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Newcastle upon Tyne, United Kingdom

Northumbria University, officially the University of Northumbria at Newcastle, is a university located in Newcastle upon Tyne in the North East of England. A former polytechnic, it was established as one of the new universities in 1992. It is a member of the University Alliance. It is the second university of Newcastle, along with Newcastle University. Wikipedia.

Kavanagh D.,Northumbria University
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2011

Atypical hemolytic uremic syndrome (aHUS) is now well recognized to be a disease characterized by excessive complement activation in the microvasculature. In both the familial and sporadic forms, inherited and acquired abnormalities affecting components of the alternative complement pathway are found in ~ 60% of patients. These include mutations in the genes encoding both complement regulators (factor H, factor I, membrane cofactor protein, and thrombomodulin) and activators (factors B and C3) and autoantibodies against factor H. Multiple hits are necessary for the disease to manifest, including a trigger, mutations, and at-risk haplotypes in complement genes. The prognosis for aHUS is poor, with most patients developing end-stage renal failure. Renal transplantation in most patients also has a poor prognosis, with frequent loss of the allograft to recurrent disease. However, improving results with combined liver-kidney transplantation and the advent of complement inhibitors such as eculizumab offer hope that the prognosis for aHUS will improve in future years.

Marshall S.M.,Northumbria University
Advances in Chronic Kidney Disease | Year: 2014

The nature of CKD in diabetes is changing. Diabetic glomerulosclerosis remains the cause of CKD in most type 1 diabetic individuals. However, the rate of progression of diabetic nephropathy has slowed because of improving glucose and blood pressure control. Most individuals with type 2 diabetes and 5% to 30% of those with type 1 diabetes with progressive CKD have normal urine albumin excretion or low-level microalbuminuria (albumin-to-creatinine ratio approximately <100mg/g), which does not progress despite the decline in glomerular filtration. People with progressive CKD but normal albuminuria have predominantly interstitial or vascular changes with much less glomerular changes. It seems likely that these histological abnormalities relate to blood pressure, aging, obesity, and intrarenal vascular disease. Initial studies suggested that 85% to 100% of diabetic individuals with microalbuminuria (Kidney Disease Improving Global Outcomes [KDIGO] CKD albuminuria A2) progressed to proteinuria (KDIGO CKD albuminuria A3). Recent data demonstrate that even after 2 to 3years of persistent microalbuminuria, most will revert to normal albumin excretion (KDIGO CKD albuminuria A1). Regression is more likely at lower levels of microalbuminuria and with improved glucose, blood pressure, and lipid control. Thus, low levels of microalbuminuria cannot be considered as established diabetic nephropathy. © 2014 National Kidney Foundation, Inc.

Zhang L.,Northumbria University
ACM Transactions on Speech and Language Processing | Year: 2013

Affect interpretation from open-ended drama improvisation is a challenging task. This article describes experiments in using latent semantic analysis to identify discussion themes and potential target audiences for those improvisational inputs without strong affect indicators. A context-based affect-detection is also implemented using a supervised neural network with the consideration of emotional contexts of most intended audiences, sentence types, and interpersonal relationships. In order to go beyond the constraints of predefined scenarios and improve the system's robustness, min-margin-based active learning is implemented. This active learning algorithm also shows great potential in dealing with imbalanced affect classifications. Evaluation results indicated that the context-based affect detection achieved an averaged precision of 0.826 and an averaged recall of 0.813 for affect detection of the test inputs from the Crohn's disease scenario using three emotion labels: positive, negative, and neutral, and an averaged precision of 0.868 and an average recall of 0.876 for the test inputs from the school bullying scenario. Moreover, experimental evaluation on a benchmark data set for active learning demonstrated that active learning was able to greatly reduce human annotation efforts for the training of affect detection, and also showed promising robustness in dealing with open-ended example inputs beyond the improvisation of the chosen scenarios. © 2013 ACM.

Current behaviour-based pain assessments for laboratory rodents have significant limitations. Assessment of facial expression changes, as a novel means of pain scoring, may overcome some of these limitations. The Mouse Grimace Scale appears to offer a means of assessing post-operative pain in mice that is as effective as manual behavioural-based scoring, without the limitations of such schemes. Effective assessment of post-operative pain is not only critical for animal welfare, but also the validity of science using animal models. This study compared changes in behaviour assessed using both an automated system ("HomeCageScan") and using manual analysis with changes in facial expressions assessed using the Mouse Grimace Scale (MGS). Mice (n = 6/group) were assessed before and after surgery (scrotal approach vasectomy) and either received saline, meloxicam or bupivacaine. Both the MGS and manual scoring of pain behaviours identified clear differences between the pre and post surgery periods and between those animals receiving analgesia (20 mg/kg meloxicam or 5 mg/kg bupivacaine) or saline post-operatively. Both of these assessments were highly correlated with those showing high MGS scores also exhibiting high frequencies of pain behaviours. Automated behavioural analysis in contrast was only able to detect differences between the pre and post surgery periods. In conclusion, both the Mouse Grimace Scale and manual scoring of pain behaviours are assessing the presence of post-surgical pain, whereas automated behavioural analysis could be detecting surgical stress and/or post-surgical pain. This study suggests that the Mouse Grimace Scale could prove to be a quick and easy means of assessing post-surgical pain, and the efficacy of analgesic treatment in mice that overcomes some of the limitations of behaviour-based assessment schemes.

Baker P.,Northumbria University
The Journal of bone and joint surgery. American volume | Year: 2012

In the United Kingdom, organizations involved in health-care commissioning have recently introduced legislation limiting access to total knee arthroplasty through the introduction of arbitrary thresholds unsupported by the literature and based on body mass index. This study aimed to establish the relationship between body mass index and patient-reported specific and general outcomes on total knee arthroplasty. Using national patient-reported outcome measures (PROMs) linked to the National Joint Registry, we identified 13,673 primary total knee arthroplasties performed for the treatment of osteoarthritis. The PROMs project involves the collection of condition-specific and general health outcomes before and at six months following total knee arthroplasty. The relationships between body mass index and the Oxford Knee Score, EuroQol 5D index, and EuroQol 5D Visual Analogue Scale were assessed with use of scatterplots and linear regression. The improvement in these measures was compared for three distinct groups based on body mass index (Group I [15 to 24.9 kg/m(2)], Group II [25 to 39.9 kg/m(2)], and Group III [40 to 60 kg/m(2)]) with use of multiple regression analysis to adjust for differences in age, sex, American Society of Anesthesiologists grade, general health rating, and number of comorbidities. The preoperative and postoperative patient-reported outcome measures declined to a similar extent with increasing body mass index. The gradient of the linear regression equation relating to the change in scores was positive in all cases, indicating that there was a tendency for scores to improve to a greater extent as body mass index increased. After adjustment, the changes in patient-reported outcome measures in Group I and Group III were equivalent for the Oxford Knee Score (mean difference, 0.5 point [95% confidence interval, -0.5 to 1.5 points]; p = 0.78), the EuroQol 5D index (mean difference, 0.014 point [95% confidence interval, -0.021 to 0.048 point]; p = 1.00), and the EuroQol 5D Visual Analogue Scale (mean difference, 1.9 points [95% confidence interval, -0.4 to 4.1 points]; p = 0.13). Wound complications were significantly higher (p < 0.001) at a rate of 17% (168 of 1018 patients) in Group III compared with 9% (121 of 1292 patients) in Group I. The improvements in patient-reported outcome measures experienced by patients were similar, irrespective of body mass index. Health policy should be based on the overall improvements in function and general health gained through surgery. Obese patients should not be excluded from the benefit of total knee arthroplasty, given that their overall improvements were equivalent to those of patients with a lower body mass index.

Nettle D.,Northumbria University
Proceedings. Biological sciences / The Royal Society | Year: 2013

Many studies in humans have shown that adverse experience in early life is associated with accelerated reproductive timing, and there is comparative evidence for similar effects in other animals. There are two different classes of adaptive explanation for associations between early-life adversity and accelerated reproduction, both based on the idea of predictive adaptive responses (PARs). According to external PAR hypotheses, early-life adversity provides a 'weather forecast' of the environmental conditions into which the individual will mature, and it is adaptive for the individual to develop an appropriate phenotype for this anticipated environment. In internal PAR hypotheses, early-life adversity has a lasting negative impact on the individual's somatic state, such that her health is likely to fail more rapidly as she gets older, and there is an advantage to adjusting her reproductive schedule accordingly. We use a model of fluctuating environments to derive evolveability conditions for acceleration of reproductive timing in response to early-life adversity in a long-lived organism. For acceleration to evolve via the external PAR process, early-life cues must have a high degree of validity and the level of annual autocorrelation in the individual's environment must be almost perfect. For acceleration to evolve via the internal PAR process requires that early-life experience must determine a significant fraction of the variance in survival prospects in adulthood. The two processes are not mutually exclusive, and mechanisms for calibrating reproductive timing on the basis of early experience could evolve through a combination of the predictive value of early-life adversity for the later environment and its negative impact on somatic state.

Adams J.,Northumbria University
Health Psychology | Year: 2012

Objective: Health-related behaviors often involve immediate costs to achieve long-term benefits. How one considers the future outcomes of present day behaviors (e.g., temporal orientation) may play a role in engagement in healthy behaviors. The Consideration of Future Consequences Scale (CFCS) measures temporal orientation on a unidimensional continuum. Recently, 2 subscales of the CFCS have been reported: immediate (CFC-I) and future (CFC-F) consequences. These support a multidimensional conceptualization of temporal orientation. Confirmatory factor analysis was performed on CFCS data. The associations between 2 health-related variables [smoking and body mass index (BMI)] and each subscale were then explored, controlling for sociodemographic variables. Method: A random sample of 2,000 individuals aged 18 years or over was selected from the edited electoral role for one English city and sent a postal questionnaire, including the CFCS and questions on age, gender, socioeconomic position, and self-reported current smoking status and BMI. Results: Complete data was provided by 800 participants (response rate = 40.0%). The 2-factor model fitted CFCS data better than the 1-factor model. In multiple linear regression, CFC-I was positively associated with BMI, B (95% confidence interval [CI]) = 0.47 (0.06 to 0.88), p = .025; and odds of being a current smoker, odds ratio (95% CI) = 1.28 (1.02 to 1.60), p = .035; CFC-F was not associated with health-related variables. Conclusions: These data support the multidimensional conceptualization of temporal orientation. Consideration of immediate consequences may be a more important determinant of health-related behaviors than consideration of future consequences. © 2011 American Psychological Association.

Burn D.J.,Northumbria University
Brain Pathology | Year: 2010

Cognitive impairment and dementia associated with Parkinson's disease (PD) are common and often have devastating effects upon the patient and their family. Early cognitive impairment in PD is frequent, and the functional impact may be underestimated. Optimal management will rely upon better identification of the predominant symptoms and greater knowledge of their pathophysiological basis. The management of dementia in PD (PD-D) also has to consider the significant neuropsychiatric burden that frequently accompanies the cognitive decline, as well as fluctuations in attention. Atypical anti-psychotics have a limited role at present in treating PD-D, although new drugs are under development. The mainstay of drug management for people with PD-D is cholinesterase inhibitors, although recent trials have suggested that the N-methyl-D aspartate antagonist memantine may also have some benefit. Disease modification remains the ultimate goal for preventing the inexorable decline in PD-D, although effective interventions are still some way off. Limited benefit may, however, be possible through exercise programmes and so-called "medical foods", although randomised trials are required to confirm largely anecdotal observations. © 2010 International Society of Neuropathology.

Shokrollahi K.,Northumbria University
Annals of the Royal College of Surgeons of England | Year: 2010

Request for Treatment (RFT) is a new approach to consent which aims to facilitate patients' understanding of their treatment and addresses some of the flaws highlighted in a literature review of current consent practice. It aims to provide a complete clinical, medicolegal, and documentary framework for consent and places patients at the centre of their care. It also provides doctors with more robust evidence that adequate consent has been obtained, and can be implemented with ease in most clinical scenarios, especially elective surgery. A thorough critical analysis and literature review is undertaken looking at the current state of consent world-wide. For the first time, a complete documentary system for 'request for treatment' is devised including Request for Treatment forms (RFTFs) alternatively termed Patient-centred Consent Forms (PCCFs). The arguments for the legal validity and other advantages of RFT are presented. A case with all the documentation of a full consent episode is provided which illustrates RFT in action, demonstrating the simplicity of implementation, and the robustness of the completed RFT form as a source of evidence for both consent and capacity. Request for Treatment (RFT) is a request-based model for consent that facilitates patient-centred care. It has a number of advantages including unrivalled documentary evidence of consent in the patient's own handwriting and vocabulary, demonstration of capacity, ease of implementation, and a sound legal basis. For those who may wish to use it, RFT provides a useful and novel patient-centred method of consent, and is likely to protect against negligent consent practice by highlighting patient misunderstandings early and by providing irrefutable documentary evidence that consent has been gained. It may also provide a simple method by which Gillick competence can be assessed and documented. RFT forms are available for download at www.rft.org.uk.

Sachdeva A.,Northumbria University
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: One of the settings where deep vein thrombosis (DVT) in the lower limb and pelvic veins occurs is in hospital with prolonged immobilisation of patients for various surgical and medical illnesses. Using graduated compression stockings (GCS) in these patients has been proposed to decrease the risk of DVT. This is an update of a Cochrane review first published in 2000 and updated in 2003. OBJECTIVES: To determine the magnitude of effectiveness of GCS in preventing DVT in various groups of hospitalised patients. SEARCH STRATEGY: For this update the Cochrane Peripheral Vascular Diseases Group searched their Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4) for randomised controlled trials of elastic or graduated compression stockings for prevention of DVT. SELECTION CRITERIA: Randomised controlled trials (RCTs) involving GCS alone; or GCS used on a background of any other DVT prophylactic method. DATA COLLECTION AND ANALYSIS: One author extracted the data, assessed the quality of trials and analysed the results; which were cross-checked and authenticated by a second author. MAIN RESULTS: Eighteen RCTs were identified. GCS were applied on the day before surgery or on the day of surgery and were worn up until discharge or until the patients were fully mobile. In the majority of the included studies DVT was identified by the radioactive I(125) uptake test.For GCS alone, eight RCTs were identified involving 1279 analytic units (887 patients). In the treatment group (GCS), of 662 units, 86 developed DVT (13%) in comparison to the control group (without GCS) of 617 units where 161 (26%) developed DVT. The Peto's odds ratio (OR) was 0.35 (95% confidence interval (CI) 0.26 to 0.47) with an overall effect favouring treatment with GCS (P < 0.00001). For GCS on a background of another prophylactic method, 10 RCTs were identified involving 1248 analytic units (576 patients). In the treatment group (GCS plus another method), of 621 units, 26 (4%) developed DVT, in the control group (the other method alone), of 627 units, 99 (16%) developed DVT (OR 0.25, 95% CI 0.17 to 0.36). The overall effect also favoured treatment with GCS on a background of another DVT prophylactic method (P < 0.00001). AUTHORS' CONCLUSIONS: GCS are effective in diminishing the risk of DVT in hospitalised patients. Data examination also suggests that GCS on a background of another method of prophylaxis is more effective than GCS on its own.

Objective: To describe prevalence, and socio-demographic correlates, of active transport participation amongst UK adults. Methods: Data was from the 2005 UK Time Use Survey. Active transport was defined as any walking, jogging or pedal biking for purposes other than enjoyment. Socio-demographic correlates of any active transport participation, meeting current UK guidelines for sufficient activity through active transport, and time spent on active transport, if any, were explored. Results: 4941 individuals took part in the survey and data from 80% were included in the analyses. 28% of respondents reported any active transport and 19% were sufficiently active through active transport. Median time spent in active transport, if any, was 40 min per day (inter-quartile range 20-60 min). Active transport participation was greater in younger people and those without access to a car or van. Being sufficiently active through active transport was additionally associated with being unemployed, being in a less affluent social class, and leaving full time education at an older age. Conclusions: There is scope for increasing active transport participation in the UK. That more than two thirds of those who report any active transport are sufficiently active through active transport alone may be a useful health promotion message. © 2010 Elsevier Inc. All rights reserved.

Reeks M.W.,Northumbria University
Flow, Turbulence and Combustion | Year: 2014

This paper describes methods and approaches that have been used to simulate and model the transport, mixing and agglomeration of small particles in a flowing turbulent gas. The transported particles because of their inertia are assumed not to follow the motion of the large scales of the turbulence and or the motion of the small dissipating scales of the turbulence. We show how both these behaviours can be represented by a PDF approach analogous to that used in classical kinetic theory. For large scale dispersion the focus is on transport in simple generic flows like statistically stationary homogeneous and isotropic turbulence and simple shear flows. Special consideration is given to the transport and deposition of particles in turbulent boundary layers. For small scale transport the focus is on how the small scales of turbulence together with the particle inertial response enhance collision processes like particle agglomeration. In this case the importance of segregation and the formation of caustics, singularities and random uncorrelated motion is highlighted and discussed. © 2013 Springer Science+Business Media Dordrecht.

Type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) are associated with elevated hepatic glucose production and fatty acid synthesis (de novo lipogenesis (DNL)). High carbohydrate diets also increase hepatic glucose production and lipogenesis. The carbohydrate-response element-binding protein (ChREBP, encoded by MLXIPL) is a transcription factor with a major role in the hepatic response to excess dietary carbohydrate. Because its target genes include pyruvate kinase (PKLR) and enzymes of lipogenesis, it is regarded as a key regulator for conversion of dietary carbohydrate to lipid for energy storage. An alternative hypothesis for ChREBP function is to maintain hepatic ATP homeostasis by restraining the elevation of phosphate ester intermediates in response to elevated glucose. This is supported by the following evidence: (i) A key stimulus for ChREBP activation and induction of its target genes is elevation of phosphate esters; (ii) target genes of ChREBP include key negative regulators of the hexose phosphate ester pool (GCKR, G6PC, SLC37A4) and triose phosphate pool (PKLR); (iii) ChREBP knock-down models have elevated hepatic hexose phosphates and triose phosphates and compromised ATP phosphorylation potential; (iv) gene defects in G6PC and SLC37A4 and common variants of MLXIPL, GCKR and PKLR in man are associated with elevated hepatic uric acid production (a marker of ATP depletion) or raised plasma uric acid levels. It is proposed that compromised hepatic phosphate homeostasis is a contributing factor to the elevated hepatic glucose production and lipogenesis that associate with type 2 diabetes, NAFLD and excess carbohydrate in the diet. © The Author 2015.

Primary visual cortex is often viewed as a "cyclopean retina", performing the initial encoding of binocular disparities between left and right images. Because the eyes are set apart horizontally in the head, binocular disparities are predominantly horizontal. Yet, especially in the visual periphery, a range of non-zero vertical disparities do occur and can influence perception. It has therefore been assumed that primary visual cortex must contain neurons tuned to a range of vertical disparities. Here, I show that this is not necessarily the case. Many disparity-selective neurons are most sensitive to changes in disparity orthogonal to their preferred orientation. That is, the disparity tuning surfaces, mapping their response to different two-dimensional (2D) disparities, are elongated along the cell's preferred orientation. Because of this, even if a neuron's optimal 2D disparity has zero vertical component, the neuron will still respond best to a non-zero vertical disparity when probed with a sub-optimal horizontal disparity. This property can be used to decode 2D disparity, even allowing for realistic levels of neuronal noise. Even if all V1 neurons at a particular retinotopic location are tuned to the expected vertical disparity there (for example, zero at the fovea), the brain could still decode the magnitude and sign of departures from that expected value. This provides an intriguing counter-example to the common wisdom that, in order for a neuronal population to encode a quantity, its members must be tuned to a range of values of that quantity. It demonstrates that populations of disparity-selective neurons encode much richer information than previously appreciated. It suggests a possible strategy for the brain to extract rarely-occurring stimulus values, while concentrating neuronal resources on the most commonly-occurring situations. © 2010 Jenny C. A. Read.

Verma A.,Indian Institute of Technology Guwahati | Scott K.,Northumbria University
Journal of Solid State Electrochemistry | Year: 2010

Inorganic/organic composite membranes have been prepared from polybenzimidazole and two different heteropolyacids; namely phosphotungstic acid and silicotungstic acid. The membranes were characterized using SEM, XRD, and proton conductivity. The conductivity of the composite membrane was relatively high when compared to PBI membrane. The fuel cell performance with the composite membranes doped with phosphoric acid was investigated using hydrogen. It was found that pre-treatment of PWA and SiWA influenced the fuel cell performance and that the performance was enhanced with the use of the composite membrane. However, from the electrode polarization and crossover current data it was revealed that the expected high performance of the fuel cell was not achieved because of voltage losses associated with contact resistance and poor ionic conductivity in the catalyst layer. The best performance of the fuel cell was achieved with a 40% SiWA/PBI composite membrane. © 2008 Springer-Verlag.

Van Laar J.M.,Northumbria University | Sullivan K.,Duke University
Current Opinion in Rheumatology | Year: 2013

PURPOSE OF REVIEW: The purpose of this review is to discuss recent published clinical and mechanistic studies on stem cell transplantation for systemic sclerosis and their implications for clinical practice. RECENT FINDINGS: Retrospective analyses of independent cohorts of systemic sclerosis patients treated with autologous stem cell transplantation showed significant improvement of skin thickening, lung function and quality of life, but at the expense of 6-17% treatment-related mortality. Right heart catheterization was employed in one study to identify and exclude patients at risk of serious cardiopulmonary toxicity. The superior efficacy of stem cell transplantation versus intravenous pulses cyclophosphamide was demonstrated in a small randomized, controlled phase 2 trial in 19 systemic sclerosis patients and a large randomized phase 3 trial in 156 patients with severe diffuse cutaneous systemic sclerosis. The latter also showed a survival benefit of transplanted patients despite a 10% transplant-related mortality. Mechanistic studies in transplanted patients have shown major shifts in circulating natural killer cells, T and B lymphocytes immediately after stem cell transplantation, similar to those observed in other autoimmune conditions. Stem cell transplantation of systemic sclerosis patients with lung involvement resulted in demonstrable attenuation of thoracic high-resolution CT (HRCT) abnormalities and serum markers of lung fibrosis. SUMMARY: Stem cell transplantation is an effective treatment option for patients with severe systemic sclerosis, but is associated with toxicity and treatment-related mortality. The available data suggest that patient selection and comprehensive cardiopulmonary screening are critical factors in determining outcome. VIDEO ABSTRACT AVAILABLE: See the Supplementary Digital content 1 (http://links.lww.com/COR/A7) © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Dance I.,University of New South Wales | Henderson R.A.,Northumbria University
Dalton Transactions | Year: 2014

Density functional calculations reveal that protonation of a μ3-S in [Fe4S4X4]2- clusters (X = halide, thiolate, phenoxide) results in the breaking of one S-Fe bond (to >3 Å, from 2.3 Å). This creates a doubly-bridging SH ligand (μ3-SH is not stable), and a unique three-coordinated planar Fe atom. The under-coordination of this unique Fe atom is the basis of revised mechanisms for the acid-catalysed ligand substitution reactions in which substitution of X by PhS occurs at the unique Fe site by an indirect pathway involving initial displacement of X by acetonitrile (solvent), followed by displacement of coordinated acetonitrile by PhSH. When X = Cl or Br the rate of attack by PhSH is slower than the dissociation of X-, and is the rate-determining step; in contrast, when X = SEt, SBut or OPh the rate of dissociation of XH is slower than attack by PhSH and is rate-determining for these clusters. A full and consistent interpretation of all kinetic data is presented including new explanations of many of the kinetic observations on the acid-catalysed substitution reactions of [Fe4S4X4]2- clusters. The proposed mechanisms are supported by density functional calculations of the structures of intermediates, and simulations of some of the steps. These findings are expected to have widespread ramifications for the reaction chemistry of both natural and synthetic clusters with the {Fe4S4} core. © 2014 the Partner Organisations.

Durrant M.C.,Northumbria University
Dalton Transactions | Year: 2014

The search for novel anti-malarial drugs that can disrupt biomineralization of ferriprotoporphyrin IX to haemozoin requires an understanding of the fundamental chemistry of the porphyrin's iron(iii) centre at the water-lipid interface. Towards this end, the binding affinities for a diverse set of 31 small ligands with iron(iii) porphine have been calculated using density functional theory, in the gas phase and also with implicit solvent corrections for both water and n-octanol. In addition, the binding of hydroxide, chloride, acetate, methylamine and water to ferriprotoporphyrin IX has been studied, and very similar trends are observed for the smaller and larger models. Anionic ligands generally give stronger binding than neutral ones; the strongest binding is observed for RO- and OH- ligands, whilst acetate binds relatively weakly among the anions studied. Electron-rich nitrogen donors tend to bind more strongly than electron-deficient ones, and the weakest binding is found for neutral O and S donors such as oxazole and thiophene. In all cases, ligand binding is stronger in n-octanol than in water, and the differences in binding energies for the two solvents are greater for ionic ligands than for neutrals. Finally, dimerization of ferriprotoporphyrin IX by means of iron(iii)-carboxylate bond formation has been modelled. The results are discussed in terms of haemozoin crystal growth and its disruption by known anti-malarial drugs. © 2014 the Partner Organisations.

Robson-Ansley P.,Northumbria University | Toit G.D.,Kings College London
Current Opinion in Allergy and Clinical Immunology | Year: 2010

Purpose of Review: The aim of this review is to challenge the current opinions of the pathophysiological mechanisms that give rise to food dependent exercise-induced anaphylaxis (FDEIA) and to consider these mechanisms within the wider context of exercise physiology to further inform our understanding and treatment of this condition. Recent findings: Exercise-induced anaphylaxis (food dependent and nonfood dependent) is a clinical syndrome in which anaphylaxis occurs in conjunction with exercise. Given the rarity of the condition, our current understanding relies on the many case studies and reviews of the topic. The pathophysiology of FDEIA remains to be fully elucidated with well constructed trials but current working hypotheses to date involve alterations in plasma osmolaltiy and pH, tissue enzyme activity, blood flow redistribution, altered gastrointestinal permeability and facilitated epitope recognition/allergen binding. Summary: Implications for future research are the physiological changes that occur during exercise need deeper consideration to ensure that proposed mechanisms are realistic and actually occur within the time frame and exercise-intensity domain during which the reported FDEIA occurred. These theories must be tested rigorously with sufficiently powered studies if progress is to be made in determining the perplexing pathophysiology of FDEIA. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Barter M.J.,Northumbria University
Current rheumatology reports | Year: 2013

Osteoarthritis (OA) is a disease typified by the loss of cartilage, the normal integrity of which is maintained by the resident cell, the chondrocyte. Alterations in chondrocyte gene expression with age, injury, loading or predisposing genetics, underpin OA cartilage loss. Cell- and tissue-specific gene expression is determined by epigenetic mechanisms, including DNA methylation, chromatin modifications and non-coding RNAs, including microRNAs and long-non-coding RNAs. A number of epigenetic changes have been identified between OA and normal cartilage, and the enzymes which impart the epigenetic code are increasingly seen as important players in a number of pathologies, including OA. Here, we will describe current and potential new epigenetic studies that are likely to reveal novel aspects of chondrocyte and cartilage biology and potentially help sub-characterise OA phenotypes. Importantly, many of these epigenetic modifiers or non-coding RNAs are proposed drug targets and could represent a therapeutic opportunity for this currently untreatable disease.

Mitrani I.,Northumbria University
Computer Journal | Year: 2010

We examine some of the problems associated with managing a server farm, that is, a collection of servers which are used to provide different types of services to paying customers. The users are charged for the services provided, but are also promised that certain Quality-of-Service (QoS) criteria will be met. Failure to satisfy those QoS undertakings incurs pre-specified penalties. In order to maximize the revenue obtained, the service provider must employ intelligent dynamic policies dealing with server allocation and job admission decisions. A number of such policies are surveyed. © The Author 2009. Published by Oxford University Press on behalf of The British Computer Society. All rights reserved.

Harrison C.J.,Northumbria University
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2013

The genetics of acute lymphoblastic leukemia are becoming well understood and the incidence of individual chromosomal abnormalities varies considerably with age. Cytogenetics provide reliable risk stratification for treatment: high hyperdiploidy and ETV6-RUNX1 are good risk, whereas BCR-ABL1, MLL rearrangements, and hypodiploidy are poor risk. Nevertheless, some patients within the good- and intermediate-risk groups will unpredictably relapse. With advancing technologies in array-based approaches (single nucleotide polymorphism arrays) and next-generation sequencing to study the genome, increasing numbers of new genetic changes are being discovered. These include deletions of B-cell differentiation and cell cycle control genes, as well as mutations of genes in key signaling pathways. Their associations and interactions with established cytogenetic subgroups and with each other are becoming elucidated. Whether they have a link to outcome is the most important factor for refinement of risk factors in relation to clinical trials. For several newly identified abnormalities, including intrachromosomal amplification of chromosome 21 (iAMP21), that are associated with a poor prognosis with standard therapy, appropriately modified treatment has significantly improved outcome. After the successful use of tyrosine kinase inhibitors in the treatment of BCR-ABL1-positive acute lymphoblastic leukemia, patients with alternative ABL1 translocations and rearrangements involving PDGFRB may benefit from treatment with tyrosine kinase inhibitors. Other aberrations, for example, CRLF2 overexpression and JAK2 mutations, are also providing potential novel therapeutic targets with the prospect of reduced toxicity.

Ng W.F.,Northumbria University
Rheumatology (Oxford, England) | Year: 2010

Chronic fatigue is one of the most prevalent and debilitating symptoms in primary SS (pSS). Approximately 70% of pSS patients suffer from disabling fatigue, which is associated with reduced health-related quality of life. In this article, we review the instruments used for evaluating pSS-related fatigue, our current understanding of the underlying psychosocial and physiological mechanisms of fatigue in pSS and the therapeutic strategies that have been studied in the management of fatigue in pSS.

Coulthard S.,Northumbria University
Current Opinion in Environmental Sustainability | Year: 2012

The concept of 'wellbeing' is increasingly visible in a range of public policy and debate. This paper gives an overview of how wellbeing has influenced policy in the domains of health and international development, and draws from these insights to suggest the relevance and contribution of wellbeing to sustainable fisheries. The paper describes the concept of eudaimonic wellbeing, which entails more than income, and happiness, but the living of, and flourishing in, a life that is valued and deemed worthwhile. A 3-dimensional framework for wellbeing which gives attention to material, social and subjective wellbeing dimensions is also discussed. It is argued that this multi-dimensional framing of wellbeing could contribute to sustainable fisheries in two ways: first, by providing a deeper form of social impact assessment, in particular in terms of capturing social and subjective impacts of fisheries decline. Second, it may give new insights into fisher behaviour, if behaviour can be understood in terms of the pursuit of wellbeing and a valued way of living. © 2012 Elsevier B.V.

Abed R.,St Georges Park | Teodorczuk A.,Northumbria University
British Journal of Psychiatry | Year: 2015

This editorial discusses current challenges faced by educators in undergraduate psychiatry in a community setting. It explores day-to-day difficulties faced by clinical educators and also considers the changing landscape of community services and how this might have an impact on learning opportunities. We call for efforts to improve undergraduate teaching in community psychiatry. © 2015, Royal College of Psychiatrists. All rights reserved.

Harriman A.,Northumbria University
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2013

There is, at present, no solar fuels industry anywhere in the world despite the well-publicized needs to replace our depleting stock of fossil fuels with renewable energy sources. Many obstacles have to be overcome in order to store sunlight in the form of chemical potential, and there are severe barriers to surmount in order to produce energy on a massive scale, at a modest price and in a convenient form. It is also essential to allow for the intermittent nature of sunlight, its diffusiveness and variability and to cope with the obvious need to use large surface areas for light collection. Nonetheless, we have no alternative but to devise viable strategies for storage of sunlight as biomass or chemical feedstock. Simple alternatives, such as solar heating, are attractive in terms of quick demonstrations but are not the answer. Photoelectrochemical devices might serve as the necessary machinery by which to generate electronic charge but the main problem is to couple these charges to the multi-electron catalysis needed to drive energystoring chemical reactions. Several potential fuels (CO, H2, HCOOH, NH3, O 2, speciality organics, etc.) are possible, but the photochemical reduction of CO2deserves particular mention because of ever-growing concerns about overproduction of greenhouse gases. The prospects for achieving these reactions under ambient conditions are considered herein. Copyright © The Royal Society 2013.

