controlled by the dip angle of the marginal LAB. When steeply dipping, shear wave splitting in vertically traveling waves (e.g., SKS phases) is most sensitive to the alignment of melt, and surface waves should reveal faster Rayleigh wave velocities than Love wave velocities (VSV > VSH). When shallowly dipping, shear wave splitting in vertically traveling body waves is controlled by olivine LPO, and surface waves show faster Love wave velocities than Rayleigh wave velocities (VSV < VSH). The formation of melt-rich networks by stress-driven segregation should be most effective where strain rates are highest. These melt-lubricated shear zones will reduce effective viscosity relative to the direct extrapolation of viscosity values derived from laboratory creep experiments on homogenous samples. A composite model of anisotropic seismic properties is developed to test the hypothesis that melt segregates along the LAB, incorporating olivine fabrics with oriented and segregated melt over a range of length scales. This model is applied to observations from the three example plate boundaries, leaving the reader to speculate on the implications for interpretation of anisotropy patterns at other geodynamic settings. Copyright 2010 by the American Geophysical Union.


Fossil specimens can be recovered easily only from exposed localities, so rock exposure area should represent a better proxy for rock availability than the frequently used outcrop (i.e., map) area. Data collected via remote sensing and GIS show that map area does not consistently correlate with exposure area in different regions. Proportional rock exposure is not geographically consistent and is influenced by a number of variables that are independent of outcrop area, including proximity to the coast, elevation, bedrock age, land use and lithology. These variables appear to be non-independent in their influence on rock exposure, and are not consistent in their effects across continents. The inconsistency in the correlation between outcrop and exposure area, and the variability in the influence of different factors on rock exposure, suggests that using outcrop area as a sampling proxy is poorly supported. The weaknesses in using outcrop area as a sampling proxy, highlighted by the lack of correlation with exposure area, suggest that a single accurate global sampling proxy may never be attained and it is premature to assume that paleodiversity curves can be corrected using such proxies. It is therefore preferable to work on a regional scale, comparing regional fossil collection data with a number of proxies representing all aspects of sampling. The lack of correlation between outcrop and exposure area suggests that the covariance detected between outcrop area and paleodiversity might be better explained by a common-cause model, and that geological megabiases may not have had as profound an effect on paleodiversity curves as previously thought. © 2012 The Paleontological Society.


Goda K.,University of Bristol
Bulletin of the Seismological Society of America | Year: 2011

Spatial correlation models of peak ground motions and response spectra are key components for extending current probabilistic seismic hazard and risk analysis for a single location into those for multiple locations and facilitate broad applications, including seismic loss estimation of spatially distributed buildings and infrastructure and ShakeMap interpolation. One of the important aspects that has not been investigated thoroughly is interevent variability of the spatial correlation among different seismic events. The current study addresses this issue. For this purpose, a consolidated extensive ground-motion database was constructed; more than 9000 records from 41 well-recorded earthquakes were used. The analysis results indicate that the extent of the spatial correlation variability, which needs to be incorporated in seismic-hazard and risk calculations, is approximately ±0.1 units with respect to a typical spatial correlation model.


Siddall M.,University of Bristol | Milne G.A.,University of Ottawa
Earth and Planetary Science Letters | Year: 2012

In recent years there have been significant advances in the observational and modeling techniques used to reconstruct and interpret paleo records that relate to changes in sea-level and/or ice extent. This special issue, which presents contributions from the PALeo constraints on Sea-level (PALSEA) PAGES/IMAGES/WUN. 11Past Global Changes/the International Marine Past Global Changes study/World University Network. working group, reflects a number of these developments. Here, we provide an overview of the papers presented in this special issue. By bringing insights from very different paleo-archives and methodologies together, we hope that this special issue will encourage new ideas and collaborations in this area of climate science. © 2011 Elsevier B.V.


Thomson W.,University of Bristol
Journal of Affective Disorders | Year: 2012

Background: The purpose of this study was to examine how sex differences in suicide rates unfolded in a long-term follow up of patients who had been diagnosed with major depression. Method: Patients who were diagnosed with major depression in the Chichester/Salisbury Catchment Area Study were followed for 49 years. Recorded deaths from suicide were compared with rates that were predicted from historical data on suicide mortality rates from 1960 onwards. Findings: An overall suicide rate of 3.4% was found in the present sample. Sixteen women and three men died from suicide. Women's suicide rates were significantly higher than the level predicted based on general population trends. Men showed a barely non-significant trend in the same direction. The diagnosis of clinical depression was associated more strongly with increased risk for suicide among women compared with men. Of the female suicides, 13 had been diagnosed with endogenous depression. Conclusions: While suicide rates are significantly higher for men in the general population, and for depressed patients of both sexes, the depression may be a particularly strong predictor of suicide risk among women. Limitations: The dataset does not provide information about processes that mediate the relationship between depression and suicide mortality. © 2012 Elsevier B.V. All rights reserved.


Popescu S.,University of Bristol
Nature Physics | Year: 2014

Nonlocality is the most characteristic feature of quantum mechanics, but recent research seems to suggest the possible existence of nonlocal correlations stronger than those predicted by theory. This raises the question of whether nature is in fact more nonlocal than expected from quantum theory or, alternatively, whether there could be an as yet undiscovered principle limiting the strength of nonlocal correlations. Here, I review some of the recent directions in the intensive theoretical effort to answer this question.© 2014 Macmillan Publishers Limited.


Pantazis C.,University of Bristol
British Journal of Criminology | Year: 2011

In 2009, in an article for this journal, we argued that UK legal and political developments, following the events of September 2001, had designated Muslims as the 'enemy within' and served to construct Muslims as the principal suspect community (Pantazis and Pemberton 2009). This work sought to utilize and extend Hillyard's original (1993) thesis, which postulated that, during the period of Irish political violence during the 1970s and into the 1990s, the whole Irish population had become a 'suspect community'. In 2010, Steven Greer responded with an uncompromising critique of these combined works. In this reply, we rearticulate our case and demonstrate why Greer's arguments are fundamentally flawed. © The Author 2011. Published by Oxford University Press. All rights reserved.


Copper exists as two isotopes: 65Cu (~30.85%) and 63Cu (~69.15%). The isotopic composition of copper in secondary minerals, surface waters and oxic groundwaters is 1-12‰% heavier than that of copper in primary sulfides. Changes in oxidation state and complexation should yield substantial isotopic fractionation between copper species but it is unclear to what extent the observed Cu isotopic variations reflect equilibrium fractionation. Here, I calculate the reduced partition function ratios for chalcopyrite (CuFeS2), cuprite (Cu2O), tenorite (CuO) and aqueous Cu+, Cu+2 complexes using periodic and molecular hybrid density functional theory to predict the equilibrium isotopic fractionation of Cu resulting from oxidation of Cu+ to Cu+2 and by complexation of dissolved Cu. Among the various copper(II) complexes in aqueous environments, there is a significant (1.3‰%) range in the reduced partition function ratios. Oxidation and congruent dissolution of chalcopyrite (CuFeS2) to dissolved Cu+2 (as Cu(H2O)5 +2) yields 65-63 δ(Cu+2-CuFeS2)=3.1‰% at 25°°C; however, chalcopyrite oxidation/dissolution is incongruent so that the observed isotopic fractionation will be less. Secondary precipitation of cuprite (Cu2O) would yield further enrichment of dissolved 65Cu since 65-63δ(Cu+2-Cu2O) is 1.2‰% at 25°°C. However, precipitation of tenorite (CuO) will favor the heavy isotope by +1.0‰% making dissolved Cu isotopically lighter. These are upper-limit estimates for equilibrium fractionation. Therefore, the extremely large (9‰%) fractionations between dissolved Cu+2(or Cu+2 minerals) and primary Cu+ sulfides observed in supergene environments must reflect Rayleigh (open-system) or kinetic fractionation. Finally the previously proposed (Asael et al., 2009) use of δ65Cu in chalcopyrite to estimate the oxidation state of fluids that transported Cu in stratiform sediment-hosted copper deposits is refined. © 2013 Elsevier Ltd.


Jones G.,University of Bristol
Current Biology | Year: 2013

New research shows how bats use echolocation unexpectedly to detect silent and stationary prey in darkness. Bats may use acoustic search images to identify potential prey when prey-generated noises, visual and olfactory cues are absent. © 2013 Elsevier Ltd.


