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Nottingham, United Kingdom

The University of Nottingham is a public research university based in Nottingham, Nottinghamshire, England, United Kingdom. It was founded as University College Nottingham in 1881 and granted a Royal Charter in 1948.Nottingham's main campus, University Park, is situated on the outskirts of the City of Nottingham, with a number of smaller campuses and a teaching hospital located elsewhere in Nottinghamshire. Outside the United Kingdom, Nottingham has campuses in Semenyih, Malaysia and Ningbo, China. Nottingham is organised into five constituent faculties, within which there are more than 50 departments, institutes and research centres. Nottingham has around 44,000 students and 9,000 staff and had a total income of £520 million in 2012/13, of which £100 million was from research grants and contracts.Nottingham is currently ranked 23rd in the UK by the Complete University Guide Table 2015. Several of its subjects have been consistently ranked in the top ten, including Economics, Law, and Pharmacy. A 2014 survey suggested it is the most targeted university by the UK's top employers. In 2012 Nottingham was ranked 13th in the world in terms of the number of alumni listed among CEOs of the Fortune Global 500. It is also ranked 2nd in the 2012 Summer Olympics table of British medal winners. In the 2011 GreenMetric World University Ranking, Nottingham was the world's most sustainable campus.It is a member of the Association of Commonwealth Universities, the Virgo Consortium, the European University Association, the Russell Group, Universities UK, Universitas 21 and participates in the Sutton Trust Summer School programme. Wikipedia.

Agency: GTR | Branch: EPSRC | Program: | Phase: Research Grant | Award Amount: 100.55K | Year: 2016

Ventilator Associated Pneumonia (VAP) is a major health problem resulting in death, prolonged intensive care unit (ICU) stay and costs of >£nbn worldwide. Endotracheal tube colonization and biofilm formation play a key role in VAP. Maintenance of the respiratory function of mechanically ventilated patients requires adequate humidification, even in non-invasive ventilation in which inadequate humidification and heating of the inspired air has been associated with functional deterioration of nasal mucosa and can also lead to VAP. Thus, humidification and temperature are important factors of modern intensive care practice. At the present, there is no technology available to conduct in situ measurement of biofilm growth on an ETT or humidity and temperature of the artificial air delivered to the lungs. The project will exploit cutting edge sensing techniques based on an array of optical fibre long period gratings in order to produce a prototype multiparameter instrument for a clinical setting to reduce VAP risk, aid early diagnosis and guide treatment. Each sensing element of the optical fibre sensor array will be modified using an appropriate sensitive layer to achieve optimal response to the key parameters of the ETT, such as temperature, humidity and biofilm formation. Novel advanced materials such as molecular imprinting and mesoporous functional films will be utilised as sensitive layers. During the course of the project the device will be tested on clinical equipment, typically used in ICU, in a laboratory setting to demonstrate proof of concept to proceed to clinical studies. The proposal combines technology push with clinical pull and matches the aspirations of the Optimising Treatment Grand Challenge identified by EPSRC to address the optimisation of care through effective diagnosis, patient-specific prediction and evidence-based intervention. The proposal is multidisciplinary in nature combining expertise in photonics, chemistry and analytical science The output and impact of the research will be maximised through the involvement of Dr Andy Norris at Nottingham University Hospitals Trust and the involvement of an ETT manufacturer (P3 Medical, a UK SME specialising in the manufacture of innovative, airway devices).

Shafqat A.,University of Nottingham
Anesthesiology | Year: 2015

BACKGROUND:: Visuospatial ability correlates positively with novice performance of simple laparoscopic tasks. The aims of this study were to identify whether visuospatial ability could predict technical performance of an ultrasound-guided needle task by novice operators and to describe how emotional state, intelligence, and fear of failure impact on this. METHODS:: Sixty medical student volunteers enrolled in this observational study. The authors used an instructional video to standardize training for ultrasound-guided needle advancement in a turkey breast model and assessed volunteers’ performance independently by two assessors using composite error score (CES) and global rating scale (GRS). The authors assessed their “visuospatial ability” with mental rotation test (MRT), group embedded figures test, and Alice Heim group ability test. Emotional state was judged with UWIST Mood Adjective Checklist (UMACL), and fear of failure and general cognitive ability were judged with numerical reasoning test. RESULTS:: High CES scores (high error rate) were associated with low MRT scores (ρ = −0.54; P < 0.001). Better GRS scores were associated with better MRT scores (ρ = 0.47; P < 0.001). Regarding emotions, GRS scores were low when anxiety levels were high (ρ = −0.35; P = 0.005) and CES scores (errors) were low when individuals reported feeling vigorous and active (ρ = −0.30; P = 0.01). CONCLUSIONS:: An MRT predicts novice performance of an ultrasound-guided needling task on a turkey model and as a trait measure could be used as a tool to focus training resources on less-able individuals. Anxiety adversely affects performance. Therefore, both may prove useful in directing targeted training in ultrasound-guided regional anesthesia. © by 2015, the American Society of Anesthesiologists, Inc. Wolters Kluwer Health, Inc. All Rights Reserved.

Blake H.,University of Nottingham
International Journal of Therapy and Rehabilitation | Year: 2014

Aims: Many patients experience physical, behavioural, cognitive and emotional problems following traumatic brain injury (TBI). They may require continuing care for many years, most of which is provided by informal caregivers, such as spouses, parents, or other family members. The caregiving role is associated with a range of adverse effects including anxiety, depression, poor physical health and lowered quality of life. This article explores issues around caregiver stress; highlighting interventions for this group and areas for further research.Methods: Literature exploring the impact of caregiving, its influencing and alleviating factors and interventions for caregivers of people with TBI is discussed, with brief critical analysis of key studies.Findings: Research suggests that caregiver characteristics, coping strategies, their appraisal of the situation and social networks may be associated with the amount of distress experienced. Many caregivers have unmet needs such as respite care and information provision on TBI. Providing information may help to alleviate strain. Community-based family therapies providing education, support and counselling can help to decrease distress and improve aspects of family functioning, although evidence for these is lacking.Conclusions: There is a need for more well-designed, controlled studies evaluating the impact of interventions to alleviate caregiver strain. © 2008, MA Healthcare Ltd. All rights reserved.

We sought to explore the interactions between roots and soil without disturbance and in four dimensions (i.e. 3-D plus time) using X-ray micro-computed tomography. The roots of tomato Solanum lycopersicum 'Ailsa Craig' plants were visualized in undisturbed soil columns for 10 consecutive days to measure the effect of soil compaction on selected root traits including elongation rate. Treatments included bulk density (1.2 vs. 1.6 g cm(-3)) and soil type (loamy sand vs. clay loam). Plants grown at the higher soil bulk density exploited smaller soil volumes (P < 0.05) and exhibited reductions in root surface area (P < 0.001), total root volume (P < 0.001) and total root length (P < 0.05), but had a greater mean root diameter (P < 0.05) than at low soil bulk density. Swelling of the root tip area was observed in compacted soil (P < 0.05) and the tortuosity of the root path was also greater (P < 0.01). Root elongation rates varied greatly during the 10-d observation period (P < 0.001), increasing to a maximum at day 2 before decreasing to a minimum at day 4. The emergence of lateral roots occurred later in plants grown in compacted soil (P < 0.01). Novel rooting characteristics (convex hull volume, centroid and maximum width), measured by image analysis, were successfully employed to discriminate treatment effects. The root systems of plants grown in compacted soil had smaller convex hull volumes (P < 0.05), a higher centre of mass (P < 0.05) and a smaller maximum width than roots grown in uncompacted soil. Soil compaction adversely affects root system architecture, influencing resource capture by limiting the volume of soil explored. Lateral roots formed later in plants grown in compacted soil and total root length and surface area were reduced. Root diameter was increased and swelling of the root tip occurred in compacted soil.

Schmitt J.,TU Dresden | Williams H.,University of Nottingham
British Journal of Dermatology | Year: 2010

Summary Current clinical research in eczema (atopic dermatitis) is hampered by a profusion of outcome measures, most of which have not been developed or tested adequately. The first Harmonising Outcome Measures for Eczema meeting (HOME 1) was an exploratory meeting to determine whether there was sufficient interest and enthusiasm in the international scientific community to form a collaborative group to define a minimum set of core outcomes for future eczema (atopic dermatitis) research. The meeting was open to all participants of the 6th Georg Rajka Symposium/International Symposium on Atopic Dermatitis/New Trends in Allergy VII meeting in Munich, 22-24 July 2010. Approximately 40 individuals attended. Prior to the meeting, an international Delphi exercise was performed to develop consensus-based sets of core outcome domains for eczema for 'controlled trials' and 'clinical recordkeeping'. The results of this Delphi exercise were presented at the meeting and critically discussed by the attendees. The constructive group discussion identified several important issues for future eczema outcomes research such as the degree to which patients and carers can be involved and the importance of involving colleagues from countries not represented at the meeting. In summary, this exploratory meeting indicated a genuine interest in the academic eczema community to form an international multiprofessional group dedicated to harmonizing outcomes research in eczema. The group decided to continue collaboratively with the HOME initiative. © 2010 British Association of Dermatologists.

The aims of this study were: (1) to review the rate of concurrent endometrial cancer in patients with a preoperative diagnosis of atypical endometrial hyperplasia (AEH); and (2) to determine the features of concurrent endometrial carcinoma and their impact on the subsequent management of AEH. We reviewed a retrospective series of 219 AEHs diagnosed locally in routine practice, over 24 years, and followed by a repeat biopsy or hysterectomy. Another series of 65 cases with a malignant diagnosis on preoperative sampling was included as a control group. Clinicopathologic parameters were obtained. In addition, published data on the risk of malignancy and features of malignant tumors after a diagnosis of AEH were collected and analyzed. This study reported on 2571 patients diagnosed in 31 published studies in addition to the current one. This showed a wide variation in the positive predictive value (PPV) of AEH in detecting endometrial cancer (6% to 63%) with an overall PPV of 37%. This variation is not only based on the differences among studies but also on the degree of atypia [mild/moderate (PPV 13%) or severe (PPV 50%)], the type of subsequent intervention (biopsy vs. hysterectomy), and more importantly the time period of diagnosis (around 20% in studies published before 1990s and up to 40% to 48% in recently published cases). Of the benign outcome cases, nearly 40% to 50% showed AEH with a potential risk of progressing to invasive carcinoma in 25% of cases. Malignant tumors after AEH diagnosis are associated with features of good prognosis with endometrioid morphology, lower grade, and early stage. Although the overall PPV of AEH is 37%, a figure of 40% to 48% is expected in the cases currently diagnosed in routine practice. Providing qualifying criteria for AEH will help identify its different associated risks and therefore should be included in routine pathology reports whenever possible. Unless there is a clinical contraindication, hysterectomy should be performed to treat concurrent carcinoma and to reduce the risk of subsequent carcinoma in nonmalignant cases with residual AEH.

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.

Morrissey O.,University of Nottingham
Oxford Review of Economic Policy | Year: 2015

Increasing tax revenues in low-income countries is essential to address future development finance requirements. This is particularly important for aid recipients, the focus of this paper. Theory shows that although there are many ways in which aid can have indirect effects on tax revenue, the direct effects arise because aid and tax are alternative sources of revenue and political economy factors influence the choices made by government. Aid may discourage tax effort if viewed as a politically less costly source of revenue. Under different conditions, the policies and reforms associated with aid may increase revenue, through promoting growth, encouraging more efficient tax structures, or supporting reforms to tax administration. While cross-country evidence reveals no systematic pattern, country studies show that aid can be associated with administrative and efficiency reforms to increase tax revenue. The conclusion discusses how aid and donors can promote increasing domestic tax revenue. © The Author 2015.

Janssen M.H.M.,VU University Amsterdam | Powis I.,University of Nottingham
Physical Chemistry Chemical Physics | Year: 2014

In this Perspective we discuss photoelectron circular dichroism (PECD), a relatively novel technique that can detect chiral molecules with high sensitivity. PECD has an enantiomeric sensitivity of typically 1-10%, which is two to three orders of magnitude larger than that of the widely employed technique of circular dichroism (CD). In PECD a chiral molecule is photoionized with circular polarized light, and the photoelectron angular scattering distribution is detected using particle imaging techniques. We present the general physical principles of photoelectron circular dichroism and we address both single- and multiphoton excitation. PECD has been measured with synchrotron radiation in single-photon ionization as well as, very recently, with femtosecond laser radiation in multiphoton ionization. We discuss the experimental implementation of PECD, focusing on velocity map coincidence imaging where the momentum distribution of both the electron and the coincident ion is measured. The coincident detection of the mass and momentum of the ion adds very powerful mass-correlated information to the PECD measurement of the chiral molecule. We illustrate the capabilities and the potential of PECD with various experimental examples and introduce computational methods that are able to model quantitatively experimental PECD results. We conclude with an outlook on novel developments and (analytical) implementations of PECD that may further broaden the application of PECD for the sensitive detection of chirality in molecules. © 2014 the Owner Societies.

Walsh D.,University of Nottingham | Devane D.,National University of Ireland
Qualitative Health Research | Year: 2012

The purpose of this metasynthesis is to describe and interpret qualitative research relating to midwife-led care to see if it sheds light on why low-risk women experience fewer birth interventions within this model of care. Eleven articles were included in the review. Three themes emerged: (a) relationally mediated benefits for women that resulted in increased agency and empathic care; (b) the problematic interface of midwife-led units with host maternity units, stemming from a clash of models and culture; and (c) greater agency for midwives within midwife-led models of care though bounded by the relationship with the host maternity unit. This metasynthesis suggests that lower rates of interventions could be linked to the greater agency experienced by women and midwives within midwife-led models, and that these effects are mediated, in part, by the smallness of scale in these settings. © The Author(s) 2012.

To develop and validate an updated version of the QFracture algorithm for estimating the risk of a patient sustaining an osteoporotic fracture or hip fracture in a primary care population. Prospective open cohort study using routinely collected data from 420 general practices in the United Kingdom to develop updated QFracture scores and 207 practices to validate scores. Cox's proportional hazards model was used in the derivation cohort to derive risk equations using several explanatory variables. We calculated measures of calibration and discrimination using the validation cohort. 3,142,673 patients in derivation cohort and 1,583,373 in validation cohort, aged 30-100 years, who contributed 23,608,337 and 11,732,106 person years of observation, respectively. We identified 59,772 incident diagnoses of osteoporotic fracture in the derivation cohort and 28,685 in the validation cohort. Incident diagnosis of osteoporotic fracture (vertebral, distal radius, proximal humerus, or hip) and incident hip fracture recorded in general practice records or linked cause of death records. We found significant independent associations with overall fracture risk in women for age, body mass index, ethnic origin, alcohol intake, smoking status, chronic obstructive pulmonary disease or asthma, any cancer, cardiovascular disease, dementia, diagnosis or treatment for epilepsy, history of falls, chronic liver disease, Parkinson's disease, rheumatoid arthritis or systemic lupus erythematosus, chronic renal disease, type 1 diabetes, type 2 diabetes, previous fracture, endocrine disorders, gastrointestinal malabsorption, any antidepressants, corticosteroids, unopposed hormone replacement therapy, and parental history of osteoporosis. Risk factors for hip fracture in women were similar except for gastrointestinal malabsorption and parental history of hip fracture. Risk factors for men were largely the same as those for women but also included care home residence. The updated hip fracture algorithm explained 71.7% (95% confidence interval 71.1% to 72.3%) of the variation in women and 70.4% (69.3% to 71.5%) in men. D statistic values for hip fracture were high for women (3.26, 3.21 to 3.31) and men (3.15, 3.06 to 3.24), and higher than for osteoporotic fracture. Values for the area under the receiver operating characteristics curves for hip fracture were 0.89 for women and 0.88 for men, compared with 0.79 and 0.71 for osteoporotic fracture, respectively. The updated algorithms performed better than the 2009 algorithms. Two QFracture algorithms were updated to predict risk of osteoporotic and hip fracture in primary care populations to include ethnic origin, all classes of antidepressants, chronic obstructive pulmonary disease, epilepsy, dementia, Parkinson's disease, cancer, systemic lupus erythematosus, chronic renal disease, type 1 diabetes, previous fragility fracture, and care home residence. These updated algorithms showed improved performance compared with previous QFracture algorithms reported in 2009.

For many organisms, respiratory gas exchange is a vital activity and different types of gas-exchange apparatus have evolved to meet individual needs. They include not only skin, gills, tracheal systems and lungs but also transient structures such as the chorioallantois of avian eggs and the placenta of eutherian mammals. The ability of these structures to allow passage of oxygen by passive diffusion can be expressed as a diffusive conductance (units: cm3O2min-1kPa-1). Occasionally, the ability to estimate diffusive conductance by physiological techniques is compromised by the difficulty of obtaining O2 partial pressures on opposite sides of the tissue interface between the delivery medium (air, water, blood) and uptake medium (usually blood). An alternative strategy is to estimate a morphometric diffusive conductance by combining stereological estimates of key structural quantities (volumes, surface areas, membrane thicknesses) with complementary physicochemical data (O2-haemoglobin chemical reaction rates and Krogh's permeability coefficients). This approach has proved valuable in a variety of comparative studies on respiratory organs from diverse species. The underlying principles were formulated in pioneering studies on the pulmonary lung but are illustrated here by taking the human placenta as the gas exchanger. © 2012 Elsevier GmbH.

Ebling F.J.P.,University of Nottingham
Hormones and Behavior | Year: 2014

This article is part of a Special Issue "Energy Balance".Seasonal cycles of adiposity and body weight reflecting changes in both food intake and energy expenditure are the norm in mammals that have evolved in temperate and polar habitats. Innate circannual rhythmicity and direct responses to the annual change in photoperiod combine to ensure that behavior and energy metabolism are regulated in anticipation of altered energetic demands such as the energetically costly processes of hibernation, migration, and lactation. In the last decade, major progress has been made into identifying the central mechanisms that underlie these profound long-term changes in behavior and physiology. Surprisingly they are distinct from the peptidergic and aminergic systems in the hypothalamus that have been identified in studies of the laboratory mouse and rat and implicated in timing meal intervals and in short-term responses to caloric restriction. Comparative studies across rodents, ungulates and birds reveal that tanycytes embedded in the ependymal layer of the third ventricle play a critical role in seasonal changes because they regulate the local availability of thyroid hormone. Understanding how this altered hormonal environment might regulate neurogenesis and plasticity in the hypothalamus should provide new insight into development of strategies to manage appetite and body weight. © 2014 The Author.

Mayhew T.M.,University of Nottingham
Placenta | Year: 2015

Introduction The placenta is a transient organ the functioning of which has health consequences far beyond the embryo/fetus. Understanding the biology of any system (organ, organism, single cell, etc) requires a comprehensive and inclusive approach which embraces all the biomedical disciplines and 'omic' technologies and then integrates information obtained from all of them. Among the latest 'omics' is morphomics. The terms morphome and morphomics have been applied incoherently in biology and biomedicine but, recently, they have been given clear and widescale definitions.Methods Morphomics is placed in the context of other 'omics' and its pertinent technologies and tools for sampling and quantitation are reviewed. Emphasis is accorded to the importance of random sampling principles in systems biology and the value of combining 3D quantification with alternative imaging techniques to advance knowledge and understanding of the human placental morphome.Results and conclusions By analogy to other 'omes', the morphome is the totality of morphological features within a system and morphomics is the systematic study of those structures. Information about structure is required at multiple levels of resolution in order to understand better the processes by which a given system alters with time, experimental treatment or environmental insult. Therefore, morphomics research includes all imaging techniques at all levels of achievable resolution from gross anatomy and medical imaging, via optical and electron microscopy, to molecular characterisation. Quantification is an important element of all 'omics' studies and, because biological systems exist and operate in 3-dimensional (3D) space, precise descriptions of form, content and spatial relationships require the quantification of structure in 3D. These considerations are relevant to future study contributions to the Human Placenta Project. © 2015 Elsevier Ltd. All rights reserved.

Bonney M.,University of Nottingham | Jaber M.Y.,Ryerson University
International Journal of Production Economics | Year: 2011

Mathematical models of inventory typically include the three inventory associated costs of surplus, shortage and ordering. These classic inventory models are then analysed so as to choose inventory parameters that usually minimise the total cost of operating the inventory system being investigated. Unfortunately, classic inventory models do not provide a meaningful basis for analysing many real and increasingly important practical inventory problems and situations. It is therefore not surprising that over recent years, several authors have discussed these issues in broad terms and suggested that a new paradigm needs to be developed. This paper develops some specific aspects of this discussion. In particular, the paper identifies a range of inventory problems that are not covered appropriately by traditional inventory analysis. One of these is to design responsible inventory systems, i.e. systems that reflect the needs of the environment. The paper then examines the importance of inventory planning to the environment in greater detail. For example, packaging is important, not only because of its costs and the protection that it provides to the inventory items, but also because of its eventual effects on the environment in terms of the use of resources and potential landfill. For similar reasons, waste, which can result from poor inventory management, is highly important. The location of stores is important because location affects transport costs. Thus the influence of the secondary aspects of most inventory models; packaging, waste and location are important but, even more important are the inter-relations with the total system. In particular, the location of the manufacturing plants and the effect that inventory planning has on the logistics chain, potentially have considerable environmental implications. Inventory is part of a wider system. However, until the cost charged for an activity reflects the true environmental cost of that activity, it is likely that decisions will be made on the basis of erroneous data. In that situation, we are faced with either determining the environmental cost of specific actions or to use environmental costs that are somewhat contrived; in which case it may be more sensible to use very different performance measures and models. The paper discusses these ideas and ways in which inventory policies may reassure us with our environmental concerns. © 2010 Elsevier B.V. All rights reserved.

Finch R.,University of Nottingham
Journal of Antimicrobial Chemotherapy | Year: 2012

The UK Government Specialist Advisory Committee on Antimicrobial Resistance and Healthcare-Associated Infections (ARHAI) was established in 2007. It has responsibility for providing practical and scientific advice to government on healthcare-associated infections (HCAIs) and to maintain the effectiveness of antimicrobial agents in the treatment and prevention of infection in man and animals. The manner in which this has been approached by ARHAI is described. In essence, key themes have been defined and issues dealt with through 'Focus Sessions', Subgroups and Working Groups. This Supplement reports on a selection of the key issues that have been addressed and the resulting recommendations and actions. Topics featured include: educational initiatives that target healthcare professionals and the public; methicillin-resistant Staphylococcus aureus and Clostridium difficile infections; surveillance priorities; healthcare management and HCAI and antimicrobial resistance (AMR); AMR in pathogens involving man and animals; technological innovation to support the control of AMR and HCAI; antimicrobial stewardship; and issues dealing with antiviral drug resistance. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Pollock K.,University of Nottingham
BMC Medical Ethics | Year: 2012

Background: Research is fundamental to improving the quality of health care. The need for regulation of research is clear. However, the bureaucratic complexity of research governance has raised concerns that the regulatory mechanisms intended to protect participants now threaten to undermine or stifle the research enterprise, especially as this relates to sensitive topics and hard to reach groups. Discussion. Much criticism of research governance has focused on long delays in obtaining ethical approvals, restrictions imposed on study conduct, and the inappropriateness of evaluating qualitative studies within the methodological and risk assessment frameworks applied to biomedical and clinical research. Less attention has been given to the different epistemologies underlying biomedical and qualitative investigation. The bioethical framework underpinning current regulatory structures is fundamentally at odds with the practice of emergent, negotiated micro-ethics required in qualitative research. The complex and shifting nature of real world settings delivers unanticipated ethical issues and (occasionally) genuine dilemmas which go beyond easy or formulaic 'procedural' resolution. This is not to say that qualitative studies are 'unethical' but that their ethical nature can only be safeguarded through the practice of 'micro-ethics' based on the judgement and integrity of researchers in the field. Summary. This paper considers the implications of contrasting ethical paradigms for the conduct of qualitative research and the value of 'empirical ethics' as a means of liberating qualitative (and other) research from an outmoded and unduly restrictive research governance framework based on abstract prinicipalism, divorced from real world contexts and values. © 2012 Pollock; licensee BioMed Central Ltd.

Villatoro E.,University of Nottingham
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Pancreatic necrosis may complicate severe acute pancreatitis, and is detectable by computed tomography (CT). If it becomes infected mortality increases, but the use of prophylactic antibiotics raises concerns about antibiotic resistance and fungal infection. OBJECTIVES: To determine the efficacy and safety of prophylactic antibiotics in acute pancreatitis complicated by CT proven pancreatic necrosis. SEARCH STRATEGY: Searches were updated in November 2008, in The Cochrane Library (Issue 2, 2008), MEDLINE, EMBASE, and CINAHL. Conference proceedings and references from found articles were also searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing antibiotics versus placebo in acute pancreatitis with CT proven necrosis. DATA COLLECTION AND ANALYSIS: Primary outcomes were mortality and pancreatic infection rates. Secondary end-points included non pancreatic infection, all sites infection, operative rates, fungal infections, and antibiotic resistance. Subgroup analyses were performed for antibiotic regimen (beta-lactam, quinolone, and imipenem). MAIN RESULTS: Seven evaluable studies randomised 404 patients. There was no statistically significant effect on reduction of mortality with therapy: 8.4% versus controls 14.4%, and infected pancreatic necrosis rates: 19.7% versus controls 24.4%. Non-pancreatic infection rates and the incidence of overall infections were not significantly reduced with antibiotics: 23.7% versus 36%; 37.5% versus 51.9% respectively. Operative treatment and fungal infections were not significantly different. Insufficient data were provided concerning antibiotic resistance.With beta-lactam antibiotic prophylaxis there was less mortality (9.4% treatment, 15% controls), and less infected pancreatic necrosis (16.8% treatment group, 24.2% controls) but this was not statistically significant. The incidence of non-pancreatic infections was non-significantly different (21% versus 32.5%), as was the incidence of overall infections (34.4% versus 52.8%), and operative treatment rates. No significant differences were seen with quinolone plus imidazole in any of the end points measured. Imipenem on its own showed no difference in the incidence of mortality, but there was a significant reduction in the rate of pancreatic infection (p=0.02; RR 0.34, 95% CI 0.13 to 0.84). AUTHORS' CONCLUSIONS: No benefit of antibiotics in preventing infection of pancreatic necrosis or mortality was found, except for when imipenem (a beta-lactam) was considered on its own, where a significantly decrease in pancreatic infection was found. None of the studies included in this review were adequately powered. Further better designed studies are needed if the use of antibiotic prophylaxis is to be recommended.

Shah M.,University of Nottingham
Sub-cellular biochemistry | Year: 2013

Stem cells are unique cells that can self-renew and differentiate into many cell types. Plasticity is a fundamental characteristic of stem cells and it is regulated by reversible epigenetic modifications. Although gene-restriction programs are established during embryonic development when cell lineages are formed, stem cells retain a degree of flexibility that is essential for tissue regeneration. For instance, quiescent adult stem cells can be induced to proliferate and trans-differentiate in response to injury. The same degree of plasticity is observed in cancer, where cancer cells with stem cell characteristics (or cancer stem cells) are formed by transformation of normal stem cells or de-differentiation of somatic cells. Reprogramming experiments with normal somatic cells and cancer cells show that epigenetic landscapes are more plastic than originally thought and that their manipulation can induce changes in cell fate. Our knowledge of stem cell function is still limited and only by understanding the mechanisms regulating developmental potential together with the definition of epigenetic maps of normal and diseased tissues we can reveal the true extent of their plasticity. In return, the control of plastic epigenetic programs in stem cells will allow us to develop effective treatments for degenerative diseases and cancer.

Grundmann R.,University of Nottingham
Science Technology and Human Values | Year: 2013

In late 2009, e-mails from a server at the Climate Research Unit at the University of East Anglia were released that showed some climate scientists in an unfavorable light. Soon this scandal was known as "Climategate" and a highly charged debate started to rage on blogs and in the mass media. Much of the debate has been about the question whether anthropogenic global warming was undermined by the revelations. But ethical issues, too, became part and parcel of the debate. This article aims to contribute to this debate, assessing the e-mail affair in the light of two normative analyses of science, one proposed by Robert Merton (and developed further by some of his followers), the second by a recent suggestion to use the concept of honest brokering in science policy interactions. On the basis of these analyses, different aspects of malpractice will be discussed and possible solutions will be suggested. © The Author(s) 2012.

This paper focuses on patients'/prisoners' narratives that discuss the National Health Service mental healthcare provided in one Her Majesty's Prison Service establishment. In comparison to the general population, the prevalence of mental illness experienced by the prisoner population is exceedingly high. The prison environment is not conducive to mental health and this custodial clinical setting is not a useful catalyst for mental healthcare for myriad reasons. The pursuit of good mental health for patients in the penal milieu is challenging. For this medical sociology case study, qualitative semi-structured interviews are conducted with male prisoners in a Category B establishment. These participants are also primary or secondary level mental health service users. Analytical discussions concern the clinician-patient relationship and patients' opinions regarding the mental healthcare received. Debated concepts include: understanding, care, trust, flexibility, cooperation, conversation, relaxation, enjoyment and patient power. Mental healthcare receipt experiences and environments are important. © 2012 Copyright Taylor and Francis Group, LLC.

Pickett K.E.,University of York | Wilkinson R.G.,University of Nottingham
Social Science and Medicine | Year: 2015

There is a very large literature examining income inequality in relation to health. Early reviews came to different interpretations of the evidence, though a large majority of studies reported that health tended to be worse in more unequal societies. More recent studies, not included in those reviews, provide substantial new evidence. Our purpose in this paper is to assess whether or not wider income differences play a causal role leading to worse health. We conducted a literature review within an epidemiological causal framework and inferred the likelihood of a causal relationship between income inequality and health (including violence) by considering the evidence as a whole. The body of evidence strongly suggests that income inequality affects population health and wellbeing. The major causal criteria of temporality, biological plausibility, consistency and lack of alternative explanations are well supported. Of the small minority of studies which find no association, most can be explained by income inequality being measured at an inappropriate scale, the inclusion of mediating variables as controls, the use of subjective rather than objective measures of health, or follow up periods which are too short.The evidence that large income differences have damaging health and social consequences is strong and in most countries inequality is increasing. Narrowing the gap will improve the health and wellbeing of populations. © 2015 Elsevier Ltd.