Lash G.E.,Northumbria University
Cold Spring Harbor Perspectives in Medicine | Year: 2015

Molecular cross-talk at the fetomaternal interface occurs between many different cell types, including uterine leukocytes, extravillous trophoblast cells, and uterine spiral arteries, is essential for the establishment and maintenance of pregnancy. This review concentrates on human pregnancy and examines three main areas in which cross-talk occurs; immune tolerance, regulation of extravillous trophoblast invasion, and remodeling of the uterine spiral arteries. © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

Durham J.,Northumbria University
Journal of orofacial pain | Year: 2013

To build an understanding of the patient's experience and from this identify recurring themes that could form part of an item pool for further testing of persistent dentoalveolar pain disorder (PDAP). Proven cases of PDAP were identified from a clinical database, and a purposive maximum variation sample was drawn. Semi-structured interviews were conducted with the sample by a single trained interviewer. Interviews were digitally recorded and transcribed verbatim. Data collection and analysis occurred until data saturation (n = 20), with no new themes emerging. Analysis of the data was an iterative and inductive process broadly following the principles of the constant comparative method. Recurrent themes emerging from the data were: difficulty in responding to history taking; duration and magnitude of pain; complex and confounding descriptors; common exacerbating factor; well-localized pain; deep pain; pressurized or pressure feeling. Several common experiences that can be considered items were identified in the data. These items will add to the limited pre-existing item pool in the literature and allow testing of this item pool to determine those items best suited to form an adjunctive self-report diagnostic instrument for PDAP.

Sherratt T.N.,Carleton University | Roberts G.,Northumbria University
Science | Year: 2012

Cooperation now has many solutions, but recent work shows how two well-known mechanisms interact.

Dai X.,Southwest University | Gao Z.,Northumbria University
IEEE Transactions on Industrial Informatics | Year: 2013

This review paper is to give a full picture of fault detection and diagnosis (FDD) in complex systems from the perspective of data processing. As a matter of fact, an FDD system is a data-processing system on the basis of information redundancy, in which the data and human's understanding of the data are two fundamental elements. Human's understanding may be an explicit input-output model representing the relationship among the system's variables. It may also be represented as knowledge implicitly (e.g., the connection weights of a neural network). Therefore, FDD is done through some kind of modeling, signal processing, and intelligence computation. In this paper, a variety of FDD techniques are reviewed within the unified data-processing framework to give a full picture of FDD and achieve a new level of understanding. According to the types of data and how the data are processed, the FDD methods are classified into three categories: model-based online data-driven methods, signal-based methods, and knowledge-based history data-driven methods. An outlook to the possible evolution of FDD in industrial automation, including the hybrid FDD and the emerging networked FDD, are also presented to reveal the future development direction in this field. © 2013 IEEE.

North M.,Northumbria University
Angewandte Chemie - International Edition | Year: 2010

Joined at the hip: By linking two salen ligands together with a strap of appropriate size and shape, the effectiveness of a bimetallic titanium(salen) complex as a catalyst for asymmetric cyanohydrin synthesis can be increased by up to two orders of magnitude. The optimal catalyst is active at a catalyst loading as low as 0.0005 mol% and will accept both trimethylsilyl cyanide and sodium cyanide/acetic anhydride as the cyanide source (see scheme). © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Data on frequency of pharmacogenetic polymorphisms in the UK population are limited. However, availability of whole genome sequencing data on 94 UK controls of European ethnicity from the 1000 genomes project together with similar data on other populations provides a valuable new source of data in this area and allows direct comparison of allele frequencies with those for other European populations. The ethnic diversity of the UK population also needs to be considered, and 1000 genomes includes data on South Asians, the most common ethnic group in the UK after White Europeans. Allele frequencies for polymorphisms in genes relevant to phase I and phase II drug metabolism for UK, Finnish, Spanish and South Asian populations were obtained from the literature and 1000 genomes. Generally there was good agreement between the literature and 1000 genomes reports. CYP2D6∗4, the most common CYP2D6 poor metabolizer allele among Europeans, appears more common in the UK than in Spain and Finland, whereas, as suggested previously, CYP2C19∗2 and CYP2C9∗2 appear more common in Finland and Spain, respectively, than in the UK. South Asians show low frequencies of CYP2C9∗2 and CYP2C19∗17 but higher frequencies of CYP2C19∗2 compared with UK residents of European ethnicity. Though personalizing drug treatment on the basis of individual genotype rather than ethnicity may be more appropriate, differences in allele frequencies across continents should be considered when designing clinical trials of new drugs. © 2015 by De Gruyter 2015.

Daly A.K.,Northumbria University
Current Drug Metabolism | Year: 2014

Adverse drug reactions involving a range of prescribed drugs and affecting the skin, liver and other organs show strong associations with particular HLA alleles. For some reactions, HLA typing prior to prescription, so that those positive for the risk allele are not given the drug associated with the reaction, shows high positive and negative predictive values. The best example of clinical implementation relates to the hypersensitivity reaction induced by the anti-HIV drug abacavir. When this reaction is phenotyped accurately, 100% of those who develop it are positive for HLA-B*57:01. Drug regulators worldwide now recommend genotyping for HLA-B*57:01 before abacavir is prescribed. Serious skin rashes including Stevens-Johnson syndrome and toxic epidermal necrosis can be induced by carbamazepine and other anticonvulsant drugs. In certain East Asians, these reactions are significantly associated with HLA-B*15:02, and typing for this allele is now recommended prior to carbamazepine prescription in these populations. Other HLA associations have been described for skin rash induced by carbamazepine, allopurinol and nevirapine and for liver injury induced by flucloxacillin, amoxicillin- clavulanate, lapatanib, lumiracoxib and ticlopidine. However, the predictive values for typing HLA alleles associated with these adverse reactions are lower. Clinical implementation therefore seems unlikely. Performing HLA typing is relatively complex compared with genotyping assays for single nucleotide polymorphisms. With emphasis on HLA-B*57:01, the approaches used commonly, including use of sequence-specific oligonucleotide PCR primers and DNA sequencing are considered, together with their successful implementation. Genotyping single nucleotide polymorphisms tagging HLA alleles is a simpler alternative to HLA typing but appears insufficiently accurate for clinical use. © 2014 Bentham Science Publishers.

Accounts of hydro-hegemony and counter hydro-hegemony provide state-based conceptions of power in international river basins. However, authority should be seen as transnationalized as small states develop coping strategies to augment their authority over decision-making processes. The article engages Rosenau’s spheres of authority concept to argue that hydro-hegemony is exercised by actors embedded in spheres of authority that reshape actor configurations as they emerge. These spheres consist of complex networks challenging customary notions of the local-global dichotomy and hydro-hegemony. Hydro-hegemony is therefore not fixed. The article examines these processes by analysing the dispute over the Xayaburi Dam in the Mekong Basin. © 2015 The Author(s). Published by Taylor & Francis.

Mann D.A.,Northumbria University
Hepatology | Year: 2014

Epigenetics is a term that encompasses a variety of regulatory processes that are able to crosstalk in order to influence gene expression and cell phenotype in response to environmental cues. A deep understanding of epigenetics offers the potential for fresh insights into the basis for complex chronic diseases and improved diagnostic and prognostic tools. Moreover, as epigenetic modifications are highly plastic and responsive to the environment, there is much excitement around the theme of epigenetic therapeutics, including not only new drugs but also more informed patient advice on lifestyle choices and their impact on pathology. This review briefly explains the molecular nature of the individual regulatory process that constitute epigenetics, including DNA methylation, histone modifications, chromatin remodeling, transcriptional control, and noncoding RNAs. The ways in which these epigenetic mechanisms influence liver physiology and disease will be considered in detail, particularly in the context of cancer, fibrosis, and nonalcoholic steatohepatitis. The current limitations associated with epigenetic profiling and therapeutics in liver disease are discussed, as is the intriguing possibility that environmental-induced epigenetic changes may become stable and heritable. Conclusion: The aim of the review is to inform hepatologists of the emerging key epigenetic ideas of relevance to liver diseases that are highly likely to form a component of patient management and care in the next decade. © 2014 The Authors. Hepatology published by Wiley on behalf of the American Association for the Study of Liver Diseases.

Urban T.J.,Duke University | Daly A.K.,Northumbria University | Aithal G.P.,University of Nottingham
Seminars in Liver Disease | Year: 2014

There is considerable evidence that susceptibility to idiosyncratic drug-induced liver injury (DILI) is genetically determined. Though genetic associations with DILI have been reported since the 1980s, the development of genome-wide association studies has enabled genetic risk factors for DILI, in common with other diseases, to be detected and confirmed more confidently. Human leukocyte antigen (HLA) genotype has been demonstrated to be a strong risk factor for development of DILI with a range of drugs and the underlying mechanism, probably involving presentation of a drug-peptide complex to T cells is increasingly well understood. However, specific HLA alleles are not associated with all forms of DILI and non-HLA genetic risk factors, especially those relating to drug disposition, also appear to contribute. For some drugs, there is evidence of a dual role for HLA and drug metabolism genes. Though the associations with non-HLA genes have been less well replicated than the HLA associations, there is increasing evidence that drug metabolism genes such as NAT2 and UGT2B7 contribute to some forms of DILI. Translating current genetic findings on DILI susceptibility to the clinic has been relatively slow, but some progress is now being made. In the future, DNA sequencing may lead to the identification of rare variants that contribute to DILI. Developments in the related area of epigenomics and in the development of improved models for DILI by use of genetically defined induced pluripotent stem cells should improve understanding of the biology of DILI and inform drug development. Copyright © 2014 by Thieme Medical Publishers, Inc.

Diffey B.L.,Northumbria University
British Journal of Dermatology | Year: 2012

Background The use of ultraviolet (UV)A lamps for curing gel nails is widespread in the cosmetic nail industry. A report that two women who had undergone this treatment subsequently developed squamous cell carcinoma (SCC) on the dorsum of hands has prompted some concern about the safety of this procedure. Objectives To estimate the number of women who would need to be exposed to UVA nail lamps for one woman to develop SCC on the dorsum of hands, who would not have done so otherwise. Methods A mathematical model that combines age and UV exposure was used to compare the risk of developing SCC due to typical sun exposure with the risk of inducing these cancers from exposure to UVA nail lamps. Results For typical usage, the analysis indicates that tens or hundreds of thousands of women would need to use a UVA nail lamp regularly for one to go on to develop SCC on the dorsum of the hands as a direct consequence. Conclusions The risk of inducing an SCC from exposure to UVA nail lamps is very low and one that is likely to be accepted by most women. Even then, the risk can be reduced to virtually zero by wearing fingerless gloves when the hands are being exposed. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.

Conrad K.P.,Florida College | Davison J.M.,Northumbria University
American Journal of Physiology - Renal Physiology | Year: 2014

During the first trimester of human pregnancy, the maternal systemic circulation undergoes remarkable vasodilation. The kidneys participate in this vasodilatory response resulting in marked increases in renal plasma flow (RPF) and glomerular filtration rate (GFR). Comparable circulatory adaptations are observed in conscious gravid rats. Administration of the corpus luteal hormone relaxin (RLN) to nonpregnant rats and humans elicits vasodilatory changes like those of pregnancy. Systemic and renal vasodilation are compromised in midterm pregnant rats by neutralization or elimination of circulating RLN and in women conceiving with donor eggs who lack a corpus luteum and circulating RLN. Although RLN exerts both rapid (minutes) and sustained (hours to days) vasodilatory actions through different molecular mechanisms, a final common pathway is endothelial nitric oxide. In preeclampsia (PE), maternal systemic and renal vasoconstriction leads to hypertension and modest reduction in GFR exceeding that of RPF. Elevated level of circulating soluble vascular endothelial growth factor receptor-1 arising from the placenta is implicated in the hypertension and disruption of glomerular fenestrae and barrier function, the former causing reduced Kf and the latter proteinuria. Additional pathogenic factors are discussed. Last, potential clinical ramifications include RLN replacement in women conceiving with donor eggs and its therapeutic use in PE. Another goal has been to apply knowledge gained from investigating circulatory adaptations in pregnancy toward identifying and developing novel therapeutic strategies for renal and cardiovascular disease in the nonpregnant population. So far, one candidate to emerge is RLN and its potential therapeutic use in heart failure. © 2014 the American Physiological Society.

Irving J.A.E.,Northumbria University
British Journal of Haematology | Year: 2016

Acute lymphoblastic leukaemia is the most common childhood cancer and for those children who relapse, prognosis is poor and new therapeutic strategies are needed. Recurrent pathways implicated in relapse include RAS, JAK STAT, cell cycle, epigenetic regulation, B cell development, glucocorticoid response, nucleotide metabolism and DNA repair. Targeting these pathways is a rational therapeutic strategy and may deliver novel, targeted therapies into the clinic. Relapse often stems from a minor clone present at diagnosis and thus analysis of persisting leukaemia during upfront therapy may allow targeted drug intervention to prevent relapse. © 2016 John Wiley & Sons Ltd.

Pike A.,Northumbria University
Transactions of the Institute of British Geographers | Year: 2011

Despite their apparently pervasive reach and relevance, the geographies of branded commodities and their branding have been unevenly recognised and under-researched. This paper presents a way of conceptualising and analysing brand and branding geographies. Focusing upon goods and services, the notion of geographical entanglements is developed to understand the spatial associations and connotations that unavoidably ensnare brands and branding. Second, it examines how such attachments shape and are shaped by brand and branding agents, including producers, circulators, consumers and regulators. Last, the placing of the geographical entanglements of brands and branding is developed as a means of lifting their 'mystical veils' and prompting reflections upon their politics and relationships to uneven development. Situating branding genealogies in geographical context, the empirical analysis comprises a socio-spatial biography of Newcastle Brown Ale (NBA). It explains how NBA's geographical entanglements have been (re)constructed in its contrasting survival in the UK and growth in the US. As a way of thinking about brand and branding geographies, the paper seeks to broaden the reach of economic geographies at their intersections with cultural economy approaches and to stimulate debate about their politics and alternatives to uneven development. © 2011 The Author. Transactions of the Institute of British Geographers © 2011 Royal Geographical Society (with the Institute of British Geographers).

Williams A.J.,Northumbria University
Transactions of the Institute of British Geographers | Year: 2011

This paper seeks to unpack the complex spatialities of UK airspace, looking beyond traditional civil aviation classifications to focus specifically on the spaces used by military aviation in the UK context. It argues that UK national sovereign airspace should not be viewed as a single homogenous entity, but instead must be reconceptualised as a plethora of multiple, vertically and horizontally, overlapping airspaces that can be activated or deactivated according to need. The paper employs a performativity-based framework that highlights specifically how these spaces are identified and named, to illustrate how these multiple military airspaces are actively performed. Within this it focuses on analysing the citational and iterative actions of professional airspace managers working within the UK Civil Aviation Authority and Royal Air Force. The paper makes extensive use of documentary sources and interviews with key personnel to illustrate how the airspaces above the UK are brought into being through the actions of these actors and how these operations can be seen as part of a wider enactment of militarism's control over space. © 2010 The Author. Transactions of the Institute of British Geographers © 2010 Royal Geographical Society (with The Institute of British Geographers).

Hopkins P.,Northumbria University
Transactions of the Institute of British Geographers | Year: 2011

This paper sets out an agenda for advancing critical geographies of the university campus. Despite the plethora of scholarship that highlights the complexity evident within other social locations, scales and sites, there is a dearth of geographical research about the construction and contestation of social and spatial relations experienced on university campuses. By exploring understandings of the contradictory and contested nature of everyday spaces developed by social and cultural geographers, I suggest that scholarship could usefully be extended to interrogate the complex ways in which different university campuses are constructed, contested and experienced. This paper explores these multiple constructions of the university campus through the narratives of 29 Muslim students attending a British higher education institution. I use these data to explore the multiple and contradictory discourses that students utilise, which simultaneously construct the university campus as tolerant and diverse and as discriminatory and exclusionary. This paper draws attention to the significance of spaces within universities as well as to the management of university space as crucial factors in providing environments suited to an increasingly diverse student body. © 2010 The Author. Transactions of the Institute of British Geographers © 2010 Royal Geographical Society (with the Institute of British Geographers).

Harriman A.,Northumbria University
European Journal of Inorganic Chemistry | Year: 2014

This essay is based on research leading to the identification of catalysts capable of the selective oxidation of water to molecular oxygen. The real need for such materials relates to the large-scale photochemical dissociation of water into its constituent elements, as opposed, for example, to the electrochemical decomposition of water at macroscopic electrodes. Combining the catalyst with the essential components needed for efficacious photochemistry brings special challenges, as does the ultimate need to scale up the system by a massive amount. Nature has developed a highly successful process for O 2 evolution under ambient illumination that makes use of a cubane tetramanganese cluster having a closely associated calcium cation in attendance. This catalyst is surprisingly delicate and it is debatable as to whether we could adapt such a system for use with artificial photosystems. Historically the latter have used colloidal metal oxides, and consideration is given here as to which materials might offer the most promising catalytic performance. Moving towards heterogeneous systems has more practical meaning, but the same materials come to mind. Recent attention to cobalt-based catalysts is highlighted as a possible breakthrough that might lead to interesting electrochemical systems when combined with wind turbines. Molecular catalysts provide interesting opportunities for photochemical O2 evolution but suffer from problems of scale-up. This field has witnessed the most important progress over the past decade or so but still needs urgent attention if advanced materials are to be identified in a timely manner. Finally, consideration is given to the actual status of the field in specific terms of developing an effective artificial photosynthetic apparatus. Moving progressively from using sacrificial redox agents as a simple means to isolate the oxidative photochemical cycle towards full water cleavage will stimulate the development of demonstration models suitable for public display. The reward should be increased investment. Mimicking natural photosynthesis that leads to CO2 fixation and concomitant O2 liberation from water remains an elusive goal. New (photo)anodes and studies of mechanisms for water oxidation continue to be reported, but there is still no sign of a viable artificial photosynthetic system worthy of scaling up to industrial proportions. This essay explores the underlying reasons for this but seeks to reassure investors that there is both a market and an outstanding chance for profitable returns. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dyson J.,Liver Unit | Day C.,Northumbria University
Digestive Diseases | Year: 2014

Non-alcoholic fatty liver disease (NAFLD) is now the commonest cause of chronic liver disease in developed countries. Treatment depends on the stage of disease, and non-invasive methods for risk stratification are urgently needed. Lifestyle modification (aimed at weight loss and increasing physical activity) and management of the features of metabolic syndrome are vital for all patients with NAFLD. Metformin is the first-line therapy for diabetic patients with NAFLD and also reduces the risk of hepatocellular carcinoma. Clinicians should have a low threshold for introducing a statin for the management of dyslipidaemia. Antihypertensive agents that target the renin-angiotensin system should be first-line in NAFLD for the management of hypertension. For patients with progressive disease, liver-directed pharmacotherapy with vitamin E should be considered. Non-alcoholic steatohepatitis cirrhosis is an increasingly common indication for liver transplantation. © 2014 S. Karger AG, Basel.

Yuzenkova Y.,Northumbria University
Transcription | Year: 2012

The active center of multi-subunit RNA polymerase consists of two modules, the Mg(2+) module, holding the catalytic Mg(2+) ion, and a module made of a flexible domain, the Trigger Loop. Uniquely, the TL module can be substituted by alternative modules, thus changing the catalytic properties of the active center.

Gao Z.,Northumbria University | Shi X.,Huawei
Automatica | Year: 2013

In the paper, a complete proof of the properness and mean-square exponential stability for stochastic Brownian systems is firstly addressed, which lays a solid foundation for system analysis and control synthesis for this kind of stochastic systems. Observer-based controller for the descriptor system with Brownian motions is then investigated. It is noticed that the system dynamics and observer dynamics are both subjected to state Brownian fluctuation, which makes it challenging either to design observer gain and controller gain simultaneously or design the observer and control gains by using a complete separation design technique. A sequential design technique is proposed to calculate the control and observer gains by solving linear matrix inequalities. The proposed design methods are readily extended to the case for stochastic descriptor systems with multiple Brownian motions. A numerical example is finally given to illustrate the design techniques, and simulated results have demonstrated the efficiency. © 2013 Published by Elsevier Ltd.

Leaper D.,Northumbria University | Tanner J.,De Montfort University | Kiernan M.,Southport and Ormskirk Hospitals NHS Trust
Journal of Hospital Infection | Year: 2013

Surgical site infection (SSI) continues to be a burden on systems that deliver healthcare and on patients who suffer morbidity, and mortality, associated with this complication of medical intervention. Surveillance of SSI is often an integral part of organizational infection prevention and control activities, but unless post-discharge surveillance is carried out in a robust manner the data may be inaccurate and misleading. Coupled with a lack of robust application of definitions, variations in methods of case-finding and incomplete follow-up, the results may lead to a false sense of security or conversely cause unnecessary anxieties. Data from national surveillance schemes that purport to be suitable for benchmarking are often at odds with published rates from well-designed studies and the reasons for this should be examined. If benchmarking is truly desirable and if clinicians are to have confidence in the outputs, surveillance schemes should ensure that participating organizations adopt a consistent approach to definitions, case-finding methodologies following discharge, and to robust follow-up, to ensure that every opportunity is taken to maximize the return rate and enhance data validity. © 2012 .

Nettle D.,Northumbria University | Penke L.,University of Edinburgh
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

The concept of personality has recently begun to attract a great deal of interest in behavioural ecology. However, there is also a large and mature literature on personality within human psychology. These two bodies of work have developed independently and at present make rather little reference to one another. The current paper has two main objectives. First, we seek to acquaint behavioural ecologists with the principal ideas and issues found in the human personality psychology literature. Second, we explore how ideas from the behavioural ecology literature might help advance research in human personality psychology. We suggest strong potential for convergence between the two literatures in the near future. Common themes of this future unified science of personality include the conception of personality traits as reaction norms, a commitment to the importance of direct measurement of behaviour, investigation of both proximate and ultimate explanations for personality variation, and a concern with the impact of personality variation on survival and reproductive success. © 2010 The Royal Society.

Honekopp J.,Northumbria University
Frontiers in Endocrinology | Year: 2013

The length ratio of the second to the fourth digit (2D:4D) is a putative marker of prenatal testosterone (T) effects. The number of CAG repeats (CAGn) in the AR gene is negatively correlated with T sensitivity in vitro. Results regarding the relationship between 2D:4D and CAGn are mixed but have featured prominently in arguments for and against the validity of 2D:4D. Here, I present random-effects meta-analyses on 14 relevant samples with altogether 1904 subjects. Results were homogeneous across studies. Even liberal estimates (upper limit of the 95% CI) were close to zero and therefore suggested no substantial relationship of CAGn with either right-hand 2D:4D, left-hand 2D:4D, or the difference between the two. However, closer analysis of the effects of CAGn on T dependent gene activation in vitro and of relationships between CAGn and T dependent phenotypic characteristics suggest that normal variability of CAGn has mostly no, very small, or inconsistent effects. Therefore, the lack of a clear association between CAGn and 2D:4D has no negative implications for the latter's validity as a marker of prenatal T effects. © 2013 Hönekopp.

McInnes I.B.,University of Glasgow | Buckley C.D.,University of Birmingham | Isaacs J.D.,Northumbria University
Nature Reviews Rheumatology | Year: 2016

Cytokine-mediated pathways are central to the pathogenesis of rheumatoid arthritis (RA). The purpose of this short Opinion article is to briefly overview the roles of cytokine families in the various phases and tissue compartments of this disease. In particular, we consider the combinatorial role played by cytokines in mediating the overlapping innate and adaptive immune responses associated with disease onset and persistence, and also those cytokine pathways that, in turn, drive the stromal response that is critical for tissue localization and associated articular damage. The success of cytokine inhibition in the clinic is also considerable, not only in offering remarkable therapeutic advances, but also in defining the hierarchical position of distinct cytokines in RA pathogenesis, especially IL-6 and TNF. This hierarchy, in turn, promises to lead to the description of meaningful clinical endotypes and the consequent possibility of therapeutic stratification in future. © 2016 Macmillan Publishers Limited.

Attems J.,Northumbria University | Thal D.R.,University of Ulm | Jellinger K.A.,Institute for Clinical Neurobiology
Biochemical Society Transactions | Year: 2012

The stepwise progression of tau pathology [NFTs (neurofibrillary tangles) and NTs (neuropil threads)] in AD (Alzheimer's disease) is generally assumed to begin in the transentorhinal region (entorhinal stage) from which it progresses to the hippocampus (limbic stage) and to neocortical regions (neocortical stage). This stepwise progression is reflected in the NFT Braak stages. However, it has been shown recently that tau pathology is frequently seen in subcortical nuclei, in particular the LC (locus coeruleus) in over 90% of individuals under 30 years of age, suggesting that AD-associated tau pathology begins in the LC and not in the transentorhinal region. On the other hand, onlyminimal amounts of tau pathology are seen in the LC in cases with considerable entorhinal tau pathology, while the severity of tau pathology in the LC significantly increases with increasing NFT Braak stages. These findings suggest that the LC becomes increasingly involved during AD progression rather than representing the site initially affected. Further studies are warranted to answer the question of whether tau pathology in the LC of young individuals is associated with AD or whether it rather reflects non-specific neuronal damage. ©The Authors Journal compilation ©2012 Biochemical Society.

Baronio F.,University of Brescia | Conforti M.,University of Brescia | Degasperis A.,University of Rome La Sapienza | Lombardo S.,Northumbria University
Physical Review Letters | Year: 2013

We introduce a novel family of analytic solutions of the three-wave resonant interaction equations for the purpose of modeling unique events, i.e., "amplitude peaks" which are isolated in space and time. The description of these solutions is likely to be a crucial step in the understanding and forecasting of rogue waves in a variety of multicomponent wave dynamics, from oceanography to optics and from plasma physics to acoustics. © 2013 American Physical Society.

Meplan C.,Northumbria University
Journal of Trace Elements in Medicine and Biology | Year: 2011

Trace elements are key regulators of metabolic and physiological pathways known to be altered during the ageing process and therefore have the capacity to modulate the rate of biological ageing. Optimal intake is required to maintain homeostasis and to increase cell protection. Deficiencies are associated with specific illnesses. However the contribution of commonly observed life-long sub-optimal intakes of trace elements to the development and severity of age-related chronic diseases is less appreciated. Additionally, reduce intake of several trace elements has been shown to be particularly challenging for elderly people. This review will use selenium as an example to illustrate how a trace element can influence ageing and how the Omics technologies could help to study the effect of trace elements on the ageing process. Although transcriptomics and proteomics approaches in animal models have so far enabled us to identify downstream targets of trace elements in pathways related to age-related diseases processes, future approaches of combining nutrigenomics with longevity studies in humans will help us to identify mechanisms whereby trace elements affect the ageing process. © 2010 Elsevier GmbH.

Oldershaw R.A.,Northumbria University
International Journal of Experimental Pathology | Year: 2012

Avascular, aneural articular cartilage has a low capacity for self-repair and as a consequence is highly susceptible to degradative diseases such as osteoarthritis. Thus the development of cell-based therapies that repair focal defects in otherwise healthy articular cartilage is an important research target, aiming both to delay the onset of degradative diseases and to decrease the need for joint replacement surgery. This review will discuss the cell sources which are currently being investigated for the generation of chondrogenic cells. Autologous chondrocyte implantation using chondrocytes expanded ex vivo was the first chondrogenic cellular therapy to be used clinically. However, limitations in expansion potential have led to the investigation of adult mesenchymal stem cells as an alternative cell source and these therapies are beginning to enter clinical trials. The chondrogenic potential of human embryonic stem cells will also be discussed as a developmentally relevant cell source, which has the potential to generate chondrocytes with phenotype closer to that of articular cartilage. The clinical application of these chondrogenic cells is much further away as protocols and tissue engineering strategies require additional optimization. The efficacy of these cell types in the regeneration of articular cartilage tissue that is capable of withstanding biomechanical loading will be evaluated according to the developing regulatory framework to determine the most appropriate cellular therapy for adoption across an expanding patient population. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

Bell D.,Northumbria University
Wiley Interdisciplinary Reviews: Climate Change | Year: 2013

Human rights have not played a significant role in the international law and politics of climate change to date. However, there has been increasing interest among legal scholars and moral and political philosophers in a human rights approach to climate change. This review focuses on the new literature in moral and political philosophy that has begun to explore the connections between human rights and climate change. The attractions of a human rights approach to climate change are explained. The idea of a moral conception of human rights is introduced and distinguished from human rights recognized in international and national law. The key features of moral human rights are identified and an important distinction between negative and positive rights is explained. The three main arguments in the literature connecting human rights and climate change are introduced and critical discussions of them are presented. The first argument (associated with Steve Vanderheiden) claims that there is a human right to a stable climate, which can be derived from a human right to an adequate environment. The second argument (associated with Simon Caney) claims that anthropogenic climate change violates basic human (negative) rights to life, health, and subsistence. The third argument claims that there is a human right to emit greenhouse gases. This argument has two versions. The first version claims that there is a human right to equal per capita emissions. The second version claims that there is a human right to subsistence emissions. © 2013 John Wiley & Sons, Ltd.

Embleton N.D.,Northumbria University
World Review of Nutrition and Dietetics | Year: 2013

The developmental origins of health and disease is an emerging area of interest that amalgamates many areas of scientific studies and encompasses a wide range of diverse disciplines from epidemiology to molecular biology. Evidence has accumulated to show that early life experiences, both in utero and in infancy have long-term effects on many body systems. There are now good data to show that suboptimal in utero growth, especially when combined with rapid growth acceleration in early postnatal life may increase the risk of later life metabolic disease. The mechanisms are complex but likely to involve epigenetic marks such as DNA methylation. Preterm infants frequently experience suboptimal nutrient intakes in early postnatal life and exhibit growth failure within the NICU. They also receive products that may not provide either an optimal quantity or quality of nutrients. Follow-up studies have now shown much higher risks for long-term chronic disease in children and adults who were born preterm. There are higher levels of insulin resistance and abnormal partitioning of fat deposition. The onset of puberty seems earlier, average height is less and blood pressure, measures of vascular health and lipid profiles suggest cardiovascular health is likely to differ from healthy term born controls. Despite this, there are no data to suggest an overall benefit of limiting nutrient intake, or restricting growth in preterm infants. There are strong data to show that the preterm brain is exquisitely vulnerable to undernutrition, and that suboptimal nutrient intakes may permanently affect later cognitive attainment. A clinical focus on early nutrient intakes and breast milk provision is key to optimising long-term health outcomes. © 2013 S. Karger AG, Basel.

Iehl J.,CNRS Molecular Chemistry Laboratory | Nierengarten J.-F.,CNRS Molecular Chemistry Laboratory | Harriman A.,Northumbria University | Bura T.,CNRS The Institute of Chemistry and Processes for Energy, Environment and Health | Ziessel R.,CNRS The Institute of Chemistry and Processes for Energy, Environment and Health
Journal of the American Chemical Society | Year: 2012

A sophisticated model of the natural light-harvesting antenna has been devised by decorating a C 60 hexa-adduct with ten yellow and two blue boron dipyrromethene (Bodipy) dyes in such a way that the dyes retain their individuality and assist solubility of the fullerene. Unusually, the fullerene core is a poor electron acceptor and does not enter into light-induced electron-transfer reactions with the appended dyes, but ineffective electronic energy transfer from the excited-state dye to the C 60 residue competes with fluorescence from the yellow dye. Intraparticle electronic energy transfer from yellow to blue dyes can be followed by steady-state and time-resolved fluorescence spectroscopy and by excitation spectra for isolated C 60 nanoparticles dissolved in dioxane at 293 K and at 77 K. The decorated particles can be loaded into polymer films by spin coating from solution. In the dried film, efficient energy transfer occurs such that photons absorbed by the yellow dye are emitted by the blue dye. Films can also be prepared to contain C 60 nanoparticles loaded with the yellow Bodipy dye but lacking the blue dye and, under these circumstances, electronic energy migration occurs between yellow dyes appended to the same nanoparticle and, at higher loading, to dye molecules on nearby particles. Doping these latter polymer films with the mixed-dye nanoparticle coalesces these multifarious processes in a single system. Thus, long-range energy migration occurs among yellow dyes attached to different particles before trapping at a blue dye. In this respect, the film resembles the natural photosynthetic light-harvesting complexes, albeit at much reduced efficacy. The decorated nanoparticles sensitize amorphous silicon photocells. © 2011 American Chemical Society.

Neill D.,Northumbria University
Ageing Research Reviews | Year: 2013

Life's timekeeper is a 'free-running' intracellular oscillator synchronised across all cells. It runs throughout life splitting lifespan into equal length phases. During the maturational period it controls the overall rate of progression whereas in the post-maturational period it controls the overall rate of ageing. This includes the rate of senescence and hence time to death. As such life's timekeeper equates maturational and post-maturational time, hence explains the tight correlation between these time periods that has existed throughout mammalian evolution.Life's timekeeper is proposed to have played an important role in vertebrate evolution. A slower oscillatory frequency results in proportional life phase prolongation. This leads to increased body and brain size, together with extended lifespan. Higher brain centres, neocortex in mammals, are disproportionately enlarged. Hence behavioural capacity is increased. The extended post-maturational period ensures that there is enough time in order that the behavioural advantages can be fully manifest in the environment. A faster oscillatory frequency would result in proportional life phase reduction. This process however would lead to reduced behavioural capacity, and is hence unlikely to be positively selected. Therefore throughout evolution life's timekeeper has operated to extend lifespan. It has hence functioned to promote longevity as opposed to ageing. © 2013 Elsevier B.V.

