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Leeds, United Kingdom

The University of Leeds is a British Redbrick university located in the city of Leeds, West Yorkshire, England. Wikipedia.


Latchford G.,University of Leeds | Duff A.J.A.,Leeds Teaching Hospitals NHS Trust
Journal of Cystic Fibrosis | Year: 2013

Introduction: The International Depression and Anxiety Epidemiological Study (TIDES) in CF attempts to provide prevalence data for mental distress in CF patients. The current study reports the results from the UK pilot in a single major CF centre in which the performances of different instruments were compared, and risk of self harm measured. Methods: Two mental health assessment screening instruments, the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire for depression (PHQ-9) were given to all adults with CF attending the Regional Adult CF Unit in Leeds, UK. Results: 232 patients took part. 13 (5.6%) scored in the clinical range for depression on the HADS and 78 (33.4%) on the PHQ9. The suicide risk item on the PHQ9 was endorsed by 24 patients (10.4%). Discussion: Major discrepancies were found in rates of depression detected by two popular screening tools. A significant minority of respondents indicated suicidal ideation. Work is needed to identify the most appropriate screening tool for depression in this population, and it is important that this includes an assessment of self harm. © 2013 European Cystic Fibrosis Society.


Emery P.,University of Leeds | Emery P.,NIHR Leeds Musculoskeletal Biomedical Research Unit | Dorner T.,Charite - Medical University of Berlin
Annals of the Rheumatic Diseases | Year: 2011

Following a greater understanding of the pathogenesis of rheumatoid arthritis (RA), the treatment of this chronic disease has improved with the availability of biological agents targeting key molecules. Despite this, initial treatment produces an inadequate response in many patients and guidance on the optimal treatment for these patients is needed. Research in specific patient populations aims to define predictive biomarkers of response to identify those patients most likely to benefit from treatment with specific agents. Although there have been conflicting results from studies of various genetic markers, single nucleotide polymorphisms in the tumour necrosis factor (TNF) -308 promoter region may play a role in response to specific TNF inhibitors. Microarray analysis of mRNA expression levels has identified unique sets of genes with differentially regulated expression in responders compared with non-responders to the TNF inhibitor infliximab. Of the various protein biomarkers studied, rheumatoid factor and/or anticitrullinated protein autoantibodies may have a future role in predicting response or guiding the order in which to use biological agents. Further research is needed with larger, well-designed studies to clarify the current understanding on the role of biomarkers in predicting treatment response in RA to help guide clinical decision-making. Individualised treatment has the potential to improve the therapeutic outcomes for patients.


Shave R.,Cardiff Metropolitan University | Oxborough D.,University of Leeds
Progress in Cardiovascular Diseases | Year: 2012

Prolonged endurance exercise in humans has been associated with an acute impairment in diastolic and systolic cardiac function and the release of cardiac troponin. In this chapter, we review recent evidence from studies using novel echocardiographic parameters and highly sensitive cardiac troponin assays. We demonstrate that the mechanics of left and right ventricular functions are acutely impaired after completion of prolonged exercise and that this reduction in function is likely multifactorial in etiology. However, we highlight that exercise-induced cardiac troponin release is not a marker of exercise-induced pathology but likely a physiologic response to exercise. Finally, we discuss the potential link between prolonged exercise and the increased incidence of cardiac pathology in veteran athletes. © 2012 Elsevier Inc..


Knippertz P.,University of Leeds | Wernli H.,ETH Zurich | Glaser G.,Johannes Gutenberg University Mainz
Journal of Climate | Year: 2013

In a recent paper, a climatology of tropical moisture exports (TMEs) to the Northern Hemisphere (NH) was constructed on the basis of 7-day forward trajectories, started daily from the tropical lower troposphere, which were required to reach a water vapor flux of at least 100 g kg-1 m s-1 somewhere north of 35°N. It was shown that TMEs contribute significantly to regional precipitation. Here, the authors complement and extend this work by (i) using 6-hourly European Centre for Medium-Range Weather Forecasts (ECMWF) Interim Re-Analysis (ERA-Interim) data from 1979 to 2010 instead of the earlier 40-yr ECMWFRe-Analysis (ERA-40), (ii) extending the climatology to the Southern Hemisphere (SH), and (iii) relating TME events to atmospheric rivers (ARs) previously discussed in the literature. The main conclusions are as follows: First, the TME climatology is not sensitive to the reanalysis dataset. Second, SH TME shows four activity centers: the central and eastern Pacific Ocean (170°-90°W, near the South Pacific convergence zone), eastern South America and the adjacent Atlantic Ocean (60°W-0°, near the South Atlantic convergence zone), the western Indian Ocean (30°-80°E), and western Australia (110°-140°E). Third, TME activity in the SH peaks in austral summer because of higher moisture contents and possibly because of increased Rossby wave activity from the NH. Fourth, El Niño warm events are associated with reduced activity over the South Pacific and increased activity over the South Atlantic and around Australia, while correlations with the southern annular mode are generally weak. Finally, around 90% of all ARs affecting the U.S. West Coast during December-May are connected to TME events, revealing their importance for heavy rain and flooding. © 2013 American Meteorological Society.


Zhou D.,University of Leeds
Biochemical Society Transactions | Year: 2012

Over the last 10 years, fluorescent semiconductor QD (quantum dot)-biomolecule conjugates have emerged as a powerful new sensing platform showing great potential in a wide range of applications in biosensing, environmental monitoring and disease diagnosis. The present mini-review is a brief account of the recent developments in QD-NA (nucleic acid), particularly NA aptamer, conjugate-based biosensors using the FRET (Förster resonance energy transfer) readout mechanism. It starts with a brief introduction to the NA aptamer and QD-FRET, followed by example approaches to compact QD-DNA conjugates, target readout strategies and sensing performance, and concludes with challenges and outlook for the QD-NA/aptamer bioconjugate sensors. ©The Authors Journal compilation ©2012 Biochemical Society.


Wadud Z.,University of Leeds
Transportation Research Part A: Policy and Practice | Year: 2014

Forecasts of passenger demand are an important parameter for aviation planners. Air transport demand models typically assume a perfectly reversible impact of the demand drivers. However, there are reasons to believe that the impacts of some of the demand drivers such as fuel price or income on air transport demand may not be perfectly reversible. Two types of imperfect reversibility, namely asymmetry and hysteresis, are possible. Asymmetry refers to the differences in the demand impacts of a rising price or income from that of a falling price or income. Hysteresis refers to the dependence of the impacts of changing price or income on previous history, especially on previous maximum price or income. We use US time series data and decompose each of fuel price and income into three component series to develop an econometric model for air transport demand that is capable of capturing the potential imperfectly reversible relationships and test for the presence or absence of reversibility. We find statistical evidence of asymmetry and hysteresis - for both, prices and income - in air transport demand. Implications for policy and practice are then discussed. © 2014 Elsevier Ltd.


Tobias S.M.,University of Leeds | Marston J.B.,Brown University
Physical Review Letters | Year: 2013

We present direct statistical simulation of jet formation on a β plane, solving for the statistics of a fluid flow via an expansion in cumulants. Here we compare an expansion truncated at second order (CE2) to statistics accumulated by direct numerical simulations. We show that, for jets near equilibrium, CE2 is capable of reproducing the jet structure (although some differences remain in the second cumulant). However, as the degree of departure from equilibrium is increased (as measured by the zonostrophy parameter), the jets meander more and CE2 becomes less accurate. We discuss a possible remedy by inclusion of higher cumulants. © 2013 American Physical Society.


Ngoduy D.,University of Leeds
Nonlinear Dynamics | Year: 2014

The effect of delay or reaction time on traffic flow dynamics has been investigated widely in the literature using microscopic traffic models. Recent studies using second-order Payne-type models have shown analytically that, on a macroscopic scale, time delay does not contribute to whether traffic instabilities occur. This paper will attempt to show that it all depends on the (macroscopic) model used for the analysis that delay does have effect on traffic instabilities or not. To this end, we will formulate a generalized (linear) stability condition for a second-order macroscopic model with delay and investigate analytically the effect of such delay on traffic instabilities in some specific macroscopic models. It is found that the choice of the equilibrium speed function in a (second order) macroscopic model will determine how delay affects such (linear) stability condition © 2014 Springer Science+Business Media Dordrecht.


Archer A.J.,Loughborough University | Rucklidge A.M.,University of Leeds | Knobloch E.,University of California at Berkeley
Physical Review Letters | Year: 2013

A two-dimensional system of soft particles interacting via a two-length-scale potential is studied. Density functional theory and Brownian dynamics simulations reveal a fluid phase and two crystalline phases with different lattice spacing. Of these the larger lattice spacing phase can form an exotic periodic state with a fraction of highly mobile particles: a crystal liquid. Near the transition between this phase and the smaller lattice spacing phase, quasicrystalline structures may be created by a competition between linear instability at one scale and nonlinear selection of the other. © 2013 American Physical Society.


Ngoduy D.,University of Leeds
Computer-Aided Civil and Infrastructure Engineering | Year: 2011

Real time traffic flow simulation models are used to provide traffic information for dynamic traffic management systems. Those simulation models are supplied by traffic data in order to estimate and predict traffic conditions in unobserved sections of a traffic network. In general, most of recent real time traffic simulators are based on the macroscopic model because the macroscopic model replicates the average traffic behavior in terms of observable variables such as (time-space) flow and speed at a relatively fast computational time. Like other simulation models, an important aspect of the real time macroscopic simulator is to calibrate the model parameters online. The most conventional way of the online calibration is to add a random walk to the parameters to constitute an augmentation of the traffic variables and the model parameters to be estimated. Actually, this method allows the parameters to vary at every time step and, therefore, describes the adaptation of the model to the prevailing traffic conditions. However, it has been reported that the use of the random walk results in a loss of information and an increase of the covariance of parameters, which consequently leads to posteriors that are far more diffuse than the theoretical posteriors for the true parameters. To this end, this article puts forward a Kernel density estimation technique in the calibration process to handle the covariance issue and to avoid the information loss. The Kernel density estimation technique is embedded in the particle filter algorithm, which is extended to the calibration problems. The proposed framework is investigated using real-life data collected in a freeway in England. © 2010 Computer-Aided Civil and Infrastructure Engineering.


Hillas A.M.,University of Leeds
Astroparticle Physics | Year: 2013

Most of what we know of cosmic gamma rays has come from spacecraft, but at energies above tens of GeV it has become possible to make observations with ground-based detectors of enormously greater collecting area. In recent years one such detector type, the cluster of imaging air Cherenkov telescopes, has reached a very productive state, whilst several alternative approaches have been explored, including converted solar power collectors and novel high-altitude particle shower detectors which promised to extend the energy range covered. Key examples of development from 1952 to 2011 are followed, noting the problems and discoveries that stimulated the current work, explaining the logic of the alternative approaches that were taken. The merits of the current major Cherenkov observatories and of other viable detectors are examined and compared, with examples of the astrophysical information they are beginning to provide. The detectors are still evolving, as we still do not understand the processes onto which the gamma rays provide a window. These include the acceleration of Galactic cosmic rays (in particular, the wide-band spectra of radiation from some individual supernova remnants are still hard to interpret), the highly relativistic and variable jets from active galactic nuclei, and aspects of the electrodynamics of pulsars. Larger groups of Cherenkov telescopes still offer the possibility of an increase in power of the technique for resolvable Galactic sources especially. © 2012 Published by Elsevier B.V.


Rosindell J.,University of Leeds | Rosindell J.,University of Idaho | Phillimore A.B.,Imperial College London
Ecology Letters | Year: 2011

Islands acquire species through immigration and speciation. Models of island biogeography should capture both processes; however quantitative island biogeography theory has either neglected speciation or treated it unrealistically. We introduce a model where the dominance of immigration on small and near islands gives way to an increasing role for speciation as island area and isolation increase. We examine the contribution of immigration and speciation to the avifauna of 35 archipelagoes and find, consistent with our model, that the zone of radiation comprises two regions: endemic species diverged from mainland sister-species at intermediate isolation and from insular sister-species at higher levels of isolation. Our model also predicts species-area curves in accord with existing research and makes new predictions about species ages and abundances. We argue that a paucity of data and theory on species abundances on isolated islands highlights the need for island biogeography to be reconnected with mainstream ecology. © 2011 Blackwell Publishing Ltd/CNRS.


Wareing C.J.,University of Leeds
Astrophysical Journal Letters | Year: 2012

Galaxy Evolution Explorer observations of the Mira AB binary system revealed a surrounding structure that has been successfully hydrodynamically interpreted as a bow shock and tail of ram-pressure-stripped material. Even the narrow tail, initially difficult to model, has been understood to be the effect of the passage of Mira from a warm neutral medium into a hot, low-density medium, postulated to be the Local Bubble. However, no model to date has explained the observed kink and associated general curvature of the tail. We test the hypothesis that before entering the Local Bubble, Mira was traveling through a shear flow with approximately 1/3 Mira's own velocity at an angle of 30°to Mira's proper motion. The hypothesis reproduces the kinked nature of Mira's tail and predicts recompression and reheating of the tail material to the same or greater levels of density and temperature predicted in the shock. This provides a heat source for the FUV emission, allowing for an extended lifetime of the FUV emission in line with other estimates of the age of the tail. The uniqueness of Mira's situation implies that the chances of observing other FUV tails behind asymptotic giant branch stars are highly unlikely. © 2012. The American Astronomical Society. All rights reserved..


Komissarov S.S.,University of Leeds
Monthly Notices of the Royal Astronomical Society | Year: 2012

The idea that cosmic relativistic jets are magnetically driven Poynting-dominated flows has many attractive features but also some problems. One of them is the low efficiency of shock dissipation in highly magnetized plasma. Indeed, the observations of gamma-ray bursts (GRBs) and their afterglow emission indicate very high radiative efficiency of relativistic jets associated with these phenomena. We have revisited the issue of shock dissipation and emission and its implications for the internal shock model of the prompt GRB emission and studied it in the context of impulsive Poynting-dominated flows. Our results show that unless the magnetization of GRB jets is extremely high, σ > 100 in the prompt emission zone, the magnetic model may still be compatible with the observations. First, for σ≃ 1 the dissipation efficiency of fast magnetosonic shock is still quite high, ∼30 percent. Secondly, the main effect of reduced dissipation efficiency is merely an increase in the size of the dissipation zone, and even for highly magnetized GRB jets, this size may remain below the external shock radius, provided the central engine can emit magnetic shells on the time-scale well below the typical observed variability scale of 1s. Our analytical and numerical results suggest that strong interaction between shells begins not during the coasting phase but well before it. As the result, the impulsive jet in the dissipation zone is best described not as a collection of shells but as a continuous highly magnetized flow with a high amplitude magnetosonic wave component. How exactly the dissipated wave energy is distributed between the radiation and the bulk kinetic energy of radial jets depends on the relative rates of radiative and adiabatic cooling. In the fast radiative cooling regime, the corresponding radiative efficiency can be as high as the wave contribution to their energy budget, independently of the magnetization. Moreover, after leaving the zone of prompt emission, the jet may still remain Poynting dominated, leading to weaker emission from the reverse shock compared to non-magnetic models. Energetically subdominant weakly magnetized 'clouds' in otherwise strongly magnetized jets may significantly increase the overall efficiency of the shock dissipation. © 2012 The Author Monthly Notices of the Royal Astronomical Society © 2012 RAS.


Guo Z.,CAS Institute of Geology and Geophysics | Wilson M.,University of Leeds
Gondwana Research | Year: 2012

Late Oligocene-Miocene leucogranites within southern Tibet form part of an extensive intrusive igneous province within the Himalayan orogen. The main rock types are tourmaline leucogranites (Tg) and two-mica leucogranites (2mg). They have high SiO 2 (70.56-75.32wt.%), Al 2O 3 (13.55-15.67wt.%) and ( 87Sr/ 86Sr) i (0.724001-0.797297), and low MgO (0.02-0.46wt.%) and ( 143Nd/ 144Nd) i (0.511693-0.511906). Chondrite-normalized rare earth element (REE) patterns display strong negative Eu anomalies. Whole-rock major and trace element and Sr-Nd isotope data for the leucogranites suggest that their source region was a two-component mixture between a fluid derived from the Lesser Himalayan (LH) crustal sequence and the bulk crust of the Higher Himalayan (HH) sequence. Trace element and Sr-Nd isotope modeling indicate that the proportion of fluid derived from the LH sequence varied from 2% to 19% and the resulting metasomatised source experienced 7-16% melting. The amount of fluid derived from the LH sequence increases from north to south. Northward underthrusting of the Indian continent resulted in infiltration of the LH-derived fluid into the overlying HH sequence. Subsequent decompression melting of this metasomatised crust, mostly during the Miocene (25-9Ma), generated the leucogranites. This may be linked to steepening of the subducted slab of Indian lithosphere beneath the orogenic belt. © 2011 International Association for Gondwana Research.


Harvey R.D.,University of Nevada, Reno | Calaghan S.C.,University of Leeds
Journal of Molecular and Cellular Cardiology | Year: 2012

Compartmentation of signalling allows multiple stimuli to achieve diverse cellular responses with only a limited pool of second messengers. This spatial control of signalling is achieved, in part, by cellular structures which bring together elements of a particular cascade. One such structure is the caveola, a flask-shaped lipid raft. Caveolae are well-recognised as signalosomes, platforms for assembly of signalling complexes of receptors, effectors and their targets, which can facilitate efficient and specific cellular responses. Here we extend this simple model and present evidence to show how the protein and lipid profiles of caveolae, as well as their characteristic morphology, define their roles in creating local signalling domains in the cardiac myocyte. This article is part of a Special Issue entitled "Local Signaling in Myocytes.". © 2011 Elsevier Ltd.


Lorger M.,University of Leeds
Cancers | Year: 2012

In addition to malignant cancer cells, tumors contain a variety of different stromal cells that constitute the tumor microenvironment. Some of these cell types provide crucial support for tumor growth, while others have been suggested to actually inhibit tumor progression. The composition of tumor microenvironment varies depending on the tumor site. The brain in particular consists of numerous specialized cell types such as microglia, astrocytes, and brain endothelial cells. In addition to these brain-resident cells, primary and metastatic brain tumors have also been shown to be infiltrated by different populations of bone marrow-derived cells. The role of different cell types that constitute tumor microenvironment in the progression of brain malignancies is only poorly understood. Tumor microenvironment has been shown to be a promising therapeutic target and diagnostic marker in extracranial malignancies. A better understanding of tumor microenvironment in the brain would therefore be expected to contribute to the development of improved therapies for brain tumors that are urgently required due to a poor availability of treatments for these malignancies. This review summarizes some of the known interactions between brain tumors and different stromal cells, and also discusses potential therapeutic approaches within this context. © 2012 by the authors; licensee MDPI, Basel, Switzerland.


Jones C.A.,University of Leeds
Annual Review of Fluid Mechanics | Year: 2011

The magnetic fields of the planets, including the Earth, are generated by dynamo action in their fluid cores. Numerical models of this process have been developed that solve the fundamental magnetohydrodynamic equations driven by convection in a rotating spherical shell. New results from these theoretical models are compared with observations of the geomagnetic field and magnetic data gathered from space missions. The mechanism by which a magnetic field is created is examined. The effects of rotation and magnetic field on the convection are of paramount importance in the simulations. A wide range of simulations with different convection models, varying boundary conditions, and parameter values have been performed over the past 10 years. The effects of these differences are assessed. Numerical considerations mean that all dynamo simulations use much enhanced values of the diffusivities. We consider to what extent this affects results and show how the asymptotic behavior at low diffusion is starting to be inferred using scaling laws. The results of specific models relating to individual planets are reviewed. © 2011 by Annual Reviews. All rights reserved.


Liaquat M.,University of Leeds
Journal of Molecular Catalysis B: Enzymatic | Year: 2011

(Z)-3-hexen-1-yl esters are important green top-note components of food flavors and fragrances. Effects of various process conditions on (Z)-3-hexen-1-yl caproate synthesis employing germinated rapeseed lipase acetone powder in organic solvent were investigated. Rapeseed lipase catalyzed ester formation more efficiently with non-polar compared to polar solvents despite high enzyme stability in both types of solvents. Maximum ester yield (90%) was obtained when 0.125 M (Z)-3-hexen-1-ol and caproic acid were reacted at 25 °C for 48 h in the presence of 50 g/L enzyme in heptane. Enzyme showed little sensitivity towards aw with optimum yield at 0.45, while added water did not affect ester yield. Esterification reduced by increasing molecular sieves (>0.0125%, w/v). The highest yields of caproic acid were obtained with isoamyl alcohol (93%) followed by butanol and (Z)-3-hexen-1-o1 (88%) respectively reflecting the enzyme specificity for straight and branched chain alcohols. Secondary alcohols showed low reactivity, while tertiary alcohol had either very low reactivity or not esterified at all. A good relationship has been found between ester synthesis and the solvent polarity (log P value); while no correlation for the effect of solvents on residual enzyme activity was observed. It may be concluded that germinated rapeseed lipase is a promising biocatalyst for the synthesis of valuable green flavor note compound. The enzyme also showed a wide range of temperature stability (5-50 °C). © 2010 Elsevier B.V. All rights reserved.


Jiang L.-H.,University of Leeds
Cell Health and Cytoskeleton | Year: 2012

Purinergic P2X receptors are plasma membrane proteins present in a wide range of mammalian cells where they act as a cellular sensor, enabling cells to detect and respond to extracellular adenosine triphosphate (ATP), an important signaling molecule. P2X receptors function as ligand-gated Ca2+-permeable cationic channels that open upon ATP binding to elevate intracellular Ca2+ concentrations and cause membrane depolarization. In response to sustained activation, P2X receptors induce formation of a pore permeable to large molecules. P2X receptors also interact with distinct functional proteins and membrane lipids to form specialized signaling complexes. Studies have provided compelling evidence to show that such P2X receptor-mediated ATP-signaling mechanisms determine and regulate a growing number and diversity of important physiological processes, including neurotransmission, muscle contraction, and cytokine release. There is accumulating evidence to support strong causative relationships of altered receptor expression and function with chronic pain, inflammatory diseases, cancers, and other pathologies or diseases. Numerous high throughput screening drug discovery programs and preclinical studies have thus far demonstrated the proof of concepts that the P2X receptors are druggable targets and selective receptor antagonism is a promising therapeutics approach. This review will discuss the recent progress in understanding the mammalian P2X receptors with respect to the ATP-signaling mechanisms, physiological and pathophysiological roles, and development and preclinical studies of receptor antagonists. © 2012 Jiang, publisher and licensee Dove Medical Press Ltd.


Dickinson E.,University of Leeds
Journal of Colloid and Interface Science | Year: 2011

The heteroaggregation behaviour of mixtures of equal-sized particles (type A+type B) exhibiting short-ranged attractive interactions is investigated using the sticky hard-sphere model. The average cluster size is calculated as a function of the total particle volume fraction, the binary mixture composition, and the A-B stickiness interaction parameter τAB-1. We show that a value of τAB-1=102, equivalent to an attractive well depth of ∼5kT in a realistic continuous pair potential, leads to a state of heteroaggregation just below the gelation threshold of the equimolar mixture of volume fraction 0.1. We discuss the conditions under which the assumptions of this statistical thermodynamic model are satisfied experimentally, with particular reference to recent data on the heteroaggregation behaviour of protein-stabilized emulsions and latex particle dispersions. © 2011 Elsevier Inc.


Wyatt H.V.,University of Leeds
OIE Revue Scientifique et Technique | Year: 2013

The disease we now know as brucellosis was first discovered in the 1850s in Malta. It came to the attention of British medical officers serving on the island after the Crimean War. It was easy to eliminate the disease in British servicemen, but very difficult to reach Maltese citizens. Over the decades, more and more Maltese were infected as the control measures introduced were half-hearted and were often not even enforced. The work of DrThemistocles Zammit showed that infected goats transmitted brucellosis and that banning use of their milk would be effective. Pasteurisation was not introduced onto the island until the 1930s, when the production of cheap, small sterile containers became possible. Transmission was also possible through sexual contact and by inhalation when people were crowded in hot airless conditions. Success in controlling the disease requires sensible, strict control of animals and the elimination of infected ones, but will fail without an educated public willing to help. In Malta, failure to control rogue flocks and small flocks kept for family use led to an epidemic caused by the sale of cheeselets (small cheeses). In 2005, nearly a century after Zammit's discovery, Malta was finally free of brucellosis.


Hoppe R.,University of Twente | Wesselink A.,University of Leeds | Cairns R.,University of Sussex
Wiley Interdisciplinary Reviews: Climate Change | Year: 2013

In this article, we explore how climate change science is connected to climate change governance. When formally institutionalized, as in Intergovernmental Panel on Climate Change (IPCC) or UN Framework Convention on Climate Change (UNFCCC), these sites may be referred to as boundary organizations. These institutions engage not only in the quality assessment of scientific research, but also in the design of innovative policy instruments, or evaluation of policy impacts-activities that we refer to as boundary work. Boundary work is inherently 'tricky business'. Science and politics are normally demarcated spheres with different sacred stories. Scientists aspire to 'speak truth to power', while policymakers want 'politics on top and science on tap'. Boundary work endeavors to coordinate these apparently incompatible aspirations. In this article, we describe, analyze, and assess whether, to what extent, and how the major international and some national boundary organizations in climate change governance have been able to avoid over-politicization and over-scientization. We demonstrate that the nature and success of boundary organizations and the ways they work depend on: (1) the degree to which the climate change problem is defined as 'wicked' or unstructured, or as (relatively) 'tame' and structured; (2) the stage of the policy process; and (3) characteristics of the policy network and the socio-political context: the degree to which relevant players insist on strict separation and a linear relation from science to politics, or, alternatively, are tolerant of a blurring of the boundaries and hence a two-way, coproductive relation between science and politics. Anna Wesselink's contribution to this article was financially supported by the European Union (European Commission, European Reintegration Grant PERG08-GA-2010-276934). WIREs Clim Change 2013, 4:283-300. doi: 10.1002/wcc.225 Conflict of interest: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. © 2013 John Wiley & Sons, Ltd.


Lovell R.M.,St Jamess Hospital | Ford A.C.,St Jamess Hospital | Ford A.C.,University of Leeds
American Journal of Gastroenterology | Year: 2012

OBJECTIVES:Irritable bowel syndrome (IBS) is thought to be commoner in women. However, no systematic review has confirmed whether this is the case, or assessed whether any proposed female preponderance remains stable according to geography and criteria used to define IBS. Nor has effect of gender on subtype of IBS been examined systematically.METHODS:MEDLINE, EMBASE, and EMBASE Classic were searched (up to October 2011) to identify population-based studies reporting prevalence of IBS in adults (15 years) according to gender, and defined using symptom-based criteria, or questionnaire. The prevalence of IBS in women and men was extracted for all studies, and according to study location and diagnostic criteria used, and compared using odds ratios (ORs) with 95% confidence intervals (CIs). Prevalence of each subtype of IBS, according to predominant stool pattern, was compared in women and men with IBS.RESULTS:Of the 390 papers evaluated, 56 studies containing 188,229 subjects were eligible. The OR for IBS in women, compared with men, in all studies was 1.67 (95% CI: 1.53-1.82). Prevalence of IBS was not significantly higher in women, compared with men, in South Asian, South American, or African studies. The OR was highest with the Rome I criteria (1.99; 95% CI: 1.76-2.25), and lowest with the Rome II criteria (1.40; 95% CI: 1.24-1.59). Women with IBS were more likely to exhibit the constipation-predominant subtype (OR: 2.38; 95% CI: 1.45-3.92), and less likely to meet criteria for the diarrhea-predominant subtype (OR: 0.45; 95% CI: 0.32-0.65) than men with IBS.CONCLUSIONS:Prevalence of IBS appeared modestly higher in women, and this remained relatively stable according to geography and criteria used to define its presence. However, among individuals with IBS, subtypes varied according to gender.


Povey M.J.W.,University of Leeds
Food Hydrocolloids | Year: 2014

Crystal nucleation in food colloids is considered in the light of recent developments in classical nucleation theory (CNT); it is shown that CNT remains a sound basis upon which to understand nucleation in colloids and in particular nucleation in lipids such as triacylglycerols. Computation of the energy barrier to nucleation for a studied triacylglycerol system (Cocoa butter oil-in-water emulsion) indicates that whilst homogeneous nucleation is unlikely at higher surface energies the addition of surfactant, lowering the interfacial energy may have a dramatic impact on surface nucleation rates. Data is included supporting this contention. The impact of reducing the size of colloidal particles to the point where the interfacial region occupies a significant proportion of the total volume of the dispersed phase is discussed and it is suggested that in these circumstances undercooling may fall significantly in comparison with the undercooling measured in micrometre emulsions. © 2014 Elsevier Ltd. All rights reserved.


Robinson P.,Leeds Teaching Hospitals | Robinson P.,University of Leeds
American Journal of Roentgenology | Year: 2012

OBJECTIVE. This article provides a review of femoroacetabular impingement (FAI) and the role MRI is attempting to fulfill in this complex and sometimes controversial condition. A perspective on the current status and on the advantages of 1.5-T MR arthrography is presented, and its usefulness in this setting is compared with the potential of nonarthrographic 3-T MRI. CONCLUSION. With its increasing availability, 3-T MRI has the potential to provide routine, less invasive assessment of the hip for FAI. © American Roentgen Ray Society.


Benton T.G.,University of Leeds
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2012

The mapping of environment, through variation in individuals' life histories, to dynamics can be complex and often poorly known. Consequently, it is not clear how important it is dynamically. To explore this, I incorporated lessons from an empirical system, a soil mite, into an individualbased model. Individuals compete for resource and allocate this according to eight 'genetic' rules that specify investment in growth or reserves (which influences survival or fecundity), size at maturation and reproductive allocation. Density dependence, therefore, emerges from competition for food, limiting individual's growth and fecundity. We use this model to examine the role that genetic and phenotypically plastic variation plays in dynamics, by fixing phenotypes, by allowing phenotypes to vary plastically and by creating genetic variation between individuals. Variation, and how it arises, influences short- and long-run dynamics in a way comparable in magnitude with halving food supply. In particular, by switching variation on and off, it is possible to identify a range of processes necessary to capture the dynamics of the 'full model'. Exercises like this can help identify key processes and parameters, but a concerted effort is needed across many different systems to search for shared understanding of both process and modelling. © 2011 The Royal Society.


Shalashilin D.V.,University of Leeds
Faraday Discussions | Year: 2011

This article briefly describes recently developed Multiconfigurational Ehrenfest dynamics method to simulate quantum dynamics in systems with many degrees of freedom. The central idea is to guide the trajectories of basis wave functions by means of the Ehrenfest trajectories. The amplitudes of guided basis functions are coupled through a system of linear equations. The approach has been applied to simulations of nonadiabatic dynamics in Spin-Boson model and in pyrazine molecule. A new application to nonadiabatic dynamics in 24D model of pyrazine, where good spectrum for is obtained with the basis of only 34 basis Ehrenfest configurations is reported. This application provides the ground for future fully quantum direct dynamics. Another new application to the model of sticking to the surface described by the System-Bath Hamiltonian is presented to demonstrate the broadness of the approach, which can be applied to both electronically adiabatic and nonadiabatic dynamics. For all applications the results are in good agreement with those of MCTDH, which is very difficult to achieve with other trajectory-based methods. Therefore MCE can serve as a starting point for future use with "on the fly" direct dynamics. MCE provides an efficient fully quantum method capable of catching coherent dynamics in multidimentional systems, which is a necessary step for developing and understanding coherent control in realistic quantum systems. © 2011 The Royal Society of Chemistry.


The maximum additional burden of water- and wastewater-related disease of 10-6 disability-adjusted life year (DALY) loss per person per year (pppy), used in the WHO Drinking-water Quality Guidelines and the WHO Guidelines for Wastewater Use in Agriculture, is based on US EPA's acceptance of a 70-year lifetime waterborne cancer risk of 10-5 per person, equivalent to an annual risk of 1.4 × 10-7 per person which is four orders of magnitude lower than the actual all-cancer incidence in the USA in 2009 of 1.8 × 10-3 pppy. A maximum additional burden of 10-4 DALY loss pppy would reduce this risk to a more cost-effective, but still low, risk of 1.4 × 10-5 pppy. It would increase the DALY loss pppy in low- and middle-income countries due to diarrhoeal diseases from the current level of 0.0119 pppy to 0.0120 pppy, and that due to ascariasis from 0.0026 pppy to 0.0027 pppy, but neither increase is of public-health significance. It is therefore recommended that the maximum additional burden of disease from these activities be increased to a DALY loss of 10-4 pppy as this provides an adequate margin of public-health safety in relation to waterborne-cancer deaths, diarrhoeal disease and ascariasis in all countries. © IWA Publishing 2011.