Martin P.,University of Bristol | Nunan R.,University of Cardiff
British Journal of Dermatology | Year: 2015

Summary A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to heal and leave behind a noticeable scar. At the extreme end, chronic wounds - defined as a barrier defect that has not healed in 3 months - have become a major therapeutic challenge throughout the Western world and will only increase as our populations advance in age, and with the increasing incidence of diabetes, obesity and vascular disorders. Here we describe the clinical problems and how, through better dialogue between basic researchers and clinicians, we may extend our current knowledge to enable the development of novel potential therapeutic treatments. What's already known about this topic? Much is known about the sequence of events contributing to normal healing. The two pathologies of wound healing are chronic wounds and scarring. What does this study add? We explain how the cell and molecular mechanisms of healing guide the therapeutic strategies. We introduce zebrafish and the fruit fly, Drosophila as novel wound healing models. We highlight unanswered questions and future directions for wound healing research. © 2015 British Association of Dermatologists.


Geofluids (2010) 10, 41-57. Complexation by ligands in hydrothermal brines is a fundamental step in the transport of metals in the Earth's crust and the formation of ore deposits. Thermodynamic models of mineral solubility require an understanding of metal complexation as a function of pressure, temperature and composition. Over the past 40 years, mineral solubilities and complexation equilibria under hydrothermal conditions have been predicted by extrapolating thermodynamic quantities using equations of state based on the Born model of solvation. However, advances in theoretical algorithms and computational facilities mean that we can now explore hydrothermal fluids at the molecular level. Molecular or atomistic models of hydrothermal fluids avoid the approximations of the Born model and are necessary for any reliable prediction of metal complexation. First principles (quantum mechanical) calculations based on density functional theory can be easily used to predict the structures and relative energies of metal complexes in the ideal gas phase. However, calculations of metal complexation in condensed fluids as a function of temperature and pressure require sampling the configuration degrees of freedom using molecular dynamics (MD). Simulations of dilute solutions require very large systems (thousands of atoms) and very long simulation times; such calculations are only practical by treating the interatomic interactions using classical two- or three-body interatomic potentials. Although such calculations provide some fundamental insights into the nature of crustal fluids, simple two- or three-body classical potentials appear to be inadequate for reliably predicting metal complexation, especially in covalent systems such as Sn2+, Au3+ and Cu+. Ab initio MD (i.e. where the bonding is treated quantum mechanically, but the molecular motions are treated classically) avoids the use of interatomic potentials. These calculations are practical for systems with hundreds of atoms over short times (<10 psec) but enable us to predict complexation as a function of pressure, temperature and composition. In this paper, I provide an introductory outline of the computational methods and illustrations of their application to NaCl brines and the complexation of Cu, Au, Sn and Zn. © 2010 Blackwell Publishing Ltd.


Wardle A.J.,University of Bristol
Archives of disease in childhood. Education and practice edition | Year: 2013

In recent times, paediatric pulmonary arterial hypertension management has been transformed to focus on disease modifying strategies that improve both quality of life and survival, rather than just symptom palliation. Sildenafil, a phosphodiesterase-V inhibitor, has been at the centre of this. Despite controversial beginnings, its success in treating pulmonary arterial hypertension has led to its consideration for related pathologies such as persistent pulmonary hypertension of the newborn and bronchopulmonary dysplasia, as well as the development of a range of alternative formulations. However, this has caused its own controversy and confusion regarding the use of sildenafil in younger patients. In addition, recent data regarding long-term mortality and the repeal of US drugs approval have complicated the issue. Despite such setbacks, sildenafil continues to be a major component of the contemporary care of paediatric pulmonary hypertension in a variety of contexts, and this does not seem likely to change in the foreseeable future.


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

Surgery is an important part of the management of oral cavity cancer with regard to both the removal of the primary tumour and removal of lymph nodes in the neck. Surgery is less frequently used in oropharyngeal cancer. Surgery alone may be treatment for early stage disease or surgery may be used in combination with radiotherapy, chemotherapy and immunotherapy/biotherapy. There is variation in the recommended timing and extent of surgery in the overall treatment regimens of people with these cancers. To determine which surgical treatment modalities for oral cavity and oropharyngeal cancers result in increased overall survival, disease free survival, progression free survival and reduced recurrence. The following electronic databases were searched: the Cochrane Oral Health Group Trials Register (to 17 February 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), MEDLINE via OVID (1950 to 17 February 2011) and EMBASE via OVID (1980 to 17 February 2011). There were no restrictions regarding language or date of publication. Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, and which compared two or more surgical treatment modalities or surgery versus other treatment modalities. Data extraction and assessment of risk of bias was undertaken independently by two or more review authors. Study authors were contacted for additional information as required. Adverse events data were collected from published trials. Seven trials (n = 669; 667 with cancers of the oral cavity) satisfied the inclusion criteria, but none were assessed as low risk of bias. Trials were grouped into three main comparisons. Four trials compared elective neck dissection (ND) with therapeutic neck dissection in patients with oral cavity cancer and clinically negative neck nodes, but differences in type of surgery and duration of follow-up made meta-analysis inappropriate. Three of these trials reported overall and disease free survival. One trial showed a benefit for elective supraomohyoid neck dissection compared to therapeutic ND in overall and disease free survival. Two trials found no difference between elective radical ND and therapeutic ND for the outcomes of overall survival and disease free survival. All four trials found reduced locoregional recurrence following elective ND.A further two trials compared elective radical ND with elective selective ND and found no difference in overall survival, disease free survival or recurrence. The final trial compared surgery plus radiotherapy to radiotherapy alone but data were unreliable because the trial stopped early and there were multiple protocol violations.None of the trials reported quality of life as an outcome. Two trials, evaluating different comparisons reported adverse effects of treatment. Seven included trials evaluated neck dissection surgery in patients with oral cavity cancers. The review found weak evidence that elective neck dissection of clinically negative neck nodes at the time of removal of the primary tumour results in reduced locoregional recurrence, but there is insufficient evidence to conclude that elective neck dissection increases overall survival or disease free survival compared to therapeutic neck dissection. There is very weak evidence from one trial that elective supraomohyoid neck dissection may be associated with increased overall and disease free survival. There is no evidence that radical neck dissection increases overall survival compared to conservative neck dissection surgery. Reporting of adverse events in all trials was poor and it was not possible to compare the quality of life of patients undergoing different surgeries.


Foster G.L.,UK National Oceanography Center | Lear C.H.,University of Cardiff | Rae J.W.B.,University of Bristol
Earth and Planetary Science Letters | Year: 2012

The middle Miocene Climatic Optimum (17-15Ma; MCO) is a period of global warmth and relatively high CO 2 and is thought to be associated with a significant retreat of the Antarctic Ice Sheet (AIS). We present here a new planktic foraminiferal δ 11B record from 16.6 to 11.8Ma from two deep ocean sites currently in equilibrium with the atmosphere with respect to CO 2. These new data demonstrate that the evolution of global climate during the middle Miocene (as reflected by changes in the cyrosphere) was well correlated to variations in the concentration of atmospheric CO 2. What is more, within our sampling resolution (~1 sample per 300kyr) there is no evidence of hysteresis in the response of ice volume to CO 2 forcing during the middle Miocene, contrary to what is understood about the Antarctic Ice Sheet from ice sheet modelling studies. In agreement with previous data, we show that absolute levels of CO 2 during the MCO were relatively modest (350-400ppm) and levels either side of the MCO are similar or lower than the pre-industrial (200-260ppm). These new data imply the presence of either a very dynamic AIS at relatively low CO 2 during the middle Miocene or the advance and retreat of significant northern hemisphere ice. Recent drilling on the Antarctic margin and shore based studies indicate significant retreat and advance beyond the modern limits of the AIS did occur during the middle Miocene, but the complete loss of the AIS was unlikely. Consequently, it seems that ice volume and climate variations during the middle Miocene probably involved a more dynamic AIS than the modern but also some component of land-based ice in the northern hemisphere. © 2012 Elsevier B.V.


Krieger U.K.,ETH Zurich | Marcolli C.,ETH Zurich | Reid J.P.,University of Bristol
Chemical Society Reviews | Year: 2012

The complex interplay of processes that govern the size, composition, phase and morphology of aerosol particles in the atmosphere is challenging to understand and model. Measurements on single aerosol particles (2 to 100 μm in diameter) held in electrodynamic, optical and acoustic traps or deposited on a surface can allow the individual processes to be studied in isolation under controlled laboratory conditions. In particular, measurements can now be made of particle size with unprecedented accuracy (sub-nanometre) and over a wide range of timescales (spanning from milliseconds to many days). The physical state of a particle can be unambiguously identified and its composition and phase can be resolved with a high degree of spatial resolution. In this review, we describe the advances made in our understanding of aerosol properties and processes from measurements made of phase behaviour, hygroscopic growth, morphology, vapour pressure and the kinetics of water transport for single particles. We also show that studies of the oxidative aging of single particles, although limited in number, can allow the interplay of these properties to be investigated. We conclude by considering the contributions that single particle measurements can continue to make to our understanding of the properties and processes occurring in atmospheric aerosol. © The Royal Society of Chemistry 2012.