Adesso G.,University of Nottingham | Datta A.,University of Oxford
Physical Review Letters | Year: 2010

Quantum discord, a measure of genuinely quantum correlations, is generalized to continuous variable systems. For all two-mode Gaussian states, we calculate analytically the quantum discord and a related measure of classical correlations, solving an optimization over all Gaussian measurements. Almost all two-mode Gaussian states are shown to have quantum correlations, while for separable states, the discord is smaller than unity. For a given amount of entanglement, it admits tight upper and lower bounds. Via a duality between entanglement and classical correlations, we derive a closed formula for the Gaussian entanglement of formation of a family of three-mode Gaussian states. © 2010 The American Physical Society.

Babu N.J.,University of Nottingham | Nangia A.,Central University of Costa Rica
Crystal Growth and Design | Year: 2011

The current phase of drug development is witnessing an oncoming crisis due to the combined effects of increasing R&D costs, decreasing number of new drug molecules being launched, several blockbuster drugs falling off the patent cliff, and a high proportion of advanced drug candidates exhibiting poor aqueous solubility. The traditional approach of salt formulation to improve drug solubility is unsuccessful with molecules that lack ionizable functional groups, have sensitive moieties that are prone to decomposition/racemization, and/or are not sufficiently acidic/basic to enable salt formation. Several novel examples of pharmaceutical cocrystals from the past decade are reviewed, and the enhanced solubility profiles of cocrystals are analyzed. The peak dissolution for pharmaceutical cocrystals occurs in a short time (<30 min), and high solubility is maintained over a sufficiently long period (4-6 h) for the best cases. The enhanced solubility of drug cocrystals is similar to the supersaturation phenomenon characteristic of amorphous drugs. However, in contrast to the metastable nature of amorphous phases, cocrystals are stable owing to their crystalline nature. Yet, cocrystals can exhibit dramatic solubility advantage over the stable crystalline drug form, often comparable to amorphous pharmaceuticals. The "spring and parachute" concept for amorphous drug dissolution is adapted to explain the solubility advantage of pharmaceutical cocrystals. Thus (1) the cocrystal dissociates to amorphous or nanocrystalline drug clusters (the spring), which (2) transform via fast dissolving metastable polymorphs to the insoluble crystalline modification following the Ostwalds Law of Stages, to give (3) high apparent solubility for cocrystals and optimal drug concentration (the parachute) in the aqueous medium. © 2011 American Chemical Society.

Background: There are three turkey β-adrenoceptors: the original turkey β-adrenoceptor from erythrocytes (tβtrunc, for which the X-ray crystal structure has recently been determined), tβ3C and tβ4C-receptors. This study examined the similarities and differences between these avian receptors and mammalian receptors with regards to binding characteristics and functional high and low affinity agonist conformations. Methodology/Principal Findings: Stable cell lines were constructed with each of the turkey β-adrenoceptors and 3HCGP12177 whole cell binding, CRE-SPAP production and 3H-cAMP accumulation assays performed. It was confirmed that the three turkey β-adrenoceptors are distinct from each other in terms of amino acid sequence and binding characteristics. The greatest similarity of any of the turkey β-adrenoceptors to human β-adrenoceptors is between the turkey β3C-receptor and the human β2-adrenoceptor. There are pharmacologically distinct differences between the binding of ligands for the tβtrunc and tβ4C and the human β-adrenoceptors (e.g. with CGP20712A and ICI118551). The tβtrunc and tβ4Cadrenoceptors appear to exist in at least two different agonist conformations in a similar manner to that seen at both the human and rat β1-adrenoceptor and human β3-adrenoceptors. The tβ3C-receptor, similar to the human β2-adrenoceptor, does not, at least so far, appear to exist in more than one agonist conformation. Conclusions/Significance: There are several similarities, but also several important differences, between the recently crystallised turkey β-adrenoceptor and the human β-adrenoceptors. These findings are important for those the field of drug discovery using the recently structural information from crystallised receptors to aid drug design. Furthermore, comparison of the amino-acid sequence for the turkey and human adrenoceptors may therefore shed more light on the residues involved in the existence of the secondary β-adrenoceptor conformation. © 2010 Jillian G. Baker.

Hill K.,University of Nottingham
Journal of Experimental Botany | Year: 2015

Plants exhibit a high level of developmental plasticity and growth is responsive to multiple developmental and environmental cues. Hormones are small endogenous signalling molecules which are fundamental to this phenotypic plasticity. Post-translational modifications of proteins are a central feature of the signal transduction pathways that regulate gene transcription in response to hormones. Modifications that affect the function of transcriptional regulators may also serve as a mechanism to incorporate multiple signals, mediate cross-talk, and modulate specific responses. This review discusses recent research that suggests hormone-responsive transcription factors are subject to multiple modifications which imply an additional level of regulation conferred by enzymes that mediate specific modifications, such as phosphorylation, ubiquitination, SUMOylation, and S-nitrosylation. These modifications can affect protein stability, sub-cellular localization, interactions with co-repressors and activators, and DNA binding. The focus here is on direct cross-talk involving transcription factors downstream of auxin, brassinosteroid, and gibberellin signalling. However, many of the concepts discussed are more broadly relevant to questions of how plants can modify their growth by regulating subsets of genes in response to multiple cues. © 2015 The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved.

Choonara I.,University of Nottingham
European Journal of Pediatrics | Year: 2013

Adverse drug reactions (ADRs) are a significant problem in children, affecting one in ten children in hospital. Within the community, one in 500 children will experience an adverse drug reaction each year. Pharmacovigilance has been useful in detecting suspected ADRs. However, most ADRs are unreported and often not suspected. Education of health professionals in relation to drug toxicity improves the reporting rate of suspected ADRs. Clinical trials are useful to evaluate the efficacy of drugs. They are, however, not the best way of looking at ADRs where surveillance following the widespread use of a drug is more appropriate. Alongside work by the regulatory agencies, independent investigators have helped collate data. This information has been useful in developing guidelines to prevent further cases of drug tox-icity. Greater awareness and understanding of drug toxicity in children should result in more rational prescribing. © 2013 Springer-Verlag Berlin Heidelberg.

Langley-Evans S.C.,University of Nottingham
Proceedings of the Nutrition Society | Year: 2013

The developmental origins of health and disease hypothesis postulates that exposure to a less than optimal maternal environment during fetal development programmes physiological function, and determines risk of disease in adult life. Much evidence of such programming comes from retrospective epidemiological cohorts, which demonstrate associations between birth anthropometry and non-communicable diseases of adulthood. The assertion that variation in maternal nutrition drives these associations is supported by studies using animal models, which demonstrate that maternal under- or over-nutrition during pregnancy can programme offspring development. Typically, the offspring of animals that are undernourished in pregnancy exhibit a relatively narrow range of physiological phenotypes that includes higher blood pressure, glucose intolerance, renal insufficiency and increased adiposity. The observation that common phenotypes arise from very diverse maternal nutritional insults has led to the proposal that programming is driven by a small number of mechanistic processes. The remodelling of tissues during development as a consequence of maternal nutritional status being signalled by endocrine imbalance or key nutrients limiting processes in the fetus may lead to organs having irreversibly altered structures that may limit their function with ageing. It has been proposed that the maternal diet may impact upon epigenetic marks that determine gene expression in fetal tissues, and this may be an important mechanism connecting maternal nutrient intakes to long-term programming of offspring phenotype. The objective for this review is to provide an overview of the mechanistic basis of fetal programming, demonstrating the critical role of animal models as tools for the investigation of programming phenomena. Copyright © The Author 2013.

Okaeme N.A.,Alstom | Zanchetta P.,University of Nottingham
IEEE Transactions on Industrial Informatics | Year: 2013

This paper explores the automated experimental control design for variable speed drives using a novel heuristic optimization algorithm. A hybrid approach, which combines desirable characteristics of two of the most widely used biologically-inspired heuristic algorithms, the genetic algorithms (GAs) and the bacterial foraging (BF) algorithms, is studied and developed in this paper. Both the structures and parameters of digital speed controllers are optimized experimentally and directly on the drive while it is subject to different types of mechanical load; the dynamics of these load profiles are generated using a programmable load emulator. The proposed hybrid bacterial foraging (HBF) algorithm is evaluated, for the purpose of control optimization for electric drives, against GA and BF, and their performances are compared and contrasted. © 2012 IEEE.

Bennett C.J.,University of Nottingham
Computational Materials Science | Year: 2013

Three different methods of representing the flow stress of a CrMoV alloy steel, tabular data, a four parameter Norton-Hoff material model and a multi-parameter set of unified constitutive equations, are investigated and compared using an FE model of the spike-forging process developed in the DEFORM-2D FE code. The form of the material models is discussed and the results of the spike-forging models using each of the material models is compared over a range of processing parameters highlighting where discrepancies occur between the models. Recommendations are made regarding the use of the different material models in forging modelling. © 2013 Elsevier B.V. All rights reserved.

Sacks H.,VA Greater Los Angeles Healthcare System | Symonds M.E.,University of Nottingham
Diabetes | Year: 2013

We will review information about and present hypotheses as to the anatomy of brown adipose tissue (BAT). Why is it located where it is in humans? Its anatomical distribution is likely to confer survival value by protecting critical organs from hypothermia by adaptive thermogenesis. Ultimately, the location and function will be important when considering therapeutic strategies for preventing and treating obesity and type 2 diabetes, in which case successful interventions will need to have a significant effect on BAT function in subjects living in a thermoneutral environment. In view of the diverse locations and potential differences in responsiveness between BAT depots, it is likely that BAT will be shown to have much more subtle and thus previously overlooked functions and regulatory control mechanisms. © 2013 by the American Diabetes Association.

Rakha E.A.,University of Nottingham
Journal of Clinical Pathology | Year: 2013

Breast cancer represents a heterogeneous group of diseases with varied presentation, morphological and biological features, behaviour, and response to therapy. Management of breast cancer relies on availability of robust predictive and prognostic factors to support decision making. Identifying and validating the prognostic and predictive value of a given marker is based on studying its association with clinical outcome with or without consideration for therapy, respectively. In the field of cancer research, clinical outcome is determined by assessing certain time-dependent events: 'endpoints' such as tumour progression, recurrence and patient mortality. Guidelines for reporting tumour markers have been published and there is a perception that outcome determination in breast cancer is well documented. However, reviewing the literature has highlighted the varied use of definitions used in clinical outcome measures and there are pitfalls in outcome analysis. This may have contributed to the discrepancies in the literature and to the inconsistent conclusions seen in published studies assessing the same markers. Identification of these pitfalls is expected to improve prognostic and predictive marker assessment. Here issues related to outcome determination in breast cancer including definitions and pitfalls and some critical views are presented.

Wood A.M.,University of Manchester | Joseph S.,University of Nottingham
Journal of Affective Disorders | Year: 2010

Background: Previous research in psychiatry has focused on how negative personality traits and impaired well-being form risk factors for depression. This study presents the first longitudinal test of whether the absence of positive well-being forms an additional unique risk factor for depression. Methods: A large cohort of 5566 people completed a survey at two time points, aged 51-56 at Time 1 and 63-67 at Time 2. Positive psychological well-being included measures self-acceptance, autonomy, purpose in life, positive relationships with others, environmental mastery, and personal growth. Personality was measured as extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience. Depression was measured with the CES-D scale. Results: People with low positive well-being were 7.16 times more likely to be depressed 10-years later. After controlling for personality, negative functioning, prior depression, demographic, economic, and physical heath variables, people with low positive well-being were still over twice as likely to be depressed. Limitations: All measures were self-report, rather than based on peer-report or physician diagnosis. An aging population was studied; replication is needed in younger populations. Conclusions: The absence of positive well-being forms a substantial risk factor for depression, independent of the presence of negative functioning and impaired physical health. Older people with low PWB are very likely to become depressed over 10 years, and preventative intervention and monitoring of these individuals are indicated. © 2009 Elsevier B.V. All rights reserved.

Christodoulou N.G.,University of Nottingham | Christodoulou G.N.,National and Kapodistrian University of Athens
Psychotherapy and Psychosomatics | Year: 2013

Economic crises are chronic stress situations and as such are likely to have psychological and psychopathological consequences. Indeed, they produce adaptive responses (normal sadness) and dysfunctional responses (mainly depression and suicidal potential). Managing the psychological consequences of financial crises is a complex undertaking, which may include political intervention. Diagnosing depression and suicide potential is important anyway but acquires greater importance during periods of economic crisis. The financial crisis in Greece has adversely affected the physical and mental health of the population. Reports from Greece are particularly relevant because on the basis of them one may predict what is likely to happen in other countries ('contagion' of the mental health effects of the crisis), especially those with similar cultural and societal characteristics. Unemployment, poverty and debt have been associated with psychiatric morbidity and suicide, and therefore measures to counter them may reduce harm. Welfare provision can limit psychiatric morbidity during periods of economic crisis, and active labour market programmes and family support programmes have been found to be effective and cost-effective. The measures to limit crisisprovoked morbidity should be culture specific. Psychiatry can respond to the challenges posed by economic crises through its holistic, biopsychosocial and person-centred ethos. Important steps include promoting advocacy and empowerment on a personal level and solidarity and social cohesion on a societal level. Furthermore, mental health professionals can help enhance resilience and mental capital for those suffering from economic crises. Mental illness prevention and mental health promotion should be integral parts of clinical management and service planning in times of financial crisis. Mental health professionals should highlight the cost-effectiveness of mental health investments. © 2013 S. Karger AG, Basel.

Bajaj N.,University of Nottingham | Hauser R.A.,USF Health Byrd Institute | Grachev I.D.,General Electric
Journal of Neurology, Neurosurgery and Psychiatry | Year: 2013

The diagnosis of movement disorders including Parkinson's disease (PD) and essential tremor is determined through clinical assessment. The difficulty with diagnosis of early PD has been highlighted in several recent clinical trials. Studies have suggested relatively high clinical diagnostic error rates for PD and essential tremor. This review was undertaken to clarify the utility of DaT-SPECT imaging with (123I)ioflupane (DaTSCAN or DaTscan or ( 123I)FP-CIT) in assisting practitioners in their clinical decision making by visualising the dopamine transporter in parkinsonian cases. In some patients with suspected parkinsonian syndromes, SPECT imaging with ( 123I)ioflupane is useful to assist in the diagnosis and to help guide prognosis and treatment decisions, including avoiding medications that are unlikely to provide benefit. Clinicians ordering (123I)ioflupane SPECT should be aware of its limitations and pitfalls and should order scans when there is diagnostic uncertainty or when the scan will be helpful in clinical decision making.

Vllasaliu D.,University of Lincoln | Fowler R.,GfK Bridgehead Ltd | Stolnik S.,University of Nottingham
Expert Opinion on Drug Delivery | Year: 2014

Introduction: Recent biopharma deals related to nanocarrier drug delivery technologies highlight the emergence of nanomedicine. This is perhaps an expected culmination of many years of research demonstrating the potential of nanomedicine as the next generation of therapeutics with improved performance. PEGylated nanocarriers play a key role within this field. Areas covered: The drug delivery advantages of nanomedicines in general are discussed, focusing on nanocarriers and PEGylated nanomedicines, including products under current development/clinical evaluation. Well-established drug delivery benefits of PEGylation (e.g., prolonged circulation) are only briefly covered. Instead, attention is deliberately made to less commonly reported advantages of PEGylation, including mucosal delivery of nanomedicines. Finally, some of the issues related to the safety of PEGylated nanomedicines in clinical application are discussed. Expert opinion: The advent of nanomedicine providing therapeutic options of refined performance continues. Although PEGylation as a tool to improve the pharmacokinetics of nanomedicines is well established and is used clinically, other benefits of 'PEGnology', including enhancement of physicochemical properties and/or biocompatibility of actives and/or drug carriers, as well as mucosal delivery, have attracted less attention. While concerns regarding the clinical use of PEGylated nanomedicines remain, evidence suggests that at least some safety issues may be controlled by adequate designs of nanosystems. © 2014 Informa UK, Ltd.

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

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

Wilson J.R.,University of Nottingham
Work | Year: 2012

Ergonomics/human factors is, above anything else, a systems discipline applying a systems philosophy and systems approaches. Many things are labeled as "systems X" in today's world, and this paper specifies just what attributes and notions define ergonomics/human factors in systems terms. These are concern for context, acknowledgement of interactions and complexity, a holistic approach, recognition of emergence and embedding of the professional effort involved within organization systems. These five notions are illustrated with examples from a large body of work on rail human factors. © 2012 - IOS Press and the authors. All rights reserved.

Sellen A.J.,University of Nottingham | Whittaker S.,IBM
Communications of the ACM | Year: 2010

Rather than try to capture everything, system design should focus on the psychological basis of human memory. © 2010 ACM.

Dovlatova N.,University of Nottingham
British Journal of Haematology | Year: 2015

Platelets play a crucial role in haemostasis by preventing bleeding at the site of vascular injury. Several defects in platelet morphology and function have been identified and described over the years. Although a range of methodologies is available to assess platelet function, a significant proportion of subjects with bleeding symptoms and normal coagulation parameters still appear to have normal results on platelet function testing. This might suggest that the reason for bleeding is multifactorial and is due to a combination of several minor defects in platelet function and/or other parts of the haemostatic system or might indicate that the currently available platelet function tests do not provide optimal diagnostic power. This review will summarize the established platelet function tests used for diagnosing inherited platelet abnormalities in adults and children, and discuss the newly developed methodologies as well as unmet challenges and potential areas for further improvement in this field. © 2015 John Wiley & Sons Ltd.

Cardenas R.,University of Chile | Pena R.,University of Concepcion | Alepuz S.,Polytechnic University of Mozambique | Asher G.,University of Nottingham
IEEE Transactions on Industrial Electronics | Year: 2013

Doubly fed induction generators (DFIGs), often organized in wind parks, are the most important generators used for variable-speed wind energy generation. This paper reviews the control systems for the operation of DFIGs and brushless DFIGs in wind energy applications. Control systems for stand-alone operation, connection to balanced or unbalanced grids, sensorless control, and frequency support from DFIGs and low-voltage ride-through issues are discussed. © 1982-2012 IEEE.

Gosling S.N.,University of Nottingham
Environmental Science and Policy | Year: 2012

This article reviews the level of current scientific understanding regarding the impact of future change in the large-scale climate-earth system on ecosystem services. Impacts from sea level rise, ocean acidification, increases in ocean temperature, potential collapse of the thermohaline circulation; failure of the South Asia monsoon; the melting of sea ice, the Greenland Ice Sheet and the West Antarctic Ice Sheet; changes in water availability; and Amazonia forest dieback, are considered. The review highlights that while a number of uncertainties remain in understanding, there is evidence to suggest that climate change may have already affected some ecosystem services. Furthermore, there is considerable evidence to show that future climate change could have impacts on biodiversity, as well as secondary impacts on issues important to human society, including; habitability; land productivity and food security; water security; and potential economic impacts. © 2012 Elsevier Ltd. All rights reserved.

The 'Implications for research' section of the Cochrane systematic review, 'Interventions for vitiligo', published in 2010, highlighted three main issues that impact the standard of vitiligo research: (i) lack of consensus on the classification and definition of vitiligo; (ii) lack of consensus on the methods of assessment and outcome measures for vitiligo; and (iii) heterogeneity of interventions compared. This article provides an update of the progress made to resolve these issues since the publication of the Cochrane systematic review in 2010, 'Interventions for vitiligo'. © 2013 British Association of Dermatologists.

Seddon A.B.,University of Nottingham
International Journal of Applied Glass Science | Year: 2011

That chalcogenide glasses potentially provide a solution for mid-infrared medical endoscopy is discussed in detail for the first time. It is shown that chalcogenide glass fiber optics could underpin new mid-infrared medical endoscopic systems for real-time molecular sensing, imaging, and analysis of tissue and for fiber laser surgery at new mid-infrared wavelengths. Moreover, chalcogenide glass fiber optic and waveguide devices and systems could provide the key to new mid-infrared communications for molecular sensing to inform decision-taking in other sectors as diverse as manufacturing, energy, the environment, and security. The development and deployment of chalcogenide glasses for mid-infrared photonics over the next decade or so could mirror the complexity and versatility of silica fiber optics developed in the 20th century for near-infrared photonics. These ideas are developed in this article and the current status of chalcogenide glass photonics is briefly surveyed. © 2011 The American Ceramic Society and Wiley Periodicals, Inc.

Haselgrove M.,University of Nottingham
Journal of Experimental Psychology: Animal Behavior Processes | Year: 2010

Beckers, Miller, De Houwer, and Urushihara (2006) described the results of 3 blocking experiments conducted with rats. Beckers et al. concluded that the results of these experiments cannot be accounted for with existing theories of associative learning, and argued, instead, that the results were a consequence of the rats engaging in a process akin to effortful reasoning. Simulations of the Rescorla and Wagner (1972) theory of learning presented here challenge this conclusion by providing an alternative, associative, explanation for the results presented by Beckers et al. © 2010 American Psychological Association.

Mostyn A.,University of Nottingham
BMC medical education | Year: 2013

Students regard biological science as one of the most difficult components of the nursing curriculum. However, a good understanding of this area is essential for effective nursing practice. The aim of this study was to explore nursing students' perceptions of the usefulness of supplementary biology podcasts for their learning. Biological science podcasts (n=9) were made available to first-year nursing students (n=189) as supplementary learning tools. On completion of their first year, students were asked to complete a survey which investigated the frequency of their podcast use, reasons for use and their perception of the usefulness of podcasts as a learning tool. 153 of these students participated in the survey study (80.9%). Two focus groups were conducted with students (n=6) to gain a detailed understanding of student experiences of the usefulness of the podcasts for their learning. Survey data demonstrated that most students (71%) accessed at least one podcast. The majority of students who reported accessing podcasts agreed that they were useful as learning tools (83%), revision aids (83%) and that they helped promote understanding of course materials (72%). Focus group participants discussed how they found podcasts especially useful in terms of revision. Students valued being able to repeatedly access the lecture materials, and appreciated having access to podcasts from a range of lecturers. Focus group members discussed the benefits of live recordings, in terms of valuing the information gleaned from questions asked during the lecture sessions, although there were concerns about the level of background noise in live recordings. Lack of awareness of the availability of podcasts was an issue raised by participants in both the survey component and the focus groups and this negatively impacted on podcast use. Nursing students found the availability of biology podcasts helpful for their learning. Successful implementation of these tools to support learning requires teaching staff to understand and promote the importance of these tools.

Kong Y.W.,Toxicology Unit | Ferland-McCollough D.,Toxicology Unit | Jackson T.J.,Toxicology Unit | Jackson T.J.,University of Nottingham | Bushell M.,Toxicology Unit
The Lancet Oncology | Year: 2012

Since the identification of microRNAs (miRNAs) in 1993, and the subsequent discovery of their highly conserved nature in 2000, the amount of research into their function-particularly how they contribute to malignancy-has greatly increased. This class of small RNA molecules control gene expression and provide a previously unknown control mechanism for protein synthesis. As such, it is unsurprising that miRNAs are now known to play an essential part in malignancy, functioning as tumour suppressors and oncogenes. This Review summarises the present understanding of how miRNAs operate at the molecular level; how their dysregulation is a crucial part of tumour formation, maintenance, and metastasis; how they can be used as biomarkers for disease type and grade; and how miRNA-based treatments could be used for diverse types of malignancies. © 2012 Elsevier Ltd.

Wheatley R.J.,University of Nottingham
Physical Review Letters | Year: 2013

A virial expansion of fluid pressure in powers of the density can be used to calculate a wealth of thermodynamic information, but the Nth virial coefficient, which multiplies the Nth power of the density in the expansion, becomes rapidly more complicated with increasing N. This Letter shows that the Nth virial coefficient can be calculated using a method that scales exponentially with N in computer time and memory. This is orders of magnitude more efficient than any existing method for large N, and the method is simple and general. New results are presented for N=11 and 12 for hard spheres, and N=9 and 10 for soft spheres. © 2013 American Physical Society.

Krasnov K.,University of Nottingham
General Relativity and Gravitation | Year: 2011

We give a pedagogical introduction into an old, but unfortunately not commonly known formulation of GR in terms of self-dual two-forms due to in particular Jerzy Plebański. Our presentation is rather explicit in that we show how the familiar textbook solutions: Schwarzschild, Volkoff-Oppenheimer, as well as those describing the Newtonian limit, a gravitational wave and the homogeneous isotropic Universe can be obtained within this formalism. Our description shows how Plebański formulation gives quite an economical alternative to the usual metric and frame-based schemes for deriving Einstein equations. © 2010 The Author(s).

Klitz W.,University of California at Berkeley | Hedrick P.,Arizona State University | Louis E.J.,University of Nottingham
Trends in Genetics | Year: 2012

Highly polymorphic exons of the major histocompatibility complex (MHC, or HLA in humans) encode critical amino acids that bind foreign peptides. Recognition of the peptide-MHC complexes by T cells initiates the adaptive immune response. The particular structure of these exons facilitates gene conversion(GC) events, leading to the generation of new alleles. Estimates for allele creation and loss indicate that more than 10. 000 such alleles are circulating at low frequencies in human populations. Empirical sampling has affirmed this expectation. This suggests that the MHC loci have a system for moving valuable and often complex variants into adaptive service. Here, we argue that HLA loci carry many new mutant alleles prepared to assume epidemiologically meaningful roles when called on by selection provoked by exposure to new and evolving pathogens. Because new mutant alleles appear in a population at the lowest possible frequency (i.e., a single copy), they have typically been thought of as having little consequence. However, this large population of rare yet potentially valuable new alleles may contribute to pathogen defense. © 2012 Elsevier Ltd.

Ralston S.H.,University of Edinburgh | Layfield R.,University of Nottingham
Calcified Tissue International | Year: 2012

Paget disease of bone (PDB) is a common disease characterized by focal areas of increased and disorganized bone turnover. Some patients are asymptomatic, whereas others develop complications such as pain, osteoarthritis, fracture, deformity, deafness, and nerve compression syndromes. PDB is primarily caused by dysregulation of osteoclast differentiation and function, and there is increasing evidence that this is due, in part, to genetic factors. One of the most important predisposing genes is SQSTM1, which harbors mutations that cause osteoclast activation in 5-20 % of PDB patients. Seven additional susceptibility loci for PDB have been identified by genomewide association studies on chromosomes 1p13, 7q33, 8q22, 10p13, 14q32, 15q24, and 18q21. Although the causal variants remain to be discovered, three of these loci contain CSF1, TNFRSF11A, and TM7SF4, genes that are known to play a critical role in osteoclast differentiation and function. Environmental factors are also important in the pathogenesis of PDB, as reflected by the fact that in many countries the disease has become less common and less severe over recent years. The most widely studied environmental trigger is paramyxovirus infection, but attempts to detect viral transcripts in tissues from patients with PDB have yielded mixed results. Although our understanding of the pathophysiology of PDB has advanced tremendously over the past 10 years, many questions remain unanswered, such as the mechanisms responsible for the focal nature of the disease and the recent changes in prevalence and severity. © Springer Science+Business Media, LLC 2012.

Corriden R.,University of Nottingham | Insel P.A.,University of California at San Diego
Purinergic Signalling | Year: 2012

The directional movement of cells can be regulated by ATP, certain other nucleotides (e. g., ADP, UTP), and adenosine. Such regulation occurs for cells that are "professional phagocytes" (e. g., neutrophils, macrophages, certain lymphocytes, and microglia) and that undergo directional migration and subsequent phagocytosis. Numerous other cell types (e. g., fibroblasts, endothelial cells, neurons, and keratinocytes) also change motility and migration in response to ATP, other nucleotides, and adenosine. In this article, we review how nucleotides and adenosine modulate chemotaxis and motility and highlight the importance of nucleotide- and adenosine-regulated cell migration in several cell types: neutrophils, microglia, endothelial cells, and cancer cells. We also discuss difficulties in conducting experiments and drawing conclusions regarding the ability of nucleotides and adenosine to modulate the migration of professional and non-professional phagocytes. © 2012 Springer Science+Business Media B.V.

Johnson S.R.,University of Nottingham
Respiratory Medicine | Year: 2010

Lymphangioleiomyomatosis (LAM) is a rare lung disease which predominantly affects young women. LAM is associated with much morbidity and can lead to respiratory failure and death unless lung transplantation is performed. There are no randomised trials of treatment and no consensus on the management of LAM. In order to produce guidelines for a rare disease where little evidence exists we have adapted existing guideline methodology to evaluate what evidence and knowledge there is to produce a consensus based statement. The process of guideline development comprised forming a group of experts in LAM and related fields including pathology, radiology, tuberous sclerosis and transplantation. Questions were formulated and the available evidence formed into a series of recommendations. Consensus agreement amongst the group was reached by a series of reviews with scoring of agreement, and proposals for modifications, using Likert statistics. The recommendation strength was graded using the American College of Chest Physicians health and science policy grading system according to the quality of evidence, magnitude of benefit, strength of recommendation and strength of consensus achieved. The guidelines describe the diagnostic criteria for LAM and recommended investigations and criteria for the diagnosis and appropriate work up for the diagnosis of LAM. All aspects of management from advice for patients to lung transplantation are discussed. To demonstrate how the guidelines have dealt with different areas of practice and differing evidence levels the specific areas of hormonal therapy, pneumothorax and lung transplantation for LAM are discussed. It is hoped that these guidelines will result in standardisation of diagnostic criteria and patient management which will further improve clinical care and facilitate research and clinical trials. © 2010 Elsevier Ltd. All rights reserved.

Individual bacterial cells can communicate via quorum sensing, cooperate to harvest nutrients from their environment, form multicellular biofilms, compete over resources and even kill one another. When the environment that bacteria inhabit is an animal host, these social behaviours mediate virulence. Over the last decade, much attention has focussed on the ecology, evolution and pathology of bacterial cooperation, and the possibility that it could be exploited or destabilised to treat infections. But how far can we really extrapolate from theoretical predictions and laboratory experiments to make inferences about 'cooperative' behaviours in hosts and reservoirs? To determine the likely importance and evolution of cooperation 'in the wild', several questions must be addressed. A recent paper that reports the dynamics of bacterial cooperation and virulence in a field experiment provides an excellent nucleus for bringing together key empirical and theoretical results which help us to frame - if not completely to answer - these questions. © 2013 WILEY Periodicals, Inc.