Califano M.,University of Leeds | Gomez-Campos F.M.,University of Granada
Nano Letters | Year: 2013

Size tunability of the optical properties and inexpensive synthesis make semiconductor nanocrystals one of the most promising and versatile building blocks for many modern applications such as lasers, single-electron transistors, solar cells, and biological labels. The performance of these nanocrystal-based devices is however compromised by efficient trapping of the charge carriers. This process exhibits different features depending on the nanocrystal material, surface termination, size, and trap location, leading to the assumption that different mechanisms are at play in each situation. Here we revolutionize this fragmented picture and provide a unified interpretation of trapping dynamics in semiconductor nanocrystals by identifying the origins of this so far elusive detrimental process. Our findings pave the way for a general suppression strategy, applicable to any system, which can lead to a simultaneous efficiency enhancement in all nanocrystal-based technologies. © 2013 American Chemical Society.


Gillard R.,University of Leeds
Global Environmental Change | Year: 2016

As climate change policies and governance initiatives struggle to produce the transformational social changes required, the search for stand out case studies continues. Many have pointed to the period between 2005 and 2008 in the United Kingdom as a promising example of national level innovation. With strong cross-party consensus and a first-of-its-kind legislation the UK established itself as a climate policy leader. However, early warning signs suggest that this institutionalised position is far from secure. Through a novel application of discursive institutionalism this article presents a detailed analysis of the role of ideas in unravelling this ambition under the Conservative-Liberal coalition administration (2010–2015). Discursive interactions among policymakers and other political actors were dominated by ideas about governmental responsibility and economic austerity, establishing an atmosphere of climate policy scepticism and restraint. By situating this conspicuous and influential process of bricolage within its institutional context the importance of how policymakers think and communicate about climate change is made apparent. The power of ideas to influence policy is further demonstrated through their cognitive and normative persuasiveness, by imposing over and excluding alternatives and in their institutional positioning. It can be concluded that despite innovative legislation, institution building and strategic coordination of different types of governance actors the ideational foundations of ambitious climate change politics in the UK have been undermined. © 2016 The Author


Povey M.J.W.,University of Leeds
Particuology | Year: 2013

Ultrasound spectrometry is one of very few methods that can size particles over the range 10 nm to 1 mm for optically opaque, undiluted materials. It has in-line, non-invasive capabilities which make it a serious contender for use in industrial process monitoring, with the potential for 100% inspection. In aqueous systems, it is more sensitive to nanoparticles than to particles in the micrometre range upwards because the scattering power varies as the inverse square of particle diameter, making it suitable for the detection of nanoparticles in concentrated, mixed systems. Future development of ultrasound spectrometers suitable for widespread laboratory and industrial use depends on meeting the challenges of complex data interpretation and the need for considerable know how. In this review we provide a brief account of ultrasound propagation and scattering theory which underlies the ultrasound spectrometer, describe several types of spectrometer and demonstrate its successful use in the characterization of colloidal silica, whole milk and protein solutions. © 2012 Chinese Society of Particuology and Institute of Process Engineering, Chinese Academy of Sciences.


Ma X.,Tsinghua University | Fung C.-H.F.,University of Hong Kong | Razavi M.,University of Leeds
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2012

Measurement-device-independent quantum key distribution with a finite number of decoy states is analyzed under finite-data-size assumption. By accounting for statistical fluctuations in parameter estimation, we investigate vacuum+weak- and vacuum+two-weak-decoy-state protocols. In each case, we find proper operation regimes, where the performance of our system is comparable to the asymptotic case for which the key size and the number of decoy states approach infinity. Our results show that practical implementations of this scheme can be both secure and efficient. © 2012 American Physical Society.


Benitez-Alfonso Y.,University of Leeds
Journal of Experimental Botany | Year: 2014

Plant cells have channel-like structures named plasmodesmata that allow for the symplastic molecular transport between neighbouring cells. The importance of plasmodesmata in whole plant development is well acknowledged. They mediate the cell-to-cell and vascular loading and unloading of metabolites, proteins, and other signalling molecules. However, it is still not clear how, mechanistically, these channels are regulated in response to developmental and environmental cues. This review aims to bring together knowledge acquired in recent years on plasmodesmata composition, regulation, and function. Progress in the discovery of factors that regulate symplastic transport and plant development in particular are discussed. This will hopefully highlight the challenges faced by the scientific community to unveil the mechanisms controlling symplastic communication during the formation and maintenance of plant meristems. © 2013 The Author.


Handyside A.H.,Gynaecology and Genetics Center | Handyside A.H.,University of Leeds
Biochimica et Biophysica Acta - Molecular Basis of Disease | Year: 2012

Chromosome aneuploidy is a major cause of pregnancy loss, abnormal pregnancy and live births following both natural conception and in vitro fertilisation (IVF) and increases exponentially with maternal age in the decade preceding the menopause. Molecular genetic analysis has shown that these are predominantly maternal in origin and trisomies most frequently occur through errors in the first meiotic division. Analysis of chromosome copy number in the three products of female meiosis, the first and second polar bodies and the corresponding zygote by microarray comparative genomic hybridisation (array CGH), in women of advanced maternal age undergoing IVF, has recently revealed a pattern of frequent multiple meiotic errors, caused by premature predivision of sister chromatids in meiosis I and a high incidence of errors in meiosis II. This pattern is similar to those observed in various mouse models which implicate the gradual depletion of cohesins, which are essential for cohesion of sister chromatids, as the primary cause of age related aneuploidy in female meiosis. However, defects in other aspects of meiosis including the formation and stabilisation of chiasmata and the spindle assembly checkpoint (SAC) may also contribute. The challenge remains to explain the molecular basis of 'physiological' rather than 'chronological' female ageing and the contribution of multifactorial causes from the fetal to adult ovary. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure. © 2012 Elsevier B.V.


Wurdak H.,University of Leeds
Future Medicinal Chemistry | Year: 2012

Several human cancer types consist of diverse cell populations that can differ in their tumor-driving potential. One breakthrough has been the identification of poorly differentiated tumor cells, herein termed cancer stem cells (CSCs). CSCs have been shown to initiate tumors in different model systems and have been implicated in cancer resistance to conventional therapies. The clinical relevance of CSCs has been increasingly recognized, and recent progress in their enrichment and characterization has paved the way for exploring CSC biology with high-throughput screening technologies. This article focuses on functional chemical and RNAi screens that have led to the identification of factors that control the CSC phenotype. Different experimental strategies, current challenges and perspectives in CSC drug discovery are discussed. © 2012 Future Science Ltd.


Watson A.A.,University of Leeds
Reports on Progress in Physics | Year: 2014

Although cosmic rays were discovered over 100 years ago their origin remains uncertain. They have an energy spectrum that extends from ∼1 GeV to beyond 1020 eV, where the rate is less than 1 particle per km 2 per century. Shortly after the discovery of the cosmic microwave background in 1965, it was pointed out that the spectrum of cosmic rays should steepen fairly abruptly above about 4 × 1019 eV, provided the sources are distributed uniformly throughout the Universe. This prediction, by Greisen and by Zatsepin and Kuz'min, has become known as the GZK effect and in this article I discuss the current position with regard to experimental data on the energy spectrum of the highest cosmic-ray energies that have been accumulated in a search that has lasted nearly 50 years. Although there is now little doubt that a suppression of the spectrum exists near the energy predicted, it is by no means certain that this is a manifestation of the GZK effect as it might be that this energy is also close to the maximum to which sources can accelerate particles, with the highest energy beam containing a large fraction of nuclei heavier than protons. The way forward is briefly mentioned. © 2014 IOP Publishing Ltd.


Turner P.C.,University of Leeds
World Mycotoxin Journal | Year: 2010

Deoxynivalenol (DON) and nivalenol (NIV) are common dietary contaminants in most temperate regions of the world. The frequency and levels of exposure will vary by geographic location, annual variations in rainfall patterns, national wealth and related agricultural and regulatory infrastructure, dietary diversity and food sufficiency. DON contamination is more frequent and at higher levels than NIV, though chronic exposure to both is predicted to occur in many parts of the world. In addition acute poisoning episodes are reported, particularly from China, and it is important to have the tools to assess both chronic and acute exposure. This review describes both traditional epidemiology and the development of biomarkers to assess exposure. The biomarker approaches are at an early stage, and it will be important to assess the applicability of these approaches in different settings and at different exposure levels. It is hoped that some of the developmental 'omics' technologies will support both 'exposure biomarker' and 'effect biomarker' development. © 2010 Wageningen Academic Publishers.


Peers C.,University of Leeds
Cell Metabolism | Year: 2015

The carotid body has long been recognized as the bodys primary acute oxygen sensor. For decades, this organ has been reluctant to reveal mechanisms underlying its sensory activity. In this issue of Cell Metabolism, Fernandez-Agüera et al. (2015) take us closer to a fuller understanding of this fundamental process.


Williamson G.,University of Leeds | Clifford M.N.,University of Surrey
British Journal of Nutrition | Year: 2010

The absorption of dietary phenols, polyphenols and tannins (PPT) is an essential step for biological activity and effects on health. Although a proportion of these dietary bioactive compounds areabsorbed intact, depending on their chemical structure and the nature of any attached moiety (e.g. sugar, organic acid), substantial amounts of lower molecular weight catabolites are absorbedafterbiotransformation by the colon microflora. The main products in the colon are (a) benzoic acids (C6-C1), especially benzoic acid and protocatechuic acid; (b) phenylaceticacids(C6-C 2), especially phenylacetic acid per se; (c) phenylpropionic acids (C6-C3), where the latter are almost entirely in the dihydro form, notablydihydrocaffeicacid, dihydroferulic acid, phenylpropionic acid and 3-(3́-hydroxyphenyl)-propionic acid. As a result of this biotransformation, some of these compounds can each reach mmconcentrations in faecalwater. Many of these catabolites are efficiently absorbed in the colon, appear in the blood and are ultimately excreted in the urine. In the case of certain polyphenols, such asanthocyanins, these catabolites are major products in vivo; protocatechuic acid is reported to represent a substantial amount of the ingested dose of cyanidin-3-O-glucoside. The major catabolites of berries, and especially blackcurrants, arepredicted based on compositional data for polyphenols from berries and other sources. Since microbial catabolites may be present at many sites of the body in higherconcentration than the parent compound,it is proposed that at least a part of the biological activities ascribed to berry polyphenols and other PPT are due to their colonic catabolites. © The Authors 2010.


Turner N.A.,University of Leeds
Journal of Molecular and Cellular Cardiology | Year: 2015

Cardiac fibroblasts (CF) are well-established as key regulators of extracellular matrix (ECM) turnover in the context of myocardial remodelling and fibrosis. Recently, this cell type has also been shown to act as a sensor of myocardial damage by detecting and responding to damage-associated molecular patterns (DAMPs) upregulated with cardiac injury. CF express a range of innate immunity pattern recognition receptors (TLRs, NLRs, IL-1R1, RAGE) that are stimulated by a host of different DAMPs that are evident in the injured or remodelling myocardium. These include intracellular molecules released by necrotic cells (heat shock proteins, high mobility group box 1 protein, S100 proteins), proinflammatory cytokines (interleukin-1α), specific ECM molecules up-regulated in response to tissue injury (fibronectin-EDA, tenascin-C) or molecules modified by a pathological environment (advanced glycation end product-modified proteins observed with diabetes). DAMP receptor activation on fibroblasts is coupled to altered cellular function including changes in proliferation, migration, myofibroblast transdifferentiation, ECM turnover and production of fibrotic and inflammatory paracrine factors, which directly impact on the heart's ability to respond to injury. This review gives an overview of the important role played by CF in responding to myocardial DAMPs and how the DAMP/CF axis could be exploited experimentally and therapeutically. © 2015 Elsevier Ltd.


O'Neill D.W.,University of Leeds
Journal of Industrial Ecology | Year: 2015

Summary: Within this article, I investigate a number of the conceptual issues that arise when attempting to translate Herman Daly's definition of a steady-state economy (SSE) into a set of national biophysical indicators. Although Daly's definition gives a high-level view of what would be held steady in an SSE, it also leaves many questions unanswered. How should stocks and flows be aggregated? What is the role of international trade? How should nonrenewable resources be treated? And where does natural capital fit in? To help answer these questions, I relate Daly's definition to key concepts and terminology from material and energy flow accounting. I explore topics such as aggregation, international trade, the relevance of throughput, and hidden flows. I conclude that a set of biophysical accounts for an SSE should include three types of indicators (stocks, flows, and scale), track how stocks and flows are changing over a 5- to 10-year period, use aggregated data that measure the quantity of resource use (rather than its quality), measure both total and nonrenewable resource use, adopt a consumption-based approach, include hidden flows, and exclude indicators that measure characteristics of the stock of natural capital (with the notable exception of indicators that measure the regenerative and assimilative capacities of ecosystems). © 2015, Yale University.


Deuchars S.A.,University of Leeds
Experimental Physiology | Year: 2015

Sympathetic control of end organs relies on the activity of sympathetic preganglionic neurones (SPNs) within the spinal cord. These SPNs exhibit heterogeneity with respect to function, neurochemistry, location, descending inputs and patterns of activity. Part of this heterogeneity is bestowed by local spinal circuitry. Our understanding of the role of these local circuits, including the significance of connections between the SPNs themselves through specialized gap junctions, is patchy. This report focuses on interneurones and gap junctions within these circuits. Gap junctions play a role in sympathetic control; they are located on SPNs in the intermediolateral cell column. Mefloquine, a chemical that blocks these gap junctions, reduces local rhythmic activity in the spinal cord slice and disrupts autonomic control in the working heart-brainstem preparation. The role that these gap junctions may play in health and disease in adult animals remains to be elucidated fully. Presympathetic interneurones are located in laminae V, VII and X and the intermediolateral cell column; those in lamina X are GABAergic and directly inhibit SPNs. The GABAergic inputs onto SPNs exert their effects through activation of synaptic and extrasynaptic receptors, which stabilize the membrane at negative potentials. The GABAergic interneurones contribute to rhythmic patterns of activity that can be generated in the spinal cord, because bicuculline reduces network oscillatory activity. These studies indicate that local spinal cord circuitry is critical in enabling appropriate levels and patterning of activity in sympathetic outflow. We need to understand how these circuits may be harnessed in the situation of spinal cord injury. © 2015 The Physiological Society.


Mobilia M.,University of Leeds
Journal of Theoretical Biology | Year: 2010

We study the oscillatory dynamics in the generic three-species rock-paper-scissors games with mutations. In the mean-field limit, different behaviors are found: (a) for high mutation rate, there is a stable interior fixed point with coexistence of all species; (b) for low mutation rates, there is a region of the parameter space characterized by a limit cycle resulting from a Hopf bifurcation; (c) in the absence of mutations, there is a region where heteroclinic cycles yield oscillations of large amplitude (not robust against noise). After a discussion on the main properties of the mean-field dynamics, we investigate the stochastic version of the model within an individual-based formulation. Demographic fluctuations are therefore naturally accounted and their effects are studied using a diffusion theory complemented by numerical simulations. It is thus shown that persistent erratic oscillations (quasi-cycles) of large amplitude emerge from a noise-induced resonance phenomenon. We also analytically and numerically compute the average escape time necessary to reach a (quasi-)cycle on which the system oscillates at a given amplitude. © 2010 Elsevier Ltd. All rights reserved.


Gershenson A.,University of Massachusetts Amherst | Gierasch L.M.,University of Massachusetts Amherst | Pastore A.,Kings College London | Radford S.E.,University of Leeds
Nature Chemical Biology | Year: 2014

Evolutionary pressure for protein function leads to unavoidable sampling of conformational states that are at risk of misfolding and aggregation. The resulting tension between functional requirements and the risk of misfolding and/or aggregation in the evolution of proteins is becoming more and more apparent. One outcome of this tension is sensitivity to mutation, in which only subtle changes in sequence that may be functionally advantageous can tip the delicate balance toward protein aggregation. Similarly, increasing the concentration of aggregation-prone species by reducing the ability to control protein levels or compromising protein folding capacity engenders increased risk of aggregation and disease. In this Perspective, we describe examples that epitomize the tension between protein functional energy landscapes and aggregation risk. Each case illustrates how the energy landscapes for the at-risk proteins are sculpted to enable them to perform their functions and how the risks of aggregation are minimized under cellular conditions using a variety of compensatory mechanisms.


Prabhakar N.R.,University of Chicago | Peers C.,University of Leeds
Physiology | Year: 2014

Carotid bodies detect hypoxia in arterial blood, translating this stimulus into physiological responses via the CNS. It is long established that ion channels are critical to this process. More recent evidence indicates that gasotransmitters exert powerful influences on O2 sensing by the carotid body. Here, we review current understanding of hypoxia-dependent production of gasotransmitters, how they regulate ion channels in the carotid body, and how this impacts carotid body function. ©2014 Int. Union Physiol. Sci./Am. Physiol. Soc.


Background: Drugs policy is made in a politically charged atmosphere. This is often not seen to be conducive to the ideals of evidence-based policymaking. In the UK over recent years the efficacy of the 1971 Misuse of Drugs Act (MDA) has been one of the most widely discussed and debated areas of UK drug policy. Since inception, the MDA 1971 has remained relatively stable with very few drugs moving up or down the scale and until recently, and with very few exceptions, there has been little public debate on the nature of the system. This changed in the run up to the cannabis reclassification in 2004 from class B to class C, through the reverse of this decision in 2009 and the fallout between the Government of the time and leading members of the Advisory Council on the Misuse of Drugs. Methods: Based on wide-ranging survey of the literature and secondary analysis of various official publications and academic commentaries, this paper considers what the cannabis episode can tell us about the current state of UK drug policy governance. Results: Previous research on drug policy governance has suggested that policy goals should be clearly articulated so as to avoid confusion over what constitutes evidence, decision-makers should be 'evidence-imbued' and there should be widespread consultation with, and transparency of, stakeholder engagement. The interpretation here is that recent changes to cannabis legislation reveal that these aspects of good governance were called into question although there were fleeting moments of good practice. Conclusion: The use of evidence in drug policy formulation continues to be bedevilled by political stalemate and reluctance to countenance radical reform. Where evidence does play a role it tends to be at the margins. There are, however, potential lessons to be learned from other policy areas but this requires a more pragmatic attitude on behalf of decision-makers. © 2014 Elsevier B.V.


Millward-Hopkins J.T.,University of Leeds
Wiley Interdisciplinary Reviews: Climate Change | Year: 2016

This short opinion article is intended to provoke debate around the use of market mechanisms and financial incentives as strategies to mitigate climate change and other ecological issues. It does so by synthesizing schools of thought that critique the 'naturalization' of the market and examining these within the context of environmental politics. The article first briefly reviews the most serious criticisms of market- and incentive-based approaches to environmental issues, drawing upon literature from sociology, (steady-state) economics, and moral and political philosophy as well as recent empirical evidence from behavioral psychology. Subsequently, with reference to anthropological observations and a number of political theorists (Michael Foucault, David Graeber and others), it outlines the contradiction between the 'naturalization' of the market (i.e., the market as a phenomena that emerges spontaneously from natural human self-interest) and the explicit function of the state within neoliberalism to construct markets and market subjects. Finally, an argument is presented that some sectors of the environmental movement have been captured (implicitly and perhaps begrudgingly) by a naturalized vision of the market and hence, inadvertently, are supporting neoliberalism in extending market relations and cultivating market subjects. WIREs Clim Change 2016, 7:13-22. doi: 10.1002/wcc.370 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.


Droop A.P.,University of Leeds
Bioinformatics | Year: 2016

Many Next Generation Sequencing analyses involve the basic manipulation of input sequence data before downstream processing (e.g. searching for specific sequences, format conversion or basic file statistics). The rapidly increasing data volumes involved in NGS make any dataset manipulation a time-consuming and error-prone process. I have developed fqtools; a fast and reliable FASTQ file manipulation suite that can process the full set of valid FASTQ files, including those with multi-line sequences, whilst identifying invalid files. Fqtools is faster than similar tools, and is designed for use in automatic processing pipelines. © 2016 The Author 2016. Published by Oxford University Press.


Childs T.H.C.,University of Leeds
Journal of Materials Processing Technology | Year: 2013

This paper reports an improved ductile shear failure model for steels and its application, through finite element simulations, to predicting the conditions for built-up edge formation in steel machining. The model has two parts, a standard damage accumulation law and (the improved part) how damage affects the steel's flow stress after failure. The accumulation law includes a strain to failure with inverse exponential dependence on hydrostatic pressure and reducing in a blue-brittle temperature range. The flow stress after failure remains finite in compressive hydrostatic conditions, to create a friction resistance to shear across the failure surface. Predictions of built-up edge formation depend strongly on strain hardening behaviour. This affects the hydrostatic stress field in the chip formation region. Simulations show the general features of built-up edge formation (a finite cutting speed range with an upper limit determined by increased ductility with temperature and a lower limit determined, depending on conditions, by insufficient heating for blue-brittleness, lower chip/tool friction or a change to unsteady chip formation). The simulations are tested against previously published observations of built-up edge formation in orthogonal cutting of a Russian steel equivalent to AISI 5130. To extend the work to a wider range of steels requires more data to be gathered on individual steels' damage accumulation law coefficients. Also, at this stage, the simulations only predict the conditions (cutting speed, uncut chip thickness) in which built-up edge forms. They are not able to follow the growth of the built-up edge to its final shape. © 2013 Elsevier B.V. All rights reserved.


Hainsworth R.,University of Leeds
Experimental Physiology | Year: 2014

New Findings: What is the topic of this review? The purpose of this review is to summarize present knowledge of the function of the afferent nerves arising from the heart and the coronary and pulmonary arteries. Although there is abundant evidence that atrial receptor stimulation influences heart rate and urine flow, with little or no effect elsewhere, and that ventricular receptors are strongly excited only by chemical stimuli, there is still the erroneous belief that they act as a homogeneous group causing cardiovascular depression. What advances does it highlight? Coronary receptors deserve to be recognized as a potentially important additional group of baroreceptors. Stimulation of pulmonary arterial baroreceptors at physiological pressures causes reflex vasoconstriction and could have a hitherto unacknowledged important role in cardiovascular control, for example in exercise. Although there has been a tendency to regard cardiac and pulmonary receptors as a single population of 'cardiopulmonary receptors', this cannot be justified as the various receptor types all induce their own particular pattern of responses. Stimulation of atrial receptors increases activity in sympathetic nerves to the sino-atrial node, causing tachycardia, but there is no effect on activity to the myocardium or to most blood vessels. Renal nerve activity, however, is decreased, and secretion of antidiuretic hormone is inhibited, causing diuresis. Ventricular receptors induce a powerful depressor response, but only in response to abnormal chemical stimulation and possibly to myocardial injury. Coronary arterial receptors function as baroreceptors, but have a lower threshold and a more prolonged effect than other baroreceptors. Pulmonary arterial baroreceptors induce vasoconstriction and respiratory stimulation at physiological pressures and may be of importance in mediating some of the responses to exercise, as well as in hypoxic conditions. © 2013 The Author. Experimental Physiology © 2013 The Physiological Society.


Berry D.,University of Leeds
Studies in History and Philosophy of Science Part C :Studies in History and Philosophy of Biological and Biomedical Sciences | Year: 2014

In the early twentieth century, Wilhelm Johannsen proposed his pure line theory and the genotype/phenotype distinction, work that is prized as one of the most important founding contributions to genetics and Mendelian plant breeding. Most historians have already concluded that pure line theory did not change breeding practices directly. Instead, breeding became more orderly as a consequence of pure line theory, which structured breeding programmes and eliminated external heritable influences. This incremental change then explains how and why the large multi-national seed companies that we know today were created; pure lines invited standardisation and economies of scale that the latter were designed to exploit. Rather than focus on breeding practice, this paper examines the plant varietal market itself. It focusses upon work conducted by the National Institute of Agricultural Botany (NIAB) during the interwar years, and in doing so demonstrates that, on the contrary, the pure line was actually only partially accepted by the industry. Moreover, claims that contradicted the logic of the pure line were not merely tolerated by the agricultural geneticists affiliated with NIAB, but were acknowledged and legitimised by them. The history of how and why the plant breeding industry was transformed remains to be written. © 2014 Elsevier Ltd.


Ngoduy D.,University of Leeds
Transportmetrica B | Year: 2013

This paper proposes a macroscopic model to describe the dynamics of intelligent traffic flow where intelligent vehicles are driving closer to each other than manual vehicles and operating in a form of many platoons each of which contains several vehicles. The model is developed from a car-following model which allows us to obtain well tractable macroscopic equations for such platoon-based traffic operation. A linear stability diagram is constructed from the developed model based on the linear stability method for a certain model parameter set. It is found analytically that platoon-based driving behaviour of intelligent vehicles enhances the stabilisation of traffic flow with respect to a small perturbation. Numerical simulation of an open freeway with an on-ramp bottleneck supports our analytical results.We have argued that the newly developed macroscopic model will provide a better insight into the dynamics of intelligent traffic flow. © 2013 Hong Kong Society for Transportation Studies Limited.


George I.J.,University of Leeds | Abbatt J.P.D.,University of Toronto
Nature Chemistry | Year: 2010

Atmospheric aerosol particles play pivotal roles in climate and air quality. Just as chemically reduced gases experience oxidation in the atmosphere, it is now apparent that solid and liquid atmospheric particulates are also subject to similar oxidative processes. The most reactive atmospheric gas-phase radicals, in particular the hydroxyl radical, readily promote such chemistry through surficial interactions. This Review looks at progress made in this field, discussing the radical-initiated heterogeneous oxidation of organic and inorganic constituents of atmospheric aerosols. We focus on the kinetics and reaction mechanisms of such processes as well as how they can affect the physicoĝ€"chemical properties of particles, such as their composition, size, density and hygroscopicity. Potential impacts on the atmosphere include the release of chemically reactive gases such as halogens, aldehydes and organic acids, reactive loss of particle-borne molecular tracer and toxic species, and enhanced hygroscopic properties of aerosols that may improve their ability to form cloud droplets. © 2010 Macmillan Publishers Limited. All rights reserved.


This paper responds to recent debates in human geography about ideal-type versus contingent neoliberalism, or what Gibson-Graham conceptualises as "strong" vs "weak" theory, by offering some reflections from an in-depth study of the private finance initiative (PFI) in England. It first introduces the history and purpose of the PFI as the Labour government's flagship public-private partnership (PPP) approach to public infrastructure modernisation. It then critically analyses its use in inner-city regeneration through a case study of a PFI housing scheme in the northern English city of Leeds. The paper argues that, when seen through the lens of "strong theory", a PFI appears to be a consciously designed "neoliberal straitjacket" intended to lock-in gentrification-based regeneration at the neighbourhood level, guarantee long-term profits to (finance) capital, and create powerful privatising and marketising pressures across the local public sphere. However, it is equally possible to construct a preliminary "weak theory" of the PFI that unhides its inherent contradictions and shows how everyday activism by local community actors can successfully influence and contest how neoliberalism is rolled out on the ground. © 2010 The Author Journal compilation © 2010 Editorial Board of Antipode.


Cardno A.G.,University of Leeds | Owen M.J.,University of Cardiff
Schizophrenia Bulletin | Year: 2014

There is substantial evidence for partial overlap of genetic influences on schizophrenia and bipolar disorder, with family, twin, and adoption studies showing a genetic correlation between the disorders of around 0.6. Results of genome-wide association studies are consistent with commonly occurring genetic risk variants, contributing to both the shared and nonshared aspects, while studies of large, rare chromosomal structural variants, particularly copy number variants, show a stronger influence on schizophrenia than bipolar disorder to date. Schizoaffective disorder has been less investigated but shows substantial familial overlap with both schizophrenia and bipolar disorder. A twin analysis is consistent with genetic influences on schizoaffective episodes being entirely shared with genetic influences on schizophrenic and manic episodes, while association studies suggest the possibility of some relatively specific genetic influences on broadly defined schizoaffective disorder, bipolar subtype. Further insights into genetic relationships between these disorders are expected as studies continue to increase in sample size and in technical and analytical sophistication, information on phenotypes beyond clinical diagnoses are increasingly incorporated, and approaches such as next-generation sequencing identify additional types of genetic risk variant. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved.


To determine whether ischaemic manifestations of GCA are associated with pre-existing hypertension, atherosclerosis or area-level socio-economic deprivation. We conducted an observational study of rheumatologist/ophthalmologist-diagnosed GCA in eight UK centres. The main outcome measure was ischaemic manifestations observed during active GCA: visual loss/blurring, aura, diplopia, jaw/tongue/limb claudication, cerebral/myocardial ischaemia or scalp necrosis. Out of 271 patients, 222 had ischaemic manifestations. Adjusted odds ratios (ORs) for the influence of hypertension and atherosclerosis were 1.6 (95% CI 0.8, 3.1) and 1.5 (0.6, 3.5). The most striking finding was an association of ischaemic manifestations with increasing Index of Deprivation 2007 score: OR 4.2 (95% CI 1.3, 13.6) for the most-deprived quartile compared with the least-deprived quartile. Similar effect sizes were seen within each recruitment centre. Deprivation was associated with smoking and negatively associated with previous polymyalgia. However, neither of these variables, nor hypertension or atherosclerosis, appeared responsible for mediating the effect of deprivation on ischaemic complications. Smoking was not associated with ischaemic manifestations. Median symptom duration before treatment was 30 days; after adjusting for symptom duration, the OR for ischaemic complications was 3.2 (95% CI 1.0, 10.8) for the most-deprived quartile compared with the least-deprived quartile. In GCA, area-level socio-economic deprivation was associated with ischaemic manifestations: this was not mediated by traditional cardiovascular risk factors. These findings are novel and require replication. Delay between first symptoms and treatment may play a role. Public awareness campaigns about GCA should aim especially to engage individuals living in more deprived areas to encourage early presentation and prompt treatment.


Auer S.,University of Leeds | Kashchiev D.,Bulgarian Academy of Science
Physical Review Letters | Year: 2010

The intrinsic property of proteins to form structural motifs such as α helices and β sheets leads to a complex phase behavior in which proteins can assemble into various types of aggregates including crystals, liquidlike phases of unfolded or natively folded proteins, and amyloid fibrils. Here we use a coarse-grained protein model that enables us to perform Monte Carlo simulations for determining the phase diagram of natively folded α-helical and unfolded β-sheet forming peptides. The simulations reveal the existence of various metastable peptide phases. The liquidlike phases are metastable with respect to the fibrillar phases, and there is a hierarchy of metastability. © 2010 The American Physical Society.


Eccleston C.,University of Bath | Morley S.J.,University of Leeds | Williams A.C.,University College London
British Journal of Anaesthesia | Year: 2013

Psychological interventions are a mainstay of modern pain management practice and a recommended feature of a modern pain treatment service. Systematic reviews for the evidence of psychological interventions are reviewed in this article. The evidence for effectiveness is strongest for cognitive behavioural therapy with a focus on cognitive coping strategies and behavioural rehearsal. Most evidence is available for treatments of adult pain, although adolescent chronic pain treatments are also reviewed. It is clear that treatment benefit can be achieved with cognitive behavioural methods. It is possible to effect change in pain, mood, and disability, changes not achieved by chance or by exposure to any other treatment. However, the overall effect sizes of treatments for adults, across all trials, are modest. Reasons for the relatively modest treatment effects are discussed within the context of all treatments for chronic pain being disappointing when measured by the average. Suggestions for improving both trials and evidence summaries are made. Finally, consideration is given to what can be achieved by the pain specialist without access to specialist psychology resource. © 2013 © The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.


Handyside A.H.,Bluegnome | Handyside A.H.,University of Leeds
Fertility and Sterility | Year: 2013

Chromosome aneuploidy, an abnormal number of chromosomes, in human gametes and embryos is a major cause of IVF failure and miscarriage and can result in affected live births. To avoid these outcomes and improve implantation and live birth rates, preimplantation genetic screening aims to identify euploid embryos before transfer but has been restricted to analysis of a limited number of chromosomes. Over the past 15 years, various technologies have been developed that allow copy number analysis of all 23 pairs of chromosomes, 22 autosomes, and the sex chromosomes, or "24-chromosome" copy number analysis in single or small numbers of cells. Herein the pros and cons of these technologies are reviewed and evaluated for their potential as screening or diagnostic tests when used in combination with oocyte or embryo biopsy at different stages. © 2013 by American Society for Reproductive Medicine.