The tendency to form conclusions based on limited evidence is known as the 'jumping to conclusions' (JTC) bias, and has been a much studied phenomena in individuals with psychosis. Previous reviews have supported the hypothesis that a JTC bias is particularly linked to the formation and maintenance of delusions. A new systematic review is required as a number of studies have since been published, and older reviews are limited by not systematically assessing methodological quality or the role of study design in influencing effect size estimates. This review aimed to investigate if there is an association between psychosis or delusions and JTC bias. The current protocol outlines the background and methodology for this systematic review and meta-analysis. Eligible articles will be identified through searches of the electronic databases PsycInfo, PubMed and Medline using relevant search terms, supplemented by hand-searches of references within eligible articles and key review articles within the field. Eligibility criteria were as follows: studies must recruit individuals with: i) schizophrenia spectrum conditions or ii) experiences of delusions. Case-control, cross-sectional, observational and prospective designs will be included but treatment trials and experimental studies excluded. Studies must use the beads task to assess JTC or a conceptually equivalent task. The outcomes will be the average number of 'draws to a decision' in the beads task (or related variant) and the proportion of the sample judged to demonstrate a JTC bias. Literature searches, study selection, data extraction, risk of bias assessment and outcome quality assessment will be undertaken by two independent reviewers. Meta-analyses will be undertaken for continuous (mean number of 'draws to a decision') and binary outcomes (number of people classified as having JTC bias). Understanding of the size of the JTC effect and the contexts within which it occurs is important both in terms of informing models of delusional thinking and in guiding treatments for those with delusions or psychosis. However, a definitive, up-to-date review and meta-analysis of the JTC bias is currently lacking. The proposed review will fill this gap and resolve key issues regarding the factors which moderate the JTC bias. CRD42014007603 http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014007603.

Moro A.,Northumbria University
Annals of Physics | Year: 2014

A thermodynamic phase transition denotes a drastic change of state of a physical system due to a continuous change of thermodynamic variables, as for instance pressure and temperature. The classical van der Waals equation of state is the simplest model that predicts the occurrence of a critical point associated with the gas-liquid phase transition. Nevertheless, below the critical temperature theoretical predictions of the van der Waals theory significantly depart from the observed physical behaviour. We develop a novel approach to classical thermodynamics based on the solution of Maxwell relations for a generalised family of nonlocal entropy functions. This theory provides an exact mathematical description of discontinuities of the order parameter within the phase transition region, it explains the universal form of the equations of state and the occurrence of triple points in terms of the dynamics of nonlinear shock wave fronts. © 2014 Elsevier Inc.

Popoola W.O.,Glasgow Caledonian University | Ghassemlooy Z.,Northumbria University | Stewart B.G.,Glasgow Caledonian University
Journal of Lightwave Technology | Year: 2014

This paper investigates the use of a pilot signal in reducing the electrical peak-to-average power ratio (PAPR) of an orthogonal frequency division multiplexing (OFDM) intensity-modulated optical wireless communication system. The phase of the pilot signal is chosen based on the selected mapping (SLM) algorithm while the maximum likelihood criterion is used to estimate the pilot signal at the receiver. Bit error rate (BER) performance of the pilot-assisted optical OFDM system is identical to that of the basic optical OFDM (with no pilot and no PAPR reduction technique implemented) at the desired BER of less than 10-3 needed to establish a reliable communication link. The pilot-assisted PAPR reduction technique results in higher reduction in PAPR for high order (M>4) constellations than the classical SLM. With respect to a basic OFDM system, with no pilot and no PAPR reduction technique implemented, a pilot-assisted M-QAM optical OFDM system is capable of reducing the electrical PAPR by over about 2.5 dB at a modest complementary cumulative distribution function (CCDF) point of 10-4 for M = 64. Greater reductions in PAPR are possible at lower values of CCDF with no degradation to the system's error performance. Clipping the time domain signal at both ends mildly (at 25 times the signal variance level) results in a PAPR reduction of about 6.3 dB at the same CCDF of 10-4 but with an error floor of about 3 × 10-5. Although it is possible to attain any desired level of electrical PAPR reduction with signal clipping, this will be at a cost of deterioration in the systems's bit error performance. © 2014 IEEE.

Heather N.,Northumbria University
Alcoholism: Clinical and Experimental Research | Year: 2014

Research on effective mechanisms of alcohol brief interventions has been neglected, but Bertholet and colleagues provide an example of such research in a re-analysis of combined data from 3 trials of brief motivational interviewing (BMI). However, it is disappointing that, in a well-designed and well-conducted analysis, little support was found for highly plausible hypotheses relating treatment processes to outcome of intervention. It is argued here that, because BMI must be assumed to work by increasing client motivation to cut down drinking, some measure of overall motivation before and after intervention is necessary to elucidate the pathway by which treatment processes are translated into positive outcomes. In pioneering research on physician advice on smoking cessation by Russell and colleagues, it was possible to distinguish between whether intervention worked by motivating more people to try to stop smoking, by increasing the success rate among those who did try, or by reducing the relapse rate among those who quit. It is recommended that similar measures be employed in research on how alcohol brief interventions work. A further consideration bearing on the relationship between treatment processes and outcome is whether or not individuals are dependent on alcohol and this is reminiscent of a dispute in the literature concerning the relative priority that should be given to motivational or dependence variables in the prediction of smoking cessation. In order to improve the effectiveness of alcohol brief interventions, future research should focus more on effective mechanisms of behavior change. © 2014 by the Research Society on Alcoholism.

O'Reilly S.,Northumbria University
BioFactors | Year: 2013

Chronic inflammation can lead to altered extracellular matrix deposition and ultimately fibrosis. Interleukin-13 (IL-13) is a cytokine that was found to promote IgE class switching and inhibit proinflammatory cytokines. However, it is now recognized as an important mediator in allergy and most importantly fibrosis. Indeed, animal studies with genetically deleted mice have demonstrated its critical role in fibrosis and although it shares over lapping functions with IL-4 it is the dominant cytokine in fibrosis. Systemic sclerosis is an autoimmune disease in which there is chronic inflammation and fibrosis. The disease is associated with a Th2 polarization and IL-13 levels are elevated both in the blood and in the skin of patients. This review will examine the role of IL-13 in driving fibrosis with a particular emphasis on systemic sclerosis as a prototypical fibrotic disease. It will highlight recent research into the role of IL-13 and how this cytokine may be targeted in systemic sclerosis. © 2013 International Union of Biochemistry and Molecular Biology.

Watkins N.J.,Northumbria University | Bohnsack M.T.,Goethe University Frankfurt
Wiley Interdisciplinary Reviews: RNA | Year: 2012

Box C/D and H/ACA RNPs are essential ribonucleoprotein particles that are found throughout both eukaryotes [small nucleolar RNPs (snoRNPs)] and archaea [snoRNP-like complexes (sRNPs)]. These complexes catalyze the site-specific pseudouridylation and most of the methylation of ribosomal RNA (rRNA). The numerous modifications, which are clustered in functionally important regions of the rRNA, are important for rRNA folding and ribosome function. The RNA component of the complexes [small nucleolar RNA (snoRNA) or small RNA (sRNA)] functions in substrate binding by base pairing with the target site and as a scaffold coordinating the organization of the complex. In eukaryotes, a subset of snoRNPs do not catalyze modification but, through base pairing to the rRNA or flanking precursor sequences, direct pre-rRNA folding and are essential for rRNA processing. In the last few years there have been significant advances in our understanding of the structure of archaeal sRNPs. High resolution structures of the archaeal C/D and H/ACA sRNPs have not only provided a detailed understanding of the molecular architecture of these complexes but also produced key insights into substrate binding and product release. In both cases, this is mediated by significant movement in the complexes. Advances have also been made in our knowledge of snoRNP recruitment and release from pre-ribosome complexes in eukaryotes. New snoRNA-rRNA interactions have been documented, and the roles of RNA helicases in releasing snoRNP complexes from the rRNA have been described. © 2011 John Wiley & Sons, Ltd.

Scully M.,University College London | Goodship T.,Northumbria University
British Journal of Haematology | Year: 2014

Thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS) are acute, rare life-threatening thrombotic microangiopathies that require rapid diagnosis and treatment. They are defined by microangiopathic haemolytic anaemia and thrombocytopenia, with renal involvement primarily in aHUS and neurological and cardiological sequelae in TTP. Prompt treatment for most cases of both conditions is with plasma exchange initially and monoclonal therapy (rituximab in TTP and eculizumab in aHUS) as the mainstay of therapy. Here we discuss the diagnosis and therapy for both disorders. © 2014 The Authors. British Journal of Haematology Published by John Wiley & Sons Ltd.

Curtin N.J.,Northumbria University
Nature Reviews Cancer | Year: 2012

Dysregulation of DNA damage repair and signalling to cell cycle checkpoints, known as the DNA damage response (DDR), is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. Dysfunction of one DNA repair pathway may be compensated for by the function of another compensatory DDR pathway, which may be increased and contribute to resistance to DNA-damaging chemotherapy and radiotherapy. Therefore, DDR pathways make an ideal target for therapeutic intervention; first, to prevent or reverse therapy resistance; and second, using a synthetic lethal approach to specifically kill cancer cells that are dependent on a compensatory DNA repair pathway for survival in the context of cancer-associated oxidative and replicative stress. These hypotheses are currently being tested in the laboratory and are being translated into clinical studies. © 2012 Macmillan Publishers Limited. All rights reserved.

White K.E.,Northumbria University
Micron | Year: 2012

The renal glomerulus and its components have been intensively studied using microscopy - both light and electron - for decades and much has been learnt about their role in the pathogenesis of chronic kidney diseases such as diabetic nephropathy. In order to get more than purely qualitative information from the images, stereological tools have been applied to obtain unbiased quantitative data and thus allow structural-functional relationships to be explored. These techniques are likely to continue to be used in the coming decades in order to provide vital information about the disease process, complementing knowledge obtained from molecular techniques. © 2012 Elsevier Ltd.

Bolam D.N.,Northumbria University | Koropatkin N.M.,University of Michigan
Current Opinion in Structural Biology | Year: 2012

The human gut Bacteroidetes employ multiple cell-envelope associated protein complexes, termed Sus-like systems, to capture and degrade glycans. Recently the structures of key glycan-binding Sus proteins, the surface located SusD proteins and the periplasmic sensor domains of the membrane spanning hybrid two-component systems (HTCS) controlling Sus expression, have been solved, providing insight into glycan acquisition and sensing in these symbionts. The α-helical SusD proteins bind glycans at the cell surface, and likely facilitate the shuttling of oligosaccharides to an associated TonB-dependent porin. The HTCS sensor domains adopt two distinct folds and the structures of these sensors with glycan suggest that signal transduction across the cytoplasmic membrane is different from classical two component systems. © 2012 Elsevier Ltd.

Home P.D.,Northumbria University
Diabetes, Obesity and Metabolism | Year: 2012

Postprandial glucose excursions can inhibit achievement of good glycaemic control, and possibly have a specific effect on the risk of vascular comorbidities. Rapid-acting analogues control these excursions better than human insulin because their pharmacokinetic/pharmacodynamic (PK/PD) profile is closer to that of meal-time endogenous insulin secretion. Review of the findings of PK/PD studies and clinical trials suggests that the three marketed rapid-acting analogues-insulin lispro, insulin aspart and insulin glulisine-are equally efficacious and safe. In comparison with human insulin when using the same basal insulin, they provide comparable glycaemic control with a reduced risk of hypoglycaemia, although the combination of rapid-acting and basal analogues reduces glycated haemoglobin (HbA1c) more than human meal-time insulin combined with neutral protamine Hagedorn (NPH) insulin. Some studies have suggested that insulin glulisine has a slightly faster onset of action compared with insulin lispro or insulin aspart, but this has not been translated into demonstrable clinical benefit. Treatment satisfaction in patients with diabetes has been higher when therapy with a rapid-acting analogue is used instead of human insulin, perhaps due to differences in advised timing of injection. The largest benefits in efficacy, hypoglycaemia incidence, treatment satisfaction and quality of life have occurred when patients receive an all-analogue meal-time plus basal regimen as compared with an all-human insulin regimen. No new safety issues have been identified with the marketed rapid-acting analogues, and their insulin-like growth factor 1receptor affinity and mitogenic activity are comparable to human insulin. © 2012 Blackwell Publishing Ltd.

Watson P.,Northumbria University
Proceedings - 2011 3rd IEEE International Conference on Cloud Computing Technology and Science, CloudCom 2011 | Year: 2011

Cloud computing has the potential to provide low-cost, scalable computing, but cloud security is a major area of concern. Many organizations are therefore considering using a combination of a secure internal cloud, along with (what they perceive to be) less secure public clouds. However, this raises the issue of how to partition applications across a set of clouds, while meeting security requirements. Currently, this is usually done on an ad-hoc basis, which is potentially error-prone, or for simplicity the whole application is deployed on a single cloud, so removing the possible performance and availability benefits of exploiting multiple clouds within a single application. This paper describes an alternative to ad-hoc approaches - a method that determines all ways in which applications structured as workflows can be partitioned over the set of available clouds such that security requirements are met. The approach is based on a Multi-Level Security model that extends Bell-LaPadula to encompass cloud computing. This includes introducing workflow transformations that are needed where data is communicated between clouds. In specific cases these transformations can result in security breaches, but the paper describes how these can be detected. Once a set of valid options has been generated, a cost model is used to rank them. The method has been implemented in a tool, which is briefly described in the paper. © 2011 IEEE.

Poulton S.W.,Northumbria University | Fralick P.W.,Lakehead University | Canfield D.E.,University of Southern Denmark
Nature Geoscience | Year: 2010

The evolution of ocean chemistry during the Proterozoic eon (2.5-0.542 billion years ago) is thought to have played a central role in both the timing and rate of eukaryote evolution. The timing of the deposition of iron formations implies that, early in the Earths history, oceans were predominantly anoxic and rich in dissolved iron. However, global deposition of iron formations ceased about 1.84 billion years ago. This termination indicates a major upheaval in ocean chemistry, but the precise nature of this change remains debated. Here we use iron and sulphur systematics to reconstruct oceanic redox conditions from the 1.88- to 1.83-billion-year-old Animikie group from the Superior region, North America. We find that surface waters were oxygenated, whereas at mid-depths, anoxic and sulphidic (euxinic) conditions extended over 100 km from the palaeoshoreline. The spatial extent of euxinia varied through time, but deep ocean waters remained rich in dissolved iron. Widespread euxinia along continental margins would have removed dissolved iron from the water column through the precipitation of pyrite, which would have reduced the supply of dissolved iron and resulted in the global cessation of the deposition of Superior-type iron formations. We suggest that incursions of sulphide from the mid-depths into overlying oxygenated surface waters may have placed severe constraints on eukaryotic evolution. © 2010 Macmillan Publishers Limited. All rights reserved.

Biggar M.A.,Royal Infirmary | Lennard T.W.J.,Royal Infirmary | Lennard T.W.J.,Northumbria University
British Journal of Surgery | Year: 2013

Background: Phaeochromocytoma in pregnancy is a rare and potentially dangerous situation for mother and fetus. This review aimed to assess current mortality rates and how medical and surgical management affect these. Methods: Articles in English published between 2000 and 2011 were obtained from a MEDLINE search. Eligible publications presented women diagnosed with phaeochromocytoma in the antenatal or immediate postnatal period, and reported management and outcomes. Results: A total of 135 reports were identified. After applying inclusion criteria, 77 pregnancies involving 78 fetuses were analysed. Fetal and maternal mortality rates were 17 per cent (13 of 78) and 8 per cent (6 of 77) respectively. Better outcomes were achieved when the diagnosis of phaeochromocytoma was made in the antenatal period than when it was made during labour or immediately postpartum (survival of both mother and fetus(es) in 48 of 56 versus 12 of 21 respectively; P = 0·012). When the diagnosis was made before 23 weeks' gestation, there was no difference in outcomes when phaeochromocytoma surgery was carried out in the second trimester, compared with when it was postponed to the third trimester or after delivery (fetal death 2 of 18 versus 2 of 8 respectively; P = 0·563). Conclusion: This review, although limited by the rarity of the condition and level of available evidence, demonstrated that survival rates are improved if the diagnosis of phaeochromocytoma can be established antenatally. With diagnosis before 23 weeks' gestation, no definite advantage of proceeding with tumour removal during the second trimester could be demonstrated. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Kemp J.,Northumbria University | Rhodes E.J.,University of California at Los Angeles
Quaternary Science Reviews | Year: 2010

Inland rivers in southeastern Australia preserve a long record of surface palaeochannels, accompanied by alluvial terraces that reflect changes in water and sediment discharges from the southeastern highlands through much of the last glacial cycle. A compilation of ages on rivers of the southern Murray-Darling Basin together with new dates from the Lachlan River suggest that the fluvial response to climate change has been regionally consistent and responsive to climate change on timescales <10 ka. For much of the last glacial cycle, inland rivers were mixed-load, sinuous single and anabranching channels that carried bankfull discharges of between 3 and 11 times present day rivers. Incision of the upper alluvial plains and valleys occurred in the lead up to the coldest part of the last glacial cycle. This was followed at 34 ka by the synchronous development of large meandering channels that may have been associated with lower evapotranspiration from alpine highland catchments accompanied by higher precipitation. Smaller channels and declining lateral channel sedimentation suggests arid climates during the last glacial maximum and late glacial period with seasonally large, actively migrating channels being maintained in rivers dominated by snowmelt runoff from the Australian Alps. During the Holocene, sensitivity to recorded changes in precipitation amounts and variability differed between catchments with some rivers constructing larger or more actively migrating channels in the early to mid-Holocene. © 2009 Elsevier Ltd. All rights reserved.

Schneider C.,University of Edinburgh | Schneider C.,Northumbria University | Kudla G.,University of Edinburgh | Wlotzka W.,University of Edinburgh | And 2 more authors.
Molecular Cell | Year: 2012

The exosome plays major roles in RNA processing and surveillance but the in vivo target range and substrate acquisition mechanisms remain unclear. Here we apply in vivo RNA crosslinking (CRAC) to the nucleases (Rrp44, Rrp6), two structural subunits (Rrp41, Csl4) and a cofactor (Trf4) of the yeast exosome. Analysis of wild-type Rrp44 and catalytic mutants showed that both the CUT and SUT classes of non-coding RNA, snoRNAs and, most prominently, pre-tRNAs and other Pol III transcripts are targeted for oligoadenylation and exosome degradation. Unspliced pre-mRNAs were also identified as targets for Rrp44 and Rrp6. CRAC performed using cleavable proteins (split-CRAC) revealed that Rrp44 endonuclease and exonuclease activities cooperate on most substrates. Mapping oligoadenylated reads suggests that the endonuclease activity may release stalled exosome substrates. Rrp6 was preferentially associated with structured targets, which frequently did not associate with the core exosome indicating that substrates follow multiple pathways to the nucleases. © 2012 Elsevier Inc.

Marshall S.M.,Northumbria University
Diabetologia | Year: 2012

This edition of Then and Now discusses three papers published in Diabetologia in the 1980s relating to diabetic nephropathy. Two epidemiological papers by Andersen et al (1983; 25:496-501) and Borch-Johnsen et al (1985; 28:590-596) described in graphic detail the ravages of diabetic nephropathy in type 1 diabetes. After 40 years of diabetes, 41% of their cohort had developed persistent proteinuria. The median time from first appearance of proteinuria to death was 7-8 years, the majority dying of uraemia or cardiovascular disease. The third paper, by Mathiesen et al (1984; 26:406-410), identified individuals with microalbuminuria, a much earlier stage of diabetic nephropathy, and analysed the risk of progression to persistent proteinuria at various levels of urine albumin excretion. Since the description of microalbuminuria, clinicians have hoped that earlier identification of individuals at high risk of end-stage kidney disease, coupled with aggressive use of reno-protective therapies, would prevent, or at the very least significantly delay, the development of end-stage renal disease. Recent data suggest that the outlook has indeed improved since the 1980s, at least in some populations. However, we may be delaying rather than preventing the development of microalbuminuria, proteinuria and kidney failure. Whilst a delay of 10 or more years in the appearance of end-stage renal disease is very welcome, further work is needed to understand why rates of chronic kidney disease vary substantially between cohorts and to develop novel therapies. © 2012 Springer-Verlag.

King M.A.,Northumbria University | Watson C.S.,University of Tasmania
Journal of Geophysical Research: Solid Earth | Year: 2010

Within analyses of Global Positioning System (GPS) observations, unmodeled subdaily signals propagate into long-period signals via a number of different mechanisms. In this paper, we investigate the effects of time-variable satellite geometry and the propagation of a time-constant unmodeled multipath signal. Multipath reflectors at H = 0.1 m, 0.2 m, and 1.5 m below the antenna are modeled, and their effects on GPS coordinate time series are examined. Simulated time series at 20 global IGS sites for 2000.0-2008.0 were derived using the satellite geometry as defined by daily broadcast orbits. We observe the introduction of time-variable biases in the time series of up to several millimeters. The frequency and magnitude of the signal is dependent on site location and multipath source. When adopting realistic GPS observation geometries obtained from real data (e.g., including the influence of local obstructions and hardware specific tracking), we observe generally larger levels of coordinate variation. In these cases, we observe spurious signals across the frequency domain, including very high frequency abrupt changes (offsets) in addition to secular trends. Velocity biases of more than 0.5 mm/yr are evident at some sites. The propagated signal has noise characteristics that fall between flicker and random walk and shows spectral peaks at harmonics of the draconitic year for a GPS satellite (∼351 days). When a perfectly repeating synthetic constellation is used, the simulations show near-negligible time correlated noise highlighting that subtle variations in the GPS constellation can propagate multipath signals differently over time, producing significant temporal variations in time series. © 2010 by the American Geophysical Union.

Santos-Beneit F.,Northumbria University
Frontiers in Microbiology | Year: 2015

One of the most important achievements of bacteria is its capability to adapt to the changing conditions of the environment. The competition for nutrients with other microorganisms, especially in the soil, where nutritional conditions are more variable, has led bacteria to evolve a plethora of mechanisms to rapidly fine-tune the requirements of the cell. One of the essential nutrients that are normally found in low concentrations in nature is inorganic phosphate (Pi). Bacteria, as well as other organisms, have developed several systems to cope for the scarcity of this nutrient. To date, the unique mechanism responding to Pi starvation known in detail is the Pho regulon, which is normally controlled by a two component system and constitutes one of the most sensible and efficient regulatory mechanisms in bacteria. Many new members of the Pho regulon have emerged in the last years in several bacteria; however, there are still many unknown questions regarding the activation and function of the whole system. This review describes the most important findings of the last three decades in relation to Pi regulation in bacteria, including: the PHO box, the Pi signaling pathway and the Pi starvation response. The role of the Pho regulon in nutritional regulation cross-talk, secondary metabolite production, and pathogenesis is discussed in detail. © 2015 Santos-Beneit.

The ability of bacterial pathogens to sense their immediate environment plays a significant role on their capacity to survive and cause disease. Salmonella enterica serovar typhi (S. typhi) is an exclusively human pathogen that causes typhoid fever. In a recent study, we have shown that S. typhi senses and responds to host neuroendocrine stress hormones to release the toxin hemolysin E. Hormone-mediated hemolysis by S. typhi was inhibited by the β-blocker propranolol and was dependent on the presence of the CpxAR signal transduction system. Furthermore, we demonstrate that normal expression of the small RNA micA is necessary for the arbitration of the response to host  neuroendocrine hormones. This leads to a significant decrease in the levels of the outer membrane protein OmpA and increased formation of membrane vesicles containing HlyE. The exploration of host pathogen interactions is  of paramount importance in deciphering pathogen virulence and the discovery of novel treatments.

Crumey A.,Northumbria University
Monthly Notices of the Royal Astronomical Society | Year: 2014

The standard visibility model in light-pollution studies is the formula of Hecht, as used e.g. by Schaefer. However, it is applicable only to point sources and is shown to be of limited accuracy. A new visibility model is presented for uniform achromatic targets of any size against background luminances ranging from zero to full daylight, produced by a systematic procedure applicable to any appropriate data set (e.g. Blackwell's), and based on a simple but previously unrecognized empirical relation between contrast threshold and adaptation luminance. The scotopic luminance correction for variable spectral radiance (colour index) is calculated. For point sources, the model is more accurate than Hecht's formula and is verified using telescopic data collected at Mount Wilson in 1947, enabling the sky brightness at that time to be determined. The result is darker than the calculation by Garstang, implying that light pollution grew more rapidly in subsequent decades than has been supposed. The model is applied to the nebular observations ofWilliam Herschel, enabling his visual performance to be quantified. Proposals are made regarding sky quality indicators for public use. & copy ; 2014 The Author Published by Oxford University Press on behalf of the Royal Astronomical Society.

Horellou C.,Chalmers University of Technology | Fletcher A.,Northumbria University
Monthly Notices of the Royal Astronomical Society | Year: 2014

Wide-band radio polarization observations offer the possibility to recover information about the magnetic fields in synchrotron sources, such as details of their three-dimensional configuration, that has previously been inaccessible. The key physical process involved is the Faraday rotation of the polarized emission in the source (and elsewhere along the wave's propagation path to the observer). In order to proceed, reliable methods are required for inverting the signals observed inwavelength space into useful data in Faraday space, with robust estimates of their uncertainty. In this paper, we examine howvariations of the intrinsic angle of polarized emissionψ0 with the Faraday depth Φ within a source affect the observable quantities. Using simple models for the Faraday dispersion F(Φ) and ψ0(Φ), along with the current and planned properties of the main radio interferometers, we demonstrate how degeneracies among the parameters describing the magneto-ionic medium can be minimized by combining observations in different wavebands. We also discuss how depolarization by Faraday dispersion due to a random component of the magnetic field attenuates the variations in the spectral energy distribution of the polarization and shifts its peak towards shorter wavelengths. This additional effect reduces the prospect of recovering the characteristics of the magnetic field helicity in magneto-ionic media dominated by the turbulent component of the magnetic field. © 2014 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.

Reliability of a hybrid renewable energy system (HRES) strongly depends on various uncertainties affecting the amount of power produced by the system. In the design of systems subject to uncertainties, both deterministic and nondeterministic design approaches can be adopted. In a deterministic design approach, the designer considers the presence of uncertainties and incorporates them indirectly into the design by applying safety factors. It is assumed that, by employing suitable safety factors and considering worst-case-scenarios, reliable systems can be designed. In fact, the multi-objective optimisation problem with two objectives of reliability and cost is reduced to a single-objective optimisation problem with the objective of cost only. In this paper the competence of deterministic design methods in size optimisation of reliable standalone wind-PV-battery, wind-PV-diesel and wind-PV-battery-diesel configurations is examined. For each configuration, first, using different values of safety factors, the optimal size of the system components which minimises the system cost is found deterministically. Then, for each case, using a Monte Carlo simulation, the effect of safety factors on the reliability and the cost are investigated. In performing reliability analysis, several reliability measures, namely, unmet load, blackout durations (total, maximum and average) and mean time between failures are considered. It is shown that the traditional methods of considering the effect of uncertainties in deterministic designs such as design for an autonomy period and employing safety factors have either little or unpredictable impact on the actual reliability of the designed wind-PV-battery configuration. In the case of wind-PV-diesel and wind-PV-battery-diesel configurations it is shown that, while using a high-enough margin of safety in sizing diesel generator leads to reliable systems, the optimum value for this margin of safety leading to a cost-effective system cannot be quantified without employing probabilistic methods of analysis. It is also shown that deterministic cost analysis yields inaccurate results for all of the investigated configurations. © 2014 Elsevier Ltd. All rights reserved.

Jackson J.C.,Northumbria University
Monthly Notices of the Royal Astronomical Society | Year: 2012

A 2.29 GHz very long baseline interferometry all-sky survey of ultra-compact radio sources due to Preston et al. has formed the basis of a number of cosmological investigations, which examine the relationship between angular size and redshift. Here I use a sample of 468 such sources with 0.5 < z ≤ 3.787 to investigate the isotropy of the Universe. The sample is divided into hemispherical sub-samples, over an all-sky 5° × 5° array, each of which is allowed to determine a value of Ω m, assuming that we are living in a spatially flat homogeneous isotropic Λ cold dark matter model. If we regard the latter as a null hypothesis, then it fails the test - the results show significant anisotropy, the smallest value of Ω m being towards (l, b) = (253.9,24.1)°, and the largest in the opposite direction. This is close to the cosmic microwave background dipole axis, but in the obverse sense. This is interpreted as meaning that the Universe is not spatially homogeneous on the largest scales, and is better represented at late times by a spherically symmetric model with a density enhancement at its centre. © 2012 The Author Monthly Notices of the Royal Astronomical Society © 2012 RAS.

Underwood C.P.,Northumbria University
Energy and Buildings | Year: 2014

In this work an improved method for the simplified modelling of the thermal response of building elements has been developed based on a 5-parameter second-order lumped parameter model. Previous methods generate the parameters of these models either analytically or by using single objective function optimisation with respect to a reference model. The analytical methods can be complex and inflexible and the single objective function method lacks generality. In this work, a multiple objective function optimisation method is used with a reference model. Error functions are defined at both internal and external surfaces of the construction element whose model is to be fitted and the resistance and capacitance distributions are adjusted until the error functions reach a minimum. Parametric results for a wide range (45) of construction element types have been presented. Tests have been carried out using a range of both random and periodic excitations in weather and internal heat flux variables resulting in a comparison between the simplified model and the reference model. Results show that the simplified model provides an excellent approximation to the reference model whilst also providing a reduction in computational cost of at least 30%. © 2014 Elsevier B.V.

Armstrong L.,Northumbria University
Stem Cell Reviews and Reports | Year: 2012

Pluripotent embryonic stem cells can give rise to almost all somatic cell types but this characteristic requires precise control of their gene expression patterns. The necessity of keeping the entire genome "poised" to enter into any of a number of developmental possibilities requires a unique and highly plastic chromatin organisation based around specific patterns of histone modifications although this state of affairs is normally short lived during embryonic development. By deriving embryonic stem cells from the early embryo, we can preserve the highly specialised genome organisation and this has permitted several detailed investigations into the molecular basis of pluripotency. © 2011 Springer Science+Business Media, LLC.

Little S.,Northumbria University
Diabetes technology & therapeutics | Year: 2011

Hypoglycemia has for the most part been studied inadequately for both of the commonly used long-acting insulin analogs in type 1 and type 2 diabetes. Almost all existing trials have been designed to investigate changes in glycemic control and not differences in hypoglycemia events. In this review, we present an overview of the hypoglycemic data available from the randomized controlled trials comparing insulin glargine and insulin detemir with NPH or continuous subcutaneous insulin infusion in type 1 and type 2 diabetes. The limited head-to-head glargine versus detemir data are also discussed with comments on early results relating to the newer insulin analog, degludec. Basal insulin analogs are associated with reduced nocturnal hypoglycemia in both type 1 and type 2 diabetes. Most studies have excluded participants with impaired awareness of hypoglycemia or previous severe events, however, and hypoglycemia reporting is variable and inconsistent. This limits interpretation for those with long-duration type 1 diabetes, and particularly impaired awareness of hypoglycemia, or long-duration more insulin-deficient type 2 diabetes. New optimally designed studies are required to elucidate the true impact of basal analogs on hypoglycemia burden in those living with long-term insulin therapy.

Hawley D.P.,Northumbria University
Rheumatology (Oxford, England) | Year: 2014

OBJECTIVES: Juvenile localized scleroderma (JLS) is a rare condition that is often difficult to assess and for which a variety of monitoring tools have been described. We aimed to describe how monitoring tools are used and perceived by clinicians in the UK, to ascertain treatments used for JLS and to provide a description of transition arrangements to adult care.METHODS: An e-survey of UK paediatric rheumatologists and dermatologists managing children and young people (CYP) with JLS was distributed using the national organisations representing these clinician groups. We asked respondents for their views and experience using 15 JLS monitoring tools, about transition services and about treatments used.RESULTS: Thirty-five dermatologists and 13 paediatric rheumatologists responded. Paediatric rheumatologists managed more CYP with JLS than dermatologists (median 16-20 and 3, respectively). Transition arrangements were reported by 43% of dermatologists and 91% of paediatric rheumatologists. Medical photography was the most frequently regularly used monitoring tool (73% respondents). The modified Rodnan skin score was the skin score used most commonly: 33% of paediatric rheumatologists and 3% of dermatologists reported using this tool frequently. Topical treatments and ultraviolet light were used by 49-80% of dermatologists and 0-8% paediatric rheumatologists. Biologic drugs and CYC were used by 0-3% of dermatologists and 31-46% of paediatric rheumatologists.CONCLUSION: How monitoring tools are accessed, used and perceived by paediatric rheumatologists and dermatologists in the UK varies between and within clinician groups, as do treatment prescribing patterns and transition arrangements. These differences will impact on the feasibility of conducting multicentre clinical trials and on standardising clinical care. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Chakraborty N.,Northumbria University | Lipatnikov A.N.,Chalmers University of Technology
Physics of Fluids | Year: 2013

The effects of global Lewis number Le on the statistics of fluid velocity components conditional in unburned reactants and fully burned products in the context of Reynolds Averaged Navier Stokes simulations have been analysed using a Direct Numerical Simulations (DNS) database of statistically planar turbulent premixed flames with a low Damköhler number and Lewis number ranging from 0.34 to 1.2. The conditional velocity statistics extracted from DNS data have been analysed with respect to the well-known Bray-Moss-Libby (BML) expressions which were derived based on bi-modal probability density function of reaction progress variable for high Damköhler number flames. It has been shown that the Lewis number substantially affects the mean velocity and the velocity fluctuation correlation conditional in products, with the effect being particularly pronounced for low Le. As far as the mean velocity and the velocity fluctuation correlation conditional in reactants are concerned, the BML expressions agree reasonably well with the DNS data reported in the present work. Based on a priori analysis of present and previously reported DNS data, the BML expressions have been empirically modified here in order to account for Lewis number effects, and the non-bimodal distribution of reaction progress variable. Moreover, it has been demonstrated for the first time that surface averaged velocity components and Reynolds stresses conditional in unburned reactants can be modelled without invoking expressions involving the Lewis number, as these surface averaged conditional quantities remain approximately equal to their conditionally averaged counterparts in the unburned mixture. © 2013 American Institute of Physics.