Earth-air tunnel ventilation is an energy efficient method of preheating or cooling of supply air to a building. The purposes of this study are to investigate the performance of earth-air heat exchangers under varying soil and atmosphere conditions and the interactions between the heat exchanger and environments. A computer program has been developed for simulation of the thermal performance of an earth-air heat exchanger for preheating and cooling of supply air, taking account of dynamic variations of climatic, load and soil conditions. The program solves equations for coupled heat and moisture transfer in soil with boundary conditions for convection, radiation and evaporation/condensation that vary with the climate both at the soil top surface and inside the heat exchanger. The importance of dynamic interactions between the heat exchanger, soil and atmosphere is illustrated from the comparison of the heat transfer rates through the heat exchanger. The predicted heat transfer rate varies with operating time and decreases along the passage of air in the heat exchanger. Neglecting the interactions would significantly over-predict the heat transfer rate and the amount of over-prediction increases with operating time. © 2014 Elsevier B.V. All rights reserved.

Flindt C.,University of Geneva | Garrahan J.P.,University of Nottingham
Physical Review Letters | Year: 2013

We investigate Lee-Yang zeros of generating functions of dynamical observables and establish a general relation between phase transitions in ensembles of trajectories of stochastic many-body systems and the time evolution of high-order cumulants of such observables. This connects dynamical free energies for full counting statistics in the long-time limit, which can be obtained via large-deviation methods and whose singularities indicate dynamical phase transitions, to observables that are directly accessible in simulation and experiment. As an illustration, we consider facilitated spin models of glasses and show that from the short-time behavior of high-order cumulants, it is possible to infer the existence and location of dynamical or "space-time" transitions in these systems. © 2013 American Physical Society.

Spiller R.C.,University of Nottingham
Gastroenterology Clinics of North America | Year: 2011

A "biomarker" (biological marker) is an indicator of a bodily function that can be objectively measured. A wide range of possible biomarkers for IBS have been considered but at present only gut transit measured using radio-isotope markers meet the criteria of reproducibility and availability. While barostat studies perform reasonably in expert centers, to do them reproducibly requires considerable effort and standardization. This makes them unsuitable for widespread use. However radio-isotope tests are expensive and of limited availability so the search for other more convenient markers including blood and stool tests is still an important goal for the future. © 2011 Elsevier Inc.

Adesso G.,University of Nottingham
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

The extremality of Gaussian states is exploited to show that Gaussian states are the most robust, among all possible bipartite continuous-variable states at fixed energy, against disentanglement due to noisy evolutions in Markovian Gaussian channels involving dissipation and thermal hopping. This proves a conjecture raised recently, providing a rigorous validation of the conclusions of that work. The problem of identifying continuous-variable states with maximum resilience to entanglement damping in more general bosonic open-system dynamical evolutions, possibly including correlated noise and non-Markovian effects, remains open. © 2011 American Physical Society.

Martin-Martinez E.,Institute Fisica Fundamental | Fuentes I.,University of Nottingham
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

We analyze the entanglement tradeoff between particle and antiparticle modes of a Dirac field from the perspective of inertial and uniformly accelerated observers. Our results show that a redistribution of entanglement between particle and antiparticle modes plays a key role in the survival of femionic field entanglement in the infinite-acceleration limit. © 2011 American Physical Society.

Guta M.,University of Nottingham
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

This paper deals with the problem of estimating the coupling constant θ of a mixing quantum Markov chain. For a repeated measurement on the chain's output we show that the outcomes' time average has an asymptotically normal (Gaussian) distribution, and we give the explicit expressions of its mean and variance. In particular, we obtain a simple estimator of θ whose classical Fisher information can be optimized over different choices of measured observables. We then show that the quantum state of the output together with the system is itself asymptotically Gaussian and compute its quantum Fisher information, which sets an absolute bound to the estimation error. The classical and quantum Fisher information are compared in a simple example. In the vicinity of θ=0 we find that the quantum Fisher information has a quadratic rather than linear scaling in output size, and asymptotically the Fisher information is localized in the system, while the output is independent of the parameter. © 2011 American Physical Society.

Powis I.,University of Nottingham
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

The influence upon molecular photoionization dynamics of vibrational motion of the nuclei in both the initial (neutral) state and the final (molecular ion) state is examined using a consistent theoretical treatment applied to the wide range of existing experimental data for the benchmark CO C 1s -1 K-shell ionization. This allows comparisons to be made against cross sections, lab-frame β-parameter measurements, and molecule-frame photoelectron angular distributions that have all been recorded both with, and without, ion vibrational-state resolution. A relatively simple multiple-scattering treatment works well in all these applications, its performance comparing very favorably with alternative relaxed core Hartree-Fock methods. The calculations are extended to examine possible effects of vibrational excitation in the neutral, and show marked effects that extend to energies lying away from the obvious center of the CO σ * shape resonance. © 2011 American Physical Society.

Background: As part of a wider study into students who experience difficulties, we examined the course files of those who had failed to graduate. This was an exploratory, descriptive study investigating how many students left after academic failure or non-academic problems, or simply changed their minds about reading medicine, and at what stage. The aim of the study was to increase our knowledge about the timings of, and reasons for, attrition. This understanding might help to reduce student loss in the future, by informing selection procedures and improving pastoral support at critical times. It might also assist in long-term workforce planning in the NHS. Methods: Relevant data on admission and course progress were extracted manually from the archived files of students who had failed to graduate from five recent consecutive cohorts (entry in 20002004 inclusive), using a customised Access database. Discrete categories of information were supplemented with free text entries. Results: 1188 students registered over the five-year entry period and 73 (6%) failed to graduate. The highest rates of attrition (46/1188, 4%) occurred during the first two years (largely preclinical studies), with 34 students leaving voluntarily, including 11 within the first semester, and 12 having their courses terminated for academic failure. Seventeen left at the end of the third year (Honours course plus early clinical practice) and the remaining ten during the final two clinical years. The reasons for attrition were not always clear-cut and often involved a mixture of academic, personal, social and health factors, especially mental health problems. Conclusions: The causes of attrition are complex. A small number of students with clear academic failure might require individual educational interventions for remediation. However, this could have substantial resource implications for the Faculty. Mental health problems predominate in late course attrition and may have been undisclosed for some time. The introduction of a structured exit interview may provide further insight, especially for those students who leave suddenly and unexpectedly early in the course. © 2012 Yates; licensee BioMed Central Ltd.

Moriarty P.J.,University of Nottingham
Surface Science Reports | Year: 2010

The adsorption of C60 and its "siblings"including the higher fullerenes, endofullerenes, substitutionally doped species, and functionalised derivativeson semiconductor surfaces has been studied for almost two decades. A broad range of techniques, spanning scanning probe microscopy (and the associated single molecule characterisation tools) to synchrotron-based methods such as photoemission and X-ray absorption spectroscopy, has been used to elucidate very many aspects of the chemical behaviour, electronic properties, and self-assembly of fullerenes on elemental and compound semiconductor surfaces. The fullerene-on-silicon system has also played a pivotal role in the development of room temperature molecular manipulation protocols. Here we review key advances (both experimental and theoretical) in our understanding of the fullerene-semiconductor interface over the last eighteen years. While the interaction of fullerene molecules with clean and adsorbate-covered silicon surfaces forms a key focus of the review, adsorption on germanium, IIIV (GaAs, InP), and IVVI (GeS) surfaces is also covered. © 2010 Elsevier B.V. All rights reserved.

We investigate probability distributions in dynamic multi-mode electromagnetic cavities, commonly referred to as mode-stirred reverberation chambers. We show that Bessel K and Bessel I distributions play a prominent role when a large but finite number of excited modes, loss of energy (through aperture leakage or dissipation), or nonstationary transient fields are involved. With the aim at reducing the number of simultaneously excited cavity modes as much as possible while maintaining a well-characterizable quasi-random field, measurement results indicate that single-mode stirring is feasible at certain frequencies well below the usual 'lowest usable frequency' of the cavity. Distributions for nonstationary fields are shown to allow for improved estimation of the maximum-to-mean ratio of the received power during stepwise rotation of the mode stirrer. © 2013 The Author.

An important tool in cell biology is the combination of immunogold labelling and transmission electron microscopy (TEM) by which target molecules (e.g. antigens) are bound specifically to affinity markers (primary antibodies) and then detected and localised with visualisation probes (e.g. colloidal gold particles bound to protein A). Gold particles are electron-dense, punctate and available in different sizes whilst TEM provides high-resolution images of particles and cell compartments. By virtue of these properties, the combination can be used also to quantify one or more defined targets in cell compartments. During the past decade, new ways of quantifying gold labelling within cells have been devised. Their efficiency and validity rely on sound principles of specimen sampling, event counting and inferential statistics. These include random selection of items at each sampling stage (e.g. specimen blocks, thin sections, microscopical fields), stereological analysis of cell ultrastructure, unbiased particle counting and statistical evaluation of a suitable null hypothesis (no difference in the intensity or pattern of labelling between compartments or groups of cells). The following approaches are possible: (i) A target molecule can be tested for preferential labelling by mapping the localisation of gold particles across a set of compartments. (ii) Data from wild-type and knockdown/knockout control cells can be used to correct raw gold particle counts, estimate specific labelling densities and then test for preferential labeling. (iii) The same antigen can be mapped in two or more groups of cells to test whether there are experimental shifts in compartment labelling patterns. (iv) A variant of this approach uses more than one size of gold particle to test whether or not different antigens colocalise in one or more compartments. (v) In studies involving antigen translocation, absolute numbers of gold particles can be mapped over compartments at specific positions within polarised, oriented or dividing cells. Here, the current state of the art is reviewed and approaches are illustrated with virtual datasets. © 2011 The Author. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.

Neurotrophins are important regulators of neuronal function in the developing and adult brain and thus play a critical role in sustaining normal behavioral function. Brain-derived neurotrophic factor (BDNF) has been the most widely studied neurotrophin because of its important role as modulator of synaptic plasticity, which is essential to the regulation of experience-dependent behavior. Extensive work implicates BDNF in hippocampus-dependent forms of learning and memory, although it also regulates other cognitive processes. A role for BDNF in anxiety-related disorders and aggressive behavior can also be suspected. More importantly, BDNF signaling has recently emerged as a key player in the development of drug addiction and is well known to be involved in adaptation to stress and stress-related disorders. NGF in the other hand is thought to be involved in aggression and alcohol dependence. Finally, BDNF appears to participate in the therapeutic effects of drugs and interventions capable of reversing or attenuating behavioral disturbances relevant to psychiatric and neurodegenerative disorders. Compounds mimicking BDNF signaling, however, are unlikely to be used in a clinical context, given their adverse side effects and pharmacokinetic limitations. Copyright 2010 Elsevier Inc. All rights reserved.

O'Neill P.D.,University of Nottingham
Statistics in Medicine | Year: 2010

Disease transmission models are becoming increasingly important both to public health policy makers and to scientists across many disciplines. We review some of the key aspects of how and why such models are related to data from infectious disease outbreaks, and identify a number of future challenges in the field. Copyright © 2010 John Wiley & Sons, Ltd.

Akyol A.,University of Nottingham
The British journal of nutrition | Year: 2012

In addition to being a risk factor for adverse outcomes of pregnancy, maternal obesity may play a role in determining the long-term disease patterns observed in the resulting offspring, with metabolic and dietary factors directly programming fetal development. The present study evaluated the potential for feeding rats an obesogenic cafeteria diet (O) pre-pregnancy, during pregnancy, during lactation and for the offspring post-weaning, to programme glucose tolerance. Early-life exposure to an O diet had no significant effect on offspring food intake. Early-life programming associated with O feeding to induce maternal obesity was associated with reduced adiposity in offspring weaned onto low-fat chow. Adult offspring exposed to an O diet in early life and weaned on a chow diet had low fasting glucose and insulin concentrations and appeared to be more sensitive to insulin during an intraperitoneal glucose tolerance test. When weaned on an O diet, male offspring were more prone to glucose intolerance than females. On the basis of the area under the glucose curve, maternal O feeding at any point from pre-mating to lactation was associated with impaired glucose tolerance. The mechanism for this was not identified, although increased hepatic expression of Akt2 may have indicated disturbance of insulin signalling pathways. The observations in the present study confirm that maternal overnutrition and obesity during pregnancy are risk factors for metabolic disturbance in the resulting offspring. Although the effects on glucose homeostasis were independent of offspring adiposity, the programming of a glucose-intolerant phenotype was only observed when offspring were weaned on a diet that induced greater fat deposition.

Osteryoung K.W.,Michigan State University | Pyke K.A.,University of Nottingham
Annual Review of Plant Biology | Year: 2014

Plastid division is fundamental to the biology of plant cells. Division by binary fission entails the coordinated assembly and constriction of four concentric rings, two internal and two external to the organelle. The internal FtsZ ring and external dynamin-like ARC5/DRP5B ring are connected across the two envelopes by the membrane proteins ARC6, PARC6, PDV1, and PDV2. Assembly-stimulated GTPase activity drives constriction of the FtsZ and ARC5/DRP5B rings, which together with the plastid-dividing rings pull and squeeze the envelope membranes until the two daughter plastids are formed, with the final separation requiring additional proteins. The positioning of the division machinery is controlled by the chloroplast Min system, which confines FtsZ-ring formation to the plastid midpoint. The dynamic morphology of plastids, especially nongreen plastids, is also considered here, particularly in relation to the production of stromules and plastid-derived vesicles and their possible roles in cellular communication and plastid functionality. Copyright © 2014 by Annual Reviews.

Li H.X.,University of Nottingham
Mechanics of Materials | Year: 2011

A nonlinear mathematical programming approach together with the finite element method and homogenization technique is developed to implement kinematic limit analysis for a microstructure and the macroscopic strength of a composite with anisotropic constituents can be directly calculated. By means of the homogenization theory, the classical kinematic theorem of limit analysis is generalized to incorporate the microstructure - Representative Volume Element (RVE) chosen from a periodic composite/heterogeneous material. Then, using an associated plastic flow rule, a general yield function is directly introduced into limit analysis and a purely-kinematic formulation is obtained. Based on the mathematical programming technique, the finite element model of microstructure is finally formulated as a nonlinear programming problem subject to only one equality constraint, which is solved by a direct iterative algorithm. The calculation is entirely based on a purely-kinematical velocity field without calculation of stress fields. Meanwhile, only one equality constraint is introduced into the nonlinear programming problem. So the computational cost is very modest. Both anisotropy and pressure-dependence of material yielding behavior are considered in the general form of kinematic limit analysis. The developed method provides a direct approach for determining the macroscopic strength domain of anisotropic composites and can serve as a powerful tool for microstructure design of composites. © 2011 Elsevier Ltd. All rights reserved.

Cragg L.,University of Nottingham | Chevalier N.,University of Nebraska - Lincoln
Quarterly Journal of Experimental Psychology | Year: 2012

It is now well established in the adult literature that the ability to engage in flexible thought and action is a complex skill that relies on a number of underlying processes. The development of this skill has received growing interest in recent years. However, theories explaining children's ability to switch between different tasks typically focus on a single underlying process and are rarely extended to explain development beyond the preschool years. This article reviews the current literature on set shifting in children in comparison with task switching in adults, in order to highlight the range of factors that impact on children's ability to flexibly shift between tasks. In doing this we hope to set the scene for future research that can begin to establish the relationships between these processes and how they change with age. © 2012 Copyright The Experimental Psychology Society.

Tian H.,Shandong University | De Smet I.,Ghent University | De Smet I.,University of Nottingham | Ding Z.,Shandong University
Trends in Plant Science | Year: 2014

Primary and lateral roots comprise root systems, which are vital to the growth and survival of plants. Several molecular mechanisms associated with primary and lateral root growth have been described, including some common regulatory factors for their initiation and development. However, in this opinion article, we discuss the distinct growth behavior of lateral roots in response to environmental cues, such as salinity, gravity, and nutrient availability, which are mediated via specific regulators. We propose that differential growth dynamics between primary and lateral roots are crucial for plants to adapt to the ever-changing environmental conditions. © 2014 Elsevier Ltd.

Holroyd J.,University of Nottingham
Consciousness and Cognition | Year: 2015

Are individuals responsible for behaviour that is implicitly biased? Implicitly biased actions are those which manifest the distorting influence of implicit associations. That they express these 'implicit' features of our cognitive and motivational make up has been appealed to in support of the claim that, because individuals lack the relevant awareness of their morally problematic discriminatory behaviour, they are not responsible for behaving in ways that manifest implicit bias. However, the claim that such influences are implicit is, in fact, not straightforwardly related to the claim that individuals lack awareness of the morally problematic dimensions of their behaviour. Nor is it clear that lack of awareness does absolve from responsibility. This may depend on whether individuals culpably fail to know something that they should know. I propose that an answer to this question, in turn, depends on whether other imperfect cognitions are implicated in any lack of the relevant kind of awareness.In this paper I clarify our understanding of 'implicitly biased actions' and then argue that there are three different dimensions of awareness that might be at issue in the claim that individuals lack awareness of implicit bias. Having identified the relevant sense of awareness I argue that only one of these senses is defensibly incorporated into a condition for responsibility, rejecting recent arguments from Washington & Kelly for an 'externalist' epistemic condition. Having identified what individuals should - and can - know about their implicitly biased actions, I turn to the question of whether failures to know this are culpable. This brings us to consider the role of implicit biases in relation to other imperfect cognitions. I conclude that responsibility for implicitly biased actions may depend on answers to further questions about their relationship to other imperfect cognitions. © 2014 .

Olver M.E.,University of Saskatchewan | Wong S.C.P.,University of Nottingham
Personality Disorders: Theory, Research, and Treatment | Year: 2015

We prospectively examined the short- and long-term prediction of several recidivism outcomes as a function of psychopathy and age in a sample of 273 Canadian federal inmates with an average 24 years postrelease follow-up. Offenders were rated using the original 22-item Hare Psychopathy Checklist (PCL: Hare, 1980) based on extensive archival file information, and the ratings were used to compute the Psychopathy Checklist-Revised (Hare, 2003) and the 4 facet scores. PCL-R total scores and the Lifestyle and Antisocial facets, but not the Interpersonal and Affective facets, showed mostly small and some moderate predictive efficacy for general and nonviolent recidivism over 3-, 5-, 10-, and 20-year fixed follow-ups, and predicted violence recidivism at shorter follow-ups. Age at release was negatively correlated with all recidivism outcomes and follow-up periods for both high and low PCL-R rated offenders, and uniquely predicted all recidivism outcomes after controlling for the PCL-R using Cox regression survival analysis. Increased age was consistently linked to recidivism reduction even for psychopathic offenders. The results showed that both PCL-R scores and age contributed to the prediction of recidivism; however, the PCL-R facets made differential contributions that varied with the type of offense (violent vs. nonviolent) and follow-up time (shorter vs. longer). The results have implications for both risk assessment using the PCL-R and potentially for risk reduction interventions. © 2014 American Psychological Association.

Monaghan T.M.,University of Nottingham
Infectious Disease Clinics of North America | Year: 2015

Clostridium difficile is associated with a spectrum of clinical manifestations ranging from asymptomatic carriage to severe life-threatening pseudomembranous colitis. Current perspectives indicate that C difficile pathogenesis is a multifactorial disease process dictated by pathogenic toxin production, gut microbial dysbiosis, and altered host inflammatory responses. This article summarizes recent findings underpinning the cellular and molecular mechanisms regulating bacterial virulence and sheds new light on the critical roles of the host immune response, intestinal microbiota, and metabolome in mediating disease pathogenesis. © 2015 Elsevier Inc.

Szabadi E.,University of Nottingham
Drug Discovery Today | Year: 2014

The level of arousal reflects the interaction between wakefulness-promoting and sleep-promoting nuclei located in the hypothalamus and brainstem. The nuclei and their connections constitute the sleep-arousal network. Mapping out this network, together with the neurotransmitters involved, has created a unique opportunity for the design of drugs for sleep disorders-it has become possible to target specific sites within the network with predictable effects on the level of arousal. Recent examples of this approach are orexin receptor and 5HT2A serotonin receptor antagonists and melatonin receptor agonists for the treatment of insomnia, and H3 histamine receptor antagonists for the treatment of excessive daytime sleepiness. © 2014 Elsevier Ltd.

Jopling C.L.,University of Nottingham
RNA Biology | Year: 2012

microRNA-122 (miR-122) was one of the first examples of a tissue-specific miRNA. It is highly expressed in liver, where it constitutes 70% of the total miRNA pool. miR-122 expression is specific to the vertebrate lineage, where the sequence of the mature miRNA is completely conserved. miR-122 is a target for extensive study due to its association with cholesterol metabolism and hepatocellular carcinoma, and its important role in promoting hepatitis C virus (HCV) replication. This review will discuss the biogenesis and function of miR-122. © 2012 Landes Bioscience.

Williams H.C.,University of Nottingham | Dellavalle R.P.,Aurora University
Journal of Investigative Dermatology | Year: 2012

Randomized controlled clinical trials remain the best method for minimizing bias when evaluating dermatological treatments. Many dermatologic clinical trials have suffered from small sample sizes, selective reporting of outcomes, publication bias, poor reporting, and heterogeneous outcomes that have hampered comparabilitydeficiencies that can be overcome by adopting good trial planning and reporting practice encouraged by this journal. Although a profusion of explanatory placebo-controlled studies have contributed little to decision making in the clinical setting, some comparative effectiveness trials such as the use of topical corticosteroids for pemphigoid may have played a pivotal role in improving the well-being of dermatological patients. Systematic reviews (SRs) of clinical trials strive to organize the entire body of evidence while minimizing bias so that policy makers and guideline developers can base their recommendations on the appropriate strength and level of evidence. In dermatology, SRs, such as those undertaken by the Cochrane Collaboration, have produced clear clinical messages despite conflicting individual studies, and also play a key role in identifying research gaps. Future challenges include optimizing the use of research resources, adopting methodological developments in health technology assessment, and prospective registration and complete reporting of all study results. © 2012 The Society for Investigative Dermatology.

Jeffcoate W.J.,University of Nottingham
Diabetes/Metabolism Research and Reviews | Year: 2012

The decision-making process involved in the management of diabetic foot wounds is complex but hinges on certain simple principles. The first is to agree the actual aim of management with the patient or their representative - and healing of an open wound may be only a part of this. The agreed plan should be discussed and reviewed if the wound is unresponsive to intervention. Management depends otherwise on regular debridement and cleansing, treatment of any infection, consideration of revascularisation and protection of the wound by dressings and off-loading. The evidence to justify the use of advanced wound care therapies is not strong, and outcome depends more on the organisation of the wound care process than on the choice of a particular wound care product. The introduction of an expert multidisciplinary team has been shown to lead to a very significant reduction in the incidence of major amputation and it is likely that it is the availability or otherwise of prompt expert advice which is the principal explanation of the major variations that are known to exist in the incidence of amputation even within single countries. © 2012 John Wiley & Sons, Ltd.

Aithal G.P.,University of Nottingham
Liver International | Year: 2015

In contrast to the studies that have explored association of genetic variants with other complex traits, those investigating hepatotoxicity have identified risk alleles with substantially higher risk ratios for the susceptibility to drug-induced liver injury (DILI). In addition, a relatively small number of human leukocyte antigen (HLA) alleles have overlapping associations with a variety of adverse reactions including DILI, cutaneous hypersensitivity and drug-induced pancreatitis. However, if used as a test prior to prescription to prevent potential adverse reaction, genotyping would have a very high negative predictive value, yet a low positive predictive value based on the low incidence of DILI. One potential consideration is to treat all relevant HLA genotypes as one panel covering different forms of adverse drug reactions, thereby improving the positive predictive value of the panel and widen its application. The majority of HLA alleles associated with DILI have a very high negative predictive value; therefore, they can be used to rule out hepatotoxicity caused by particular drugs. A high negative predictive value of a genetic test can be used to identify the correct agent underlying DILI when the patient had been exposed to two concomitant medications with a potential to cause DILI. Inclusion of genetic tests in the causality assessment of an event, where DILI is suspected, may improve consistency and precision of causality assessment tools. A recent clinical trial used N-acetyltransferase 2 genotyping to determine the appropriate dose of isoniazid in an anti-tuberculosis therapeutic regimen and demonstrated that pharmacogenetic-based clinical algorithms have the potential to improve efficacy of a drug and to reduce DILI. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Grant N.H.,University of Nottingham
The Cochrane database of systematic reviews | Year: 2013

Gastroschisis is an uncommon congenital defect of the anterior abdominal wall that results in herniation of intestinal loops outside the abdominal cavity. Babies with gastroschisis generally do well, but there remains a mortality rate of 5% to 10% and some require prolonged parenteral nutrition and intensive care. Significant injury to the exposed bowel may occur in-utero, and earlier birth may reduce this, improve long-term outcomes and reduce complications, such as necrotising enterocolitis. However, it may also increase complications related to prematurity. There is a lack of published data in this area. To assess the effects of elective preterm birth for fetal gastroschisis in pregnancies complicated by this condition. The mode of birth may be either vaginal or by caesarean section, but this review is studying only timing, not the route, of birth. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (16 January 2013). Individual patient randomised controlled trials of planned preterm birth in pregnancies complicated by fetal gastroschisis, diagnosed by ultrasound scanning in time for preterm birth to be an option, and without other fetal anomalies. The intervention is planned preterm birth, prior to 37 weeks and 0 days' gestation, versus planned later birth, at or after 37 weeks and 0 days' gestation (mode of birth is not part of the intervention).We did not include quasi-randomised controlled trials and cluster trials. Cross-over trials are not appropriate for this condition. Studies that were presented in abstract form only were eligible for inclusion, providing that the population included women with pregnancies affected by fetal gastroschisis, the interventions were defined and the treatment selection was randomised. Two review authors independently assessed for inclusion the one trial identified as a result of the search strategy and assessed trial quality. Two review authors extracted data and checked it for accuracy. We included one study, involving 40 infants and 42 women. The trial was underpowered to detect clinically important outcome differences between the two policies. There were no significant benefits or adverse effects of elective preterm birth at 36 weeks' gestation for fetal gastroschisis. The primary outcomes were caesarean section and neonatal survival to discharge. Two babies died after birth but before discharge in the elective (intervention) group versus none in the spontaneous group (risk ratio (RR) 5.00; 95% confidence interval (CI) 0.26 to 98.00; one study, n = 40). Seven women (33%) in the elective group and nine women (43%) in the spontaneous group delivered by caesarean section (RR 0.78; 95% CI 0.36 to 1.70).Similarly, for the secondary outcomes, there were no statistical differences in birthweight, ventilation requirements, necrotising enterocolitis and requirement for repeat surgery between the two groups. None of our prespecified maternal secondary outcomes were reported in the included study.We also examined gestational age at birth as a non-prespecified outcome. There was a difference in gestational age at birth between the two arms of the trial (35.8 weeks (SD 0.7) in the elective group and 36.7 (SD 1.5) in the spontaneous group. Possible reasons for this small mean difference include a trend towards spontaneous preterm birth in pregnancies complicated by fetal gastroschisis. This review is unable to draw any firm conclusions regarding preterm birth for infants with gastroschisis. It is not possible to say whether the intervention is beneficial or harmful for these babies or their mothers. Only one small trial is included. Further research is needed in this area.

Krasnov K.,University of Nottingham
Journal of High Energy Physics | Year: 2015

Abstract: In the metric formulation gravitons are described with the parity symmetric S+ 2 ⊗ S− 2 representation of Lorentz group. General Relativity is then the unique theory of interacting gravitons with second order field equations. We show that if a chiral S+ 3 ⊗ S− representation is used instead, the uniqueness is lost, and there is an infinite-parametric family of theories of interacting gravitons with second order field equations. We use the language of graviton scattering amplitudes, and show how the uniqueness of GR is avoided using simple dimensional analysis. The resulting distinct from GR gravity theories are all parity asymmetric, but share the GR MHV amplitudes. They have new all same helicity graviton scattering amplitudes at every graviton order. The amplitudes with at least one graviton of opposite helicity continue to be determinable by the BCFW recursion. © 2015, The Author(s).

An exact finite difference (FD) representation of the second-order derivative on three nodes is presented and used to obtain an FD algorithm that allows achieving an arbitrary truncation order. The FD weights are calculated analytically using the series that expresses the field value at a given FD node in terms of the field value and its derivatives at a neighboring node, when a stepwise discontinuity in the refractive index distribution is present between the nodes. The results obtained confirm that the proposed algorithm is accurate, efficient, and achieves the predicted improved performance. © 2010 Optical Society of America.

Sotiriou T.P.,University of Nottingham
Lecture Notes in Physics | Year: 2015

Gravity theories with non-minimally coupled scalar fields are used as characteristic examples in order to demonstrate the challenges, pitfalls and future perspectives of considering alternatives to general relativity. These lecture notes can be seen as an illustration of features, concepts and subtleties that are present in most types of alternative theories, but they also provide a brief review of generalised scalar-tensor theories. © Springer International Publishing Switzerland 2015.

Koppelman G.H.,University of Groningen | Sayers I.,University of Nottingham
Journal of Allergy and Clinical Immunology | Year: 2011

There has been great progress in identifying new asthma susceptibility genes. In asthmatic subjects there is variable airway remodeling that includes features such as smooth muscle hypertrophy/hyperplasia, basement membrane thickening, and increased extracellular matrix deposition. Does airway remodeling have a genetic contribution in asthma? Data from different murine strains suggest there is a genetic contribution to the development and progression of airway remodeling. In human subjects it is important to consider what surrogate markers of remodeling have been used in genetic studies. Baseline FEV1 and airway hyperresponsiveness are determined by a complex interplay of factors, including nonremodeling mechanisms; however, we consider a decline in FEV1 as a robust marker of remodeling. To date, single nucleotide polymorphisms spanning ADAM33, ESR1, PLAUR, and VEGF have been associated with an excess decline in lung function in asthmatic subjects carrying the rare alleles (FEV1, -13.0 to 55.2 mL/y excess). Interestingly these genes have overlapping functions in proteolytic pathways in the airways. There is accumulating evidence that genetic factors are important in the development of airway remodeling in asthmatic subjects, and further longitudinal studies with additional remodeling phenotypes and genome-wide association studies will identify novel susceptibility genes, leading to new approaches to target remodeling in asthmatic subjects. © 2011 American Academy of Allergy, Asthma & Immunology.