Robinson M.A.,University of Leeds
Journal of the American Society for Information Science and Technology | Year: 2010

The importance of the acquisition and provision of information within knowledge work such as engineering is widely acknowledged. This article reports an extensive empirical study of such information behaviors in engineers, using a novel and effective work sampling method. Seventy-eight design engineers each carried a portable handheld computer (PDA) for 20 working days. Once every hour, they were prompted to enter data concerning the task they were currently performing, including the information behaviors in which they were engaging. The resultant data represent a comprehensive picture of engineers' information behaviors and the percentage of their working time for which each of these behaviors accounts (55.75% in total). Specific hypotheses concerning the time spent engaged in these behaviors were also tested. Accordingly, it was found that participants spent substantially more time receiving information they had not requested than information they had, and this pattern was also reflected when they provided others with information. Furthermore, although there was no difference found between the time participants spent searching for information from other people compared with nonhuman sources, in the former case they spent relatively less time locating the information source and information within that source, and relatively more time engaged in problem solving and decision making. The results are discussed in terms of their implications for theory and organizational practice. © 2010 ASIS&T.


Ariens R.A.S.,University of Leeds
Journal of Thrombosis and Haemostasis | Year: 2013

Fibrinogen is an abundant plasma protein that, when converted to fibrin by thrombin, provides the main building blocks for the clot. Dys-, a-, and hypo-fibrinogenemias have been variably linked to a normal phenotype, bleeding or even thrombosis. Meanwhile, increased fibrinogen concentrations in the blood have been associated with risk for thrombosis. More recently, studies have focussed on abnormal fibrin structure as a cause for thrombosis. Fibrin clots that have high fiber density and increased resistance to fibrinolysis have been consistently associated with risk for thrombosis. Fibrin structure measurements can (i) provide an overall assessment of hemostatic capacity of a sample, (ii) include effects of thrombin generation and fibrinogen concentrations, (iii) include effects of fibrinogen mutations, polymorphisms, and modifications, and (iv) give an indication of clot mechanical strength and resistance to fibrinolysis. A fibrinogen splice variation of the γ-chain (γ') is discussed as a model for changes in fibrin structure in relation to thrombosis. Results from prospective studies on fibrin structure are awaited. Studies of fibrin formation under flow, interactions of fibrin with blood cells, the mechanical properties of the fibrin clot, and nanoscale/molecular characterization of fibrin formation are likely to expose new causal mechanisms for the role of fibrin in thrombotic disease. Future studies into the causality and mechanisms may lead to new opportunities using fibrin structure in the diagnosis or treatment of thrombosis. © 2013 International Society on Thrombosis and Haemostasis.


Wardman M.,University of Leeds
Transportation | Year: 2012

In contrast with reviews of values of time and price elasticities, the literature contains little by way of detailed reviews of travel time based choice and demand elasticities. This paper reports the most extensive meta-analysis of time-based demand elasticities yet undertaken, supplemented with a review of literature not previously in the public domain. The meta-analysis is based upon 427 direct elasticities covering travel time, generalised journey time (GJT) and service headway and drawn from 69 UK studies. The elasticities are found to vary, as expected, across attributes, and quite strong effects have been detected according to distance. We provide interesting insights into the relationship between long and short run elasticities and elasticities obtained from static models and choice models based on actual and hypothetical preferences. Significantly, the results seem to indicate that the duration for the long run demand impact to work through depends upon the periodicity of the model estimated. There is little variation apparent by journey purpose, source of the evidence, nor over time or by region/flow type, whilst travel time elasticities for high speed rail are not materially different from conventional contexts. The findings support some official elasticity recommendations and conventions but challenge others, and can be used to provide time-based elasticities where none exist or to assess new empirical evidence. © 2011 Springer Science+Business Media, LLC.


Wen X.,University of Leeds
International Journal for Numerical Methods in Fluids | Year: 2013

In this paper, a new numerical method is developed for two-dimensional interfacial (free surface) flows, based on the control volume method and conservative integral form of the Navier-Stokes equations with a standard staggered grid. The new method deploys two continuity equations, the continuity equation of the mass conservation for better convergence of the implicit scheme and the continuity equation of the volume conservation for the equation of pressure correction. The convection terms (the total momentum flux) on the surfaces of control volume are accurately calculated from the wet area exposed to the water, and the dry area exposed to the air. The numerical results produced by the new numerical method agree very well with the analytical solution, experimental images and experimentally measured velocity. © 2012 John Wiley & Sons, Ltd.


Hassan Ibrahim N.,University of Leeds
Journal of Information Technology in Construction | Year: 2013

In today's digital economy, the construction industry is at the verge of a technological revolution. Myriad technologies are promising innovative solutions to age-old problems of coordination and delivering projects on-time, on-budget and to clients' specifications, through what has come to be known as integrated project delivery. However, there is limited understanding of how these technologies are actually implemented to separate myth from reality. This paper reports on a study, the main aim of which is to enable a better understanding of how digital collaboration technologies are actually used in major construction projects and to what benefit. The objective is to unearth the research evidence through a rigorous process, and to identify, synthesize and interpret this evidence. Through an adaptation of the systematic review methodology, this paper explores the evidence, showing how digital collaboration technologies are being used in the delivery of major building and infrastructure projects. The review finds that these technologies have been severally theorised as boundary objects and digital infrastructure, and as tightly-coupled and clean technologies. The main trajectories that characterise their development and use include visualisation, coordination, automation, integration and transformation. The evidence suggests that integration of people, processes and systems is the underlying and predominant theme in a majority of projects. However, instead of a truly integrated approach, projects have often used digital technologies to achieve partial integration, with design and construction phases having more applications than operations and facilities management. It was also found that digital technology implementations addressing sustainability issues have received less attention, in spite of current government and industry focus on that agenda. The review indicates a diversity of approaches to achieving integration, which means that a clear and uniform approach has yet to be established. Nonetheless, Building Information Modelling (BIM) appears to be the emerging leading paradigm, although it also means different things to different people. The perennial challenge of interoperability still remains, prompting calls for a broader definition to include non-technical aspects. Other major challenges identified in the review include the technologies' material constraints and affordances, leadership, information-risks, training and the measurement of value. Finally, the review highlights areas that could benefit from further research attention. These include more focus on actual BIM implementations in major projects, the challenges of integrating multiple technologies across the whole project/asset lifecycle; and closer attention to their use for addressing sustainability issues. © 2013 The authors.


Foyer C.H.,University of Leeds | Noctor G.,University Paris - Sud
Plant, Cell and Environment | Year: 2012

Light-driven redox chemistry is a powerful source of redox signals that has a decisive input into transcriptional control within the cell nucleus. Like photosynthetic electron transport pathways, the respiratory electron transport chain exerts a profound control over gene function, in order to balance energy (reductant and ATP) supply with demand, while preventing excessive over-reduction or over-oxidation that would be adversely affect metabolism. Photosynthetic and respiratory redox chemistries are not merely housekeeping processes but they exert a controlling influence over every aspect of plant biology, participating in the control of gene transcription and translation, post-translational modifications and the regulation of assimilatory reactions, assimilate partitioning and export. The number of processes influenced by redox controls and signals continues to increase as do the components that are recognized participants in the associated signalling pathways. A step change in our understanding of the overall importance of the cellular redox hub to plant cells has occurred in recent years as the complexity of the management of the cellular redox hub in relation to metabolic triggers and environmental cues has been elucidated. This special issue describes aspects of redox regulation and signalling at the cutting edge of current research in this dynamic and rapidly expanding field. © 2011 Blackwell Publishing Ltd.


Carless D.,University of Leeds
Qualitative Health Research | Year: 2014

In the wake of recent wars, some military personnel face considerable physical and mental health problems. In this article I explore the effects of an adapted sport and inclusive adventurous training course for military personnel who have experienced physical injury and/or psychological trauma. Using a dialogical narrative approach, I analyzed stories shared by six soldiers during the course to explore the effects of involvement. Participation in the course seemed to facilitate a narrative transformation or opening corresponding to a broadening identity and sense of self. Story plots progressed from a failing monological narrative, through a chaos narrative, toward a dialogical quest narrative prioritizing immersion in an intense present, a developing self, and a relational orientation. On the basis of narrative theory, I suggest this transformation holds positive consequences for the health and well-being of military personnel who have experienced injury and/or trauma. © The Author(s) 2014.


Halcrow M.A.,University of Leeds
Chemical Communications | Year: 2010

Phase-pure solid solutions of [Co(terpy) 2][BF 4] 2 and [M(bpp) 2][BF 4] 2 (M = Fe or Ru, bpp = 2,6-dipyrazol-1-ylpyridine) have been prepared. The spin-state of the [Co(terpy) 2] 2+ dopant is modulated by the spin-state of the [Fe(bpp) 2] 2+ centres in the iron-containing materials. © 2010 The Royal Society of Chemistry.


Dickinson E.,University of Leeds
Colloids and Surfaces B: Biointerfaces | Year: 2010

The flocculation properties of oil-in-water emulsions stabilized by proteins are reviewed from the colloid science perspective. Emphasis is placed on insight from systematic studies of the stability of emulsions prepared with a milk protein ingredient as the sole emulsifying agent. The main factors considered are pH, ionic strength, calcium ion concentration, thermal processing, and the presence of cosolutes (alcohol, sugars). Contrasting dependences of the flocculation behaviour on these factors are observed for the pH-sensitive disordered caseins (αs1-casein or β-casein) and the heat-sensitive globular proteins (especially β-lactoglobulin). In comparing characteristic emulsion properties obtained with different proteins, we consider the relative importance of the different kinds of molecular and colloidal interactions-electrostatic, steric, hydrophobic and covalent. © 2010 Elsevier B.V.


This study used high-resolution PET to explore the pattern of DIP joint bone metabolism to test the hypothesis that the nail was functionally integrated with the bone, based on patterns of distal phalange (DP) bone metabolism in PsA compared with OA and normal joints. A total of 234 DIP joints were scanned in 30 subjects (10 PsA, 10 OA, 10 healthy control) with [18F]fluoride using the quad-high-density avalanche chamber nano PET scanner. The images were assessed blinded to diagnosis and symptoms for site and intensity of increased [18F]fluoride uptake. [18F]fluoride uptake in the DP was strong relative to the intermediate phalange in both PsA and OA. In PsA there was a trend for uptake to occur in a diffuse pattern involving the entire DP. There was also greater uptake at the enthesis, the periosteum and at the tufts of the DP of PsA compared with OA. In OA, uptake was greatest in the subchondral region adjacent to known sites of osteophytosis and erosions. Both PsA and OA joints with uptake at the subchondral or periosteal bone are likely to be more symptomatic. This exploratory study suggested diffuse increased bone metabolism involving the entire DP, periosteum and entheses, especially in PsA. The subchondral bone and periosteum at the DP have large concentrations of enthesis attachments, including attachments from the nail, supporting the concept of an integrated nail and joint apparatus leading to a wide area of abnormal bone metabolism in PsA.


Watling D.P.,University of Leeds | Cantarella G.E.,University of Salerno
Transportmetrica B | Year: 2013

The last 20 years has seen a growing interest in models of transportation networks which explicitly represent the epoch-to-epoch adaptive behaviour of travellers, such as the day-to-day dynamics of drivers'route choices. These models may represent the system as either a stochastic or deterministic process (DP).A body of theoretical literature now exists on this topic, and the purpose of the present paper is to both synthesise and advance this theory. To provide a focus to thework we analyse such models in terms of their ability to capture various contributory sources of variance in transportation systems. Dealing separately with the cases of uncongested and congested networks, we examine how moment-based deterministic dynamical systems may be exactly or approximately derived from some underlying stochastic process (SP). This opens up such problems to the tools of both deterministic dynamical systems (e.g. stability analysis) and SPs (e.g. Monte Carlo methods, statistical inference). In analysing these sources of variation, we also make several new advances to the existing body of theory, in terms of: extending the model assumptions (e.g. randomly varying choice probabilities and stochastic demand); deriving exact, explicit connections between stochastic and DPs in uncongested networks; applying stability analysis in novel ways to moment characterisations; and last, but not least, providing new limit theorems for asymptotic (large demand) analysis of the dynamics of SP models in congested networks. © 2013 Hong Kong Society for Transportation Studies Limited.


Hartley R.,University of Leeds
Journal of Computer Assisted Learning | Year: 2010

This article comments on how the core idea of the computer as an assistant to teaching and learning became reconfigured through changing technologies, pedagogies and educational cultures. Early influential researchers in computer assisted learning (CAL) made strong but differing links to theories and representations of learning, showing a relevance to pedagogy through innovative projects. Amid controversy, the educational potential of CAL became recognized and hardware-software developments stimulated the involvement of teachers in shaping applications and practices within contexts that favoured a constructivist student focus. Further advances in technology gave students greater autonomy in the style and management of learning, and enabled CAL to be redefined as a participative and collaborative enterprise. Institutions responded through supports and structures in ways that suited their wider educational policies. Technological developments (and controversies) continue to extend and reshape the applications of CAL, and this reflection points to the significance of the interplay between theory and practice in this evolving and redefining process. © 2010 Blackwell Publishing Ltd.


The role of conformational dynamics in allosteric signaling of proteins is increasingly recognized as an important and subtle aspect of this ubiquitous phenomenon. Cooperative binding is commonly observed in proteins with twofold symmetry that bind two identical ligands. We construct a coarse-grained model of an allosteric coupled dimer and show how the signal can be propagated between the distant binding sites via change in slow global vibrational modes alone. We demonstrate that modulation on substrate binding of as few as 5-10 slow modes can give rise to cooperativity observed in biological systems and that the type of cooperativity is given by change of interaction between the two monomers upon ligand binding. To illustrate the application of the model, we apply it to a challenging test case: the catabolite activator protein (CAP). CAP displays negative cooperativity upon association with two identical ligands. The conformation of CAP is not affected by the binding, but its vibrational spectrum undergoes a strong modification. Intriguingly, the first binding enhances thermal fluctuations, yet the second quenches them. We show that this counterintuitive behavior is, in fact, necessary for an optimal anticooperative system, and captured within a well-defined region of the model's parameter space. From analyzing the experimental results, we conclude that fast local modes take an active part in the allostery of CAP, coupled to the more-global slow modes. By including them into the model, we elucidate the role of the modes on different timescales. We conclude that such dynamic control of allostery in homodimers may be a general phenomenon and that our model framework can be used for extended interpretation of thermodynamic parameters in other systems. Copyright 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.


Califano M.,University of Leeds
ACS Nano | Year: 2015

Recent experimental studies have identified at least two nonradiative components in the fluorescence decay of solutions of CdTe colloidal quantum dots (CQDs). The lifetimes reported by different groups, however, differed by orders of magnitude, raising the question of whether different types of traps were at play in the different samples and experimental conditions and even whether different types of charge carriers were involved in the different trapping processes. Considering that the use of these nanomaterials in biology, optoelectronics, photonics, and photovoltaics is becoming widespread, such a gap in our understanding of carrier dynamics in these systems needs addressing. This is what we do here. Using the state-of-the-Art atomistic semiempirical pseudopotential method, we calculate trapping times and nonradiative population decay curves for different CQD sizes considering up to 268 surface traps. We show that the seemingly discrepant experimental results are consistent with the trapping of the hole at unsaturated Te bonds on the dot surface in the presence of different dielectric environments. In particular, the observed increase in the trapping times following air exposure is attributed to the formation of an oxide shell on the dot surface, which increases the dielectric constant of the dot environment. Two types of traps are identified, depending on whether the unsaturated bond is single (type I) or part of a pair of dangling bonds on the same Te atom (type II). The energy landscape relative to transitions to these traps is found to be markedly different in the two cases. As a consequence, the trapping times associated with the different types of traps exhibit a strikingly contrasting sensitivity to variations in the dot environment. Based on these characteristics, we predict the presence of a sub-nanosecond component in all photoluminescence decay curves of CdTe CQDs in the size range considered here if both trap types are present. The absence of such a component is attributed to the suppression of type I traps. © 2015 American Chemical Society.


Gonzalez S.,University of Leeds
European Urban and Regional Studies | Year: 2011

Despite the entrenched and long-term nature of the Italian and English North/South divide, this has not always been considered a relevant scale at which to redress spatial inequalities. To explain this apparent conundrum, this paper has two interlinked aims: (1) to investigate why, how, for whom and when the North/South divide is held to be a relevant 'policy geography' and (2) to explain the accompanying debates about the internal geography of this North/South divide. To do this, the paper develops a cultural politics of scales approach that compares the discursive (re)construction of the North/South divide in Italy and England by focusing on key moments, particularly the Keynesian consensus after the Second World War and the more current turn to neoliberal policies. Two parallel trends are identified: that support for an interventionist state and regional subsidies to poorer regions has decreased and that the North/South divide as a dual national partition has been dissolved into a micro-diverse geography. The paper concludes that the North/South divide is a contested political geography interpreted in different ways and used as a 'discursive device' by different actors to fit wider political projects. © The Author(s) 2011.


Sourbron S.,University of Leeds
European Journal of Radiology | Year: 2010

The most common methods for measuring perfusion with MRI are arterial spin labelling (ASL), dynamic susceptibility contrast (DSC-MRI), and T1-weighted dynamic contrast enhancement (DCE-MRI). This review focuses on the latter approach, which is by far the most common in the body and produces measures of capillary permeability as well. The aim is to present a concise but complete overview of the technical issues involved in DCE-MRI data acquisition and analysis. For details the reader is referred to the references. The presentation of the topic is essentially generic and focuses on technical aspects that are common to all DCE-MRI measurements. For organ-specific problems and illustrations, we refer to the other papers in this issue. In Section 1 "Theory" the basic quantities are defined, and the physical mechanisms are presented that provide a relation between the hemodynamic parameters and the DCE-MRI signal. Section 2 "Data acquisition" discusses the issues involved in the design of an optimal measurement protocol. Section 3 "Data analysis" summarizes the steps that need to be taken to determine the hemodynamic parameters from the measured data. © 2010 Elsevier Ireland Ltd. All rights reserved.


Krivov S.V.,University of Leeds
Journal of Physical Chemistry B | Year: 2011

To simplify the description of a complex multidimensional dynamical process, one often projects it onto a single reaction coordinate. In protein folding studies, the folding probability pfold is an optimal reaction coordinate which preserves many important properties of the dynamics. The construction of the coordinate is difficult. Here, an efficient numerical approach to construct the pfold reaction coordinate for a Markov process (satisfying the detailed balance) is described. The coordinate is obtained by optimizing parameters of a chosen functional form to make a generalized cut-based free energy profile the highest. The approach is illustrated by constructing the pfold reaction coordinate for the equilibrium folding simulation of FIP35 protein reported by Shaw et al. (Science2010, 330, 341-346). © 2011 American Chemical Society.


Pickering J.D.,University of Leeds
Anatomical Sciences Education | Year: 2015

The traditional lecture remains an essential method of disseminating information to medical students. However, due to the constant development of the modern medical curriculum many institutions are embracing novel means for delivering the core anatomy syllabus. Using mobile media devices is one such way, enabling students to access core material at a time and place that suits their specific learning style. This study has examined the effect of five anatomy drawing screencasts that replicate the popular anatomy drawing element of a lecture. These resources were uploaded to the University's Virtual Learning Environment for student access. Usage data and an end of module questionnaire were used to assess the impact of the screencasts on student education. The data revealed a high level of usage that varied in both the time of day and day of the week, with the number of downloads dramatically increasing towards the end of the module when the assessment was approaching. The student group found the additional resources extremely useful in consolidating information and revision, with many commenting on their preference to the screencasts compared to the more traditional approaches to learning. Scrutinizing the screencasts in relation to cognitive load theory and the cognitive theory of multimedia learning indicates a high correlation with an evidence-based approach to designing learning resources. Overall the screencasts have been a well-received enhancement that supports the student learning and has been shown to promote flexible learning. Anat Sci Educ 8: 249-257. © 2014 American Association of Anatomists.


Holmes G.,University of Leeds
Conservation and Society | Year: 2013

The idea that the support of local people is essential for the success of protected areas is widespread in conservation, underpinning various conservation paradigms and policies, yet it has rarely been critically examined. This paper explores the circumstances which determine whether or not local opposition to protected areas can cause them to fail. It focuses on the power relations between protected areas and local communities, and how easily they can influence one another. We present a case study from the Dominican Republic, where despite two decades of resentment with protected policies, local people are unable to significantly challenge them because of fears of violence from guards, inability to reach important political arenas, social ties with guards, and the inability to coordinate action. It concludes by arguing that there are often substantial barriers that prevent local people from challenging unpopular conservation policies, and that local support is not necessarily essential for conservation.


Boots M.,University of Exeter | Roberts K.E.,University of Leeds
Proceedings of the Royal Society B: Biological Sciences | Year: 2012

Maternal effects can be adaptive and because of their intrinsic time delays may have important effects on population dynamics. In vertebrates, and increasingly invertebrates, it is well established that offspring defence is in part determined by maternal parasite exposure. It has also been suggested that there may be indirect maternal effects on immunity mediated by other components of the maternal environment, including density and resource availability. Here, we examine the effect maternal resource availability has on the immunity of offspring in an insect-virus system. We use five different maternal resource levels and examine immunity in the offspring both directly, by challenge with a virus, and by measuring a major component of the immune system, across three offspring environments. Both the direct infection assay and the measure of immunocompetence show clearly that offspring from mothers in poor environments are more resistant to parasites. This may result from life-history optimization of mothers in poor environments, or because the poor environment acts as a cue for higher disease risk in the next generation. This emphasizes the importance of maternal effects on disease resistance, mediated through indirect environmental factors that will have important implications to both the ecological and evolutionary dynamics of host-parasite interactions. © 2012 The Royal Society.


Chandra Y.,University of Leeds | Leenders M.A.A.M.,University of Amsterdam
Technovation | Year: 2012

While prior studies have investigated factors, processes and pathways traversed in user innovation and user entrepreneurship within the real world, there is scant attention for user innovation and user entrepreneurship that take place within the virtual world. We report on an exploratory study of a select group of user innovators-entrepreneurs in Second Life, using virtual participant observation and in-depth interviews. Results suggest that the paths traversed by user innovators and user entrepreneurs in the virtual life broadly resemble those in the real life as reported in the literature. Interestingly, our study also suggests that Second Life as a virtual world breeds opportunities leading to entrepreneurial acts in the 'real' world as well as further opportunities in the Second Life. The virtual world itself, as a technological platform, also generates a range of opportunities. We formulate testable propositions and further link our insights to existing research on the drivers and pathways of user innovation and entrepreneurship in the 'real' world (i.e.; the role of prior knowledge and networks), Austrian economics theory of entrepreneurial discovery, and creative collective theory. © 2012 Elsevier Ltd. All rights reserved.


Jones C.A.,University of Leeds
Icarus | Year: 2014

Jupiter's dynamo is modelled using the anelastic convection-driven dynamo equations. The reference state model is taken from French et al. [2012]. Astrophys. J. Suppl. 202, 5, (11pp), which used density functional theory to compute the equation of state and the electrical conductivity in Jupiter's interior. Jupiter's magnetic field is approximately dipolar, but self-consistent dipolar dynamo models are rather rare when the large variation in density and the effective internal heating are taken into account. Jupiter-like dipolar magnetic fields were found here at small Prandtl number, Pr = 0.1. Strong differential rotation in the dynamo region tends to destroy a dominant dipolar component, but when the convection is sufficiently supercritical it generates a strong magnetic field, and the differential rotation in the electrically conducting region is suppressed by the Lorentz force. This allows a magnetic field to develop which is dominated by a steady dipolar component. This suggests that the strong zonal winds seen at Jupiter's surface cannot penetrate significantly into the dynamo region, which starts approximately 7000. km below the surface. © 2014 The Authors.


Tyson S.F.,University of Salford | Kent R.M.,University of Leeds
Archives of Physical Medicine and Rehabilitation | Year: 2013

Objective: To determine the effectiveness of an ankle-foot orthosis (AFO) on mobility, walking, and balance in people with stroke. Data Sources: The following databases were searched from inception to November 2011: Cochrane Stroke, Movement Disorders and Injuries Groups, MEDLINE, Embase, CINAHL, AMED, PsycINFO, and the Physiotherapy Evidence Database. Previous reviews, reference lists, and citation tracking of the selected articles were screened, and the authors of selected trials were contacted for any further unpublished data. Study Selection: Randomized controlled trials of AFOs in people with stroke, which measured balance, walking impairments, or mobility and were reported in English, were selected. Then we independently identified trials, extracted data, and assessed trial quality. Data Extraction: Trials with a low risk of selection, performance, and attrition bias were selected for analysis. Information on the trial design, population recruited, intervention delivered, outcomes measured, and the mean ± SD values for the treatment and control groups were extracted. Data Synthesis: Continuous outcomes were combined using weighted or standardized mean differences with 95% confidence intervals and a fixed-effect model. Thirteen trials with 334 participants were selected. The effect of an AFO on walking activity (P=.000-.001), walking impairment (P=.02), and balance (weight distribution) (P=.003) was significant and beneficial. The effect on postural sway (P=.10) and timed mobility tests (P=.07-.09) was nonsignificant, and the effect on functional balance was mixed. The selected trials were all crossover trials of the immediate effects; long-term effects are unexplored. Conclusions: An AFO can improve walking and balance after stroke, but only the immediate effects have been examined. The effects and acceptability of long-term usage need to be evaluated. © 2013 by the American Congress of Rehabilitation Medicine.


Alldred D.P.,University of Leeds
Cochrane database of systematic reviews (Online) | Year: 2013

There is a substantial body of evidence that prescribing for care home residents is suboptimal and requires improvement. Consequently, there is a need to identify effective interventions to optimise prescribing and resident outcomes in this context. The objective of the review was to determine the effect of interventions to optimise prescribing for older people living in care homes. We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library (Issue 11, 2012); Cochrane Database of Systematic Reviews, The Cochrane Library (Issue 11, 2012); MEDLINE OvidSP (1980 on); EMBASE, OvidSP (1980 on); Ageline, EBSCO (1966 on); CINAHL, EBSCO (1980 on); International Pharmaceutical Abstracts, OvidSP (1980 on); PsycINFO, OvidSP (1980 on); conference proceedings in Web of Science, Conference Proceedings Citation Index - SSH & Science, ISI Web of Knowledge (1990 on); grey literature sources and trial registries; and contacted authors of relevant studies. We also reviewed the references lists of included studies and related reviews (search period November 2012). We included randomised controlled trials evaluating interventions aimed at optimising prescribing for older people (aged 65 years or older) living in institutionalised care facilities. Studies were included if they measured one or more of the following primary outcomes, adverse drug events; hospital admissions;mortality; or secondary outcomes, quality of life (using validated instrument); medication-related problems; medication appropriateness (using validated instrument); medicine costs. Two authors independently screened titles and abstracts, assessed studies for eligibility, assessed risk of bias and extracted data. A narrative summary of results was presented. The eight included studies involved 7653 residents in 262 (range 1 to 85) care homes in six countries. Six studies were cluster-randomised controlled trials and two studies were patient-randomised controlled trials. The interventions evaluated were diverse and often multifaceted. Medication review was a component of seven studies, three studies involved multidisciplinary case-conferencing, two studies involved an educational element for care home staff and one study evaluated the use of clinical decision support technology. Due to heterogeneity, results were not combined in a meta-analysis. There was no evidence of an effect of the interventions on any of the primary outcomes of the review (adverse drug events, hospital admissions and mortality). No studies measured quality of life. There was evidence that the interventions led to the identification and resolution of medication-related problems. There was evidence from two studies that medication appropriateness was improved. The evidence for an effect on medicine costs was equivocal. Robust conclusions could not be drawn from the evidence due to variability in design, interventions, outcomes and results. The interventions implemented in the studies in this review led to the identification and resolution of medication-related problems, however evidence of an effect on resident-related outcomes was not found. There is a need for high-quality cluster-randomised controlled trials testing clinical decision support systems and multidisciplinary interventions that measure well-defined, important resident-related outcomes.


O'Meara S.,University of Leeds
The Cochrane database of systematic reviews | Year: 2013

Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their lives. Many of these wounds are colonised by bacteria or show signs of clinical reporting 12 comparisons); povidone-iodine (six RCTs reporting seven comparisons); peroxide-based preparations (four RCTs reporting four comparisons); honey-based preparations (two RCTs reporting two comparisons); silver-based preparations (12 RCTs reporting 13 comparisons); other topical antibiotics (three RCTs reporting five comparisons); and other topical antiseptics (two RCTs reporting two comparisons). Few RCTs provided a reliable estimate of time to healing; most reported the proportion of participants with complete healing during the trial period. Systemic antibioticsMore participants were healed when they were prescribed levamisole (normally used to treat roundworm infection) compared with placebo: risk ratio (RR) 1.31 (95% CI 1.06 to 1.62). No between-group differences were detected in terms of complete healing for other comparisons: antibiotics given according to antibiogram versus usual care; ciprofloxacin versus standard care/placebo; trimethoprim versus placebo; ciprofloxacin versus trimethoprim; and amoxicillin versus topical povidone-iodine. Topical antibiotics and antisepticsCadexomer iodine: more participants were healed when given cadexomer iodine compared with standard care. The pooled estimate from four RCTs for complete healing at four to 12 weeks was RR 2.17 (95% CI 1.30 to 3.60). No between-group differences in complete healing were detected when cadexomer iodine was compared with the following: hydrocolloid dressing; paraffin gauze dressing; dextranomer; and silver-impregnated dressings.Povidone iodine: no between-group differences in complete healing were detected when povidone-iodine was compared with the following: hydrocolloid; moist or foam dressings according to wound status; and growth factor. Time to healing estimates for povidone-iodine versus dextranomer, and for povidone-iodine versus hydrocolloid, were likely to be unreliable.Peroxide-based preparations: four RCTs reported findings in favour of peroxide-based preparations when compared with usual care for surrogate healing outcomes (change in ulcer area). There was no report of complete healing.Honey-based preparations: no between-group difference in time to healing or complete healing was detected for honey-based products when compared with usual care.Silver-based preparations: no between-group differences in complete healing were detected when 1% silver sulphadiazine ointment was compared with standard care/placebo and tripeptide copper complex; or when different brands of silver-impregnated dressings were compared; or when silver-impregnated dressings were compared with non-antimicrobial dressings.Other topical antibiotics: data from one RCT suggested that more participants healed at four weeks when treated with an enzymatic cleanser (a non-antibiotic preparation) compared with a chloramphenicol-containing ointment (additional active ingredients also included in the ointment): RR 0.13 (95% CI 0.02 to 0.99). No between-group differences in complete healing were detected for framycetin sulphate ointment versus enzymatic cleanser; chloramphenicol ointment versus framycetin sulphate ointment; mupirocin ointment versus vehicle; and topical antibiotics given according to antibiogram versus an herbal ointment.Other topical antiseptics: data from one RCT suggested that more participants receiving an antiseptic ointment (ethacridine lactate) had responsive ulcers (defined as > 20% reduction in area) at four weeks when compared with placebo: RR 1.45 (95% CI 1.21 to 1.73). Complete healing was not reported. No between-group difference was detected between chlorhexidine solution and usual care. At present, no evidence is available to support the routine use of systemic antibiotics in promoting healing of venous leg ulcers. However, the lack of reliable evidence means that it is not possible to recommend the discontinuation of any of the agents reviewed. In terms of topical preparations, some evidence supports the use of cadexomer iodine. Current evidence does not support the routine use of honey- or silver-based products. Further good quality research is required before definitive conclusions can be drawn about the effectiveness of povidone-iodine, peroxide-based preparations, ethacridine lactate, chloramphenicol, framycetin, mupirocin, ethacridine or chlorhexidine in healing venous leg ulceration. In light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial preparations should be used only in cases of clinical infection, not for bacterial colonisation.


Spracklen D.V.,University of Leeds | Righelato R.,University of Reading
Biogeosciences | Year: 2014

Tropical montane forests (TMFs) are recognized for the provision of hydrological services and the protection of biodiversity, but their role in carbon storage is not well understood. We synthesized published observations (n=94) of above-ground biomass (AGB) from forest inventory plots in TMFs (defined here as forests between 23.5° N and 23.5° S with elevations ≥1000 m a.s.l.). We found that mean (median) AGB in TMFs is 271 (254) t per hectare of land surface. We demonstrate that AGB declines moderately with both elevation and slope angle but that TMFs store substantial amounts of biomass, both at high elevations (up to 3500 m) and on steep slopes (slope angles of up to 40°). We combined remotely sensed data sets of forest cover with high resolution data of elevation to show that 75% of the global planimetric (horizontal) area of TMF are on steep slopes (slope angles greater than 27°). We used our remote sensed data sets to demonstrate that this prevalence of steep slopes results in the global land surface area of TMF (1.22 million km2) being 40% greater than the planimetric area that is the usual basis for reporting global land surface areas and remotely sensed data. Our study suggests that TMFs are likely to be a greater store of carbon than previously thought, highlighting the need for conservation of the remaining montane forests. © 2014 Author(s).


This paper explores how the so-called Bilbao effect and Barcelona Model are diffused internationally through what may be called urban policy tourism: short trips made to Bilbao and Barcelona by policy-makers to learn from their regeneration in the past 15 years. The paper reveals for the first time the substantial extent of this practice and contextualises it within a wider phenomenon of urban policy transfer and the international 'motion' of urban policies. Although both models are internationally known for a set of elements, this research shows that in fact the messages mutate and shift as they circulate through the policy circuits. Ultimately, however, the popularity of the Bilbao and Barcelona models suggests a process of global urban policy convergence. © 2010 Urban Studies Journal Limited.