Donovan J.L.,University of Bristol
Journal of the National Cancer Institute - Monographs | Year: 2012

Presenting treatment options to men with localized prostate cancer is difficult because of the lack of definitive evidence and the range of treatment options available. Active surveillance and monitoring programs are now a recognized treatment option for men with low-risk localized prostate cancer, but many patients are not fully aware of the details of such programs, and most still opt for immediate radical (surgery or radiotherapy) treatment. The provision of high-quality information with decision aids has been shown to increase the acceptability of active surveillance/monitoring programs. This chapter outlines techniques for providing high-quality information about active surveillance/monitoring, based on the findings of a randomized controlled trial of treatments for localized prostate cancer. The ProtecT (Prostate testing for cancer and Treatment) trial has randomized over 1500 men between active monitoring, radical surgery, and radical radiotherapy by ensuring that information was tailored to men's existing knowledge and views. Care was taken with the content, order, and enthusiasm of the presentation of treatments by recruitment staff, and clinicians and other health professionals were supported to feel comfortable with being open about the uncertainties in the evidence and helped to rephrase terminology likely to be misinterpreted by patients. These techniques of information provision should be added to the use of decision aids to enable patients diagnosed with clinically localized prostate cancer in routine practice to reach well-informed and reasoned decisions about their treatment, including full consideration of active surveillance and monitoring programs. © The Author 2012. Published by Oxford University Press. All rights reserved.


Bastow I.D.,University of Bristol
Geophysical Journal International | Year: 2012

The interpretation of seismic tomographic images of upper-mantle seismic wave speed structure is often a matter of considerable debate because the observations can usually be explained by a range of hypotheses, including variable temperature, composition, anisotropy, and the presence of partial melt. An additional problem, often overlooked in tomographic studies using relative as opposed to absolute arrival-times, is the issue of the resulting velocity model's zero mean. In shield areas, for example, relative arrival-time analysis strips off a background mean velocity structure that is markedly fast compared to the global average. Conversely, in active areas, the background mean is often markedly slow compared to the global average. Appreciation of this issue is vital when interpreting seismic tomographic images: 'high' and 'low' velocity anomalies should not necessarily be interpreted, respectively, as 'fast' and 'slow' compared to 'normal mantle'. This issue has been discussed in the seismological literature in detail over the years, yet subsequent tomography studies have still fallen into the trap of mis-interpreting their velocity models. I highlight here some recent examples of this and provide a simple strategy to address the problem using constraints from a recent global tomographic model, and insights from catalogues of absolute traveltime anomalies. Consultation of such absolute measures of seismic wave speed should be routine during regional tomographic studies, if only for the benefit of the broader Earth Science community, who readily follow the red = hot and slow, blue = cold and fast rule of thumb when interpreting the images for themselves. © 2012 The Author Geophysical Journal International © 2012 RAS.


Claesson M.,Sahlgrenska University Hospital | Armitage W.J.,University of Bristol
Cornea | Year: 2013

Purpose: To compare the clinical outcome of regrafts with first grafts. Methods: Two-year outcome data were obtained from the Swedish Cornea Transplant Register for patients undergoing penetrating keratoplasty between 2001 and 2008. Only data from the 3 centers with follow-up return rates .75% were included. The survival and visual outcome of regrafts with the original diagnoses of keratoconus, Fuchs endothelial dystrophy (FED), or bullous keratopathy (BK) were compared with first grafts for the same diagnoses by univariate and logistic regression methods. Results: For keratoconus, the failure rate increased 3-fold in regrafts compared with first grafts (ie, 17% vs. 6%; P = 0.002) and doubled in FED regrafts (33% vs. 15%; P = 0.001). In BK, the failure rate was already high in first grafts, and the increase in failure of regrafts was minimal (P = 0.9). Visual acuity was also worse in regrafts compared with first grafts, mainly in the keratoconus and FED patients. In the keratoconus group, visual acuity with preferred correction was ≥0.5 in 69% of first grafts compared with only 55% in regrafts (P = 001). In FED, 52% of first grafts but only 19% of regrafts achieved visual acuity ≥0.5 (P = 0.001). The visual outcome of regrafts in BK was poor but little different from first grafts where fewer than 20% achieved visual acuity ≥0.5. Conclusions: This analysis confirmed the poorer survival of regrafts where the original indication was keratoconus or FED. In addition, visual outcome was also worse than in the first grafts. However, the outcomes of regrafts in BK were similar to first grafts.© 2013 by Lippincott Williams & Wilkins.


Valente C.,University of Bristol
Journal of Health Economics | Year: 2015

A sizeable economics literature explores the effect of prenatal shocks on later health or socioeconomic status. Work in other disciplines, following the seminal contribution of Trivers and Willard (1973), suggests that prenatal shocks may increase fetal loss and reduce the number of boys relative to girls at birth. This has been largely ignored in the economics literature and could affect the interpretation of estimates of the effect of prenatal shocks and that of gender in other applied economics contexts. This paper analyzes the effect of in utero exposure to a shock - civil conflict in Nepal - on (i) fetal loss, and (ii) gender and (iii) health at birth. Maternal fixed effects estimates show that exposed pregnancies are more likely to result in a miscarriage and in a female birth, but exposed newborns are neither smaller nor more subject to neonatal mortality. © 2014 Elsevier B.V.


Woolfson D.N.,University of Bristol
Biopolymers | Year: 2010

Over the decade and a half, interest has soared in the development of peptide-based biomaterials and their potential applications in biotechnology. This review outlines the advances during this time in the construction of biomaterials based on the alpha-helical coiled-coil and collagen-like peptides. These structures and the resulting designs are distinct from the more commonly used beta-structured peptides, which often lead to hydrogels comprising amyloid-like fibrils. The review covers basic design rules for these helical assemblies, and the various fibrous biomaterials that can be accomplished with them, which include rigid structures with straight, branched, or networked structures, decorated and functionalized systems, and most recently flexible fibers and entangled hydrogel networks. This plethora of alpha-helix-based biomaterials, together with more recent collagen-like assemblies, that are emerging from various laboratories complement those developed using beta-structured peptides, and open exciting new avenues for biomaterials research and potential new application areas. (c) 2010 Wiley Periodicals, Inc.


Bedford R.B.,University of Bristol
Accounts of Chemical Research | Year: 2015

ConspectusThe catalytic cross-coupling reactions of organic halides or related substrates with organometallic nucleophiles form the cornerstone of many carbon-carbon bond-forming processes. While palladium-based catalysts typically mediate such reactions, there are increasing concerns about the long-term sustainability of palladium in synthesis. This is due to the high cost of palladium, coupled with its low natural abundance, environmentally deleterious extraction (∼6 g of metal are produced per ton of ore), toxicity, and competition for its use from the automotive and consumer electronics sectors. Therefore, there is a growing interest in replacing palladium-based catalysts with those incorporating more earth-abundant elements.With its low cost, high natural abundance, and low toxicity, iron makes a particularly appealing alternative, and accordingly, the development of iron-catalyzed cross-coupling is undergoing explosive growth. However, our understanding of the mechanisms that underpin the iron-based catalytic cycles is still very much in its infancy. Mechanistic insight into catalytic reactions is not only academically important but also allows us to maximize the efficiency of processes or even to develop entirely new transformations.Key to the development of robust mechanistic models for cross-coupling is knowing the lowest oxidation state in the cycle. Once this is established, we can explore subsequent redox processes and build the catalytic manifold. Until we know with confidence what the lowest oxidation state is, any cycles proposed are largely just guesswork.To date, Fe(-II), Fe(-I), Fe(0), Fe(I), and Fe(II) have been proposed as contenders for the lowest-oxidation-state species in the cycle in iron-catalyzed cross-coupling; the aim of this Account is to pull together the various pieces of evidence in support, or otherwise, of each of these suggestions in turn.There currently exists no direct evidence that oxidation states below Fe(0) are active in the catalytic cycle. Meanwhile, the reactivity required of the lowest-oxidation-state species has been observed with model compounds in higher oxidation states, implying that there is no need to invoke such low oxidation states. While subzero-valent complexes do indeed act as effective precatalysts, it is important to recognize that this tells us that they are efficiently converted to an active catalyst but says nothing about the oxidation states of the species in the catalytic cycle.Zero-valent heterogeneous iron nanoparticles can be formed under typical catalytic conditions, but there is no evidence to suggest that homogeneous Fe(0) complexes can be produced under comparable conditions. It seems likely that the zero-valent nanoparticles act as a reservoir for soluble higher-oxidation-state species.Fe(II) complexes can certainly be formed under catalytically relevant conditions, and when bulky nucleophilic coupling partners are exploited, potential intermediates can be isolated. However, the bulky reagents act as poor proxies for most nucleophiles used in cross-coupling, as they give Fe(II) organometallic intermediates that are kinetically stabilized with respect to reductive elimination. When more realistic substrates are exploited, reduction or disproportionation to Fe(I) is widely observed, and while it still has not been conclusively proved, this oxidation state currently represents a likely candidate for the lowest one active in many iron-catalyzed cross-coupling processes. © 2015 American Chemical Society.