Turnbull B.,University of Nottingham
Physical Review Letters | Year: 2011

This Letter describes an investigation of interfacial melting in ice-bearing granular flows. It is proposed that energy associated with granular collisions causes melting at an ice particle's surface, which can thus occur at temperatures well below freezing. A laboratory experiment has been designed that allows quantification of this process and its effect on the dynamics of a granular shear flow of ice spheres. This experiment employs a rotating drum, half filled with ice particles, situated in a temperature controlled laboratory. Capillary forces between the wetted melted particle surfaces lead to the clumping of particles and enhanced flow speeds, in turn leading to further melting. Dimensional analysis defines a parameter space for further experimentation. © 2011 American Physical Society.

Martin-Martinez E.,Institute Fisica Fundamental | Fuentes I.,University of Nottingham | Mann R.B.,University of Waterloo
Physical Review Letters | Year: 2011

We show that a detector acquires a Berry phase due to its motion in spacetime. The phase is different in the inertial and accelerated case as a direct consequence of the Unruh effect. We exploit this fact to design a novel method to measure the Unruh effect. Surprisingly, the effect is detectable for accelerations 109 times smaller than previous proposals sustained only for times of nanoseconds. © 2011 American Physical Society.

Krasnov K.,University of Nottingham
Physical Review Letters | Year: 2011

It has already been known for two decades that general relativity can be reformulated as a certain gauge theory, so that the only dynamical field is an SO(3) connection and the spacetime metric appears as a derived object. However, no simple action principle realizing these ideas has been available. A new elegant action principle for such a "pure connection" formulation of GR is described. © 2011 American Physical Society.

Ferreira H.R.C.,University of Nottingham
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We demonstrate that the warped AdS3 black hole solutions of topologically massive gravity are classically stable against massive scalar field perturbations by analyzing the quasinormal and bound state modes of the scalar field. In particular, it is found that although classical superradiance is present it does not give rise to superradiant instabilities. The stability is shown to persist even when the black hole is enclosed by a stationary mirror with Dirichlet boundary conditions. This is a surprising result in view of the similarity between the causal structure of the warped AdS3 black hole and the Kerr spacetime in 3+1 dimensions. This work provides the foundations for the study of quantum field theory in this spacetime. © 2013 American Physical Society.

Pappas G.,University of Nottingham
Monthly Notices of the Royal Astronomical Society | Year: 2015

In recent years, a lot of work was done that has revealed some very interesting properties of neutron stars. One can relate the first few multipole moments of a neutron star, or quantities that can be derived from them, with relations that are independent of the equation of state (EoS). This is a very significant result that has great implications for the description of neutron stars and in particular for the description of the spacetime around them. Additionally, it was recently shown that there is a four-parameter analytic spacetime, known as the two-soliton spacetime, which can accurately capture the properties of the geometry around neutron stars. This allows for the possibility of describing in a unified formalism the astrophysically relevant properties of the spacetime around a neutron star independently of the particulars of the EoS for the matter of the star. More precisely, the description of these astrophysical properties is done using an EoS omniscient spacetime that can describe the exterior of any neutron star. In the present work, we investigate properties such as the location of the innermost stable circular orbit RISCO (or the surface of the star when the latter overcomes the former), the various frequencies of perturbed circular equatorial geodesics, the efficiency of an accretion disc, its temperature distribution, and other properties associated with the emitted radiation from the disc, in a way that holds for all possible choices of a realistic EoS for the neutron star. Furthermore, we provide proof of principle that if one were to measure the right combinations of pairs of these properties, with the additional knowledge of the mass of the neutron star, one could determine the EoS of the star. © 2015 The Authors. Published by Oxford University Press on behalf of the Royal Astronomical Society.

Harwood R.H.,University of Nottingham
Journal of the Royal College of Physicians of Edinburgh | Year: 2014

When close to death, people stop eating. In neurodegenerative conditions swallowing may become unsafe, and artificial nutrition and hydration (ANH) may be proposed or requested. But nutrition is surrounded by other considerations: opportunity, help, environment, enjoyment, mood, social being and symbolic importance. Poor care or deliberate attempts to end life might also result in poor nutrition and dehydration. Decisions about ANH are open to conventional ethical analysis and subject to mental capacity law. Most people with appetite or swallowing failure have advanced dementia and lack capacity. Determining someone’s best interests means considering values and preferences, previous and current wishes, and requires consultation with families and other carers. Short-term prognosis is difficult to judge in non-malignant conditions. We often do not know the views of the individual. Moreover, we are unsure if ANH can achieve the goals intended of it – there is little evidence that tube feeding prolongs life, prevents aspiration or improves wellbeing. Palliative care and best practice dementia care have much in common. Open communication, good relationships with families and carers, skilled approaches to problems and respect for individuals and their diversity. Modified oral feeding will be appropriate for most; ANH is rarely appropriate, but some individuals and their families feel differently. Careful assessment for potentially treatable causes of swallowing and appetite problems, honest communication about uncertainties over prognosis and the impact of interventions and ascertainment of individuals’ values and beliefs make for better care for people with dementia and better decisions about feeding. © 2014 Royal College of Physicians of Edinburgh.

This paper presents the findings from a comparative qualitative study of British Indian and British Pakistani gay men, all of whom self-identified as members of their religious communities. Data were analysed using thematic analysis and identity process theory. Results suggest that the intersection between sexuality and religion is more relevant to British Pakistani participants, while the intersection between sexuality and ethnicity is more relevant to British Indian participants. For British Indian participants in particular, homosexuality seems to be socially problematic, posing potential obstacles for interpersonal and intergroup relations. Conversely, for British Pakistanis, homosexuality is both socially and psychologically problematic, affecting intrapsychic as well as interpersonal levels of human interdependence. Theoretical and practical implications are discussed. © 2012 Copyright Taylor and Francis Group, LLC.

Thul R.,University of Nottingham
Cold Spring Harbor Protocols | Year: 2014

The stochastic dynamics of the inositol-1,4,5-trisphosphate (IP3) receptor (IP3R) is key to understanding a wide range of observed calcium (Ca2+) signals. The stochastic nature results from the constant binding and unbinding of Ca2+ and IP3 to and from their respective binding sites and is especially important in the initiation of a Ca2+ puff (i.e., the release of Ca2+ through a cluster of IP3Rs). Once the first IP3R opens, the Ca2+ concentration rises significantly around the ion channel, increasing the open probability for neighboring IP3Rs. This opening may trigger the activation of further receptors, giving rise to a Ca2+ puff. In this protocol, we determine the time that it takes for a single IP3R to open from rest. We explicitly take into account the tetrameric structure of the IP3R and the fact that multiple subunits must be active before the channel opens. We develop code for a stochastic simulation of the IP3R and simulate it using the software package MATLAB. This protocol shows the basic form of a stochastic simulation algorithm and may serve as a starting point to investigate more complex gating dynamics. © 2014 Cold Spring Harbor Laboratory Press.

Spencer G.,University of Nottingham
Health, Risk and Society | Year: 2013

Concern about health-related risks dominates modern day public health discourses on young people's health. Based on 'official' notions of health, the public health risk-based approach not only downplays the potentially different meanings young people attach to concepts of health, but it also has a tendency to problematise and pathologise young people and their health. Drawing on findings from an ethnographic study with young people aged 15-16 years in England (n = 55); in this article, I examine young people's understandings of health and health-related risks. I used group discussions, individual interviews and observational work in a school and surrounding community settings to collect the data on which this article is based. In this article, I show the importance young people in my study attached to 'being happy' and 'having fun', but also how dominant constructions of youth as a time of risk were taken up and reproduced by young people themselves to create and sustain differences amongst young people. I examine the implications of these differences for young people's health and the possibilities for empowerment - highlighting some of the emergent contradictions between young people's constructions of the 'healthy self' and 'risky' young Other. Specifically, in this article, I highlight young people's preference for a more positive conceptualisation of their health, one which recognises the importance of their shared social positioning for the promotion of health. © 2013 Copyright Taylor and Francis Group, LLC.

Devalia B.,University of Nottingham
International Journal of Clinical Practice | Year: 2010

Background: Diabetic ketoacidosis (DKA) is a hyperglycaemic emergency associated with major morbidity and mortality. It has been shown that treating patients admitted with DKA using an integrated care pathway, or protocol, reduces time taken to initiate management thus optimising care. Early input from diabetes specialist services should also be sought. A new protocol for managing DKA was introduced in Sherwood Forest Trust in July 2008. Aims: To assess whether the trust DKA protocol is being followed at Kingsmill and Newark District General Hospitals during acute management (first 4 h) of patients. Methods: Retrospective case note review of all adult patients coded as DKA from July 2008 to February 2009. Results: Seventy-eight percent of patients were correctly diagnosed according to protocol. Hundred percent of patients had IV access and correct blood tests within 1 h of admission. Eighty percent were given appropriate fluid resuscitation within the first hour. Seventy-two percent had correct insulin prescribed and 73% were on the correct sliding scale. Seventy-eight to ninety percent of patients had correct initial investigations ordered. However only 46% of patients requiring High Dependency Unit care were referred appropriately. Between hours 2 and 4 only 38% had repeat electrolytes checked and only 35-60% of patients had the correct fluid prescribed. Conclusions: The findings indicated that there was awareness of the new DKA protocol. It was referred to and placed in clinical notes but not always followed. Management of patients with DKA within the first hour was compliant. However, subsequent fluid management and electrolyte monitoring was poor. It was found that using a protocol does help to standardise initial management of patients but further education is needed and referral criteria need clarifying. Access to 24-hour specialist services may also help to optimise management. © 2010 Blackwell Publishing Ltd.

McMurran M.,University of Nottingham
Legal and Criminological Psychology | Year: 2011

Purpose. Research into alcohol-related aggression has typically focused on perpetrators' externalizing characteristics. The purpose of this exploratory review is to examine the contribution of anxiety to alcohol-related aggression. Arguments. Anxiety disorders are associated with externalizing disorders in childhood, but anxiety appears to protect against extreme antisocial behaviours. In contrast, in adolescence and early adulthood, anxiety appears to be associated with increased risk of antisocial behaviour. One possible explanation for this disjunction may be alcohol use, which typically starts in adolescence. Alcohol is an anxiolytic drug, which may appeal to certain young people who are socially anxious but not socially avoidant. Alcohol myopia, the cognitive mechanism whereby alcohol exerts an anxiolytic effect, is also a mechanism by which alcohol serves to increase aggression. Therefore, in anxious antisocial people, drinking to cope with anxiety is likely to increase aggression. Conclusions. Interventions that flow from the research on anxiety, alcohol, and aggression are suggested. © 2011 The British Psychological Society.

Jain K.,University of Nottingham
The Cochrane database of systematic reviews | Year: 2013

Early diagnosis and treatment of lower respiratory tract infections, particularly those with Pseudomonas aeruginosa, are the mainstay of management of lung disease in cystic fibrosis. When sputum samples are unavailable, treatment relies mainly on cultures from oropharyngeal specimens; however, there are concerns regarding the sensitivity of these to identify lower respiratory organisms.Bronchoscopy and related procedures (including bronchoalveolar lavage) though invasive, allow the collection of lower respiratory specimens from non-sputum producers. Cultures of bronchoscopic specimens provide a higher yield of organisms compared to those from oropharyngeal specimens. Regular use of bronchoscopy and related procedures may help in a more accurate diagnosis of lower respiratory tract infections and guide the selection of antimicrobials, which may lead to clinical benefits. To evaluate the use of bronchoscopy-guided antimicrobial therapy in the management of lung infection in adults and children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched two registries of ongoing studies and the reference lists of relevant articles and reviews.Date of latest search: 28 November 2013. We included randomized controlled studies including patients of any age with cystic fibrosis, comparing outcomes following therapies guided by the results of bronchoscopy (including bronchoalveolar lavage or protected bronchial brush sampling) with outcomes following therapies guided by the results of any other type of sampling (including cultures from sputum, throat swab and cough swab). Two review authors independently selected studies, assessed their risk of bias and extracted data. We contacted study investigators for further information. The search identified nine studies, but only one study with data from 157 participants (170 patients were enrolled) was eligible for inclusion in the review. This study compared outcomes following therapy directed by bronchoalveolar lavage for pulmonary exacerbations during the first five years of life with standard treatment based on clinical features and oropharyngeal cultures. The study enrolled infants with CF who were under six months of age and diagnosed through newborn screening and followed them until they were five years old.We considered this study to have a low risk of bias; however, the statistical power to detect a significant difference in the prevalence of Pseudomonas aeruginosa was limited due to the prevalence (of Pseudomonas aeruginosa isolation in bronchoalveolar lavage samples at five years age) being much lower in both the groups compared to that which was expected and which was used for the power calculation. The sample size was adequate to detect a difference in high-resolution computed tomography scoring. The quality of evidence for the key parameters was graded as moderate except for high-resolution computed tomography scoring, which was graded as high.At five years of age, there was no clear benefit of bronchoalveolar lavage-directed therapy on lung function z scores or nutritional parameters. Evaluation of total and component high-resolution computed tomography scores showed no significant difference in evidence of structural lung disease in the two groups.In addition, this study did not show any difference between the number of isolates of Pseudomonas aeruginosa per child per year diagnosed in the bronchoalveolar lavage-directed therapy group compared to the standard therapy group. The eradication rate following one or two courses of eradication treatment was comparable in the two groups, as were the number of pulmonary exacerbations. However, the number of hospitalizations was significantly higher in the bronchoalveolar lavage-directed therapy group, but the mean duration of hospitalizations was significantly less compared to the standard therapy group.Mild adverse events were reported in a proportion of patients, but these were generally well-tolerated. The most common adverse event reported was transient worsening of cough after 29% of procedures. Significant clinical deterioration was documented during or within 24 hours of bronchoalveolar lavage in 4.8% of procedures. This review, which only includes a single study, shows that there is no clear evidence to support the routine use of bronchoalveolar lavage for the diagnosis and management of pulmonary infection in pre-school children with cystic fibrosis compared to the standard practice of providing treatment based on results of oropharyngeal culture and clinical symptoms. No evidence was available for adult and adolescent populations.

Skowron S.T.,University of Nottingham
Nanoscale | Year: 2013

The recent progress in high-resolution transmission electron microscopy (HRTEM) has given rise to the possibility of in situ observations of nanostructure transformations and chemical reactions induced by electron irradiation. In this article we briefly summarise experimental observations and discuss in detail atomistic modelling of irradiation-induced processes in HRTEM, as well as mechanisms of such processes recognised due to modelling. Accurate molecular dynamics (MD) techniques based on first principles or tight-binding models are employed in the analysis of single irradiation-induced events, and classical MD simulations are combined with a kinetic Monte Carlo algorithm to simulate continuous irradiation of nanomaterials. It has been shown that sulphur-terminated graphene nanoribbons are formed inside carbon nanotubes as a result of an irradiation-selective chemical reaction. The process of fullerene formation in HRTEM during continuous electron irradiation of a small graphene flake has been simulated, and mechanisms driving this transformation analysed.

Smyth A.R.,University of Nottingham
The Cochrane database of systematic reviews | Year: 2014

People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis. We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: 25 November 2013. All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis. The two authors independently selected the studies to be included in the review and assessed the risk of bias of each study. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies. Fifteen studies were identified for possible inclusion in the review. Four studies reporting results from a total of 328 participants were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One study had a low risk of bias for all criteria assessed; the remaining three included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk of bias.There was no significant difference between treatment groups in: forced expiratory volume at one second, mean difference 0.33 (95% confidence interval -2.81 to 3.48); forced vital capacity, mean difference 0.29 (95% confidence interval -6.58 to 7.16); % weight for height, mean difference -0.82 (95% confidence interval -3.77 to 2.13); body mass index, mean difference 0.00 (95% confidence interval -0.42 to 0.42); or in the incidence of ototoxicity, relative risk 0.56 (95% confidence interval 0.04 to 7.96). The percentage change in creatinine significantly favoured once-daily treatment in children, mean difference -8.20 (95% confidence interval -15.32 to -1.08), but showed no difference in adults, mean difference 3.25 (95% confidence interval -1.82 to 8.33). Once- and three-times daily aminoglycoside antibiotics appear to be equally effective in the treatment of pulmonary exacerbations of cystic fibrosis. There is evidence of less nephrotoxicity in children.

Fletcher-Smith J.C.,University of Nottingham
The Cochrane database of systematic reviews | Year: 2013

Stroke is a worldwide problem and is a leading cause of adult disability, resulting in dependency in activities of daily living (ADL) for around half of stroke survivors. It is estimated that up to 25% of all care home residents in the USA and in the UK have had a stroke. Stroke survivors who reside in care homes are likely to be more physically and cognitively impaired and therefore more dependent than those able to remain in their own home. Overall, 75% of care home residents are classified as severely disabled, and those with stroke are likely to have high levels of immobility, incontinence and confusion, as well as additional co-morbidities. It is not known whether this clinically complex population could benefit from occupational therapy in the same way as community-dwelling stroke survivors. The care home population with stroke differs from the general stroke population living at home, and a review was needed to examine the benefits of occupational therapy provided to this specific group. This review therefore focused on occupational therapy interventions for ADL for stroke survivors residing in care homes. To measure the effects of occupational therapy interventions (provided directly by an occupational therapist or under the supervision of an occupational therapist) targeted at improving, restoring and maintaining independence in ADL among stroke survivors residing in long-term institutional care, termed collectively as 'care homes'. As a secondary objective, we aimed to evaluate occupational therapy interventions for reducing complications such as depression and low mood. We searched the Cochrane Stroke Group Trials Register (August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, September 2012), MEDLINE (1948 to September 2012), EMBASE (1980 to September 2012), CINAHL (1982 to September 2012) and 10 additional bibliographic databases and six trials registers. We also handsearched seven journals, checked reference lists and obtained further information from individual trialists. Randomised controlled trials investigating the impact of an occupational therapy intervention for care home residents with stroke versus standard care. The lead review author performed all searches. Two review authors then independently assessed all titles and abstracts of studies and selected trials for inclusion, with a third review author resolving any discrepancies. The same two review authors independently extracted data from all included published sources to ensure reliability. Primary outcomes were performance in ADL at the end of scheduled follow-up and death or a poor outcome. Secondary outcomes aimed to reflect the domains targeted by an occupational therapy intervention. We included in the review one study involving 118 participants. We found one ongoing study that also met the inclusion criteria for the review, but the data were not yet available. We found insufficient evidence to support or refute the efficacy of occupational therapy interventions for improving, restoring or maintaining independence in ADL for stroke survivors residing in care homes. The effectiveness of occupational therapy for the population of stroke survivors residing in care homes remains unclear, and further research in this area is warranted.

Bath P.M.,University of Nottingham
The Cochrane database of systematic reviews | Year: 2013

Colony stimulating factors (CSFs), also called haematopoietic growth factors, regulate bone marrow production of circulating red and white cells, and platelets. Some CSFs also mobilise the release of bone marrow stem cells into the circulation. CSFs have been shown to be neuroprotective in experimental stroke. To assess (1) the safety and efficacy of CSFs in people with acute or subacute ischaemic or haemorrhagic stroke, and (2) the effect of CSFs on circulating stem and blood cell counts. We searched the Cochrane Stroke Group Trials Register (last searched September 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 4), MEDLINE (1985 to September 2012), EMBASE (1985 to September 2012) and Science Citation Index (1985 to September 2012). In an attempt to identify further published, unpublished and ongoing trials we contacted manufacturers and principal investigators of trials (last contacted April 2012). We also searched reference lists of relevant articles and reviews. We included randomised controlled trials recruiting people with acute or subacute ischaemic or haemorrhagic stroke. CSFs included stem cell factor (SCF), erythropoietin (EPO), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage-colony stimulating factor (M-CSF, CSF-1), thrombopoietin (TPO), or analogues of these. The primary outcome was functional outcome at the end of the trial. Secondary outcomes included safety at the end of treatment, death at the end of follow-up, infarct volume and haematology measures. Two review authors (TE and NS) independently extracted data and assessed trial quality. We contacted study authors for additional information. We included a total of 11 studies involving 1275 participants. In three trials (n = 782), EPO therapy was associated with a significant increase in death by the end of the trial (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.19 to 3.3, P = 0.009) and a non-significant increase in serious adverse events. EPO significantly increased the red cell count with no effect on platelet or white cell count, or infarct volume. Two small trials of carbamylated EPO have been completed but have yet to be reported. We included eight small trials (n = 548) of G-CSF. G-CSF was associated with a non-significant reduction in early impairment (mean difference (MD) -0.4, 95% CI -1.82 to 1.01, P = 0.58) but had no effect on functional outcome at the end of the trial. G-CSF significantly elevated the white cell count and the CD34+ cell count, but had no effect on infarct volume. Further trials of G-CSF are ongoing. There are significant safety concerns regarding EPO therapy for stroke. It is too early to know whether other CSFs improve functional outcome.

Gurung V.,University of Nottingham
The Cochrane database of systematic reviews | Year: 2013

Obstetric cholestasis has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been empiric. The first version of this review, published in 2001, and including nine randomised controlled trials involving 227 women, concluded that there was insufficient evidence to recommend any of the interventions alone or in combination. This is the first update. To evaluate the effectiveness and safety of therapeutic and delivery interventions in women with cholestasis of pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 February 2013) and reference lists of identified studies. Randomised controlled trials that compared two intervention strategies for women with a clinical diagnosis of obstetric cholestasis. The review authors independently assessed trials for eligibility and risk of bias. We independently extracted data and checked these for accuracy. We included 21 trials with a total of 1197 women. They were mostly at moderate to high risk of bias. They assessed 11 different interventions resulting in 15 different comparisons.Compared with placebo, ursodeoxycholic acid (UDCA) showed improvement in pruritus in five (228 women) out of seven trials. There were no significant differences in instances of fetal distress in the UDCA groups compared with placebo (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.22 to 2.02; five trials, 304 women; random-effects analysis: T2 = 0.74; I2 = 48%). There were significantly fewer total preterm births with UDCA (RR 0.46; 95% CI 0.28 to 0.73; two trials, 179 women). The difference for spontaneous preterm births was not significant (RR 0.99; 95% CI 0.41 to 2.36, two trials, 109 women).Two trials (48 women) reported lower (better) pruritus scores for S-adenosylmethionine (SAMe) compared with placebo, while two other trials of 34 women reported no significant differences between groups.UDCA was more effective in improving pruritus than either SAMe (four trials; 133 women) or cholestyramine (one trial; 84 women), as was combined UDCA+SAMe when compared with placebo (one trial; 16 women) and SAMe alone (two trials; 68 women). However, combined UDCA+SAMe was no more effective than UDCA alone in regard to pruritus improvement (one trial; 53 women) and two trials (80 women) reported data were insufficient to draw any conclusions from. In one trial comparing UDCA and dexamethasone (83 women), a significant improvement with UDCA was seen only in a subgroup of women with severe obstetric cholestasis (23 women).Danxiaoling significantly improved pruritus in comparison to Yiganling. No significant differences were seen in pruritus improvement with other interventions.Eight trials reported fetal or neonatal deaths, with two deaths reported overall (both in the placebo groups).Women receiving UDCA and cholestyramine experienced nausea, vomiting and diarrhoea. Guar gum caused mild abdominal distress, diarrhoea and flatulence during the first days of treatment. Women found charcoal suspension unpleasant to swallow. Dexamethasone caused nausea, dizziness and stomach pain in one woman.One trial (62 women) looked at the timing of delivery intervention. There were no stillbirths or neonatal deaths in 'early delivery' or the 'await spontaneous labour' group. There were no significant differences in the rates of caesarean section, meconium passage or admission to neonatal intensive care unit between the two groups. Different approaches to assessing and reporting pruritus precluded pooling of trials comparing the effects of UDCA versus placebo on pruritus, but examination of individual trials suggests that UDCA significantly improves pruritus, albeit by a small amount. Fewer instances of fetal distress/asphyxial events were seen in the UDCA groups when compared with placebo but the difference was not statistically significant. Large trials of UDCA to determine fetal benefits or risks are needed.A single trial was too small to rule in or out a clinically important effect of early term delivery on caesarean section.There is insufficient evidence to indicate that SAMe, guar gum, activated charcoal, dexamethasone, cholestyramine, Salvia, Yinchenghao decoction (YCHD), Danxioling and Yiganling, or Yiganling alone or in combination are effective in treating women with cholestasis of pregnancy.

Crewe L.,University of Nottingham
Environment and Planning D: Society and Space | Year: 2011

This paper focuses on practices and spaces of acquisition, possession, and destruction in order to understand object value. It is framed around the list, or inventory, as one way in which we attempt to organise and order consumption. Exploring three different categories of list (the abandoned shopping list, Michael Landy's inventory of personal possessions, and the 'Pieces of Me' listings of individuals' fifteen most-valued possessions), I argue that lists act as systems of labeling and orderingo-scripting devices that help us to manage the mundanity and weighty materiality of consumption. But in ordering objects, such taxonomies also materialise our wishes, dreams, hopes, fears, and failures. They reveal too the ambiguities of value that are attributed to different categories of good and the impossibilities of erasure. Things linger and haunt materially and in our memory. The paper makes two broad conceptual points. It reveals that value and significance can reside in the most unlikely of places, and may emerge through practices of discard, loss, and remembering as well as through more conventional processes of production and purchase. It attests to the enduring power of the absent presence and the difficulties of erasure: objects die but do not disappear; things are dismantled, destroyed, and disposed of but remain in countless material and immaterial formso- traces, remnants, fragments, and memories. Objects have immaterial lives that continue long beyond their material presence in the world. It reveals the ways in which our possessions accrue meaning-value through biogeography. Things come to matter through our intimate relations with them, object and subject combined and entwined, inseparable in mind and memory. Our relations to our things are sensory, bodily, evocative, and profound. They are also enduring, potent, powerful, inarticulate, and at times unbearably evocative. © 2011 Pion Ltd and its Licensors.

Weston D.,University of Nottingham
Cultural Geographies | Year: 2011

For cultural geographers, uncertainties inhabit the concept of 'landscape'. The term shuttles between describing embodied practice of immersion in an environment, and indicating representational strategies for looking at an environment. This article provides a reading of W.G. Sebald's The Rings of Saturn as a platform from which to offer a critique of current understandings of landscape from a critical perspective that looks to assimilate the findings of cultural geography and literary studies. Sebald's record of an ambulatory journey through coastal Suffolk aims not to resolve the instabilities of 'landscape', but to collapse into one another its discrete meanings: it is through the history of previous artistic visitation, coupled with his own sensory involvement, that Sebald engages with and inhabits the landscape that he describes. Derrida's notion of 'supplementarity' is employed to provide purchase by which to recognize the interdependence of practice and representation in the production of landscape in Sebald's text, and in a widely applicable understanding of the term's complexities. © The Author(s) 2011.

Huang Q.-G.,CAS Institute of Theoretical Physics | Piao Y.-S.,University of Chinese Academy of Sciences | Zhou S.-Y.,University of Nottingham
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

It has recently been shown that the graviton can consistently gain a constant mass without introducing the Boulware-Deser ghost. We propose a gravity model where the graviton mass is set by a scalar field and prove that this model is free of the Boulware-Deser ghost by analyzing its constraint system and showing that two constraints arise. We also initiate the study of the model's cosmic background evolution and tentatively discuss possible cosmological implications of this model. In particular, we consider a simple scenario where the scalar field setting the graviton mass is identified with the inflaton and the graviton mass evolves from a high to a low energy scale, giving rise to the current cosmic acceleration. © 2012 American Physical Society.

Kemp E.,University of Nottingham
Cochrane database of systematic reviews (Online) | Year: 2013

Epidural analgesia for pain relief in labour prolongs the second stage of labour and results in more instrumental deliveries. It has been suggested that a more upright position of the mother during all or part of the second stage may counteract these adverse effects. To assess the effects of different birthing positions (upright versus recumbent) during the second stage of labour, on important maternal and fetal outcomes for women with epidural analgesia. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2012) and reference lists of retrieved studies All randomised or quasi-randomised trials including pregnant women (either primigravidae or multigravidae) in the second stage of induced or spontaneous labour receiving epidural analgesia of any kind.We assumed the experimental type of intervention to be the maternal use of any upright position during the second stage of labour, compared with the control intervention of the use of any recumbent position. Two review authors independently assessed trials for inclusion, assessed risk of bias, and extracted data. Data were checked for accuracy. We contacted authors to try to obtain missing data. Five randomised controlled trials, involving 879 women, were included in the review.Overall, we identified no statistically significant difference between upright and recumbent positions on our primary outcomes of operative birth (caesarean or instrumental vaginal) (average risk ratio (RR) 0.97; 95% confidence interval (CI) 0.76 to 1.29; five trials, 874 women), or duration of the second stage of labour measured as the randomisation to birth interval (average mean difference -22.98 minutes; 95% CI -99.09 to 53.13; two trials, 322 women). Nor did we identify any clear differences in the incidence of instrumental birth or caesarean section separately, nor in any other important maternal or fetal outcome, including trauma to the birth canal requiring suturing, operative birth for fetal distress, low cord pH or admission to neonatal intensive care unit. However, the CIs around each estimate were wide, and clinically important effects have not been ruled out.There were no data reported on excess blood loss, prolonged second stage or maternal experience and satisfaction with labour. Similarly, there were no analysable data on Apgar scores, and no data reported on the need for ventilation or for perinatal death. There are insufficient data to say anything conclusive about the effect of position for the second stage of labour for women with epidural analgesia. Women with an epidural should be encouraged to use whatever position they find comfortable in the second stage of labour. Future research should involve large trials of positions that women can maintain and predefined endpoints. One large trial is ongoing.

Mepham B.,University of Nottingham
British Medical Bulletin | Year: 2011

Background: Food additives are an integral part of the modern food system, but opinion polls showing most Europeans have worries about them imply an urgent need for ethical analysis of their use. Sources of data: The existing literature on food ethics, safety assessment and animal testing. Areas of agreement: Food additives provide certain advantages in terms of many peoples lifestyles. Areas of controversy: There are disagreements about the appropriate application of the precautionary principle and of the value and ethical validity of animal tests in assessing human safety. Growing points: Most consumers have a poor understanding of the relative benefits and risks of additives, but concerns over food safety and animal testing remain high. Areas timely for developing research: Examining the impacts of food additives on consumer sovereignty, consumer health and on animals used in safety testing should allow a more informed debate about their appropriate uses. © The Author 2010. Published by Oxford University Press. All rights reserved.