Middlemiss L.,University of Leeds
Local Environment | Year: 2011

There has been increased interest in the role of community-based action in promoting sustainable lifestyles in recent years, but relatively limited evidence on the effects of such activity on participants' behaviours. In this paper, I present an evaluation of the effects of community-based action for sustainability on participants' lifestyles. I draw on extensive qualitative research to assess how much change participants of community sustainability projects report, what kinds of participants these projects attract and how the circumstances of these projects affect the changes that participants make. The main findings are that these initiatives have different effects on different people. Those who are new to sustainability and who are actively involved in cohesive groups, which are specifically targeting their lifestyles, are more likely to report substantial changes. I present a model to explain what change occurs, for which types of participants, in what circumstances as a result of community-based action. © 2011 Taylor & Francis.


Hodkinson S.,University of Leeds
Housing Studies | Year: 2011

Despite the enormous body of scholarship that has tracked the transformation of social housing from the 'public housing model' of the welfare state era to the 'social housing model' of today, large gaps remain in our understanding of this shift. This paper addresses on one such vacuum-the controversial use of the Private Finance Initiative (PFI) as part of the Labour Government's Decent Homes programme in England. Focusing on 'council housing' schemes, a critical overview is presented of the housing PFI experience so far. The main purpose is to understand the motives and drivers behind the use of PFI in housing at different scales, assess the progress of the national PFI programme and explore the significant issues, controversies and challenges encountered. The paper concludes that PFI has proved to be more complicated and expensive than its proponents predicted and should be discontinued in the social housing sector. © 2011 Taylor & Francis.


Foxon T.J.,University of Leeds
Ecological Economics | Year: 2011

This paper proposes a coevolutionary framework for analysing a transition to a sustainable low-carbon economy, based on the coevolution of ecosystems, technologies, institutions, business strategies and user practices, within a multi-level micro-meso-macro perspective. This builds on and develops previous coevolutionary analyses of long-term technological and industrial change, and recent renewed interest within ecological economics on coevolutionary approaches. Previous work has analysed how the coevolution of technologies and institutions has led to the lock-in of current high-carbon energy systems; and how the coevolution of physical and social technologies and business strategies has brought significant material and welfare benefits to the minority of the world's population living in industrialised countries. The coevolutionary framework proposed here may be used to undertake: (1) detailed empirical analyses at a micro-meso level of the challenges relating to the innovation and adoption of particularly low-carbon technologies; (2) as a framework for analysing the multi-level interaction of social and technological elements within potential transition pathways to a low carbon energy system; (3) to assess the implications for economic growth and prosperity of a transition to a low carbon economy; and (4) to assist in the development of more formal, multi-level evolutionary economic models. © 2011 Elsevier B.V.


Jones L.,Overseas Development Institute (ODI) | Boyd E.,University of Leeds
Global Environmental Change | Year: 2011

As the challenges and opportunities posed by climate change become increasingly apparent, the need for facilitating successful adaptation and enhancing adaptive capacity within the context of sustainable development is clear. With adaptation high on the agenda, the notion of limits and barriers to adaptation has recently received much attention within both academic and policymaking spheres. While emerging literature has been quick to depict limits and barriers in terms of natural, financial, or technologic processes, there is a clear shortfall in acknowledging social barriers to adaptation. It is against such a backdrop that this paper sets out to expose and explore some of the underlying features of social barriers to adaptation, drawing on insights from two case studies in the Western Nepal. This paper exposes the significant role of cognitive, normative and institutional factors in both influencing and prescribing adaptation. It explores how restrictive social environments can limit adaptation actions and influence adaptive capacity at the local level, particularly for the marginalised and socially excluded. The findings suggest a need for greater recognition of the diversity and complexity of social barriers, strategic planning and incorporation at national and local levels, as well as an emphasis on tackling the underlying drivers of vulnerability and social exclusion. © 2011 Elsevier Ltd.


Sturman R.,University of Leeds
Advances in Applied Mechanics | Year: 2012

Chaotic advection in fluids is traditionally associated with stretching and folding. Although this is an effective and widely used technique to produce efficient mixing, it is not the only mechanism by which complicated dynamics can be achieved. We discuss the mathematical theory and potential applications connected with mixing by cutting and shuffling, in which all complexity occurs as a result of discontinuities rather than stretching. The interplay of such dynamics with diffusion and stretching and folding is also considered. © 2012 Elsevier Inc.


Bekker H.L.,University of Leeds
Patient Education and Counseling | Year: 2010

Objective: To discuss whether using the International Patient Decision Aids Standards (IPDAS) Collaboration checklist as a gold standard to judge interventions' quality is premature and potentially detrimental to the validity of resources designed to help patients make treatment choices. Methods: Conceptual review integrating the science behind individuals' decision making with the demands of designing complex, healthcare interventions. Results: Patient decision aids are promoted as interventions to help professionals engage in shared and/or patient-centred care. The IPDAS domains were informed by experts' opinions of best practice. Decision scientists study how individuals make decisions, what biases their choices and how best to support decisions. There is debate from decision scientists about which component parts are the active ingredients that help people make decisions. Conclusions: Interventions to help patients make choices have different purposes, component parts and outcomes to those facilitating professional-patient communications. The IPDAS checklist will change to respond to new evidence from the decision sciences. Practice implications: Adhering uncritically to the IPDAS checklist may reduce service variation but is not sufficient to ensure interventions enable good patient decision making. Developers must be encouraged to reason about the IPDAS checklist to identify those component parts that do (not) meet their intervention's purpose. © 2010 Elsevier Ireland Ltd.


Braganza J.M.,Royal Infirmary | Lee S.H.,Royal Infirmary | McCloy R.F.,Lancashire Teaching Hospitals | McMahon M.J.,University of Leeds
The Lancet | Year: 2011

Chronic pancreatitis is a progressive fibroinflammatory disease that exists in large-duct (often with intraductal calculi) or small-duct form. In many patients this disease results from a complex mix of environmental (eg, alcohol, cigarettes, and occupational chemicals) and genetic factors (eg, mutation in a trypsin-controlling gene or the cystic fibrosis transmembrane conductance regulator); a few patients have hereditary or autoimmune disease. Pain in the form of recurrent attacks of pancreatitis (representing paralysis of apical exocytosis in acinar cells) or constant and disabling pain is usually the main symptom. Management of the pain is mainly empirical, involving potent analgesics, duct drainage by endoscopic or surgical means, and partial or total pancreatectomy. However, steroids rapidly reduce symptoms in patients with autoimmune pancreatitis, and micronutrient therapy to correct electrophilic stress is emerging as a promising treatment in the other patients. Steatorrhoea, diabetes, local complications, and psychosocial issues associated with the disease are additional therapeutic challenges. © 2011 Elsevier Ltd.


Harland D.,University of Leeds
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2014

A topological lower bound on the Skyrme energy which depends explicitly on the pion mass is derived This bound coincides with the previously best known bound when the pion mass vanishes, and improves on it whenever the pion mass is non-zero. The new bound can in particular circumstances be saturated New energy bounds are also derived for the Skyrme model on a compact manifold, for the Faddeev-Skyrme model with a potential term, and for the Aratyn-Ferreira-Zimerman and Nicole models. © 2013 The Author. Published by Elsevier B.V.


Undas A.,Jagiellonian University | Ariens R.A.S.,University of Leeds
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2011

The formation of fibrin clots that are relatively resistant to lysis represents the final step in blood coagulation. We discuss the genetic and environmental regulators of fibrin structure in relation to thrombotic disease. In addition, we discuss the implications of fibrin structure for treatment of thrombosis. Fibrin clots composed of compact, highly branched networks with thin fibers are resistant to lysis. Altered fibrin structure has consistently been reported in patients with several diseases complicated by thromboembolic events, including patients with acute or prior myocardial infarction, ischemic stroke, and venous thromboembolism. Relatives of patients with myocardial infarction or venous thromboembolism display similar fibrin abnormalities. Low-dose aspirin, statins, lowering of homocysteine, better diabetes control, smoking cessation, and suppression of inflammatory response increase clot permeability and susceptibility to lysis. Growing evidence indicates that abnormal fibrin properties represent a novel risk factor for arterial and venous thrombotic events, particularly of unknown etiology in young and middle-aged patients. © 2011 American Heart Association, Inc.


Gilbert H.J.,Northumbria University | Knox J.P.,University of Leeds | Boraston A.B.,University of Victoria
Current Opinion in Structural Biology | Year: 2013

Plant cell walls are complex configurations of polysaccharides that are recalcitrant to degradation. The enzymes deployed by microbes to degrade these materials comprise glycoside hydrolases, polysaccharide lyases, carbohydrate esterases and polysaccharide oxidases. Non-catalytic carbohydrate-binding modules (CBMs) are found as discretely folded units within the multi-modular structures of these enzymes where they play critical roles in the recognition of plant cell wall components and potentiating the activity of the enzymes. Here we propose a refinement to the Types A, B, and C classification of CBMs whereby the Type A CBMs remain those that bind the surfaces of crystalline polysaccharides but the Type B CBMs are redefined as those that bind internally on glycan chains ( endo-type), CBMs that bind to the termini of glycan chains are defined as Type C modules ( exo-type). In this context, we discuss recent advances, primarily driven by structural studies, which reveal the molecular modes of CBM-sugar interactions and how this specifically underpins and influences the biological function of CBMs in cell wall recognition and degradation. © 2013 Elsevier Ltd.


Chronic lymphocytic leukaemia (CLL) is the most common clonal B-cell disorder characterized by clonal diversity, a relapsing and remitting course, and in its aggressive forms remains largely incurable. Current front-line regimes include agents such as fludarabine, which act primarily via the DNA damage response pathway. Key to this is the transcription factor p53. Mutations in the TP53 gene, altering p53 functionality, are associated with genetic instability, and are present in aggressive CLL. Furthermore, the emergence of clonal TP53 mutations in relapsed CLL, refractory to DNA-damaging therapy, suggests that accurate detection of sub-clonal TP53 mutations prior to and during treatment may be indicative of early relapse. In this study, we describe a novel deep sequencing workflow using multiple polymerases to generate sequencing libraries (MuPol-Seq), facilitating accurate detection of TP53 mutations at a frequency as low as 0.3%, in presentation CLL cases tested. As these mutations were mostly clustered within the regions of TP53 encoding DNA-binding domains, essential for DNA contact and structural architecture, they are likely to be of prognostic relevance in disease progression. The workflow described here has the potential to be implemented routinely to identify rare mutations across a range of diseases.Oncogene advance online publication, 4 April 2016; doi:10.1038/onc.2016.73. © 2016 Macmillan Publishers Limited


Romheld V.,University of Hohenheim | Kirkby E.A.,University of Leeds
Plant and Soil | Year: 2010

This review highlights future needs for research on potassium (K) in agriculture. Current basic knowledge of K in soils and plant physiology and nutrition is discussed which is followed by sections dealing specifically with future needs for basic and applied research on K in soils, plants, crop nutrition and human and animal nutrition. The section on soils is devoted mainly to the concept of K availability. The current almost universal use of exchangeable K measurements obtained by chemical extraction of dried soil for making fertilizer recommendations is questioned in view of other dominant controlling factors which influence K acquisition from soils by plants. The need to take account of the living root which determines spatial K availability is emphasized. Modelling of K acquisition by field crops is discussed. The part played by K in most plant physiological processes is now well understood including the important role of K in retranslocation of photoassimilates needed for good crop quality. However, basic research is still needed to establish the role of K from molecular level to field management in plant stress situations in which K either acts alone or in combination with specific micronutrients. The emerging role of K in a number of biotic and abiotic stress situations is discussed including those of diseases and pests, frost, heat/drought, and salinity. Breeding crops which are highly efficient in uptake and internal use of K can be counterproductive because of the high demand for K needed to mitigate stress situations in farmers' fields. The same is true for the need of high K contents in human and animal diets where a high K/Na ratio is desirable. The application of these research findings to practical agriculture is of great importance. The very rapid progress which is being made in elucidating the role of K particularly in relation to stress signalling by use of modern molecular biological approaches is indicative of the need for more interaction between molecular biologists and agronomists for the benefit of agricultural practice. The huge existing body of scientific knowledge of practical value of K in soils and plants presents a major challenge to improving the dissemination of this information on a global scale for use of farmers. To meet this challenge closer cooperation between scientists, the agrochemical industry, extension services and farmers is essential. © 2010 Springer Science+Business Media B.V.


Foyer C.H.,University of Leeds | Noctor G.,University Paris - Sud
Antioxidants and Redox Signaling | Year: 2013

Our aim is to deliver an authoritative and challenging perspective of current concepts in plant redox signaling, focusing particularly on the complex interface between the redox and hormone-signaling pathways that allow precise control of plant growth and defense in response to metabolic triggers and environmental constraints and cues. Plants produce significant amounts of singlet oxygen and other reactive oxygen species (ROS) as a result of photosynthetic electron transport and metabolism. Such pathways contribute to the compartment-specific redox-regulated signaling systems in plant cells that convey information to the nucleus to regulate gene expression. Like the chloroplasts and mitochondria, the apoplast-cell wall compartment makes a significant contribution to the redox signaling network, but unlike these organelles, the apoplast has a low antioxidant-buffering capacity. The respective roles of ROS, low-molecular antioxidants, redox-active proteins, and antioxidant enzymes are considered in relation to the functions of plant hormones such as salicylic acid, jasmonic acid, and auxin, in the composite control of plant growth and defense. Regulation of redox gradients between key compartments in plant cells such as those across the plasma membrane facilitates flexible and multiple faceted opportunities for redox signaling that spans the intracellular and extracellular environments. In conclusion, plants are recognized as masters of the art of redox regulation that use oxidants and antioxidants as flexible integrators of signals from metabolism and the environment. © Copyright 2013, Mary Ann Liebert, Inc.


Peterfy C.,Spire science LLC | Ostergaard M.,Copenhagen University | Conaghan P.G.,University of Leeds
Annals of the Rheumatic Diseases | Year: 2013

The success of modern rheumatoid arthritis (RA) therapies and treatment strategies has led to extended placebo phases being unethical in RA randomised controlled trials (RCTs). Modern trials therefore increasingly involve active comparator designs, and this together with some technical issues has meant difficulties in differentiating structural progression using traditional radiographic outcome measures. Magnetic resonance imaging (MRI) has been demonstrated to assess damage more sensitively than radiographs, but importantly it can measure the upstream drivers of erosions and cartilage loss, synovitis and osteitis. An increasing number of recent RCTs using the RA MRI scoring system (RAMRIS) have demonstrated the ability of MRI to discriminate progression and treatment effect. Consistency of erosion progression determination was seen across the majority of these studies. In most studies, MRI demonstrated reduction in synovitis and osteitis at early (12 week) timepoints, and MRI predicted subsequent radiographic findings. Often small numbers of patients were required to demonstrate such changes. The time is right for regulatory authorities to include MRI as an alternative to radiographic data in support of claims of inhibition of progression of structural damage in RA trials.


Conaghan P.G.,University of Leeds
Clinical Rheumatology | Year: 2011

Biologic therapies have brought improved efficacy in the field of rheumatoid arthritis (RA), but their use in clinical practice may be limited by concerns over cost. Predictive models are, therefore, needed to identify those people with RA with the worst potential outcomes, who will benefit most from the use of these drugs. A variety of studies have investigated factors that will predict the onset of RA to allow preventative intervention and the identification of prognostic factors to guide the need for aggressive treatment at the time of diagnosis and prognostic factors in patients who have failed on optimal traditional therapies-all strategies to guide the cost-effective use of modern therapies. Prediction rules have been developed that are sensitive and specific, but many are limited by their complexity or the need for biomarkers that will never be routinely measured in the clinic. Most rules to date have therefore failed to have a major impact on clinical practice. Probably most interesting is the prediction of response to therapy based upon early treatment response, with outcomes at as early as 3 months predicting response at 12 months. Further work is needed, however, to identify the efficacy of current therapies in preventing disease onset and the long-term cost-effectiveness of appropriately targeted treatment with biologics. © 2011 Clinical Rheumatology.


The present paper seeks to establish a logical foundation for studying axiomatically multi-agent probabilistic reasoning over a discrete space of outcomes. We study the notion of a social inference process which generalises the concept of an inference process for a single agent which was used by Paris and Vencovská to characterise axiomatically the method of maximum entropy inference. Axioms for a social inference process are introduced and discussed, and a particular social inference process called the Social Entropy Process, or SEP, is defined which satisfies these axioms. SEP is justified heuristically by an information theoretic argument, and incorporates both the maximum entropy inference process for a single agent and the multi-agent normalised geometric mean pooling operator. © 2015 by the author.


Childs T.H.C.,University of Leeds
CIRP Journal of Manufacturing Science and Technology | Year: 2010

Finite element simulations of continuous chip formation have been carried out over a range of uncut chip thicknesses from 0.002 to 0.25 mm and for tools with cutting edge radii from 5 to 160. μm, using material models for annealed or normalised medium carbon steels. Expressions are derived for the dependence of ploughing forces on edge radius, uncut chip thickness and chip shear plane angle and flow stress. Non-linearity of force variation with uncut chip thickness is demonstrated, in addition to what might result from ploughing, caused by variations of temperature and strain-rate and hence of work material shear flow stress. These ploughing and non-linearity effects quantitatively account for the well-known size effects associated with machining, certainly for the machining of steels. There is no need to include ductile fracture energy from forming fresh surfaces in models of continuous chip formation in order to account for the size effect. © 2010 CIRP.


Recently, the modelling of heterogeneous traffic flow has gained significant attention from traffic theorists. The influence of slow vehicles (e.g. trucks) on traffic operations has been studied both from a micro and macroscopic level. Though multiclass traffic models have been successfully developed in literature, few of them are adequately used to describe traffic network operations. To this end, this article aims to propose a model to study the (heterogeneous) traffic network operations based on the macroscopic modelling approach. More specifically, on the one hand, we introduce an extension of the classic Lighthill-Whitham-Richards model to describe multiclass traffic operations in the network. The proposed model is based on solving a system of hyperbolic partial differential equations describing multiclass traffic dynamics with discontinuous fluxes. On the other hand, a dynamic routing algorithm is applied to determine the turning flow at nodes based on the information provision of the current network situation. Numerical results have shown that the proposed model can capture some real traffic phenomena in multiclass traffic networks. © 2010 Hong Kong Society for Transportation Studies Limited.


De Tute R.M.,University of Leeds
Histopathology | Year: 2011

The last decade has seen major advances in flow cytometric immunophenotyping and this has expanded the utility of flow cytometry to investigate the antigens present on normal and neoplastic haematopoietic cells. This review summarizes how flow cytometry is used currently in the diagnosis and management of mature lymphoid malignancies. The establishment of disease-specific phenotypes allows the creation of assays which can detect neoplastic cells with high specificity and sensitivity. Certain lymphoid neoplasms are well defined immunophenotypically, while others are more heterogeneous. The availability of more sophisticated cytometers and a wider selection of antibodies in routine diagnostic laboratories will lead to the resolution of these more complex disease entities. © 2011 Blackwell Publishing Limited.


Suares N.C.,Leeds Gastroenterology Institute | Ford A.C.,Leeds Gastroenterology Institute | Ford A.C.,University of Leeds
American Journal of Gastroenterology | Year: 2011

Objectives: Chronic idiopathic constipation (CIC) is a common functional gastrointestinal disorder in the community, yet no previous systematic review and meta-analysis has estimated the global prevalence, or potential risk factors for the condition. Methods: MEDLINE, EMBASE, and EMBASE Classic were searched (up to December 2010) to identify population-based studies reporting the prevalence of CIC in adults (≥15 years), according to self-report, questionnaire, or specific symptom-based criteria. The prevalence of CIC was extracted for all studies, and according to country, age, gender, socioeconomic status, and presence or absence of irritable bowel syndrome (IBS) where reported. Pooled prevalence overall, and according to study location and certain other characteristics, as well as odds ratios (ORs), with 95% confidence intervals (CIs) were calculated. Results: Of the 100 papers evaluated, 45 reported the prevalence of CIC in 41 separate study populations, containing 261,040 subjects. Pooled prevalence of CIC in all studies was 14% (95% CI: 12-17%). The prevalence of CIC was lower in South East Asian studies, and in studies using the Rome II or III criteria. The prevalence of CIC was higher in women (OR: 2.22; 95% CI: 1.87-2.62), and increased with age and lower socioeconomic status. The prevalence was markedly higher in subjects who also reported IBS (OR: 7.98; 95% CI: 4.58-13.92), suggesting common pathogenic mechanisms. Conclusions: Pooled prevalence of CIC in the community was 14%, and of similar magnitude in most geographical regions. Rates were higher in women, older individuals, and those of lower socioeconomic status. Presence of IBS was strongly associated with CIC. © 2011 by the American College of Gastroenterology.


Yusoff A.,University Technology of MARA | Murray B.S.,University of Leeds
Food Hydrocolloids | Year: 2011

Oil-in-water (O/W) emulsions of 20. vol% n-tetradecane have been prepared using food-compatible hydrophobic starch particulates as the primary emulsifier. As such, the systems appear to be Pickering emulsions. The starch particulates were generated from chemically cross-linked granules that do not swell on prolonged contact with water and which were made partially hydrophobic by reaction with octenyl succinic anhydride. The degree of substitution was of the order of 0.03. The size of the modified starch particulates was reduced by freezer-milling before preparing the emulsions via a jet homogenizer. Conventional light transmission microscopy, confocal laser scanning microscopy, scanning electron microscopy, multi-angle light scattering and laser Doppler light scattering all suggested that a wide range of starch particle sizes was produced. Some particles were considerably smaller than the original starch granule sizes, but a large proportion appeared to be above several microns in size. The emulsion droplets produced using 1-3. wt.% of starch as emulsifier were quite large (from approximately 1 to 20. μm in diameter), i.e., of the same order of size as a large proportion of the starch particulates. Consequently, the emulsions creamed readily, but they were extremely stable to coalescence with no significant change in the emulsion droplet-size distributions appearing for over 3 months. Further tests on the surface tensions of the homogenized and non-homogenized starch dispersions themselves confirmed the supposition that the O/W emulsions were stabilized by starch particulates and not starch molecules. © 2010 Elsevier Ltd.


Eisele H.,University of Leeds
Electronics Letters | Year: 2010

An InP Gunn device with a graded doping profile was evaluated for third-harmonic power extraction around 480GHz. The oscillator used the configuration of a WR-6 waveguide cavity for the InP Gunn device, two back-to-back waveguide transitions, WR-3→1.5 and WR-1.7→3, to block fundamental and second-harmonic frequencies, and WR-6 waveguide spacers to optimise the location of the reactive termination at the fundamental frequency. With 350m-thick spacers, the oscillator yielded an RF output power of more than 85 μW at 479.01GHz. © 2010 The Institution of Engineering and Technology.


Dickinson E.,University of Leeds
Food Hydrocolloids | Year: 2011

Mixed biopolymer layers are commonly involved in the stabilization of food emulsions and foams. The interfacial composition and structure of mixed layers are predominantly determined by two mechanistic phenomena-competitive adsorption from mixed solution and cooperative adsorption into multilayers. The surface-active protein components typically dominate primary layers around droplets and bubbles, and the interacting polysaccharides form outer secondary stabilizing layers. This article reviews progress in understanding the factors controlling the nanoscale structure and physico-chemical properties of adsorbed layers in colloidal systems containing mixtures of biopolymers. Contributions from different experimental techniques are described, with particular attention directed towards the role of surface shear rheology in providing information on competitive adsorption of proteins and macromolecular interactions at fluid interfaces. We also consider here the phenomenon of phase separation in mixed protein monolayers, the balance of thermodynamic and kinetic factors in determining biopolymer layer properties, and the involvement of electrostatic interactions in the stabilization of emulsions by protein-polysaccharide complexes. © 2010 Elsevier Ltd.


Prabhakaran P.,University of Leeds | Priya G.,CSIR - National Chemical Laboratory | Sanjayan G.J.,CSIR - National Chemical Laboratory
Angewandte Chemie - International Edition | Year: 2012

A new door is open! Foldamers have been successfully utilized for the development of a molecular device. Termed foldaxanes by analogy with rotaxanes, these structures are formed through a multitude of noncovalent interactions between double-helical foldamers and rod-shaped guest molecules. The foldaxanes move in a screw-type motion and open up yet another promising application of foldamers in materials science. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Gierula J.,University of Leeds
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology | Year: 2013

Heart failure and left ventricular (LV) systolic dysfunction (LVSD) are common in patients with permanent pacemakers. The aim was to determine if cardiac resynchronization therapy (CRT) at the time of pulse generator replacement (PGR) is of benefit in patients with unavoidable RV pacing and LVSD. Fifty patients with unavoidable RV pacing, LVSD, and mild or no symptoms of heart failure, listed for PGR were randomized 1 : 1 to either standard RV-PGR (comparator) or CRT. The primary endpoint was the difference in change in LV ejection fraction (LVEF) between RV-PGR and CRT groups from baseline to 6 months. Secondary endpoints included peak oxygen consumption, quality of life, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. At 6 months there was a difference in change in median (interquartile range) LVEF [9 (6-12) vs. -1.5 (-4.5 to -0.8)%; P < 0.0001] between the CRT and RV-PGR arms. There were also improvements in exercise capacity (P = 0.007), quality of life (P = 0.03), and NT-proBNP (P = 0.007) in those randomized to CRT. After 809 (729-880) days, 17 patients had died or been hospitalized (6 in CRT group and 11 in the comparator RV-PGR group) and two patients in the RV-PGR arm had required CRT for deteriorating heart failure. Patients with standard RV-PGR had more days in hospital during follow-up than those in the CRT group [4 (2-7) vs. 11 (6-16) days; P = 0.047]. Performing CRT in pacemaker patients with unavoidable RV pacing and LVSD but without severe symptoms of heart failure, at the time of PGR, improves cardiac function, exercise capacity, quality of life, and NT-pro-BNP levels.


Del Bianco M.,University of Leeds
Cold Spring Harbor perspectives in biology | Year: 2011

Auxin is a simple molecule with a remarkable ability to control plant growth, differentiation, and morphogenesis. The mechanistic basis for this versatility appears to stem from the highly complex nature of the networks regulating auxin metabolism, transport and response. These heavily feedback-regulated and inter-dependent mechanisms are complicated in structure and complex in operation giving rise to a system with self-organizing properties capable of generating highly context-specific responses to auxin as a single, generic signal.


Grace J.,University of Edinburgh | Mitchard E.,University of Edinburgh | Gloor E.,University of Leeds
Global Change Biology | Year: 2014

The carbon budget of the tropics has been perturbed as a result of human influences. Here, we attempt to construct a 'bottom-up' analysis of the biological components of the budget as they are affected by human activities. There are major uncertainties in the extent and carbon content of different vegetation types, the rates of land-use change and forest degradation, but recent developments in satellite remote sensing have gone far towards reducing these uncertainties. Stocks of carbon as biomass in tropical forests and woodlands add up to 271 ± 16 Pg with an even greater quantity of carbon as soil organic matter. Carbon loss from deforestation, degradation, harvesting and peat fires is estimated as 2.01 ± 1.1 Pg annum-1; while carbon gain from forest and woodland growth is 1.85 ± 0.09 Pg annum-1. We conclude that tropical lands are on average a small carbon source to the atmosphere, a result that is consistent with the 'top-down' result from measurements in the atmosphere. If they were to be conserved, they would be a substantial carbon sink. Release of carbon as carbon dioxide from fossil fuel burning in the tropics is 0.74 Pg annum-1 or 0.57 MgC person-1 annum-1, much lower than the corresponding figures from developed regions of the world. © 2014 John Wiley & Sons Ltd.


Smith M.W.,University of Leeds
Earth-Science Reviews | Year: 2014

Rough surfaces are ubiquitous in nature. Near-surface processes both encounter and create surface roughness. Recent advances in surveying have improved the resolution, extent and availability of topographic datasets. This broad review synthesises efforts to represent surface roughness in such datasets, drawing examples from a number of branches of Earth Science, with the aim of facilitating a more systematic exchange of roughness formulations. A number of issues surround the definition of roughness. The term 'roughness' has been applied variously to represent a property of a surface, a property of a flow and as a model tuning parameter; yet these distinctions are articulated rarely. There has been a proliferation of methods of quantifying surface roughness. Given the wide range of applications of roughness in the Earth Sciences, attempts to create a standardised parameter set will likely be problematic. Yet a standard protocol for reporting roughness calculation would be appropriate, especially considering the importance of the choice of partition scale in the distinction between roughness and topography. Applications of surface roughness treat it as a variable (in the mapping of landforms, for example), a surrogate for less measurable variables (as in the estimation of resistance to flows) or as an indicator of near-surface processes. Recent developments examining interactions between roughness elements (e.g. sheltering) highlight the need to consider the pattern of surface roughness (e.g. anisotropy, connectivity of peaks) if appropriate parameterisations are to be developed. Addressing these issues will maximise the exciting potential offered by advances in topographic surveys. © 2014 Elsevier B.V.


Lenton T.M.,University of Exeter | Boyle R.A.,University of Exeter | Poulton S.W.,University of Leeds | Shields-Zhou G.A.,University College London | Butterfield N.J.,University of Cambridge
Nature Geoscience | Year: 2014

The Neoproterozoic era (about 1,000 to 542 million years ago) was a time of turbulent environmental change. Large fluctuations in the carbon cycle were associated with at least two severe-possible Snowball Earth-glaciations. There were also massive changes in the redox state of the oceans, culminating in the oxygenation of much of the deep oceans. Amid this environmental change, increasingly complex life forms evolved. The traditional view is that a rise in atmospheric oxygen concentrations led to the oxygenation of the ocean, thus triggering the evolution of animals. We argue instead that the evolution of increasingly complex eukaryotes, including the first animals, could have oxygenated the ocean without requiring an increase in atmospheric oxygen. We propose that large eukaryotic particles sank quickly through the water column and reduced the consumption of oxygen in the surface waters. Combined with the advent of benthic filter feeding, this shifted oxygen demand away from the surface to greater depths and into sediments, allowing oxygen to reach deeper waters. The decline in bottom-water anoxia would hinder the release of phosphorus from sediments, potentially triggering a potent positive feedback: phosphorus removal from the ocean reduced global productivity and ocean-wide oxygen demand, resulting in oxygenation of the deep ocean. That, in turn, would have further reinforced eukaryote evolution, phosphorus removal and ocean oxygenation. © 2014 Macmillan Publishers Limited. All rights reserved.


Shepherd S.P.,University of Leeds
Transportmetrica B | Year: 2014

It is 20 years since Abbas and Bell [1994. "System Dynamics Applicability to Transportation Modeling." Transportation Research Part A 28 (5): 373-390] evaluated the strengths and weaknesses of system dynamics (SD) as an approach for modelling in the transportation area. They listed 12 advantages of the approach and in particular suggested it was well suited to strategic issues and that it could provide a useful tool for supporting policy analysis and decision-making in the transport field. This paper sets out a review of over 50 peer-reviewed journal papers since 1994 categorising them by area of application and providing a summary of particular insights raised. The fields of application include the take-up of alternate fuel vehicles, supply chain management affecting transport, highway maintenance, strategic policy, airport infrastructure and airline business cycles and a set of emerging application areas. The paper concludes with recommendations for future application of the SD approach. © 2014 Hong Kong Society for Transportation Studies Limited.