Bauza A.,University of the Balearic Islands | Mooibroek T.J.,University of Bristol | Frontera A.,University of the Balearic Islands
Chemical Communications | Year: 2015

A statistical survey of the Cambridge Structural Database reveals that the interaction between the π-holes of nitro groups and electron-rich atoms is somewhat directional. High-level ab initio computations indicate energies up to -6.6 kcal mol-1. This journal is © The Royal Society of Chemistry.


Eggers J.,University of Bristol
Physics of Fluids | Year: 2012

We consider the dynamics of a fluid thread near pinch-off, in the limit that inertial effects can be neglected. There exists an infinite hierarchy of similarity solutions corresponding to pinch-off. Only one of the similarity solutions (the "ground state") is stable, all other solutions are linearly unstable to perturbationsthus cannot be observed. Eigenvalues and eigenfunctions are calculated analytically. © 2012 American Institute of Physics.


Perryman M.,University of Bristol
European Physical Journal H | Year: 2012

The history of astrometry, the branch of astronomy dealing with the positions of celestial objects, is a lengthy and complex chronicle, having its origins in the earliest records of astronomical observations more than two thousand years ago, and extending to the high accuracy observations being made from space today. Improved star positions progressively opened up and advanced fundamental fields of scientific enquiry, including our understanding of the scale of the solar system, the details of the Earth's motion through space, and the comprehension and acceptance of Newtonianism. They also proved crucial to the practical task of maritime navigation. Over the past 400 years, during which positional accuracy has improved roughly logarithmically with time, the distances to the nearest stars were triangulated, making use of the extended measurement baseline given by the Earth's orbit around the Sun. This led to quantifying the extravagantly vast scale of the Universe, to a determination of the physical properties of stars, and to the resulting characterisation of the structure, dynamics and origin of our Galaxy. After a period in the middle years of the twentieth century in which accuracy improvements were greatly hampered by the perturbing effects of the Earth's atmosphere, ultra-high accuracies of star positions from space platforms have led to a renewed advance in this fundamental science over the past few years. © 2012 EDP Sciences and Springer-Verlag Berlin Heidelberg.


Kuhl H.S.,Max Planck Institute for Evolutionary Anthropology | Burghardt T.,University of Bristol
Trends in Ecology and Evolution | Year: 2013

Animal biometrics is an emerging field that develops quantified approaches for representing and detecting the phenotypic appearance of species, individuals, behaviors, and morphological traits. It operates at the intersection between pattern recognition, ecology, and information sciences, producing computerized systems for phenotypic measurement and interpretation. Animal biometrics can benefit a wide range of disciplines, including biogeography, population ecology, and behavioral research. Currently, real-world applications are gaining momentum, augmenting the quantity and quality of ecological data collection and processing. However, to advance animal biometrics will require integration of methodologies among the scientific disciplines involved. Such efforts will be worthwhile because the great potential of this approach rests with the formal abstraction of phenomics, to create tractable interfaces between different organizational levels of life. © 2013 Elsevier Ltd.


Briscoe W.H.,University of Bristol
Current Opinion in Colloid and Interface Science | Year: 2015

Understanding depletion forces between colloidal particles mediated by nanofluids, i.e. liquids containing hard or soft nanostructures, is immensely important in a number of industrial processes. We anticipate added complexities due to enhanced and multifactorial inter-depletant interactions associated with their size, shape, surface chemistry, and concentration. Here we briefly review recent efforts in direct measurement of depletion forces mediated by nanofluids, as well as a number of related studies on the phase transition in binary colloid mixtures with large size and shape asymmetry, a process in which depletion forces play an important role. We will also discuss the often under-appreciated importance of depletion forces mediated by proteo-nanofluids (liquids containing proteins) in facilitating cellular organisation. Some challenges and outstanding questions will emerge from the above discussions, as briefly summarised. © 2014 Elsevier Ltd.


Kehoe P.G.,University of Bristol | Passmore P.A.,Queens University of Belfast
Journal of Alzheimer's Disease | Year: 2012

There is an urgent need to improve upon Alzheimer's disease (AD) treatments. Limitations of existing drugs are that they target specific downstream neurochemical abnormalities while the upstream underlying pathology continues unchecked. Preferable treatments would be those that can target a number of the broad range of molecular and cellular abnormalities that occur in AD such as amyloid-β (Aβ) and hyperphosphorylated tau-mediated damage, inflammation, and mitochondrial dysfunction, as well more systemic abnormalities such as brain atrophy, impaired cerebral blood flow (CBF), and cerebrovascular disease. Recent pre-clinical, epidemiological, and a limited number of clinical investigations have shown that prevention of the signaling of the multifunctional and potent vasoconstrictor angiotensin II (Ang II) may offer broad benefits in AD. In addition to helping to ameliorate co-morbid hypertension, these drugs also likely improve diminished CBF which is common in AD and can contribute to focal Aβ pathology. These drugs, angiotensin converting enzyme (ACE) inhibitors, or angiotensin receptor antagonists (ARAs) may also help deteriorating cognitive function by preventing Ang II-mediated inhibition of acetylcholine release as well as interrupt the upregulation of deleterious inflammatory pathways that are widely recognized in AD. Given the current urgency to find better treatments for AD and the relatively immediate availability of drugs that are already widely prescribed for the treatment of hypertension, one of the largest modifiable risk factors for AD, this article reviews current knowledge as to the eligibility of ACE-inhibitors and ARAs for consideration in future clinical trials in AD. © 2012 - IOS Press and the authors. All rights reserved.


Kennedy H.J.,University of Bristol
JARO - Journal of the Association for Research in Otolaryngology | Year: 2012

In the mature mammalian auditory system, inner hair cells are responsible for converting sound-evoked vibrations into graded electrical responses, resulting in release of neurotransmitter and neuronal transmission via the VIIIth cranial nerve to auditory centres in the central nervous system. Before the cochlea can reliably respond to sound, inner hair cells are not merely immature quiescent pre-hearing cells, but instead are capable of generating 'spontaneous' calcium-based action potentials. The resulting calciumsignal promotes transmitter release that drives action potential firing in developing spiral ganglion neurones. These early signalling events that occur before sound-evoked activity are thought to be important in guiding and refining the initial phases of development of the auditory circuits. This review will summarise our current knowledge of the mechanisms that underlie spontaneous action potentials in developing inner hair cells and how these events are triggered and regulated. © 2012 Association for Research in Otolaryngology.


Fisher J.P.,University of Birmingham | Paton J.F.R.,University of Bristol
Journal of Human Hypertension | Year: 2012

A neurogenic component to primary hypertension (hypertension) is now well established. Along with raised vasomotor tone and increased cardiac output, the chronic activation of the sympathetic nervous system in hypertension has a diverse range of pathophysiological consequences independent of any increase in blood pressure. This review provides a perspective on the actions and interactions of angiotensin II, inflammation and vascular dysfunction/brain hypoperfusion in the pathogenesis and progression of neurogenic hypertension. The optimisation of current treatment strategies and the exciting recent developments in the therapeutic targeting of the sympathetic nervous system to control hypertension (for example, catheter-based renal denervation and carotid baroreceptor stimulation) will be outlined. © 2012 Macmillan Publishers Limited All rights reserved.


Thomas G.H.,University of Bristol | Freckleton R.P.,University of Sheffield
Methods in Ecology and Evolution | Year: 2012

Models of trait macroevolution on trees (MOTMOT) is a new software package that tests for variation in the tempo and mode of continuous character evolution on phylogenetic trees. MOTMOT provides tools to fit a range of models of trait evolution with emphasis on variation in the rate of evolution between clades and character states. We introduce a new method, trait MEDUSA, to identify the location of major changes in the rate of evolution of continuous traits on phylogenetic trees. We demonstrate trait MEDUSA and the other main functions of MOTMOT, using body size of Anolis lizards. MOTMOT is open source software written in the R language and is freely available from CRAN (http://cran.r-project.org/web/packages/). © 2011 The Authors. Methods in Ecology and Evolution © 2011 British Ecological Society.