Tanasescu R.,Carol Davila University of Medicine and Pharmacy | Constantinescu C.S.,University of Nottingham
Immunobiology | Year: 2010

Cannabinoids can influence the immune network. Data on the impact of exogenous cannabinoid ligands on immune function serve not only to understand how the endocannabinoid system modulates immune phenomena associated with infection or inflammation, but also to identify therapeutic targets for immune diseases. Cannabinoids can modulate immune reactions in the periphery but also in the brain, influence T cell subset balance and cytokine expression and play a role in the balance between neuroinflammation and neurodegeneration. Immune cells can synthesize endocannabinoids and also be influenced by cannabinoid analogues. Cannabinoid receptors show different expression on immune cells depending on activation status and stimuli. The complexity of relation between cannabinoid ligands of various classes and cannabinoid receptors brought the need to refine the simple conceptual frame of agonist-antagonists and offered potential implications for understanding interactions in pathological conditions. The immune influence of cannabinoid ligands is not fully elucidated. However, aspects of their immunomodulatory effects provide the basis for a context-dependent targeted therapeutic approach, thus leading to the possibility for the use of cannabinoids in the treatment of inflammatory disease. © 2010 Elsevier GmbH.

Hussein N.R.,University of Nottingham
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2010

Helicobacter pylori is associated with the development of ulceration and gastric cancer. Recently, a novel virulence factor, duodenal ulcer promoting gene A (dupA), has been identified and found to associate with disease in some populations but not others. We investigated the relationship of dupA genotypes and H. pylori-related clinical outcomes by meta-analysis using previous reports of 2,358 patients from around the world. dupA-positive genotypes was found in 48% and was associated with duodenal ulcer (p=0.001, odds ratio [OR]=1.4, confidence interval [CI]=1.1-1.7). The prevalence of dupA-positivity and its association with disease differed among the various regions around the world. In South America, the highest prevalence was recorded (Colombia and Brazil) and a significant relationship was found between dupA-negative strains and both gastric ulcer (GU) and gastric cancer (GC) (for GU, p=0.001, OR=0.2, CI=0.1-0.4 and for GC, p=0.001, OR=0.3, CI=0.2-0.6). In China, a significant correlation between dupA-positive strains and GU (p=0.001, OR=5.5, CI=2.4-12.4) and GC (p=0.009, OR=2, Cl=1.1-3.1) was found. To conclude, dupA promotes duodenal ulceration in some populations and GU and GC in others. This is typical of other virulence factors, such as cagA. Hence, it was concluded that the H. pylori virulence factor, dupA, is a true virulence factor. © 2010 Springer-Verlag.

Lewis N.R.,University of Nottingham | Scott B.B.,Lincoln County Hospital
Alimentary Pharmacology and Therapeutics | Year: 2010

Background: Following the appreciation of the importance of gliadin deamidation in the immunopathogenesis of coeliac disease, diagnostic tests based on antibodies to deamidated gliadin peptides have been developed and shown to have high sensitivity and specificity. Aim To compare the performance of the deamidated gliadin peptides antibody test with the current standard, the tissue transglutaminase antibody test, through a meta-analysis of published studies. Methods Databases from 1998 to 2008 were searched for relevant studies. These were assessed for methodological quality and standard statistical tests were applied to compare particularly the sensitivity and specificity of the two tests for the diagnosis of coeliac disease. Results Most studies had methodological flaws, especially ascertainment bias. The pooled sensitivities for the deamidated gliadin peptides antibody and tissue transglutaminase antibody tests were 87.8% (95% CI, 85.6-89.9) and 93.0% (95% CI, 91.2-94.5) respectively and the pooled specificities were 94.1% (95% CI, 92.5-95.5) and 96.5% (95% CI, 95.2-97.5) respectively. Conclusion Although both tests perform well, the tissue transglutaminase antibody test outperforms the deamidated gliadin peptides antibody test and remains the preferred serological test for the diagnosis and/or exclusion of coeliac disease. © 2010 Blackwell Publishing Ltd.

Rotchford A.P.,Tennent Institute of Ophthalmology | King A.J.,University of Nottingham
Ophthalmology | Year: 2010

Purpose: To determine (1) the extent to which the definition of success of glaucoma surgery varies in the literature and (2) the degree to which the reported outcome after trabeculectomy is affected by the criteria used to define success. Design: A systematic review of the literature and application of definitions to a retrospective cohort. Participants: A cohort of 100 patients who previously underwent trabeculectomy. Methods: A literature search was performed of PubMed using the search term trabeculectomy for a 5-year period. Studies presenting original data relating to longitudinal intraocular pressure (IOP) control after glaucoma surgery were included. The definitions of success and failure used were documented for each publication. Each IOP-related definition of success was applied to a cohort of patients who previously underwent trabeculectomy. Success rates were derived for each published definition up to 36 months after surgery. Main Outcome Measures: Intraocular pressure measured by Goldmann applanation tonometry. Results: From 100 publications meeting the inclusion criteria, 92 distinct IOP-related definitions of success were identified. Using these definitions, success rates for this series of 100 trabeculectomies varied between 36.0% and 98.0% after 3 years of follow-up. Conclusions: Over a recent 5-year period, there were nearly as many different definitions of success after glaucoma surgery as publications on the subject. The definition used markedly affects the quoted success rate after trabeculectomy, making interpretation of and comparison between published results extremely difficult. Standardization of published outcome parameters after glaucoma surgery is essential to allow meaningful comparisons between different study reports. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. © 2010 American Academy of Ophthalmology.

Morriss R.,University of Nottingham
Cochrane database of systematic reviews (Online) | Year: 2013

Schizophrenia has a lifetime prevalence of less than one per cent. Studies have indicated that early symptoms that are idiosyncratic to the person with schizophrenia (early warning signs) often precede acute psychotic relapse. Early warning signs interventions propose that learning to detect and manage early warning signs of impending relapse might prevent or delay acute psychotic relapse. To compare the effectiveness of early warning signs interventions plus treatment as usual involving and not involving a psychological therapy on time to relapse, hospitalisation, functioning, negative and positive symptomatology. Search databases included the Cochrane Schizophrenia Group Trials Register (July 2007 and May 2012) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. References of all identified studies were reviewed for inclusion. We inspected the UK National Research Registe and contacted relevant pharmaceutical companies and authors of trials for additional information. We included all randomised clinical trials (RCTs) comparing early warning signs interventions plus treatment as usual to treatment as usual for people with schizophrenia or other non-affective psychosis We assessed included studies for quality and extracted data. If more than 50% of participants were lost to follow-up, the study was excluded. For binary outcomes, we calculated standard estimates of risk ratio (RR) and the corresponding 95% confidence intervals (CI), for continuous outcomes, we calculated mean differences (MD) with standard errors estimated, and for time to event outcomes we calculated Cox proportional hazards ratios (HRs) and associated 95 % CI. We assessed risk of bias for included studies and assessed overall study quality using the GRADE approach. Thirty-two RCTs and two cluster-RCTs that randomised 3554 people satisfied criteria for inclusion. Only one study examined the effects of early warning signs interventions without additional psychological interventions, and many of the outcomes for this review were not reported or poorly-reported. Significantly fewer people relapsed with early warning signs interventions than with usual care (23% versus 43%; RR 0.53, 95% CI 0.36 to 0.79; 15 RCTs, 1502 participants; very low quality evidence). Time to relapse did not significantly differ between intervention groups (6 RCTs, 550 participants; very low quality evidence). Risk of re-hospitalisation was significantly lower with early warning signs interventions compared to usual care (19% versus 39%; RR 0.48, 95% CI 0.35 to 0.66; 15 RCTS, 1457 participants; very low quality evidence). Time to re-hospitalisation did not significantly differ between intervention groups (6 RCTs; 1149 participants; very low quality evidence). Participants' satisfaction with care and economic costs were inconclusive because of a lack of evidence. This review indicates that early warning signs interventions may have a positive effect on the proportions of people re-hospitalised and on rates of relapse, but not on time to recurrence. However, the overall quality of the evidence was very low, indicating that we do not know if early warning signs interventions will have similar effects outside trials and that it is very likely that further research will alter these estimates. Moreover, the early warning signs interventions were used along side other psychological interventions, and we do not know if they would be effective on their own. They may be cost-effective due to reduced hospitalisation and relapse rates, but before mental health services consider routinely providing psychological interventions involving the early recognition and prompt management of early warning signs to adults with schizophrenia, further research is required to provide evidence of high or moderate quality regarding the efficacy of early warning signs interventions added to usual care without additional psychological interventions, or to clarify the kinds of additional psychological interventions that might aid its efficacy. Future RCTs should be adequately-powered, and designed to minimise the risk of bias and be transparently reported. They should also systematically evaluate resource costs and resource use, alongside efficacy outcomes and other outcomes that are important to people with serious mental illness and their carers.

Kendrick D.,University of Nottingham
The Cochrane database of systematic reviews | Year: 2013

Parent education and training programmes can improve maternal psychosocial health, child behavioural problems and parenting practices. This review assesses the effects of parenting interventions for reducing child injury. To assess the effects of parenting interventions for preventing unintentional injury in children aged under 18 years and for increasing possession and use of safety equipment and safety practices by parents. We searched CENTRAL, MEDLINE, EMBASE, BIOSIS Preview, PsycINFO, Sociological Abstracts, Social Science Citation Index, CINAHL, ProQuest Dissertations and Theses, ERIC, DARE, ASSIA, Web of Science, SIGLE and ZETOC. We also handsearched abstracts from the World Conferences on Injury Prevention & Control and the journal Injury Prevention. The searches were conducted in January 2011. We included randomised controlled trials (RCTs), non-randomised controlled trials (non-RCTs) and controlled before and after studies (CBAs), which evaluated parenting interventions administered to parents of children aged 18 years and under, and reported outcome data on injuries for children (unintentional or unspecified intent), possession and use of safety equipment or safety practices (including the Home Observation for Measurement of the Environment (HOME) scale which contained an assessment of home safety) by parents. Parenting interventions were defined as those with a specified protocol, manual or curriculum aimed at changing knowledge, attitudes or skills covering a range of parenting topics. Studies were selected, data were extracted and quality appraised independently by two authors. Pooled relative risks (RR) were estimated using random effect models. Twenty two studies were included in the review: 16 RCTs, two non-RCTs, one partially randomised trial which contained two randomised intervention arms and one non-randomised control arm, two CBA studies and one quasi randomised controlled trial. Seventeen studies provided interventions comprising parenting education and other support services; 15 of which were home visiting programmes and two of which were paediatric practice-based interventions. Two provided solely educational interventions. Nineteen studies recruited families who were from socio-economically disadvantaged populations, were at risk of adverse child outcomes or people who may benefit from extra support, such as single mothers, teenage mothers, first time mothers and mothers with learning difficulties. Ten RCTs involving 5074 participants were included in the meta-analysis, which indicated that intervention families had a statistically significant lower risk of injury than control families (RR 0.83, 95% CI 0.73 to 0.94). Sensitivity analyses undertaken including only RCTs at low risk of various sources of bias found the findings to be robust to including only those studies at low risk of detection bias in terms of blinded outcome assessment and attrition bias in terms of follow up of fewer than 80% of participants in each arm. When analyses were restricted to studies at low risk of selection bias in terms of inadequate allocation concealment the effect size was no longer statistically significant. Several studies found statistically significant fewer home hazards or a greater number of safety practices in intervention families. Of ten studies reporting scores on the HOME scale, data from three RCTs were included in a meta-analysis which found no evidence of a difference in quality of the home environment between treatment arms (mean difference 0.57, 95% CI -0.59 to 1.72). Most of the studies reporting home safety practices, home hazards or composite home safety scores found statistically significant effects favouring intervention arm families. Overall, using GRADE, the quality of the evidence was rated as moderate. Parenting interventions, most commonly provided within the home using multi-faceted interventions are effective in reducing child injury. There is fairly consistent evidence that they also improve home safety. The evidence relates mainly to interventions provided to families from disadvantaged populations, who are at risk of adverse child health outcomes or whose families may benefit from extra support. Further research is required to explore mechanisms by which these interventions may reduce injury, the features of parenting interventions that are necessary or sufficient to reduce injury and the generalisability to different population groups.

The β1-adrenoceptor exists in two agonist conformations/states: 1) a high-affinity state where responses to catecholamines and other agonists (e.g., cimaterol) are potently inhibited by β1-adrenoceptor antagonists, and 2) a low-affinity secondary conformation where agonist responses, particularly CGP12177 [(-)-4-(3-tert-butylamino-2-hydroxypropoxy)-benzimidazol-2-one] are relatively resistant to inhibition by β1-adrenoceptor antagonists. Although both states have been demonstrated in many species (including human), the precise nature of the secondary state is unknown and does not occur in the closely related β2-adrenoceptor. Here, using site-directed mutagenesis and functional measurements of production of a cyclic AMP response element upstream of a secreted placental alkaline phosphatase reporter gene and accumulation of (3)H-cAMP, we examined the pharmacological consequences of swapping transmembrane (TM) regions of the human β1- and β2-adrenoceptors, followed by single point mutations, to determine the key residues involved in the β1-adrenoceptor secondary conformation. We found that TM4 (particularly amino acids L195 and W199) had a major role in the generation of the secondary β1-adrenoceptor conformation. Thus, unlike at the human β1-wild-type adrenoceptor, at β1-TM4 mutant receptors, cimaterol and CGP12177 responses were both potently inhibited by antagonists. CGP12177 acted as a simple partial agonist with similar KB and EC50 values in the β1-TM4 but not β1-wild-type receptors. Furthermore pindolol switched from a biphasic concentration response at human β1-wild-type adrenoceptors to a monophasic concentration response in the β1-TM4 mutant receptors. Mutation of these amino acids to those found in the β2-adrenoceptor (L195Q and W199Y), or mutation of a single residue (W199D) in the human β1-adrenoceptor thus abolished this secondary conformation and created a β1-adrenoceptor with only one high-affinity agonist conformation.

Gan G.,University of Nottingham
Energy and Buildings | Year: 2010

Two computational domains have been used for simulation of buoyancy-driven natural ventilation in vertical cavities for different total heat fluxes and wall heat distributions. Results were compared between cavities with horizontal and vertical inlets. The predicted ventilation rate and heat transfer coefficient have been found to depend on the domain size and inlet position as well as the cavity size and heat distribution ratio. The difference in the predicted ventilation rate or heat transfer coefficient using two domains is generally larger for wider cavities with asymmetrical heating and is also larger for ventilation cavities with a horizontal inlet than those with a vertical inlet. The difference in the heat transfer coefficient is generally less than that in the ventilation rate. In addition, a ventilation cavity with symmetrical heating has a higher ventilation rate but generally lower heat transfer coefficient than does an asymmetrically heated cavity. A computational domain larger than the physical size should be used for accurate prediction of the flow rate and heat transfer in ventilation cavities or naturally ventilated buildings with large openings, particularly with multiple inlets and outlets. This is demonstrated with two examples for natural ventilation of buildings. © 2010 Elsevier B.V. All rights reserved.

Tseng M.Y.,University of Nottingham
Neurocritical Care | Year: 2011

Statins were shown to have neuroprotective effects, with reduced vasospasm and delayed ischemic deficits in statin-treated patients after aneurysmal subarachnoid hemorrhage in two small, randomized, controlled clinical trials published in 2005. This review consolidated data from available published studies evaluating statin treatment for subarachnoid hemorrhage. A literature search was conducted to identify original research studies published through October 2010 testing immediate treatment with a statin in statin-naïve patients following aneurysmal SAH. Six randomized controlled clinical trials and four observational studies were identified. Despite inconsistent results among studies, a meta-analysis of randomized controlled data showed a significant reduction in delayed ischemic deficits with statins. Effect on vasospasm was more difficult to determine, due to differences in definitions used among studies. Interpretations from observational studies were limited by the use of relatively small sample sizes, historical controls, and treatment variability. © Springer Science+Business Media, LLC 2011.

Wahle E.,Martin Luther University of Halle Wittenberg | Winkler G.S.,University of Nottingham
Biochimica et Biophysica Acta - Gene Regulatory Mechanisms | Year: 2013

Shortening and removal of the 3' poly(A) tail of mature mRNA by poly(A)-specific 3' exonucleases (deadenylases) is the initial and often rate-limiting step in mRNA degradation. The majority of cytoplasmic deadenylase activity is associated with the Ccr4-Not and Pan2-Pan3 complexes. Two distinct catalytic subunits, Caf1/Pop2 and Ccr4, are associated with the Ccr4-Not complex, whereas the Pan2 enzymatic subunit forms a stable complex with Pan3. In this review, we discuss the composition and activity of these two deadenylases. In addition, we comment on generic and specific mechanisms of recruitment of Ccr4-Not and Pan2-Pan3 to mRNAs. Finally, we discuss specialised and redundant functions of the deadenylases and review the importance of Ccr4-Not subunits in the regulation of physiological processes. This article is part of a Special Issue entitled: RNA Decay mechanisms. © 2013 Elsevier B.V.

Castellazzi A.,University of Nottingham
IEEE Transactions on Power Electronics | Year: 2010

This paper proposes the model development of a packaged semiconductor power module, for use in a circuit simulation environment. Focusing on railway traction applications, it considers a state-of-the-art 6.5 kV insulated gate bipolar transistor (IGBT) module, taking into account the antiparallel connection of IGBTs and free-wheeling diodes, and including all main electrothermal and electromagnetic effects associated with the multichip structure. The description of semiconductor physics is coupled with self-heating effects; electromagnetic phenomena associated with the packaging, layout, and interconnections are also taken into account. To optimize the compromise between accuracy and computational effort, the device models are based on a mixed physical and behavioral description, and are scalable to be representative of a desired number of parallel devices and to allow for the introduction of parasitic elements, as required. Electromagnetic effects are modeled by means of equivalent lumped elements, extracted by numerical simulation of an accurate 3-D structural assembly model. The description of transient thermal phenomena relies on a finite-difference approach that considers the use of both essentially 1-D lumped equivalent models and fully 3-D distributed description. The model is validated statically and dynamically, against both data-sheet information and measurements; a selection of simulation examples demonstrates its usefulness and versatility. Although developed for a specific application scenario, the proposed approach is of general validity. © 2006 IEEE.

Gan G.,University of Nottingham
Open Construction and Building Technology Journal | Year: 2010

Design of natural ventilation systems for many types of building is based on buoyancy force. However, external wind flow can have significant effects on buoyancy-driven natural ventilation. Simulation has been carried out for combined wind- and buoyancy-driven natural ventilation of a building with two wings of offices and a central atrium. Results show that wind would adversely affect the air flow patterns in the building designed with buoyancy-driven natural ventilation. Wind can simultaneously assist and oppose buoyancy in the windward and leeward wings, respectively, whereas buoyancy can oppose wind-driven flow in both wings. To achieve or maintain a desired environmental quality in the naturally ventilated building would require intelligent control of ventilation openings and/or careful consideration of wind-driven ventilation at the design stage. The importance of measurements of variables such as pressure, velocity and temperature for real size buildings is also highlighted. © Guohui Gan; Licensee Bentham Open.

Ainsworth S.,University of Nottingham | Prain V.,La Trobe University | Tytler R.,Deakin University
Science | Year: 2011

Emerging research suggests drawing should be explicitly recognized as a key element in science education.

Aithal G.P.,University of Nottingham
Nature Reviews Rheumatology | Year: 2011

Antirheumatic agents are among commonly used drugs associated with adverse hepatic reactions. Sulfasalazine and azathioprine are among the most important causes of acute hepatotoxicity. Because such a large number of people take NSAIDs, even the rare occurrence of hepatotoxicity from these agents might contribute substantially to the total burden of drug-induced liver disease. A wide spectrum of hepatotoxic effects is described with antirheumatic drugs. Studies investigating genetic susceptibility to diclofenac hepatotoxicity have expanded our understanding of the potential drug-specific, class-specific and general factors involved in its pathogenesis, and methotrexate-associated liver disease demonstrates the interaction between drug, host and environmental factors that determines the likelihood and magnitude of liver disease. Infliximab therapy is associated with typical drug-induced autoimmune hepatitis. Although validated causality assessment methods have been used to objectively assess the strength of the association between a drug and a clinical event, in practice the diagnosis of drug-induced liver injury (DILI) involves a clinical index of suspicion, pattern recognition, the establishment of a temporal relationship between drug exposure and the adverse event, and the exclusion of alternative explanations for the clinical presentation. Detailed understanding of genetic and environmental factors underlying an individual's susceptibility would enable risk reduction and potentially primary prevention of hepatotoxicity. © 2011 Macmillan Publishers Limited. All rights reserved.

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

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

Krasnov K.,University of Nottingham
Journal of High Energy Physics | Year: 2015

Abstract: We continue to study an infinite-parametric family of gauge theories with an arbitrary function of the self-dual part of the field strength as the Lagrangian. The arising one-loop divergences are computed using the background field method. We show that they can all be absorbed by a local redefinition of the gauge field, as well as multiplicative renormalisations of the couplings. Thus, this family of theories is one-loop renormalisable. The infinite set of β-functions for the couplings is compactly stored in a renormalisation group flow for a single function of the curvature. The flow is obtained explicitly. © 2015, The Author(s).

The subject of place is salient certainly when deliberating the health of prisoners as a social group. This paper provides an overview and assessment of health and place in relation to mental health and the prison locale. Particular attention is devoted to prison culture, both staff and inmate. The incarceration experience (i.e. the nature of enforced residence in the prison environment) can affect negatively prisoners' mental health. The mental health of the prison population is poor, and mental health services in the prison setting have need of further improvement. However, the provision of mental healthcare and the pursuit of good mental health in the prison milieu are challenging. The prison-based-exceedingly complex-three-way relationship between culture-mental and health-mental healthcare is debated. © 2011 Elsevier Ltd.

Kaloper N.,University of California at Davis | Padilla A.,University of Nottingham
Physical Review Letters | Year: 2015

Recently, we proposed a mechanism for sequestering the standard model vacuum energy that predicts that the Universe will collapse. Here we present a simple mechanism for bringing about this collapse, employing a scalar field whose potential is linear and becomes negative, providing the negative energy density required to end the expansion. The slope of the potential is chosen to allow for the expansion to last until the current Hubble time, about 1010 years, to accommodate our Universe. Crucially, this choice is technically natural due to a shift symmetry. Moreover, vacuum energy sequestering selects radiatively stable initial conditions for the collapse, which guarantee that immediately before the turnaround the Universe is dominated by the linear potential which drives an epoch of accelerated expansion for at least an e fold. Thus, a single, technically natural choice for the slope ensures that the collapse is imminent and is preceded by the current stage of cosmic acceleration, giving a new answer to the "why now?" problem. © 2015 American Physical Society.

Louko J.,University of Nottingham
Journal of High Energy Physics | Year: 2014

We investigate a two-level Unruh-DeWitt detector coupled to a massless scalar field or its proper time derivative in (1 + 1)-dimensional Minkowski spacetime, in a quantum state whose correlation structure across the Rindler horizon mimics the stationary aspects of a firewall that Almheiri et al. have argued to ensue in an evaporating black hole spacetime. Within first-order perturbation theory, we show that the detector's response on falling through the horizon is sudden but finite. The difference from the Minkowski vacuum response is proportional to ω -2ln(|ω|) for the non-derivative detector and to ln(|ω|) for the derivative-coupling detector, both in the limit of a large energy gap ω and in the limit of adiabatic switching. Adding to the quantum state high Rindler temperature excitations behind the horizon increases the detector's response proportionally to the temperature; this situation has been suggested to model the energetic curtain proposal of Braunstein et al. We speculate that the (1 + 1)-dimensional derivative-coupling detector may be a good model for a non-derivative detector that crosses a firewall in 3 + 1 dimensions. © 2014 The Author(s).

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

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

Ossipov A.,University of Nottingham
Physical Review Letters | Year: 2014

We study the ground-state entanglement entropy of a finite subsystem of size L of an infinite system of noninteracting fermions scattered by a potential of finite range a. We derive a general relation between the scattering matrix and the overlap matrix and use it to prove that for a one-dimensional symmetric potential the von Neumann entropy, the Rényi entropies, and the full counting statistics are robust against potential scattering, provided that L/1. The results of numerical calculations support the validity of this conclusion for a generic potential. © 2014 American Physical Society.

Standard biologically inspired spatio-temporal energy models of how humans perceive moving two-dimensional patterns often have two critical stages. In the first stage, suitable filters are convolved with the pattern over time to extract information at the " component" level. Motion energy is then computed for each component. The second stage typically computes pattern velocity using the intersection of constraints rule (IOC). This paper describes a new implementation of the Component Level Feature Model (Bowns, 2002) that computes motion direction that is similar to these two stages except that it does not compute motion energy. Here the model computes direction for 200 randomly generated plaids. The output linearly matched that predicted by the IOC. The model was also able to predict the perceived direction even when it deviated from the IOC due to the following variables - speed ratio (Bowns, 1996); duration (Yo & Wilson, 1992); adaptation (Bowns & Alais, 2006). The model provides a novel explanation for each of the above and for why multiple directions can be represented for the same stimuli (Bowns & Alais, 2006); and why some second-order information attributed to non-linearities (Derrington, Badcock, & Holroyd, 1992) reverses perceived motion direction. Finally, CLFM is invariant to contrast and phase. © 2011 Elsevier Ltd.

Fares U.,University of Nottingham
Journal of cataract and refractive surgery | Year: 2012

Post-keratoplasty astigmatism remains a challenge for corneorefractive surgeons. While maintaining a healthy graft is the most crucial issue in keratoplasty procedures, astigmatism is a limiting factor in the visual rehabilitation of otherwise successful corneal grafts. The management of post-keratoplasty astigmatism takes place at 2 stages: when sutures are still present at the graft-host junction and when all sutures have been removed. Excessive suture-in post-keratoplasty astigmatism is usually managed by selective suture manipulation, ie, suture adjustment and/or suture removal along the steep meridian of astigmatism. A small amount of suture-out post-keratoplasty astigmatism can be managed by spectacles. Higher magnitudes of astigmatism can be addressed by contact lenses or surgical intervention, such as relaxing and compressing procedures. Laser lamellar refractive surgery can also be used to manage post-keratoplasty astigmatism, and toric phakic intraocular lenses have recently been recommended. In this review, we discuss the etiology and management of post-keratoplasty astigmatism and provide recommendations and tips to minimize it. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Lesanovsky I.,University of Nottingham
Physical Review Letters | Year: 2011

We study a one-dimensional atomic lattice gas in which Rydberg atoms are excited by a laser and whose external dynamics is frozen. We identify a parameter regime in which the Hamiltonian is well approximated by a spin Hamiltonian with quasilocal many-body interactions which possesses an exact analytic ground state solution. This state is a superposition of all states of the system that are compatible with an interaction induced constraint weighted by a fugacity. We perform a detailed analysis of this state which exhibits a crossover between a paramagnetic phase with short-ranged correlations and a crystal. This study also leads us to a class of spin models with many-body interactions that permit an analytic ground state solution. © 2011 American Physical Society.

Yu D.,University of Nottingham
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2014

Precisely controlling the atom number challenges the single-photon generation based on an individual neutral atom in experiments. A straightforward solution is to directly produce single photons via a number of atoms. We theoretically investigate such a single-photon emitter in which a bunch of Sr atoms are tightly confined in a blue-detuned optical lattice and weakly driven by an external field. The strong long-range interatomic interactions inducing large excitation-energy shifts results in a significant suppression of multiphoton emission. We consider two common approaches, which are widely used in experiments to generate single photons, in detail. The results indicate a potential to built up a single-photon source based on an ensemble of interacting atoms. © 2014 American Physical Society.

Mobasheri A.,University of Nottingham
Frontiers in Physiology | Year: 2011

The incidence of agerelated musculoskeletal impairment is steadily rising throughout the world. Musculoskeletal conditions are closely linked with aging and inflammation. They are leading causes of morbidity and disability in man and beast. Aging is a major contributor to musculoskeletal degeneration and the development of osteoarthritis (OA). OA is a degenerative disease that involves structural changes to joint tissues including synovial inflammation, catabolic destruction of articular cartilage and alterations in subchondral bone. Cartilage degradation and structural changes in subchondral bone result in the production of fragments of extracellular matrix molecules. Some of these biochemical markers or "biomarkers" can be detected in blood, serum, synovial fluid, and urine and may be useful markers of disease progression.The ability to detect biomarkers of cartilage degradation in body fluids may enable clinicians to diagnose subclinical OA as well as determining the course of disease progression. New biomarkers that indicate early responses of the joint cartilage to degeneration will be useful in detecting early, preradiographic changes. Systems biology is increasingly applied in basic cartilage biology and OA research. Proteomic techniques have the potential to improve our understanding of OA physiopathology and its underlying mechanisms. Proteomics can also facilitate the discovery of diseasespecific biomarkers and help identify new therapeutic targets. Proteomic studies of cartilage and other joint tissues may be particularly relevant in diagnostic orthopedics and therapeutic research. This perspective article discusses the relevance and potential of proteomics for studying agerelated musculoskeletal diseases such as OA and reviews the contributions of key investigators in the field. © 2011 Mobasheri.