Molnar P.,University of Colorado at Boulder | Houseman G.A.,University of Leeds
Journal of Geophysical Research: Solid Earth | Year: 2013

Surface topography and associated gravity anomalies above a layer resembling continental lithosphere, whose mantle part is gravitationally unstable, depend strongly on the ratio of viscosities of the lower-density crustal part to that of the mantle part. For linear stability analysis, growth rates of Rayleigh-Taylor instabilities depend largely on the wave number, or wavelength, of the perturbation to the base of the lithosphere and weakly on this viscosity ratio, on plausible density differences among crust, mantle lithosphere, and asthenosphere, and on ratios of crustal to total lithospheric thicknesses. For all likely densities, viscosities, and thicknesses, the Moho is drawn down (pushed up) where the base of the lithosphere subsides (rises). For large viscosities of crust compared to mantle lithosphere (ratios>~30), a sinking and thickening mantle lithosphere also pulls the surface down. For smaller viscosity ratios, crustal thickening overwhelms the descent of the Moho, and the surface rises (subsides) above regions where mantle lithosphere thickens and descends (thins and rises). Ignoring vertical variations of viscosity within the crust and mantle lithosphere, we find that the maximum surface height occurs for approximately equal viscosities of crust and mantle lithosphere. For large crust/mantle lithosphere viscosity ratios, gravity anomalies follow those of surface topography, with negative (positive) free-air anomalies over regions of descent (ascent). In this case, topography anomalies are smaller than those that would occur if the lithosphere were in isostatic equilibrium. Hence, flow-induced stresses-dynamic pressure and deviatoric stress-create smaller topography than that expected for an isostatic state. For small crust/mantle viscosity ratios (< ~10), however, calculated surface topography at long wavelengths is greater than it would be if the lithospheric column were in isostatic equilibrium, and at short wavelengths local isostasy predicts surface deflections of the wrong sign. For the range of wavelengths appropriate for convergent mountain belts (~150-600 km), calculated gravity anomalies are negative over regions of lithospheric thickening, especially when allowance for flexural rigidity of a surface layer is included. Correspondingly, calculated values of admittance, the ratio of Fourier transforms of surface topography and free-air gravity anomalies, are also negative for wave numbers relevant to mountain belts. For essentially all mountain belts, however, measured free-air anomalies and admittance are positive. Whether gravitational instability of the lithosphere affects the structure of convergent belts or not, its contribution to the topography of mountain belts seems to be small compared to that predicted for isostatic balance of crustal thickness variations. © 2013. American Geophysical Union. All Rights Reserved.


Ngoduy D.,University of Leeds
Transportmetrica | Year: 2012

In this article, we propose an extended multiclass gas-kinetic theory applicable to mixed traffic flow of manual and adaptive cruise control (ACC) vehicles. In the model, the acceleration/deceleration of ACC vehicles is specified explicitly using microscopic models. The macroscopic multiclass traffic equations are obtained from the proposed gas-kinetic model using the well-known method of moments. The influencing conditions to traffic flow stability with respect to a small perturbation are derived by the linear stability method. The analytical results show that ACC vehicles contribute to the improved stabilisation of traffic flow. The numerical simulations of our developed multiclass macroscopic model on a circular freeway support our analytical findings and indicate that increasing the penetration of ACC vehicles results in more stable traffic flow. Simulations of merging flows at an on-ramp in an open freeway are carried out to describe the effects of the penetration of ACC vehicles on the bottleneck capacity. It is found that around 30% ACC vehicles in traffic flow leads to significantly increased capacity and reduced travel time. We argue that, together with other microscopic models, our model provides a wider picture of the effects of ACC vehicles on traffic flow characteristics. © 2011 Copyright Taylor and Francis Group, LLC.


Gadsby E.W.,University of Leeds
International Journal of Health Planning and Management | Year: 2011

Increasing attention, and a concomitant increase in funds, is being devoted to the strengthening of research capacity for health within low- and middle-income countries. Yet approaches to research capacity strengthening (RCS) are still new, and there is much debate about how to strengthen something that is so difficult to define, let alone measure. This paper aims to inform our understanding of how research capacity is being strengthened, and how we might consider the effectiveness of these initiatives. It does this by examining (a) understandings of and approaches to RCS, and (b) different ways in which RCS is monitored and evaluated. The study included a literature review, internet search, and analysis of the web pages and available documents for six donor organizations key to health RCS. E-mail and telephone discussions were conducted with experts in the area of health RCS, as well as semi-structured telephone interviews with representatives from the six identified organizations. The study found that understandings of and approaches to RCS are wide ranging. We are at the early stages of knowing how best to identify, target and affect the many factors that are important for stronger research capacity. Furthermore, as RCS initiatives become more wide-ranging and complex, they become more difficult to monitor and evaluate. Donors are struggling with many challenges associated with tracking RCS initiatives. There is no consensus on the best methods or tools to use. There is a clear need for improved strategies and the development of a tried and tested framework for RCS tracking. © 2010 John Wiley & Sons, Ltd.


He Q.,CAS Shanghai Institute of Ceramics | He Q.,University of Leeds | Shi J.,CAS Shanghai Institute of Ceramics
Advanced Materials | Year: 2014

In the anti-cancer war, there are three main obstacles resulting in high mortality and recurrence rate of cancers: the severe toxic side effect of anti-cancer drugs to normal tissues due to the lack of tumor-selectivity, the multi-drug resistance (MDR) to free chemotherapeutic drugs and the deadly metastases of cancer cells. The development of state-of-art nanomedicines based on mesoporous silica nanoparticles (MSNs) is expected to overcome the above three main obstacles. In the view of the fast development of anti-cancer strategy, this review highlights the most recent advances of MSN anti-cancer nanomedicines in enhancing chemotherapeutic efficacy, overcoming the MDR and inhibiting metastasis. Furthermore, we give an outlook of the future development of MSNs-based anti-cancer nanomedicines, and propose several innovative and forward-looking anti-cancer strategies, including tumor tissue-cell-nuclear successionally targeted drug delivery strategy, tumor cell-selective nuclear-targeted drug delivery strategy, multi-targeting and multi-drug strategy, chemo-/radio-/photodynamic-/ultrasound-/thermo-combined multi-modal therapy by virtue of functionalized hollow/rattle-structured MSNs. Anti-cancer nanomedicine: mesoporous silica nanoparticle (MSN) nanomedicines functionalized with targeting, burst responsive, and payload units, as well as a stealth coating, can enhance the chemotherapeutic efficacy and lower toxic side effects by tumor/cell membrane/nuclear-targeted drug delivery and pH/redox/protease- responsive drug release. Moreover, MSN nanomedicines overcome multi-drug resistance by the multi-drug synergy strategy, the effluxcircumventing strategy, and the multimodal combination therapy strategy, and inhibit tumor metastasis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Thornton P.K.,CGIAR Research Programme on Climate Change | Ericksen P.J.,Kenya International Livestock Research Institute | Herrero M.,CSIRO | Challinor A.J.,University of Leeds
Global Change Biology | Year: 2014

The focus of the great majority of climate change impact studies is on changes in mean climate. In terms of climate model output, these changes are more robust than changes in climate variability. By concentrating on changes in climate means, the full impacts of climate change on biological and human systems are probably being seriously underestimated. Here, we briefly review the possible impacts of changes in climate variability and the frequency of extreme events on biological and food systems, with a focus on the developing world. We present new analysis that tentatively links increases in climate variability with increasing food insecurity in the future. We consider the ways in which people deal with climate variability and extremes and how they may adapt in the future. Key knowledge and data gaps are highlighted. These include the timing and interactions of different climatic stresses on plant growth and development, particularly at higher temperatures, and the impacts on crops, livestock and farming systems of changes in climate variability and extreme events on pest-weed-disease complexes. We highlight the need to reframe research questions in such a way that they can provide decision makers throughout the food system with actionable answers, and the need for investment in climate and environmental monitoring. Improved understanding of the full range of impacts of climate change on biological and food systems is a critical step in being able to address effectively the effects of climate variability and extreme events on human vulnerability and food security, particularly in agriculturally based developing countries facing the challenge of having to feed rapidly growing populations in the coming decades. © 2014 The Authors.


Angus D.A.,University of Leeds
Surveys in Geophysics | Year: 2014

The study of seismic body waves is an integral aspect in global, exploration and engineering scale seismology, where the forward modeling of waves is an essential component in seismic interpretation. Forward modeling represents the kernel of both migration and inversion algorithms as the Green's function for wavefield propagation and is also an important diagnostic tool that provides insight into the physics of wave propagation and a means of testing hypotheses inferred from observational data. This paper introduces the one-way wave equation method for modeling seismic wave phenomena and specifically focuses on the so-called operator-root one-way wave equations. To provide some motivation for this approach, this review first summarizes the various approaches in deriving one-way approximations and subsequently discusses several alternative matrix narrow-angle and wide-angle formulations. To demonstrate the key strengths of the one-way approach, results from waveform simulation for global scale shear-wave splitting modeling, reservoir-scale frequency-dependent shear-wave splitting modeling and acoustic waveform modeling in random heterogeneous media are shown. These results highlight the main feature of the one-way wave equation approach in terms of its ability to model gradual vector (for the elastic case) and scalar (for the acoustic case) waveform evolution along the underlying wavefront. Although not strictly an exact solution, the one-way wave equation shows significant advantages (e.g., computational efficiency) for a range of transmitted wave three-dimensional global, exploration and engineering scale applications. © 2013 Springer Science+Business Media Dordrecht.


Baird A.J.,University of Leeds | Heppell C.M.,Queen Mary, University of London
Geophysical Research Letters | Year: 2013

We measured the escape of methane-containing gas bubbles to the water table in two microhabitats (muddy hollows and Sphagnum-plus-sedge lawns) in a raised bog in West Wales, typical of many northern peatlands. Our study was unusual in its degree of replication (14 gas traps in each microhabitat). Seasonally integrated bubble loss of CH4 to the water table did not differ significantly between microhabitats. After applying an oxidation correction to give CH4 fluxes to the atmosphere, the microhabitats still did not differ. Our results suggest that ebullition is an important mechanism of CH 4 loss to the atmosphere, with mean summer rates of 11.7 mg CH 4 m-2 d-1 (muddy hollows) and 6.8 mg CH 4 m-2 d-1 (Sphagnum-plus-sedge lawns). Our data show that the process is spatially and temporally very variable, and that the small sample sizes of many studies (e.g., n = 5) may lead to considerable errors in flux estimation. © 2013 American Geophysical Union. All Rights Reserved.


Chopra I.,University of Leeds
Journal of Antimicrobial Chemotherapy | Year: 2013

The discovery and development of antibacterial drugs in the twentieth century were major scientific and medical achievements that have had profound benefits for human society. However, in the twenty-first century the widespread global occurrence of bacteria resistant to the antibiotics and synthetic drugs discovered in the previous century threatens to reverse our ability to treat infectious diseases. Although some new drugs are in development they do not adequately cover growing medical needs. Furthermore, these drugs are mostly derivatives of older classes already in use and therefore prone to existing bacterial resistance mechanisms. Thus, new drug classes are urgently needed. Despite investment in antibacterial drug discovery, no new drug class has been discovered in the past 20 years. In this review, based upon my career as a research scientist in the field of antibacterial drug discovery, I consider some of the technical reasons for the recent failure and look to the future developments that may help to reverse the poor current success rate. Diversification of screening libraries to include new natural products will be important as well as ensuring that the promising drug hits arising from structure-based drug design can achieve effective concentrations at their target sites within the bacterial cell. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Abstract A systematic approach was used for the cloning and amplified expression in Escherichia coli of the genes for each of three inositol transport proteins (IolF, IolT, YfiG) from Bacillus subtilis that are evolutionarily-related to human transporters. Inducible amplified expression of each was achieved to levels of ∼ 10-15% of total protein in E. coli inner membrane preparations. The functional integrity of each heterologously-expressed protein was demonstrated by measuring the kinetics of (3)H-myo-inositol transport into energized whole cells; this confirmed that IolT is the major inositol transporter, IolF is an inefficient transporter of this substrate and demonstrated that YfiG is an inositol transport protein for the first time. Competition for (3)H-myo-inositol transport by 17 unlabelled compounds revealed all three proteins to be highly specific in recognizing inositols over sugars. IolT was confirmed to be highly specific for both myo- and D-chiro-inositol and IolF was confirmed to prefer D-chiro-inositol over myo-inositol. YfiG selectively recognized myo-inositol, D-chiro-inositol and, uniquely, L-chiro-inositol. All three proteins were successfully solubilized and purified in milligram quantities from inner membrane preparations and their suitability for inclusion in crystallization trials was assessed by analysis of structural integrity and thermal stability using circular dichroism spectroscopy followed by examination for monodispersity using gel filtration chromatography.


Van Wezel G.P.,Leiden University | McDowall K.J.,University of Leeds
Natural Product Reports | Year: 2011

Streptomycetes and other actinobacteria are renowned as a rich source of natural products of clinical, agricultural and biotechnological value. They are being mined with renewed vigour, supported by genome sequencing efforts, which have revealed a coding capacity for secondary metabolites in vast excess of expectations that were based on the detection of antibiotic activities under standard laboratory conditions. Here we review what is known about the control of production of so-called secondary metabolites in streptomycetes, with an emphasis on examples where details of the underlying regulatory mechanisms are known. Intriguing links between nutritional regulators, primary and secondary metabolism and morphological development are discussed, and new data are included on the carbon control of development and antibiotic production, and on aspects of the regulation of the biosynthesis of microbial hormones. Given the tide of antibiotic resistance emerging in pathogens, this review is peppered with approaches that may expand the screening of streptomycetes for new antibiotics by awakening expression of cryptic antibiotic biosynthetic genes. New technologies are also described that have potential to greatly further our understanding of gene regulation in what is an area fertile for discovery and exploitation. © 2011 The Royal Society of Chemistry.


Bedingfield P.T.,University of Leeds
Journal of medicinal chemistry | Year: 2012

The de novo pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase is an emerging drug target for the treatment of malaria. In this context a key property of Plasmodium falciparum DHODH (PfDHODH) is that it can be selectively inhibited over its human homologue (HsDHODH). However, HsDHODH is also a validated drug target for autoimmune diseases such as arthritis. Here a series of novel inhibitors is described that includes compounds that switch specificity between the two enzymes as a result of small alterations in chemical structure. Structure-activity relationship (SAR), crystallography, docking, and mutagenesis studies are used to examine the binding modes of the compounds within the two enzymes and to reveal structural changes induced by inhibitor binding. Within this series, compounds with therapeutically relevant HsDHODH activity are described and their binding modes characterized using X-ray crystallography, which reveals a novel conformational shift within the inhibitor binding site.


Etienne R.S.,University of Groningen | Rosindell J.,University of Groningen | Rosindell J.,University of Leeds
Systematic Biology | Year: 2012

Phylogenetic trees show a remarkable slowdown in the increase of number of lineages towards the present, a phenomenon which cannot be explained by the standard birth-death model of diversification with constant speciation and extinction rates. The birth-death model instead predicts a constant or accelerating increase in the number of lineages, which has been called the pull of the present. The observed slowdown has been attributed to nonconstancy of the speciation and extinction rates due to some form of diversity dependence (i.e., species-level density dependence), but the mechanisms underlying this are still unclear. Here, we propose an alternative explanation based on the simple concept that speciation takes time to complete. We show that this idea of "protracted" speciation can be incorporated in the standard birth-death model of diversification. The protracted birth-death model predicts a realistic slowdown in the rate of increase of number of lineages in the phylogeny and provides a compelling fit to four bird phylogenies with realistic parameter values. Thus, the effect of recognizing the generally accepted fact that speciation is not an instantaneous event is significant; even if it cannot account for all the observed patterns, it certainly contributes substantially and should therefore be incorporated into future studies. © 2011 The Author(s).


Vaziri H.,University of Leeds
Molecular membrane biology | Year: 2013

Nucleosides play key roles in biology as precursors for salvage pathways of nucleotide synthesis. Prokaryotes import nucleosides across the cytoplasmic membrane by proton- or sodium-driven transporters belonging to the Concentrative Nucleoside Transporter (CNT) family or the Nucleoside:H(+) Symporter (NHS) family of the Major Facilitator Superfamily. The high resolution structure of a CNT from Vibrio cholerae has recently been determined, but no similar structural information is available for the NHS family. To gain a better understanding of the molecular mechanism of nucleoside transport, in the present study the structures of two conformations of the archetypical NHS transporter NupG from Escherichia coli were modelled on the inward- and outward-facing conformations of the lactose transporter LacY from E. coli, a member of the Oligosaccharide:H(+) Symporter (OHS) family. Sequence alignment of these distantly related proteins (∼ 10% sequence identity), was facilitated by comparison of the patterns of residue conservation within the NHS and OHS families. Despite the low sequence similarity, the accessibilities of endogenous and introduced cysteine residues to thiol reagents were found to be consistent with the predictions of the models, supporting their validity. For example C358, located within the predicted nucleoside binding site, was shown to be responsible for the sensitivity of NupG to inhibition by p-chloromercuribenzene sulphonate. Functional analysis of mutants in residues predicted by the models to be involved in the translocation mechanism, including Q261, E264 and N228, supported the hypothesis that they play important roles, and suggested that the transport mechanisms of NupG and LacY, while different, share common features.


Tooze R.M.,University of Leeds
Frontiers in Immunology | Year: 2013

Plasma cells are heterogenous in terms of their origins, secretory products, and lifespan. A current paradigm is that cell cycle exit in plasma cell differentiation is irreversible, following a pattern familiar in short-lived effector populations in other hemopoietic lineages. This paradigm no doubt holds true for many plasma cells whose lifespan can be measured in days following the completion of differentiation. Whether this holds true for long-lived bone marrow plasma cells that are potentially maintained for the lifespan of the organism is less apparent. Added to this the mechanisms that establish and maintain cell cycle quiescence in plasma cells are incompletely defined. Gene expression profiling indicates that in the transition of human plasmablasts to long-lived plasma cells a range of cell cycle regulators are induced in a pattern that suggests a quiescence program with potential for cell cycle re-entry. Here a model of relative quiescence with the potential for replicative self-renewal amongst long-lived plasma cells is explored. The implications of such a mechanism would be diverse, and the argument is made here that current evidence is not sufficiently strong that the possibility should be disregarded. © 2013 Tooze.


Ngoduy D.,University of Leeds
Transportmetrica | Year: 2011

The first-order continuum traffic model has been extensively studied in the stateof- the-art of traffic flow theory due to its simplicity and capability to represent many real traffic problems, such as a shock-wave formation. Furthermore, recent extension of the first-order model to multiclass traffic dynamics has revealed some interesting non-linear traffic phenomena such as hysteresis and capacity drop. However, most of the existing first-order continuum models do not display the widely scattered flow-density relationship. We argue in this article that the widely scattered flow-density relationship might be caused by the random variations in driving behaviour. It is shown that both of the hysteresis transitions and the wide scattering can be reproduced by a multiclass first-order model with a stochastic setting in the model parameters. The simulation results support our findings and are in good agreement with the real data. © 2011 Hong Kong Society for Transportation Studies Limited.


Foyer C.H.,University of Leeds
Plant signaling & behavior | Year: 2012

The cellular reduction-oxidation (redox) hub processes information from metabolism and the environment and so regulates plant growth and defense through integration with the hormone signaling network. One key pathway of redox control involves interactions with ABSCISIC ACID (ABA). Accumulating evidence suggests that the ABA-INSENSITIVE-4 (ABI4) transcription factor plays a key role in transmitting information concerning the abundance of ascorbate and hence the ability of cells to buffer oxidative challenges. ABI4 is required for the ascorbate-dependent control of growth, a process that involves enhancement of salicylic acid (SA) signaling and inhibition of jasmonic acid (JA) signaling pathways. Low redox buffering capacity reinforces SA- JA- interactions through the mediation of ABA and ABI4 to fine-tune plant growth and defense in relation to metabolic cues and environmental challenges. Moreover, ABI4-mediated pathways of sugar sensitivity are also responsive to the abundance of ascorbate, providing evidence of overlap between redox and sugar signaling pathways.


Migliore M.,University of Leeds
Antiviral Chemistry and Chemotherapy | Year: 2010

Bicyclic aryl furano pyrimidines represent the most potent anti-varicella zoster virus (VZV) agents reported to date. Lead compounds have 50% effective concentration (EC50) values in vitro that are in the subnanomolar range and selectivity index values that exceed 1 million. They have an absolute requirement for VZV thymidine kinase and most likely act as their phosphate forms. Some structural modification (such as aryl substitution in the base moiety) is tolerated, whereas little sugar modification is acceptable. The Cf1743 compound has proved to be significantly more potent than all reference anti-VZV compounds, as measured either by inhibition of infectious virus particles and/ or viral DNA production; however, the high lipophilicity and very low water solubility of this compound gives poor oral bioavailability (<14%). Use of the modified cyclodextrin captisol and the synthesis of the 5′-monophosphate prodrug of Cf1743 has significantly improved water solubility, but does not give any enhancement in oral bioavailability. By contrast, the synthesis of the ether series does not give any further improvement in terms of solubility. The most promising prodrug to emerge to date is the hydrochloric salt of the 5′-valyl-ester, designated as FV-100. Its uptake into cells has been studied using fluorescent microscopy and biological assays, which have indicated that the compound is efficiently taken up by the cells after a short period of incubation. ©2010 International Medical Press.


Watson A.A.,University of Leeds
Astroparticle Physics | Year: 2014

After a brief review of the discovery of extensive air showers, I summarise the remarkable advances made in the decade 1948-1958. During this period many of the techniques of instrumentation and analysis that are used today were introduced. I then discuss current data with emphasis on recent work on the measurement of the mass composition between 1015 and 1017 eV and above 1018 eV, and on the energy spectrum at the highest energies. © 2013 Elsevier B.V. All rights reserved.


Johnson A.P.,Public Health England | Wilcox M.H.,University of Leeds
Journal of Antimicrobial Chemotherapy | Year: 2012

The two drugs currently recommended for the treatment of Clostridium difficile infection (CDI), namely vancomycin and metronidazole, are both associated with high rates of recurrence of infection. Hence there is a need for new treatment options. The novel oral macrocyclic antibiotic fidaxomicin (previously known as PAR-101, OPT-80 and difimicin) was recently approved in the USA and in Europe for the treatment of CDI. Clinical trials have shown non-inferiority with regard to clinical cure when compared with oral vancomycin, and reduced rates of recurrence of infection, with a concomitant increase in the overall rate of sustained response, although improved sustained response was not seen in the sub-group of patients infected with the C. difficile NAP1/B1/027 strain. The introduction of fidaxomicin extends the options for the treatment of CDI and may help to reduce the burden of this disease if fewer patients have recurrence of infection. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Background:Patients diagnosed with cancer in the context of an emergency presentation (EP) have poorer outcomes. It is often assumed that such patients present to the emergency department without consulting their general practitioner (GP). Little work has been done to identify primary care involvement before hospital attendance.Methods:Participating primary care practices completed a significant event audit (SEA) report for the last patient diagnosed with cancer as a result of an EP. Accounts were synthesised and a qualitative approach to analysis undertaken.Results:SEAs for 222 patients were analysed. A range of cancers were included, the most common being lung (32.4%) and upper gastrointestinal (19.8%). In most cases, patients had contact with their practice before diagnosis, primarily in the period immediately before admission. In only eight cases had there been no input from primary care. Accounts of protracted primary care contact generally demonstrated complexity, often related to comorbidity, patient-mediated factors or reassurance provided by negative investigations. Learning points identified by practices centred on the themes of presentation and diagnosis, consultation and safety-netting, communication and system issues, patient factors and referral guidelines.Conclusions:There is extensive primary care input into patients whose diagnosis results from EP, and for the most part potential ‘delay’ in referral can be reasonably explained by the complexity of the presentation or by coexisting patient factors.British Journal of Cancer advance online publication, 3 March 2015; doi:10.1038/bjc.2015.42 www.bjcancer.com. © 2015 Cancer Research UK


Pottage C.L.,University of Leeds | Schaefer A.,Durham University
Emotion | Year: 2012

The emotional enhancement of memory is often thought to be determined by attention. However, recent evidence using divided attention paradigms suggests that attention does not play a significant role in the formation of memories for aversive pictures. We report a study that investigated this question using a paradigm in which participants had to encode lists of randomly intermixed negative and neutral pictures under conditions of full attention and divided attention followed by a free recall test. Attention was divided by a highly demanding concurrent task tapping visual processing resources. Results showed that the advantage in recall for aversive pictures was still present in the DA condition. However, mediation analyses also revealed that concurrent task performance significantly mediated the emotional enhancement of memory under divided attention. This finding suggests that visual attentional processes play a significant role in the formation of emotional memories. © 2011 American Psychological Association.


Dyer M.,University of Leeds | Richerby D.,University of Liverpool
SIAM Journal on Computing | Year: 2013

Bulatov [Proceedings of the 35th International Colloquium on Automata, Languages and Programming (Part 1), Lecture Notes in Comput. Sci. 5125, Springer, New York, 2008, pp. 646- 661] gave a dichotomy for the counting constraint satisfaction problem #CSP. A problem from #CSP is characterized by a constraint language Ã, a fixed, finite set of relations over a finite domain D. An instance of the problem uses these relations to constrain an arbitrarily large finite set of variables. Bulatov showed that the problem of counting the satisfying assignments of instances of any problem from #CSP is either in polynomial time (FP) or is #P-complete. His proof draws heavily on techniques from universal algebra and cannot be understood without a secure grasp of that field. We give an elementary proof of Bulatov's dichotomy, based on succinct representations, which we call frames, of a class of highly structured relations, which we call strongly rectangular. We show that these are precisely the relations which are invariant under a Mal'tsev polymorphism. En route, we give a simplification of a decision algorithm for strongly rectangular constraint languages due to Bulatov and Dalmau [SIAM J. Comput., 36 (2006), pp. 16-27]. We establish a new criterion for the #CSP dichotomy, which we call strong balance, and we prove that this property is decidable. In fact, we establish membership in NP. Thus, we show that the dichotomy is effective, resolving the most important open question concerning the #CSP dichotomy. © 2013 Society for Industrial and Applied Mathematics.


Foyer C.H.,University of Leeds
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2014

Chloroplasts are important sensors of environment change, fulfilling key roles in the regulation of plant growth and development in relation to environmental cues. Photosynthesis produces a repertoire of reductive and oxidative (redox) signals that provide information to the nucleus facilitating appropriate acclimation to a changing light environment. Redox signals are also recognized by the cellular innate immune system allowing activation of non-specific, stress-responsive pathways that underpin cross tolerance to biotic-abiotic stresses. While these pathways have been intensively studied in recent years, little is known about the different components that mediate chloroplast-to-nucleus signalling and facilitate cross tolerance phenomena. Here, we consider the properties of the WHIRLY family of proteins and the REDOX-RESPONSIVE TRANSCRIPTION FACTOR 1 (RRTF1) in relation to chloroplast redox signals that facilitate the synergistic co-activation of gene expression pathways and confer cross tolerance to abiotic and biotic stresses. We propose a new hypothesis for the role of WHIRLY1 as a redox sensor in chloroplast-to-nucleus retrograde signalling leading to cross tolerance, including acclimation and immunity responses. By virtue of its association with chloroplast nucleoids and with nuclear DNA, WHIRLY1 is an attractive candidate coordinator of the expression of photosynthetic genes in the nucleus and chloroplasts. We propose that the redox state of the photosynthetic electron transport chain triggers the movement of WHIRLY1 from the chloroplasts to the nucleus, and draw parallels with the regulation of NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1).


Robinson C.,University of Leeds
Frontiers in Physiology | Year: 2014

The maturation stage of enamel development begins once the final tissue thickness has been laid down. Maturation includes an initial transitional pre-stage during which morphology and function of the enamel organ cells change. When this is complete, maturation proper begins. Fully functional maturation stage cells are concerned with final proteolytic degradation and removal of secretory matrix components which are replaced by tissue fluid. Crystals, initiated during the secretory stage, then grow replacing the tissue fluid. Crystals grow in both width and thickness until crystals abut each other occupying most of the tissue volume i.e. full maturation. If this is not complete at eruption, a further post eruptive maturation can occur via mineral ions from the saliva. During maturation calcium and phosphate enter the tissue to facilitate crystal growth. Whether transport is entirely active or not is unclear. Ion transport is also not unidirectional and phosphate, for example, can diffuse out again especially during transition and early maturation. Fluoride and magnesium, selectively taken up at this stage can also diffuse both in an out of the tissue. Crystal growth can be compromised by excessive fluoride and by ingress of other exogenous molecules such as albumin and tetracycline. This may be exacerbated by the relatively long duration of this stage, 10 days or so in a rat incisor and up to several years in human teeth rendering this stage particularly vulnerable to ingress of foreign materials, incompletely mature enamel being the result. © 2014 Robinson.


Carsten O.,University of Leeds
Accident Analysis and Prevention | Year: 2012

There have been 30 years of research on Intelligent Speed Adaptation (ISA), the in-vehicle system that is designed to promote compliance with speed limits. Extensive trials of ISA in real-world driving have shown that ISA can significantly reduce speeding, users have been found to have generally positive attitudes and at least some sections of the public have been shown to be willing to purchase ISA systems. Yet large-scale deployment of a system that could deliver huge accident reductions is still by no means guaranteed. © 2010 Elsevier Ltd.


Hollstein M.,University of Leeds | Hainaut P.,International Agency for Research on Cancer
Journal of Pathology | Year: 2010

Intensive study of the TP53 gene over the last three decades has revealed a highly complex network of factors that regulate its performance. The gene has several promoters, alternative splicing occurs and there are alternative translation initiation sites. Up to 10 p53 isoforms have been identified. At the post-translational level, p53 activity depends on its quantity in the cell and on qualitative changes in its structure, intracellular localization, DNA-binding activity and interactions with other proteins. Both accumulation and activation are regulated by an intricate pattern of post-translational modifications, including phosphorylation, acetylation, ubiquitination, sumoylation, neddylation, methylation and glycosylation. The Mdm2 protein, a negative regulator of p53, is the most important determinant of p53 abundance and subcellular localization. Enzymes that post-translationally modify p53 by phosphorylation, methylation and acetylation fine-tune p53 binding to recognition sequences in DNA and p53 interactions with transcription cofactors at promoters of target genes, thereby exerting a discriminatory role in p53 function. This multitude of parameters determining expression, modification, accumulation and localization of p53 proteins may explain how a single gene can display an extensive repertoire of activities. Presumably this is needed, because the p53 protein can have such profound consequences for a cell. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.


Speight J.M.,University of Leeds
Journal of Physics A: Mathematical and Theoretical | Year: 2010

The static baby Skyrme model is investigated in the extreme limit where the energy functional contains only the potential and Skyrme terms, but not the Dirichlet energy term. It is shown that the model with potential V = 1/2 (1+Φ3)2 possesses solutions with extremely unusual localization properties, which we call semi-compactons. These minimize energy in the degree 1 homotopy class, have support contained in a semi-infinite rectangular strip and decay along the length of the strip as x-logx. By gluing together several semicompactons, it is shown that every homotopy class has linearly stable solutions of arbitrarily high, but quantized, energy. For various other choices of potential, compactons are constructed with support in a closed disc, or in a closed annulus. In the latter case, one can construct higher winding compactons and complicated superpositions in which several closed string-like compactons are nested within one another. The constructions make heavy use of the invariance of the model under area-preserving diffeomorphisms, and of a topological lower energy bound, both of which are established in a general geometric setting. All the solutions presented are classical, that is, they are (at least) twice continuously differentiable and satisfy the Euler-Lagrange equation of the model everywhere. © 2010 IOP Publishing Ltd.


Wilcox M.H.,University of Leeds
Injury | Year: 2011

There is a choice of anti-MRSA antibiotic available with proven efficacy in the treatment of complicated skin and skin structure infection (cSSSI). Additional anti-MRSA antibiotics are in development, which have the potential to influence how such infections are managed. The emergence of resistance to current anti-MRSA agents, toxicity, and general lack of oral agents with proven efficacy for deep seated infection justify the development of new agents. However, there is a relative dearth of information specific to patients with orthopaedic-related infection. Combination therapy is often used in these patients, although there is a paucity of controlled trial data to support particular antibiotic combinations. As the choice of anti-MRSA agents increases, so does the need to identify which are best for the large variety of infections included in the group of cSSSIs. This is particular true for infections occurring in orthopaedic patients where poorly vascularised tissue, trauma or implanted prosthetic material, pose specific challenges. © 2011 Elsevier Ltd. All rights reserved.


Helliwell P.S.,University of Leeds
Journal of Rheumatology | Year: 2011

Patients with psoriasis attending general practitioner and dermatology clinics may complain about their joints, but it may be difficult for the nonrheumatologist to distinguish psoriatic arthritis (PsA) from other forms of arthritis. A screening tool for PsA would therefore be useful to both general practitioners and dermatologists and help identify patients for further evaluation by a rheumatologist. Although several screening tools have been developed, the Psoriasis Epidemiology Screening Tool (PEST) has the advantage of simplicity and ease of use. This new instrument consists of 5 simple questions supported by the addition of a manikin for patient markup. During development, the questionnaire has shown a sensitivity of 0.94 and a specificity of 0.78. Further validation of this and the other questionnaires is now required. A "head to head" study of the PEST, ToPAS (Toronto Psoriatic Arthritis Screening questionnaire), and PASE (Psoriatic Arthritis Screening and Evaluation) tools is planned in a secondary-care population with psoriasis. This study is important not only to confirm the comparative performance of the instruments, but also to confirm the high figures for sensitivity in a secondary-care population. The Journal of Rheumatology Copyright © 2011. All rights reserved.