Yeates J.W.,University of Bristol
Veterinary Journal | Year: 2012

This article looks at the existing evidence-base by which veterinary surgeons can make welfare-focused treatment choices. Narrative and structured reviews were conducted. Papers were categorised under headings based on (1) themes in the UK Animal Welfare Act (AWA 2006) - behaviour, environment, nutrition, company and health; (2) iatrogenic harm induced by treatment; (3) decision-making methods, and (4) the subjects' context (e.g. home versus laboratory).There is more information available about 'overt' problems (e.g. acute disease), than 'covert' issues (e.g. chronic pain, lack of company and obesity). Forty of 109 papers covered pain, suffering, injury and disease, compared to 69 across four other themes in the AWA. Twelve papers were identified as focusing on welfare assessment and clinical decision-making. Veterinary surgeons should consider each of the five welfare themes described in the AWA in both veterinary practice and in determining veterinary research priorities. © 2011 Elsevier Ltd.


Wilson J.A.,University of Bristol
Journal of Physics Condensed Matter | Year: 2010

FeSe is employed as reference material to elucidate the observed high Tc superconducting behaviour of the related layered iron pnictides. The structural and ensuing semimetallic band structural forms are here rather unusual, with the resulting ground state details extremely sensitive to the precise shape of the Fe-X coordination unit. The superconductivity is presented as coming from a combination of resonant valence bond and excitonic insulator physics, and incorporating boson-fermion degeneracy. Although sourced in a very different fashion, the latter leads to some similarities with the high temperature superconducting (HTSC) cuprates. The excitonic insulator behaviour sees spin density wave, charge density wave/periodic structural distortion, and superconductive instabilities all vie for ground state status. The conflict leads to a very sensitive and complex set of properties, frequently mirroring HTSC cuprate behaviour. The delicate balance between ground states is made particularly difficult to unravel by the micro-inhomogeneity of structural form which it can engender. It is pointed out that several other notable superconductors, layered in form, semimetallic with indirect overlap and possessing homopolar bonding, would look to fall into the same general category, β-ZrNCl and MgB2 and the high pressure forms of several elements, like sulfur, phosphorus, lithium and calcium, being cases in point. © 2010 IOP Publishing Ltd.


Benton M.J.,University of Bristol
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

Comparative studies of large phylogenies of living and extinct groups have shown that most biodiversity arises from a small number of highly species-rich clades. To understand biodiversity, it is important to examine the history of these clades on geological time scales. This is part of a distinct 'phylogenetic expansion' view of macroevolution, and contrasts with the alternative, nonphylogenetic 'equilibrium' approach to the history of biodiversity. The latter viewpoint focuses on density-dependent models in which all life is described by a single global-scale model, and a case is made here that this approach may be less successful at representing the shape of the evolution of life than the phylogenetic expansion approach. The terrestrial fossil record is patchy, but is adequate for coarse-scale studies of groups such as vertebrates that possess fossilizable hard parts. New methods in phylogenetic analysis, morphometrics and the study of exceptional biotas allow new approaches. Models for diversity regulation through time range from the entirely biotic to the entirely physical, with many intermediates. Tetrapod diversity has risen as a result of the expansion of ecospace, rather than niche subdivision or regional-scale endemicity resulting from continental break-up. Tetrapod communities on land have been remarkably stable and have changed only when there was a revolution in floras (such as the demise of the Carboniferous coal forests, or the Cretaceous radiation of angiosperms) or following particularly severe mass extinction events, such as that at the end of the Permian. This journal is © 2010 The Royal Society.


Diagnostic selective nerve root block (SNRB) involves injection of local anaesthetic, sometimes in conjunction with corticosteroids, around spinal nerves. It is used to identify symptomatic nerve roots in patients with probable radicular pain that is not fully concordant with imaging findings. (1) Determine the diagnostic accuracy of SNRB in patients with low back and radiating pain in a lower limb; (2) evaluate whether or not accuracy varies by patient subgroups; (3) review injection-related adverse events; and (4) evaluate the cost-effectiveness of SNRB. MEDLINE, EMBASE, Science Citation Index, Bioscience Information Service (BIOSIS), Latin American and Caribbean Health Sciences Literature (LILACS) and grey literature databases were searched from inception to August 2011. Reference lists of included studies were screened. A systematic review (SR) of studies that assessed the accuracy of SNRB or adverse events in patients with low back pain and symptoms in a lower limb for the diagnosis of lumbar radiculopathy. Study quality was assessed using the quality assessment of diagnostic accuracy studies (QUADAS)-2 checklist. We used random-effects meta-analysis to pool diagnostic accuracy data. Decision tree and Markov models were developed, combining SR results with information on the costs and outcomes of surgical and non-surgical care. Uncertainty was assessed using probabilistic and deterministic sensitivity analyses. Five studies assessed diagnostic accuracy: three diagnostic cohort and two within-patient case-control studies. All were judged to be at high risk of bias and had high concerns regarding applicability. In individual studies, sensitivity ranged from 57% [95% confidence interval (CI) 43% to 70%] to 100% (95% CI 76% to 100%) and specificity from 9.5% (95% CI 1% to 30%) to 86% (95% CI 76% to 93%). The most reliable estimate was judged to come from two cohort studies that used post-surgery outcome as the reference standard; summary sensitivity and specificity were 93% (95% CI 86% to 97%) and 26% (95% CI 5% to 68%), respectively. No study provided sufficient detail to judge whether or not accuracy varied by patient subgroup. Seven studies assessed adverse events. There were no major or permanent complications; minor complications were reported in 0-6% of patients. The addition of SNRB to the diagnostic work-up was not cost-effective with an incremental cost per quality-adjusted life-year of £1,576,007. Sensitivity analyses confirmed that SNRB was unlikely to be a cost-effective method for diagnosis and planning surgical therapy. We identified very few studies; all were at high risk of bias. The conduct and interpretation of SNRBs varied and there was no gold standard for diagnosis. Limited information about the impact of SNRB on subsequent care and the long-term costs and benefits of surgery increased uncertainty about cost-effectiveness. There were few studies that estimated the diagnostic accuracy of SNRB in patients with radiculopathy and all were limited by the difficulty of making a reference standard diagnosis. Summary estimates suggest that specificity is low, but results are based on a small number of studies at a high risk of bias. Based on current weak evidence, it is unlikely that SNRB is a cost-effective method for identifying the symptomatic nerve root prior to lumbar spine surgery. Future research should focus on randomised controlled trials to evaluate whether or not SNRB improves patient outcomes at acceptable cost. The National Institute for Health Research Health Technology Assessment programme.


Skinner A.L.,University of Bristol
Journal of vision | Year: 2012

Evidence suggests that underlying the human system processing facial expressions are two types of representation of expression: one dependent on identity and the other independent of identity. We recently presented findings indicating that identity-dependent representations are encoded using a prototype-referenced scheme, in a manner notably similar to that proposed for facial identity. Could it be that identity-independent representations are encoded this way too? We investigated this by adapting participant to anti-expressions and asking them to categorize the expression aftereffect in a prototype probe that was either the same (congruent) or different (incongruent) identity to that of the adapter. To distinguish between encoding schemes, we measured how aftereffect magnitude changed in response to variations in the strength of adapters. The increase in aftereffect magnitude with adapter strength characteristic of prototype-referenced encoding was observed in both congruent and, crucially, incongruent conditions. We conclude that identity-independent representations of expression are indeed encoded using a prototype-referenced scheme. The striking similarity between the encoding of facial identity and both representations of expression raises the possibility that prototype-referenced encoding might be a common scheme for encoding the many types of information in faces needed to enable our complex social interactions.


Jandt K.D.,Friedrich - Schiller University of Jena | Mills R.W.,University of Bristol
Dental Materials | Year: 2013

Objectives: The majority of modern resin-based oral restorative biomaterials are cured via photopolymerization processes. A variety of light sources are available for this light curing of dental materials, such as composites or fissure sealants. Quartz-tungsten-halogen (QTH) light curing units (LCUs) have dominated light curing of dental materials for decades and are now almost entirely replaced by modern light emitting diode light curing units (LED LCUs). Exactly 50 years ago, visible LEDs were invented. Nevertheless, it was not before the 1990s that LEDs were seriously considered by scientists or manufactures of commercial LCUs as light sources to photopolymerize dental composites and other dental materials. The objective of this review paper is to give an overview of the scientific development and state-of-the-art of LED photopolymerization of oral biomaterials. Methods: The materials science of LED LCU devices and dental materials photopolymerized with LED LCU, as well as advantages and limits of LED photopolymerization of oral biomaterials, are discussed. This is mainly based on a review of the most frequently cited scientific papers in international peer reviewed journals. The developments of commercial LED LCUs as well as aspects of their clinical use are considered in this review. Results: The development of LED LCUs has progressed in steps and was made possible by (i) the invention of visible light emitting diodes 50 years ago; (ii) the introduction of high brightness blue light emitting GaN LEDs in 1994; and (iii) the creation of the first blue LED LCUs for the photopolymerization of oral biomaterials. The proof of concept of LED LCUs had to be demonstrated by the satisfactory performance of resin based restorative dental materials photopolymerized by these devices, before LED photopolymerization was generally accepted. Hallmarks of LED LCUs include a unique light emission spectrum, high curing efficiency, long life, low energy consumption and compact device form factor. Significance: By understanding the physical principles of LEDs, the development of LED LCUs, their strengths and limitations and the specific benefits of LED photopolymerization will be better appreciated. © 2013 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.