Leonardi-Bee J.,University of Nottingham
Cochrane database of systematic reviews (Online) | Year: 2011

Infantile haemangiomas (also known as strawberry birthmarks) are soft, raised swellings of the skin which are usually uncomplicated and tend to regress spontaneously over time. Some haemangiomas occur in high-risk areas or can develop complications; therefore, intervention may be necessary. Various interventions have been proposed, but it is unclear whether any of these interventions are effective. To assess the effects of interventions for infantile haemangiomas. We searched the following databases up to March 2011: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (Clinical Trials) in The Cochrane Library, MEDLINE, EMBASE, PsycINFO, AMED (Allied and Complementary Medicine), LILACS (Latin American and Caribbean Health Science Information database), CINAHL, and reference lists of articles. We also searched online trials registries for ongoing trials and grey literature. We included children with haemangiomas. Two authors independently screened titles, abstracts, and the full text of publications; extracted data; and assessed risk of bias. We included 4 studies with a total of 271 participants.One randomised controlled trial (RCT) compared pulsed dye laser (PDL) therapy versus the 'wait and see' approach. At one year PDL was significantly more likely to result in complete clearance. The risk ratio (RR) was 6.10 (95% CI [confidence interval] 1.89 to 19.64); however, there was no difference when clearance was defined as 'complete or minimal residual signs'. Redness was significantly less pronounced in the PDL group, but no differences were seen for height or surface area. Significant increases in atrophy and skin hypopigmentation were seen in the PDL group.One very old RCT assessed radiation versus mock-radiation; there was no significant difference in clearance at six years (RR 1.08, 95% CI 0.63 to 1.87) between the groups, irrespective of the size of the haemangioma and the skin colour.In one small RCT there was a significantly greater reduction in size of the haemangioma with oral prednisolone compared to intravenous methylprednisolone at three months (mean difference [MD] was 58 mm [95% CI 29.24 to 86.76]), and one year. Similar adverse events occurred in both groups.In another small RCT there was a significant reduction in the surface area of the haemangioma with bleomycin compared to the control (RR 21, 95% CI 1.34 to 328.86). This review has found limited evidence from individual RCTs to support some of the existing interventions (corticosteroid and PDL) for infantile haemangiomas. There is a need for further high-quality RCTs to validate the findings from these studies, and RCTs to assess the effect of other treatments, in particular relating to propranolol.

Martinez-Pomares L.,University of Nottingham
Journal of Leukocyte Biology | Year: 2012

The MR is a highly effective endocytic receptor with a broad binding specificity encompassing ligands of microbial and endogenous origin and a poorly characterized ability to modulate cellular activation. This review provides an update of the latest developments in the field. It discusses how MR biology might be affected by glycosylation and proteolytic processing, MR involvement in antigen delivery, and the potential contribution of MR to T cell differentiation and cellular activation. Further understanding of these areas will, no doubt, inform the design of novel, therapeutic tools for improved vaccination, control of inflammation, and tumor chemotherapy, which will benefit from exploiting MR-efficient internalization properties and unique pattern of expression. © Society for Leukocyte Biology.

Soultanas P.,University of Nottingham
Molecular Microbiology | Year: 2012

Threading of DNA through the central channel of a replicative ring helicase is known as helicase loading, and is a pivotal event during replication initiation at replication origins. Once loaded, the helicase recruits the primase through a direct protein-protein interaction to complete the initial 'priming step' of DNA replication. Subsequent assembly of the polymerases and processivity factors completes the structure of the replisome. Two replisomes are assembled, one on each strand, and move in opposite directions to replicate the parental DNA during the 'elongation step' of DNA replication. Replicative helicases are the motor engines of replisomes powered by the conversion of chemical energy to mechanical energy through ATP binding and hydrolysis. Bidirectional loading of two ring helicases at a replication origin is achieved by strictly regulated and intricately choreographed mechanisms, often through the action of replication initiation and helicase-loader proteins. Current structural and biochemical data reveal a wide range of different helicase-loading mechanisms. Here we review advances in this area and discuss their implications. © 2012 Blackwell Publishing Ltd.

Mowles S.L.,University of Nottingham
Animal Behaviour | Year: 2014

During courtship interactions, males typically perform displays that are assumed to demonstrate some aspect of their quality. While some displays are elaborate and spectacular in appearance, others involve comparatively simple repetitive actions. The functions of these dynamic repeated courtship displays are hypothesized to fall into two broad categories. Either the signal is repeated as a process of validation to counter errors in transmission, or the process of repetition itself advertises the ability to bear signalling costs. The function of any repetitive courtship display can thus be identified by investigating the nature of production costs as well as the pattern of repetition. In the present study, I investigated the function of signal repetition using a commonly used organism, the Mediterranean field cricket, Gryllus bimaculatus. Male G.bimaculatus court females by producing acoustic signals using rapid, repeated movements of their wings. I tested for the presence of energetic costs by analysing haemolymph lactate concentrations after time-controlled courtship interactions. Males that had performed 5. min of courtship were found to have higher levels of haemolymph lactate relative to controls. Furthermore, those individuals producing more rapid song had higher levels of haemolymph lactate. The song produced by courting crickets therefore incurs significant energetic costs, and probably serves to advertise the energetic cost capacity of the calling male. Thus, I confirm that stridulation is an energetically costly signal and demonstrate that anaerobic metabolism appears to be a significant cost of repeated courtship displays. © 2013 The Association for the Study of Animal Behaviour.

Brax P.,CEA Saclay Nuclear Research Center | Burrage C.,University of Nottingham
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

Light scalar fields can naturally couple disformally to matter fields. Static, nonrelativistic sources do not generate a classical field profile for a disformally coupled scalar, and so such scalars are free from the constraints on the existence of fifth forces that are so restrictive for conformally coupled scalars. In this paper we show that disformally coupled scalars can still be studied and constrained through their microscopic interactions with fermions and photons, both in terrestrial laboratories and from observations of stars. The strongest constraint on the coupling scale comes from mono-photon searches at the LHC and requires M3102GeV. © 2014 American Physical Society.

Wilkinson R.D.,University of Nottingham
Statistical Applications in Genetics and Molecular Biology | Year: 2013

Approximate Bayesian computation (ABC) or likelihood-free inference algorithms are used to find approximations to posterior distributions without making explicit use of the likelihood function, depending instead on simulation of sample data sets from the model. In this paper we show that under the assumption of the existence of a uniform additive model error term, ABC algorithms give exact results when sufficient summaries are used. This interpretation allows the approximation made in many previous application papers to be understood, and should guide the choice of metric and tolerance in future work. ABC algorithms can be generalized by replacing the 0 - 1 cut-off with an acceptance probability that varies with the distance of the simulated data from the observed data. The acceptance density gives the distribution of the error term, enabling the uniform error usually used to be replaced by a general distribution. This generalization can also be applied to approximate Markov chain Monte Carlo algorithms. In light of this work, ABC algorithms can be seen as calibration techniques for implicit stochastic models, inferring parameter values in light of the computer model, data, prior beliefs about the parameter values, and any measurement or model errors.

Hobson-West P.,University of Nottingham
Journal of Medical Ethics | Year: 2010

Animal research remains a deeply controversial topic in biomedical science. While a vast amount has been written about the ethical status of laboratory animals, far less academic attention has been devoted to the public and, more specifically, to public opinion. Rather than what the public think, this article considers the role of 'public opinion'. It draws on a recent empirical study which involved interviews with laboratory scientists who use animals in their research, and with other UK stakeholders. The first section of the paper demonstrates that public opinion has become a kind of resource in the animal research debate. Public opinion polls, in particular, are frequently cited. The second section explores this further and argues that, for all sides, appealing to public opinion is a key way to show legitimacy. Finally, the paper shifts gear to consider whether public opinion should matter, both for ethical reasoning and for science policy.

Conselice C.J.,University of Nottingham
Annual Review of Astronomy and Astrophysics | Year: 2014

I present a comprehensive review of the evolution of galaxy structure in the Universe from the first galaxies currently observable at z ∼ 6 down to galaxies observable in the local Universe. Observed changes in galaxy structures reveal formation processes that only galaxy structural analyses can provide. This pedagogical review provides a detailed discussion of the major methods used to study galaxies morphologically and structurally, including the well-established visual method for morphology; Sérsic fitting to measure galaxy sizes and surface brightness profile shapes; and nonparametric structural methods [such as the concentration (C), asymmetry (A), clumpiness (S) (CAS) method and the Gini/M20 parameters, as well as newer structural indices]. These structural indices measure fundamental properties of galaxies, such as their scale, star-formation rate, and ongoing merger activity. Extensive observational results demonstrate how broad galaxy morphologies and structures change with time up to z ∼ 3, from small, compact and peculiar systems in the distant Universe to the formation of the Hubble sequence, dominated by spirals and ellipticals. Structural methods accurately identify galaxies in mergers and allow measurements of the merger history out to z ∼ 3. I depict properties and evolution of internal structures of galaxies, such as bulges, disks, bars, and at z>1 large star-forming clumps. I describe the structure and morphologies of host galaxies of active galactic nuclei and starbursts/ submillimeter galaxies, along with how morphological galaxy quenching occurs. The role of environment in producing structural changes in galaxies over cosmic time is also discussed. Galaxy sizes can also change with time, with measured sizes up to a factor of 2-5 smaller at high redshift at a given stellar mass. I conclude with a discussion of how the evolving trends, in sizes, structures, and morphologies, reveal the formation mechanisms behind galaxies and provides a new and unique way to test theories of galaxy formation. Copyright © 2014 by Annual Reviews.

Szabadi E.,University of Nottingham
Journal of Psychopharmacology | Year: 2015

The sleep disorder narcolepsy is caused by the loss of orexinergic neurones in the lateral hypothalamus. A troublesome symptom of narcolepsy is cataplexy, the sudden loss of muscle tone in response to strong emotions. It can be alleviated by antidepressants and sodium oxybate (γ-hydroxybutyric acid (GHB)). It is likely that the noradrenergic nucleus locus coeruleus (LC) is involved since it is essential for the maintenance of muscle tone, and ceases to fire during cataplectic attacks. Furthermore, alpha-2 adrenoceptors proliferate in the LC in cataplexy, probably due to 'heterologous denervation supersensitivity' resulting from the loss/weakening of the orexinergic input to the LC. This would lead to the sensitization of the autoinhibition mechanism of LC neurones mediated by inhibitory alpha-2 adrenoceptors ('autoreceptors'). Thus the excitatory input from the amygdala to the LC, activated by an emotional stimulus, would lead to the 'switching off' of LC activity via the supersensitive auto-inhibition mechanism. GHB is an agonist at both γ-aminobutyric acid (GABA) GABA (B) and GHB receptors that may be a subtype of an extrasynaptic GABA(A) receptor. GHB may prevent a cataplectic attack by dampening the tone of LC neurones via the stimulation of inhibitory extrasynaptic GABA receptors in the LC, and thus increasing the threshold for autoinhibition. © The Author(s) 2015.

In 1999, the UK government initiated a programme for the assessment and treatment of individuals deemed to have 'dangerous and severe personality disorder' (DSPD). After over 10 years of specialist service development, it is not clear whether DSPD patients represent a distinct group. The aim of this study was to establish whether people admitted to DSPD hospital units could be distinguished in presentation or personality traits from people with personality disorder admitted to standard secure hospital services. Thirty-eight men detained in high-security hospital DSPD units were compared with 62 men detained in conventional medium or high security hospital units, using the Psychopathy Checklist-Revised (PCL-R) and other standard personality disorder, clinical and offending measures. Compared with their counterparts in standard services, the DSPD group had higher scores on PCL-R psychopathy, significantly more convictions before age 18 years, greater severity of institutional violence and more prior crimes of sexual violence. Regression analysis confirmed that only PCL-R Factor 1, reflecting core interpersonal and affective features of psychopathy, predicted group membership. The DSPD group emerged as having higher psychopathy scores, but as there is currently no evidence that the core personality features of psychopathy are amenable to treatment, there is little justification for treating high-psychopathy forensic patients differently from those with other disorders of personality. Copyright © 2011 John Wiley & Sons, Ltd.

Li R.,Emory University | Emsley J.,University of Nottingham
Journal of Thrombosis and Haemostasis | Year: 2013

The glycoprotein (GP)Ib-IX-V complex is the platelet receptor for von Willebrand factor and many other molecules that are critically involved in hemostasis and thrombosis. The lack of functional GPIb-IX-V complexes on the platelet surface is the cause of Bernard-Soulier syndrome, a rare hereditary bleeding disorder that is also associated with macrothrombocytopenia. GPIb-IX-V contains GPIbα, GPIbβ, GPIX and GPV subunits, all of which are type I transmembrane proteins containing leucine-rich repeat domains. Although all of the subunits were identified decades ago, not until recently did the mechanism of complex assembly begin to emerge from a systematic characterization of inter-subunit interactions. This review summarizes the forces driving the assembly of GPIb-IX-V, discusses their implications for the pathogenesis of Bernard-Soulier syndrome, and identifies questions that remain about the structure and organization of GPIb-IX-V. © 2013 International Society on Thrombosis and Haemostasis.

This chapter describes the characteristics of adult patients starting renal replacement therapy (RRT) in the UK in 2008 and the acceptance rates for RRT in Primary Care Trusts and Local Authorities (PCT/LAs) in the UK. The basic demographics and clinical characteristics are reported on patients starting RRT from all UK renal centres. Late referral, defined as time between first being seen by a nephrologist and start of RRT being <90 days was also studied. Age and gender standardised ratios for acceptance rate in PCT/LAs were calculated. In 2008, the acceptance rate in the UK was 108 per million population (pmp). Acceptance rates in Scotland (103 pmp), Northern Ireland (97 pmp) and Wales (117 pmp) have all fallen although Wales still remains the country with the highest acceptance rate. There were wide variations between PCT/LAs with respect to the standardised ratios, which were lower in more PCT/LAs in the North West and South East of England and higher in London, the West Midlands, Scotland, Northern Ireland, and Wales. The median age of all incident patients was 64.1 years and for non-Whites 56.1 years. Diabetic renal disease remains the single most common cause of renal failure (24%). By 90 days, 67.7% of patients were on haemodialysis, 19.8% on peritoneal dialysis, 5.9% had had a transplant and 6.6% had died or had stopped treatment. By 90 days, 77.4% of all dialysis patients were on HD. The geometric mean eGFR at the start of RRT was 8.6 ml/min/ 1.73 m(2) which was similar to the eGFR of those starting in 2007. The incidence of late presentation (<90 days) has fallen from 28% in 2003 to 22% in 2008. There was no relationship between social deprivation and referral pattern. Acceptance rates have fallen in Northern Ireland, Scotland and Wales whilst they have plateaued in England over the last three years. Wales continued to have the highest acceptance rate of the countries making up the UK. (c) 2010 S. Karger AG, Basel.

Ferguson E.,University of Nottingham
Health Psychology Review | Year: 2013

This paper sets out the case that personality traits are central to health psychology. To achieve this, three aims need to be addressed. First, it is necessary to show that personality influences a broad range of health outcomes and mechanisms. Second, the simple descriptive account of Aim 1 is not sufficient, and a theoretical specification needs to be developed to explain the personality-health link and allow for future hypothesis generation. Third, once Aims 1 and 2 are met, it is necessary to demonstrate the clinical utility of personality. In this review I make the case that all three Aims are met. I develop a theoretical framework to understand the links between personality and health drawing on current theorising in the biology, evolution, and neuroscience of personality. I identify traits (i.e., alexithymia, Type D, hypochondriasis, and empathy) that are of particular concern to health psychology and set these within evolutionary cost-benefit analysis. The literature is reviewed within a three-level hierarchical model (individual, group, and organisational) and it is argued that health psychology needs to move from its traditional focus on the individual level to engage group and organisational levels. © 2013 Copyright Taylor and Francis Group, LLC.

Baker J.G.,University of Nottingham
British Journal of Pharmacology | Year: 2010

Background and purpose: There are two important properties of receptor-ligand interactions: affinity (the ability of the ligand to bind to the receptor) and efficacy (the ability of the receptor-ligand complex to induce a response). Ligands are classified as agonists or antagonists depending on whether or not they have efficacy. In theory, it is possible to develop selective agonists based on selective affinity, selective intrinsic efficacy or both. This study examined the affinity and intrinsic efficacy of 31 β-adrenoceptor agonists at the three human β-adrenoceptors to determine whether the current agonists are subtype selective because of affinity or intrinsic efficacy. Experimental approach: Stable clonal CHO-K1 cell lines, transfected with either the human β 1, β 2 or β 3-adrenoceptor, were used, and whole-cell 3H-CGP 12177 radioligand binding and 3H-cAMP accumulation were measured. Key results: Several agonists were found to be highly subtype selective because of selective affinity (e.g. salmeterol and formoterol, for the β 2- adrenoceptor over the β 1 or β 3), while others (e.g. isoprenaline) had little affinity-selectivity. However, the intrinsic efficacy of salmeterol, formoterol and isoprenaline was similar across all three receptor subtypes. Other ligands (e.g. denopamine for β 1; clenbuterol, AZ 40140d, salbutamol for β 2) were found to have subtype-selective intrinsic efficacy. Several ligands appeared to activate two agonist conformations of the β 1- and β 3- adrenoceptors. Conclusions and implications: There are agonists with subtype selectivity based upon both selective affinity and selective intrinsic efficacy. © 2010 The British Pharmacological Society.

Adesso G.,University of Nottingham
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2014

The interferometric power of a bipartite quantum state quantifies the precision, measured by quantum Fisher information, that such a state enables for the estimation of a parameter embedded in a unitary dynamics applied to one subsystem only, in the worst-case scenario where a full knowledge of the generator of the dynamics is not available a priori. For finite-dimensional systems, this quantity was proven to be a faithful measure of quantum correlations beyond entanglement. Here we extend the notion of interferometric power to the technologically relevant setting of optical interferometry with continuous-variable probes. By restricting to Gaussian local dynamics, we obtain a closed formula for the interferometric power of all two-mode Gaussian states. We identify separable and entangled Gaussian states which maximize the interferometric power at fixed mean photon number of the probes and discuss the associated metrological scaling. At fixed entanglement of the probes, highly thermalized states can guarantee considerably larger precision than pure two-mode squeezed states. © 2014 American Physical Society.

Objective: To determine the efficacy of dexamethasone in the treatment of mechanically ventilated children with respiratory syncytial virus-severe lower respiratory tract infection. Design: International, multicenter, randomized, double-blind, placebo-controlled trial. Setting: Twelve pediatric intensive care units. Subjects: Children (<2 yrs) mechanically ventilated for respiratory syncytial virus lower respiratory tract infection. Children were prestratified for severity of oxygen abnormalities on admission. Intervention: Intravenous dexamethasone (0.6 mg/kg/day, 48 hrs) or placebo. Measurements and Main Results: A superiority approach was used in the subgroup of patients with mild oxygen abnormalities (arterial partial pressure of oxygen/fractional inspired oxygen concentration [PaO2/Fio2] >200 mm Hg and/or mean arterial pressure ≤10 cm H2O) and a noninferiority approach in those with severe oxygen abnormalities (PaO2/Fio2 ≤200 mm Hg and mean arterial pressure >10 cm H2O). Primary outcome was the duration of mechanical ventilation. In the subgroup with mild oxygenation abnormalities, 45 of the 89 included patients received dexamethasone and 44 placebo; in the subgroup with severe oxygenation abnormalities, 28 of the 56 included patients received dexamethasone and 28 placebo. Baseline characteristics in both treatment arms were similar for both subgroups. After the third interim analysis, the trial was stopped early for futility taking the slow enrollment into account. At that time, the median duration (interquartile range) of mechanical ventilation was 137 (91-195) hrs in the dexamethasone- and 139 (117-188) hrs in the placebo-treated patients in the subgroup with mild oxygenation abnormalities (p = .6). In the subgroup with severe oxygenation abnormalities, it was 171 (136-212) hrs in the dexamethasone- and 170 (125-201) hrs in the placebo-treated patients (p = .6). Conclusion: In this prematurely ended trial in children mechanically ventilated for severe respiratory syncytial virus-lower respiratory tract infection, we found no evidence of a beneficial effect of dexamethasone in children with mild oxygenation abnormalities. Neither was evidence found that dexamethasone may prolong mechanical ventilation in those with severe oxygenation abnormalities. Copyright © 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.

Haque M.,University of Nottingham
Mathematical Biosciences | Year: 2012

The study of reaction-diffusion system constitutes some of the most fascinating developments of late twentieth century mathematics and biology. This article investigates complexity and chaos in the complex patterns dynamics of the original Beddington-DeAngelis predator-prey model which concerns the influence of intra species competition among predators. We investigate the emergence of complex patterns through reaction-diffusion equations in this system. We derive the conditions for the codimension-2 Turing-Hopf, Turing-Saddle-node, and Turing-Transcritical bifurcation, and the codimension-3 Turing-Takens-Bogdanov bifurcation. These bifurcations give rise to very complex patterns that have not been observed in previous predator-prey models. A large variety of different types of long-term behavior, including homogenous distributions and stationary spatial patterns are observed through extensive numerical simulations with experimentally-based parameter values. Finally, a discussion of the ecological implications of the analytical and numerical results concludes the paper. © 2012 Elsevier Inc.

Liddle S.T.,University of Nottingham
Angewandte Chemie - International Edition | Year: 2015

Prior to the year 2000, non-aqueous uranium chemistry mainly involved metallocene and classical alkyl, amide, or alkoxide compounds as well as established carbene, imido, and oxo derivatives. Since then, there has been a resurgence of the area, and dramatic developments of supporting ligands and multiply bonded ligand types, small-molecule activation, and magnetism have been reported. This Review 1) introduces the reader to some of the specialist theories of the area, 2) covers all-important starting materials, 3) surveys contemporary ligand classes installed at uranium, including alkyl, aryl, arene, carbene, amide, imide, nitride, alkoxide, aryloxide, and oxo compounds, 4) describes advances in the area of single-molecule magnetism, and 5) summarizes the coordination and activation of small molecules, including carbon monoxide, carbon dioxide, nitric oxide, dinitrogen, white phosphorus, and alkanes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dunlop M.,University of Nottingham | Murray A.D.,Scottish Government Sport and Physical Activity Policy Team
British Journal of Sports Medicine | Year: 2013

Background: Education of health professionals is a key element of the wider strategy to increase society's physical activity levels. To date, no study has directly assessed UK medical students' knowledge of physical activity guidelines or their ability/willingness to prescribe exercise. Methods: A questionnaire survey of final year medical students in Scottish Universities was conducted prior to a presentation on the current UK guidelines. Results: Completed questionnaires (n=177) represented 37% of the final year cohorts. Physical inactivity was incorrectly perceived to be the least important risk factor to global mortality. 40% stated they were aware of current guidelines, but in a forced choice, 68% were able to correctly identify them for adults. In comparison, 97% correctly identified the UK's alcohol guidelines. 52% stated they felt adequately trained to give physical activity advice to the general public. Conclusions: The medical students in this study underestimated the risk of physical inactivity, and did not know the physical activity guidelines as well as other health promotion guidelines. A large proportion remained unconfident about giving physical activity advice. Improved education of this group is required.

Infection control for hospital pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) often takes the form of a package of interventions, including the use of patient isolation and decolonization treatment. Such interventions, though widely used, have generated controversy because of their significant resource implications and the lack of robust evidence with regard to their effectiveness at reducing transmission. The aim of this study was to estimate the effectiveness of isolation and decolonization measures in reducing MRSA transmission in hospital general wards. Prospectively collected MRSA surveillance data from 10 general wards at Guy's and St. Thomas' hospitals, London, United Kingdom, in 2006-2007 were used, comprising 14,035 patient episodes. Data were analyzed with a Markov chain Monte Carlo algorithm to model transmission dynamics. The combined effect of isolation and decolonization was estimated to reduce transmission by 64% (95% confidence interval: 37, 79). Undetected MRSA-positive patients were estimated to be the source of 75% (95% confidence interval: 67, 86) of total transmission events. Isolation measures combined with decolonization treatment were strongly associated with a reduction in MRSA transmission in hospital general wards. These findings provide support for active methods of MRSA control, but further research is needed to determine the relative importance of isolation and decolonization in preventing transmission. © 2013 © The Author 2013. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Padilla A.,University of Nottingham
Journal of Physics: Conference Series | Year: 2010

I review the good, the bad and the ugly of the non-projectable versions of Hoava gravity. I explain how this non-relativistic theory was constructed and why it was touted with such excitement as a quantum theory of gravity. I then review some of the issues facing the theory, explaining how strong coupling occurs and why this is such a problem for both phenomenology and the question of renormalisability. Finally I comment on possible violations of Equivalence Principle, and explain why these could be an issue for Blas et al's "healthy extension". © 2010 IOP Publishing Ltd.

Brax P.,CEA Saclay Nuclear Research Center | Burrage C.,University of Nottingham
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We analyze the consequences of a disformal interaction between a massless scalar and matter particles in the context of atomic physics. We focus on the displacement of the atomic energy levels that it induces, and in particular the change in the Lamb shift between the 2s and 2p states. We find that the correction to the Lamb shift depends on the mass of the fermion orbiting around the nucleus, implying a larger effect for muonic atoms. Taking the cutoff scale describing the effective scalar field theory close to the QCD scale, we find that the disformal interaction can account for the observed difference in the proton radius of muonic versus electronic hydrogen. Explaining the proton radius puzzle is only possible when the scalar field is embedded in nonlinear theories which alleviate constraints from collider and stellar physics. Short distance properties of the Galileon where nonperturbative effects in vacuum are present ensure that unitarity is preserved in high-energy particle collisions. In matter, the chameleon mechanism alleviates the constraints on disformal interactions coming from the burning rates for stellar objects. We show how to combine these two properties in a single model which renders the proposed explanation of the proton radius puzzle viable. © 2015 American Physical Society.

White S.M.,University of Sussex | Moppett I.K.,University of Nottingham | Griffiths R.,Peterborough and Stamford Hospitals NHS Trust
Anaesthesia | Year: 2014

Large observational studies of accurate data can provide similar results to more arduous and expensive randomised controlled trials. In 2012, the National Hip Fracture Database extended its dataset to include 'type of anaesthesia' data fields. We analysed 65 535 patient record sets to determine differences in outcome. Type of anaesthesia was recorded in 59 191 (90%) patients. Omitting patients who received both general and spinal anaesthesia or in whom an uncertain type of anaesthesia was recorded, there was no significant difference in either cumulative five-day (2.8% vs 2.8%, p = 0.991) or 30-day (7.0% vs 7.5%, p = 0.053) mortality between 30 130 patients receiving general anaesthesia and 22 999 patients receiving spinal anaesthesia, even when 30-day mortality was adjusted for age and ASA physical status (p = 0.226). Mortality within 24 hours after surgery was significantly higher among patients receiving cemented compared with uncemented hemiarthroplasty (1.6% vs 1.2%, p = 0.030), suggesting excess early mortality related to bone cement implantation syndrome. If these data are accurate, then either there is no difference in 30-day mortality between general and spinal anaesthesia after hip fracture surgery per se, and therefore future research should focus on how to make both types of anaesthesia safer, or there is a difference, but mortality is not the correct outcome to measure after anaesthesia, and therefore future research should focus on differences between general and spinal anaesthesia. These could include more anaesthesia-sensitive outcomes, such as hypotension, pain, postoperative confusion, respiratory infection and mobilisation. © 2014 The Association of Anaesthetists of Great Britain and Ireland.

Dhir A.,University of Oxford | Dhir S.,University of Oxford | Proudfoot N.J.,University of Oxford | Jopling C.L.,University of Nottingham
Nature Structural and Molecular Biology | Year: 2015

MicroRNAs (miRNAs) play a major part in the post-transcriptional regulation of gene expression. Mammalian miRNA biogenesis begins with cotranscriptional cleavage of RNA polymerase II (Pol II) transcripts by the Microprocessor complex. Although most miRNAs are located within introns of protein-coding transcripts, a substantial minority of miRNAs originate from long noncoding (lnc) RNAs, for which transcript processing is largely uncharacterized. We show, by detailed characterization of liver-specific lnc-pri-miR-122 and genome-wide analysis in human cell lines, that most lncRNA transcripts containing miRNAs (lnc-pri-miRNAs) do not use the canonical cleavage-and-polyadenylation pathway but instead use Microprocessor cleavage to terminate transcription. Microprocessor inactivation leads to extensive transcriptional readthrough of lnc-pri-miRNA and transcriptional interference with downstream genes. Consequently we define a new RNase III-mediated, polyadenylation-independent mechanism of Pol II transcription termination in mammalian cells. © 2015 Nature America, Inc. All rights reserved.

Pickett K.E.,University of York | Wilkinson R.G.,University of Nottingham
British Journal of Psychiatry | Year: 2010

Greater income inequality is associated with higher prevalence of mental illness and drug misuse in rich societies. There are threefold differences in the proportion of the population suffering from mental illness between more and less equal countries. This relationship is most likely mediated by the impact of inequality on the quality of social relationships and the scale of status differentiation in different societies.

Seddon A.B.,University of Nottingham
Physica Status Solidi (B) Basic Research | Year: 2013

After an introduction to the mid-infrared (IR) spectral region, the tremendous significance of mid-IR spectroscopic sensing is highlighted. The remarkable progress made towards mid-IR spectral in vitro mapping of tissue and cancer detection is reviewed, with emphasis on diagnosis of skin cancer. The status quo of chalcogenide glass mid-IR fibre optics and photonics for meeting opportunities for remote mid-IR sensing in general, and in in vivo cancer detection in particular, is assessed. Raman spectroscopy is a sister technique to mid-IR spectroscopy. The current success of Raman spectroscopy in medical diagnosis is appraised, with particular emphasis on Raman spectral imaging of tissue towards skin cancer diagnosis in vivo, based on a silica-glass fibreoptic sensor-head. The challenges to be met in chalcogenide glass science and technology towards facilitating analogous fibreoptic diagnostics based on mid-IR spectroscopy are addressed. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Docherty J.R.,Royal College of Surgeons in Ireland | Green A.R.,University of Nottingham
British Journal of Pharmacology | Year: 2010

Hyperthermia is probably the most widely known acute adverse event that can follow ingestion of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) by recreational users. The effect of MDMA on body temperature is complex because the drug has actions on all three major monoamine neurotransmitters 5-hydroxytryptamine (5-HT), dopamine and noradrenaline, both by amine release and by direct receptor activation. Hyperthermia and hypothermia can be induced in laboratory animals by MDMA, depending on the ambient temperature, and involve both central thermoregulation and peripheral changes in blood flow and thermogenesis. Acute 5-HT release is not directly responsible for hyperthermia, but 5-HT receptors are involved in modulating the hyperthermic response. Impairing 5-HT function with a neurotoxic dose of MDMA or p-chlorophenylalanine alters the subsequent MDMA-induced hyperthermic response. MDMA also releases dopamine, and evidence suggests that this transmitter is involved in both the hyperthermic and hypothermic effects of MDMA in rats. The noradrenergic system is also involved in the hyperthermic response to MDMA. MDMA activates central α2A-adrenoceptors and peripheral α1- adrenoceptors to produce cutaneous vasoconstriction to restrict heat loss, and β3-adrenoceptors in brown adipose tissue to increase heat generation. The hyperthermia occurring in recreational users of MDMA can be fatal, but data reviewed here indicate that it is unlikely that any single pharmaceutical agent will be effective in reversing the hyperthermia, so careful body cooling remains the principal clinical approach. Crucially, educating recreational users about the potential dangers of hyperthermia and the control of ambient temperature should remain key approaches to prevent this potentially fatal problem. © 2010 The British Pharmacological Society.