Wood T.S.,Northumbria University | Hollerbach R.,University of Leeds
Physical Review Letters | Year: 2015

We present the first fully self-consistent three dimensional model of a neutron star's magnetic field, generated by electric currents in the star's crust via the Hall effect. We find that the global-scale field converges to a dipolar Hall-attractor state, as seen in recent axisymmetric models, but that small-scale features in the magnetic field survive even on much longer time scales. These small-scale features propagate toward the dipole equator, where the crustal electric currents organize themselves into a strong equatorial jet. By calculating the distribution of magnetic stresses in the crust, we predict that neutron stars with fields stronger than 1014G can still be subject to starquakes more than 105yr after their formation. © 2015 American Physical Society.


Krivov S.V.,University of Leeds
Journal of Physical Chemistry B | Year: 2011

A fundamental problem in the analysis of protein folding and other complex reactions is the determination of the reaction free energy landscape. The current experimental techniques lack the necessary spatial and temporal resolution to construct such landscapes. The properties of the landscapes can be probed only indirectly. Simulation, assuming that it reproduces the experimental dynamics, can provide the necessary spatial and temporal resolution. It is, arguably, the only way for direct rigorous construction of the quantitatively accurate free energy landscapes. Here, such landscape is constructed from the equilibrium folding simulation of FIP35 protein reported by Shaw et al. Science2010, 330, 341-346. For the dynamics to be accurately described as diffusion on the free energy landscape, the choice of reaction coordinates is crucial. The reaction coordinate used here is such that the dynamics projected on it is diffusive, so the description is consistent and accurate. The obtained landscape suggests an alternative interpretation of the simulation, markedly different from that of Shaw et al. In particular, FIP35 is not an incipient downhill folder, it folds via a populated on-pathway intermediate separated by high free energy barriers; the high free energy barriers rather than landscape roughness are a major determinant of the rates for conformational transitions; the preexponential factor of folding kinetics 1/k0 ∼ 10 ns rather than 1 μs. © 2011 American Chemical Society.


Sourbron S.,University of Leeds
IEEE Transactions on Medical Imaging | Year: 2014

Dynamic imaging data are currently analyzed with a tracer-kinetic theory developed for individual time curves measured over whole organs. The assumption is that voxels represent isolated systems which all receive indicator through the same arterial inlet. This leads to well-known systematic errors, but also fails to exploit the spatial structure of the data. In this study, a more general theoretical framework is developed which makes full use of the specific structure of image data. The theory encodes the fact that voxels receive indicator from their immediate neighbors rather than from an upstream arterial input. This results in a tracer-kinetic field theory where the tissue parameters are functions of space which can be measured by analyzing the temporal and spatial patterns in the concentrations. The implications are evaluated through a number of field models for common tissue types. The key benefits of a tracer-kinetic field theory are that: 1) long-standing systematic errors can be corrected, specifically the issue of bolus dispersion and the contamination of large-vessel blood flow on tissue perfusion measurements; 2) additional tissue parameters can be measured that characterize convective or diffusive exchange between voxels; 3) the need to measure a separate arterial input function can be eliminated. © 2014 IEEE.


Leking moths present an evolutionary problem in their apparently simultaneous reversal of male-female attraction. The mating system of Phymatopus (or Hepialus) hecta embraces an unusually wide range of procedures. Both males and females use medium-range olfactory attractants (also probably visual signals), and both sexes will lure, and both will approach, the other, either when flying or perched. This produces an 'infinite variety' which includes the classic moth mating procedure (males fly to sessile female); a typical lek procedure (female flies to sessile male); a mating swarm (hovering male follows passing female); and intermediates such as a mutual courtship dance. Male behaviour includes a flying display, two sessile displays, and an escalating war of attrition. The system is versatile, persistent, and probably evolutionarily stable. The lek site has a high density of perches suitable for copulation which facilitate predator-escape by means of a dead drop. The whole supports a model for the evolution of resource-based leks which commence with a concentration of females on a hotspot, leading to a concentration of males; and then an escalating process of sexual selection as males become increasingly attractive over a distance to females, and females use the males as a way of locating the resource. The main stabilizing pressure may be selection for efficient mate acquisition, and as with grouse leking systems, the precondition for evolution was probably having travelling females that actively sought a reproductive resource or a predator free space. © 2014 The Linnean Society of London.


Wilcox M.H.,University of Leeds
Clinical Microbiology and Infection | Year: 2012

With the frequency of cases of Clostridium difficile infection (CDI) increasing in many developed countries, accurate and reliable laboratory diagnosis of CDI is more important than ever. However, the diagnosis of CDI has been handicapped by the existence of two reference standards, one of which detects C. difficile toxin (cytotoxin assay) and the other only toxigenic strains (cytotoxigenic culture). Being relatively slow and laborious to perform, these reference methods were largely abandoned as routine diagnostic methods for toxin detection in favour of stand-alone rapid enzyme immunoassays (EIAs), which have suboptimal sensitivity and specificity. The management of CDI is undermined by high rates of both false-positive and false-negative test results. More recently developed nucleic acid amplification tests (NAATs) for toxin gene detection offer improved sensitivity over immunoassays, but fail to discriminate between CDI and asymptomatic colonization with C. difficile, and have clear drawbacks as stand-alone diagnostic tests. Two-step or three-step diagnostic algorithms have been proposed as a solution. In a large study of the effectiveness of currently available tests, a diagnostic algorithm was developed that combines available tests to more effectively distinguish patients with CDI from uninfected patients. This two-test protocol, which is now used in National Health Service laboratories in England, comprises an EIA for glutamate dehydrogenase detection or NAATs for toxin gene detection, followed by a relatively sensitive toxin EIA. This algorithm also identifies 'potential C. difficile excretors', individuals with diarrhoeal samples that contain C. difficile but without demonstrable toxin, who may be a source of transmission of C. difficile to susceptible patients. © 2012 The Author Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.


Bennett R.,University of Leeds
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2014

The Casimir force between two objects is notoriously difficult to calculate in anything other than parallel-plate geometries due to its nonadditive nature. This means that for more complicated, realistic geometries one usually has to resort to approaches such as making the crude proximity force approximation (PFA). Another issue with calculation of Casimir forces in real-world situations (such as with realistic materials) is that there are continuing doubts about the status of Lifshitz's original treatment as a true quantum theory. Here we demonstrate an alternative approach to the calculation of Casimir forces for arbitrary geometries which sidesteps both of these problems. Our calculations are based upon a Born expansion of the Green's function of the quantized electromagnetic vacuum field, interpreted as multiple scattering, with the relevant coupling strength being the difference in the dielectric functions of the various materials involved. This allows one to consider arbitrary geometries in single or multiple scattering simply by integrating over the desired shape, meaning that extension beyond the PFA is trivial. This work is mostly dedicated to illustration of the method by reproduction of known parallel-slab results - a process that turns out to be nontrivial and provides several useful insights. We also present a short example of calculation of the Casimir energy for a more complicated geometry; namely, that of two finite slabs. © 2014 American Physical Society.


Dickinson E.,University of Leeds
Journal of Colloid and Interface Science | Year: 2015

We consider the influence of spherical colloidal particles on the structure and stabilization of dispersions, emulsions and foams. Emphasis is placed on developments in the use of the methods of liquid state theory and computer simulation to understand short-range structuring of concentrated colloidal dispersions and ordering of particle layers near surfaces and within liquid films. Experimental information on the structuring of surfactant micelles and caseinate particles in thin liquid films is described, including an assessment of the effect of particle polydispersity on depletion interactions and kinetic structural stabilization. We specifically discuss the relevance of some of these structural concepts to the stability of food colloids. © 2014 Elsevier Inc.


Smolen J.S.,Medical University of Vienna | Emery P.,University of Leeds
Arthritis Research and Therapy | Year: 2011

Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are immune-mediated conditions that share an inflammatory mechanism fuelled by excessive cytokines, particularly TNF. Control of inflammation and rapid suppression of cytokines are important in treating these diseases. With this understanding and the corresponding advent of TNF inhibitors, RA patients, AS patients and PsA patients have found more choices than ever before and have greater hope of sustained relief. As a widely used TNF inhibitor, infliximab has a deep and established record of efficacy and safety data. Extensive evidence - from randomised controlled clinical trials, large registries and postmarketing surveillance studies - shows that infliximab effectively treats the signs and symptoms, provides rapid and prolonged suppression of inflammation, prevents radiologically observable disease progression and offers an acceptable safety profile in RA, AS and PsA. In very recent studies, investigators have observed drug-free remission in some patients. Additionally, infliximab may interfere with rapidly progressing disease in RA by early addition to methotrexate in patients with signs of an aggressive course. Finally, infliximab has been shown to reduce PsA clinical manifestations such as nail involvement. With our current understanding, substantial data and increasing confidence regarding use in practice, infliximab can be considered a well-known drug in our continued campaign against inflammatory rheumatic diseases. © 2011 Smolen et al; licensee BioMed Central Ltd.


King E.J.,University of Leeds
Developmental medicine and child neurology | Year: 2012

The aim of this study was to assess whether acute symptomatic epileptic seizures associated with central nervous system infections (AS(inf) ) have a different ictal and postictal course to seizures of other aetiologies. A case note analysis of 81 children (47 males; 34 females; age range 1mo-15y 6mo; median age 12mo) with central nervous system infections was undertaken. Seizure type, duration, aetiology, and timing were recorded. Recovery time to full consciousness in those not intubated was determined. Intubation rates and recovery times were compared with those from previous studies. Of the 81 children, 40 (49.4%) had one or more AS(inf) . The different aetiologies were bacterial meningitis, aseptic meningitis, abscess/empyema, encephalitis, and postoperative infection. Twenty-two had status epilepticus. The intubation rate in children with AS(inf) was higher than that in children with seizures of other aetiologies (21/40 [52.5%] vs 4/124 [3.23%]; p < 0.0001). Median postictal recovery time was 4.33 hours (0-207h). Children with AS(inf) took 4.3 (p<0.01), 3.0 (p=0.004), and 8.8 (p<0.001) times longer to recover than children who had seizures from all causes, remote symptomatic seizures, and febrile seizures respectively. AS(inf) in children are often longer, more likely to be associated with status epilepticus, more likely to necessitate intubation, and take longer to recover from than seizures of other aetiologies. This may help in the early diagnosis of central nervous system infection in children presenting with seizures. © The Authors. Developmental Medicine & Child Neurology © 2012 Mac Keith Press.


Woodward G.,Queen Mary, University of London | Perkins D.M.,Queen Mary, University of London | Brown L.E.,University of Leeds
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

Fresh waters are particularly vulnerable to climate change because (i) many species within these fragmented habitats have limited abilities to disperse as the environment changes; (ii) water temperature and availability are climate-dependent; and (iii) many systems are already exposed to numerous anthropogenic stressors. Most climate change studies to date have focused on individuals or species populations, rather than the higher levels of organization (i.e. communities, food webs, ecosystems). We propose that an understanding of the connections between these different levels, which are all ultimately based on individuals, can help to develop a more coherent theoretical framework based on metabolic scaling, foraging theory and ecological stoichiometry, to predict the ecological consequences of climate change. For instance, individual basal metabolic rate scales with body size (which also constrains food web structure and dynamics) and temperature (which determines many ecosystem processes and key aspects of foraging behaviour). In addition, increasing atmospheric CO2 is predicted to alter molar CNP ratios of detrital inputs, which could lead to profound shifts in the stoichiometry of elemental fluxes between consumers and resources at the base of the food web. The different components of climate change (e.g. temperature, hydrology and atmospheric composition) not only affect multiple levels of biological organization, but they may also interact with the many other stressors to which fresh waters are exposed, and future research needs to address these potentially important synergies. © 2010 The Royal Society.


Mackie S.L.,University of Leeds
Rheumatology (Oxford, England) | Year: 2010

To identify the features of PMR that may predict the duration of steroid therapy, the occurrence of relapses and the late development of GCA. Prospective cohort study of 176 patients with PMR, followed up for 5 years. Baseline factors associated with the duration of steroids therapy were identified using Cox regression. Predictors of relapse and the late development of GCA were identified using binary logistic regression. A total of 176 patients with PMR were included, of whom 124 stopped steroids within 5 years. The probability of stopping steroids within 5 years was independently reduced by an elevated plasma viscosity (PV) [hazard ratio (HR) = 0.49; 95% CI 0.29, 0.82 for a PV > or = 2.00 mPa s compared with a PV < or = 1.80 mPa s; overall P = 0.024] and by starting treatment at >15 mg prednisolone (HR = 0.63; 95% CI 0.41, 0.97; P = 0.036). Either of these independently reduced the chances of stopping steroids within a given time interval between 27 and 51%. No significant predictors of relapse were identified. Predictors of late GCA on univariable analysis were female sex [odds ratio (OR) = 8.16; 95% CI 1.06, 63.13; P = 0.044], HLA-DRB1*0101 or -*0401 alleles (OR = 4.95; 95% CI 1.05, 23.34; P = 0.043), PV > or = 2.00 mPa s compared with PV < or = 1.80 mPa s (OR = 10.64; 95% CI 1.28, 88.38; P = 0.029) and initial prednisolone dose >15 mg (OR = 4.53; 95% CI 1.61, 12.79; P = 0.004). A higher PV in PMR increases the risk of prolonged steroid therapy and late GCA. Female sex and particular HLA alleles may increase the risk of late GCA. Starting patients on >15 mg prednisolone is associated with a prolonged steroid duration.


Halcrow M.A.,University of Leeds
New Journal of Chemistry | Year: 2014

Developments in the chemistry of 2,6-di(pyrazol-1-yl)pyridine (1-bpp) and 2,6-di(pyrazol-3-yl)pyridine (3-bpp), their derivatives and their complexes are surveyed, with emphasis on the last eight years. Particular advances include the synthesis of multi-functional spin-crossover switches; the incorporation of emissive f-element podand centres into biomedical sensors; the self-assembly of a variety of functional soft materials and surface structures; and, the use of 3-bpp complexes in catalysis. © 2014 The Partner Organisations.


Taylor-Robinson A.W.,University of Leeds
Experimental Parasitology | Year: 2010

Malaria, a disease caused by the protozoan parasite Plasmodium, remains a serious healthcare problem in developing countries worldwide. While the host-parasite relationship in humans has been difficult to determine, the pliability of murine malaria models has enabled valuable contributions to the understanding of the pathogenesis of disease. Although no single model reflects precisely malaria infection of the human, different models collectively provide important information on the mechanisms of protective immunity and immunopathogenesis. This review summarizes progress towards understanding the broad spectrum of immune responsiveness to the blood stages of the malaria parasite during experimental infections in mice and highlights how examination of murine malarias sheds light on the factors involved in the modulation of vaccine-potentiated immunity. © 2010 Elsevier Inc.


Dickinson E.,University of Leeds
Trends in Food Science and Technology | Year: 2015

A gel is a conventionally defined on the macroscopic scale as a state of matter with a connected network of structural elements (polymers) and predominantly solid-like mechanical properties. When gel-like features are expressed on the microscopic scale, we get a special type of colloidal entity, the microgel, which possesses both polymeric and particle-like characteristics. Microgels are increasingly being viewed as valuable colloidal building blocks and stabilizing agents due to their deformability, surface activity, reversible swelling behaviour, and responsiveness to pH and temperature. For the case of biopolymer-based microgels, a novel functional application is the stabilization of food emulsions. © 2015 Elsevier Ltd.


Duff F.J.,University of York | Clarke P.J.,University of Leeds
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2011

Background: Two developmental reading disorders, dyslexia and reading comprehension impairment, are identified by different behavioural characteristics and traced back to different underlying cognitive impairments. Thus, reading interventions designed to address each of these reading disorders differ in content. Method: This review summarises the nature of dyslexia and reading comprehension impairment, and current understanding of best practice in associated reading interventions. Conclusion: There is strong evidence for the effectiveness of phonological-based reading interventions in supporting children with dyslexic difficulties, and a growing understanding of how to meet the needs of children with reading comprehension impairment, with vocabulary instruction offering a promising approach. Although the content of interventions must be tailored to an individual's reader profile, general principles regarding the implementation and evaluation of intervention programmes can be extracted. © 2010 The Authors. Journal of Child Psychology and Psychiatry. © 2010 Association for Child and Adolescent Mental Health.


Dickinson E.,University of Leeds
Current Opinion in Colloid and Interface Science | Year: 2010

Recent advances in the stabilization of emulsions and foams by particles of nanoscale and microscopic dimensions are described. Ongoing research in this highly active field is providing insight into (i) the molecular factors controlling particle wettability and adsorption, (ii) the structural and mechanical properties of particle-laden liquid interfaces, and (ii) the stabilization mechanisms of particle-coated droplets and bubbles. There is much potential for exploiting the emerging knowledge in new food product applications. The preparation of cheap and effective colloidal particles based on food-grade ingredients, especially proteins, is the key technological challenge. © 2009 Elsevier B.V. All rights reserved.


Herod A.A.,Imperial College London | Bartle K.D.,University of Leeds | Morgan T.J.,European Commission | Kandiyoti R.,Imperial College London
Chemical Reviews | Year: 2012

By attempting to arrive at improved definitions of the heavy ends of coal and petroleum derived liquids, the paper aims to facilitate process development for improved utilization of heavy fractions (asphaltenes, resids). Historically much heavy petroleum derived material has been used as cheap fuel or simply thrown away. The proposition that the large molecular mass components consist of molecular aggregates lacks evidence to sustain it. While it is understood that aggregates may form in a dense phase, what is at issue in the present discussion is the elucidation of fundamental structures and molecular masses of high mass material, as identified in dilute phase. Although the misapprehension is widespread, no experimental evidence has been presented, to date, showing that large molecules encountered in dilute phase are aggregates, or indeed that they may be disaggregated. Furthermore, the "aggregates" model of large molecules, widely upheld in the petroleum industry over the decades, has led to no improvements in processing methods. With the rising cash value of the "bottom of the barrel, " greater emphasis on the detailed chemistry of these materials has become an imperative. This paper has reviewed analytical techniques used for estimating molecular mass distributions and structural features of complex polydispersed hydrocarbons, with masses above those identifiable by gas-chromatography (or GC-MS). The features of the least soluble and usually large molecular mass materials in complex mixtures are not generally observable by examination prior to the fractionation of (i.e., "whole") complex samples. This has been observed even in cases where the "heavy" fraction accounts for about 50% of the total sample. The major approach reviewed covers the combined use of UV?F spectroscopy, size exclusion chromatography, mass spectrometry and NMR-spectroscopy. This is preceded by a description of useful sample fractionation methods found in the literature. © 2012 American Chemical Society.


Although well studied, there are still interesting features about the ignition and steady burning rate behaviour of PMMA when heated by thermal radiation. In this contribution, the dependence on external heat flux of ignition delay time and steady mass flux of PMMA are investigated numerically. Ignition is modelled by the critical mass flux criterion. The heat transfer model includes effects of heat lost by out gassing, change of volume during degradation and absorption of radiation in both condensed and gaseous phases. Model results are compared to experimental data for both ignition delay time and quasi-steady mass flux across a range of heat fluxes from 20 to 210kWm-2 and the importance of both gas-phase and condensed-phase radiation absorption effects are discussed. © 2014 The Combustion Institute..


Morgan J.E.,University of Leeds
Human mutation | Year: 2010

Using conventional Sanger sequencing as a reference standard, we compared the sensitivity, specificity, and capacity of the Illumina GA II platform for the detection of TP53, BRCA1, and BRCA2 mutations in established tumor cell lines and DNA from patients with germline mutations. A total of 656 coding variants were identified in four cell lines and 65 patient DNAs. All of the known pathogenic mutations (including point mutations and insertions/deletions of up to 16 nucleotides) were identified, using a combination of the Illumina data analysis pipeline with custom and commercial sequence alignment software. In our configuration, clonal sequencing outperforms current diagnostic methods, providing a reduction in analysis times and in reagent costs compared with conventional sequencing. These improvements open the possibility of BRCA1/2 testing for a wider spectrum of at-risk women, and will allow the genetic classification of tumors prior to the use of novel PARP inhibitors to treat BRCA-deficient breast cancers. (c) 2010 Wiley-Liss, Inc.


Stoet G.,University of Leeds
Evolution and Human Behavior | Year: 2011

The hunter-gatherer theory of sex differences states that female cognition has evolutionarily adapted to gathering and male cognition to hunting. Existing studies corroborate that men excel in hunting-related skills, but there is only indirect support for women excelling in gathering tasks. This study tested if women would outperform men in laboratory-based computer tests of search and gathering skills. In Experiment 1, men found target objects faster and made fewer mistakes than women in a classic visual search study. In Experiment 2, participants gathered items (fruits or letters presented on screen), and again, men performed significantly better. In Experiment 3, participants' incidental learning of object locations in a search experiment was studied, but no statistically significant sex differences were observed. These findings found the opposite of what was expected based on the hypothesis that female cognition has adapted to gathering. Alternative interpretations of the role of object location memory, female gathering roles and the division of labor between the sexes are discussed. © 2011 Elsevier Inc.


Lydon J.,University of Leeds
Journal of Materials Chemistry | Year: 2010

Chromonic systems are lyotropic liquid crystal phases formed by soluble aromatic compounds. They occur as the result of the face-to-face aggregation of the molecules into columns. There are two principal chromonic phases; the N phase which consists of a nematic array of columns and at higher concentrations, the M phase, in which the columns lie in a hexagonal array. Chromonic phases are formed by a range of multi-ring aromatic compounds including drugs, dyes and nucleic acids. They have characteristic multi-peritectic phase diagrams and distinctive optical textures.The exploitation of the unique properties of chromonic systems has scarcely started. Recent promising studies show that the combination of self-ordering, ease of alignment, sensitivity to changing conditions and additives, coupled with their optical properties and electro-optical properties, makes possible a range of sophisticated devices, including polarizers, optical compensators, light-harvesting devices and micro-patterned materials - and the fact that they are water-based, suggests a future role in biosensors for medical diagnosis. © 2010 The Royal Society of Chemistry.


Assaf M.,Stanford University | Mobilia M.,University of Leeds
Physical Review Letters | Year: 2012

We study the influence of complex graphs on the metastability and fixation properties of a set of evolutionary processes. In the framework of evolutionary game theory, where the fitness and selection are frequency dependent and vary with the population composition, we analyze the dynamics of snowdrift games (characterized by a metastable coexistence state) on scale-free networks. Using an effective diffusion theory in the weak selection limit, we demonstrate how the scale-free structure affects the system's metastable state and leads to anomalous fixation. In particular, we analytically and numerically show that the probability and mean time of fixation are characterized by stretched- exponential behaviors with exponents depending on the network's degree distribution. © 2012 American Physical Society.


Carrivick J.L.,University of Leeds | Tweed F.S.,Staffordshire University
Quaternary Science Reviews | Year: 2013

Proglacial lakes are ubiquitous within the Quaternary record and can provide exceptional breadth and depth of palaeoenvironmental information. Present deglaciation is increasing the number and size of proglacial lakes around the world. This study provides a synthesis of knowledge on proglacial lake character and behaviour and critically evaluates the importance of proglacial lakes from a geological perspective. We show how 'ice-marginal' or 'ice-contact' lakes and other distal proglacial lakes can be distinguished from each other by geomorphological, sedimentological, chemical and biological characteristics. The key controls on proglacial lake geomorphology and sedimentology are outlined and discussed. Proglacial lakes can exacerbate mountain glacier and ice sheet margin ablation via mechanical and thermal stresses, but very large lakes can moderate summer air temperatures and relatively retard summer ice ablation. Proglacial lakes interrupt meltwater flux and are very efficient sediment traps. Hydrological routing and consequent geomorphological activity can be radically modified by sudden drainage of proglacial lakes and resultant glacial lake outburst floods; exceptionally large proglacial lake drainages affected global ocean circulation and global climate during the Quaternary. Overall, analyses of proglacial lakes can provide a valuable insight into (i) patterns, character and behaviour of mountain glaciers, ice sheets and glaciations, and (ii) the impacts of past, present and future deglaciation. © 2013 Elsevier Ltd.


Auer S.,University of Leeds
Biophysical Journal | Year: 2015

One and the same protein can self-assemble into amyloid fibrils with different morphologies. The phenomenon of fibril polymorphism is relevant biologically because different fibril polymorphs can have different toxicity, but there is no tool for predicting which polymorph forms and under what conditions. Here, we consider the nucleation of polymorphic amyloid fibrils occurring by direct polymerization of monomeric proteins into fibrils. We treat this process within the framework of our newly developed nonstandard nucleation theory, which allows prediction of the concentration dependence of the nucleation rate for different fibril polymorphs. The results highlight that the concentration dependence of the nucleation rate is closely linked with the protein solubility and a threshold monomer concentration below which fibril formation becomes biologically irrelevant. The relation between the nucleation rate, the fibril solubility, the threshold concentration, and the binding energies of the fibril building blocks within fibrils might prove a valuable tool for designing new experiments to control the formation of particular fibril polymorphs. © 2015 Biophysical Society.


Christenson H.K.,University of Leeds
CrystEngComm | Year: 2013

There are many examples where classical nucleation theory does not provide a correct description of the formation of a crystal from a solution. Many of these examples have been grouped together under the term "two-step mechanisms of crystal nucleation", because the common denominator is the initial formation of a denser, often metastable fluid phase, followed by nucleation of the crystal from this precursor. A number of well established routes to crystallisation, such as those involving amorphous precursor phases to biominerals like calcite and hydroxyapatite would fit into this category, as would the many recently discovered cases of protein nucleation from dense fluid clusters of molecules. We here discuss a two-step mechanism that has been experimentally identified in heterogeneous crystal nucleation from vapour. In this process, supercooled liquid condenses from vapour in surface cavities and then freezes, most likely via homogeneous nucleation. As a result, crystal deposition may under favourable conditions occur from saturated vapour with no need whatsoever for supersaturation. These results are of great potential significance for atmospheric ice nucleation, and similar ideas were advanced almost 50 years ago, but were never experimentally tested. Thermodynamic analogies with solution crystallisation lead us to suggest that heterogeneous nucleation in solution might in many cases proceed by a similar route, as has been found in computer simulation studies of protein nucleation in surface pits. © 2013 The Royal Society of Chemistry.


Plane J.M.C.,University of Leeds
Chemical Society Reviews | Year: 2012

This review discusses the magnitude of the cosmic dust input into the earth's atmosphere, and the resulting impacts from around 100 km to the earth's surface. Zodiacal cloud observations and measurements made with a spaceborne dust detector indicate a daily mass input of interplanetary dust particles ranging from 100 to 300 tonnes, which is in agreement with the accumulation rates of cosmic-enriched elements (Ir, Pt, Os and super-paramagnetic Fe) in polar ice cores and deep-sea sediments. In contrast, measurements in the middle atmosphere - by radar, lidar, high-flying aircraft and satellite remote sensing - indicate that the input is between 5 and 50 tonnes per day. There are two reasons why this huge discrepancy matters. First, if the upper range of estimates is correct, then vertical transport in the middle atmosphere must be considerably faster than generally believed; whereas if the lower range is correct, then our understanding of dust evolution in the solar system, and transport from the middle atmosphere to the surface, will need substantial revision. Second, cosmic dust particles enter the atmosphere at high speeds and undergo significant ablation. The resulting metals injected into the atmosphere are involved in a diverse range of phenomena, including: the formation of layers of metal atoms and ions; the nucleation of noctilucent clouds, which are a sensitive marker of climate change; impacts on stratospheric aerosols and O 3 chemistry, which need to be considered against the background of a cooling stratosphere and geo-engineering plans to increase sulphate aerosol; and fertilization of the ocean with bio-available Fe, which has potential climate feedbacks. © The Royal Society of Chemistry 2012.


This paper explores conservation as an elite process in the Dominican Republic. It begins by showing how conservation at a global level is an elite process, driven by a small powerful elite. Looking at the Dominican Republic, it demonstrates how the extraordinary levels of protection have been achieved by a small network of well connected individuals, who have been able to shape conservation as they like, while limiting the involvement by the large international conservation NGOs who are considered so dominant throughout Latin America. Despite this, conservation both globally and in the Dominican Republic is shown to share similar political structures and the same lack of critique of capitalism or its environmental impacts. © 2010 The Author Journal compilation © 2010 Editorial Board of Antipode.


Dickinson E.,University of Leeds
Food Hydrocolloids | Year: 2012

Many food products can be categorized as emulsion gels. This is especially the case for protein-based oil-in-water emulsions which can be converted into soft-solid-like materials by common food processing operations such as heating, acidification, and enzyme action. This review article outlines how the rheological and structural properties of protein-stabilized emulsion gels are influenced by the dispersed oil volume fraction, the oil-water interfacial composition, and the colloidal interactions of the constituent emulsion droplets. For model systems of variable oil content and containing different food proteins, some general trends of rheological behaviour at small and large deformations are identified. Experimental rigidity data are considered in relation to: (i) material science theories of the reinforcement of solid materials by active and inactive filler particles, and (ii) Brownian dynamics simulations of aggregated particle networks containing bonded and non-bonded particles. Influences of interfacial composition and particle-matrix interactions on microstructure and rheology are explained with particular reference to the role of small-molecule surfactants. Compositional and structural factors affecting the large-deformation rheology and fracture properties are described. Finally, the practical relevance of the model system studies to the behaviour of real food products is critically assessed. © 2011 Elsevier Ltd.


Kirkby M.J.,University of Leeds
Earth Surface Processes and Landforms | Year: 2010

This commentary brings together, as a virtual Special Issue, a number of recent papers in Earth Surface Processes and Landforms that are all related to issues of scale in soil erosion. Empirical concepts that were developed in the 1940s are now in need of re-thinking, and papers are increasingly exploring, through modelling and measurement, appropriate ways to recognize the mechanisms that connect processes across time and space scales. Issues include a more nuanced approach to selective transportation, responses to variability in surface and sub-surface conditions and the need to analyse measurements in ways that can be transferred between sites and storms. © 2010 John Wiley & Sons, Ltd.


Chatterton P.,University of Leeds | Pickerill J.,University of Leicester
Transactions of the Institute of British Geographers | Year: 2010

This article aims to broaden and deepen debates on the everyday practices of autonomous activists. To do this we present three main research findings from a recent research project that looked in detail at what we called 'autonomous geographies'. First, in terms of political identity, we highlight how participants in political projects problematise and go beyond the simple idea of the militant subject, set apart from the everyday who opposes the present condition. Second, we highlight how everyday practices are used to build hoped-for futures in the present, but that this process is experimental, messy and contingent, and necessarily so. Finally, we illuminate the contested spatialities embedded within political activism that are neither locally bounded nor easily transferable to the transnational. This exploration of everyday activism has illuminated that the participants we engaged with express identities, practices and spatial forms that are simultaneously anti-, despite- and post- capitalist. We argue that it is through its everyday rhythms that meaning is given to post-capitalism and it is this reconceptualisation that makes post-capitalist practice mundane, but at the same time also accessible, exciting, feasible and powerful. This paper draws upon material collected during a 30-month empirical research project into the everyday lives of grassroots, non-party political activists in the UK between 2005 and 2008. Three case studies were explored in detail - autonomous social centres, Low Impact Developments, and tenants' networks resisting gentrification. © 2010 The Authors. Transactions of the Institute of British Geographers © 2010 Royal Geographical Society (with The Institute of British Geographers) 2010.


Dickinson E.,University of Leeds
Trends in Food Science and Technology | Year: 2012

Solid particles of nanoscale and microscale dimensions are becoming recognized for their potential application in the formulation of novel dispersed systems containing emulsified oil or water droplets. This review describes developments in the formation and properties of food-grade emulsion systems based on traditional edible dispersed particles (fat crystals), commercial nanoparticles (silica nanoparticles), and novel particles of biological origin (starch microparticles, chitin nanocrystals). The special features characterizing the properties of particle-stabilized droplets are highlighted in comparison with those of conventional protein-stabilized emulsions. Complexities arising from synergistic interactions of particles with other surface-active ingredients are discussed. © 2011 Elsevier Ltd.


Grainger A.,University of Leeds
Progress in Physical Geography | Year: 2010

Knowledge of tropical forest change remains uncertain, affecting our ability to produce accurate estimates of globally aggregated parameters to support clear global statements about 'the tropical forests'. This paper reviews current methods for constructing global knowledge of changes in tropical forest area, carbon density, biodiversity and ecosystem services. It finds a deficiency in formal institutions for global measurement and constructing global knowledge. In their absence, informal institutions have proliferated, increasing the spread of estimates. This is exacerbated by dependence on inaccurate official statistics, which has limited construction of knowledge about forest area change through modelling. Employing the new concept of the Knowledge Exchange Chain shows the interdependence of different disciplines in constructing composite information. Limitations linked to compartmentalization and scale are present, as predicted by the 'post-normal hypothesis'. Disciplinary compartmentalization has impeded construction of information about forest carbon and biodiversity change. There is growth in interdisciplinary research into modelling forest change and estimating carbon emissions using remote sensing data, but not in studying biodiversity. Continuing uncertainty has implications for implementing the Reduced Emissions from Deforestation and Degradation (REDD) scheme. Uncertainty could be reduced by expanding formal scientific institutions, e.g. by establishing an operational scientific global forest monitoring system, and devising formal generic rules for constructing global environmental knowledge. © The Author(s) 2010.