Eming S.A.,University of Cologne | Martin P.,University of Bristol | Martin P.,University of Cardiff | Tomic-Canic M.,University of Miami
Science Translational Medicine | Year: 2014

The cellular and molecular mechanisms underpinning tissue repair and its failure to heal are still poorly understood, and current therapies are limited. Poor wound healing after trauma, surgery, acute illness, or chronic disease conditions affects millions of people worldwide each year and is the consequence of poorly regulated elements of the healthy tissue repair response, including inflammation, angiogenesis, matrix deposition, and cell recruitment. Failure of one or several of these cellular processes is generally linked to an underlying clinical condition, such as vascular disease, diabetes, or aging, which are all frequently associated with healing pathologies. The search for clinical strategies that might improve the body's natural repair mechanisms will need to be based on a thorough understanding of the basic biology of repair and regeneration. In this review, we highlight emerging concepts in tissue regeneration and repair, and provide some perspectives on how to translate current knowledge into viable clinical approaches for treating patients with wound-healing pathologies. © 2014, American Association for the Advancement of Science. All rights reserved.


Halestrap A.P.,University of Bristol
Cell Metabolism | Year: 2012

The mitochondrial pyruvate carrier (MPC) is essential for several major pathways of carbohydrate, fat, and amino acid metabolism, yet its molecular identity has remained elusive. Two recent papers in Science (Herzig et al., 2012; Bricker et al., 2012) implicate three newly identified inner mitochondrial membrane proteins as MPC components. © 2012 Elsevier Inc.


Wisnom M.R.,University of Bristol
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2012

The mechanisms by which delamination contributes to the failure of fibre-reinforced composites are reviewed. Through-thickness failure owing to interlaminar stresses is considered first, and the effect of delamination in impact and compression after impact. The way in which in-plane failure can occur by delamination and matrix cracks joining up to produce a fracture surface without the need to break fibres is considered next. Examples of quasi-isotropic laminates loaded at different off-axis angles, and with different numbers and thicknesses of ply blocks show large differences in unnotched tensile strength controlled by delamination from the free edge. Similar mechanisms determine the strength of notched specimens and give rise to the hole size effect, whereby tensile strength increases with decreasing hole diameter owing to increased delamination and splitting. Open hole tension and over-height compact tension tests with constant inplane dimensions show a transition in failure mode with increasing ply block thickness from fibre-dominated fracture to complete delamination. In all these cases, the critical factor controlling strength is the relative propensity to delaminate. This journal is © 2012 The Royal Society.


One unexpected property of selective serotonin reuptake inhibitors is their ability, at doses well below those that effect 5-HT systems, to raise brain concentrations of neuroactive steroids such as the progesterone metabolite allopregnanolone. In women, rapid withdrawal from allopregnanolone when progesterone secretion drops sharply in the late luteal phase precipitates menstrual cycle-linked disorders such as premenstrual syndrome and catamenial epilepsy. Short-term, low-dose fluoxetine during the late luteal phase has the potential to prevent the development of such disorders, by raising brain allopregnanolone concentration. In female rats, withdrawal from allopregnanolone, as ovarian progesterone secretion falls rapidly in the late diestrus phase (similar to late luteal phase in women), induces upregulation of extrasynaptic GABAA receptors on GABAergic neurons in brain regions involved in mediating anxiety-like behaviors. The functional consequence of this receptor plasticity is disinhibition of principal neurons, hyperexcitable neuronal circuitry and increased behavioral responsiveness to anxiogenic stress. These withdrawal responses were prevented by short-term treatment with fluoxetine during the late diestrus phase, which raised brain allopregnanolone concentration, so blunting the rapid physiological fall. The steroid-stimulating properties of fluoxetine offer untapped opportunities for developing new treatments for menstrual cycle-linked disorders in women, which are precipitated by abrupt falls in brain concentration of allopregnanolone. © The Author(s) 2013.


Thomson W.,University of Bristol
Journal of Stroke and Cerebrovascular Diseases | Year: 2014

Background This study examined clinically diagnosed depression as a risk factor for incidence of death by stroke in a prospective clinically based design study. Risk for stroke was examined separately by sex in a long-term follow-up study spanning 40 years. Methods Patients who were diagnosed with depression in the Chichester (population 100,000)/Salisbury (population 85,000) Catchment Area Study were followed up for 40 years. Death certificates were used to determine the cause of death in the cohort. Death rates in the general population, adjusted for age, gender, and year, were used as a control. Results Clinical depression was found to be a risk factor for subsequent death from stroke in men but not in women. Death by stroke was a statistically significant cause of death in the men with diagnoses of endogenous depression but not in those men diagnosed with reactive depression. The strength of the relationship of depression with stroke increased over time. Conclusions These findings suggest that the identification of depressive symptoms at younger ages may have an impact on the primary prevention of stroke in later life. The notion that depression has stronger effects over a long period is consistent with a view that severe clinical depression and physical illness occur concurrently, one exacerbating the other, and health is degraded through slow-acting, cumulative processes. Data were unavailable for the type of stroke or the health-risk behaviors (smoking, diet, and so forth) in the cohort which constituted a limitation of the study. Neither is it known what proportion of the cohort suffered a nonlethal stroke nor to what extent the treatment of clinical depression militates against suffering a lethal stroke. © 2014 by National Stroke Association.


Birchley G.,University of Bristol
Health Care Analysis | Year: 2014

In the western healthcare, shared decision making has become the orthodox approach to making healthcare choices as a way of promoting patient autonomy. Despite the fact that the autonomy paradigm is poorly suited to paediatric decision making, such an approach is enshrined in English common law. When reaching moral decisions, for instance when it is unclear whether treatment or non-treatment will serve a child's best interests, shared decision making is particularly questionable because agreement does not ensure moral validity. With reference to current common law and focusing on intensive care practice, this paper investigates what claims shared decision making may have to legitimacy in a paediatric intensive care setting. Drawing on key texts, I suggest these identify advantages to parents and clinicians but not to the child who is the subject of the decision. Without evidence that shared decision making increases the quality of the decision that is being made, it appears that a focus on the shared nature of a decision does not cohere with the principle that the best interests of the child should remain paramount. In the face of significant pressures toward the displacement of the child's interests in a shared decision, advantages of a shared decision to decisional quality require elucidation. Although a number of arguments of this nature may have potential, should no such advantages be demonstrable we have cause to revise our commitment to either shared decision making or the paramountcy of the child in these circumstances. © 2013 The Author(s).


Urry G.,University of Bristol
Transactions of the Institute of British Geographers | Year: 2014

This paper contributes to debates that consider the affective nature of immaterial labour practices upon the working subject. Drawing on call centre work as an example of immaterial labour - specifically in relation to Hardt and Negri's definitional typology - it explores a different way of theorising the subject in order to reconsider our sensory relation to the world. Going further than Hardt and Negri's attunement to our material engagement with the world, the paper uses Jean-Luc Nancy's conceptualisation of human subjectivity, apprehended as a motioning between pre-cognitive sensation and meaningful signification. Sense, for Nancy, is that which is felt non-consciously, thus creating a vital political space whereby the world itself becomes affectual aside from interpretation. Contrastingly, signification is that which makes meaningful, and hence adjusts the subject's relation in and to the world, transforming what is sensed into a representation. It is the motion between the two, for Nancy, that makes us alive beings-in-the-world but immaterial labour practices hinder this movement for capital gain, reducing possibilities for sensing while simultaneously overloading the being with signification. As such, this paper asks whether the call centre can have a stultifying affect upon the agent's capacity to 'live'. Furthermore, it asks how this dampening is resisted through subtle and vivacious tangents out of routine by those living the labour of the call centre. © 2013 The Author. Transactions of the Institute of British Geographers © 2013 Royal Geographical Society (with the Institute of British Geographers).