Vollmer W.,Northumbria University | Seligman S.J.,New York Medical College
Trends in Microbiology | Year: 2010

Peptidoglycan forms a net-like sacculus made of glycan strands crosslinked by peptides. The length of the glycan strands and the degree of crosslinkage vary with bacterial species, strains and growth conditions. Several models for the three-dimensional architecture of peptidoglycan have been proposed, some of which have been tested experimentally. The new data support a layered model in Gram-negative bacteria, and a more elaborate peptidoglycan architecture, with bands made of coiled bundles of glycan strands, in the rod-shaped Bacillus subtilis. However, many questions remain unanswered and, therefore, more data and more models are required to decipher the complex cell wall architecture in bacteria. © 2009 Elsevier Ltd. All rights reserved.

Calvert H.,Northumbria University | Azzariti A.,National Cancer Center Giovanni Paolo
Annals of Oncology | Year: 2011

A number of inhibitors of DNA repair have been evaluated or are undergoing development as potential cancer treatments. Inhibitors of poly(ADP-ribose) polymerase (PARP) are of particular interest in treating hereditary breast cancers occurring in patients who are carriers of BRCA1 or BRCA2 mutations. In vitro PARP inhibitors are highly cytotoxic to cell lines carrying BRCA mutations while only minimally toxic to cell lines without these mutations. This is thought to be due to a phenomenon known as synthetic lethality where the accumulation of single-strand breaks consequent on PARP inhibition are converted to double-strand breaks on cell division. Cancer cells in BRCA carriers are uniquely unable to repair the consequent double-strand breaks that result during cell division. PARP inhibitors were initially developed as possible chemo-potentiating agents but have now been evaluated clinically in BRCA-related tumors, showing remarkable single-agent activity. The potential future development and use is reviewed. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Yakovlev A.,Northumbria University
Proceedings -Design, Automation and Test in Europe, DATE | Year: 2011

For years people have been designing electronic and computing systems focusing on improving performance but "keeping power and energy consumption in mind". This is a way to design energy-aware or power-efficient systems, where energy is considered as a resource whose utilization must be optimized in the realm of performance constraints. Increasingly, energy and power turn from optimization criteria into constraints, sometimes as critical as, for example, reliability and timing. Furthermore, quanta of energy or specific levels of power can shape the system's action. In other words, the system's behavior, i.e. the way how computation and communication is carried out, can be determined or modulated by the flow of energy into the system. This view becomes dominant when energy is harvested from the environment. In this paper, we attempt to pave the way to a systematic approach to designing computing systems that are energy-modulated. To this end, several design examples are considered where power comes from energy harvesting sources with limited power density and unstable levels of power. Our design examples include voltage sensors based on self-timed logic and speed-independent SRAM operating in the dynamic range of Vdd 0.2-1V. Overall, this work advocates the vision of designing systems in which a certain quality of service is delivered in return for a certain amount of energy. © 2011 EDAA.

Askins K.,Northumbria University | Pain R.,Durham University
Environment and Planning D: Society and Space | Year: 2011

Recent debates around urban encounter, integration cosmopolitanism, and renewed engagement with contact theory have raised questions about the spaces of interaction that may enable meaningful encounters between different social groups. Reflecting on a participatory art project with young people of African and British heritage in northeast England, we argue that discussion and practice around participatory action research, including the deployment of contact zones as theory and method, can cast some light on what fosters transformative spaces. Through analysis of two different approaches to community art used in the project, we show how elements of each enabled and disabled meaningful interaction between young people. We draw attention to the materiality of art (the tools) within participatory practices (the doing of it) in contributing to a space where interactions might take place, emphasising a complex interplay across/between actors, materials, and space that frames encounters as emergent, transitory, fragile, and yet hopeful. We examine the potential of a focus on the material in thinking beyond moments of encounter to how transformative social relations may be 'scaled up' before considering the implications for research and policy. © 2011 Pion Ltd and its Licensors.

Ewen J.,Northumbria University
Journal of Hydrology | Year: 2011

Despite all the progress made over the years on developing automatic methods for analysing hydrographs and measuring the performance of rainfall-runoff models, automatic methods cannot yet match the power and flexibility of the human eye and brain. Very simple approaches are therefore being developed that mimic the way hydrologists inspect and interpret hydrographs, including the way that patterns are recognised, links are made by eye, and hydrological responses and errors are studied and remembered. In this paper, a dynamic programming algorithm originally designed for use in data mining is customised for use with hydrographs. It generates sets of " rays" that are analogous to the visual links made by the hydrologist's eye when linking features or times in one hydrograph to the corresponding features or times in another hydrograph. One outcome from this work is a new family of performance measures called " visual" performance measures. These can measure differences in amplitude and timing, including the timing errors between simulated and observed hydrographs in model calibration. To demonstrate this, two visual performance measures, one based on the Nash-Sutcliffe Efficiency and the other on the mean absolute error, are used in a total of 34 split-sample calibration-validation tests for two rainfall-runoff models applied to the Hodder catchment, northwest England. The customised algorithm, called the Hydrograph Matching Algorithm, is very simple to apply; it is given in a few lines of pseudocode. © 2011 Elsevier B.V.

Bardgett R.D.,Lancaster University | Manning P.,Northumbria University | Morrien E.,Netherlands Institute of Ecology | De Vries F.T.,Lancaster University
Journal of Ecology | Year: 2013

Interactions between plant and soil communities play a major role in determining the impact of climate change on ecosystem functioning and the carbon cycle, and the mechanisms involved operate over a wide range of spatial and temporal scales. We present a framework for understanding the consequences of climate-induced changes in plant-soil feedback for the carbon cycle. The framework describes a hierarchy of mechanisms by which changes in climate impact on ecosystem carbon dynamics at three levels of response, namely individual and community reordering and species immigration and loss. For each level, we identify the mechanisms by which climate change impacts on plant-soil interactions with consequences for the carbon cycle. We also demonstrate that the potential for decoupling of plant-soil interactions increases across the three levels of response, being greatest with species immigration and/or loss, for example, if plants were to undergo a biome shift, but their associated soil communities did not. Such decoupling is a largely unrecognized, but potentially important regulator of the future global carbon cycle. Synthesis. The framework presented here highlights a need for a new approach to the study of climate change impacts on plant-soil interactions and carbon cycling that integrates this hierarchy of responses, and incorporates the decoupling of above-ground and below-ground networks, across a range of temporal and spatial scales, and ecosystems. © 2013 The Authors. Journal of Ecology © 2013 British Ecological Society.

Rodriguez-Ezpeleta N.,Northumbria University | Embley T.M.,Tecnalia
PLoS ONE | Year: 2012

Although free living, members of the successful SAR11 group of marine alpha-proteobacteria contain a very small and A+T rich genome, two features that are typical of mitochondria and related obligate intracellular parasites such as the Rickettsiales. Previous phylogenetic analyses have suggested that Candidatus Pelagibacter ubique, the first cultured member of this group, is related to the Rickettsiales+mitochondria clade whereas others disagree with this conclusion. In order to determine the evolutionary position of the SAR11 group and its relationship to the origin of mitochondria, we have performed phylogenetic analyses on the concatenation of 24 proteins from 5 mitochondria and 71 proteobacteria. Our results support that SAR11 group is not the sistergroup of the Rickettsiales+mitochondria clade and confirm that the position of this group in the alpha-proteobacterial tree is strongly affected by tree reconstruction artefacts due to compositional bias. As a consequence, genome reduction and bias toward a high A+T content may have evolved independently in the SAR11 species, which points to a different direction in the quest for the closest relatives to mitochondria and Rickettsiales. In addition, our analyses raise doubts about the monophyly of the newly proposed Pelagibacteraceae family. © 2012 Rodríguez-Ezpeleta.

Meyer T.D.,University of Tubingen | Meyer T.D.,Northumbria University | Hautzinger M.,University of Tubingen
Psychological Medicine | Year: 2012

Background The efficacy of adjunctive psychosocial interventions such as cognitive behaviour therapy (CBT) for bipolar disorder (BD) has been demonstrated in several uncontrolled and controlled studies. However, these studies compared CBT to either a waiting list control group, brief psycho-education or treatment as usual (TAU). Our primary aim was to determine whether CBT is superior to supportive therapy (ST) of equal intensity and frequency in preventing relapse and improving outcome at post-treatment. A secondary aim was to look at predictors of survival time.Method We conducted a randomized controlled trial (RCT) at the Department of Psychology, University of Tubingen, Germany (n=76 patients with BD). Both CBT and ST consisted of 20 sessions over 9 months. Patients were followed up for a further 24 months.Results Although changes over time were observed in some variables, they were not differentially associated with CBT or ST. CBT showed a non-significant trend for preventing any affective, specifically depressive episode during the time of therapy. Kaplan-Meier survival analyses revealed that 64.5% of patients experienced a relapse during the 33 months. The number of prior episodes, the number of therapy sessions and the type of BD predicted survival time.Conclusions No differences in relapse rates between treatment conditions were observed, suggesting that certain shared characteristics (e.g. information, systematic mood monitoring) might explain the effects of psychosocial treatment for BD. Our results also suggest that a higher number of prior episodes, a lower number of therapy sessions and a diagnosis of bipolar II disorder are associated with a shorter time before relapse. © 2011 Cambridge University Press.

Johnson D.,Northumbria University
Applied Geography | Year: 2013

Whilst analysis of crime for tactical and strategic reasons within the criminal justice arena has now become an established need, predictive analysis of crime remains, and probably always will be, a goal to be desired. Opening a window on this over the last 2 decades, prominent research from academia has focused on the phenomenon of repeat victimisation and more recently 'near repeat' victimisation, both firmly grounded in the geography of crime. Somewhat limited to the establishment of near repeat behavioural patterns in whole area data, these can be utilised for crime prevention responses on a local scale. Research reported here however, explores the phenomenon through the examination of serial offending by individual offenders to establish if such spatio-temporal patterns are apparent in the spatial behavioural patterns of the individual burglar, and if so how they may be defined and therefore utilised on a micro rather than macro scale. It is hypothesised that offenders' responsible for more than one series of offences will display consistency across their crime series within time and distance parameters for their closest offences in space. Results improve upon current knowledge concerning near repeat offending being the actions of common offenders. Testing of the extracted data indicates that offenders maintain personal boundaries of 'closeness' in time and space even when actions are separated by significant time spans, creating stylised behavioural signatures appertaining to their use of and movement through space when offending. © 2013 Elsevier Ltd.

Vallance P.,Northumbria University
Environment and Planning A | Year: 2011

Recent work in economic geography suggests the emergence of a distinctive relational and practice-centred set of perspectives on knowledge, based around concepts including communities of practice and relational proximity. This paper will argue that, despite the significant advances in understanding this work contributes, it does not yet provide a complete account of knowing-in- practice, and proposes a stronger focus on work activity as a first step in addressing this gap. The first half critically reviews this economic geography literature, focusing on how it articulates a view of practice in relation to knowledge, organisation, and space. The second half develops an alternative conceptualisation of knowing as work practice, particularly drawing on cultural - historical activity theory. This is organised around the dual spatially inflected concepts of situated and distributed knowledge. The paper concludes by arguing that, far from being mutually exclusive, the situated and distributed parts of knowing coexist in a dialectical relationship, and their interaction in work practice leads to the production of spaces of collective knowing. © 2011 Pion Ltd and its Licensors.

Klerkx L.,Wageningen University | Proctor A.,Northumbria University
Land Use Policy | Year: 2013

The growing multifunctionality in agriculture, combined with privatisation of previously public agricultural extension services, has resulted in a pluralistic land management advisory system. Despite benefits in terms of increased client orientation and greater advisor diversity, it is argued that these changes have resulted in the fragmentation of the land management advisory system and a reduction of interaction within the advisory system and between the advisory system and science. Hence, concerns have been voiced as regards the capacity of the advisory system to be able to incorporate new knowledge, resulting in a growing interest in how advisors obtain and construct the knowledge necessary for offering adequate advisory services to their clients. In this article we explore how advisors within the English land management advisory system (land agents, applied ecologists and veterinarians) develop and optimise their knowledge by engaging in different kinds of networks (centralised, distributed and decentralised), each of which employs a different type of social capital. Key findings suggest that to obtain the knowledge needed to solve complex queries of clients, advisors use distributed networks and draw upon informal 'communities of practice' within their own advisory profession characterised by bonding social capital, but also draw upon broader 'networks of practice' involving multiple advisors from different advisory professions, which rely on bridging social capital. The employment of decentralised networks which rely on linking social capital, to solve complex queries or develop new services, for example through contacts with scientific institutes, appears to be less developed, despite brokering activities of the professional associations. Whereas fragmentation and disconnect due to competition and epistemological differences do play a role; they do not appear to prevent overall knowledge exchange among advisors within and across different professions. Assumptions of a collapse of interaction within the land management advisory system are not supported by the evidence, as there appears to be much bonding and bridging social capital. However, to optimise interactions between professions, and between advisors and the science system, either informal brokers or formal brokers in the form of professional associations or other organisations could play a bigger role. © 2012 Elsevier Ltd.

Britton E.,University of Ulster | Coulthard S.,Northumbria University
Marine Policy | Year: 2013

The concept of 'wellbeing' has received growing interest in policy domains in the UK, and internationally, as a multi-dimensional approach to understanding and measuring social progress and development. Policy makers and scientists alike are debating the potential of wellbeing to deliver a people-centred, and holistic, analysis of what matters to people in terms of the quality of life people pursue and are able to achieve. There is also growing interest in how the concept of wellbeing might be applied to fisheries, especially in terms of deepening assessment of the ways in which decline in the fisheries sector is affecting fishing-dependent families, and the wider community. This paper applies a three-dimensional wellbeing framework and methodology to gain insight into the wellbeing of fishing society in Northern Ireland, a region that has faced substantial decline in its fisheries over the past 100 years. A three-dimensional approach considers material, relational and cognitive dimensions; putting resources, relationships and subjective reflections on life satisfaction together as a whole assessment. All three dimensions are important for a full assessment of wellbeing. Following an overview of the methodology used and data collected, the paper then assesses the extent to which a three-dimensional well-being approach can provide useful insights for sustainable fisheries policy in Northern Ireland. © 2012 Elsevier Ltd.

Gillespie C.S.,Northumbria University
Journal of Statistical Software | Year: 2015

Over the last few years, the power law distribution has been used as the data gener- ating mechanism in many disparate elds. However, at times the techniques used to fit the power law distribution have been inappropriate. This paper describes the poweRlaw R package, which makes fitting power laws and other heavy-tailed distributions straight forward. This package contains R functions for ftting, comparing and visualizing heavy tailed distributions. Overall, it provides a principled approach to power law fitting. © 2015 American Statistical Association. All rights reserved.

Vlachos I.P.,Northumbria University
Expert Systems with Applications | Year: 2014

The primary purpose of this study was to evaluate the impact of radio frequency identification (RFID) practices on supply chain performance. We examined eight variables of RFID applications grouped in two categories: location (supplier's warehouse, retailer's central warehouse, retailer's local warehouse, retailer's owned stores) and utilisation (standards, transportation, pallet level, specialised software). Given the inherent difficulty in assessing supply chain performance and the widespread use of different performance models, such as the SCOR and balanced scorecard, we developed a list of performance indicators. Factor analysis produced 7 supply chain performance factors: supplier, inventory, distribution, ordering, plan, sales, and forecasting. Empirical data were collected via an online survey administered to 300 retail companies. 130 usable questionnaires were returned, for a 43.3% response rate. To the best of our knowledge, this is the first study to provide an analytical model that places supply chain performance indicators as dependent variables in a hierarchical regression equation with RFID variables as independent variables. Results found that the implementation of RFID practices significantly affect the supply chain performance in the following areas: supplier, inventory, distribution, plan, sales, and forecasting. RFID can improve the performance of distribution systems, including products dispatched and inventory in transit by 33.8% and stock availability by 45.6%. This study contributes to both the RFID and the supply chain performance literatures. Limitations and suggestions for further research are also discussed. © 2013 Elsevier Ltd. All rights reserved.

Burda P.,Durham University | Gregory R.,Durham University | Gregory R.,Perimeter Institute | Moss I.G.,Northumbria University
Physical Review Letters | Year: 2015

We discuss the effect of gravitational interactions on the lifetime of the Higgs vacuum where generic quantum gravity corrections are taken into account. Using a "thin-wall" approximation, we provide a proof of principle that small black holes can act as seeds for vacuum decay, spontaneously nucleating a new Higgs phase centered on the black hole with a lifetime measured in millions of Planck times rather than billions of years. The corresponding parameter space constraints are, however, extremely stringent; therefore, we also present numerical evidence suggesting that with thick walls, the parameter space may open up. Implications for collider black holes are discussed. © 2015 uk. Published by the American Physical Society.

Rodriguez-Ezpeleta N.,Northumbria University
PloS one | Year: 2012

Although free living, members of the successful SAR11 group of marine alpha-proteobacteria contain a very small and A+T rich genome, two features that are typical of mitochondria and related obligate intracellular parasites such as the Rickettsiales. Previous phylogenetic analyses have suggested that Candidatus Pelagibacter ubique, the first cultured member of this group, is related to the Rickettsiales+mitochondria clade whereas others disagree with this conclusion. In order to determine the evolutionary position of the SAR11 group and its relationship to the origin of mitochondria, we have performed phylogenetic analyses on the concatenation of 24 proteins from 5 mitochondria and 71 proteobacteria. Our results support that SAR11 group is not the sistergroup of the Rickettsiales+mitochondria clade and confirm that the position of this group in the alpha-proteobacterial tree is strongly affected by tree reconstruction artefacts due to compositional bias. As a consequence, genome reduction and bias toward a high A+T content may have evolved independently in the SAR11 species, which points to a different direction in the quest for the closest relatives to mitochondria and Rickettsiales. In addition, our analyses raise doubts about the monophyly of the newly proposed Pelagibacteraceae family.

Bull S.J.,Northumbria University
Journal of Vacuum Science and Technology A: Vacuum, Surfaces and Films | Year: 2012

In this study, the mechanical properties of atomic layer deposition (ALD) alumina coatings deposited at a range of temperatures from 80 C onto substrates with differing stiffness including hard, stiff materials (silicon and glass) and soft, compliant materials (PET) have been investigated by nanoindentation. Approaches necessary to extract coating properties from the coating/substrate composite data have been developed in order to obtain reliable data from 150 nm thick coatings on hard, stiff substrates. This has shown that the elastic modulus of ALD alumina increases with deposition temperature as might be expected from the variation in density. Measurements for the ALD alumina coatings on PET using the same analysis method give lower elastic Modulus and hardness values; this is not due to an intrinsic difference in coating properties but is a consequence of the effect of modulus mismatch between coating and substrate on the measurement method. Reliable data for the coatings on PET are therefore more difficult to obtain but can be determined if a suitable modeling approach is adopted. © 2012 American Vacuum Society.

Grunze H.,Northumbria University
Pharmacopsychiatry | Year: 2011

This article summarizes key facts on the epidemiology, diagnosis and clinical treatment of bipolar disorder. Bipolar disorder is a common mental disorder with a high disease burden, but still does not get the attention it deserves in research and clinical training. The nature of the disorder is complex, but it is apparent that biological factors are decisive. Thus, understanding the biological systems and cycles affected will become crucial for developing more targeted interventions. Currently, standard treatments seem to have a low specificity for Bipolar Disorder, and only few experimental interventions target directly potential underlying disturbances as HPA axis or circadian clock dysregulation. Systemic analysing and modelling of bipolar disorder is a novel approach which might open up new ways in developing more selective therapies. © Georg Thieme Verlag KG Stuttgart - New York.

Diffey B.L.,Northumbria University
Journal of Cosmetic Dermatology | Year: 2011

Background Exposure to solar ultraviolet (UV) radiation is believed to be an important contributor to facial photoaging. Daily application of topical photoprotectants is thought to mitigate this process. Objectives To examine the importance of a number of independent factors in reducing the lifetime UV exposure of facial skin achieved by daily use of photoprotective products. Methods A behavioral model of solar UV exposure to the face is incorporated with the spectral profile of two different candidate topical products, the age at which regular photoprotection begins, the SPF of the products, and whether the product is applied year-round or just in the summer months to examine the reduction in lifetime UV exposures achieved by daily use of photoprotective products. Results The results show that regular use of topical photoprotective agents reduces significantly lifetime UV exposure to the face compared with nonuse. Analysis of variance shows that the most important factor is to begin regular daily use early in life. The SPF and spectral profile of the product is of lesser importance, as is whether daily use is confined to the summer months rather than year-round. Conclusions While it remains unproven and speculative, there is good reason to suppose that regular use of daily facial topical products containing UV filters, particularly if started early in adult life, will be translated into fewer visible signs of aging later in life. © 2011 Wiley Periodicals, 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.

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.

Schneider C.,Northumbria University | Tollervey D.,University of Edinburgh
Trends in Biochemical Sciences | Year: 2013

In eukaryotes, the exosome complex degrades RNA backbones and plays key roles in RNA processing and surveillance. It was predicted that RNA substrates are threaded through a central channel. This pathway is conserved between eukaryotic and archaeal complexes, even though nuclease activity was lost from the nine-subunit eukaryotic core (EXO-9) and transferred to associated proteins. The exosome cooperates with nuclear and cytoplasmic cofactors, including RNA helicases Mtr4 and Ski2, respectively. Structures of an RNA-bound exosome and both helicases revealed how substrates are channeled through EXO-9 to the associated nuclease Rrp44. Recent high-throughput analyses provided fresh insights relating exosome structure to its diverse in vivo functions. They also revealed surprisingly high degradation rates for newly synthesized RNAs, particularly RNA polymerase III transcripts. © 2013 Elsevier Ltd.

Stoll E.A.,Northumbria University | Horner P.J.,University of Washington | Rostomily R.C.,University of Washington
Aging Cell | Year: 2013

Paradoxically, aging leads to both decreased regenerative capacity in the brain and an increased risk of tumorigenesis, particularly the most common adult-onset brain tumor, glioma. A shared factor contributing to both phenomena is thought to be age-related alterations in neural progenitor cells (NPCs), which function normally to produce new neurons and glia, but are also considered likely cells of origin for malignant glioma. Upon oncogenic transformation, cells acquire characteristics known as the hallmarks of cancer, including unlimited replication, altered responses to growth and anti-growth factors, increased capacity for angiogenesis, potential for invasion, genetic instability, apoptotic evasion, escape from immune surveillance, and an adaptive metabolic phenotype. The precise molecular pathogenesis and temporal acquisition of these malignant characteristics is largely a mystery. Recent studies characterizing NPCs during normal aging, however, have begun to elucidate mechanisms underlying the age-associated increase in their malignant potential. Aging cells are dependent upon multiple compensatory pathways to maintain cell cycle control, normal niche interactions, genetic stability, programmed cell death, and oxidative metabolism. A few multi-functional proteins act as 'critical nodes' in the coordination of these various cellular activities, although both intracellular signaling and elements within the brain environment are critical to maintaining a balance between senescence and tumorigenesis. Here, we provide an overview of recent progress in our understanding of how mechanisms underlying cellular aging inform on glioma pathogenesis and malignancy. © 2013 The Anatomical Society and John Wiley & Sons Ltd.

Steven S.,Northumbria University
Diabetic medicine : a journal of the British Diabetic Association | Year: 2013

Following publication of the Counterpoint Study (on the reversibility of Type 2 diabetes using a very low energy diet), the extent of public interest prompted the authors to make available, on a website, general information about reversing diabetes. Shortly thereafter, individuals began to feed back their personal experiences of attempting to reverse their diabetes. We have collated this information on the effects of energy restriction in motivated individuals with Type 2 diabetes that has been achieved outside a research setting. Emails, letters and telephone communications received between July 2011 and September 2012 were evaluated (n = 77: 66 men, 11 women). Median diabetes duration was 5.5 years (3 months-28 years). Reversal of diabetes was defined as achieving fasting capillary blood glucose < 6.1 mmol/l and/or, if available, HbA1c less than 43 mmol/mol (6.1%) off treatment. Self-reported weight fell from 96.7 ± 17.5 kg at baseline to 81.9 ± 14.8 kg after weight loss (P < 0.001). Self-reported fasting blood glucose levels fell from 8.3 mmol/l (5.9-33.0) to 5.5 mmol/l (4.0-10.0) after the weight loss period (P < 0.001). Diabetes reversal was considered to have occurred in 61% of the population. Reversal of diabetes was observed in 80, 63 and 53% of those with > 20, 10-20 and < 10 kg weight loss, respectively. There was a significant correlation between degree of weight loss and reported fasting glucose levels (Rs -0.38, P = 0.006). Reversal rates according to diabetes duration were: short (< 4 years) = 73%, medium (4-8 years) = 56% and long (> 8 years) = 43%. These data demonstrate that intentional weight loss achieved at home by health-motivated individuals can reverse Type 2 diabetes. Diabetes reversal should be a goal in the management of Type 2 diabetes. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

Curtin N.J.,Northumbria University | Szabo C.,University of Texas Medical Branch
Molecular Aspects of Medicine | Year: 2013

The aim of this article is to describe the current and potential clinical translation of pharmacological inhibitors of poly(ADP-ribose) polymerase (PARP) for the therapy of various diseases. The first section of the present review summarizes the available preclinical and clinical data with PARP inhibitors in various forms of cancer. In this context, the role of PARP in single-strand DNA break repair is relevant, leading to replication-associated lesions that cannot be repaired if homologous recombination repair (HRR) is defective, and the synthetic lethality of PARP inhibitors in HRR-defective cancer. HRR defects are classically associated with BRCA1 and 2 mutations associated with familial breast and ovarian cancer, but there may be many other causes of HRR defects. Thus, PARP inhibitors may be the drugs of choice for BRCA mutant breast and ovarian cancers, and extend beyond these tumors if appropriate biomarkers can be developed to identify HRR defects. Multiple lines of preclinical data demonstrate that PARP inhibition increases cytotoxicity and tumor growth delay in combination with temozolomide, topoisomerase inhibitors and ionizing radiation. Both single agent and combination clinical trials are underway. The final part of the first section of the present review summarizes the current status of the various PARP inhibitors that are in various stages of clinical development. The second section of the present review summarizes the role of PARP in selected non-oncologic indications. In a number of severe, acute diseases (such as stroke, neurotrauma, circulatory shock and acute myocardial infarction) the clinical translatability of PARP inhibition is supported by multiple lines of preclinical data, as well as observational data demonstrating PARP activation in human tissue samples. In these disease indications, PARP overactivation due to oxidative and nitrative stress drives cell necrosis and pro-inflammatory gene expression, which contributes to disease pathology. Accordingly, multiple lines of preclinical data indicate the efficacy of PARP inhibitors to preserve viable tissue and to down-regulate inflammatory responses. As the clinical trials with PARP inhibitors in various forms of cancer progress, it is hoped that a second line of clinical investigations, aimed at testing of PARP inhibitors for various non-oncologic indications, will be initiated, as well. © 2013 Elsevier Ltd. All rights reserved.

Wild P.J.,Northumbria University
CIRP Journal of Manufacturing Science and Technology | Year: 2010

Cross-disciplinary research programmes often entail an integrative goal, that is, to integrate theory and findings from the multiple disciplines involved in the research. Services research has been frequently described as existing in silos. Little has been put forwards towards remedying this beyond the view that one theoretical perspective could dominate the discipline. This paper presents a framework for systematically relating streams services research. Working from the view that services are consistently defined as activities, rather than objects or artefacts the concepts of the framework are drawn from Activity Modelling approaches (e.g. Task Analysis, Domain/Process modelling, and Soft Systems). We compare the framework against a range of approaches. We cover techniques (Service Blueprinting, Enterprise Imaging), and some Service Evaluation approaches; and theories/frameworks (the Service-Dominant Logic; Service Blueprinting; the IHIP characteristics (Intangibility, Heterogeneity, Inseparability, and Perishability); Product-Service Systems; and the Unified Service Theory). © 2010 CIRP.

O'Brien J.T.,Northumbria University | Burns A.,University of Manchester
Journal of Psychopharmacology | Year: 2011

The British Association for Psychopharmacology (BAP) coordinated a meeting of experts to review and revise its first (2006) Guidelines for clinical practice with anti-dementia drugs. As before, levels of evidence were rated using accepted standards which were then translated into grades of recommendation A to D, with A having the strongest evidence base (from randomized controlled trials) and D the weakest (case studies or expert opinion). Current clinical diagnostic criteria for dementia have sufficient accuracy to be applied in clinical practice (B) and brain imaging can improve diagnostic accuracy (B). Cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) are effective for mild to moderate Alzheimer's disease (A) and memantine for moderate to severe Alzheimer's disease (A). Until further evidence is available other drugs, including statins, anti-inflammatory drugs, vitamin E and Ginkgo biloba, cannot be recommended either for the treatment or prevention of Alzheimer's disease (A). Neither cholinesterase inhibitors nor memantine are effective in those with mild cognitive impairment (A). Cholinesterase inhibitors are not effective in frontotemporal dementia and may cause agitation (A), though selective serotonin reuptake inhibitors may help behavioural (but not cognitive) features (B). Cholinesterase inhibitors should be used for the treatment of people with Lewy body dementias (Parkinson's disease dementia and dementia with Lewy bodies (DLB)), especially for neuropsychiatric symptoms (A). Cholinesterase inhibitors and memantine can produce cognitive improvements in DLB (A). There is no clear evidence that any intervention can prevent or delay the onset of dementia. Although the consensus statement focuses on medication, psychological interventions can be effective in addition to pharmacotherapy, both for cognitive and non-cognitive symptoms. Many novel pharmacological approaches involving strategies to reduce amyloid and/or tau deposition are in progress. Although results of pivotal studies are awaited, results to date have been equivocal and no disease-modifying agents are either licensed or can be currently recommended for clinical use. © The Author(s) 2011 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Daly A.K.,Northumbria University
Genome Medicine | Year: 2013

Considerable progress has been made in identifying genetic risk factors for idiosyncratic adverse drug reactions in the past 30 years. These reactions can affect various tissues and organs, including liver, skin, muscle and heart, in a drug-dependent manner. Using both candidate gene and genome-wide association studies, various genes that make contributions of varying extents to each of these forms of reactions have been identified. Many of the associations identified for reactions affecting the liver and skin involve human leukocyte antigen (HLA) genes and for reactions relating to the drugs abacavir and carbamazepine, HLA genotyping is now in routine use prior to drug prescription. Other HLA associations are not sufficiently specific for translation but are still of interest in relation to underlying mechanisms for the reactions. Progress on non-HLA genes affecting adverse drug reactions has been less, but some important associations, such as those of SLCO1B1 and statin myopathy, KCNE1 and drug-induced QT prolongation and NAT2 and isoniazid-induced liver injury, are considered. Future prospects for identification of additional genetic risk factors for the various adverse drug reactions are discussed. © 2013 BioMed Central Ltd.

Agius L.,Northumbria University
Biochemical Pharmacology | Year: 2013

In population studies hepatic steatosis in subjects with Non-alcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance. This association has encouraged debate whether hepatic steatosis is the cause or the consequence of hepatic insulin resistance? Although genome-wide studies have identified several gene variants associated with either hepatic steatosis or type 2 diabetes, no variants have been identified associated with both hepatic steatosis and insulin resistance. Here, the hypothesis is proposed that high-carbohydrate diets contribute to the association between hepatic steatosis and insulin resistance through activation of the transcription factor ChREBP (Carbohydrate response element binding protein). Postprandial hyperglycaemia raises the hepatic concentrations of phosphorylated intermediates causing activation of ChREBP and induction of its target genes. These include not only enzymes of glycolysis and lipogenesis that predispose to hepatic steatosis but also glucose 6-phosphatase (G6PC) that catalyses the final reaction in glucose production and GCKR, the inhibitor of hepatic glucokinase that curtails hepatic glucose uptake. Induction of G6PC and GCKR manifests as hepatic glucose intolerance or insulin resistance. Induction of these two genes by high glucose serves to safeguard intrahepatic homeostasis of phosphorylated intermediates. The importance of GCKR in this protective mechanism is supported by "less-active" GCKR variants in association not only with hepatic steatosis and hyperuricaemia but also with lower fasting plasma glucose and decreased insulin resistance. This supports a role for GCKR in restricting hepatic glucose phosphorylation to maintain intrahepatic homeostasis. Pharmacological targeting of the glucokinase-GCKR interaction can favour either glucose clearance by the liver or intrahepatic metabolite homeostasis. © 2012 Elsevier Inc. All rights reserved.