Cooper S.B.,University of Leeds
Communications of the ACM | Year: 2012

Embodied and disembodied computing at the Turing Centenary. © 2012 ACM.


Peh K.S.-H.,University of Leeds
Biodiversity and Conservation | Year: 2010

This review deals with alien species invasion in Southeast Asia, an important conservation and management concern in the region. I report on the current and potential future impacts of biological invasions on biodiversity in Southeast Asia. Current knowledge of the invasive species in Southeast Asia is mostly based on anecdotal observations. Nevertheless, I attempt to compile existing empirical evidence on the negative effects of the biological invaders found in the region. These impacts include displacement of native biota, modification of ecosystems, hybridization, environmental disturbance, and economic loss. Any effective counter-measure will need to involve a multi-national strategy, yet such measure is challenging due to a broad spectrum of political and economic development models among the Southeast Asian countries. An overview of the taxonomic structure of the invasive species in Southeast Asia shows that the invasive plant and fish are the most represented taxonomic groups in all countries. The current research effort in invasion ecology from Southeast Asia is not being up to international standard in comparison to other regions, and the absence of recent international journal articles on invasive plant species reveals the biases in biological invasion-related research. The lack of research capacity and financial support from governments, and the inability to disseminate scholarly data in international journals are the possible reasons for the dearth of research literature on biological invasions from the region. Finally, a forward-looking agenda for the region should include improving the quality and quantity of biological invasion research; adopting a tough approach to the illegal release of wildlife; and applying multi-national strategies that integrate data sharing, prioritization, public awareness, policy work, capacity building, conservation actions and surveillance. © Springer Science+Business Media B.V. 2009.


Mountney N.P.,University of Leeds
Sedimentology | Year: 2012

Wet aeolian systems, in which the water table or its capillary fringe are in contact with the accumulation surface, such that moisture influences sedimentation, are well-known from modern aeolian systems and several ancient preserved successions are recognized from outcrop. One common mechanism by which accumulation of wet aeolian system deposits occurs is via a progressive rise in the relative water-table level that is coincident with ongoing dune and interdune migration, the angle of dune climb being determined by the ratio between the rate of relative water-table rise and the rate of downwind migration of the bedforms. Accumulations of wet aeolian system deposits tend to be characterized by units of climbing dune strata separated by units of damp or wet interdune strata. For simple geometric configurations, where the size of the dune and interdune units, the rate of bedform migration and the rate of aggradation all remain constant over space and time, the resulting accumulation has a simple architecture characterized by sets of uniform thickness inclined at a constant angle. However, the dynamic nature of most aeolian dune systems means that such simple configurations are unlikely in nature. The complexity inherent in these systems is accounted for here by a numerical model in which key controlling parameters, including dune and interdune wavelength and spacing, migration rate and aggradation rate, are allowed to vary systematically both spatially (from a dune-field centre to its margin) and temporally (in response to changes in sediment availability or water-table level). The range of synthetic stratigraphic architectures generated by the model accounts for all the best-known examples of aeolian dune and interdune stratigraphic configurations documented from the stratigraphic record. Modelling results have enabled the erection of a scheme for the classification of dune system type whereby the many elaborate stratal architectures known to exist in nature can effectively be accounted for by only four parameters that are allowed to vary over space and time: dune and interdune wavelength and spacing, rate of bedform migration and rate of accumulation. Results have applied implications, including the modelling of reservoir heterogeneity and the prediction of fluid flow pathways of hydrocarbons, water, CO 2 and contaminants in subsurface reservoirs and aquifers, in which low permeability interdune units might act as baffles or barriers. © 2011 The Author. Journal compilation © 2011 International Association of Sedimentologists.


Ross A.N.,University of Leeds
Quarterly Journal of the Royal Meteorological Society | Year: 2012

An analytical model is developed for flow within and above a forest canopy with a slowly varying canopy density. Results are compared with existing analytical models for flow over a surface with slowly varying roughness length, and also with numerical simulations. The results show that the analytical solution is successful in capturing the behaviour of the flow for small and slowly changing variations in canopy density. Previous models which only vary the roughness length and neglect changes in displacement height fail to capture the near-surface flow accurately. Including changes in displacement height as well as roughness length changes gives results closer to those obtained with the full canopy model, but even then the flow induced in the canopy leads to significant differences. The analytical model also highlights the sensitivity of the results to the parametrization of the vertical component of the turbulent stress tensor, τ zz. For shorter wavelength variations in the canopy density, the analytical model breaks down as the more rapid changes in density induce larger flow perturbations which lead to increased flow into and out of the canopy. This kind of idealised analytical study provides important insights into the role of canopy heterogeneities on boundary-layer flow. This is important both for understanding near-surface winds and transport, and also for parametrizing the effects of surface heterogeneities in large-scale weather and climate models. © 2011 Royal Meteorological Society.


Chen J.,University of Leeds | Stokes J.R.,University of Queensland
Trends in Food Science and Technology | Year: 2012

Oral processing of food is a dynamic process involving a range of deformation processes. The mechanical properties and the rheology of food have been widely used to understand and predict in mouth flow properties and to discover relationships with sensory perception. However, only limited success has been realised using such approaches to characterise and to interpret food texture. Tribology is emerging as a contributing discipline for understanding oral processing of food as well as texture and mouthfeel, since it encompasses both the fluid's (lubricant's) rheological properties as well as the surface properties of the interacting substrates in relative motion. © 2011.


Knox J.P.,University of Leeds
Methods in Enzymology | Year: 2012

Cellulose is generally found in the context of complex plant cell wall materials and mostly in association with other glycans. Cellulose-directed carbohydrate-binding modules (CBMs) can be readily adapted to a range of methods for the in situ imaging of cellulose structures within plant cell walls or other cellulose-based materials. Protocols for the preparation and selection of plant materials, their fixation and processing for preparation of sections for CBM labeling, and fluorescence imaging procedures are described. Approaches to direct methods in which CBMs are directly coupled to fluorophores and indirect methods in which staged incubations with secondary reagents are used for the fluorescence imaging of CBM binding to materials are discussed and presented. © 2012 Elsevier Inc.


An introduction to the applications of organometallic complexes in fluorescence cell imaging is presented. A brief summary of the chemical and photophysical properties which enable such applications is given, along with descriptions of the structures and properties of the commonest families of complexes encountered in such applications: i.e. rhenium tricarbonyls and iridium cyclometalates. The unique features which qualify these organometallics as suitable imaging agents are identified with contrasts drawn with analogues from other fields of coordination chemistry. A summary of structural diversity and cellular properties is given for each of these classes of agents, along with rarer examples of other metals, and future prospects and challenges are discussed. © 2012 American Chemical Society.


Skrimshire S.,University of Leeds
Wiley Interdisciplinary Reviews: Climate Change | Year: 2014

For at least as long as the birth of environmentalism, discourses of ecological crisis have adopted, both consciously and unconsciously, themes and concepts derived from Jewish and Christian Apocalypses. These are ancient texts remembered best for their cosmic and spiritual revelations about the world and the world to come. The scope and methods of this adoption have varied widely: from symbolic representation (images of the Four Horsemen, for instance) to the influence of end-time belief upon environmental policy. More recently, references to apocalypse have accompanied the study of climate change specifically. However, they have tended to do so without more than a superficial engagement with the theological and philosophical underpinnings of apocalyptic faith. This review article addresses this issue by engaging the meanings of apocalyptic faith within four distinct areas in the interdisciplinary study of climate change: (1) Christian ecotheology; (2) critical and social scientific discourse; (3) policy and media communications; and (4) contemporary philosophy and ethics. © 2013 John Wiley & Sons, Ltd.


Eisele H.,University of Leeds
Electronics Letters | Year: 2010

A review is presented of the state of the art of electronic sources based on semiconductor devices that have either demonstrated substantial amounts of output power or have a strong potential of producing significant output powers at frequencies above 300GHz. Both fundamental sources and harmonic power generation using varactor or varistor diodes are discussed. The key devices are Schottky diodes, heterojunction barrier varactors, heterojunction bipolar transistors, high-electron mobility transistors, resonant tunnelling diodes, tunnel-injection transit-time devices, Gunn devices, and superlattice electron devices. © 2010 The Institution of Engineering and Technology.


Nelson A.,University of Leeds
Current Opinion in Colloid and Interface Science | Year: 2010

The field of supported monolayers and bilayers on mercury (Hg) electrodes has been reviewed. The paper has focused initially on the development of the area from the classical ideas and experiments of interfacial electrochemistry in particular the adsorption of organic compounds on Hg. This development includes the structure and properties of water soluble synthetic and biological polymers at Hg/electrolyte interfaces and investigations of the adsorption of insoluble compounds specifically lipids at the Hg/electrolyte interface. The review then discusses the applications of the monolayer on the Hg membrane model to understand better biological membrane structure and function including the following areas: phospholipid behaviour in electric field, monolayer permeability to ions, gramicidin ion channel properties, electron and proton transfer to ubiquinone-10 and, biosensor applications. Finally the most recent developments of the model are detailed including advances in the impedance analysis of ultra-thin films, the transformation of the monolayer to a more relevant bilayer model and the ruggedisation of the model for on-line toxicity testing. Major recent advances during 2009-2010: 1. Robust platform for on-line biomembrane active compound and nanomaterial screening. 2. Model relating impedance of thin films on electrodes to their structure and properties. 3. Single ion channel activity in phospholipid bilayer on Hg film microelectrode. 4. Full development of bilayer system to mimic biological membrane function in bilayers. © 2010 Elsevier Ltd.


Staggs J.E.J.,University of Leeds
Fire Safety Journal | Year: 2010

The effective thermal conductivity of fully expanded intumescent chars is estimated numerically using the finite element method. Digital images are used in conjunction with information regarding total porosity from bulk and helium density measurements to construct the FE model, where one pixel of the image corresponds to one element in the model. In order to account for micro-porous inclusions (at resolutions below the digital images), a thermal conductivity sub-model is employed. This is necessary in order to restrict the number of elements in the model to a reasonable size (∼107 or fewer). Corrections to account for assumed 3D structure from the observed 2D image and also radiation augmentation across pores are also used in order to obtain better estimates of effective thermal conductivity. Calculations are compared to experimental values for a wide range of temperatures and surprisingly good agreement is found, given the severe assumptions adopted in the model. © 2010 Elsevier Ltd. All rights reserved.


Turner G.,Southern Health NHS Foundation Trust | Clegg A.,University of Leeds
Age and Ageing | Year: 2014

Older people are majority users of health and social care services in the UK and internationally. Many older people who access these services have frailty, which is a state of vulnerability to adverse outcomes. The existing health care response to frailty is mainly secondary care-based and reactive to the acute health crises of falls, delirium and immobility. A more proactive, integrated, person-centred and community-based response to frailty is required. The British Geriatrics Society Fit for Frailty guideline is consensus best practice guidance for the management of frailty in community and outpatient settings. Recognition of frailtyThe BGS recommends that all encounters between health and social care staff and older people in community and outpatient settings should include an assessment for frailty. A gait speed <0.8m/s; a timed-up-and-go test >10s; and a score of ≥3 on the PRISMA 7 questionnaire can indicate frailty. The common clinical presentations of frailty(falls, delirium, sudden immobility) can also be used to indicate the possible presence of frailty. Management of frailty The BGS recommends an holistic medical review based on the principles of comprehensive geriatric assessment (CGA) for all older people identified with frailty. This will: diagnose medical illnesses to optimise treatment; apply evidence-based medication review checklists (e.g. STOPP/START criteria); include discussion with older people and carers to define the impact of illness; work with the older person to create an individualised care and support plan. Screening for frailtyThe BGS does not recommend population screening for frailty using currently available instruments. © The Author 2014.


Xie Z.,University of Leeds
European Journal of Mechanics, B/Fluids | Year: 2014

Wind effects on breaking solitary waves are investigated in this study using a two-phase flow model. The model solves the Reynolds-averaged Navier-Stokes equations with the k - . turbulence model simultaneously for the flows both in the air and water, with the air-water interface calculated by the volume of fluid method. First, the proposed model was validated with the computations of a breaking solitary wave run-up on a 1:19.85 sloping beach in the absence of wind, and fairly good agreement between the computational results and experimental measurements was obtained. Further, detailed information of the water surface profiles, velocity fields, vorticity, turbulent stress, maximum run-up, evolution of maximum wave height, energy dissipation, plunging jet and splash-up phenomena is presented and discussed for breaking solitary waves in the presence of wind. The inclusion of wind alters the air flow structure above water waves, increases the generation of vorticity and turbulent stress, and affects the solitary wave shoaling, breaking and run-up processes. Wind increases the water particle velocities and causes water waves to break earlier and seaward, which agrees with the previous experiment. © 2013 Elsevier Masson SAS. All rights reserved.


Lovell R.M.,St Jamess Hospital | Ford A.C.,St Jamess Hospital | Ford A.C.,University of Leeds
Clinical Gastroenterology and Hepatology | Year: 2012

Background & Aims: Many cross-sectional surveys have reported the prevalence of irritable bowel syndrome (IBS), but there have been no recent systematic review of data from all studies to determine its global prevalence and risk factors. Methods: MEDLINE, EMBASE, and EMBASE Classic were searched (until October 2011) to identify population-based studies that reported the prevalence of IBS in adults (≥15 years old); IBS was defined by using specific symptom-based criteria or questionnaires. The prevalence of IBS was extracted for all studies and based on the criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Results: Of the 390 citations evaluated, 81 reported the prevalence of IBS in 80 separate study populations containing 260,960 subjects. Pooled prevalence in all studies was 11.2% (95% CI, 9.8%-12.8%). The prevalence varied according to country (from 1.1% to 45.0%) and criteria used to define IBS. The greatest prevalence values were calculated when ≥3 Manning criteria were used (14%; 95% CI, 10.0%-17.0%); by using the Rome I and Rome II criteria, prevalence values were 8.8% (95% CI, 6.8%-11.2%) and 9.4% (95% CI, 7.8%-11.1%), respectively. The prevalence was higher for women than men (OR, 1.67; 95% CI, 1.53-1.82) and lower for individuals older than 50 years, compared with those younger than 50 (OR, 0.75; 95% CI, 0.62-0.92). There was no effect of socioeconomic status, but only 4 studies reported these data. Conclusions: The prevalence of IBS varies among countries, as well as criteria used to define its presence. Women are at slightly higher risk for IBS than men. The effects of socioeconomic status have not been well described. © 2012 AGA Institute.


Bradley D.,University of Leeds
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2012

The origins of autoignition at hot spots are analysed and the pressure pulses that arise from them are related to knock in gasoline engines and to developing detonations in ducts. In controlled autoignition engines, autoignition is benign with little knock. There are several modes of autoignition and the existence of an operational peninsula, within which detonations can develop at a hot spot, helps to explain the performance of various engines. Earlier studies by Urtiew and Oppenheim of the development of autoignitions and detonations ahead of a deflagration in ducts are interpreted further, using a simple one-dimensional theory of the generation of shock waves ahead of a turbulent flame. The theory is able to indicate entry into the domain of autoignition in an 'explosion in the explosion'. Importantly, it shows the influence of the turbulent burning velocity, and particularly its maximum attainable value, upon autoignition. This value is governed by localized flame extinctions for both turbulent and laminar flames. The theory cannot show any details of the transition to a detonation, but regimes of eventually stable or unstable detonations can be identified on the operational peninsula. Both regimes exhibit transverse waves, triple points and a cellular structure. In the case of unstable detonations, transverse waves are essential to the continuing propagation. For hazard assessment, more needs to be known about the survival, or otherwise, of detonations that emerge from a duct into the same mixture at atmospheric pressure. © 2012 The Royal Society.


Calcium entry through Orai1 channels drives vascular smooth muscle cell migration and neointimal hyperplasia. The channels are activated by the important growth factor platelet-derived growth factor (PDGF). Channel activation is suggested to depend on store depletion, which redistributes and clusters stromal interaction molecule 1 (STIM1), which then coclusters and activates Orai1. To determine the relevance of STIM1 and Orai1 redistribution in PDGF responses. Vascular smooth muscle cells were cultured from human saphenous vein. STIM1 and Orai1 were tagged with green and red fluorescent proteins to track them in live cells. Under basal conditions, the proteins were mobile but mostly independent of each other. Inhibition of sarco-endoplasmic reticulum calcium ATPase led to store depletion and dramatic redistribution of STIM1 and Orai1 into coclusters. PDGF did not evoke redistribution, even though it caused calcium release and Orai1-mediated calcium entry in the same time period. After chemical blockade of Orai1-mediated calcium entry, however, PDGF caused redistribution. Similarly, mutagenic disruption of calcium flux through Orai1 caused PDGF to evoke redistribution, showing that calcium flux through the wild-type channels had been filling the stores. Acidification of the extracellular medium to pH 6.4 caused inhibition of Orai1-mediated calcium entry and conferred capability for PDGF to evoke complete redistribution and coclustering. The data suggest that PDGF has a nonclustering mechanism by which to activate Orai1 channels and maintain calcium stores replete. Redistribution and clustering become important, however, when the endoplasmic reticulum stress signal of store depletion arises, for example when acidosis inhibits Orai1 channels.


Staggs J.E.J.,University of Leeds
Fire Safety Journal | Year: 2011

The problem of estimating the convection heat transfer coefficient (CHTC) in the Cone Calorimeter (horizontal sample orientation) is revisited. In this contribution the CHTC is modelled by a Nusselt number correlation of the form Nu=CRan, where Ra is the Rayleigh number. The parameters C and n are estimated using optimisation techniques applied to two different heat transfer modelsone that assumes the sample is perfectly insulated on its unexposed face and the other that includes heat transfer to the insulation layer beneath the test sample. The results suggest that the insulation layer influences the derived values of CHTC and this observation is explored. © 2010 Elsevier Ltd All rights reserved.


Ye J.,University of Leeds
IEEE Sensors Journal | Year: 2012

The images reconstructed by electrical capacitance tomography (ECT) for two-phase flows are usually blurry at the phase interface. To improve the image quality, image filtering with associative Markov networks (AMNs), which support efficient graph-cut inference for insulation segmentation, is presented. An ECT sensor with 12 electrodes is investigated and the capacitance between different electrode pairs is calculated for some typical permittivity distributions using a finite element method. The initial images are reconstructed by liner back-projection and Landweber iterative algorithm, respectively. The obtained images are then processed using AMNs. Simulation results show significant improvement in the quality of images. © 2012 IEEE.


Drife J.,University of Leeds
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2015

Obesity increases the risk of venous thromboembolism, and pregnancy also increases the risk, particularly around delivery and in the puerperium. Pregnancy complications, which often involve bed rest in hospital, increase the risk still further. This chapter reviews recent studies aimed at quantifying these risks and discusses the mechanisms linking obesity, pregnancy and thromboe embolism. It is now apparent that obesity is a proinflammatory condition that creates a prothrombotic milieu, but as yet little is known about how this interacts with pregnancy. Awareness of interacting risk factors has led to guidelines for risk assessment in pregnancy, and implementation of thromboprophylaxis guidelines has been followed by a dramatic fall in deaths from thromboeme bolism, which was for many years the leading cause of direct maternal deaths in the UK. This chapter summarises the guidelines on the prevention, diagnosis and treatment of thromboembolism in pregnancy and discusses the next steps to further reduce mortality. © 2014 Published by Elsevier Ltd.


Cutland M.,University of Leeds
Archives of Disease in Childhood | Year: 2012

Amid the high income nations the first recognisable child abuse society was founded in the late 19th century in North America, but it was a century before the first global rights-based legislation in the form of the United Nations Convention on the Rights of the Child (UNCRC) came into play. In isolation, international legislation is insufficient to protect children but becoming party to international law sends a clear signal to the community and stakeholders that a country is committed to ensuring child protection. Incorporating and implementing the UNCRC and other child protection based legislation on a global scale is not without difficulty and there are many obstacles to fulfilling its principles and monitoring its progress. The author reviews the global pandemic of violence against children and provides an overview of the legislation that has evolved over the last century in response to it. The author also seeks to examine some of the practical difficulties and limitations in implementing global child abuse legislation with reference to three important areas: the prohibition of violence, professional capacity enhancement, and data collection and research. The role of the paediatrician is also discussed in applying a rights-based approach to promoting global child protection. Copyright Article author (or their employer) 2012.


Dickinson R.,University of Leeds
The British journal of general practice : the journal of the Royal College of General Practitioners | Year: 2010

High rates of long-term antidepressant prescribing have been identified in the older population. To explore the attitudes of older patients and their GPs to taking long-term antidepressant therapy, and their accounts of the influences on long-term antidepressant use. Qualitative study using in-depth semi-structured interviews. One primary care trust in North Bradford. Thirty-six patients aged > or =75 years and 10 GPs were interviewed. Patients were sampled to ensure diversity in age, sex, antidepressant type, and home circumstances. Participants perceived significant benefits and expressed little apprehension about taking long-term antidepressants, despite being aware of the psychological and social factors involved in onset and persistence of depression. Barriers to discontinuation were identified following four themes: pessimism about the course and curability of depression; negative expectations and experiences of ageing; medicine discontinuation perceived by patients as a threat to stability; and passive (therapeutic momentum) and active (therapeutic maintenance) decisions to accept the continuing need for medication. There is concern at a public health level about high rates of long-term antidepressant prescribing, but no evidence was found of a drive for change either from the patients or the doctors interviewed. Any apprehension was more than balanced by attitudes and behaviours supporting continuation. These findings will need to be incorporated into the planning of interventions aimed at reducing long-term antidepressant prescribing in older people.


Meyer P.,University of Leeds
Journal of Experimental Botany | Year: 2015

Environmental conditions can change the activity of plant genes via epigenetic effects that alter the competence of genetic information to be expressed. This may provide a powerful strategy for plants to adapt to environmental change. However, as epigenetic changes do not modify DNA sequences and are therefore reversible, only those epimutations that are transmitted through the germline can be expected to contribute to a long-term adaptive response. The major challenge for the investigation of epigenetic adaptation theories is therefore to identify genomic loci that undergo epigenetic changes in response to environmental conditions, which alter their expression in a heritable way and which improve the plant's ability to adapt to the inducing conditions. This review focuses on the role of DNA methylation as a prominent epigenetic mark that controls chromatin conformation, and on its potential in mediating expression changes in response to environmental signals. © The Author 2015.


Heald C.L.,Massachusetts Institute of Technology | Spracklen D.V.,University of Leeds
Chemical Reviews | Year: 2015

The authors review current understanding of the interplay between land use change and atmospheric chemistry, with a focus on short-lived atmospheric pollutants. Both natural and anthropogenic land use change may substantially impact global air quality, with significant radiative effects on global and local climate. In particular, they focus on how historical and projected land use change will alter emissions of BVOC, soil NOx, dust, smoke, and bioaerosol, as well as the dry deposition of ozone. These constitute the key drivers of air quality changes related to a dynamic land surface. The review suggests that land use change has led to an overall cooling over the 20th century, with aerosol effects alone equivalent to 10-50% of the aerosol direct radiative forcing due to anthropogenic emissions. This cooling is likely to continue through the 21st century, but is subject to large uncertainties associated with future agricultural practices. In an era of declining pollution emissions, anthropogenic land use change may become the dominant human fingerprint on ozone and aerosol climate forcing. In addition, natural land use change represents a critical climate feedback which impacts both air quality and our assessment of how anthropogenic pollution has affected cloud formation, and the associated climate cooling.


Dickinson E.,University of Leeds
Annual Review of Food Science and Technology | Year: 2015

This article reviews progress in the field of food colloids with particular emphasis on advances in novel functional ingredients and nanoscale structuring. Specific aspects of ingredient development described here are the stabilization of bubbles and foams by the protein hydrophobin, the emulsifying characteristics of Maillard-type protein-polysaccharide conjugates, the structural and functional properties of protein fibrils, and the Pickering stabilization of dispersed droplets by food-grade nanoparticles and microparticles. Building on advances in the nanoscience of biological materials, the application of structural design principles to the fabrication of edible colloids is leading to progress in the fabrication of functional dispersed systems-multilayer interfaces, multiple emulsions, and gel-like emulsions. The associated physicochemical insight is contributing to our mechanistic understanding of oral processing and textural perception of food systems and to the development of colloid-based strategies to control delivery of nutrients during food digestion within the human gastrointestinal tract. Copyright ©2015 by Annual Reviews. All rights reserved.


Speight J.M.,University of Leeds
Communications in Mathematical Physics | Year: 2014

Necessary conditions for a soliton on a torus (Formula presented.) to be a soliton crystal, that is, a spatially periodic array of topological solitons in stable equilibrium, are derived. The stress tensor of the soliton must be L2 orthogonal to (Formula presented.), the space of parallel symmetric bilinear forms on TM, and, further, a certain symmetric bilinear form on (Formula presented.), called the hessian, must be positive. It is shown that, for baby Skyrme models, the first condition actually implies the second. It is also shown that, for any choice of period lattice Λ, there is a baby Skyrme model which supports a soliton crystal of periodicity Λ. For the three-dimensional Skyrme model, it is shown that any soliton solution on a cubic lattice which satisfies a virial constraint and is equivariant with respect to (a subgroup of) the lattice symmetries automatically satisfies both tests. This verifies, in particular, that the celebrated Skyrme crystal of Castillejo et al., and Kugler and Shtrikman, passes both tests. © 2014 Springer-Verlag Berlin Heidelberg.


Murray B.S.,University of Leeds
Current Opinion in Colloid and Interface Science | Year: 2011

The scientific literature from 2002 to the present on the interfacial rheology of protein films has been reviewed, concentrating on the implications for biological systems and in particular for food emulsions and foams. The areas covered include: new methods of measurement; proteins. +. polysaccharides and protein-polysaccharide complexes; the effects of cross-linking within protein films and the origins of film viscoelasticity; proteins. +. low molecular weight surfactants; experimental and theoretical studies of the interfacial rheology and its relationship to emulsion and foam stability. There has been a something of a resurgence of interest in these areas, resulting in a number of important advances that should aid further understanding and exploitation of proteins as surface active agents and colloid stabilizers. © 2010 Elsevier B.V.


Pilling M.J.,University of Leeds
Journal of Physical Chemistry A | Year: 2013

Experimental measurements of the rate coefficients for several types of gas phase radical reactions are reviewed. They include radical isomerization and dissociation, radical + radical association, and unimolecular reactions of peroxy radicals. Some reactions of methylene in its lowest singlet state are also considered. The links to theories of chemical reaction rates and especially of capture rates for radical + radical reactions are examined. Many of the reactions involve formation of adducts, which can isomerize and dissociate. Such reactions frequently involve energy distributions of the adducts that are far from Boltzmann, and the interpretation of measurements requires the use of master equation techniques. The basis of these methods and the use of matrix diagonalization and eigenvector/eigenvalue analysis to extract phenomenological rate coefficients are discussed. The relevance of the measurements to applications in atmospheric chemistry and, especially, in combustion is briefly considered. © 2013 American Chemical Society.


Fordy A.P.,University of Leeds | Hone A.,University of Kent
Communications in Mathematical Physics | Year: 2014

We consider nonlinear recurrences generated from cluster mutations applied to quivers that have the property of being cluster mutation-periodic with period 1. Such quivers were completely classified by Fordy and Marsh, who characterised them in terms of the skew-symmetric matrix that defines the quiver. The associated nonlinear recurrences are equivalent to birational maps, and we explain how these maps can be endowed with an invariant Poisson bracket and/or presymplectic structure. Upon applying the algebraic entropy test, we are led to a series of conjectures which imply that the entropy of the cluster maps can be determined from their tropical analogues, which leads to a sharp classification result. Only four special families of these maps should have zero entropy. These families are examined in detail, with many explicit examples given, and we show how they lead to discrete dynamics that is integrable in the Liouville-Arnold sense. © 2013 Springer-Verlag Berlin Heidelberg.


Merkin J.H.,University of Leeds
European Journal of Mechanics, B/Fluids | Year: 2012

The natural convection boundary-layer flow on a vertical surface in a porous medium with local heat generation proportional to (T- T∞) p, where T is the local temperature and T∞ is the ambient temperature, is considered when there is a constant surface heat flux. For small x, where x measures the distance along the surface, the flow and heat transfer are determined by the surface heat flux, with the local heating becoming more significant as x increases. Two different situations arise, depending on the exponent p, as to how the flow develops from the leading edge. For p<2 the flow evolves to large distances with the local heating being the dominant effect for large x. For p>2 a singularity develops in the solution at a finite value xs of x, with xs being dependent on p, leading to a thermal runaway. The nature of this singularity is discussed as well as the special case when p=2. © 2012 Elsevier Masson SAS. All rights reserved.


Davidson J.,Durham University | Wilson M.,University of Leeds
Journal of Petrology | Year: 2011

Volcanic rocks erupted at Mt Pelée (Martinique; central Lesser Antilles) and the Quill volcano (Statia; northern Lesser Antilles) define distinct differentiation trends, each of which can be accounted for largely by fractional crystallization of plagioclase, amphibole and Fe-Ti oxides. This assemblage is seen commonly in associated cumulate nodules, although the petrography of the lavas is pyroxene + plagioclase + Fe-Ti oxides. Thus differentiation is controlled, in part, by cryptic amphibole fractionation. At a given degree of differentiation incompatible trace element abundances tend to be higher at Mt Pelée, and REE patterns are more fractionated than is the case at the Quill. Isotopic ratios of Sr and Pb correlate with indices of differentiation (e.g. wt % SiO2) at both volcanoes (more convincingly at Mt Pelée), indicating that differentiation is also an open-system process. When the differentiation trends for the two volcanoes are compared they do not converge towards a single parental magma composition, suggesting that the primary magmas for the Quill and Mt Pelée are different. This difference is most probably due to mantle source variations. The source of the Mt Pelée magmas appears to be more enriched in incompatible elements, consistent with a greater proportion of admixed subducted sediment. This observation is in agreement with previous studies that have documented an increasing sediment contribution southwards along the arc. However, comparison with available data for other volcanoes along the arc does not reveal a consistent along-arc trend, suggesting that a model of sediment-source mixing is oversimplified and that additional factors such as variable fluid contributions from the subducted slab may be important. © The Author 2011. Published by Oxford University Press. All rights reserved.


Visser M.,Victoria University of Wellington | Molina-Paris C.,University of Leeds
New Journal of Physics | Year: 2010

'Acoustic spacetimes', in which techniques of differential geometry are used to investigate sound propagation in moving fluids, have attracted considerable attention over the last few decades. Most of the models currently considered in the literature are based on non-relativistic barotropic irrotational fluids, defined in a flat Newtonian background. The extension, first to special relativistic barotropic fluid flow and then to general relativistic barotropic fluid flow in an arbitrary background, is less straightforward than it might at first appear. In this paper, we provide a pedagogical and simple derivation of the general relativistic 'acoustic spacetime' in an arbitrary (d + 1)-dimensional curved-space background. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.


Subramanian V.,University of Leeds | Ragunath K.,University of Nottingham
Clinical Gastroenterology and Hepatology | Year: 2014

The rapid strides made in innovative endoscopic technology to improve mucosal visualization have revolutionized endoscopy. Improved lesion detection has allowed the modern endoscopist to provide real-time optical diagnosis. Improvements in image resolution, software processing, and optical filter technology have resulted in the commercial availability of high-definition endoscopy as well as optical contrast techniques such as narrow-band imaging, flexible spectral imaging color enhancement, and i-scan. Along with autofluorescence imaging and confocal laser endomicroscopy, these techniques have complemented and enhanced traditional white light endoscopy. They have the potential to serve as red-flag techniques to improve detection of mucosal abnormalities as well as allow optical diagnosis and virtual histology of detected lesions. This review will focus on these emerging commercially available technologies and aims to provide an overview of the technologies, their clinical applicability, and current status. © 2014 AGA Institute.


Ross A.N.,University of Leeds
Boundary-Layer Meteorology | Year: 2011

Numerical simulations of scalar transport in neutral flow over forested ridges are performed using both a 1. 5-order mixing-length closure scheme and a large-eddy simulation. Such scalar transport (particularly of CO 2) has been a significant motivation for dynamical studies of forest canopy-atmosphere interactions. Results from the 1. 5-order mixing-length simulations show that hills for which there is significant mean flow into and out of the canopy are more efficient at transporting scalars from the canopy to the boundary layer above. For the case with a source in the canopy this leads to lower mean concentrations of tracer within the canopy, although they can be very large horizontal variations over the hill. These variations are closed linked to flow separation and recirculation in the canopy and can lead to maximum concentrations near the separation point that exceed those over flat ground. Simple scaling arguments building on the analytical model of Finnigan and Belcher (Q J Roy Meteorol Soc 130:1-29, 2004) successfully predict the variations in scalar concentration near the canopy top over a range of hills. Interestingly this analysis suggests that variations in the components of the turbulent transport term, rather than advection, give rise to the leading order variations in scalar concentration. The scaling arguments provide a quantitative measure of the role of advection, and suggest that for smaller/steeper hills and deeper/sparser canopies advection will be more important. This agrees well with results from the numerical simulations. A large-eddy simulation is used to support the results from the mixing-length closure model and to allow more detailed investigation of the turbulent transport of scalars within and above the canopy. Scalar concentration profiles are very similar in both models, despite the fact that there are significant differences in the turbulent transport, highlighted by the strong variations in the turbulent Schmidt number both in the vertical and across the hill in the large-eddy simulation that are not represented in the mixing-length model. © 2011 Springer Science+Business Media B.V.