Binmore K.,University of Bristol
Journal of Evolutionary Biology | Year: 2010

This paper surveys the economic theory of bargaining with a view to applications in biology, using Roughgarden's recent Genial Gene as a case study in mistakes to be avoided. © 2010 The Author. Journal Compilation © 2010 European Society For Evolutionary Biology.


Background Developmental problems in children can be alleviated to a great extent with early detection and intervention through periodic screening for developmental delays during pre-school ages. Currently, there is no established system for developmental screening of children in Sri Lanka. Although some developmental norms, which are similar to those of Denver Developmental Screening Test-II (DDST-II), have been introduced into the Sri Lankan Child Health Developmental Record (CHDR), those norms have not been standardized to the Sri Lankan child population. The aim of this research was to establish Sri Lankan norms for DDST-II and to test the universal and regional applicability of developmental screening tests by comparing the Sri Lankan norms with the norms of DDST-II and DDST-Singapore norms, the geographically nearest standardization of DDST-II. The norms were also compared with the milestones already available in the CHDR. Methods DDST-II was adapted and standardized on a sample of 4251 Sri Lankan children aged 0-80 months. Thirteen public health nursing sisters were trained to collect the data as part of their routine work. The 25th, 50th, 75th and 90th percentile ages of acquiring each developmental milestone were then calculated using logistic regression. Results The Denver Developmental Screening Test for Sri Lankan Children (DDST-SL) was created. Most of the established DDST-SL norms were different to the comparable norms in DDST-II, DDST-Singapore and the CHDR. Conclusions In view of the results of the study, it is imperative that developmental screening tests are used in context and are adapted and standardized to the populations in question before utilization. © 2011 Blackwell Publishing Ltd.


Cullen P.J.,University of Bristol
Biochemical Society Transactions | Year: 2011

From the pioneering work of Mabel and Lowell Hokin in the 1950s, the biology of this specific isomer of hexahydroxycyclohexane and its phosphorylated derivatives, in the form of inositol phosphates and phosphoinositides, has expanded to fill virtually every corner of cell biology, whole-organism physiology and development. In the present paper, I give a personal view of the role played by phosphoinositides in regulating the function of the endosomal network, and, in so doing, highlight some of the basic properties through which phosphoinositides regulate cell function. ©The Authors Journal compilation ©2011 Biochemical Society.


Savery N.,University of Bristol
Transcription | Year: 2011

Transcription-coupled DNA repair pathways enable lesions that block transcription to be repaired more quickly than similar lesions in other parts of the genome. Here I consider the recent progress that has been made in understanding how bacteria prioritize certain lesions for nucleotide excision repair. © 2011 Landes Bioscience.


Murdock D.J.,University of Bristol
Proceedings. Biological sciences / The Royal Society | Year: 2013

The morphological disparity of conodont elements rivals the dentition of all other vertebrates, yet relatively little is known about their functional diversity. Nevertheless, conodonts are an invaluable resource for testing the generality of functional principles derived from vertebrate teeth, and for exploring convergence in a range of food-processing structures. In a few derived conodont taxa, occlusal patterns have been used to derive functional models. However, conodont elements commonly and primitively exhibit comparatively simple coniform morphologies, functional analysis of which has not progressed much beyond speculation based on analogy. We have generated high-resolution tomographic data for each morphotype of the coniform conodont Panderodus acostatus. Using virtual cross sections, it has been possible to characterize changes in physical properties associated with individual element morphology. Subtle changes in cross-sectional profile have profound implications for the functional performance of individual elements and the apparatus as a whole. This study has implications beyond the ecology of a single conodont taxon. It provides a basis for reinterpreting coniform conodont taxonomy (which is based heavily on cross-sectional profiles), in terms of functional performance and ecology, shedding new light on the conodont fossil record. This technique can also be applied to more derived conodont morphologies, as well as analogous dentitions in other vertebrates and invertebrates.


Fuchsbauer G.,University of Bristol
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2011

Verifiable encryption allows one to encrypt a signature while preserving its public verifiability. We introduce a new primitive called commuting signatures and verifiable encryption that extends this in multiple ways, such as enabling encryption of both signature and message while proving validity. More importantly, given a ciphertext, a signer can create a verifiably encrypted signature on the encrypted (unknown) message, which leads to the same result as first signing the message and then verifiably encrypting the message/signature pair; thus, signing and encrypting commute. Our instantiation is based on the recently introduced automorphic signatures and Groth-Sahai proofs, which we show to be homomorphic. We also prove a series of other properties and provide a novel approach to simulation. As an application, we give an instantiation of delegatable anonymous credentials, a primitive introduced by Belenkiy et al. Our construction is arguably simpler than theirs and it is the first to provide non-interactive (and thus concurrently secure) issuing and delegation protocols, which are significantly more efficient. Moreover, the size of our credentials and the cost of verification are less than half of those of the previous instantiation. All our constructions are proven secure in the standard model under known non-interactive assumptions. © 2011 International Association for Cryptologic Research.


Joinson C.,University of Bristol
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2013

Objective: To examine whether early menarche is associated with depressive symptoms from adolescence to young adulthood. Method: The study is based on 3,648 girls from a large UK birth cohort (Avon Longitudinal Study of Parents and Children) who provided data on age at onset of menarche and at least 1 measure of depressive symptoms assessed using the Short Mood and Feelings Questionnaire at ages 13, 14, 16.5, 18, and 19 years. Depressive symptoms were examined as binary outcomes (sum score ≥11) and continuous latent traits (using confirmatory factor analysis). Results were adjusted for socioeconomic disadvantage, paternal absence, and body mass index (BMI). Results: In early to midadolescence, there was strong evidence for increased odds of depressive symptoms in girls with early compared with late menarche. Differences remained after adjusting for confounders (adjusted odds ratio [OR] = 2.07, 95% confidence interval [CI] = 1.28-3.35 at 13 years; OR = 2.09, 95% CI = 1.41-3.09 at 14 years). At the later time points there was weak evidence for an association between early menarche and depressive symptoms in the unadjusted models. Adjusting for confounders explained a moderate amount of the effect (adjusted OR = 1.26, 95% CI = 0.86-1.85 at 16.5 years; OR = 1.33, 95% CI = 0.91-1.95 at 18 years; and OR = 1.40, 95% CI = 0.93-2.13 at 19 years). Findings were similar when we repeated the analysis using continuous depressive symptom latent traits. Conclusions: Girls who experience earlier menarche than their peers have increased levels of depressive symptoms in early to midadolescence, but there is little evidence for an effect of early menarche on depressive symptoms in later adolescence and young adulthood. © 2013 American Academy of Child and Adolescent Psychiatry.


Gray O.,University of Bristol
Communications in Mathematical Physics | Year: 2012

Aiming at a complete classification of unitary N = 2 minimal models (where the assumption of space-time supersymmetry has been dropped), it is shown that each modular invariant candidate partition function of such a theory is indeed the partition function of a fully-fledged unitary N = 2 minimal model, subject to the assumptions that orbifolding is a 'physical' process and that the space-time supersymmetric models are physical. A family of models constructed via orbifoldings of either the diagonal model or of the space-time supersymmetric exceptional models then demonstrates that there exists a unitary N = 2 minimal A-D-C model for every one of the allowed partition functions in the list obtained from Gannon's work (Gannon in Nucl Phys B 491:659-688, 1997). Kreuzer and Schellekens' conjecture (Nucl Phys B 411:97-121, 1994) that all simple current invariants can be obtained as orbifolds of the diagonal model, even when the extra assumption of higher-genus modular invariance is dropped, is confirmed in the case of the unitary N = 2 minimal models by simple counting arguments. © 2012 Springer-Verlag.


Trodden P.,University of Edinburgh | Richards A.,University of Bristol
Automatica | Year: 2013

This paper develops a cooperative, distributed form of MPC for linear systems subject to persistent, bounded disturbances. The distributed control agents make decisions locally and communicate plans with each other. Cooperation is promoted by consideration of a greater portion of the system-wide objective by each local agent; specifically, a local agent designs hypothetical plans for other agents, sacrificing local performance for the benefit of system-wide performance. These hypothetical plans are never communicated and no negotiation takes place. The method guarantees robust feasibility by permitting only one agent to optimize per time step, while 'freezing' the plans of others, and sufficient conditions are given for robust stability. These properties hold for all structures of cooperation between agents. Thus, a key feature is that coupled constraint satisfaction is compatible with inter-agent cooperation. © 2012 Elsevier Ltd. All rights reserved.