Corris P.A.,Northumbria University
Clinics in Chest Medicine | Year: 2011

The development of targeted therapies for pulmonary arterial hypertension currently based on prostaglandin, nitric oxide, and endothelin pathways has resulted in major advances in the treatment of patients with pulmonary arterial hypertension. This article reviews the current evidence that supports both the use of mono- and combination therapy. The article also considers the role of atrial septostomy in the treatment of pulmonary arterial hypertension, particularly as a bridge to transplantation. Finally, the article provides a review of the role and outcomes of pulmonary thromboendartertectomy for patients with chronic thromboembolic pulmonary hypertension. © 2011.

Green T.A.,Northumbria University
Gold Bulletin | Year: 2014

The etching of gold is a key enabling technology in the fabrication of many microdevices and is widely used in the electronic, optoelectronic and microelectromechanical systems (MEMS) industries. In this review, we examine some of the available methods for patterning gold thin films using dry and wet etching techniques. Dry methods which utilise reactive ion etching (RIE) have a number of important advantages over other methods, but the low volatility of gold etch products has made the development of suitable processes problematic. More recently, the adoption of high-density plasma reactors with optimised chlorine-based chemistries has allowed improved processes to be developed, and etching in hydrogen plasmas also shows promise. Wet etching methods for gold have also been critically reviewed. Traditionally, iodine- and cyanide-based etch processes have been used, but in the last decade, a number of alternative etchants have been studied. Of particular interest is the recent development of a range of novel non-aqueous-based gold etchants, and the suitability of these etchants for microfabrication is assessed. © 2014 The Author(s).

Bone M.C.,Northumbria University
The Journal of hand surgery, European volume | Year: 2013

The two-piece Van Straten Leuwen Poeschmann Metal (LPM) prosthesis was intended for the proximal interphalangeal joints. However, revision rates of 29% after 19 months were reported, as well as massive osteolysis. Five failed LPM titanium-niobium coated cobalt chromium components were obtained, three distal and two proximal, and subjected to a forensic retrieval analysis. Components were analyzed using a Talysurf contacting profilometer, ZYGO noncontacting profilometer, and environmental-scanning electron microscope. All components were heavily worn. In some regions the titanium-niobium coating had been scratched and penetrated. Elsewhere this coating had been removed where there was minimal scratching, which may have been due to corrosion between the coating and substrate. The osteolysis reported clinically was likely to be linked to the wear debris from the failed titanium-niobium coating and substrate.

Jackson A.,Northumbria University | Fetz E.E.,University of Washington
IEEE Transactions on Neural Systems and Rehabilitation Engineering | Year: 2011

Neuroscience is just beginning to understand the neural computations that underlie our remarkable capacity to learn new motor tasks. Studies of natural movements have emphasized the importance of concepts such as dimensionality reduction within hierarchical levels of redundancy, optimization of behavior in the presence of sensorimotor noise and internal models for predictive control. These concepts also provide a framework for understanding the improvements in performance seen in myoelectric-controlled interface and brain-machine interface paradigms. Recent experiments reveal how volitional activity in the motor system combines with sensory feedback to shape neural representations and drives adaptation of behavior. By elucidating these mechanisms, a new generation of intelligent interfaces can be designed to exploit neural plasticity and restore function after neurological injury. © 2011 IEEE.

Shapiro A.B.,Astrazeneca | Austin C.A.,Northumbria University
Analytical Biochemistry | Year: 2014

Because of their essentiality for DNA replication, transcription, and repair, type II topoisomerases are targets for antibacterial and anticancer drugs. There are two type II topoisomerases in humans, topoisomerase IIα (TOP2A) and topoisomerase IIβ (TOP2B), and two in bacteria, gyrase and topoisomerase IV. Inhibition of one or both of the human type II topoisomerases by antibacterial compounds targeting their bacterial counterparts could result in toxicity. In addition, side effects of anticancer drugs targeting TOP2A could result from inhibition of TOP2B. A simple and rapid biochemical assay for the activity of TOP2A and TOP2B would be advantageous for screening for novel inhibitors, testing them for selectivity for one enzyme over the other, and testing for potential toxicity of antibacterial type II topoisomerases mediated by human topoisomerase II inhibition. In this paper, we show that a previously reported high-throughput, fluorescence anisotropy-based assay for ATP-dependent relaxation of supercoiled DNA by human TOP2A can also be used under identical conditions for human TOP2B. We used this assay to compare the potencies versus both enzymes of 19 compounds reported in the literature to inhibit human and/or bacterial type II topoisomerases. We also used the assay to investigate the effect of ATP concentration on inhibitor potencies. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Campbell C.G.,Northumbria University
Monthly Notices of the Royal Astronomical Society | Year: 2010

The AM Herculis binaries are an important class of cataclysmic variables in which the accreting white dwarf primary is observed to rotate synchronously with the orbit. The torque needed to spin the primary towards synchronism is believed to be generated by the interaction of the primary's magnetic field with the tidally synchronized secondary star. It is shown here that such a torque is generated by the interaction of the magnetosphere of an asynchronous primary with the turbulent secondary. The effects of magnetic diffusion, shearing and field advection are accounted for and the resulting magnetic torques are calculated for a range of degrees of asynchronism. Non-central magnetic forces enable the primary to exchange angular momentum with the orbit, while a torque acts on the star which spins it towards synchronism. This torque has the form of a resonance curve, with a maximum value at moderate asynchronism. © 2010 The Author. Journal compilation © 2010 RAS.

Liang Q.,Northumbria University
Journal of Hydraulic Engineering | Year: 2010

This work extends and improves a one-dimensional shallow flow model to two-dimensional (2D) for real-world flood simulations. The model solves a prebalanced formulation of the fully 2D shallow water equations, including friction source terms using a finite volume Godunov-type numerical scheme. A reconstruction method ensuring nonnegative depth is used along with a Harten, Lax, and van Leer approximate Riemann solver with the contact wave restored for calculation of interface fluxes. A local bed modification method is proposed to maintain the well-balanced property of the algorithm for simulations involving wetting and drying. Second-order accurate scheme is achieved by using the slope limited linear reconstruction together with a Runge-Kutta time integration method. The model is applicable to calculate different types of flood wave ranging from slow-varying inundations to extreme and violent floods, propagating over complex domains including natural terrains and dense urban areas. After validating against an analytical case of flow sloshing in a domain with a parabolic bed profile, the model is applied to simulate an inundation event in a 36 km 2 floodplain in Thamesmead near London. The numerical predictions are compared with analytical solutions and alternative numerical results. © 2010 ASCE.

Benniston A.C.,Northumbria University
Philosophical transactions. Series A, Mathematical, physical, and engineering sciences | Year: 2013

Here, we recognize the growing significance of miniaturized devices as medical diagnostic tools and highlight the need to provide a convenient means of powering such instruments when implanted into the body. One of the most promising approaches to this end involves using a light-collection facility to absorb incident white light and transfer the photonic energy to a tiny semiconductor embedded on the device. Although fluorescent organic molecules offer strong potential as modules for such solar collectors, we emphasize the promise offered by transition metal complexes. Thus, an extended series of binuclear Ru(II)/Os(II) poly(pyridine) complexes has been shown to be highly promising sensitizers for amorphous silicon solar cells. These materials absorb a high fraction of visible light while the Ru(II)-based units possess triplet energies that are comparable to those of the naphthalene-based bridge. The metal complex injects a triplet exciton into the bridge and this, in turn, is trapped by the Os(II)-based terminal. The result is extremely efficacious triplet-energy transfer; at room temperature the rate of energy transfer is independent of distance over some 6 nm and only weakly dependent on temperature.

Burgess J.G.,Northumbria University
Current Opinion in Biotechnology | Year: 2012

Marine biotechnology is the industrial, medical or environmental application of biological resources from the sea. Since the marine environment is the most biologically and chemically diverse habitat on the planet, marine biotechnology has, in recent years delivered a growing number of major therapeutic products, industrial and environmental applications and analytical tools. These range from the use of a snail toxin to develop a pain control drug, metabolites from a sea squirt to develop an anti-cancer therapeutic, and marine enzymes to remove bacterial biofilms. In addition, well known and broadly used analytical techniques are derived from marine molecules or enzymes, including green fluorescence protein gene tagging methods and heat resistant polymerases used in the polymerase chain reaction. Advances in bacterial identification, metabolic profiling and physical handling of cells are being revolutionised by techniques such as mass spectrometric analysis of bacterial proteins. Advances in instrumentation and a combination of these physical advances with progress in proteomics and bioinformatics are accelerating our ability to harness biology for commercial gain. Single cell Raman spectroscopy and microfluidics are two emerging techniques which are also discussed elsewhere in this issue. In this review, we provide a brief survey and update of the most powerful and rapidly growing analytical techniques as used in marine biotechnology, together with some promising examples of less well known earlier stage methods which may make a bigger impact in the future. © 2012 .

Diffey B.L.,Northumbria University
British Journal of Nutrition | Year: 2013

A mathematical model is described for estimating changes in plasma 25-hydroxyvitamin D (25(OH)D) levels throughout the year as a consequence of varying the oral intake of vitamin D and the behaviour outdoors of white British adults resident in different regions of the UK. The model yields seasonal and geographical patterns of 25(OH)D concentrations that agree closely with observational studies. Use of the model allows estimates to be easily made of the sun exposure and oral intake necessary to avoid vitamin D deficiency in defined proportions of the population, as well as strategies that would lead to vitamin D sufficiency throughout the year. The analysis demonstrates that addressing concerns about insufficient vitamin D levels, especially during the winter, may be achieved by modifying oral vitamin D intake over the winter, increasing summer sun exposure or a combination of both. © 2013 The Authors.

Brownlee I.A.,Northumbria University
Food Hydrocolloids | Year: 2011

The term dietary fibre (indigestible carbohydrates of plant origin) encompasses a range of divergent compounds that differentially affect numerous important gastrointestinal and systemic bodily processes. The main role of the gut is to absorb nutrients following digestion. Complex neurohumoral pathways control gut secretion and motility. Dietary fibres that inhibit intestinal digestive processes result in decreased upper GI transit times, which may affect satiety and satiation. The large intestine houses a varied microflora. Dietary fibre is a major energy source for these bacteria, and therefore markedly affects microfloral diversity/toxicity. Dietary fibres can also affect innate immune responses of the gut mucosa both directly and indirectly. Dietary fibre impacts all processes of the gut, which as a result may impact on cardiovascular/systemic health. As many commonly-used hydrocolloids are viscous, palatable dietary fibres, they have the potential to be used in acceptable foodstuffs that offer a wide range of added health benefits. © 2009.

Deckers J.,Northumbria University
Journal of Bioethical Inquiry | Year: 2013

Partly in response to rising rates of obesity, many governments have published healthy eating advice. Focusing on health advice related to the consumption of animal products (APs), I argue that the individualistic paradigm that prevails must be replaced by a radically new approach that emphasizes the duty of all human beings to restrict their negative "Global Health Impacts" (GHIs). If they take human rights seriously, many governments from nations with relatively large negative GHIs-including the Australian example provided here-must develop strategies to reduce their citizens' negative GHIs. As the negative GHIs associated with the consumption of many APs are excessive, it is my view that many governments ought to adopt a qualified ban on the consumption of APs. © 2012 Springer Science+Business Media Dordrecht.

Ziessel R.,University of Strasbourg | Harriman A.,Northumbria University
Chemical Communications | Year: 2011

Electronic energy transfer (EET) plays a critical role in many biological processes and is used by nature to direct energy to a site where chemical reactions need to be initiated. Such EET can occur over large distances and can involve many individual molecules of identical, similar or disparate chemical identity. Advances in spectroscopy and data processing have allowed the rates of EET to be measured on extremely fast timescales such that improved mechanistic insight becomes feasible. At the same time, highly sophisticated synthetic operations have been devised that facilitate the isolation and purification of elaborate multi-component molecular arrays. A key feature of these arrays concerns the logical positioning of individual units in a way that favours directed EET along the molecular axis or along some other preferred pathway. The availability of these novel molecular materials allows close examination of popular theoretical models and paves the way for the development of advanced molecular sensors, artificial light harvesters, fluorescent labels and sensitizers. Of particular interest is the spectacular growth in the application of boron dipyrromethene dyes as basic reagents in such artificial photon collectors and these compounds have dominated the market in recent years because of their synthetic versatility and valuable photophysical properties. In this article, recent developments in the field are highlighted in terms of synthesis and subsequent spectroscopic exploration. © The Royal Society of Chemistry 2011.

Mathers J.C.,Northumbria University
Proceedings of the Nutrition Society | Year: 2013

Over the past two centuries human life expectancy has increased by nearly 50 years. Genetic factors account for about one-third of the variation in life expectancy so that most of the inter-individual variation in lifespan is explained by stochastic and environmental factors, including diet. In some model organisms, dietary (energy) restriction is a potent, and highly reproducible, means of increasing lifespan and of reducing the risk of age-related dysfunction although whether this strategy is effective in human subjects is unknown. This is ample evidence that the ageing process is plastic and research demonstrates that ageing is driven by the accumulation of molecular damage, which causes the changes in cell and tissue function that characterise the ageing phenotype. This cellular, tissue and organ damage results in the development of age-related frailty, disabilities and diseases. There are compelling observational data showing links between eating patterns, e.g. The Mediterranean dietary pattern, and ageing. In contrast, there is little empirical evidence that dietary changes can prolong healthy lifespan and there is even less information about the intervention modalities that can produce such sustainable dietary behaviour changes. In conclusion, current research needs include (1) a better understanding of the causal biological pathways linking diet with the ageing trajectory, (2) the development of lifestyle-based interventions, including dietary changes, which are effective in preventing age-related disease and disability and (3) the development of robust markers of healthy ageing, which can be used as surrogate outcome measures in the development and testing of dietary interventions designed to enhance health and well-being long into old age. Copyright © The Author 2013.

The objective of this paper is to compare the topology and the emerging urban geographies of two infrastructural networks across European cities: the international intercity Internet backbone and aviation networks. Both of them are facilitators of the knowledge economy and contribute to what was identified by Castells as the first layer of the space of flows, supporting the world city process. In order to compare them, network analysis methods and complex networks theory are employed. The results indicate the different attributes of these networks, the lack of scale-free characteristics but also the different roles different cities perform in these networks. © 2011 Pion Ltd and its Licensors.

Objectives: To describe the patterns and trends in waist circumference and abdominal obesity for those aged 70-89 contrasting the standard and new age-related cut-points, and to investigate how they vary with time, age and educational level. Methods: The subjects were 7129 men and 9244 women aged 70-89 years who participated in the Health Survey for England during 1993-2010. The outcome measures were the percentiles of waist circumference and standard and new indicators of abdominal obesity based on waist circumference. Binomial and quantile regression were used to investigate the relationship with key explanatory variables. Results: The distribution of waist circumference among community-dwelling older adults in England has shifted upwards since 1993 (an increase in median of 4.5 cm in men and 5.1 cm in women). The prevalence of abdominal obesity has increased, while those in the low-risk group have decreased. Abdominal obesity was higher in those aged 70-79 compared to 80-89, and in those who left education earlier. The prevalence of abdominal obesity varies considerably with new and standard cut-points, which makes it impractical to use the new ones on a population that includes subjects across the adult age range. Conclusions: Obesity is increasing among the elderly, but more work is needed on devising age-appropriate indicators of high risk based on waist circumference. © 2012 Denise Howel.

Taylor R.,Northumbria University | Holman R.R.,University of Oxford
Clinical Science | Year: 2015

Type 2 diabetes (T2DM) is frequently regarded as a disease of obesity and its occurrence in individuals of normal body mass index (BMI) is often regarded as indicating a non-obesity-related subtype. However, the evidence for such a distinct, common subtype is lacking. The United Kingdom Prospective Diabetes Study (UKPDS) cohort of people diagnosed with T2DM in the 1970s and 1980s had a median BMI of only 28 kg/m2. UKPDS data form the basis of current understanding of the condition even though one in three of those studied had a BMI of less than 25 kg/m2. BMI, though, is a population measure and not a rigid personal guide. Weight loss is considered de rigueur for treating obese diabetic individuals, but it is not usually considered for those deemed to have a normal BMI. Given the new evidence that early T2DM can be reversed to normal glucose tolerance by substantial weight loss, it is important to explain why non-overweight people respond to this intervention as well as obese individuals. We hypothesize that each individual has a personal fat threshold (PFT) which, if exceeded, makes likely the development of T2DM. Subsequent weight loss to take the individual below their level of susceptibility should allow return to normal glucose control. Crucially, the hypothesized PFT is independent of BMI. It allows both understanding of development of T2DM in the non-obese and remission of diabetes after substantial weight loss in people who remain obese by definition. To illustrate this concept, we present the distribution curve of BMI at diagnosis for the UKPDS cohort, together with a diagram explaining individual behaviour within the population. The concept of PFT is of practical benefit in explaining the onset of diabetes and its logical management to the non-obese majority of people with T2DM. © The Authors Journal compilation © 2015 Biochemical Society.

Silberberg D.,University of Pennsylvania | Anand N.P.,U.S. National Institutes of Health | Michels K.,U.S. National Institutes of Health | Kalaria R.N.,Northumbria University
Nature | Year: 2015

This is an exciting time for scientific discovery that aims to reduce the frequency and impact of neurological, mental health and substance-use disorders. As it became increasingly clear that low-and middle-income countries have a disproportionate share of these disorders, and that many of the problems are best addressed by indigenous researchers who can seek context-sensitive solutions, the US National Institutes of Health and other research funders began to invest more in low-and middle-income country-focused research and research capacity-building to confront this significant public health challenge. In an effort to identify existing information, knowledge gaps, and emerging research and research capacity-building opportunities that are particularly relevant to low-and middle-income countries, in February 2014 the Center for Global Health Studies at the National Institutes of Health Fogarty International Center held a workshop to explore these issues with scientific experts from low-and middle-income countries and the United States. This evolved into the preparation of the Reviews in this supplement, which is designed to highlight opportunities and challenges associated with topical areas in brain-disorders research over the coming decade. This Introduction highlights some of the over-arching and intersecting priorities for addressing causes, prevention, treatment and rehabilitation as well as best practices to promote overall nervous system health. We review some brain disorders in low-and middle-income countries, while the Reviews describe relevant issues and the epidemiology of particular conditions in greater depth.This article has not been written or reviewed by Nature editors. Nature accepts no responsibility for the accuracy of the information provided.

Gao Z.,Northumbria University
IEEE Transactions on Industrial Electronics | Year: 2015

Unknown measurement delays usually degrade system performance and even damage a system under output feedback control, which motivate us to develop an effective method to attenuate or offset the adverse effect from the measurement delays. In this paper, an augmented observer is proposed for discrete-time Lipschitz nonlinear systems subjected to unknown measurement delays, enabling a simultaneous estimation for system states and perturbed terms caused by output delays. On the basis of the estimates, a sensor compensation technique is addressed to remove the influence from the measurement delays to the system performance. Furthermore, an integrated robust estimation and compensation technique is proposed to decouple constant piecewise disturbances, attenuate other disturbances/noise, and offset the adverse effect caused by the measurement delays. The proposed methods are applied to a two-stage chemical reactor with delayed recycle and to an electromechanical servosystem, which demonstrate the effectiveness of the present techniques. © 1982-2012 IEEE.

Rowe C.,Northumbria University | Healy S.D.,University of St. Andrews
Behavioral Ecology | Year: 2014

Across a range of disciplines, researchers are becoming increasingly interested in studying the variation in cognitive abilities found within populations. Behavioral ecology is no exception: the pursuit to understand the evolution of cognition has lead to a rapidly expanding literature that uses various tasks to measure individuals' cognitive abilities. While this is an exciting time, we are concerned that without being clearer as to the cognitive abilities under test it will be difficult to design appropriate experiments and the interpretation of the data may be unsound. The aim of this review is 3-fold: 1) to highlight problems with designing tasks for measuring individual variation in cognitive abilities and interpreting their outcomes; 2) to increase awareness that noncognitive factors can cause variation in performance among individuals; and 3) to question the theoretical basis for thinking that performance in any cognitive task should necessarily correlate with a measure of fitness. Our take-home message is that variability in performance in cognitive tasks does not necessarily demonstrate individual variation in cognitive ability, and that we need to both design more stringent cognitive tests and be more cautious in their interpretation. © 2014 International Society for Behavioral Ecology. All rights reserved.

De Schepper S.,University of Bergen | Gibbard P.L.,University of Cambridge | Salzmann U.,Northumbria University | Ehlers J.,Hellberg 2a
Earth-Science Reviews | Year: 2014

The Pliocene climate is globally warm and characterised by high atmospheric carbon dioxide concentrations, yet the terrestrial and marine scientific communities have gathered considerable evidence for substantial glaciation events in both the Northern and Southern Hemisphere prior to the Quaternary. Evidence on land is fragmentary, but marine records of glaciation present a more complete history of Pliocene glaciation. Here we present a global compilation of the terrestrial and marine glacial evidence for the Pliocene and demonstrate four glaciation events that can be identified in the Southern and/or Northern Hemisphere prior to the latest Pliocene intensification of Northern Hemisphere glaciation. There are two globally recognisable glacial events in the early Pliocene (c. 4.9-4.8. Ma and c. 4.0. Ma), one event around the early/late Pliocene transition (c. 3.6. Ma), and one event during Marine Isotope Stage M2 (c. 3.3. Ma). Long-term climate cooling, decreasing carbon dioxide concentrations in the atmosphere and high climate sensitivity in the Pliocene probably facilitated each glaciation event, however the mechanisms behind the early Pliocene glacial events are unclear. The global glaciation at c. 3.3. Ma may be caused by changes in ocean gateways, whereas the decline in carbon dioxide concentrations is important for the latest Pliocene intensification of Northern Hemisphere glaciation. © 2014 Elsevier B.V.

Franks J.R.,Northumbria University
Food Policy | Year: 2014

Sustainable intensification (SI) is a term that has increasingly been used to describe the agricultural production systems that will be needed to feed a growing global population whilst ensuring adequate ecosystem service provision. However, key definitions of SI support quite different approaches; a report published by the Royal Society (Baulcombe et al., 2009) favours the land sparing model whilst a Foresight report (2011) favours land sharing. SI will require pragmatic and innovative policies, including further revision of the Environmental Stewardship Scheme and the development of landscape-scale governance within an over-arching strategic approach to planning. However, its innovation is its focus on unlocking the social at the expense of the private value of land (at those locations where non-market ecosystem services have a higher value than marketable agricultural products). Though scientific advances may help raise production efficiency through a better understanding of the trade-offs between agricultural production and ecosystem service provision, issues related to who controls the use of land will be the most difficult to resolve, which suggests a role for Boundary Organisational Theory (BOT) because of the insights this theory lends to negotiating complex problems. Within BOT terminology SI can be considered a "boundary object" about which stakeholders are able to negotiate site-specific issues to incrementally arrive at solutions which draw on the full range of land sharing and land sparing options and so avoid prescriptive approaches and technologies. © 2014 Elsevier Ltd.

Hallinan J.S.,Northumbria University
Methods in Microbiology | Year: 2013

The large-scale engineering of novel bacterial systems is a complex, challenging task. Although small circuits can be designed manually, using the domain knowledge of the designer, this approach is not feasible for designs involving multiple pathways or even complete genomes. In this chapter, we address the value of computational intelligence approaches to the design of synthetic genetic circuits. Computational intelligence algorithms were designed to operate in complex, poorly understood domains in which the quality of a solution is more important than the route taken to achieve it and, as such, are potentially valuable to synthetic biology. To date, evolutionary computation has been used extensively in this field, but other computational intelligence algorithms, of potentially equal value, have been neglected. We review the basic principles of these algorithms and the way in which they have been, and may in the future be, of value in synthetic biology. © 2013 Elsevier Ltd.

Jenkins K.,Northumbria University
Extractive Industries and Society | Year: 2014

This critical review argues that the experiences and perspectives of women in relation to the extractive industries have often been absent from analysis of the impacts of mining in the global South. This paper therefore explores the ways in which women in developing countries are affected by the expansion of extractive industries, bringing together a dispersed literature, scattered across disciplines and relating to geographically diverse locations, in order to provide a comprehensive overview of key debates in relation to women and mining, and generate momentum for a new research agenda in this area. The review concentrates on four key intersecting areas - women as mineworkers; the gendered impacts of mining, and specifically the disproportionately negative impacts on women; women's changing roles and identities in communities affected by mining; and finally gendered inequalities in relation to the benefits of mining. © 2014 Elsevier Ltd.

Grunze H.C.R.,Northumbria University
Journal of Mental Health | Year: 2010

Anticonvulsant drugs are widely used in psychiatric indications. This includes alcohol and benzodiazepine withdrawal symptoms, panic and anxiety disorders, dementia, schizophrenia, and to some extent personality disorders. Besides pain syndromes, their main domain outside epilepsy, however, is bipolar disorder. Carbamazepine, valproate, and lamotrigine are meanwhile recognized mood stabilizers, but several other antiepileptic drugs have also been tried out with diverging or inconclusive results. Understanding the mechanisms of action and identifying similarities between anticonvulsants effective in bipolar disorder may also enhance our understanding of the underlying pathophysiology of the disorder. © 2010 Informa UK Ltd.

Smith K.,Northumbria University | Wonnacott E.,University of Oxford
Cognition | Year: 2010

Human languages may be shaped not only by the (individual psychological) processes of language acquisition, but also by population-level processes arising from repeated language learning and use. One prevalent feature of natural languages is that they avoid unpredictable variation. The current work explores whether linguistic predictability might result from a process of iterated learning in simple diffusion chains of adults. An iterated artificial language learning methodology was used, in which participants were organised into diffusion chains: the first individual in each chain was exposed to an artificial language which exhibited unpredictability in plural marking, and subsequent learners were exposed to the language produced by the previous learner in their chain. Diffusion chains, but not isolate learners, were found to cumulatively increase predictability of plural marking by lexicalising the choice of plural marker. This suggests that such gradual, cumulative population-level processes offer a possible explanation for regularity in language. © 2010 Elsevier B.V.

Errington J.,Northumbria University
Nature Reviews Microbiology | Year: 2015

Work over the past decade has highlighted the pivotal role of the actin-like MreB family of proteins in the determination and maintenance of rod cell shape in bacteria. Early images of MreB localization revealed long helical filaments, which were suggestive of a direct role in governing cell wall architecture. However, several more recent, higher-resolution studies have questioned the existence or importance of the helical structures. In this Opinion article, I navigate a path through these conflicting reports, revive the helix model and summarize the key questions that remain to be answered. © 2015 Macmillan Publishers Limited.

Optimal design of a standalone wind-PV-diesel hybrid system is a multi-objective optimisation problem with conflicting objectives of cost and reliability. Uncertainties in renewable resources, demand load and power modelling make deterministic methods of multi-objective optimisation fall short in optimal design of standalone hybrid renewable energy systems (HRES). Firstly, deterministic methods of analysis, even in the absence of uncertainties in cost modelling, do not predict the levelised cost of energy accurately. Secondly, since these methods ignore the random variations in parameters, they cannot be used to quantify the second objective, reliability of the system in supplying power. It is shown that for a given site and uncertainties profile, there exist an optimum margin of safety, applicable to the peak load, which can be used to size the diesel generator towards designing a cost-effective and reliable system. However, this optimum value is problem dependent and cannot be obtained deterministically. For two design scenarios, namely, finding the most reliable system subject to a constraint on the cost and finding the most cost-effective system subject to constraints on reliability measures, two algorithms are proposed to find the optimum margin of safety. The robustness of the proposed design methodology is shown through carrying out two design case studies. © 2014 Elsevier Ltd.

Serinaldi F.,Northumbria University | Serinaldi F.,A+ Network
Energy Economics | Year: 2011

In the context of the liberalized and deregulated electricity markets, price forecasting has become increasingly important for energy company's plans and market strategies. Within the class of the time series models that are used to perform price forecasting, the subclasses of methods based on stochastic time series and causal models commonly provide point forecasts, whereas the corresponding uncertainty is quantified by approximate or simulation-based confidence intervals. Aiming to improve the uncertainty assessment, this study introduces the Generalized Additive Models for Location, Scale and Shape (GAMLSS) to model the dynamically varying distribution of prices. The GAMLSS allow fitting a variety of distributions whose parameters change according to covariates via a number of linear and nonlinear relationships. In this way, price periodicities, trends and abrupt changes characterizing both the position parameter (linked to the expected value of prices), and the scale and shape parameters (related to price volatility, skewness, and kurtosis) can be explicitly incorporated in the model setup. Relying on the past behavior of the prices and exogenous variables, the GAMLSS enable the short-term (one-day ahead) forecast of the entire distribution of prices. The approach was tested on two datasets from the widely studied California Power Exchange (CalPX) market, and the less mature Italian Power Exchange (IPEX). CalPX data allow comparing the GAMLSS forecasting performance with published results obtained by different models. The study points out that the GAMLSS framework can be a flexible alternative to several linear and nonlinear stochastic models. © 2011 Elsevier B.V.

Perry E.,Northumbria University | Howes M.-J.R.,Jodrell Laboratory
CNS Neuroscience and Therapeutics | Year: 2011

An escalating "epidemic" of diseases like Alzheimer's has not yet been met by effective symptomatic treatments or preventative strategies. Among a few current prescription drugs are cholinesterase inhibitors including galantamine, originating from the snowdrop. Research into ethnobotanicals for memory or cognition has burgeoned in recent years. Based on a multi-faceted review of medicinal plants or phytochemicals, including traditional uses, relevant bioactivities, psychological and clinical evidence on efficacy and safety, this overview focuses on those for which there is promising clinical trial evidence in people with dementia, together with at least one other of these lines of supporting evidence. With respect to cognitive function, such plants reviewed include sage, Ginkgo biloba, and complex mixtures of other traditional remedies. Behavioral and psychological symptoms of dementia (BPSD) challenge carers and lead to institutionalization. Symptoms can be alleviated by some plant species (e.g., lemon balm and lavender alleviate agitation in people with dementia; St John's wort treats depression in the normal population). The ultimate goal of disease prevention is considered from the perspective of limited epidemiological and clinical trial evidence to date. The potential value of numerous plant extracts or chemicals (e.g., curcumin) with neuroprotective but as yet no clinical data are reviewed. Given intense clinical need and carer concerns, which lead to exploration of such alternatives as herbal medicines, the following research priorities are indicated: investigating botanical agents which enhance cognition in populations with mild memory impairment or at earliest disease stages, and those for BPSD in people with dementia at more advanced stages; establishing an ongoing authoritative database on herbal medicine for dementia; and further epidemiological and follow up studies of promising phytopharmaceuticals or related nutraceuticals for disease prevention. © 2010 Blackwell Publishing Ltd.

Finlay M.R.V.,Astrazeneca | Griffin R.J.,Northumbria University
Bioorganic and Medicinal Chemistry Letters | Year: 2012

Modulation of DNA repair pathways in oncology has been an area of intense interest in the last decade, not least as a consequence of the promising clinical activity of poly(ADP-ribose) polymerase (PARP) inhibitors. In this review article, we highlight inhibitors of the phosphatidylinositol 3-kinase related kinase (PIKK) family as of potential interest in the treatment of cancer, both in combination with DNA-damaging therapies and as stand-alone agents. © 2012 Elsevier Ltd. All rights reserved.

Cao Y.-C.,Northumbria University
Journal of Colloid and Interface Science | Year: 2012

In this work, a method to prepare a thermally stable QDs/clay powder is reported. First, several water soluble CdTe QDs characterised by different size-dependent emission wavelengths were synthesised through wet chemistry. Montmorillonite-Na + clay in water was dispersed into a muddy suspension by sonication. Then, the clay-water suspension was used as the host media for CdTe QDs to prepare the QDs/clay powder by freeze drying. The experiments showed that QDs/clay powder could be re-dispersed in water without changing the luminescent property of the QDs; this process was reversible. EDX showed that Cd and Te elements existed in the QDs/clay powder and the XRD tests showed that the clay [001] reflection peaks for raw clay, QDs (λ em=514nm)/clay and QDs (λ em=560nm)/clay were the same, namely 2θ=7.4°. Finally, QDs/clay powder was applied to the HDPE polymer extrusion process at 200°C to produce thin films; the resultant QDs-polymer nanocomposite film exhibited strong fluorescence. © 2011 Elsevier Inc.