Holden J.,University of Leeds | Rose R.,UK Center for Ecology and Hydrology
International Journal of Climatology | Year: 2011

A homogenized 76-year daily-mean temperature series is presented for Moor House, an upland peatland meteorological station in northern England, which provides the longest instrumental temperature record in the UK uplands. This paper assesses trends in the temperature record over time compared to the nearby lowland temperature record at Durham. Overall warming for 1991-2006 compared with 1931-1960 and 1961-1990 was approximately the same at the upland site (0.53 °C and 0.73 °C for the two time periods, respectively) as at Durham (0.61 °C and 0.71 °C), maintaining a similar lapse rate. However, winter warming is dominant at Moor House and more pronounced and concentrated over a shorter period than at Durham; summer warming is more prominent at Durham. Therefore, seasonal lapse rates have changed and become more divergent between winter and summer half-years. Rather than changes in the dominance of particular air-masses over the study area accounting for seasonal lapse rate changes, there had been significant steepening of lapse rates over time for some air flow types. Minimum temperatures have increased more than maximum temperatures at Moor House with a consequent significant reduction in diurnal range. At Durham minimum and maximum temperatures have changed in approximate tandem so that there is no significant change in diurnal temperature range. The frequency of air frosts reduced by approximately 23% (from 129 days per year to 99) at Moor House from 1991-2006 compared to 1953-1980, and this may have major implications for the functioning of terrestrial and aquatic systems in the region. These results demonstrate that while overall annual warming in the uplands and lowlands within particular regions may be similar, even where annual lapse rates have been maintained, the seasonal distribution of that warming may be quite different even over short distances and so lowland records are not a reliable indicator of regional upland temperature change. © 2010 Royal Meteorological Society.


Buse C.E.,University of Leeds
Ageing and Society | Year: 2010

This paper explores the embodied dimensions of computer and internet use in later life, and examines how technology use relates to constructions and experiences of the ageing body. It is argued that previous research on technology use and embodiment has neglected older bodies, in contrast to research on gender and disability. Furthermore, while earlier theorisations presented internet use as disembodied, it is argued that the experience of using such technologies is grounded in our embodiment. In the light of these limitations and arguments for more complete theories of the body, this paper explores how technology use relates to various aspects of embodiment. These issues are examined in the light of data from qualitative interviews and time-use diaries completed by retirees in 17 households in the United Kingdom. By examining the technobiographies of these older computer users, it is shown that changes in body techniques are prompted and in some cases required by broader cultural and technological change. The findings evince the process of acquiring computing skills as an embodied competency, and as a form of practical knowledge that can only be learned by doing. These experiences of technology use were embedded within constructions and experiences of ageing bodies. Although the participants drew on discourses of ageing in complex ways, their coding of computer technologies in terms of the competences of youth often reproduced hierarchies between young and old bodies. Copyright © Cambridge University Press 2010.


Nelson E.A.,University of Leeds
Cochrane database of systematic reviews (Online) | Year: 2012

Up to 1% of adults will have a leg ulcer at some time. The majority of leg ulcers are venous in origin and are caused by high pressure in the veins due to blockage or weakness of the valves in the veins of the leg. Prevention and treatment of venous ulcers is aimed at reducing the pressure either by removing/repairing the veins, or by applying compression bandages/stockings to reduce the pressure in the veins.The majority of venous ulcers heal with compression bandages, however ulcers frequently recur. Clinical guidelines therefore recommend that people continue to wear compression, usually in the form of hosiery (tights, stockings, socks) after their ulcer heals, to prevent recurrence. To assess the effects of compression (socks, stockings, tights, bandages) in preventing the recurrence of venous ulcers. If compression does prevent ulceration compared with no compression, then to identify whether there is evidence to recommend particular levels of compression (high, medium or low, for example), types of compression, or brands of compression to prevent ulcer recurrence after healing. For this update we searched The Cochrane Wounds Group Specialised Register (searched 1 March 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2); Ovid MEDLINE (1950 to February Week 4 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, February 29, 2012); Ovid EMBASE (1980 to 2012 Week 08); and EBSCO CINAHL (1982 to 1 March 2012). Randomised controlled trials evaluating compression bandages or hosiery for preventing the recurrence of venous ulcers. Two review authors undertook data extraction and risk of bias assessment independently. Four trials (979 participants) were eligible for inclusion in this review. One trial in patients with recently healed venous ulcers (n = 153) compared recurrence rates with and without compression and found that compression significantly reduced ulcer recurrence at six months (Risk ratio (RR) 0.46, 95% CI 0.27 to 0.76).Two trials compared high-compression hosiery (equivalent to UK class 3) with moderate-compression hosiery (equivalent to UK class 2). The first study (n=300) found no significant reduction in recurrence at five years follow up with high-compression hosiery compared with moderate-compression (RR 0.82, 95% CI 0.61 to 1.12). The second study (n = 338) assessed ulcer recurrence at three years follow up and found that high-compression hosiery reduced recurrence compared with moderate-compression (RR 0.57, 95% CI 0.39 to 0.81). Statistically significant heterogeneity precluded meta-analysis of the results from these studies. Patient-reported compliance rates were reported in both trials;,there was significantly higher compliance with medium-compression than with high-compression hosiery in one and no significant difference in the second.A fourth trial (166 patients) found no statistically significant difference in recurrence between two types of medium (UK class 2) compression hosiery (Medi versus Scholl: RR 0.74, 95% CI 0.45 to 1.2).No trials of compression bandages for preventing ulcer recurrence were identified. There is evidence from one trial that compression hosiery reduces rates of reulceration of venous ulcers compared with no compression. Results from one trial suggest that recurrence is lower in high-compression hosiery than in medium-compression hosiery at three years whilst another trial found no difference at 5 years. Rates of patient intolerance of compression hosiery were high. There is insufficient evidence to aid selection of different types, brands, or lengths of compression hosiery.


Alcott B.,University of Leeds
Journal of Cleaner Production | Year: 2012

The environmental structural change strategy claims that by shifting our expenditures to economic sectors with lower environmental intensity, absolute resource consumption and environmental impact can be lowered. Environmental Input-Output methodologies for computing these intensities attribute no resource consumption to labour or households because these are not classified as sectors. The suggestion that service sectors entail less environmental impact, however, loses force if a unit of labour contains embodied energy, and attributing these inputs to labour drastically reduces intensity variation between sectors. Relative growth of service sectors has furthermore not been accompanied by decreased resource consumption; thus models whose intensity computations cover not only inter-firm payments but also labour earnings and household expenditures may have superior predictive power. If moreover natural-resource and labour inputs to product are incommensurable, intensity ratios themselves have perhaps only monetary, rather than real, significance. © 2011 Elsevier Ltd. All rights reserved.


Raiswell R.,University of Leeds
Deep-Sea Research Part II: Topical Studies in Oceanography | Year: 2011

Sediments from icebergs and glaciers contain nanopartculate Fe(III) oxyhydroxides (including ferrihydrite) which form in aqueous, oxic (micro)environments where Fe(II)-bearing rock minerals oxidise and high degrees of supersaturation are promoted by freezing and thawing. An ascorbic acid extraction dissolves only labile Fe present in fresh (loosely aggregated) ferrihydrite that is directly or indirectly bioavailable. Glacial and iceberg sediments contain ferrihydrite aggregates that provide 0.04 to 0.17% Fe soluble in ascorbic acid, rather larger than the concentrations in a limited suite of atmospheric dusts. The dissolution behaviour of labile Fe from glacial and iceberg sediments by ascorbic acid is controlled by the access of reactant, or removal of solute, through micropores to or from active sites in the interior of ferrihydrite aggregates. A first-order kinetic model is presented to examine the rates at which bioavailable Fe can be supplied by melting icebergs in the Weddell Sea. The model utilizes rate constants from the literature for the processes which solubilise Fe from nanoparticulate ferrihydrite (dissolution, photochemical reduction and grazing) and the processes that remove Fe nanoparticulates (sinking, scavenging and incorporation in faecal material), and render them less reactive (transformation, aging). Model results demonstrate that icebergs can supply bioavailable Fe to the Weddell Sea by the dissolution of nanoparticulate ferrihydrite (despite loss/removal of nanoparticles by sinking, aging, transformation, scavenging and incorporation into faecal pellets) at rates that are comparable to atmospheric dust. Dissolution enhanced by photochemical reduction and grazing provides the most rapid rates of bioavailable Fe production. © 2010 Elsevier Ltd.


Raiswell R.,University of Leeds
Elements | Year: 2011

The biogeochemical cycle of iron plays a key role in the ocean by delivering bioavailable iron that controls plankton productivity. Transport through the iron cycle occurs mainly as nanoparticulate (oxyhydr)-oxides, which are physically and chemically intermediate between aqueous and particulate forms and can be directly or indirectly bioavailable. Iron nanoparticles transform with time to more stable forms by increased crystallinity, aggregation and growth, and they also alter to other nanominerals. These age transformations can be inhibited or reversed. The resulting aging-rejuvenation cycle frst produces stability during long-distance transport and then reverses the process such that bioavailable and labile iron can be produced and delivered to the open ocean.


Two scales of levee confinement are commonly recognised from submarine channel-levee systems on the seafloor and in the subsurface. Large-scale external levees bound the entire system whilst smaller-scale internal levees bound individual thalweg channels within the channel-belt. Although thin beds are commonly identified in core and well logs, their origin, and consequently their stratigraphic significance is currently poorly understood. This knowledge gap stems, in part, from the lack of unambiguously identified outcrop analogues of channel-levees, and in particular the lack of identifiable internal and external levees. Here we report from two exhumed channel-levee systems where both scales of confinement can be recognised: the Rosario Fm. of Baja California, and the Fort Brown Fm. of South Africa. A suite of characteristic sedimentary features are recognised from internal and external levees respectively: internal levees are characterised by structures indicative of complexity in the waxing-waning style of overspill, interactions with topography and flow magnitude variability; in contrast, external levees are characterised by structures indicative of simple surge-like waning flows, relatively uniform flow directions, laterally extensive beds, and a lack of erosive events. Using these observations, together with published literature, we propose a simple nomenclatural scheme for levee sub-environments, and criteria to differentiate between levee sub-environments in core or outcrop. © 2010 Elsevier Ltd.


Plane J.M.C.,University of Leeds
Journal of Atmospheric and Solar-Terrestrial Physics | Year: 2011

Meteoric ablation injects similar quantities of Fe, Mg and Si vapours into the upper mesosphere; these vapours recondense to form meteoric smoke particles. Electronic structure theory is used to argue that the metal silicate molecules, FeSiO3 and MgSiO3, should form in the upper atmosphere. These molecules, which may be regarded as the smallest smoke particles, have extremely large electric dipole moments of 9.5 and 12.2 Debye, respectively. H2O molecules therefore bind very effectively to them, with free energy changes in excess of -100kJmol-1. Indeed, the addition of up to 8H2Os occurs more favourably than the sublimation of H2O to bulk ice. FeSiO3 and MgSiO3 should therefore nucleate ice particles under polar mesospheric conditions at temperatures around 140K. These silicates should form readily and are shown to be stable in the mesosphere. Their daily production should be between 2000 and 8000cm-3 around 85km, which is sufficient to compete with transport out of the polar mesosphere by the meridional circulation. © 2010 Elsevier Ltd.


Evans R.M.L.,University of Leeds
Contemporary Physics | Year: 2010

Complex fluids are easily and reproducibly driven into non-equilibrium steady states by the action of shear flow. The statistics of the microstructure of non-equilibrium fluids is important to the material properties of every complex fluid that flows, e.g. axle grease on a rotating bearing; blood circulating in capillaries; molten plastic flowing into a mould; the non-equilibrium onion phase of amphiphiles used for drug delivery; the list is endless. Such states are as diverse and interesting as equilibrium states, but are not governed by the same statistics as equilibrium materials. I review some recently discovered principles governing the probabilities of various types of molecular re-arrangements taking place within a sheared fluid. As well as providing new foundations for the study of non-equilibrium matter, the principles are applied to some simple models of particles interacting under flow, showing that the theory exhibits physically convincing behaviour. © 2010 Taylor & Francis.


Stell J.G.,University of Leeds
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2014

Formal Concept Analysis (FCA) provides an account of classification based on a binary relation between two sets. These two sets contain the objects and attributes (or properties) under consideration. In this paper I propose a generalization of formal concept analysis based on binary relations between hypergraphs, and more generally between pre-orders. A binary relation between any two sets already provides a bipartite graph, and this is a well-known perspective in FCA. However the use of graphs here is quite different as it corresponds to imposing extra structure on the sets of objects and of attributes. In the case of objects the resulting theory should provide a knowledge representation technique for structured collections of objects. The generalization is achieved by an application of work on mathematical morphology for hypergraphs. © Springer International Publishing Switzerland 2014.


Grainger A.,University of Leeds
Journal of Arid Environments | Year: 2015

The aspirational goal of a land degradation neutral world, to be realized by reducing the rate of land degradation and increasing the rate of restoration of degraded land, was agreed at the Rio+20 Conference in 2012. This paper evaluates the feasibility of introducing a Land Degradation Neutral (LDN) scheme as an activity of the United Nations Convention to Combat Desertification (UNCCD). It concludes that national and international implementation would involve political, organizational and technological challenges. Monitoring restoration of desertified land by revegetation would be feasible immediately, but monitoring cuts in national rates of desertification would not, because no baseline rates are currently available national and international scientific capacities to measure desertification are limited; and further scientific knowledge is required to supplement existing knowledge of desertification processes and of land use and land cover change processes generally. This paper therefore suggests introducing an LDN scheme in phases. Phase 1 would focus on restoring degraded lands, improving national land use planning systems, and establishing international and national monitoring capacities. Phase 2 would reduce desertification rates with the help of fully integrated land use planning and monitoring systems. Phase 3 would set a target year for realizing an LDN goal, based on experiences in Phases 1 and 2. All three phases would be informed by accessing existing scientific knowledge, and gaining new knowledge by launching a scientific LDN process that can evolve in parallel with the political process. © 2014 Elsevier Ltd.


Brown J.E.,University of Leeds | Sim S.,University of Sheffield
Neoplasia | Year: 2010

The preferential metastasis of prostate cancer cells to bone disrupts the process of bone remodeling and results in lesions that cause significant pain and patient morbidity. Although prostate-specific antigen (PSA) is an established biomarker in prostate cancer, it provides only limited information relating to bone metastases and the treatment of metastatic bone disease with bisphosphonates or novel noncytotoxic targeted or biological agents that may provide clinical benefits without affecting PSA levels. As bone metastases develop, factors derived from bone metabolism are released into blood and urine, including N- and C-terminal peptide fragments of type 1 collagen and bone-specific alkaline phosphatase, which represent potentially useful biomarkers for monitoring metastatic bone disease. A number of clinical trials have investigated these bone biomarkers with respect to their diagnostic, prognostic, and predictive values. Results suggest that higher levels of bone biomarkers are associated with an increased risk of skeletal-related events and/or death. As a result of these findings, bone biomarkers are now being increasingly used as study end points, particularly in studies investigating novel agents with putative bone effects. Data from prospective clinical trials are needed to validate the use of bone biomarkers and to confirm that marker levels provide additional information beyond traditional methods of response evaluation for patients with metastatic prostate cancer. © 2010 Neoplasia Press, Inc.


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.


Carter M.C.,University of Leeds
Journal of medical Internet research | Year: 2013

There is growing interest in the use of information communication technologies to treat obesity. An intervention delivered by smartphone could be a convenient, potentially cost-effective, and wide-reaching weight management strategy. Although there have been studies of texting-based interventions and smartphone applications (apps) used as adjuncts to other treatments, there are currently no randomized controlled trials (RCT) of a stand-alone smartphone application for weight loss that focuses primarily on self-monitoring of diet and physical activity. The aim of this pilot study was to collect acceptability and feasibility outcomes of a self-monitoring weight management intervention delivered by a smartphone app, compared to a website and paper diary. A sample of 128 overweight volunteers were randomized to receive a weight management intervention delivered by smartphone app, website, or paper diary. The smartphone app intervention, My Meal Mate (MMM), was developed by the research team using an evidence-based behavioral approach. The app incorporates goal setting, self-monitoring of diet and activity, and feedback via weekly text message. The website group used an existing commercially available slimming website from a company called Weight Loss Resources who also provided the paper diaries. The comparator groups delivered a similar self-monitoring intervention to the app, but by different modes of delivery. Participants were recruited by email, intranet, newsletters, and posters from large local employers. Trial duration was 6 months. The intervention and comparator groups were self-directed with no ongoing human input from the research team. The only face-to-face components were at baseline enrollment and brief follow-up sessions at 6 weeks and 6 months to take anthropometric measures and administer questionnaires. Trial retention was 40/43 (93%) in the smartphone group, 19/42 (55%) in the website group, and 20/43 (53%) in the diary group at 6 months. Adherence was statistically significantly higher in the smartphone group with a mean of 92 days (SD 67) of dietary recording compared with 35 days (SD 44) in the website group and 29 days (SD 39) in the diary group (P<.001). Self-monitoring declined over time in all groups. In an intention-to-treat analysis using baseline observation carried forward for missing data, mean weight change at 6 months was -4.6 kg (95% CI -6.2 to -3.0) in the smartphone app group, -2.9 kg (95% CI -4.7 to -1.1) in the diary group, and -1.3 kg (95% CI -2.7 to 0.1) in the website group. BMI change at 6 months was -1.6 kg/m(2) (95% CI -2.2 to -1.1) in the smartphone group, -1.0 kg/m(2) (95% CI -1.6 to -0.4) in the diary group, and -0.5 kg/m(2) (95% CI -0.9 to 0.0) in the website group. Change in body fat was -1.3% (95% CI -1.7 to -0.8) in the smartphone group, -0.9% (95% CI -1.5 to -0.4) in the diary group, and -0.5% (95% CI -0.9 to 0.0) in the website group. The MMM app is an acceptable and feasible weight loss intervention and a full RCT of this approach is warranted. ClinicalTrials.gov NCT01744535; http://clinicaltrials.gov/ct2/show/NCT01744535 (Archived by WebCite at http://www.webcitation.org/6FEtc3PVB).


Plane J.M.C.,University of Leeds
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2013

Understanding the nature of dust condensation in the outflow from oxygen-rich asymptotic giant branch stars is a continuing problem. A kinetic model has been developed to describe the formation of gasphase precursors from Ca, Mg, Fe, SiO and TiO in an outflow cooling from 1500 to 1000 K. Electronic structure calculations are used to identify efficient reaction pathways that lead to the formation of metal titanates and silicates. The molecular properties of the stationary points on the relevant potential energy surfaces are then used in a multi-well master equation solver to calculate pertinent rate coefficients. The outflow model couples an explicit treatment of gas-phase chemistry to a volumeconserving particle growthmodel. CaTiO3 is shown to be the overwhelming contributor to the formation of condensation nuclei (CN), with less than 0.01 per cent provided by CaSiO3, (TiO 2)2 and FeTiO3. Magnesium species make a negligible contribution. Defining CN as particles with radii greater than 2 nm, the model shows that for stellar mass loss rates above 3 × 10 -5M⊙M yr-1, more than 10-13 CN per H nucleus will be produced when the outflow temperature is still well above 1000 K. This is sufficient to explain the observed number density of grains in circumstellar dust shells.© 2013 The Author(s) Published by the Royal Society. All rights reserved.


Kisil V.V.,University of Leeds
Journal of Physics A: Mathematical and Theoretical | Year: 2012

We describe connections between the localization technique introduced by I B Simonenko and operator covariant transform produced by nilpotent Lie groups. This article is part of a special issue of Journal of Physics A: Mathematical and Theoretical devoted to Coherent states: mathematical and physical aspects. © 2012 IOP Publishing Ltd.


Lozano R.,University of Leeds
Journal of Cleaner Production | Year: 2012

Corporate leaders and employees have been increasingly recognising their role in contributing to sustainability. In this context, different voluntary tools, approaches, and initiatives have been developed by and for corporations to engage with sustainability. However, there has been a lack of clarity in explaining how the initiatives address the different elements of the company system (operations and processes, management and strategy, organisational systems, procurement and marketing, and assessment and communication), how they contribute to sustainability's dimensions (economic, environmental, social, and time), how they are linked, or combined to help leaders better embed sustainability into their company's system. The paper provides an analysis of sixteen of the most widely used initiatives (e.g. life cycle assessment, eco-design, cleaner production, corporate social responsibility, and sustainability reporting). Each initiative was analysed on how it contributes or addresses the four dimensions of sustainability, and the company system. It was found that each initiative has advantages with respect to scope and focus for the sustainability dimensions and the company system's elements, but it has certain disadvantages when it comes to dealing with the complexity and broadness of sustainability. The paper discusses how relying on one initiative can result in a limited and narrow contribution to sustainability and curtail coverage of the company's system. The results indicate that the least addressed elements of the company system have been organisational systems and procurement and marketing. A new framework, the Corporate Integration of Voluntary Initiatives for Sustainability (CIVIS), is proposed with two purposes: (1) to help company leaders better understand how to improve their company's contribution to sustainability, and (2) to foster a holistic approach through the combination of company initiatives that would help to embed sustainability into a company's system with the least effort and maximum results. © 2011 Elsevier Ltd. All rights reserved.


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

Venous leg ulcers affect up to 1% of people at some time in their lives and are often painful. The main treatments are compression bandages and dressings. Topical treatments to reduce pain during and between dressing changes are sometimes used. To determine the effects of topical agents or dressings for pain in venous leg ulcers. For this third update the following databases were searched: Cochrane Wounds Group Specialised Register (searched 9 May 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 4); Ovid MEDLINE (2009 to April Week 4 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations May 08, 2012); Ovid EMBASE (2009 to 2012 Week 18); and EBSCO CINAHL (2009 to May 2 2012). No date or language restrictions were applied. Published or unpublished randomised controlled trials (RCTs) that evaluated the effects of topical agents or dressing for the treatment of pain in venous ulcers were included. Two review authors independently performed trial selection, data extraction and risk of bias assessment. Six trials (343 participants) evaluated Eutectic Mixture of Local Anaesthetics (EMLA): lidocaine-prilocaine cream for the pain associated with ulcer debridement. The between-group difference in pain measured on a 100 mm scale was statistically significant in favour of EMLA (MD -20.65, 95% CI -12.19 to -29.11). No significant between-group differences in burning or itching were observed.Two trials (470 participants with venous leg ulcers) evaluated ibuprofen slow-release foam dressings for persistent venous leg ulcer pain. Compared with local best practice, significantly more participants in the ibuprofen dressing group achieved the outcome of >50% of the total maximum pain relief score between day 1 and day 5 than participants in the local best practice group (RR 1.63, 95% CI 1.24 to 2.15). The number needed to treat was 6 (95% CI 4 to 12). In the second trial, compared with an identical non-ibuprofen foam dressing, there was no statistically significant difference in the proportion of participants experiencing slight to complete pain relief on the first evening of treatment.Limited data were available to assess healing rates or adverse events. There is some evidence to suggest that ibuprofen dressings may offer pain relief to people with painful venous leg ulcers. EMLA (5%) appears to provide effective pain relief during the debridement of venous leg ulcers. Further research should consider standardised pain assessment methods and assess both the effect on ulcer healing and the impact of long term use of these treatments.


Foxon T.J.,University of Leeds
Energy Policy | Year: 2013

Achieving long-term targets for greenhouse gas emissions reductions, such as the UK's legally-binding target of reducing its emissions by 80% by 2050, will require a transition in systems for meeting and shaping energy service demands, involving radical substitution to low-carbon supply technologies and improvements in end-use energy efficiency. This paper describes the development and high-level analysis of a set of transition pathways to a UK low carbon electricity system, explaining key features of the core pathways developed and the distinctiveness and value of the approach. The pathways use an 'action space' concept to explore the dynamic interactions between choices made by actors, which are influenced by the competing governance 'framings' or 'logics' that different actors pursue. The paper sets out three core transition pathways - Market Rules, Central Co-ordination and Thousand Flowers, in which market, government and civil society logics respectively dominate. It summarises the key technological and institutional changes in these pathways, and the roles of actors in bringing these about. This leads to an identification of the key risks to the realisation of each of the pathways, and of the challenges for individuals, businesses, social movements and policy-makers in taking action to bring them about and sustain them. © 2012 Elsevier Ltd.


Bruine De Bruin W.,University of Leeds | Bruine De Bruin W.,Carnegie Mellon University | Bostrom A.,University of Washington
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

As members of a democratic society, individuals face complex decisions about whether to support climate change mitigation, vaccinations, genetically modified food, nanotechnology, geoengineering, and so on. To inform people's decisions and public debate, scientific experts at government agencies, nongovernmental organizations, and other organizations aim to provide understandable and scientifically accurate communication materials. Such communications aim to improve people's understanding of the decision-relevant issues, and if needed, promote behavior change. Unfortunately, existing communications sometimes fail when scientific experts lack information about what people need to know to make more informed decisions or what wording people use to describe relevant concepts. We provide an introduction for scientific experts about how to use mental models research with intended audience members to inform their communication efforts. Specifically, we describe how to conduct interviews to characterize people's decision-relevant beliefs or mental models of the topic under consideration, identify gaps and misconceptions in their knowledge, and reveal their preferred wording. We also describe methods for designing follow-up surveys with larger samples to examine the prevalence of beliefs as well as the relationships of beliefs with behaviors. Finally, we discuss how findings from these interviews and surveys can be used to design communications that effectively address gaps and misconceptions in people's mental models in wording that they understand. We present applications to different scientific domains, showing that this approach leads to communications that improve recipients' understanding and ability to make informed decisions.


Emery P.,University of Leeds | Emery P.,NIHR Leeds Musculoskeletal Biomedical Research Unit | Sebba A.,University of South Florida | Huizinga T.W.J.,Leiden University
Annals of the Rheumatic Diseases | Year: 2013

Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX.


Morrissey B.,University of Leeds
Molecular & cellular proteomics : MCP | Year: 2012

The PapC usher is a β-barrel outer membrane protein essential for assembly and secretion of P pili that are required for adhesion of pathogenic E. coli, which cause the development of pyelonephritis. Multiple protein subunits form the P pilus, the highly specific assembly of which is coordinated by the usher. Despite a wealth of structural knowledge, how the usher catalyzes subunit polymerization and orchestrates a correct and functional order of subunit assembly remain unclear. Here, the ability of the soluble N-terminal (UsherN), C-terminal (UsherC2), and Plug (UsherP) domains of the usher to bind different chaperone-subunit (PapDPapX) complexes is investigated using noncovalent electrospray ionization mass spectrometry. The results reveal that each usher domain is able to bind all six PapDPapX complexes, consistent with an active role of all three usher domains in pilus biogenesis. Using collision induced dissociation, combined with competition binding experiments and dissection of the adhesin subunit, PapG, into separate pilin and adhesin domains, the results reveal why PapG has a uniquely high affinity for the usher, which is consistent with this subunit always being displayed at the pilus tip. In addition, we show how the different soluble usher domains cooperate to coordinate and control efficient pilus assembly at the usher platform. As well as providing new information about the protein-protein interactions that determine pilus biogenesis, the results highlight the power of noncovalent MS to interrogate biological mechanisms, especially in complex mixtures of species.


Willans C.E.,University of Leeds
Organometallic Chemistry | Year: 2010

Since their isolation in 1991,1 N-heterocyclic carbenes (NHCs) have become ubiquitous in organometallic chemistry. In more recent years investigations into the coordination of NHCs to other elements have expanded, and there are examples of their coordination to elements across the whole periodic table. This report gives an overview of NHC complexes of non-transition metal elements, ranging from the s-block elements, through the p-block and on to the lanthanides. © The Royal Society of Chemistry 2010.


Collins T.,University of Leeds
Transactions of the Institute of British Geographers | Year: 2016

Civic pride relates to how places promote and defend local identity and autonomy. It is often championed as a key value and aspiration of local government. This paper argues that civic pride has been under-examined in geography, and in particular the emotional meanings of pride need to be better understood. In response, I present an emotional analysis of civic pride and discuss its role in British cities, particularly in the context of urban regeneration and the UK's new localism agenda. In the latter part of the paper I provide a case study of Nottingham in England, where I employ a discourse analysis of recent urban policy and local media to examine how civic pride is being mobilised and contested in the city. Examining civic pride is important because it shapes and reflects the political values that local governments stand for and provides a basis for thinking about how emotions are used strategically (and problematically) in urban policy. This paper complements and challenges existing literature on cities by showing how civic pride shapes, but also obscures, the ideological politics of local government and how, as geographers, we might consider more seriously the ways forms of power, identity and inequality are reproduced and contested through emotions such as pride. © 2016 Royal Geographical Society (with the Institute of British Geographers).


May A.D.,University of Leeds
International Journal of Sustainable Transportation | Year: 2013

This article provides an overview of trends in demand for urban transport, considers their implications for the achievement of a set of urban transport policy objectives, and summarizes the principal problems which are likely to arise. It notes in particular the challenge of meeting climate change goals, which is likely to dominate the development of urban transport policy over the next four decades. It considers the range of policy instruments available, and summarizes evidence on their effectiveness. On this basis it argues that a package of policy instruments is needed, and provides evidence of good practice in the design of such packages. It reviews the barriers to the design and implementation of such packages, and summarizes international guidance on ways of overcoming these barriers. Finally, in a concluding section, it identifies the principal areas in which innovations are needed in urban transport policy and, in its role in providing the context for a special issue on modeling, suggests the resulting requirements for model development. © 2013 Copyright Taylor and Francis Group, LLC.


Shepherd S.,University of Leeds
International Journal of Sustainable Transportation | Year: 2013

Private toll operators generally seek to maximize their profit while accounting for the re-routing and demand response of the road users and, in the case of competitive toll operation, the response of other toll operators. Traditionally, the literature assumes that toll operators act under perfect information or set up a game-theoretic approach to find the competitive equilibrium. This article takes a different approach. A system-dynamics approach is used to model both the users' route choice and demand response to changes in generalized cost and to model the toll operators' decision rules or toll-update strategies. Simple examples are used to demonstrate that the approach can lead to the traditional equilibrium solution under the assumption of perfect knowledge, but that other solutions may occur when operators use estimates of elasticities based on observed data. The solutions are shown to depend upon the frequency of the decision or change in toll level, and errors are related to the disequilibrium which is present as users respond to changes in toll levels. Finally, alternative toll-setting strategies are investigated whereby one operator may act aggressively to increase its share of the market while maximizing profit. This tactic is compared to the traditional Nash and Stackelberg solutions. © 2013 Copyright Taylor and Francis Group, LLC.


Rossiter H.B.,University of Leeds
Comprehensive Physiology | Year: 2011

The activities of daily living typically occur at metabolic rates below the maximum rate of aerobic energy production. Such activity is characteristic of the nonsteady state, where energy demands, and consequential physiological responses, are in constant flux. The dynamics of the integrated physiological processes during these activities determine the degree to which exercise can be supported through rates of O2 utilization and CO2 clearance appropriate for their demands and, as such, provide a physiological framework for the notion of exercise intensity. The rate at which O2 exchange responds to meet the changing energy demands of exercise-its kinetics-is dependent on the ability of the pulmonary, circulatory, and muscle bioenergetic systems to respond appropriately. Slow response kinetics in pulmonary O2 uptake predispose toward a greater necessity for substrate-level energy supply, processes that are limited in their capacity, challenge system homeostasis and hence contribute to exercise intolerance. This review provides a physiological systems perspective of pulmonary gas exchange kinetics: from an integrative view on the control of muscle oxygen consumption kinetics to the dissociation of cellular respiration from its pulmonary expression by the circulatory dynamics and the gas capacitance of the lungs, blood, and tissues. The intensity dependence of gas exchange kinetics is discussed in relation to constant, intermittent, and ramped work rate changes. The influence of heterogeneity in the kinetic matching of O2 delivery to utilization is presented in reference to exercise tolerance in endurance-trained athletes, the elderly, and patients with chronic heart or lung disease. © 2011 American Physiological Society.