Szabadi E.,University of Nottingham
Journal of Psychopharmacology | Year: 2013

The central noradrenergic neurone, like the peripheral sympathetic neurone, is characterized by a diffusely arborizing terminal axonal network. The central neurones aggregate in distinct brainstem nuclei, of which the locus coeruleus (LC) is the most prominent. LC neurones project widely to most areas of the neuraxis, where they mediate dual effects: neuronal excitation by α1-adrenoceptors and inhibition by α2-adrenoceptors. The LC plays an important role in physiological regulatory networks. In the sleep/arousal network the LC promotes wakefulness, via excitatory projections to the cerebral cortex and other wakefulness-promoting nuclei, and inhibitory projections to sleep-promoting nuclei. The LC, together with other pontine noradrenergic nuclei, modulates autonomic functions by excitatory projections to preganglionic sympathetic, and inhibitory projections to preganglionic parasympathetic neurones. The LC also modulates the acute effects of light on physiological functions ('photomodulation'): stimulation of arousal and sympathetic activity by light via the LC opposes the inhibitory effects of light mediated by the ventrolateral preoptic nucleus on arousal and by the paraventricular nucleus on sympathetic activity. Photostimulation of arousal by light via the LC may enable diurnal animals to function during daytime. LC neurones degenerate early and progressively in Parkinson's disease and Alzheimer's disease, leading to cognitive impairment, depression and sleep disturbance. © The Author(s) 2013.

Sotiriou T.P.,University of Nottingham | Zhou S.-Y.,International School for Advanced Studies | Zhou S.-Y.,National Institute of Nuclear Physics, Italy
Physical Review Letters | Year: 2014

The most general action for a scalar field coupled to gravity that leads to second-order field equations for both the metric and the scalar - Horndeski's theory - is considered, with the extra assumption that the scalar satisfies shift symmetry. We show that in such theories, the scalar field is forced to have a nontrivial configuration in black hole spacetimes, unless one carefully tunes away a linear coupling with the Gauss-Bonnet invariant. Hence, black holes for generic theories in this class will have hair. This contradicts a recent no-hair theorem which seems to have overlooked the presence of this coupling. © 2014 American Physical Society.

Jopling C.L.,University of Nottingham
Viruses | Year: 2010

Abstract: An important host factor for hepatitis C virus (HCV) is microRNA-122 (miR-122). miR-122 is a liver-specific member of a family of small, non-coding RNA molecules known as microRNAs that play major roles in the regulation of gene expression by direct interaction with RNA targets. miR-122 binds directly to two sites in the 5′ untranslated region (UTR) of HCV RNA and positively regulates the viral life cycle. The mechanism by which this regulation occurs is still not fully understood. There has been a great deal of interest in potential therapeutics based on small RNAs, and targeting miR-122 to combat HCV is one of the furthest advanced. Chemical inhibitors of miR-122 can be introduced into mammals intravenously and result in potent and specific knockdown of the microRNA, with no detectable adverse effects on liver physiology. This strategy was recently applied to chimpanzees chronically infected with HCV and resulted in a sustained reduction in viral load in the animals. Inhibition of miR-122 therefore presents a very attractive novel approach to treating HCV, a virus for which improved therapeutics are urgently needed. © 2010 by the authors.

Durugbo C.,University of Nottingham
Expert Systems with Applications | Year: 2012

User participation (UP) means activities that individuals perform for processes to develop systems or to act collectively and is an important factor for gaining user commitment and minimising user resistance. This is due to the ability of UP to shape the structure and behaviour of organisations through leveraged user expertise, minimised redundant processes and improved understanding of systems. Grounded on social network analysis and UP research, this article proposes a mathematical model for analysing UP in 'organisations as networks'. The model identifies concepts for characterising network structures for UP and introduces indicators for assessing the network behaviour of human participants within organisations. The article concludes by discussing implications for researchers and practitioners, and limitations of the proposed model. © 2012 Elsevier Ltd. All rights reserved.

Gan G.,University of Nottingham
Building and Environment | Year: 2010

Traditional solar heated cavity structures such as solar chimneys make use of the stored solar energy in the interior wall to enhance natural ventilation of buildings but integration of photovoltaic devices into the exterior wall of such a structure can result in different proportions of heat distribution on both interior and exterior walls. This paper presents results of CFD simulation of the buoyancy-driven airflow and heat transfer in vertical cavities of different heights and widths with different total heat fluxes and wall heat distributions for ventilation cooling. Two sizes of computational domain were used for simulation - a small domain same as the physical size of a cavity and a large extended domain that is much larger than the cavity. The predicted natural ventilation rate and heat transfer coefficient have been found to depend on not only the cavity size and the quantity and proportion of heat distribution on the cavity walls but also the domain size. The difference in the predicted ventilation rate or heat transfer coefficient using the small and large domains is generally larger for wider cavities where heat distribution on two vertical walls is highly asymmetrical; incoming air would be distorted from symmetrical distribution across the inlet opening; and/or significant reverse flow would occur at the outlet opening. The difference in the heat transfer coefficient is generally less than that in the ventilation rate. In addition, a cavity with symmetrical heating has a higher ventilation rate but lower heat transfer coefficient than does an asymmetrically heated cavity. © 2009 Elsevier Ltd. All rights reserved.

Foster T.J.,University of Nottingham
Food Hydrocolloids | Year: 2011

This review covers the emerging science and application of the use of cell wall materials in the manufacture of soft solid composites. The achievement thus far has been in the area of food products, but alternative product types e.g. cosmetics and detergent based systems are not beyond the scope of this technology. The recent development in the understanding of such composite systems is allowing the precision structuring of the end product, but also may serve to determine the molecular requirements from natural primary production. Here functionalisation of the composite through physical, chemical and biochemical processes is outlined and examples of use in food formulations are covered. Future challenges of delivering Food Security for the world may also be achieved by application of such findings. © 2011.

Background Cellulitis (erysipelas) of the leg is a common, painful infection of the skin and underlying tissue. Repeat episodes are frequent, cause significant morbidity and result in high health service costs. Objectives To assess whether prophylactic antibiotics prescribed after an episode of cellulitis of the leg can prevent further episodes. Methods Double-blind, randomized controlled trial including patients recently treated for an episode of leg cellulitis. Recruitment took place in 20 hospitals. Randomization was by computer-generated code, and treatments allocated by post from a central pharmacy. Participants were enrolled for a maximum of 3 years and received their randomized treatment for the first 6 months of this period. Results Participants (n = 123) were randomized (31% of target due to slow recruitment). The majority (79%) had suffered one episode of cellulitis on entry into the study. The primary outcome of time to recurrence of cellulitis included all randomized participants and was blinded to treatment allocation. The hazard ratio (HR) showed that treatment with penicillin reduced the risk of recurrence by 47% [HR 0·53, 95% confidence interval (CI) 0·26-1·07, P = 0·08]. In the penicillin V group 12/60 (20%) had a repeat episode compared with 21/63 (33%) in the placebo group. This equates to a number needed to treat (NNT) of eight participants in order to prevent one repeat episode of cellulitis [95% CI NNT(harm) 48 to ∞ to NNT(benefit) 3]. We found no difference between the two groups in the number of participants with oedema, ulceration or related adverse events. Conclusions Although this trial was limited by slow recruitment, and the result failed to achieve statistical significance, it provides the best evidence available to date for the prevention of recurrence of this debilitating condition. © 2011 British Association of Dermatologists.

Walker J.G.,University of Nottingham
Measurement Science and Technology | Year: 2012

Nano-particle tracking is a method to estimate a particle size distribution by tracking the movements of individual particles, using multiple images of particles moving under Brownian motion. A novel method to recover a particle size distribution from nano-particle tracking data is described. Unlike a simple histogram-based method, the method described is able to account for the finite number of steps in each particle track and consequently for the measurement uncertainty in the step-length data. Computer simulation and experimental results are presented to demonstrate the performance of the approach compared with the current method. © 2012 IOP Publishing Ltd.

Lu M.,GL Nobel Denton | McDowell G.R.,University of Nottingham
Geotechnique | Year: 2010

Triaxial samples of railway ballast have been modelled using clumps of spheres. The bulk of the clump is formed from ten balls in a tetrahedral shape. The interlocking and breaking of very small asperities which find their way into the voids is modelled using weak parallel bonds between clumps. The interlocking and fracture of larger asperities has been modelled by bonding eight small balls to the clump. Monotonic tests have been performed on triaxial samples under a range of confining pressures from 15 kPa to 240 kPa and the results compared with existing experimental data. Tests were also simulated using uncrushable clumps to highlight the important role of asperity abrasion. Cyclic triaxial tests were then simulated on the same aggregates using the same microparameters as the monotonic tests under a range of stress conditions and the results were compared to existing experimental data for the same simulated ballast. The results show that the clumps are able to capture the behaviour of ballast under both monotonic and cyclic conditions and asperity abrasion is shown to play an important role in governing strength and volumetric strain under monotonic loading, and on permanent strains under cyclic loading. The new contribution is therefore to show that it is possible to model a real granular material under static and cyclic conditions, thus providing much micromechanical insight.

Thom N.,University of Nottingham
Quaternary Science Reviews | Year: 2010

This topic area has been a controversial one since the concept of a catastrophic Black Sea flood was first proposed, and there is still considerable disagreement between experts as to the exact sequence of events. This paper describes a numerical model of the Caspian and Black sea basins together with flows through the Manych spillway and the Bosphorus strait. The model has been calibrated against the deductions made by various researchers concerning past water levels, and parameters such as river flow volumes and evaporation rates have been assigned to give reasonable agreement with these deductions. The model successfully predicts flow through the Manych spillway during the early Khvalynian transgression of the Caspian Sea between 15.2 and 12.3. ky. BP - and not thereafter. The Black Sea is predicted to reach a lowstand of -163. m in about 11. ky. BP and then to fill relatively rapidly due to increased river inflow combined with a breakthrough of Mediterranean water across the Bosphorus sill in about 10.5. ky. BP. This is followed by a period of high outflow through the Bosphorus and, between 9.3 and 8. ky. BP, by rapidly rising salinity due to marine inflow at depth. The model also highlights two significant points of conflict with the physical evidence. These concern the lack of apparent reason for the sudden onset of sapropel formation in the Black Sea in 7.6. ky. BP and the significant erosion that has apparently occurred across the Manych sill. © 2010 Elsevier Ltd.

Stirling J.,University of Nottingham
Beilstein Journal of Nanotechnology | Year: 2013

We propose a geometry for a piezoelectric SPM sensor that can be used for combined AFM/LFM/STM. The sensor utilises symmetry to provide a lateral mode without the need to excite torsional modes. The symmetry allows normal and lateral motion to be completely isolated, even when introducing large tips to tune the dynamic properties to optimal values. © 2013 Stirling; licensee Beilstein-Institut.

Herrerias M.J.,University of Nottingham
Applied Energy | Year: 2013

This paper provides evidence on the relevance of modeling the seasonal nature of electricity intensity across Chinese regions in a suitable manner with monthly data from 2003 to 2009. In contrast to previous works, this study relaxes the assumption of deterministic seasonality, allowing for time and regional variation in the Chinese economy. In doing so, unobserved-components models are used to analyze the type of seasonality - stochastic or deterministic - that prevails. Regional differences in the seasonal patterns and their evolution over time are also examined. Results provide new empirical evidence on the stochastic nature of electricity intensity in the majority of the provinces. In addition, we find four main effects as regards seasonal patterns: (i) Lunar New Year, (ii) Summer, (iii) Spring, and (iv) Winter effects. In the first two effects seasonality becomes positive, thus indicating that electricity intensity increases, and the last two are negative, showing improvements in the use of electricity per unit of output. However, differences are observed between northern regions and the east-south of China. In addition, once we control our estimates for temperature and prices, no significant differences are seen in the results. Conclusions from this analysis are useful for empirical modeling in the energy-economics literature, and also for designing energy policies to improve the efficiency of the use of energy resources across Chinese regions. © 2013 Elsevier Ltd.

A linear instability analysis for the inception of double-diffusive convection with a concentration based internal heat source is presented. The system encompasses a layer of fluid which lies above a porous layer saturated with the same fluid. Detailed stability characteristics results are presented for key physical parameters including the solute Rayleigh number, depth ratio of the fluid to porous layer and strength of radiative heating. © 2012 Springer Science+Business Media B.V.

Shortall O.K.,University of Nottingham | Shortall O.K.,Copenhagen University
Energy Policy | Year: 2013

The idea of using less productive or "marginal land" for energy crops is promoted as a way to overcome the previous land use controversies faced by biofuels. It is argued that marginal land use would not compete with food production, is widely available and would incur fewer environmental impacts. This term is notoriously vague however, as are the details of how marginal land use for energy crops would work in practice. This paper explores definitions of the term "marginal land" in academic, consultancy, NGO, government and industry documents in the UK. It identifies three separate definitions of the term: land unsuitable for food production; ambiguous lower quality land; and economically marginal land. It probes these definitions further by exploring the technical, normative and political assumptions embedded within them. It finds that the first two definitions are normatively motivated: this land should be used to overcome controversies and the latter definition is predictive: this land is likely to be used. It is important that the different advantages, disadvantages and implications of the definitions are spelled out so definitions are not conflated to create unrealistic expectations about the role of marginal land in overcoming biofuels land use controversies. © 2013 Elsevier Ltd.

Iglesias M.A.,University of Nottingham
Computational Geosciences | Year: 2015

We propose the application of iterative regularization for the development of ensemble methods for solving Bayesian inverse problems. In concrete, we construct (i) a variational iterative regularizing ensemble Levenberg-Marquardt method (IR-enLM) and (ii) a derivative-free iterative ensemble Kalman smoother (IR-ES). The aim of these methods is to provide a robust ensemble approximation of the Bayesian posterior. The proposed methods are based on fundamental ideas from iterative regularization methods that have been widely used for the solution of deterministic inverse problems (Katltenbacher et al. de Gruyter, Berlin 2008). In this work, we are interested in the application of the proposed ensemble methods for the solution of Bayesian inverse problems that arise in reservoir modeling applications. The proposed ensemble methods use key aspects of the regularizing Levenberg-Marquardt scheme developed by Hanke (Inverse Problems 13,79–95 1997) and that we recently applied for history matching in Iglesias (Comput. Geosci. 1–21 2013). Unlike most existing methods where the stopping criteria and regularization parameters are typically selected heuristically, in the proposed ensemble methods, the discrepancy principle is applied for (i) the selection of the regularization parameters and (ii) the early termination of the scheme. The discrepancy principle is key for the theory of iterative regularization, and the purpose of the present work is to apply this principle for the development of ensemble methods defined as iterative updates of solutions to linear ill-posed inverse problems. The regularizing and convergence properties of iterative regularization methods for deterministic inverse problems have long been established. However, the approximation properties of the proposed ensemble methods in the context of Bayesian inverse problems is an open problem. In the case where the forward operator is linear and the prior is Gaussian, we show that the tunable parameters of the proposed IR-enLM and IR-ES can be chosen so that the resulting schemes coincide with the standard randomized maximum likelihood (RML) and the ensemble smoother (ES), respectively. Therefore, the proposed methods sample from the posterior in the linear-Gaussian case. Similar to RML and ES methods, in the nonlinear case, one may not conclude that the proposed methods produce samples from the posterior. The present work provides a numerical investigation of the performance of the proposed ensemble methods at capturing the posterior. In particular, we aim at understanding the role of the tunable parameters that arise from the application of iterative regularization techniques. The numerical framework for our investigations consists of using a state-of-the art Markov chain Monte Carlo (MCMC) method for resolving the Bayesian posterior from synthetic experiments. The resolved posterior via MCMC then provides a gold standard against to which compare the proposed IR-enLM and IR-ES. Our numerical experiments show clear indication that the regularizing properties of the regularization methods applied for the computation of each ensemble have significant impact of the approximation properties of the proposed ensemble methods at capturing the Bayesian posterior. Furthermore, we provide a comparison of the proposed regularizing methods with respect to some unregularized methods that have been typically used in the literature. Our numerical experiments showcase the advantage of using iterative regularization for obtaining more robust and stable approximation of the posterior than unregularized methods. © 2014, Springer International Publishing Switzerland.

Altomonte S.,University of Nottingham | Schiavon S.,University of California at Berkeley
Building and Environment | Year: 2013

Occupant satisfaction with indoor environmental quality (IEQ) in office buildings has been positively correlated to self-estimated job performance and, potentially, to overall company productivity. LEED is a voluntary, consensus-based, market-driven program that provides third-party certification of green buildings, contributing to promote sustainability into the mainstream of building design and construction. From the literature, however, it is unclear the extent to which LEED certification also improves occupant satisfaction with IEQ. The aim of this paper is to study if LEED certified buildings lead to a higher, equal or lower satisfaction with indoor environmental quality than non-LEED rated buildings. Occupant satisfaction has been evaluated on a subset of the Center for the Built Environment Occupant Indoor Environmental Quality Survey database featuring 144 buildings (65 LEED certified) and 21,477 individual occupant responses (10,129 in LEED buildings). Differently from previous studies of the CBE database, the results show that occupants of LEED certified buildings have equal satisfaction with the building overall and with the workspace than occupants of non-LEED rated buildings. The difference in mean satisfaction scores between LEED and non-LEED buildings for other 15 IEQ parameters investigated is always lower than 6% with a negligible effect size. Therefore, it can be concluded that there is not a significant influence of LEED certification on occupant satisfaction with indoor environmental quality, although the analysis of mean votes of satisfaction reveals that occupants of LEED buildings tend to be slightly more satisfied with air quality, and slightly more dissatisfied with amount of light. © 2013 Elsevier Ltd.

Bilous R.,Newcastle University | Donnelly R.,University of Nottingham
Handbook of Diabetes | Year: 2010

Over three editions the Handbook of Diabetes has built a reputation as an essential practical manual on the assessment and management of patients with diabetes. Previously written by Gareth Williams and John Pickup, the book has been completely revised by Rudy Bilous and Richard Donnelly to reflect recent changes in diabetes treatment and care. It contains information on the new IFCC units for measuring blood glucose and the latest drugs being used to combat diabetes, as well as alternative methods of insulin delivery. The book has been fully updated and redesigned to make it even more user-friendly, and contains case histories, practice points, and landmark clinical trials highlighted in color in each chapter where appropriate. It also features an entirely new set of clinical photographs, and all 250 images from the book can be downloaded from the companion CD for use in presentations. The Handbook of Diabetes is the ideal practical handbook for all health professionals with an interest in diabetes care. © 2010 Rudy Bilous and Richard Donnelly.

Huston I.,Queen Mary, University of London | Christopherson A.J.,University of Nottingham
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

Isocurvature perturbations naturally occur in models of inflation consisting of more than one scalar field. In this paper, we calculate the spectrum of isocurvature perturbations generated at the end of inflation for three different inflationary models consisting of two canonical scalar fields. The amount of nonadiabatic pressure present at the end of inflation can have observational consequences through the generation of vorticity and subsequently the sourcing of B-mode polarization. We compare two different definitions of isocurvature perturbations and show how these quantities evolve in different ways during inflation. Our results are calculated using the open source Pyflation numerical package which is available to download. © 2012 American Physical Society.

Forsyth I.,University of Nottingham
Environment and Planning A | Year: 2013

During the mid-20th century there was new utility in combining scientific, artistic, and military knowledge for the development of effective military camouflage. When WWII was declared the military began recruiting seemingly disparate specialists, such as surrealist artists, a zoologist, and a magician to train in concealment: to become camoufleurs. Across diverse environments and battlefields these camoufleurs plied their trade of secrecy, in the process militarising landscapes and their knowledges. This paper will explore how camouflage was developed for different interrelated surfaces during war, whether for the sea in WWI, the earth, or in response to aerial warfare. In particular this paper will explore the surface of sand in the Desert War in WWII, which demanded a new relationship between modern militarism and knowledge of the earth's surface, in order to develop effective camouflage. In turn, it will reveal that camouflage was a defining factor influencing the geographies of the desert as a theatre of war, transforming it into a bewildering topography requiring, as one soldier put it, 'mental guts'.

Spiller R.C.,University of Nottingham
Digestive Diseases | Year: 2011

Irritable bowel syndrome (IBS) is characterised by abdominal pain and an erratic bowel habit, which depending on the definition used affects 5-10% of the population. As a typical complex disease, it is likely that the condition will develop when a genetically susceptible individual is exposed to an appropriate environment stimulus. This bio-psycho-social model assumes that there is no one cause of IBS, but rather that it is the product of complex interactions between host and environment. Host factors include gender, age and psychological characteristics, while environmental factors include psychosocial stressors, gastrointestinal infections, antibiotics and food. Copyright © 2011 S. Karger AG, Basel.

Luca N.R.,University of Nottingham | Suggs L.S.,University of Lugano
Journal of Health Communication | Year: 2013

The existing literature suggests that theories and models can serve as valuable frameworks for the design and evaluation of health interventions. However, evidence on the use of theories and models in social marketing interventions is sparse. The purpose of this systematic review is to identify to what extent papers about social marketing health interventions report using theory, which theories are most commonly used, and how theory was used. A systematic search was conducted for articles that reported social marketing interventions for the prevention or management of cancer, diabetes, heart disease, HIV, STDs, and tobacco use, and behaviors related to reproductive health, physical activity, nutrition, and smoking cessation. Articles were published in English, after 1990, reported an evaluation, and met the 6 social marketing benchmarks criteria (behavior change, consumer research, segmentation and targeting, exchange, competition and marketing mix). Twenty-four articles, describing 17 interventions, met the inclusion criteria. Of these 17 interventions, 8 reported using theory and 7 stated how it was used. The transtheoretical model/stages of change was used more often than other theories. Findings highlight an ongoing lack of use or underreporting of the use of theory in social marketing campaigns and reinforce the call to action for applying and reporting theory to guide and evaluate interventions. © 2013 Taylor & Francis Group, LLC.

Crewe L.,University of Nottingham
Environment and Planning A | Year: 2013

This paper explores the impact of digitally mediated communications technologies on the fashion sector. It argues that material and virtual fashion worlds are perpetually intersecting social realities that coexist relationally, simultaneously, and in mutual connection. The paper explores these shifting fashion landscapes in three particular ways in order to understand how fashion worlds are being transformed, enhanced, and reproduced in space and time. Firstly, it is argued that emergent digital technologies are remediating and refashioning existing cultural forms of signification such as fashion magazines and photography. Secondly, the potential disintermediatory effects that the Internet is having on fashion markets and consumption are explored, questioning to what extent digital technologies are enabling the devolution of fashion authority from traditional power brokers such as magazine editors and designers towards a more diversified assemblage of participants, including fashion bloggers and consumers. Thirdly, the transformative effects that digital technology is having on fashion consumption are explored. The Internet has opened up new spaces of fashion consumption that are unprecedented in their levels of ubiquity, immersion, fluidity, and interactivity. Fashion spaces are increasingly portable, must follow us around, travel with us through time and space. The network effects made possible by the Internet are enabling the creation of always-on, always-connected consumer communities. Increasingly we are adrift without the Internet, not with it. This is generating new ways of being in space where the absence of physical presence becomes second nature. Taken together, the collision between virtual and material fashion spaces requires a fundamental rethink about the role of fashion production, consumption, knowledge, and the laws of markets. © 2013 Louise Crewe.

Bath-Hextall F.J.,University of Nottingham
Cochrane database of systematic reviews (Online) | Year: 2012

Many people with atopic eczema are reluctant to use the most commonly recommended treatments because they fear the long-term health effects. As a result, many turn to dietary supplements as a possible treatment approach, often with the belief that some essential ingredient is 'missing' in their diet. Various supplements have been proposed, but it is unclear whether any of these interventions are effective. To evaluate dietary supplements for treating established atopic eczema/dermatitis.Evening primrose oil, borage oil, and probiotics are covered in other Cochrane reviews. We searched the following databases up to July 2010: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), PsycINFO (from 1806), AMED (from 1985), LILACS (from 1982), ISI Web of Science, GREAT (Global Resource of EczemA Trials) database, and reference lists of articles. We searched ongoing trials registers up to April 2011. Randomised controlled trials (RCTs) of dietary supplements for the treatment of those with established atopic eczema/dermatitis. Two authors independently screened the titles and abstracts, read the full text of the publications, extracted data, and assessed the risk of bias. We included 11 studies with a total of 596 participants. Two studies assessed fish oil versus olive oil or corn oil placebo. The following were all looked at in single studies: oral zinc sulphate compared to placebo, selenium versus selenium plus vitamin E versus placebo, vitamin D versus placebo, vitamin D versus vitamin E versus vitamins D plus vitamin E together versus placebo, pyridoxine versus placebo, sea buckthorn seed oil versus sea buckthorn pulp oil versus placebo, hempseed oil versus placebo, sunflower oil (linoleic acid) versus fish oil versus placebo, and DHA versus control (saturated fatty acids of the same energy value). Two small studies on fish oil suggest a possible modest benefit, but many outcomes were explored. A convincingly positive result from a much larger study with a publicly-registered protocol is needed before clinical practice can be influenced. There is no convincing evidence of the benefit of dietary supplements in eczema, and they cannot be recommended for the public or for clinical practice at present. Whilst some may argue that at least supplements do not do any harm, high doses of vitamin D may give rise to serious medical problems, and the cost of long-term supplements may also mount up.

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

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

Corcoran R.,University of Nottingham
Psychological Medicine | Year: 2010

Delusional beliefs are characteristic of psychosis and, of the delusions, the paranoid delusion is the single most common type associated with psychosis. The many years of research focused on neurocognition in schizophrenia, using standardized neurocognitive tests, have failed to find conclusive cognitive deficits in relation to positive symptoms. However, UK-based psychological research has identified sociocognitive anomalies in relation to paranoid thinking in the form of theory of mind (ToM), causal reasoning and threat-related processing anomalies. Drawing from recent neuroscientific research on the default mode network, this paper asserts that the common theme running through the psychological tests that are sensitive to the cognitive impairment of paranoia is the need to cognitively project the self through time, referred to as mental time travel. Such an understanding of the cognitive roots of paranoid ideation provides a synthesis between psychological and biological accounts of psychosis while also retaining the powerful argument that understanding abnormal thinking must start with models of normal cognition. This is the core theme running through the cognitive psychological literature of psychiatric disorders that enables research from this area to inform psychological therapy. © Cambridge University Press 2010.

Dolan G.,University of Nottingham
Haemophilia | Year: 2010

Life expectancy for haemophilia has increased significantly in many countries. This represents a major success of the improved safety of therapeutic materials to treat haemophilia and of improved quality of care. This improved longevity will generate a population of older individuals with haemophilia with complex medical problems associated with age and managing such clinical issues is likely to be challenging. © 2010 The Author. Journal compilation © 2010 Blackwell Publishing Ltd.

Garvey S.D.,University of Nottingham
Renewable Energy | Year: 2012

An integrated compressed air renewable energy system is defined here as one which harvests renewable energy directly in the form of compressed air and later converts that to the form of electrical power for transmission. There are two main motivations for considering such systems: firstly the lifetime cost per kW h exported has the potential to be substantially lower than the lifetime cost per kW h of a system generating electricity directly. Secondly these systems offer the intrinsic capability to store large amounts of energy in a very cost effective way. The only marginal costs associated with energy storage are those connected with providing some means for storing the compressed air and some means for managing heat. This paper describes an approach to simulating the performance of such systems including a controller to determine how much power to generate at a given time and it explains an appropriate rationale for the design of that controller. The simulations conducted indicate three remarkable performance measures. Specifically: (a) the marginal loss of energy associated with passing some energy through storage may be below 15% even with energy residency times in the order of months, (b) the marginal increase in total output electrical energy arising from integrating some solar heat capture can be as high as 60% of the captured solar heat for solar heat inputs up to 5% of total mechanical power and (c) the average value of the total power output may easily be raised by over 30% if power values continue to fluctuate at rates exhibited today and if the capacity for expansion-generation matches the peak input power of the primary (mechanical) energy harvesters. © 2011 Elsevier Ltd.

Foody G.M.,University of Nottingham
IEEE Transactions on Geoscience and Remote Sensing | Year: 2012

Accuracy assessment should be a fundamental component of an image classification analysis and is typically undertaken following either a non-site- or a site-specific methodology. The assessment of classification accuracy is, however, often difficult, with many challenges associated with the ground data typically required. Using a series of classifications of two test sites, this paper shows that accuracy assessment from both perspectives is possible through the use of a latent class modeling approach in the absence of ground data. This is possible because the parameters of a latent class model that explains the observed associations in class labeling made by a series of classifications provide estimates of class cover and conditional probabilities of class membership that equate to popular non-site- and site-specific (producer's accuracy) measures of accuracy, respectively. Additionally, the latent class model provides a new classification that could be evaluated by traditional means if ground data are available. The classification of each test site derived from the latent class model was accurate, being of equivalent accuracy to a conventional ensemble classification that was based on the same series of classifications for a site. The ability to derive a highly accurate classification and yield estimates of classification accuracy without ground data to form a testing set indicates the considerable promise of the method and a means to reduce demands for costly ground data that may also be a source of error due to imperfections. © 2011 IEEE.