Kim J.S.,Seoul National University of Science and Technology | Kaiser M.,Northumbria University
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2014

The connectome, or the entire connectivity of a neural system represented by a network, ranges across various scales from synaptic connections between individual neurons to fibre tract connections between brain regions. Although the modularity they commonly show has been extensively studied, it is unclear whether the connection specificity of such networks can already be fully explained by the modularity alone. To answer this question, we study two networks, the neuronal network of Caenorhabditis elegans and the fibre tract network of human brains obtained through diffusion spectrum imaging. We compare them to their respective benchmark networks with varying modularities, which are generated by link swapping to have desired modularity values. We find several network properties that are specific to the neural networks and cannot be fully explained by the modularity alone. First, the clustering coefficient and the characteristic path length of both C. elegans and human connectomes are higher than those of the benchmark networks with similar modularity. High clustering coefficient indicates efficient local information distribution, and high characteristic path length suggests reduced global integration. Second, the total wiring length is smaller than for the alternative configurations with similar modularity. This is due to lower dispersion of connections, which means each neuron in the C. elegans connectome or each region of interest in the human connectome reaches fewer ganglia or cortical areas, respectively. Third, both neural networks show lower algorithmic entropy compared with the alternative arrangements. This implies that fewer genes are needed to encode for the organization of neural systems. While the first two findings show that the neural topologies are efficient in information processing, this suggests that they are also efficient from a developmental point of view. Together, these results show that neural systems are organized in such a way as to yield efficient features beyond those given by their modularity alone. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Morton R.J.,Northumbria University
Astronomy and Astrophysics | Year: 2014

Aims. The observation of propagating magneto-hydrodynamic kink waves in magnetic structures and measurement of their properties (amplitude, phase speed) can be used to diagnose the plasma conditions in the neighbourhood of the magnetic structure via magneto-seismology. We aim to reveal properties of the chromosphere/transition region above the sunspot penumbra using this technique. Methods. Hinode SOT observed a sunspot as it was crossing over the limb, providing a unique side on view of the atmosphere above a sunspot. The presence of large spicule-like jets is evident in Ca ii H images. The jets are found to support transverse wave motions that displace the central axis of the spicules, which can be interpreted as the kink wave. The properties of a specific wave event are measured and used to determine the magnetic and density stratification along the structure. In addition, we measure the width of the spicule and the intensity profile along the structure in order to provide a test for the magneto-seismological results. Results. The measurements of the wave properties reveal an initial rapid increase in amplitude with height above the solar surface, followed by a decrease in amplitude. The magneto-seismological inversions suggests this initial increase corresponds to large changes in density and magnetic field strength. In addition, we provide the first measurements of spicule width with height, which confirm that the spicule under goes rapid expansion. The measured rates of expansion show good agreement with the results from the magneto-seismology. The observed rapid variations in plasma parameters are suggested to be partly due to the presence of a gravitational stratified, ambient atmosphere. Combining width measurements with phase speed measurements implies the observed decrease in wave amplitude at greater heights can be explained by wave damping. Hence, we provide the first direct evidence of wave damping in chromospheric spicules and the quality factor of the damping is found to be significantly smaller than estimated coronal values. © 2014 ESO.

Wyatt T.,Northumbria University
Crime, Law and Social Change | Year: 2014

Transnational environmental crime is a global problem encompassing not only criminal violations of the law, but harms against the environment and the people reliant upon it as a natural resource. Grounded in the green criminological theory of eco-global criminology, this paper explores the transnational environmental crime of the illegal timber trade in the Russian Far East unpicking the threats to ecological well-being and the global nature and impacts of this crime. In researching transnational environmental crime, it is crucial to uncover the distinct local and regional variations of the forces at play; for this paper that means analyzing the role of organized crime and corruption in Russia's timber black market. This information was obtained by using the current literature and interviews with Russian and international experts in order to uncover the role of these actors in the harvesting, smuggling and selling of timber. From this exploration, a structure of the illegal timber trade in this region is proposed including at which points along the black market chain organized crime and/or corruption are involved. Additionally, from an eco-global criminological foundation this paper analyzes the consequences to Russia's people, its environment and the global community if the illegal timber trade is to continue in its current state. © 2013 Springer Science+Business Media Dordrecht.

Meechan J.G.,Northumbria University
Journal of the American Dental Association (1939) | Year: 2011

The author describes the use of the infiltration anesthetic technique to anesthetize mandibular teeth in adults and explores its mechanism of action. The author reviewed articles describing randomized controlled trials of the mandibular infiltration anesthetic technique in healthy participants. The author found that using the mandibular infiltration anesthetic technique can produce anesthesia in adult mandibular teeth. The success was dose dependent and the choice of anesthetic solution was significant; 4 percent articaine with 1:100,000 epinephrine was more effective than 2 percent lidocaine with 1:100,000 epinephrine. Combining buccal and lingual infiltrations increased success in the mandibular incisor region. The success of the mechanism of infiltration of anesthetic at the mandibular first molar appeared to depend on the mental foramen. The mandibular infiltration anesthetic technique is an effective method of anesthetizing mandibular incisors. Four percent articaine with epinephrine appears to be the preferred solution. The choice of anesthetic solution is important when using the infiltration anesthetic technique in the adult mandible.

Ames C.,Institute of Psychiatry | Fletcher-Watson S.,Northumbria University
Developmental Review | Year: 2010

Atypical attention, while not a diagnostic feature, is common in individuals with autism spectrum disorders (ASD). The study of these atypicalities has recently gained in both quantity and quality, due in part to an increased focus on attentional atypicalities as one of the earliest signs of ASD in infancy. A range of attentional processes and components have been investigated, and the methods used are varied, from Posner-type paradigms, to the more recent use of eye-movement recording and change-detection techniques. This methodological complexity is one factor in the production of conflicting evidence on the topic of attention in ASD. This review uses a focus on methodology to clarify the literature to date and provide a resource for researchers wishing to study attention in ASD. Other factors that have contributed to the current discrepancies in findings are discussed, particularly the role of individual and group differences within the population of people with ASD. © 2010 Elsevier Inc. All rights reserved.

Renfree A.,University of Worcester | Martin L.,University of Worcester | Micklewright D.,University of Essex | St Clair Gibson A.,Northumbria University
Sports Medicine | Year: 2014

Successful participation in competitive endurance activities requires continual regulation of muscular work rate in order to maximise physiological performance capacities, meaning that individuals must make numerous decisions with regards to the muscular work rate selected at any point in time. Decisions relating to the setting of appropriate goals and the overall strategic approach to be utilised are made prior to the commencement of an event, whereas tactical decisions are made during the event itself. This review examines current theories of decision-making in an attempt to explain the manner in which regulation of muscular work is achieved during athletic activity. We describe rational and heuristic theories, and relate these to current models of regulatory processes during self-paced exercise in an attempt to explain observations made in both laboratory and competitive environments. Additionally, we use rational and heuristic theories in an attempt to explain the influence of the presence of direct competitors on the quality of the decisions made during these activities. We hypothesise that although both rational and heuristic models can plausibly explain many observed behaviours in competitive endurance activities, the complexity of the environment in which such activities occur would imply that effective rational decision-making is unlikely. However, at present, many proposed models of the regulatory process share similarities with rational models. We suggest enhanced understanding of the decision-making process during self-paced activities is crucial in order to improve the ability to understand regulation of performance and performance outcomes during athletic activity. © 2013 Springer International Publishing Switzerland.

Sutcliffe I.C.,Northumbria University
Trends in Microbiology | Year: 2010

Improved understanding of the bacterial phylogenetic tree has allowed the distinction of at least 25 phyla with cultured representatives. This review surveys the diversity of cell envelope types present in these phyla and emphasises that it is important to define bacterial cell envelopes according to whether they have one (monoderm) or two (diderm) cellular membranes and, in the latter case, lipopolysaccharide as well. A comparative genomics approach, facilitated by the recent vast expansion in genome sequence information, is used here to survey the distribution of key lipopolysaccharide biosynthesis enzymes across the bacterial world and to consider alternative diderm cell envelope architectures. These data add to our understanding of microbial diversity and it is notable that the majority of phyla are likely to comprise diderm, lipopolysaccharide containing bacteria. This analysis and a critical review of the literature also suggest that members of the phylum Chloroflexi are typically monoderm. © 2010 Elsevier Ltd.

Manning D.A.C.,Northumbria University
Proceedings of the Geologists' Association | Year: 2015

By 2050, the world's population will have reached 9 billion. To feed that many people, soil fertility will have to be maintained artificially. All fertiliser materials depend on a geological resource: nitrogen (N) fertilizer production needs fossil fuels, and both phosphate (P) and potassium (K) are derived by mining. Irrespective of new biological techniques in plant breeding and genetic modification, soils still need to supply the mineral nutrients that plants require, and these are exported from soil with every harvest.Studies of global offtake of N, P and K from soils through crop production show that although N and P are roughly in balance, removal of K from soils greatly exceeds inputs. World mine production of K needs to double to replace the amount removed in crops. Recent revision of reserve estimates for potash and phosphate rock show significant increases for phosphate rock and reductions for potash. Potash supply is now potentially of much greater concern than phosphate.Against this background, it is clear that new potash mining ventures are required. In the developed world, the supply of potash from conventional sources will continue. However, in other countries the high price of potash means that novel unconventional sources are being considered. K silicate minerals (such as micas, feldspar and nepheline) have the potential to provide an adequate source of K for communities that cannot afford conventional fertiliser. However, it is not the total K content of these materials that controls their ability to supply plant nutrients, but the rate at which they dissolve. © 2015 The Geologists' Association.

Benwell M.C.,Northumbria University
Transactions of the Institute of British Geographers | Year: 2016

Young people's geopolitical subjectivities are heavily informed by past events in ways that have not been sufficiently acknowledged in the existing literature on youth geopolitics. This paper demonstrates how work on memory can be brought into dialogue with critical geopolitics to identify the assemblage of socio-spatial practices that shape how young people learn about geopolitics. It interrogates what memories and their attendant landscape manifestations and rituals 'do' to young people growing up in the Falkland Islands, a society that continues to live with the legacies of a sovereignty dispute that triggered the Falklands War just over 30 years ago. Young Islanders' embodied and relational encounters with memory through the surrounding environment and adults are shown to play an important role in shaping their perceptions of contemporary geopolitical relations with Argentina. These can both reproduce and/or rework collective memory narratives, emphasising the importance of looking beyond mnemonic discourses manifest in institutional and official spaces. The paper makes a conceptual contribution to debates about young people's agency in relation to geopolitics. While children and young people are considered active agents capable of forming their own views, they are also presented with potent memories of past geopolitical eras that propagate certain understandings of international relations. Engaging scholarship on memory can help address the tensions inherent to recognising children and young people as social and (geo)political actors, within the context of structures, institutions and relationships that have a strong bearing on how their agency is expressed. In a methodological sense the paper illustrates how research might productively incorporate the adults who are influential in the formation of young people's geopolitical subjectivities. © 2016 Royal Geographical Society (with the Institute of British Geographers).

Mackinnon D.,Northumbria University
Geographical Journal | Year: 2015

Devolution has become a key 'global trend' over recent decades as many states have decentralised power to sub-state governments. The UK resisted this trend until the late 1990s when devolution was enacted by the then Labour Government, taking a highly asymmetrical form in which different territories have been granted different powers and institutional arrangements. Devolution allows the devolved governments to develop policies that are tailored to the needs of their areas, encouraging policy divergence, although this is countered by pressures to ensure that devolved approaches do not contradict those of the central state, promoting convergence. This review paper aims to assess the unfolding dynamics of devolution and policy divergence in the UK, spanning different policy areas such as economic development, health and social policy. The paper emphasises that devolution has altered the institutional landscape of public policy in the UK, generating some high-profile examples of policy divergence, whilst also providing evidence of policy convergence. In addition, the passage of time underlines the nature of UK devolution as an unfolding process. Its underlying asymmetries have become more pronounced as the tendency towards greater autonomy for Scotland and Wales clashes with a highly centralised mode of policymaking in Westminster, the consequences of which have spilt over into the devolved territories in the context of the post-2007 economic crisis through public expenditure cuts. © 2013 Royal Geographical Society (with the Institute of British Geographers).

Lim M.,Northumbria University
Geological Society Memoir | Year: 2014

The aim of this chapter is to provide a review of the recent advances and innovations that have added to the understanding of the cliffs in the British Isles. The chapter introduces the key components of coastal cliff systems, what defines and shapes them and how they have been conceptualized in Britain. The review sets the context for academic research into British coastal cliffs and then focuses on the contributions made to monitoring and modelling cliff changes and the processes that drive them. The chapter concludes with a summary of forthcoming avenues of enquiry and opportunities that have the potential to further knowledge of coastal cliff behaviour in the British Isles and beyond. © The Geological Society of London 2014.

Yang W.,Northumbria University
Journal of Solar Energy Engineering, Transactions of the ASME | Year: 2014

The benefit of wind turbine (WT) can be significantly improved through a well-organized condition-based maintenance strategy. However, such a target has not been fully achieved today. One of the major reasons is lack of an efficient WT condition monitoring system (CMS). The existing WT CMSs often involve high initial capital cost, with complex structure, suffer from inefficient management and show unsatisfactory hardware reliability. So, the operators still have desire for an economical, effective, and reliable CMS for their machines. The work reported in this paper is intended to meet such a demand. Because direct drive permanent magnet (PM) WTs are showing increased market share, but the existing WT CMSs are not designed to deal specifically with this new design, this paper reports on a CM technique dedicated to monitoring the drive train of direct drive WTs. Instead of taking the vibration analysis approach that is being popularly adopted by commercial WT CMSs, a novel CM strategy is researched in this paper by introducing generator electrical signals into WT CM and interpreting them by using a dedicated criterion named instantaneous variance (IV) and Teager-Huang transform (THT), i.e. the generator electrical signals will be evaluated first by using the IV, of which the fault detection capability can be further enhanced with the aid of empirical mode decomposition (EMD). Once an abnormality is detected, then detailed THT analysis of the signal will be conducted for further investigation. The technique has been verified experimentally on a specifically designed WT drive train test rig, on which a PM generator rotates at slow variable speed and is subjected to varying load like a real WT does. Considering the electric subassemblies and rotor blades of direct drive WTs are most vulnerable to damage in practice, rotor unbalance and generator winding faults were emulated on the test rig. Experimental results show that the proposed CM technique is effective in detecting both types of faults occurring in the drive train of direct drive PM WTs. In summary, the proposed CM technique can be identified by (i) the CM is accomplished through analyzing the generator electrical signals without resorting to any other information (e.g. vibro-acoustic). Hence, the data acquisition work will be eased off; (ii) no more transducer other than current and voltage sensors are required. Thus, the cost of the CMS will be significantly reduced; (iii) attributed to the distinguished superiorities of THT to traditional spectral analyses in processing nonlinear signals, the proposed technique is more reliable in interpreting WT CM signals; and (iv) the CM criterion IV has a simple computational algorithm. It is therefore suited to both online and offline WT CM applications. Copyright © 2014 by ASME.

Jennings D.J.,Northumbria University
Animal Behaviour | Year: 2014

Under certain models of animal competition, individuals are expected to gather information about opponent quality in order to determine whether they should fight or withdraw. However, the ability to process complex information differs between individuals and across brain hemispheres: a feature of vertebrate cognition known as lateralization that is not anticipated by contest models. I investigated the relationship between aggressive behaviour and mating success during the fallow deer, Dama dama, rut and a measure of lateralization derived from eye preference during parallel walking. Results show that there was no relationship between the tendency to escalate to fighting or predictability in the tendency to engage in fighting and lateralization. Conversely, there was a quadratic relationship between third-party intervention behaviour and lateralization: the greater the tendency to intervene in ongoing fights the lower the degree of lateralization. However, individuals that showed lateralization for right-eye use were least likely to be targeted by the intervening male; thus lateralization is beneficial in this context because targeted males are highly likely to lose this subsequent encounter. The relationship between lateralization and mating success was also nonlinear: males that showed little evidence for an eye bias during lateral displays had the greatest mating success. Taken together, individuals that showed lateralization benefited from avoiding being targeted after third-party intervention; conversely, individuals that showed little evidence for lateralization actively intervened during ongoing fights and had higher mating success. These results suggest that, although lateralization does appear to confer a fitness advantage on individuals, this is not as extensive as anticipated. © 2014 The Association for the Study of Animal Behaviour.

Armstrong J.L.,Northumbria University
Journal of Investigative Dermatology | Year: 2015

Although the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain <10%. Novel treatment strategies are therefore urgently required, particularly for patients bearing BRAF/NRAS wild-type tumors. Targeting autophagy is a means to promote cancer cell death in chemotherapy-resistant tumors, and the aim of this study was to test the hypothesis that cannabinoids promote autophagy-dependent apoptosis in melanoma. Treatment with Δ9-Tetrahydrocannabinol (THC) resulted in the activation of autophagy, loss of cell viability, and activation of apoptosis, whereas cotreatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro. Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wild-type melanoma xenografts substantially inhibited melanoma viability, proliferation, and tumor growth paralleled by an increase in autophagy and apoptosis compared with standard single-agent temozolomide. Collectively, our findings suggest that THC activates noncanonical autophagy-mediated apoptosis of melanoma cells, suggesting that cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.Journal of Investigative Dermatology advance online publication, 12 March 2015; doi:10.1038/jid.2015.45. © 2015 The Society for Investigative Dermatology, Inc

Flavonoids and other polyphenols are ubiquitous plant chemicals that fulfill a range of ecologic roles for their home plant, including protection from a range of biotic and abiotic stressors and a pivotal role in the management of pathogenic and symbiotic soil bacteria and fungi. They form a natural part of the human diet, and evidence suggests that their consumption is associated with the beneficial modulation of a number of health-related variables, including those related to cardiovascular and brain function. Over recent years, the consensus as to the mechanisms responsible for these effects in humans has shifted away from polyphenols having direct antioxidant effects and toward their modulation of cellular signal transduction pathways. To date, little consideration has been given to the question of why, rather than how, these plant-derived chemicals might exert these effects. Therefore, this review summarizes the evidence suggesting that polyphenols beneficially affect human brain function and describes the current mechanistic hypotheses explaining these effects. It then goes on to describe the ecologic roles and potential endogenous signaling functions that these ubiquitous phytochemicals play within their home plant and discusses whether these functions drive their beneficial effects in humans via a process of "cross-kingdom" signaling predicated on the many conserved similarities in plant, microbial, and human cellular signal transduction pathways. © 2014 American Society for Nutrition.

In this paper, a review is presented of academic literature regarding urban wind speeds for building mounted wind turbines. Site measurement of wind speed requires time and money that often are not available for small micro-generation projects. Research into wind speed estimation for the urban environment has shown that street canyons affect urban wind flow, that wind speed up over the roof ridge is only evident for isolated single buildings, that the wind resource "seen" by a building mounted wind turbine is affected by positioning (height above roof ridge and position relative to the prevailing wind direction), that urban terrain roughness is high, and that adjacent buildings can cause wind shadow. This multiplicity of factors makes it difficult to generalise a wind resource estimation methodology for the urban environment. Scaling factors may prove to be a practical solution, provided the accuracy of their use is well understood. © 2011 Elsevier B.V. All rights reserved.

Prenatal testosterone (PT) effects have been proposed to increase systemizing (the drive to understand lawful input-output relationships), to decrease empathizing (the drive to understand others), and to cause autism via hypermasculinization of the brain. Digit ratio 2D:4D is a putative marker of PT effects in humans. An online study (n=1896) into the relationship between the Reading the Mind in the Eyes Test (a widely used measure of empathizing) and self-measured 2D:4D in a nonclinical sample is reported. No evidence for a link between empathizing and 2D:4D in either females or males emerged. Further, three meta-analyses are presented that look into the relationships of 2D:4D with autism spectrum disorder (ASD), systemizing, and empathizing. 2D:4D was substantially lower (more masculine) in ASD-affected individuals than in normal controls (d=-0.58, P<0.001). However, 2D:4D was found to be virtually unrelated to systemizing and empathizing in normal adults. The results support the idea that high PT is a risk factor for autism, but they challenge the view that PT substantially contributes to sex differences in systemizing and empathizing. Possibly, this pattern reflects an interaction effect, whereby PT drives ASD characteristic changes only in brains with a specific damage. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.

Background:Endometrial cancer (EC) is a hormone-driven disease, and androgen receptor (AR) expression in high-grade EC (HGEC) and metastatic EC has not yet been described.Methods:The expression pattern and prognostic value of AR in relation to oestrogen (ERα and ERβ) and progesterone (PR) receptors, and the proliferation marker Ki67 in all EC subtypes (n=85) were compared with that of healthy and hyperplastic endometrium, using immunohistochemisty and qPCR.Results:Compared with proliferative endometrium, postmenopausal endometrtial epithelium showed significantly higher expression of AR (P<0.001) and ERα (P=0.035), which persisted in hyperplastic epithelium and in low-grade EC (LGEC). High-grade EC showed a significant loss of AR (P<0.0001), PR (P<0.0001) and ERβ (P<0.035) compared with LGEC, whilst maintaining weak to moderate ERα. Unlike PR, AR expression in metastatic lesions was significantly (P=0.039) higher than that in primary tumours. Androgen receptor expression correlated with favourable clinicopathological features and a lower proliferation index. Loss of AR, with/without the loss of PR was associated with a significantly lower disease-free survival (P<0.0001, P<0.0001, respectively).Conclusions:Postmenopausal endometrial epithelium acquires AR whilst preserving other steroid hormone receptors. Loss of AR, PR with retention of ERα and ERβ may promote the unrestrained growth of HGEC. Androgen receptor may therefore be a clinically relevant prognostic indicator and a potential therapeutic target in EC.British Journal of Cancer advance online publication 1 March 2016; doi:10.1038/bjc.2016.16 www.bjcancer.com. © 2016 Cancer Research UK

Tang X.,Tsinghua University | Xu Z.,Tsinghua University | Ghassemlooy Z.,Northumbria University
Journal of Lightwave Technology | Year: 2013

An optical signal suffers from irradiance and phase fluctuations when propagating through the free space optical (FSO) turbulence channel, thus resulting in the degradation of the bit error rate (BER) performance. The BER performance can be improved by adopting the multiple-input multiple-output (MIMO) scheme. In this paper, we propose a coherent binary polarization shift keying (BPOLSK) modulation scheme with MIMO employing maximum ratio combining and equal gain combining diversity techniques to mitigate the turbulence effect. The gamma-gamma statistical channel model is adopted for all the turbulence regimes. The BER performance for the proposed BPOLSK-MIMO FSO link is compared with the single-input single-output and ON-OFF-keying systems by means of computer simulation. The optical power gain is investigated and demonstrated under different turbulence regimes for a number of transmitters/receivers. © 2013 IEEE.

Bathurst J.C.,Northumbria University
Geomorphology | Year: 2013

Initiation of particle motion in a bed material of nonuniform size distribution may be quantified by (qci/qcr)=(Di/Dr)b, where qci is the critical unit discharge at which particle size Di enters motion, qcr is the critical condition for a reference size Dr unaffected by the hiding/exposure effects associated with nonuniform size distributions, i and r refer to percentiles of the distribution and b varies from 0 (equal mobility in entrainment of all particle sizes) to 1.5-2.5 (full size selective transport). Currently there is no generally accepted method for predicting the value of b. Flume and field data are therefore combined to investigate the above relationship. Thirty-seven sets of flume data quantify the relationship between critical unit discharge and particle size for bed materials with uniform size distributions (used here to approximate full size selective transport). Field data quantify the relationship for bed materials of nonuniform size distribution at 24 sites, with b ranging from 0.15 to 1.3. Intersection of the two relationships clearly demonstrates the hiding/exposure effect; in some but not all cases, Dr is close to the median size D50. The exponent has two clusters of values: b>1 for sites subject to episodic rain-fed floods and data collected by bedload pit trap and tracers; and b<0.7 for sites with seasonal snowmelt/glacial melt flow regimes and data collected by bedload sampler and large aperture trap. Field technique appears unlikely to cause variations in b of more than about 0.25. However, the clustering is consistent with possible variations in bed structure distinguishing: for b>1, sites with relatively infrequent bedload transport where particle embedding and consolidation could reduce the mobility of coarser particles; and, for b<0.7, a looser bed structure with frequent transport events allowing hiding/exposure and size selection effects to achieve their balance. As yet there is no firm evidence for such a dependency on bed structure but variations in b could potentially be caused by factors outside those determining equal mobility or size selection but appearing to affect b in the same way. © 2013 Elsevier B.V.

Recent research has convincingly documented cases of mitochondrial heteroplasmy in a small set of wild and cultivated plant species. Heteroplasmy is suspected to be common in flowering plants and investigations of additional taxa may help understand the mechanisms generating heteroplasmy as well as its effects on plant phenotypes. The role of mitochondrial heteroplasmy is of particular interest in plants as cytoplasmic male sterility is controlled by mitochondrial genotypes, sometimes leading to co-occurring female and hermaphroditic individuals (gynodioecy). Paternal leakage may be important in the evolution of mating systems in such populations. We conducted a genetic survey of the gynodioecious plant Plantago lanceolata, in which heteroplasmy has not previously been reported, and estimated the frequencies of mitochondrial genotypes and heteroplasmy. Sanger sequence genotyping of 179 individuals from 15 European populations for two polymorphic mitochondrial loci, atp6 and rps12, identified 15 heteroplasmic individuals. These were distributed among 6 of the 10 populations that had polymorphisms in the target loci and represented 8% of all sampled individuals and 15% of the individuals in those 6 populations. The incidence was highest in Northern England and Scotland. Our results are consistent with geographic differences in the incidence of paternal leakage and/or the rates of nuclear restoration of male fertility.Heredity advance online publication, 9 March 2016; doi:10.1038/hdy.2016.15. © 2016 The Genetics Society

Novaco R.W.,University of California at Irvine | Taylor J.L.,Northumbria University
Behaviour Research and Therapy | Year: 2015

Anger is related to violence prior to hospitalization, during hospitalization, and after discharge. Meta-analyses have established treatment efficacy in reducing anger, but few studies have addressed whether reduced anger leads to lowered aggressive behavior. This study concerns individually-delivered anger treatment, specialized for offenders with intellectual disabilities, delivered twice weekly for 18 sessions to 50 forensic hospital patients. Assessments involved patient self-report of anger, staff ratings of anger and aggression, and case records of assaultive incidents. Physical assault data were obtained from records 12 months pre-treatment and 12 months post-treatment. Significant reductions in assaults following treatment were found by GEE analyses, controlling for age, gender, length of stay, IQ, and pre-hospital violence. Following treatment, physical attacks reduced by more than half, dropping from approximately 3.5 attacks per patient 6 months prior to treatment, versus approximately 1 attack per patient in the 6-12 month interval post-treatment. In hierarchical regressions, controlling for IQ, reduction in physical assaults was associated with pre-to post-treatment change in anger level. These findings buttress the efficacy of anger treatment for patients having histories of violence and have significance for patient mental health, hospital staff well-being, therapeutic milieu, hospital management, and service delivery costs. © 2014 Elsevier Ltd.

Deckers J.,Northumbria University
Journal of Bioethical Inquiry | Year: 2011

The argument has been made that future generations of human beings are being harmed unjustifiably by the actions individuals commit today. This paper addresses what it might mean to harm future generations, whether we might harm them, and what our duties toward future generations might be. After introducing the "Global Health Impact" (GHI) concept as a unit of measurement that evaluates the effects of human actions on the health of all organisms, an incomplete theory of human justice is proposed. Having shown that the negative GHIs of our current generation cause unfair harm to future generations, I argue that each human being must be allocated a fair threshold of negative GHIs that should not be exceeded. By emphasising the need to consider all the GHIs of human actions, the theory of human justice developed here is highly relevant to evaluate human actions that might affect future generations, for example those related to climate change. © 2011 Springer Science+Business Media B.V.

Lochmuller H.,Northumbria University
Advances in Experimental Medicine and Biology | Year: 2010

Biobanks are collections of biomaterials with associated data. Biobanking is an essential tool to provide access to high quality human biomaterial for fundamental and translational research. Research for rare disorders benefits from the provision of human biomaterials through biobanks, and each human sample from a person with a rare disorder has a high value as it may hold the key to answer an important research question. Transnational cooperation in biobanking is an important catalyst to share limited resources and achieve optimal outcomes as in other areas of rare disorder research. Networks of biobanks aim to assure common practices and quality standards, and facilitate access to rare disorder biomaterials for the scientific community. © Springer Science+Business Media B.V. 2010.

Simmons P.J.,Northumbria University
Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology | Year: 2011

In Schistocerca gregaria ocellar pathways, large second-order L-neurons use graded potentials to communicate signals from the ocellar retina to third-order neurons in the protocerebrum. A third-order neuron, DNI, converts graded potentials into axonal spikes that have been shown in experiments at room temperature to be sparse and precisely timed. I investigated effects of temperature changes that a locust normally experiences on these signals. With increased temperature, response latency decreases and frequency responses of the neurons increase. Both the graded potential responses in the two types of neuron and the spikes in DNI report greater detail about a fluctuating light stimulus. Over a rise from 22 to 35°C the power spectrum of the L-neuron response encompasses higher frequencies and its information capacity increases from about 600 to 1,700 bits/s. DNI generates spikes more often during a repeated stimulus but at all temperatures it reports rapid decreases in light rather than providing a continual measure of light intensity. Information rate carried by spike trains increases from about 50 to 185 bits/s. At warmer temperatures, increased performance by ocellar interneurons may contribute to improved aerobatic performance by delivering spikes earlier and in response to smaller, faster light stimuli. © 2011 Springer-Verlag.

Lehnik-Habrink M.,University of Gottingen | Lewis R.J.,Northumbria University | Mader U.,University of Greifswald | Stulke J.,University of Gottingen
Molecular Microbiology | Year: 2012

RNAprocessing and degradation are key processes in the control of transcript accumulation and thus in the control of gene expression. In Escherichia coli, the underlying mechanisms and components of RNA decay are well characterized. By contrast, Grampositive bacteria do not possess several important players of E. coli RNA degradation, most notably the essential enzyme RNase E. Recent research on the model Gram-positive organism, Bacillus subtilis, has identified the essential RNases J1 and Y as crucial enzymes in RNA degradation. While RNase J1 is the first bacterial exoribonuclease with 5'-to-3' processivity, RNase Y is the founding member of a novel class of endoribonucleases. Both RNase J1 and RNase Y have a broad impact on the stability of B. subtilis mRNAs; a depletion of either enzyme affects more than 25% of all mRNAs. RNases J1 and Y as well as RNase J2, the polynucleotide phosphorylase PNPase, the RNA helicase CshA and the glycolytic enzymes enolase and phosphofructokinase have been proposed to form a complex, the RNA degradosome of B. subtilis. This review presents a model, based on recent published data, of RNA degradation in B. subtilis. Degradation is initiated by RNase Y-dependent endonucleolytic cleavage, followed by processive exoribonucleolysis of the generated fragments both in 3'-to-5' and in 5'-to-3' directions. The implications of these findings for pathogenic Gram-positive bacteria are also discussed. © 2012 Blackwell Publishing Ltd.

Gao Z.,Northumbria University
IEEE Transactions on Industrial Electronics | Year: 2015

In this paper, a novel discrete-time estimator is proposed, which is employed for simultaneous estimation of system states, and actuator/sensor faults in a discrete-time dynamic system. The existence of the discrete-time simultaneous estimator is proven mathematically. The systematic design procedure for the derivative and proportional observer gains is addressed, enabling the estimation error dynamics to be internally proper and stable, and robust against the effects from the process disturbances, measurement noise, and faults. Based on the estimated fault signals and system states, a discretetime fault-tolerant design approach is addressed, by which the system may recover the system performance when actuator/sensor faults occur. Finally, the proposed integrated discrete-time fault estimation and fault-tolerant control technique is applied to the vehicle lateral dynamics, which demonstrates the effectiveness of the developed techniques. 0278-0046 © 2015 IEEE.

This paper describes the development of the first set of national guidance focused on the prevention of alcohol problems in England. These guidelines were produced by the National Institute for Health and Clinical Excellence (NICE) working with a multidisciplinary program development group of scientists, practitioners and lay members. In this work, screening and brief alcohol interventions represent a key element of a comprehensive public health strategy to prevent alcohol-related risk and harm across the population. The first controlled trials of brief alcohol intervention were published in the mid to late 1980's and there are now around 60 published trials in this field. After 25 years of accumulated evidence in this field, brief alcohol interventions have yet to make a significant impact on routine clinical practice. While it is imperative to have good science to make the case for brief intervention delivery, this work is in vain if practitioners are unwilling or unable to use these interventions with their patients. Evidence from the alcohol field and other clinical areas indicates that national prioritisation of brief alcohol intervention activity, by a body, such as NICE, is likely to be a key driver of implementation by practitioners. This paper summarises a suite of complementary system-level and practice recommendations, which were published by NICE in June 2010, and considers their likely impact on screening and brief alcohol in England. © 2010 Australasian Professional Society on Alcohol and other Drugs.