Day M.J.,University of Bristol
Parasites and Vectors | Year: 2011

The canine vector-borne infectious diseases (CVBDs) are an emerging problem in veterinary medicine and the zoonotic potential of many of these agents is a significant consideration for human health. The successful diagnosis, treatment and prevention of these infections is dependent upon firm understanding of the underlying immunopathology of the diseases in which there are unique tripartite interactions between the microorganism, the vector and the host immune system. Although significant advances have been made in the areas of molecular speciation and the epidemiology of these infections and their vectors, basic knowledge of the pathology and immunology of the diseases has lagged behind. This review summarizes recent studies of the pathology and host immune response in the major CVBDs (leishmaniosis, babesiosis, ehrlichiosis, hepatozoonosis, anaplasmosis, bartonellosis and borreliosis). The ultimate application of such immunological investigation is the development of effective vaccines. The current commercially available vaccines for canine leishmaniosis, babesiosis and borreliosis are reviewed. © 2011 Day; licensee BioMed Central Ltd.


Galobardes B.,University of Bristol
BMC Public Health | Year: 2012

In the last decades we have accumulated substantial knowledge about the risk factors that lead to cardiovascular disease. Despite this progress, in this issue of BMC Public Health we learn that little improvement has been made towards reducing inequalities in these risk factors in the UK. Characterizing changes over time can help understanding the mechanisms that underpin health inequalities. These pathways are complex and operate at different levels, from the individual to the context where someone lives. In this commentary I highlight some of the issues and uncertainties that may arise when individual and area level measures are used indistinctively. © 2012 Galobardes; licensee BioMed Central Ltd.


Mills H.L.,University of Bristol | Cohen T.,Boston Dynamics | Cohen T.,Brigham and Womens Hospital | Colijn C.,Imperial College London
Science Translational Medicine | Year: 2013

Tuberculosis (TB) control is especially difficult in settings of high HIV prevalence; HIV co-infection erodes host immunity and increases risk of progression to active TB. Studies have demonstrated that a 6-month (or longer) course of monotherapy with isoniazid [isoniazid preventive therapy (IPT)] can reduce this risk. The World Health Organization endorses IPT for symptom-free individuals with HIV/TB co-infection and has recommended expanding IPT to entire communities (community-wide IPT). Although previous reviews have not found a statistically significant elevated risk of isoniazid-resistant TB among individuals previously treated with IPT, community-wide IPT programs may nonetheless generate substantial selective pressure and increase the burden of drug-resistant TB (DRTB). We developed mathematical models to identify the conditions under which community-wide IPT interventions could increase the burden of isoniazid-resistant Mycobacterium tuberculosis, even when we assumed that IPT does not select for resistance among those treated with IPT. We found that in models that included any mechanism of interstrain competition (such as partial immunity conferred by a previous M. tuberculosis infection), communitywide IPT interventions conferred an indirect benefit to drug-resistant strains through selective suppression of drugsensitive infections. This result suggests that the absence of an observed elevation in the risk of DRTB among those receiving IPT in small-scale studies of limited duration does not imply that the selective pressure imposed by community-wide IPT will not be substantial. Community-wide IPT may play an important role in TB control in these settings, and its rollout should be accompanied by interventions to detect and treat drug-resistant disease. Copyright 2013 by the American Association for the Advancement of Science; all rights reserved.


Lovick T.A.,University of Bristol
Neuroscience and Biobehavioral Reviews | Year: 2014

Panic disorder is twice a common in women than in men. In women, susceptibility to panic increases during the late luteal (premenstrual) phase of the menstrual cycle, when progesterone secretion is in rapid decline. This article considers the evidence for the midbrain periaqueductal grey (PAG) as a locus for panic and for the use of PAG stimulation as an animal model of panic in both sexes. We show in females how a rapid fall in progesterone secretion, such as occurs during the late dioestrus phase of the ovarian cycle in rats (similar to the late luteal phase in women), triggers a neuronal withdrawal response during which the excitability of the midbrain panic circuitry increases as a result of upregulation of extrasynaptic GABAA receptors on inhibitory interneurones in the PAG. The withdrawal effect is due not to the native hormone but to its neuroactive metabolite allopregnanolone. Differences in the kinetics of allopregnanolone metabolism may contribute to individual differences in susceptibility to panic in women. © 2014 Elsevier Ltd.


Cipriani A.,University of Verona | Higgins J.P.T.,University of Bristol | Geddes J.R.,University of Oxford | Salanti G.,University of Ioannina
Annals of Internal Medicine | Year: 2013

The increase in treatment options creates an urgent need for comparative effectiveness research. Randomized, controlled trials comparing several treatments are usually not feasible, so other methodological approaches are needed. Meta-analyses provide summary estimates of treatment effects by combining data from many studies. However, an important drawback is that standard metaanalyses can compare only 2 interventions at a time. A new metaanalytic technique, called network meta-analysis (or multiple treatments meta-analysis or mixed-treatment comparison), allows assessment of the relative effectiveness of several interventions, synthesizing evidence across a network of randomized trials. Despite the growing prevalence and influence of network metaanalysis in many fields of medicine, several issues need to be addressed when constructing one to avoid conclusions that are inaccurate, invalid, or not clearly justified. This article explores the scope and limitations of network meta-analysis and offers advice on dealing with heterogeneity, inconsistency, and potential sources of bias in the available evidence to increase awareness among physicians about some of the challenges in interpretation.


Dettmann C.P.,University of Bristol
Journal of Statistical Physics | Year: 2012

The Lorentz gas is a billiard model involving a point particle diffusing deterministically in a periodic array of convex scatterers. In the two dimensional finite horizon case, in which all trajectories involve collisions with the scatterers, displacements scaled by the usual diffusive factor √t are normally distributed, as shown by Bunimovich and Sinai in 1981. In the infinite horizon case, motion is superdiffusive, however the normal distribution is recovered when scaling by √ t in t, with an explicit formula for its variance. Here we explore the infinite horizon case in arbitrary dimensions, giving explicit formulas for the mean square displacement, arguing that it differs from the variance of the limiting distribution, making connections with the Riemann Hypothesis in the small scatterer limit, and providing evidence for a critical dimension d=6 beyond which correlation decay exhibits fractional powers. The results are conditional on a number of conjectures, and are corroborated by numerical simulations in up to ten dimensions. © 2011 Springer Science+Business Media, LLC.


Grose J.,University of Bristol
Biology and Philosophy | Year: 2011

The story of the fall and rise of Zahavi's handicap principle is one of a battle between models. Early attempts at formal modeling produced negative results and, unsurprisingly, scepticism about the principle. A major change came in 1990 with Grafen's production of coherent models of a handicap mechanism of honest signalling. This paper's first claim is that acceptance of the principle, and its dissemination into other disciplines, has been driven principally by that, and subsequent modeling, rather than by empirical results. Secondly, there is a vast literature on biological signalling but few studies that make all of the observations necessary to diagnose the handicap mechanism. My final claim is that many of the applications of "costly signalling theory" in other disciplines are conceptually confused. Misinterpretations of what is meant by "costly signalling" are common. Demonstrating that a signal is costly is insufficient and is not always necessary in order to prove that, and explain why, a signal is honest. In addition to the biological modelling of signals, there is an economic literature on the same subject. The two run in parallel in the sense that they have had little mutual interaction. Additionally, it is the biological modelling that has been picked up, and often misapplied, by other disciplines. © 2011 Springer Science+Business Media B.V.


Chitty D.M.,University of Bristol
Soft Computing | Year: 2012

Genetic Programming (GP) is a computationally intensive technique which is also highly parallel in nature. In recent years, significant performance improvements have been achieved over a standard GP CPU-based approach by harnessing the parallel computational power of many-core graphics cards which have hundreds of processing cores. This enables both fitness cases and candidate solutions to be evaluated in parallel. However, this paper will demonstrate that by fully exploiting a multi-core CPU, similar performance gains can also be achieved. This paper will present a new GP model which demonstrates greater efficiency whilst also exploiting the cache memory. Furthermore, the model presented in this paper will utilise Streaming SIMD Extensions to gain further performance improvements. A parallel version of the GP model is also presented which optimises multiple thread execution and cache memory. The results presented will demonstrate that a multi-core CPU implementation of GP can yield performance levels that match and exceed those of the latest graphics card implementations of GP. Indeed, a performance gain of up to 420-fold over standard GP is demonstrated and a threefold gain over a graphics card implementation. © 2012 Springer-Verlag.


When constructing its responses to cases concerning the treatment and non-treatment of patients, both competent and incompetent, English medical law primarily uses two analytic tools: the autonomy and the welfare (or best interests) of the patient. I argue, however, that the construction going on behind the facade involves the use of more- and more precise-tools. In such cases, the law effectively asks three questions. The first, autonomy, question asks: is the proposed c