Heather N.,Northumbria University
Drug and Alcohol Review | Year: 2010

This article amplifies the decision to subtitle the INEBRIA2009 Conference 'Breaking New Ground'. The effectiveness of screening and brief intervention (SBI) for hazardous and harmful drinking is now well-established for primary health care and is promising for other medical settings. In addition, significant advances in the implementation of SBI are being made in various parts of the world. But, because of the need to establish efficacy and effectiveness, and perhaps too because of a preoccupation with meta-analysis of existing research findings, progress in other aspects of the theory and practice of SBI has been slower than ideal. There may also be a risk of complacency in the SBI field of study. For these reasons and others, the Conference Organizing Committee decided to focus the conference and invite presentations on a number of specific topics in the field of alcohol SBI and these are listed here followed by a discussion of other areas in which new ground needs to be broken. © 2010 Australasian Professional Society on Alcohol and other Drugs.

Rugg-Gunn A.,Northumbria University
Acta medica academica | Year: 2013

To provide a brief commentary review of fluoride-containing toothpastes and mouthrinses with emphasis on their use at home. Toothpastes and mouthrinses are just two of many ways of providing fluoride for the prevention of dental caries. The first investigations into incorporating fluoride into toothpastes and mouthrinses were reported in the middle 1940s. Unlike water fluoridation (which is 'automatic fluoridation'), fluoride-containing toothpastes and fluoridecontaining mouthrinses are, primarily, for home use and need to be purchased by the individual. By the 1960s, research indicated that fluoride could be successfully incorporated into toothpastes and clinical trials demonstrated their effectiveness. By the end of the 1970s, almost all toothpastes contained fluoride. The widespread use of fluoride- containing toothpastes is thought to be the main reason for much improved oral health in many countries. Of the many fluoride compounds investigated, sodium fluoride, with a compatible abrasive, is the most popular, although amine fluorides are used widely in Europe. The situation is similar for mouthrinses. Concentrations of fluoride (F), commonly found, are 1500 ppm (1500 μg F/g) for toothpastes and 225 ppm (225 μg F/ml) for mouthrinse. Several systematic reviews have concluded that fluoride-containing toothpastes and mouthrinses are effective, and that there is added benefit from their use with other fluoride delivery methods such as water fluoridation. Guidelines for the appropriate use of fluoride toothpastes and mouthrinses are available in many countries. Fluoride toothpastes and mouthrinses have been developed and extensive testing has demonstrated that they are effective and their use should be encouraged. Copyright © 2013 by Academy of Sciences and Arts of Bosnia and Herzegovina.

Bull S.J.,Northumbria University
Philosophical Magazine | Year: 2015

This paper describes a simple method to determine the elastic modulus of a coating on a substrate using nanoindentation based on the load support of a truncated cone of material beneath the indenter. The cone angle is shown to be 32.48°in all cases. The effect of the coating on the measured contact modulus increases more rapidly as the contact scale is reduced. The model describes the behaviour of a range of coating substrate systems very well, but deviations are observed in cases where pile-up or tip end-shape variations affect the experimental data. It is possible to use a fit of a simplified form of the model to experimental data for coatings on stiff substrates to determine the elastic properties of the coating independent of the substrate. The model can be generalized for multilayer coatings; this is essential when compliant coating layers are sandwiched between stiffer layers. The model shows that the mechanical properties of thin stiff coatings on compliant substrates cannot be successfully determined from indentation data. The ISO14577 extrapolation method should therefore not be used in such circumstances. © 2015 Taylor & Francis.

Jones D.E.J.,Northumbria University | Mells G.,University of Cambridge
Hepatology | Year: 2011

We genotyped individuals with primary biliary cirrhosis and unaffected controls for suggestive risk loci (genome-wide association P < 1 × 10-4) identified in a previous genome-wide association study. Combined analysis of the genome-wide association and replication datasets identified IRF5-TNPO3 (combined P = 8.66 × 10-13), 17q12-21 (combined P = 3.50 × 10-13) and MMEL1 (combined P = 3.15 × 10-8) as new primary biliary cirrhosis susceptibility loci. Fine-mapping studies showed that a single variant accounts for the IRF5-TNPO3 association. As these loci are implicated in other autoimmune conditions, these findings confirm genetic overlap among such diseases. © 2011.

Campbell C.G.,Northumbria University
Monthly Notices of the Royal Astronomical Society | Year: 2010

Wind flows and collimated jets are believed to be a feature of a range of disc accreting systems. These include active galactic nuclei, T Tauri stars, X-ray binaries and cataclysmic variables. The observed collimation implies large-scale magnetic fields and it is known that dipole-symmetry fields of sufficient strength can channel wind flows emanating from the surfaces of a disc. The disc inflow leads to the bending of the poloidal magnetic field lines, and centrifugally driven magnetic winds can be launched when the bending exceeds a critical value. Such winds can result in angular momentum transport at least as effective as turbulent viscosity, and hence they can play a major part in driving the disc inflow. It is shown here that if the standard boundary condition of vanishing viscous stress close to the stellar surface is applied, together with the standard connection between viscosity and magnetic diffusivity, then poloidal magnetic field bending increases as the star is approached with a corresponding increase in the wind mass loss rate. A significant amount of material can be lost from the system via the enhanced wind from a narrow region close to the stellar surface. This occurs for a Keplerian angular velocity distribution and for a modified form of angular velocity, which allows for matching of the disc and stellar rotation rates through a boundary layer above the stellar surface. The enhanced mass loss is significantly affected by the behaviour of the disc angular velocity as the stellar surface is approached, and hence by the stellar rotation rate. Such a mechanism may be related to the production of jets from the inner regions of disc accreting systems. © 2009 RAS.

De Zubicaray G.,University of Queensland | Johnson K.,University of Queensland | Howard D.,Northumbria University | McMahon K.,University of Queensland
Cortex | Year: 2014

The context in which objects are presented influences the speed at which they are named. We employed the blocked cyclic naming paradigm and perfusion functional magnetic resonance imaging (fMRI) to investigate the mechanisms responsible for interference effects reported for thematicallyand categorically related compared to unrelated contexts. Naming objects in categorically homogeneous contexts induced a significant interference effect that accumulated from the second cycle onwards. This interference effect was associated with significant perfusion signal decreases in left middle and posterior lateral temporal cortex and the hippocampus. By contrast, thematically homogeneous contexts facilitated naming latencies significantly in the first cycle and did not differ from heterogeneous contexts thereafter, nor were they associated with any perfusion signal changes compared to heterogeneous contexts. These results are interpreted as being consistent with an account in which the interference effect both originates and has its locus at the lexical level, with an incremental learning mechanism adapting the activation levels of target lexical representations following access. We discuss the implications of these findings for accounts that assume thematic relations can be active lexical competitors or assume mandatory involvement of top-down control mechanisms in interference effects during naming. © 2014 Elsevier Ltd.

Kotter R.,Northumbria University
International Journal of Environmental Studies | Year: 2013

This paper attempts to connect debates on decarbonisation at international and European scale with discussions on smart grid developments,in the interaction of the international automotive industry,and government policy. Thus,the paper reviews policy frameworks and business strategies. © 2013 © 2013 Taylor & Francis.

Taylor R.,Northumbria University
Diabetic Medicine | Year: 2013

It has become widely accepted that Type 2 diabetes is inevitably life-long, with irreversible and progressive beta cell damage. However, the restoration of normal glucose metabolism within days after bariatric surgery in the majority of people with Type 2 diabetes disproves this concept. There is now no doubt that this reversal of diabetes depends upon the sudden and profound decrease in food intake, and does not relate to any direct surgical effect. The Counterpoint study demonstrated that normal glucose levels and normal beta cell function could be restored by a very low calorie diet alone. Novel magnetic resonance methods were applied to measure intra-organ fat. The results showed two different time courses: a) resolution of hepatic insulin sensitivity within days along with a rapid fall in liver fat and normalisation of fasting glucose levels; and b) return of normal beta cell insulin secretion over weeks in step with a fall in pancreas fat. Now that it has been possible to observe the pathophysiological events during reversal of Type 2 diabetes, the reverse time course of events which determine the onset of the condition can be identified. The twin cycle hypothesis postulates that chronic calorie excess leads to accumulation of liver fat with eventual spill over into the pancreas. These self-reinforcing cycles between liver and pancreas eventually cause metabolic inhibition of insulin secretion after meals and onset of hyperglycaemia. It is now clear that Type 2 diabetes is a reversible condition of intra-organ fat excess to which some people are more susceptible than others. © 2012 Diabetes UK.

Juggins S.,Northumbria University
Quaternary Science Reviews | Year: 2013

Quantitative reconstructions from biological proxies have revolutionised palaeolimnology but the methodology is not without problems. The most important of these result from attempts to reconstruct non-causal environmental variables and from the effects of secondary variables. Non-causal variables act as surrogates for often unknown or unquantified ecological factors and the method assumes that these relationships are invariant in space and time. This assumption is almost never met and examples of diatom models for water depth and summer temperature demonstrate how violation leads to spurious and misleading reconstructions. In addition, comparison of published species optima indicate that a number of models have little or no predictive power outside their current spatial setting. Finally, experiments using simulated training sets of known properties demonstrate how changes in secondary "nuisance" variables can lead to large, consistent, and interpretable trends in a reconstruction that are completely spurious and independent of any real change in the reconstructed variable. These problems pervade many quantitative reconstructions in palaeolimnology and other disciplines. Palaeoecologists must give greater attention to what can and cannot be reconstructed and explicitly address the dangers of reconstructing surrogate and confounded variables if our reconstructions are to remain credible. © 2012 Elsevier Ltd.

Bilotkach V.,Northumbria University | Lakew P.A.,University of California at Irvine
Transportation Research Part A: Policy and Practice | Year: 2014

A firm can obtain market power through its dominant position on the product market, or via control of a key resource. In particular, it has been argued that airport dominance is a more important source of market power in the US airline industry than route dominance. We examine this contention by analyzing a seventeen-year panel of airport-level prices in the United States. We demonstrate that even though on average airport-level concentration appears to be the strongest source of market power, concentration on routes originating at an airport is the strongest predictor of price levels for the sub-set of large and medium hub airports. There is little evidence that either airport or route dominance significantly affect prices in the sub-sample of medium and small hub airports. There is also little evidence that an airport's dominant carrier exerts market power beyond the level predicted by the airport or route dominance. Our results imply that consumer welfare losses due to airline consolidation can be concentrated in smaller communities, and related to changes in airport-level concentration. We provide a simple evaluation of the possible effects of two recent and one projected mergers (Delta-Northwest, United-Continental, and American-US Airways) in light of this finding, and suggest that the former consolidation event can potentially lead to non-trivial consumer welfare losses to travelers in over 30 small communities. © 2013 Elsevier Ltd.

Hablot D.,French National Center for Scientific Research | Harriman A.,Northumbria University | Ziessel R.,French National Center for Scientific Research
Angewandte Chemie - International Edition | Year: 2011

A switch in time: A sequence of highly efficient, intramolecular electronic energy transfer steps follows from selective illumination of the fluorescent center (DPP) present in a new class of molecular triads (see picture). The direction of energy flow depends on the protonation state of one of the termini (B and G), which can be modulated by direct or sensitized photolysis of a photoacid generator (PAG). © 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Boddy A.V.,Northumbria University
Clinical Pharmacology and Therapeutics | Year: 2013

Replication of findings in clinical pharmacogenetic studies is essential but often neglected. The observation that TPMT and COMT genotypes, in combination with ABCC3 genotype, are predictive of ototoxicity following cisplatin treatment has been confirmed. However, translating this observation into a useful preventive strategy requires more mechanistic insight. © 2013 American Society for Clinical Pharmacology and therapeutics.

Lord P.,Northumbria University
PloS one | Year: 2010

Many areas of biology are open to mathematical and computational modelling. The application of discrete, logical formalisms defines the field of biomedical ontologies. Ontologies have been put to many uses in bioinformatics. The most widespread is for description of entities about which data have been collected, allowing integration and analysis across multiple resources. There are now over 60 ontologies in active use, increasingly developed as large, international collaborations. There are, however, many opinions on how ontologies should be authored; that is, what is appropriate for representation. Recently, a common opinion has been the "realist" approach that places restrictions upon the style of modelling considered to be appropriate. Here, we use a number of case studies for describing the results of biological experiments. We investigate the ways in which these could be represented using both realist and non-realist approaches; we consider the limitations and advantages of each of these models. From our analysis, we conclude that while realist principles may enable straight-forward modelling for some topics, there are crucial aspects of science and the phenomena it studies that do not fit into this approach; realism appears to be over-simplistic which, perversely, results in overly complex ontological models. We suggest that it is impossible to avoid compromise in modelling ontology; a clearer understanding of these compromises will better enable appropriate modelling, fulfilling the many needs for discrete mathematical models within computational biology.

Sanz A.,Northumbria University
Biochimica et Biophysica Acta - Bioenergetics | Year: 2016

Testing the predictions of the Mitochondrial Free Radical Theory of Ageing (MFRTA) has provided a deep understanding of the role of reactive oxygen species (ROS) and mitochondria in the aging process. However those data, which support MFRTA are in the majority correlative (e.g. increasing oxidative damage with age). In contrast the majority of direct experimental data contradict MFRTA (e.g. changes in ROS levels do not alter longevity as expected). Unfortunately, in the past, ROS measurements have mainly been performed using isolated mitochondria, a method which is prone to experimental artifacts and does not reflect the complexity of the in vivo process. New technology to study different ROS (e.g. superoxide or hydrogen peroxide) in vivo is now available; these new methods combined with state-of-the-art genetic engineering technology will allow a deeper interrogation of, where, when and how free radicals affect aging and pathological processes. In fact data that combine these new approaches, indicate that boosting mitochondrial ROS in lower animals is a way to extend both healthy and maximum lifespan. In this review, I discuss the latest literature focused on the role of mitochondrial ROS in aging, and how these new discoveries are helping to better understand the role of mitochondria in health and disease. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi. © 2016 The Author.

Binda O.,Northumbria University
Epigenetics | Year: 2013

Lysine methylation of histones and non-histone proteins has emerged in recent years as a posttranslational modification with wide-ranging cellular implications beyond epigenetic regulation. The molecular interactions between lysine methyltransferases and their substrates appear to be regulated by posttranslational modifications surrounding the lysine methyl acceptor. Two very interesting examples of this cross-talk between methyl-lysine sites are found in the SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domaincontaining lysine methyltransferases SET7 and SETDB1, whereby the histone H3 trimethylated on lysine 4 (H3K4me3) modification prevents methylation by SETDB1 on H3 lysine 9 (H3K9) and the histone H3 trimethylated on lysine 9 (H3K9me3) modification prevents methylation by SET7 on H3K4. A similar cross-talk between posttranslational modifications regulates the functions of non-histone proteins such as the tumor suppressor p53 and the DNA methyltransferase DNMT1. Herein, in cis effects of acetylation, phosphorylation, as well as arginine and lysine methylation on lysine methylation events will be discussed. © 2013 Landes Bioscience.

Best K.E.,Northumbria University
Archives of disease in childhood. Fetal and neonatal edition | Year: 2012

The epidemiology of congenital small intestinal atresia (SIA) has not been well studied. This study describes the presence of additional anomalies, pregnancy outcomes, total prevalence and association with maternal age in SIA cases in Europe. Cases of SIA delivered during January 1990 to December 2006 notified to 20 EUROCAT registers formed the population-based case series. Prevalence over time was estimated using multilevel Poisson regression, and heterogeneity between registers was evaluated from the random component of the intercept. In total 1133 SIA cases were reported among 5126, 164 registered births. Of 1044 singleton cases, 215 (20.6%) cases were associated with a chromosomal anomaly. Of 829 singleton SIA cases with normal karyotype, 221 (26.7%) were associated with other structural anomalies. Considering cases with normal karyotype, the total prevalence per 10 000 births was 1.6 (95% CI 1.5 to 1.7) for SIA, 0.9 (95% CI 0.8 to 1.0) for duodenal atresia and 0.7 (95% CI 0.7 to 0.8) for jejunoileal atresia (JIA). There was no significant trend in SIA, duodenal atresia or JIA prevalence over time (RR=1.0, 95% credible interval (CrI): 1.0 to 1.0 for each), but SIA and duodenal atresia prevalence varied by geographical location (p=0.03 and p=0.04, respectively). There was weak evidence of an increased risk of SIA in mothers aged less than 20 years compared with mothers aged 20 to 29 years (RR=1.3, 95% CrI: 1.0 to 1.8). This study found no evidence of a temporal trend in the prevalence of SIA, duodenal atresia or JIA, although SIA and duodenal atresia prevalence varied significantly between registers.

In this review Alzheimer's disease is seen as a maladaptive interaction between human brain evolution and senescence. It is predicted to occur in everyone although does not necessarily lead to dementia. The pathological process is initiated in relation to a senescence mediated functional down-regulation in the posteromedial cortex (Initiation Phase). This leads to a loss of glutamatergic excitatory input to layer II entorhinal cortex neurons. A human specific maladaptive neuroplastic response is initiated in these neurons leading to neuronal dysfunction, NFT formation and death. This leads to further loss of glutamatergic excitatory input and propagation of the maladaptive response along excitatory pathways linking evolutionary progressed vulnerable neurons (Propagation Phase). Eventually neurons are affected in many brain areas resulting in dementia. Possible therapeutic approaches include enhancing glutamatergic transmission. The theory may have implications with regards to how Alzheimer's disease is classified. © 2011 Elsevier B.V.

Thomas K.,Northumbria University
Medicine and Science in Sports and Exercise | Year: 2016

PURPOSE: We tested the hypothesis that central and peripheral fatigue after constant-load cycling exercise would vary with exercise intensity and duration. METHODS: Twelve, well-trained male cyclists (V[Combining Dot Above]O2max, 4.49±0.35 L·min) completed three constant-load cycling trials to the limit of tolerance in a randomized, crossover design. Exercise intensities were set according to the respiratory responses to a preliminary ramp test to elicit cardiorespiratory and metabolic responses consistent with exercise in the severe and heavy exercise domains; 1) at power at V[Combining Dot Above]O2max (S+, 379±31 W), 2) at 60% of the difference between gas exchange threshold and V[Combining Dot Above]O2max (S−, 305±23 W) and 3) at the respiratory compensation point (RCP, 254±26 W). Pre- and post-exercise twitch responses from the quadriceps to electrical stimulation of the femoral nerve and magnetic stimulation of the motor cortex were recorded to assess neuromuscular and corticospinal function, respectively. RESULTS: Exercise time was 3.14±0.59 min, 11.11±1.86 min and 42.14±9.09 min for S+, S− and RCP respectively. All trials resulted in similar reductions in maximum voluntary force (P=0.61). However, the degree of peripheral fatigue varied in an intensity-dependent manner, with greater reductions in potentiated twitch force after S+ (−33±9%) compared to both S− (−16±9%, P<0.001) and RCP trials (−11±9%, P<0.001) and greater after S− compared to RCP (P<0.05). For central fatigue this trend was reversed, with smaller reductions in voluntary activation after S+ compared to RCP (−2.7±2.2% vs. –9.0±4.7%, P<0.01). CONCLUSION: These data suggest the magnitude of peripheral and central fatigue after locomotor cycling exercise is exacerbated with exercise intensity and duration, respectively. © 2016 American College of Sports Medicine

Zuliani P.,Northumbria University
International Journal on Software Tools for Technology Transfer | Year: 2015

In this paper,we survey recentwork on the use of statistical model checking techniques for biological applications. We begin with an overviewof the basic modelling techniques for biochemical reactions and their corresponding stochastic simulation algorithm—the Gillespie algorithm. We continue by giving a brief description of the relation between stochastic models and continuous (ordinary differential equation) models. Next, we present a literature survey, divided into two general areas. In the first area, we focus on works addressing verification of biological models, while in the second area we focus on papers tackling the parameter synthesis problem. We conclude with some open problems and directions for further research. © Springer-Verlag Berlin Heidelberg 2014.

Howel D.,Northumbria University | Ball H.,Durham University
Journal of Human Lactation | Year: 2013

Background: Although breastfeeding initiation rates have improved, later prevalence is very low in the United Kingdom, and Northeast England is the region with the lowest rates. Objective: This study aimed to investigate novel in addition to well-established risk factors for cessation of breastfeeding among women in this region. Methods: Participants were 870 women considering breastfeeding prior to birth who were enrolled in the postnatal ward North East Cot trial at a tertiary hospital in Northeast England from 2008 to 2010. They provided weekly data on feeding and sleeping practices for 26 weeks postpartum using an automated telephone system with reminder postcards and contact by telephone, letter, or email if necessary. Cox proportional hazards regression was used to investigate factors associated with terminating any and exclusive breastfeeding in this period. Results: Ninety-four percent of women started any breastfeeding and 66% initiated exclusive breastfeeding. By 26 weeks postpartum, 47% were still breastfeeding, but 1% were breastfeeding exclusively. Multivariate analysis showed that women who exclusively breastfed for at least 4 weeks breastfed for significantly longer after supplementation started (P < .001). Bed-sharing at home during the first 13 weeks was a significant predictor of both any and exclusive breastfeeding, as well as any breastfeeding after supplementation (P < .001). We also confirmed some recognized socio-demographic predictors of breastfeeding cessation in this location. Conclusion: We found that exclusive breastfeeding for at least 4 weeks was significantly associated with longer breastfeeding continuation after supplementation, and bed-sharing at home was associated with longer breastfeeding regardless of the definition used. © The Author(s) 2013.

Luiz O.J.,University of Campinas | Edwards A.J.,Northumbria University
Biological Conservation | Year: 2011

Detecting and determining the validity of local extinctions is an important conservation measure in order to uncover management failures. There are quantitative and qualitative methods that estimate extinction probability based on past sighting records. However, because current baselines about species' abundances and distributions in the sea were mostly established after humans had started affecting marine populations, researchers must often rely on historical data to elucidate past environmental conditions. We review early historical records from the Archipelago of Saint Paul's Rocks, together with data from recent expeditions, with the aim of testing the hypothesis that reef sharks (Carcharhinus spp.) have become extinct there. Our analyses are based on non-parametric probabilistic tests for extinction and on a qualitative framework to examine and judge as objectively as possible the likelihood of local extinction. Until the mid-20th century, visitors to St. Paul's Rocks invariably commented on the remarkable number of sharks around the Archipelago. These observations contrast with those of expeditions carried out during the last decade, which report no carcharhinid reef sharks while scuba diving in the archipelago, despite many more hours of underwater fieldwork than previous expeditions. All quantitative and qualitative methods conclude that the reef shark Carcharhinus galapagensis is locally extinct at St. Paul's Rocks after a sharp decrease in abundance that took place following the commencement of fishing. However, the persistence of occasional individuals of the once locally common Carcharhinus falciformis in the vicinity of the Archipelago, as a result of constant immigration of this oceanic species from outside the area, suggest that the population might recover if the present fishing pressure was removed. © 2011 Elsevier Ltd.

Daly A.K.,Northumbria University
Clinical Pharmacology and Therapeutics | Year: 2014

Pharmacogenetics/pharmacogenomics has been subject to considerable development during the past 10 years and seems likely to advance even more rapidly in the next decade. Several surveys suggest that initial training for health-care professionals - particularly physicians and pharmacists - frequently includes education in this area, but equipping these professions more generally to deal with ongoing development of the field and to make best use of new knowledge remains an important challenge.

Underground coal gasification (UCG) using boreholes drilled from the surface has been feasible for almost a century, but is only now being implemented in market economies. Good analogues for the hydrogeological effects of UCG are provided by longwall mining. Careful planning of UCG void locations and dimensions can result in minimal disturbance of overlying aquifers as close as 40 m above the burn zone. Moreover, development of a pressure arch above the zone of net strata extension can provide a hydraulic seal to prevent vertical fluid migration. Injection of CO2 into former UCG voids ought to be possible where these are present at depths in excess of ≈ 800 m. Analogies to longwall mining suggest that extensional deformation immediately above the burn zone will render sufficient pore space accessible to accommodate all of the CO2 arising from gasification. In the absence of adequate engineering, the boreholes used in the UCG-CCS processes represent the most likely leakage pathways for injected CO2. Hence high-quality borehole engineering will be required, taking full account of thermal performance of casing and grout, and geophysical testing of borehole integrity. An agenda for management of groundwater issues at all stages in the life-cycle of UCG and UCG-CCS has been developed, as an aide memoire for future developments. © 2011 Springer-Verlag.

Walker S.L.,Northumbria University
Renewable Energy | Year: 2012

UK Government analysis has predicted the feed-in tariff policy (FIT) and Renewables Obligation (RO) will result in 2% of electricity supply from projects less than 5MW installed capacity by 2020. Analysis of UK Government data (2000-2009) has identified failure of the RO to achieve targets for electricity supply from renewable energy sources. Is the predicted contribution of FIT projects also at risk? Green-X software is used to predict the installed capacity and generation of electricity projects in receipt of RO or FIT support. Results are compared with Government predictions within the FIT impact assessment and aspirational targets within the UK "Renewable Energy Strategy". © 2012 Elsevier Ltd.

Degnen C.,Northumbria University
Environment and Planning D: Society and Space | Year: 2013

Through the lens of 'knowing', which is simultaneously an expression in colloquial English and a set of cognate practices, this paper considers the ways in which relations come to have ontological depth which is both spatial and temporal. The significance of knowing people and places in everyday life exceeds a simple 'familiarity with' or 'knowledge of'. Instead, knowing speaks to what it is that is said to matter in the webs of relations which connect (and sometimes disconnect) people and place, connections that accumulate in uneven and unequal ways. The paper thus builds on recent literature in human geography on absence, presence, and postindustrial ruins and weds it with anthropological theory on connectedness, relatedness, and ruination to examine knowing. This cross-fertilisation of disciplinary perspectives permits me to pay critical attention to seemingly incommensurate and yet overlapping webs of relations (relations with people alive and dead, relations with places present and absent, relations with memory, relations with change and the past). Following Navaro-Yashin's recent work in Northern Cyprus, I argue that knowing in regard to absence sheds light on the theoretical bind of object-centred versus subject-centred approaches. © 2013 Pion and its Licensors.

Gazzola P.,Northumbria University
Environmental Impact Assessment Review | Year: 2013

The issue of mainstreaming has witnessed a revival over the last few years, not least because the latest financial crisis has triggered a renewed enthusiasm and a remarkable comeback amongst policy-making and environmental appraisal (EA) communities. Traditionally, environmental mainstreaming is linked to ideas of (environmental) integration and to the 'greening' of public policies. Yet, more recent mainstreaming efforts are building on the idea that the achievement of economic growth and of social well-being is not only dependent upon the protection of the environment, but on the fact that the environment should be valued as a source of goods and a provider of services, as well. In this context and despite the many shortcomings that EA has experienced as a mainstreaming tool over the last two decades, calls for EA to engage with ecosystem services and incorporate pricing valuations in its approach to mainstreaming are emerging, raising questions about the role and purpose of EA as an environmental mainstreaming tool.This paper aims to reflect on the role of EA as a mainstreaming tool, in terms of the extent to which it is mainstreaming the environment into policies for sustainable development and changing 'the mainstream' by breaking down the false dichotomy of environment and (economic) development. If mainstreaming through EA was to incorporate both greening and pricing logics, could EA be more effective in reframing the environment and development as correlated variables rather than competing variables? © 2013 Elsevier Inc.

Egred M.,Northumbria University
Catheterization and Cardiovascular Interventions | Year: 2012

The experience with a new approach of using combined debulking technique for treating heavily calcified coronary artery lesions with both LASER and high speed rotational atherectomy, which is being labeled as RASER PCI, is described. The RASER PCI approach has been used in three different patients with severely calcified, undilatable coronary artery lesions that were unresponsive to either technique alone, with successful and satisfactory outcome. © 2011 Wiley-Liss, Inc.

Attems J.,Northumbria University
Acta Neuropathologica | Year: 2010

The prevalence of Alzheimer disease (AD) and vascular dementia (VD) increases with advancing age, but less so after age 90 years. A retrospective hospital-based study of the relative prevalence of different disorders was performed in 1, 110 consecutive autopsy cases of demented elderly in Vienna, Austria (66% females, MMSE <20; mean age 83.3 ± 5.4 SD years). It assessed clinical, general autopsy data and neuropathology including immunohistochemistry. Neuropathologic diagnosis followed current consensus criteria. Four age groups (7-10th decade) were evaluated. In the total cohort AD pathology was seen in 82.9% ("pure" AD 42.9%; AD+ other pathologies 39.9%), VD in 10.8% (mixed dementia, MIX, i.e. AD+ vascular encephalopathy in 5.5%); other disorders in 5.7%, and negative pathology in 0.8%. The relative prevalence of AD increased from age 60 to 89 years and decreased slightly after age 90+, while "pure" VD diagnosed in the presence of vascular encephalopathy of different types with low neuritic AD pathology (Braak stages<3; mean 1.2-1.6) decreased progressively from age 60 to 90+; 85-95% of these patients had histories of diabetes, morphologic signs of hypertension, 65% myocardial infarction/cardiac decompensation, and 75% a history of stroke(s). Morphologic subtypes, subcortical arteriosclerotic (the most frequent), multi-infarct encephalopathy, and strategic infarct dementia showed no age-related differences. The relative prevalence of AD+ Lewy pathology remained fairly constant with increasing age. Mixed dementia and AD with minor cerebrovascular lesions increased significantly with age, while other dementias decreased. This retrospective study using strict morphologic criteria confirmed increased prevalence of AD with age, but mild decline at age 90+, and progressive decline of VD, while AD + vascular pathologies including MIX showed considerable age-related increase, confirming that mixed pathologies account for most dementia cases in very old persons. A prospective clinicopathologic study in oldest- old subjects showed a significant increase in both AD and cerebral amyloid angiopathy (CAA), but decrease in VD over age 85, while in a small group of old subjects CAA without considerable AD pathology may be an independent risk factor for cognitive decline. ©Springer-Verlag 2010.

Serinaldi F.,Northumbria University | Serinaldi F.,A+ Network
Water Resources Research | Year: 2013

Moving from univariate to multivariate frequency analysis, this study extends the Klemeš' critique of the widespread belief that the increasingly refined mathematical structures of probability functions increase the accuracy and credibility of the extrapolated upper tails of the fitted distribution models. In particular, we discuss key aspects of multivariate frequency analysis applied to hydrological data such as the selection of multivariate design events (i.e., appropriate subsets or scenarios of multiplets that exhibit the same joint probability to be used in design applications) and the assessment of the corresponding uncertainty. Since these problems are often overlooked or treated separately, and sometimes confused, we attempt to clarify properties, advantages, shortcomings, and reliability of results of frequency analysis. We suggest a selection method of multivariate design events with prescribed joint probability based on simple Monte Carlo simulations that accounts for the uncertainty affecting the inference results and the multivariate extreme quantiles. It is also shown that the exploration of the p-level probability regions of a joint distribution returns a set of events that is a subset of the p-level scenarios resulting from an appropriate assessment of the sampling uncertainty, thus tending to overlook more extreme and potentially dangerous events with the same (uncertain) joint probability. Moreover, a quantitative assessment of the uncertainty of multivariate quantiles is provided by introducing the concept of joint confidence intervals. From an operational point of view, the simulated event sets describing the distribution of the multivariate p-level quantiles can be used to perform multivariate risk analysis under sampling uncertainty. As an example of the practical implications of this study, we analyze two case studies already presented in the literature. Key Points Refined multivariate distributions do not improve extrapolation Joint confidence intervals are introduced Appropriate multivariate design events are derived ©2013. The Authors. Water Resources Research published by Wiley on behalf of American Geophysical Union.

Pitceathly R.D.S.,Kings College London | McFarland R.,Northumbria University
Current Opinion in Neurology | Year: 2014

Purpose of review: The clinical and genetic heterogeneity of mitochondrial myopathies presents considerable diagnostic challenges. In addition, mitochondrial dysfunction seems to contribute to the development and progression of many age-related neurodegenerative diseases. This review presents recently published data concerning prevalence, phenotype, gene discovery, disease mechanisms, diagnostic tools and treatment strategies for mitochondrial diseases, and summarizes current understanding concerning the role mitochondria play in the pathogenesis of other common neurological disorders. Recent findings: Heteroplasmic levels of pathogenic mitochondrial DNA mutations are common amongst the general population, although there is considerable geographic variation. Mitochondrial abnormalities also occur in common neurodegenerative disorders, implying a mechanistic link between mitochondrial dysfunction and development or progression of disease. The phenotypic spectrum associated with well recognized pathogenic variants continues to expand, whereas next-generation sequencing is identifying new disease-causing nuclear genetic mutations. Biomarkers and imaging modalities for diagnosis and disease monitoring are now in place and novel treatment strategies are emerging. Alas, no clinical trial data for treatment in mitochondrial disease have been published in the last 12 months. Summary: Despite rapid advances in gene discovery, details concerning the altered protein products and cellular pathways that result in mitochondrial disease remain elusive. Understanding the consequences of deleterious mutations and the cellular adaptive response is imperative so that therapeutic targets can be identified. Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

The potential benefits of public space frequently translate into inequitable social and spatial outcomes for specific groups. Young people in particular are being excluded from public spaces through a range of explicit and implicit measures. In the UK, one significant trend constraining their ability to access such space is the extent to which they are commonly perceived as perpetrators of anti-social behaviour. The perceived levels of anti-social behaviour associated with the 'ASBO generation' are exacerbating concerns over youths' presence in, as opposed to absence from, public space. Synthesising new ethnographic research with existing debates about the relationship between young people, anti-social behaviour and public space, this paper argues that it is necessary to address the multifarious discursive processes and material practices influencing young people's use of public space. The paper demonstrates how, as opposed to eradicating young people from public space, Community Wardens in Dundee often provide them with the opportunity for positive and meaningful encounters with places (and people) in their local communities. © 2013 Urban Studies Journal Limited.

Chen J.,Northumbria University
Journal of Physics D: Applied Physics | Year: 2012

There are many techniques to determine fracture toughness. Experimental simplicity and amenability to materials evaluation are features of general indentation testing. Sometimes indentation is the only practical means of obtaining fundamental information on critical lifetime-limiting damage modes in some ceramics and coatings. Fracture patterns are dependent on the indenter geometry and material properties. The analysis of interfacial toughness by indentation has been well documented. However, no such comprehensive review is available for the analysis of fracture toughness for thin coatings based on (nano)indentation. Therefore, this paper tends to fill this gap. The mechanisms of various crack patterns and existing models used to determine the fracture toughness have been discussed in this study. © 2012 IOP Publishing Ltd.

May F.E.B.,Northumbria University
Cancer Management and Research | Year: 2014

The incidence of breast cancer continues to rise: 1.7 million women were diagnosed with and 521,000 women died from breast cancer in 2012. This review considers first current treatment options: surgery; radiotherapy; and systemic endocrine, anti-biological, and cytotoxic therapies. Clinical management includes prevention, early detection by screening, treatment with curative intent, management of chronic disease, and palliative control of advanced breast cancer. Next, the potential of novel drugs that target DNA repair, growth factor dependence, intracellular and intercellular signal transduction, and cell cycle are considered. Estrogen-related receptor alpha has attracted attention as a therapeutic target in triple-negative breast cancers with de novo resistance to, and in breast cancers with acquired resistance to, endocrine therapies such as antiestrogens and aromatase inhibitors. Estrogen-related receptor alpha is an orphan receptor and transcription factor. Its activity is regulated by coregulator proteins and posttranslational modification. It is an energy sensor that controls adaptation to energy demand and may facilitate glycolytic metabolism and mitochondrial oxidative respiration in breast cancer cells. Estrogen-related receptor alpha increases breast cancer cell migration, proliferation, and tumor development. It is expressed at high levels in estrogen receptor-negative tumors, and is proposed to activate estrogen-responsive genes in endocrine-resistant tumors. The structures and functions of the ligand-binding domains of estrogen receptor alpha and estrogen-related receptor alpha, their ability to bind estrogens, phytoestrogens, and synthetic ligands, and the effects of ligand agonists, antagonists, and inverse agonists on biological activity, are evaluated. Synthetic ligands of estrogen-related receptor alpha have activity in preclinical models of metabolic disorders, diabetes, osteoporosis, and oncology. The clinical settings in which these novel drugs might have utility in the management of advanced breast cancer, and biomarkers for stratification of patients likely to benefit, are discussed. Finally, the potential side effects of the novel drugs on metabolism, osteoporosis, osteo-metastasis, and cachexia are considered. © 2014 May.

Riddle C.N.,University of Cambridge | Baker S.N.,Northumbria University
Journal of Neurophysiology | Year: 2010

We investigated the control of spinal interneurons by corticospinal and medial brain stem descending tracts in two macaque monkeys. Stimulating electrodes were implanted in the left pyramidal tract (PT), and the right medial longitudinal fasciculus (MLF), which contains reticulospinal, vestibulospinal, and some tectospinal fibers. Single unit discharge was recorded from 163 interneurons in the intermediate zone of the right spinal cord (segmental levels C6-C8) in the awake state; inputs from descending pathways were assessed from the responses to stimulation through the PT and MLF electrodes. Convergent input from both pathways was the most common finding (71/163 cells); responses to PT and MLF stimulation were of similar amplitude. Interneuron discharge was also recorded while the animal performed a reach and grasp task with the right hand; the output connections of the recorded cells were determined by delivering intraspinal microstimulation (ISMS) at the recording sites. Convergent input from MLF/PT stimulation was also common when analysis was restricted to cells that increased their rate during grasp (14/23 cells) or to cells recorded at sites where ISMS elicited finger or wrist movements (23/57 cells). We conclude that medial brain stem and corticospinal descending pathways have largely overlapping effects on spinal interneurons, including those involved in the control of the hand. This may imply a more important role for the brain stem in coordinating hand movements in primates than commonly assumed; brain stem pathways could contribute to the restoration of function seen after lesions to the corticospinal tract. Copyright © 2010 The American Physiological Society.

Bateson M.,Northumbria University
Current Biology | Year: 2015

An interview with Melissa Bateson, Professor of Ethology at Newcastle University, who has particular interest in emotion in animals: what it is, how we can measure it in non-verbal subjects and the developmental origins of low mood.

Agius L.,Northumbria University
Expert Opinion on Therapeutic Patents | Year: 2014

The concept of activation of glucokinase (encoded by the Gck gene) as a potential therapy for type 2 diabetes has been explored by several pharmaceutical companies. Small-molecule Gck activators (GKAs) were found to be effective at increasing glucose disposal by hepatocytes and lowering blood glucose in animal models of diabetes during acute or chronic exposure and in human type 2 diabetes during short-term exposure. However, several clinical trials of GKAs were discontinued because of declining efficacy during chronic exposure or other issues. In some cases, declining efficacy was associated with an increase in plasma triglycerides. Accordingly, increased hepatic triglyceride production or steatosis was inferred as the likely cause for declining efficacy. However, other mechanisms of tachyphylaxis need to be considered. For example, elevated glucose concentration causes induction of glucose 6-phosphatase (G6pc) and repression of Gck in hepatocytes. This is best explained as an adaptative mechanism to maintain intracellular phosphometabolite homeostasis. Enhancement of G6pc induction and Gck repression by GKAs because of perturbed phosphometabolite homeostasis could explain the decline in GKA efficacy during chronic exposure. Progress in understanding the mechanisms of intracellular phosphometabolite homeostasis is crucial for development of better drug therapies and appropriate dietary intervention for type 2 diabetes. © 2014 Informa UK, Ltd.

Elder G.J.,Northumbria University
Sleep medicine reviews | Year: 2014

The stress hormone cortisol is the end product of the hypothalamic-pituitary-adrenal (HPA) axis, and the cortisol awakening response (CAR) refers to the rapid rise in cortisol levels observed immediately following awakening. During the CAR period, cortisol levels typically increase by 38%-75%, peaking approximately 30 min after awakening. Evidence suggests the function of the CAR may be related to arousal, energy boost and/or anticipation, although its precise function is still unknown. The CAR has been investigated in a range of clinical populations including the assessment of daytime dysfunction in insomnia; however little research, if any, has specifically examined its relation to sleep architecture, or night-time difficulties associated with insomnia. The aim of this review is to provide an overview of the CAR, a description of the factors which can affect it, and to outline the CAR in relation to the '3P' model of insomnia. This review concludes with a description of a standard protocol for measurement of the CAR, which can be adapted and applied within sleep medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chen T.,Nanyang Technological University | Zhang J.,Northumbria University
Computers and Chemical Engineering | Year: 2010

This paper considers multivariate statistical monitoring of batch manufacturing processes. It is known that conventional monitoring approaches, e.g. principal component analysis (PCA), are not applicable when the normal operating conditions of the process cannot be sufficiently represented by a multivariate Gaussian distribution. To address this issue, Gaussian mixture model (GMM) has been proposed to estimate the probability density function (pdf) of the process nominal data, with improved monitoring results having been reported for continuous processes. This paper extends the application of GMM to on-line monitoring of batch processes. Furthermore, a method of contribution analysis is presented to identify the variables that are responsible for the onset of process fault. The proposed method is demonstrated through its application to a batch semiconductor etch process. © 2009 Elsevier Ltd. All rights reserved.

Shemilt I.,Northumbria University
Systematic reviews | Year: 2013

Methods for systematic reviews of the effects of health interventions have focused mainly on addressing the question of 'What works?' or 'Is this intervention effective in achieving one or more specific outcomes?' Addressing the question 'Is it worth it given the resources available?' has received less attention. This latter question can be addressed by applying an economic lens to the systematic review process.This paper reflects on the value and desire for the consideration by end users for coverage of an economic perspective in a Cochrane review and outlines two potential approaches and future directions. Two frameworks to guide review authors who are seeking to include an economic perspective are outlined. The first involves conducting a full systematic review of economic evaluations that is integrated into a review of intervention effects. The second involves developing a brief economic commentary. The two approaches share a set of common stages but allow the tailoring of the economic component of the Cochrane review to the skills and resources available to the review team. The number of studies using the methods outlined in the paper is limited, and further examples are needed both to explore the value of these approaches and to further develop them. The rate of progress will hinge on the organisational leadership, capacity and resources available to the CCEMG, author teams and other Cochrane entities. Particular methodological challenges to overcome relate to understanding the key economic trade-offs and casual relationships for a given decision problem and informing the development of evaluations designed to support local decision-makers. Methods for incorporating economic perspectives and evidence into Cochrane intervention reviews are established. Their role is not to provide a precise estimate of 'cost-effectiveness' but rather to help end-users of Cochrane reviews to determine the implications of the economic components of reviews for their own specific decisions.

Tillett W.,Northumbria University
Rheumatology (Oxford, England) | Year: 2015

OBJECTIVE: The aim of this study was to determine the extent to which structural damage, clinical disease activity, demographic and social factors are associated with work disability (WD) in PsA.METHODS: Four hundred patients fulfilling CASPAR (Classification Criteria for Psoriatic Arthritis) criteria for PsA were recruited from 23 hospitals across the UK. Demographic, socio-economic, work, clinical and radiographic data were collected. WD was assessed with the Work Productivity and Activity Impairment Specific Health Problem (WPAI-SHP) questionnaire reporting WD as a percentage of absenteeism (work time missed), presenteeism (impairment at work/reduced effectiveness) and work productivity loss (overall work impairment/absenteeism plus presenteeism). Logistic and linear regressions were conducted to investigate associations with WD.RESULTS: Two hundred and thirty-six participants of any age were in work. Absenteeism, presenteeism and productivity loss rates were 14% (s.d. 29.0), 39% (s.d. 27.2) and 46% (s.d. 30.4), respectively. Ninety-two (26%) participants of working age were unemployed. Greater age, disease duration of 2-5 years and worse physical function were associated with unemployment. Patients reported that employer awareness and helpfulness exerted a strongly positive influence on remaining in employment. Higher levels of global and joint-specific disease activity and worse physical function were associated with greater levels of presenteeism and productivity loss among those who remained in work.CONCLUSION: Reduced effectiveness at work was associated with measures of disease activity, whereas unemployment, considered the endpoint of WD, was associated with employer factors, age and disease duration. A longitudinal study is under way to determine whether treatment to reduce disease activity ameliorates WD in the real-world setting. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Liang Q.,Northumbria University
International Journal for Numerical Methods in Fluids | Year: 2011

In large-scale shallow flow simulations, local high-resolution predictions are often required in order to reduce the computational cost without losing the accuracy of the solution. This is normally achieved by solving the governing equations on grids refined only to those areas of interest. Grids with varying resolution can be generated by different approaches, e.g. nesting methods, patching algorithms and adaptive unstructured or quadtree gridding techniques. This work presents a new structured but non-uniform Cartesian grid system as an alternative to the existing approaches to provide local high-resolution mesh. On generating a structured but non-uniform Cartesian grid, the whole computational domain is first discretized using a coarse background grid. Local refinement is then achieved by directly allocating a specific subdivision level to each background grid cell. The neighbour information is specified by simple mathematical relationships and no explicit storage is needed. Hence, the structured property of the uniform grid is maintained. After employing some simple interpolation formulae, the governing shallow water equations are solved using a second-order finite volume Godunov-type scheme in a similar way as that on a uniform grid. © 2010 John Wiley & Sons, Ltd.

Manning D.A.C.,Northumbria University
Agronomy for Sustainable Development | Year: 2010

Recently published assessments of nutrient budgets on a national basis have shown that K deficits for developing countries are so substantial that a doubling of world production of potash fertilisers would be required to balance inputs and offtake, simply to meet demands in Africa alone. The price of potassium fertiliser raw materials has increased by a factor of 4 during 2007-2009, approaching $1000 per tonne in some markets. Thus an annual investment of the order of US$5600 million is required to replenish soil K stocks in Africa. In this context it is appropriate to review current knowledge of alternative sources of K, which is the seventh most abundant element in the Earth's continental crust, present in feldspars and (much less commonly) feldspathoid minerals including nepheline and leucite. Theoretical considerations based on the experimental determination of mineral dissolution rates indicate that nepheline dissolves 100 times more quickly than potassium feldspar, and this suggests that nepheline-bearing rocks are more effective as sources of K for plant growth than granitic rocks, even though these have higher K contents. Crop trials with silicate rocks and minerals as sources of K show increased K availability and uptake for nepheline-bearing rocks compared with granitic rocks. Under conditions where soils are rapidly leached (especially tropical soils such as oxisols that contain quartz, aluminium oxy-hydroxides and kaolinite), with low capacity to retain soluble nutrients, the use of potassium feldspar or crushed granite does give a yield response, although no greater than for conventional fertilisers. In other experiments with crushed ultramafic, basaltic and andesitic rocks improvements in crop yield are claimed, although this cannot be unambiguously related to the mineralogical or chemical composition of the rock used. In conclusion, the present high cost of conventional potassium fertilisers justifies further investigation of potassium silicate minerals and their host rocks (which in some cases include basic rocks, such as basalt) as alternative sources of K, especially for systems with highly weathered soils that lack a significant cation exchange capacity. Such soils commonly occur in developing countries, and so this approach provides an opportunity to develop indigenous silicate rock sources of K as an alternative to sometimes prohibitively expensive commercial fertilisers. © 2009 INRA, EDP Sciences.

Rowe C.,Northumbria University | Healy S.D.,University of St. Andrews
Science | Year: 2011

Female perceptual limitations may explain why sexual selection doesn't always lead to exaggerated male traits.

Sutcliffe I.C.,Northumbria University
Antonie van Leeuwenhoek, International Journal of General and Molecular Microbiology | Year: 2011

Protein secretion is an important aspect of bacterial interaction with the environment. The WXG100 secretion system is a poorly understood pathway for the secretion of members of the WXG100 protein family in Firmicutes and Actinobacteria, notably Mycobacteria. This pathway has also been termed the Type VII secretion system but there are semantic problems with this nomenclature. This Perspective reviews the phylum level distribution of WXG100 secretion systems and presents comparative genomic evidence that these systems are present in several Chloroflexi and in some members of the phyla Cyanobacteria, Lentisphaerae, Proteobacteria (notably Helicobacter pylori) and Verrucomicrobiae. These findings have implications for the nomenclature of the WXG100 secretion pathway. © 2010 Springer Science+Business Media B.V.

Halpin C.G.,Northumbria University
Proceedings. Biological sciences / The Royal Society | Year: 2014

Avian predators readily learn to associate the warning coloration of aposematic prey with the toxic effects of ingesting them, but they do not necessarily exclude aposematic prey from their diets. By eating aposematic prey 'educated' predators are thought to be trading-off the benefits of gaining nutrients with the costs of eating toxins. However, while we know that the toxin content of aposematic prey affects the foraging decisions made by avian predators, the extent to which the nutritional content of toxic prey affects predators' decisions to eat them remains to be tested. Here, we show that European starlings (Sturnus vulgaris) increase their intake of a toxic prey type when the nutritional content is artificially increased, and decrease their intake when nutritional enrichment is ceased. This clearly demonstrates that birds can detect the nutritional content of toxic prey by post-ingestive feedback, and use this information in their foraging decisions, raising new perspectives on the evolution of prey defences. Nutritional differences between individuals could result in equally toxic prey being unequally predated, and might explain why some species undergo ontogenetic shifts in defence strategies. Furthermore, the nutritional value of prey will likely have a significant impact on the evolutionary dynamics of mimicry systems.

Muth A.,Bangor University | Honekopp J.,Northumbria University | Falter C.M.,University of Cologne
Journal of Autism and Developmental Disorders | Year: 2014

Visuo-spatial skills are believed to be enhanced in autism spectrum disorders (ASDs). This meta-analysis tests the current state of evidence for Figure Disembedding, Block Design, Mental Rotation and Navon tasks in ASD and neurotypicals. Block Design (d = 0.32) and Figure Disembedding (d = 0.26) showed superior performance for ASD with large heterogeneity that is unaccounted for. No clear differences were found for Mental Rotation. ASD samples showed a stronger local processing preference for Navon tasks (d = 0.35); less clear evidence for performance differences of a similar magnitude emerged. We discuss the meta-analysis results together with other findings relating to visuo-spatial processing and three cognitive theories of ASD: Weak Central Coherence, Enhanced Perceptual Functioning and Extreme Male Brain theory. © 2014, Springer Science+Business Media New York.

Plummer R.,Northumbria University
Clinical Oncology | Year: 2014

Poly(ADP-ribose)polymerase (PARP) inhibitors are a novel class of anticancer agents that target the DNA damage response pathways. The enzyme target, PARP, plays a key role in signalling DNA single-strand breaks. Clinical development to date has focused on their potential role in combination with DNA-damaging chemotherapy, where efficacy has been limited by enhanced normal tissue toxicity, and as single agents in the context of synthetic lethality. This article reviews these data in the context of future development as radio-potentiating agents. © 2014 The Royal College of Radiologists.

Alston C.L.,Northumbria University
Neurology | Year: 2013

Mutations in nuclear genes involved in the maintenance of mitochondrial DNA (mtDNA) are associated with an extensive spectrum of clinical phenotypes, manifesting as either mtDNA depletion syndromes or multiple mtDNA deletion disorders.(1.)

Bingham R.J.,Northumbria University | Hughes C.W.,National Oceanography Center
Journal of Geophysical Research: Oceans | Year: 2012

In the open ocean, sea level variability is primarily steric in origin. Steric sea level is given by the depth integral of the density field, raising the question of how tide gauges, which are situated in very shallow water, feel deep ocean variability. Here this question is examined in a high-resolution global ocean model. By considering a series of assumptions we show that if we wish to reconstruct coastal sea level using only local density information, then the best assumption we can make is one of no horizontal pressure gradient, and therefore no geostrophic flow, at the seafloor. Coastal sea level can then be determined using density at the ocean's floor. When attempting to discriminate between mass and volume components of sea level measured by tide gauges, the conventional approach is to take steric height at deep-ocean sites close to the tide gauges as an estimate of the steric component. We find that with steric height computed at 3000 m this approach only works well in the equatorial band of the Atlantic and Pacific eastern boundaries. In most cases the steric correction can be improved by calculating steric height closer to shore, with the best results obtained in the depth range 500-1000 m. Yet, for western boundaries, large discrepancies remain. Our results therefore suggest that on time scales up to about 5 years, and perhaps longer, the presence of boundary currents means that the conventional steric correction to tide gauges may not be valid in many places. Copyright 2012 by the American Geophysical Union.

Heer R.,Northumbria University
Renal failure | Year: 2013

There is considerable interest in the use of multi-potent stem cells in kidney tissue regeneration. We studied if spermatogonial stem cells have the ability to undergo kidney differentiation. Spermatogonial stem cell differentiation was induced using in vitro and ex vivo co-culture techniques. Conditioned media from human kidney fibroblasts induced the expression of epithelial and endothelial lineages in spermatogonial stem cells, consistent with nephrogenesis. Furthermore, we showed that these cells up-regulated renal tubular-specific markers alkaline phosphatase, mineralocorticoid receptor, renal epithelial sodium channel and sodium-glucose transporter-2 (p<0.05). GFP-labeled spermatogonial stem cells were engrafted into metanephric kidney organ cultures harvested from E12.5 mouse embryos. After 5 days of organ culture, focal anti-GFP staining was detectable in all inoculated kidneys demonstrating integration of spermatogonial stem cells into the developing kidney (p<0.01). Histological assessment showed early nephron-like architecture. In summary, we show that spermatogonial stem cells have the potential to generate renal tissue and lay the foundations for further investigations into a novel therapeutic approach for renal insufficiency.

Megoran N.,Northumbria University
Transactions of the Institute of British Geographers | Year: 2010

Geographers have been better at studying war than peace. Critical geopolitics in particular has proved adept at uncovering and explicating the circumstances and techniques whereby geopolitical reasoning constructs and reinforces divisions and thus underwrites exclusion, fear and ultimately violence. However, it has been much weaker at exploring the conditions whereby these processes might be reversed. It is thus important that geographers move beyond oppositional critiques and develop the tools to identify and explore transformative possibilities for peace. This is here termed 'pacific geopolitics', defined as the study of how ways of thinking geographically about world politics can promote peaceful and mutually enriching human coexistence. This is demonstrated with reference to the Reconciliation Walk, a grassroots US evangelical Christian project that retraced the route of the First Crusade in apology for it. It catalysed a remarkable transformation in its leaders' geopolitical understandings of Arab-Israeli disputes. This points to the power of intimate geographical knowledge to challenge abstract geopolitical visions, exemplifying the potential contribution of pacific geopolitics. © 2010 The Author. Journal compilation © Royal Geographical Society (with The Institute of British Geographers) 2010.

Poulton S.W.,Northumbria University | Canfeld D.E.,University of Southern Denmark
Elements | Year: 2011

The reconstruction of oceanic paleoredox conditions on Earth is essential for investigating links between biospheric oxygenation and major periods of biological innovation and extinction, and for unravelling feedback mechanisms associated with paleoenvironmental change. The occurrence of anoxic, iron-rich (ferruginous) oceanic conditions often goes unrecognized, but refned techniques are currently providing evidence to suggest that ferruginous deep-ocean conditions were likely dominant throughout much of Earth's history. The prevalence of this redox state suggests that a detailed appraisal of the infuence of ferruginous conditions on the evolution of biogeochemical cycles, climate, and the biosphere is increasingly required.

Liang Q.,Northumbria University
Communications in Computational Physics | Year: 2010

Based on the recent development in shallow flow modelling, this paper presents a finite volume Godunov-type model for solving a 4×4 hyperbolic matrix system of conservation laws that comprise the shallow water and depth-averaged solute transport equations. The adopted governing equations are derived to preserve exactly the solution of lake at rest so that no special numerical technique is necessary in order to construct a well-balanced scheme. The HLLC approximate Riemann solver is used to evaluate the interface fluxes. Second-order accuracy is achieved using the MUSCL slope limited linear reconstruction together with a Runge-Kutta time integration method. The model is validated against several benchmark tests and the results are in excellent agreement with analytical solutions or other published numerical predictions. © 2010 Global-Science Press.

Read J.C.A.,Northumbria University
Eye (Basingstoke) | Year: 2015

Binocular stereopsis, or stereo vision, is the ability to derive information about how far away objects are, based solely on the relative positions of the object in the two eyes. It depends on both sensory and motor abilities. In this review, I briefly outline some of the neuronal mechanisms supporting stereo vision, and discuss how these are disrupted in strabismus. I explain, in some detail, current methods of assessing stereo vision and their pros and cons. Finally, I review the evidence supporting the clinical importance of such measurements. © 2015 Macmillan Publishers Limited. All rights reserved.

Kunadian V.,James Cook University | Zaman A.,Northumbria University | Qiu W.,Brigham and Womens Hospital
European Journal of Heart Failure | Year: 2011

AimsCoronary artery bypass graft (CABG) surgery is the standard of care for the management of patients with severe three-vessel and left main coronary artery disease (CAD). However, the optimal strategy for management of patients with CAD and severe left ventricular (LV) dysfunction [ejection fraction (EF) ≤35] is not clear. A meta-analysis of observational studies was performed to determine the operative mortality and long-term (5-year actuarial survival) outcomes among patients with severe LV dysfunction undergoing CABG.Methods and resultsA systematic computerized literature search was performed and observational studies consisting of patients undergoing isolated CABG for CAD and severe LV dysfunction were included. Studies that did not report operative mortality, long-term (<1 year) survival data, or pre-operative EF and multiple studies from the same group were excluded. In total, 4119 patients from 26 observational clinical studies were included. The estimated mean age was 63.9 years and 82.4 of patients were men. The mean (estimate) pre-operative EF was 24.7 (95 CI 22.527.0). The operative mortality among patients (26 studies, n 3621) who underwent on-pump CABG was 5.4, n 189 (95 CI 4.56.4). The 5-year actuarial survival among patients (13 studies, n 1980) who underwent on-pump CABG was 73.4, n 1483 (95 CI 68.777.7). Patients who underwent off-pump CABG (7 studies, n 498) tended to have reduced operative mortality of 4.4, n 20 (95 CI 2.86.4). The mean (estimate) post-operative EF was 35.19 (95 CI 31.9538.43).ConclusionThe present meta-analysis demonstrates that based on data from available observational clinical studies, CABG can be performed with acceptable operative mortality and 5-year actuarial survival in patients with severe LV dysfunction. © 2011 The Author.

Progress in improving animal welfare is currently limited by the lack of objective methods for assessing lifetime experience. I propose that telomere attrition, a cellular biomarker of biological age, provides a molecular measure of cumulative experience that could be used to assess the welfare impact of husbandry regimes and/or experimental procedures on non-human animals. I review evidence from humans that telomere attrition is accelerated by negative experiences in a cumulative and dose-dependent manner, but that this attrition can be mitigated or even reversed by positive life-style interventions. Evidence from non-human animals suggests that despite some specific differences in telomere biology, stress-induced telomere attrition is a robust phenomenon, occurring in a range of species including mice and chickens. I conclude that telomere attrition apparently integrates positive and negative experience in an accessible common currency that translates readily to novel species - the Holy Grail of a cumulative welfare indicator. © 2015 The Author. BioEssays published by WILEY Periodicals, Inc.

Pfeffer G.,Northumbria University
Cochrane database of systematic reviews (Online) | Year: 2012

Mitochondrial respiratory chain disorders are the most prevalent group of inherited neurometabolic diseases. They present with central and peripheral neurological features usually in association with other organ involvement including the eye, the heart, the liver, and kidneys, diabetes mellitus and sensorineural deafness. Current treatment is largely supportive and the disorders progress relentlessly causing significant morbidity and premature death. Vitamin supplements, pharmacological agents and exercise therapy have been used in isolated cases and small clinical trials, but the efficacy of these interventions is unclear. The first review was carried out in 2003, and identified six clinical trials. This major update was carried out to identify new studies and grade the original studies for potential bias in accordance with revised Cochrane Collaboration guidelines. To determine whether there is objective evidence to support the use of current treatments for mitochondrial disease. We searched the Cochrane Neuromuscular Disease Group Specialized Register (4 July 2011), CENTRAL (2011, Issue 2, MEDLINE (1966 to July 2011), and EMBASE (January 1980 to July 2011), and contacted experts in the field. We included randomised controlled trials (including cross-over studies). Two of the authors independently selected abstracts for further detailed review. Further review was performed independently by all five authors to decide which trials fit the inclusion criteria and graded risk of bias. Participants included males and females of any age with a confirmed diagnosis of mitochondrial disease based upon muscle histochemistry, respiratory chain complex analysis of tissues or cell lines or DNA studies. Interventions included any pharmacological agent, dietary modification, nutritional supplement, exercise therapy or other treatment. The review authors excluded studies at high risk of bias in any category. The primary outcome measures included an change in muscle strength and/or endurance, or neurological clinical features. Secondary outcome measures included quality of life assessments, biochemical markers of disease and negative outcomes. Two of the authors (GP and PFC) independently identified studies for further evaluation from all abstracts within the search period. For those studies identified for further review, all five authors then independently assessed which studies met the entry criteria. For the included studies, we extracted details of the number of randomised participants, treatment, study design, study category, allocation concealment and other risk of bias criteria, and participant characteristics. Analysis was based on intention-to-treat data. We planned to use meta-analysis, but this did not prove necessary. The authors reviewed 1335 abstracts, and from these identified 21 potentially eligible abstracts. Upon detailed review, 12 studies fulfilled the entry criteria. Of these, eight were new studies that had been published since the previous version of this review. Two studies which were included in the previous version of this review were excluded because of potential for bias. The comparability of the included studies is extremely low because of differences in the specific diseases studied, differences in the therapeutic agents used, dosage, study design, and outcomes. The methodological quality of included studies was generally high, although risk of bias was unclear in random sequence generation and allocation concealment for most studies. Otherwise, the risk of bias was low for most studies in the other categories. Serious adverse events were uncommon, except for peripheral nerve toxicity in a long-term trial of dichloroacetate (DCA) in adults.One trial studied high-dose coenzyme Q10 without clinically meaningful improvement (although there were multiple biochemical, physiologic, and neuroimaging outcomes, in 30 participants). Three trials used creatine monohydrate alone, with one reporting evidence of improved measures of muscle strength and post-exercise lactate, but the other two reported no benefit (total of 38 participants). One trial studied the effects of a combination of coenzyme Q10, creatine monohydrate, and lipoic acid and reported a statistically significant improvement in biochemical markers and peak ankle dorsiflexion strength, but overall no clinical improvement in 16 participants. Five trials studied the effects of DCA: three trials in children showed a statistically significant improvement in secondary outcome measures of mitochondrial metabolism (venous lactate in three trials, and magnetic resonance spectroscopy (MRS) in one trial; total of 63 participants). One trial of short-term DCA in adults demonstrated no clinically relevant improvement (improved venous lactate but no change in physiologic, imaging, or questionnaire findings, in eight participants). One longer-term DCA trial in adults was terminated prematurely due to peripheral nerve toxicity without clinical benefit (assessments included the GATE score, venous lactate and MRS, in 30 participants). One trial using dimethylglycine showed no significant effect (measurements of venous lactate and oxygen consumption (VO(2)) in five participants). One trial using a whey-based supplement showed statistically significant improvement in markers of free radical reducing capacity but no clinical benefit (assessments included the Short Form 36 Health Survey (SF-36) questionnaire and UK Medical Research Council (MRC) muscle strength, in 13 participants). Despite identifying eight new trials there is currently no clear evidence supporting the use of any intervention in mitochondrial disorders. Further research is needed to establish the role of a wide range of therapeutic approaches. We suggest further research should identify novel agents to be tested in homogeneous study populations with clinically relevant primary endpoints.

Farrag M.E.A.,Glasgow Caledonian University | Putrus G.A.,Northumbria University
IEEE Transactions on Power Delivery | Year: 2012

This paper presents a new approach to control the operation of the unified power-flow controller (UPFC) based on the adaptive neurofuzzy inference controller (ANFIC) concept. The training data for the controller are extracted from an analytical model of the transmission system incorporating a UPFC. The operating points' space is dynamically partitioned into two regions: 1) an inner region where the desired operating point can be achieved without violating any of the UPFC constraints and 2) an outer region where it is necessary to operate the UPFC beyond its limits. The controller is designed to achieve the most appropriate operating point based on the real power priority. In this study, the authors investigated and analyzed the effect of the system short-circuit level on the UPFC operating feasible region which defines the limitation of its parameters. In order to illustrate the effectiveness of the control algorithm, simulation and experimental studies have been conducted using the MATLAB/SIMULINK and dSPACE DS1103 data-acquisition board. The obtained results show a clear agreement between simulation and experimental results which verify the effective performance of the ANFIC controller. © 2006 IEEE.

Loughlin J.,Northumbria University
Arthritis Research and Therapy | Year: 2010

Genetics highlights relationships between biological systems, and as the number of defined osteoarthritis susceptibility alleles increases, there is the natural tendency to assess whether the alleles influence other musculoskeletal phenotypes. That has proven to be the case for the GDF5 polymorphism rs143383, a risk factor for knee osteoarthritis and several other common conditions, including lumbar-disc degeneration and developmental dysplasia of the hip. Another interesting example has recently emerged in the repeat polymorphism of the asporin gene, ASPN, which is also associated with these three phenotypes. Such discoveries increase our understanding of shared disease etiology but also emphasize the complexity of common genetic risk. © 2011 BioMed Central Ltd.

Williams S.D.P.,National Oceanography Center | Penna N.T.,Northumbria University
Geophysical Research Letters | Year: 2011

GPS observations used in geophysical studies are not usually corrected for non-tidal ocean loading (NTOL) displacement. Here we investigate NTOL effects on 3-4 year GPS height time series from 17 sites around the southern North Sea, and compute the NTOL displacement according to two ocean models; the global ECCO model and a high resolution regional model, POLSSM, which covers the northwest European continental shelf. To assess the susceptibility of GPS height estimates to NTOL, reprocessed GIPSY PPP daily solutions are corrected for the resulting displacement, together with atmospheric pressure loading (ATML). We find that the displacements due to NTOL are comparable in size to ATML and the combined correction reduces the variance by 12-22 mm2 (20-30% reduction in RMS). We find that POLSSM outperforms ECCO, with around an 11% greater variance reduction, and hence high resolution models are recommended to correct GPS heights for NTOL. Copyright © 2011 by the American Geophysical Union.