Green A.R.,University of Nottingham | Nutt D.J.,Imperial College London
Journal of Psychopharmacology | Year: 2014

Despite the publication of a substantial body of preclinical and clinical information on recent recreational drugs such as 3,4- methylenedioxymethamphetamine (MDMA, 'ecstasy') and cathinone compounds such as mephedrone there remains a disturbing lack of consensus as to how dangerous these compounds are to the health of the individual and to society in general. This perspective proposes that use of good pharmacological practice should be mandatory in all preclinical and clinical studies. Its use will assist both translation and reverse translation of information produced in animals and clinical subjects. We propose several basic rules to be followed in all future studies. Preclinical studies should employ pharmacokinetic-pharmacodynamic integration thereby exposing animals to known or calculable drug concentrations. This will provide results relevant to pharmacology rather than toxicology and, crucially, data relevant to human drug use. Full experimental detail should be routinely provided, to allow comparison with other similar work. In clinical studies evidence should be provided that the drug under investigation has been ingested by the subjects being examined, and details given of all other drugs being ingested. Drug-drug interactions are an unavoidable confound but studies of a size that allows reliable statistical evaluation and preferably allows sub-group analysis, particularly by using meta-analysis, should help with this problem. This may require greater collaboration between investigative groups, as routinely occurs during pharmaceutical clinical trials. Other proposals include greater integration of preclinical and clinical scientists in both preclinical and clinical studies and changes in the law regarding Good Manufacturing Process (GMP) sourcing of drug for human studies. © The Author(s) 2014.

Knowledge of the absolute risk (AR) for venous thromboembolism (VTE) in women around pregnancy and how potential risk factors modify this risk is crucial in identifying women who would benefit most from thromboprophylaxis. We examined a large primary care database containing 376 154 pregnancies ending in live birth or stillbirth from women aged 15 to 44 years between 1995 and 2009 and assessed the effect of risk factors on the incidence of antepartum and postpartum VTE in terms of ARs and incidence rate ratios (IRR), using Poisson regression. During antepartum, varicose veins, inflammatory bowel disease (IBD), urinary tract infection, and preexisting diabetes were associated with an increased risk for VTE (ARs, ≥139/100 000 person-years; IRRs, ≥1.8/100 000 person-years). Postpartum, the strongest risk factor was stillbirth (AR, 2444/100 000 person-years; IRR, 6.2/100 000 person-years), followed by medical comorbidities (including varicose veins, IBD, or cardiac disease), a body mass index (BMI) of 30 kg/m(2) or higher, obstetric hemorrhage, preterm delivery, and caesarean section (ARs, ≥637/100 000 person-years; IRRs, ≥1.9/100 000 person-years). Our findings suggest that VTE risk varies modestly by recognized factors during antepartum; however, women with stillbirths, preterm births, obstetric hemorrhage, caesarean section delivery, medical comorbidities, or a BMI of 30 kg/m(2) or higher are at much higher risk for VTE after delivery. These risk factors should receive careful consideration when assessing the potential need for thromboprophylaxis during the postpartum period.

Moghaddas Tafreshi S.N.,K. N. Toosi University of Technology | Dawson A.R.,University of Nottingham
Geotextiles and Geomembranes | Year: 2012

The results of laboratory-model tests on strip footings supported on unreinforced and geocell-reinforced sand beds under a combination of static and repeated loads are presented. The influences of various parameters are studied including reinforcement width, height of the geocell below the footing base and various amplitudes of repeated load. Mostly, a stable, resilient response is observed once incrementally accumulated plastic strain has ceased (usually during the first 10 cycles of loading). The reinforcement reduces the magnitude of the final settlement, acts as a settlement retardant, permits higher loads or increased cycling. The reinforcement's efficiency in reducing the maximum footing settlement decreased as the height and width of geocell were increased. Plastic deformation was limited by geocells more under repeated loading than under a similar static loading, with the reduction being greatest when more reinforcement was present and when the loading rate was fastest. It is deduced that the greater resilient stiffness of a rapidly loaded polymeric geocell attracts load to itself thereby protecting the soil from some of the more challenging stress states and, hence, reduces deformation. Simple dimensional analysis showed the need for an increased stiffness of the geosynthetic components in order to deliver full-scale performance similitude. © 2011 Elsevier Ltd.

Abhishek A.,Astrazeneca | Abhishek A.,University of Nottingham
Annals of the rheumatic diseases | Year: 2014

OBJECTIVES: To examine the association between bone mineral density (BMD), soft-tissue calcification, vascular calcification and chondrocalcinosis (CC).METHODS: A case-control study within the Genetics of Osteoarthritis and Lifestyle (GOAL) database (n=3170). All GOAL participants completed a questionnaire self-reporting current and early adult life exposures. Radiographs of knees, hands and pelvis were scored for osteoarthritis (OA), CC, pelvic vascular calcification, peri-articular knee calcification and metacarpal index (MCI-measure of cortical BMD). Calcaneal dual-energy X-ray absorptiometry (DEXA) was performed. Cases had radiographic CC, while controls did not have CC at any radiographed site. OR, 95% CI were used to measure association between risk factors and CC. Logistic regression was used to adjust for confounding and to estimate the adjusted OR (aOR).RESULTS: Low MCI (aOR (95%) for CC in 1st tertile 1.41 (1.06 to 1.89), with 3rd tertile referent), soft-tissue calcification (aOR (95%) for CC 1.81 (1.36 to 2.42)), and vascular calcification (aOR (95%) for CC 1.76 (1.13 to 2.75)) independently associated with CC. There was a negative association between body mass index and CC (aOR (95%) for CC in 2nd and 3rd tertiles 0.68 (0.53 to 0.89), and 0.67 (0.51 to 0.88) respectively with 1st tertile referent). Age and OA associated with CC. However, only age and low MCI independently associated with CC at >1 joint. Self-reported meniscectomy, low cortical BMD, vascular calcification, and soft-tissue calcification independently associated with knee CC.CONCLUSIONS: This study identifies several novel associations of CC including low cortical BMD. The association between vascular calcification, soft-tissue calcification, and CC suggests a generalised constitutional predisposition to calcium crystal formation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Dealing with the threat of anthropogenic climate change has been a challenge for policy makers for a long time. In recent years, the problems posed by climate change and solutions proposed to mitigate its effects have been framed by lexical 'carbon compounds', such as carbon footprint or carbon trading and by one dominant metaphor, the market metaphor. Through a detailed content analysis of industry and press coverage from 1985 to the present, this paper examines the fate of one important lexical compound in this context, namely low carbon, which can be used as an adjective or a noun. Over the last two decades this lexical compound moved across and between three discourses, the steel industry, the car industry and what one might call the climate change industry. Using insights from ecolinguistics and the sociology of expectations, the paper discusses how the lexical compound low carbon in general and the metaphor low carbon future in particular came to prominence in policy discourses, especially in the UK, and how they were used to frame expectations of a prosperous low carbon future, while sidelining deeper social and cultural reflections on climate change mitigation. © 2011 Springer Science+Business Media B.V.

To conserve biodiversity, it is necessary to understand how species are distributed and which aspects of the environment determine distributions. In large parts of the world and for the majority of species, data describing distributions are very scarce. Museums, private collections and the historical literature offer a vast source of information on distributions. Records of the occurrence of species from these sources are increasingly being captured in electronic databases and made available over the internet. These records may be very valuable in conservation efforts. However, there are a number of limitations with museum data. These limitations are dealt with in the first part of this review. Even if the limitations of museum data can be overcome, these data present a far-from-complete picture of the distributions of species. Species distribution models offer a means to extrapolate limited information in order to estimate the distributions of species over large areas. The second part of this paper reviews the challenges of developing species distribution models for use with museum data and describes some of the questions that species distribution models have been used to address. Given the rapidly increasing number of museum records of species occurrence available over the internet, a review of their usefulness in conservation and ecology is timely. © The Author(s) 2010.

Tse Y.K.,University of York | Tan K.H.,University of Nottingham
International Journal of Production Economics | Year: 2012

The Chinese melamine milk recall and a series of product harm scandals ranging from milk powder to chocolate bar indicate that firms and consumers alike are vulnerable to quality risks in a global supply chain. Supply chains are extended by outsourcing and stretched by globalization, which greatly increase the complexity of supply network and decrease the visibility in risk and operation process. It is hard for firms to manage the product quality of such a multi-layer supply chain which has a low traceability of material origin. In this paper, we argue that better visibility of risk in supply chain could minimize the threat of product harm. A supply chain product quality risk management framework, integrating both the incremental calculus and marginal analysis, is proposed. Case study results indicate that the proposed approach has the following benefits: (i) providing evaluation of the product quality risk in supply chain layers; (ii) allowance for firms to have a better 'visibility' of product quality risks in supply chain; and (iii) a traceable justification path for multi-sourcing decision. © 2010 Elsevier B.V. All rights reserved.

Swarup R.,University of Nottingham | Peret B.,CEA Cadarache Center
Frontiers in Plant Science | Year: 2012

Auxin regulates several aspects of plant growth and development. Auxin is unique among plant hormones for exhibiting polar transport. Indole-3-acetic acid (IAA), the major form of auxin in higher plants, is a weak acid and its intercellular movement is facilitated by auxin influx and efflux carriers. Polarity of auxin movement is provided by asymmetric localization of auxin carriers (mainly PIN efflux carriers). PIN-FORMED (PIN) and P-GLYCOPROTEIN (PGP) family of proteins are major auxin efflux carriers whereas AUXIN1/LIKE-AUX1 (AUX/LAX) are major auxin influx carriers. Genetic and biochemical evidence show that each member of the AUX/LAX family is a functional auxin influx carrier and mediate auxin related developmental programmes in different organs and tissues. Of the four AUX/LAX genes, AUX1 regulates root gravitropism, root hair development and leaf phyllotaxy whereas LAX2 regulates vascular development in cotyledons. Both AUX1 and LAX3 have been implicated in lateral root (LR) development as well as apical hook formation whereas both AUX1 and LAX1 and possibly LAX2 are required for leaf phyllotactic patterning. © 2012 Swarupand Péret.

Mowles S.L.,University of Nottingham | Ord T.J.,University of New South Wales
Animal Behaviour | Year: 2012

Courtship displays are important in governing mate choice, ubiquitous throughout the animal kingdom and often spectacular in appearance. As such, they have received a long history of study that has greatly advanced our knowledge of intersexual selection. Yet despite this historical interest, critical gaps remain in our understanding of what aspects of courtship mates find attractive. In particular, the importance of signal repetition during courtship is beginning to become more apparent, but its functional significance in mate choice is still unclear. We outline how models of repeated displays, which have allowed us to make great strides in understanding agonistic contests, can also help us to understand mate choice. In fact, we contend that such models are essential for understanding the existence of repetitious courtship signals and the decision rules used by females when choosing among possible mates. Models of repeated displays offer an important, and currently unutilized, tool for the study of mate choice that we anticipate will provide new insights on intersexual selection. To facilitate this end, we present a practical guide of how researchers can implement a game theory approach in their studies of courtship displays and mate choice. © 2012 The Association for the Study of Animal Behaviour.

Jungwirth T.,ASCR Institute of Physics Prague | Jungwirth T.,University of Nottingham | Wunderlich J.,ASCR Institute of Physics Prague | Wunderlich J.,Hitachi Cambridge Laboratory | And 2 more authors.
Nature Materials | Year: 2012

The spin Hall effect is a relativistic spin-orbit coupling phenomenon that can be used to electrically generate or detect spin currents in non-magnetic systems. Here we review the experimental results that, since the first experimental observation of the spin Hall effect less than 10 years ago, have established the basic physical understanding of the phenomenon, and the role that several of the spin Hall devices have had in the demonstration of spintronic functionalities and physical phenomena. We have attempted to organize the experiments in a chronological order, while simultaneously dividing the Review into sections on semiconductor or metal spin Hall devices, and on optical or electrical spin Hall experiments. The spin Hall device studies are placed in a broader context of the field of spin injection, manipulation, and detection in non-magnetic conductors. © 2012 Macmillan Publishers Limited. All rights reserved.

Swann G.E.A.,University of Nottingham | Patwardhan S.V.,University of Strathclyde
Climate of the Past | Year: 2011

The development of a rapid and non-destructive method to assess purity levels in samples of biogenic silica prior to geochemical/isotope analysis remains a key objective in improving both the quality and use of such data in environmental and palaeoclimatic research. Here a Fourier Transform Infrared Spectroscopy (FTIR) mass-balance method is demonstrated for calculating levels of contamination in cleaned sediment core diatom samples from Lake Baikal, Russia. Following the selection of end-members representative of diatoms and contaminants in the analysed samples, a mass-balance model is generated to simulate the expected FTIR spectra for a given level of contamination. By fitting the sample FTIR spectra to the modelled FTIR spectra and calculating the residual spectra, the optimum best-fit model and level of contamination is obtained. When compared to X-ray Fluorescence (XRF) the FTIR method portrays the main changes in sample contamination through the core sequence, permitting its use in instances where other, destructive, techniques are not appropriate. The ability to analyse samples of <1 mg enables, for the first time, routine analyses of small sized samples. Discrepancies between FTIR and XRF measurements can be attributed to FTIR end-members not fully representing all contaminants and problems in using XRF to detect organic matter external to the diatom frustule. By analysing samples with both FTIR and XRF, these limitations can be eliminated to accurately identify contaminated samples. Future, routine use of these techniques in palaeoenvironmental research will therefore significantly reduce the number of erroneous measurements and so improve the accuracy of biogenic silica/diatom based climate reconstructions. © Author(s) 2011.

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

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

Jewitt S.,University of Nottingham
Applied Geography | Year: 2011

There is huge geographical variation in the extent to which excrement represents a threat to human and environmental health. In the UK, we tend to think little of such risks. By contrast, 52% of all people in Asia have no access to basic sanitation and 95% of sewage in developing world cities is discharged untreated into rivers, lakes and coastal areas where it destroys aquatic life, reduces the potential of these ecosystems to support food security, facilitates the transmission of diseases and has a significant economic impact in terms of working days and earnings lost due to ill health. At the same time human excrement represents a resource that could be better utilized to promote human livelihoods and improve environmental quality through use as manure and as a source of biogas energy. This paper seeks to provide an overview of the importance of human waste (as both a threat and an opportunity) in different spatial, historical and cultural contexts and to highlight potential areas of interest for applied geographical research in future. © 2010 Elsevier Ltd.

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

Ocular surface burns can be caused by chemicals (alkalis and acids) or by direct heat. Amniotic membrane transplantation (AMT) performed in the acute phase (day 0 to day 7) of an ocular surface burn is reported to relieve pain, accelerate healing and reduce scarring and blood vessel formation. The surgery involves applying a patch of amniotic membrane (AM) over the entire ocular surface up to the eyelid margins. To assess the effects of AMT on the eyes of people having suffered acute ocular surface burns. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 6), MEDLINE (January 1946 to June 2012), EMBASE (January 1980 to June 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 June 2012. We included randomised trials of medical therapy and AMT applied in the first seven days after an ocular surface burn compared to medical therapy alone. Two authors independently assessed the risk of bias of included studies and extracted relevant data. We contacted trial investigators for missing information. We summarised data using risk ratios (RRs) and mean differences (MDs) as appropriate. We included one RCT of 100 participants with ocular burns that were randomised to treatment with AMT and medical therapy or medical therapy alone. A subset of patients (n = 68) who were treated within the first seven days of the injury met the inclusion criteria and were included in the analysis. The remaining 32 eyes were excluded. The included subset consisted of 36 moderate (Dua classification II-III) and 32 severe (Dua classification IV-VI) ocular burns from alkali, acid and thermal injuries. In the moderate category, 13/20 control eyes and 14/16 treatment eyes had complete epithelialisation by 21 days. The RR of failure of epithelialisation by day 21 was 0.18 in the treatment group (95% confidence interval (CI) 0.02 to 1.31; P = 0.09). Mean LogMAR final visual acuities were 0.06 (standard deviation (SD) 0.10) in the treatment group and 0.38 (SD 0.52) in the control group, representing a MD of -0.32 (95% CI -0.05 to -0.59). In the severe category, 1/17 treatment and 1/15 control eyes were epithelialised by day 21. The RR of failure of epithelialisation in the treatment group was 1.01 (95% CI 0.84 to 1.21; P = 0.93). Final visual acuity was 1.77 (SD 1.31) in the treated eyes and 1.64 (SD 1.48) in the control group (MD 0.13; 95% CI -0.88 to 1.14). The risks of performance and detection biases were high, because treating personnel and outcome assessors could not be masked to treatment. There was also a high risk of bias in the visual outcomes of the moderate category, since mean visual acuity was significantly worse at presentation in the control eyes. This reduced confidence in the study findings. Conclusive evidence supporting the treatment of acute ocular surface burns with AMT is lacking. Heterogeneity of disease presentation, variations in treatment, undefined criteria for treatment success and failure, and non-uniform outcome measures are some of the factors complicating the search for clear evidence regarding this treatment.

Moss A.,University of Nottingham | Pogosian L.,Simon Fraser University
Physical Review Letters | Year: 2014

Scaling networks of cosmic defects, such as strings and textures, actively generate scalar, vector, and tensor metric perturbations throughout the history of the Universe. In particular, vector modes sourced by defects are an efficient source of the cosmic microwave background B-mode polarization. We use the recently released BICEP2 and POLARBEAR B-mode polarization spectra to constrain properties of a wide range of different types of cosmic strings networks. We find that in order for strings to provide a satisfactory fit on their own, the effective interstring distance needs to be extremely large - spectra that fit the data best are more representative of global strings and textures. When a local string contribution is considered together with the inflationary B-mode spectrum, the fit is improved. We discuss implications of these results for theories that predict cosmic defects. © 2014 American Physical Society.

das Nair R.,University of Nottingham
Cochrane database of systematic reviews (Online) | Year: 2012

Impairments in cognitive function, particularly memory, are common in patients with Multiple Sclerosis (MS) and these can potentially affect their ability to complete functional activities. There is evidence from single-case or small group studies that memory rehabilitation can be beneficial for patients with MS but findings from randomised controlled trials (RCTs) and systematic reviews have been inconclusive. To determine the effectiveness of memory rehabilitation for patients with MS who have memory problems, and the effect of such interventions on functional abilities. We searched the Cochrane Multiple Sclerosis Group's Specialised Trials Register (last searched February 2011), and the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, latest issue), NIHR Clinical Research Network database, MEDLINE (1966 to February 2011), EMBASE (1980 to February 2011), CINAHL (1982 to April 2010), PsycINFO (1980 to February 2011), AMED (1985 to April 2010), British Nursing Index (1985 to April 2010) and CAB Abstracts (1973 to April 2010). We handsearched relevant journals and reference lists. We selected RCTs of memory rehabilitation or cognitive rehabilitation for patients with MS in which a memory rehabilitation treatment group was compared to a control group. Selection was conducted independently first and confirmed through group discussion. Studies that included participants whose memory deficits were the result of conditions other than MS were excluded unless a subgroup of participants with MS with separate results could be identified. Four reviewers were involved in study selection, quality assessment and data extraction. Investigators of primary studies were contacted for further information where required. Data analysis and synthesis were conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. A 'best evidence' synthesis was performed based on the methodological quality of the primary studies included. Eight studies, involving 521 participants, were included. The interventions involved various memory retraining techniques, such as computerised programmes and training on internal and external memory aids. Control groups varied in format from assessment-only groups, discussion and games, non-specific cognitive retraining and attention or visuospatial training. The risk of bias of the included studies was generally low; three of the studies were evaluated to have high risk of bias related to certain aspects of their methodology. Meta-analysis showed no significant effects of memory rehabilitation on memory function or functional abilities immediately or long-term. No significant effect of intervention was found, either immediately or long-term, on subjective reports of memory problems [Standard mean difference (SMD)  0.06 (95% confidence interval [CI] -0.21 to 0.34) and SMD 0.04 (95% CI -0.24 to 0.31)] respectively; on objective memory [SMD 0.24 (95% CI -0.02 to 0.49) and SMD 0.19 (95% CI -0.09 to 0.47)]; on mood [SMD -0.04 (95% CI -0.26 to 0.17) and SMD 0.13 (95% CI -0.10 to 0.36)]; and on Quality of Life [SMD -0.13 (95% CI -0.12 to 0.39) and SMD -0.11 (95% CI -0.39 to 0.17)]. On Activities of Daily Living, no immediate treatment effect was observed [SMD -0.13 (95% CI -0.60 to 0.33)], but on long-term follow up the intervention group performed significantly worse than the control group [SMD -0.33 (95% CI -0.63 to -0.03)]. There is no evidence to support the effectiveness of memory rehabilitation on memory function or functional abilities in patients with MS. However, this conclusion has been arrived because of the limited quality of some of the primary studies reviewed in this area. Further robust, RCTs of higher methodological quality and better quality of reporting are needed.

Chandler D.,University of California at Berkeley | Garrahan J.P.,University of Nottingham
Annual Review of Physical Chemistry | Year: 2010

We review a theoretical perspective of the dynamics of glass-forming liquids and the glass transition, a perspective developed during this past decade based on the structure of trajectory space. This structure emerges from spatial correlations of dynamics that appear in disordered systems as they approach nonergodic or jammed states. It is characterized in terms of dynamical heterogeneity, facilitation, and excitation lines. These features are associated with a newly discovered class of nonequilibrium phase transitions. Equilibrium properties have little, if anything, to do with it. The broken symmetries of these transitions are obscure or absent in spatial structures, but they are vivid in space-time (i.e., trajectory space). In our view, the glass transition is an example of this class of transitions. The basic ideas and principles we review were originally developed through the analysis of idealized and abstract models. Nevertheless, the central ideas are easily illustrated with reference to molecular dynamics of more realistic atomistic models, and we use that illustrative approach here. Copyright © 2010 by Annual Reviews. All rights reserved.

Brown S.F.,University of Nottingham
Geotechnique | Year: 2013

Information and records presented in previous papers describing the creation and early life of Geotechnique have been augmented by documents recently discovered in archives created by the late Hugh Golder, one of the journal's founding fathers. Correspondence with members of the European geotechnical community and with Karl Terzaghi in the 1940s and 1950s presents some new insights into the birth of Géotechnique and the characters involved notably Hugh Golder himself This paper summarises the principal information, and reproduces some of the interesting documents in the archive. It is presented within the context of earlier papers on the subject by the founding fathers of Géotechnique and by the author.

Qiu G.,University of Nottingham
Renewable Energy | Year: 2013

The present study aims to investigate flue gas emissions, particularly pollutants CO, NO x and particle emissions, of a domestic biomass boiler under various operating conditions. The experimental methodologies are systematically introduced. If the primary and secondary air supply for the biomass furnace are provided by the factory-set openings and vent tubes, the flue gas emissions measured are NO x 54.92 ppmv, CO 2 11.98 vol%, CO 0.24 vol%, O 2 8.19 vol% and PM 0.1-10 concentrations 72.7 mg/Nm 3 by burning wood pellets. In addition, the three kinds of cleaning technologies reducing particle emissions are also introduced. © 2012 Elsevier Ltd.

Kazerani T.,University of Nottingham
International Journal of Rock Mechanics and Mining Sciences | Year: 2013

A discrete element model is proposed to examine rock strength and failure. The model is implemented into UDEC to incorporate a new constitutive law for particle boundary behaviour. This purpose is achieved through establishing a user-defined model by creating a dynamic link library (DLL) and attaching it to the code. Rock material is represented as a collection of irregular-sized deformable particles interacting at their cohesive boundaries. The interface between two adjacent particles is viewed as a flexible contact whose constitutive law controls the material fracture and fragmentation properties. To reproduce different behaviours of rock in compression and tension, an orthotropic cohesive law is developed for contact, which allows the interfacial shear and tensile behaviours to be different from each other. The model is applied to a crystallised igneous and a soft sedimentary rock, and the individual and interactional effects of the microstructure parameters on the rocks compressive and tensile failure response are examined quantitatively and qualitatively. Statistical analysis and analytical solutions are employed to establish a methodical calibration process. It is shown that micro-shear mechanisms control rocks failure in a variety of rock types and loadings except for crystallised rocks under uniaxial compression where failure is mainly dominated by micro-tensile fractures. A practical way using the standard laboratory data is also presented to identify the controlling micro-scale failure mechanism. © 2013 Elsevier Ltd.

Foody G.M.,University of Nottingham
Remote Sensing of Environment | Year: 2010

The ground data used as a reference in the validation of land cover change products are often not an ideal gold standard but degraded by error. The effects of ground reference data error on the accuracy of land cover change detection and the accuracy of estimates of the extent of change were evaluated. Twelve data sets were simulated to allow the exploration of the impacts of a spectrum of ground data imperfections on the estimation of the producer's and user's accuracy of change as well as of change extent. Simulated data were used since this ensured that the actual properties of the data were known and to exclude effects due to other sources of ground reference data error; although the impacts of simulated reference data error on two real confusion matrices are also illustrated. The imperfections evaluated ranged from the inclusion of small amounts of known error into the ground reference data through to the extreme situation in which ground data were absent. The results show that even small amounts of error in the ground reference data can introduce large error into studies of land cover change by remote sensing and reinforce the desire to avoid the expression ground truth as this might imply that the data are a gold standard reference. The effect of reference data imperfections was dependent on the degree of association between the errors in the cross-tabulated data sets. For example, in the scenarios investigated, a 10% error in the reference data set introduced an underestimation of the producer's accuracy of 18.5% if the errors were independent but an over-estimation of the producer's accuracy of 12.3% if the errors were correlated. The magnitude of the mis-estimation of the producer's accuracy was also a function of the amount of change and greatest at low levels of change. The amount of land cover change estimated also varied greatly as a function of ground reference data error. Some possible methods to reduce or even remove the impacts of ground reference data error were illustrated. These ranged from simple algebraic means to estimate the actual values of accuracy and change extent if the imperfections were known through to a latent class analysis that allowed the assessment of classification accuracy and estimation of change extent without the use of ground reference data if the underlying model is defined appropriately. © 2010 Elsevier Inc.

Weiner K.,University of Nottingham
Social Science and Medicine | Year: 2010

This paper explores how users of foods containing phytosterols are 'configured' within biomedical research and writing on these substances. A growing range of such foods have been launched and marketed on the basis that they actively lower cholesterol. They are among the most prominent examples of a set of foods designated as 'functional foods'. The paper is based on an analysis of biomedical journal articles which address the use of phytosterols as a cholesterol lowering agent in humans. These include both original research papers and commentaries such as review articles, letters, editorials, news items and professional guidelines. My analysis suggests that users are constituted variously as autonomous, self-motivated consumers, patients and publics needing advice, people resistant to pill use, and practitioners looking for something to offer their patients. I characterise the imagined uses of the products as healthy/holistic, lazy/busy/contemporary, and incompetent use. These varying portrayals of users and their use of these food products entail different ways of understanding health identities and different allocations of responsibilities between the technology, user and health care professionals. I conclude that, while experts and regulators may attempt to configure 'correct' uses of these products, relatively little is known about the rationales and practices of actual users. © 2010 Elsevier Ltd.

The impact of neuraminidase inhibitor (NAI) treatment on clinical outcomes of public health importance during the 2009-2010 pandemic has not been firmly established. We conducted a systematic review and meta-analysis, searching 11 databases (2009 through April 2012) for relevant studies. We used standard methods conforming to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random effects models. Regarding mortality we observed a nonsignificant reduction associated with NAI treatment (at any time) versus none (OR, 0.72 [95% CI, .51-1.01]). However we observed significant reductions for early treatment (≤48 hours after symptom onset) versus late (OR, 0.38 [95% CI, .27-.53]) and for early treatment versus none (OR, 0.35 [95% CI, .18-.71]). NAI treatment (at any time) versus none was associated with an elevated risk of severe outcome (OR, 1.76 [95% CI, 1.22-2.54]), but early versus late treatment reduced the likelihood (OR, 0.41 [95% CI, .30-.56]). During the 2009-2010 influenza A(H1N1) pandemic, early initiation of NAI treatment reduced the likelihood of severe outcomes compared with late or no treatment. PROSPERO REGISTRATION: CRD42011001273.

Reid K.L.,University of Nottingham
Molecular Physics | Year: 2012

The last decade has seen photoelectron angular distributions from isolated molecules used for an increasing variety of purposes, including examining details of electron correlation, demonstrating electron diffraction as a structural probe of single molecules, and probing photochemical processes. In this article these developments are reviewed and it is shown that the stage is set for another decade of innovation in which we can expect to see exciting results from pump-probe experiments using the emerging XUV and X-ray free-electron laser sources. © 2012 Copyright Taylor and Francis Group, LLC.

Marshall A.M.,University of Nottingham
Journal of Geotechnical and Geoenvironmental Engineering | Year: 2012

Evaluation of the impact of tunnel construction on existing buried structures is an important problem. This paper presents an analytical method for estimating the effect of tunnel construction on end-bearing piles located above the tunnel. The method can be used to estimate the safe relative distance between existing piles and newly constructed tunnels. Spherical and cylindrical cavity expansion/contraction analyses are used to evaluate pile end-bearing capacity and the reduction of confining pressure at the pile tip that results from tunnel volume loss. Pile end-bearing capacity is then reevaluated based on the reduced confining pressure at the pile tip.Amodified shear modulus is used to account for the effect of pile installation on soil stiffness. The method is used to analyze centrifuge experiments conducted to study this problem. For the experimental data, where the service load applied to the piles during tunnel volume loss ranged between 50 and 60% of the maximum jacking force, the analytical method showed that pile failure occurred when the load-carrying capacity was reduced below 80% of its original value. A parametric analysis is included that highlights the effect of key soil properties on results. © 2012 American Society of Civil Engineers.

Colnaghi R.,University of Sussex | Wheatley S.P.,University of Nottingham
Journal of Biological Chemistry | Year: 2010

Survivin and Plk1 kinase are important mediators of cell survival that are required for chromosome alignment, cytokinesis, and protection from apoptosis. Interference with either survivin or Plk1 activity manifests many similar outcomes: prometaphase delay/arrest, multinucleation, and increased apoptosis. Moreover, the expression of both survivin and Plk1 is deregulated in cancer. Given these similarities, we speculated that these two proteins may cooperate during mitosis and/or in cell death pathways. Here we report that survivin and Plk1 interact during mitosis and that Plk1 phosphorylates survivin at serine 20. Importantly, we find that overexpression of a non-phosphorylatable version, S20A, is unable to correct chromosomes connected to the spindle in a syntelic manner during prometaphase and allows cells harboring these maloriented chromosomes to enter anaphase, evading the spindle tension checkpoint. By contrast, the constitutive phosphomimic, S20D, completes congression and division ahead of schedule and, unlike S20A, is able to support proliferation in the absence of the endogenous protein. Despite the importance of this residue in mitosis, its mutation does not appear to affect the anti-apoptotic activity of survivin in response to TRAIL. Together, these data suggest that phosphorylation of survivin at Ser20 by Plk1 kinase is essential for accurate chromosome alignment and cell proliferation but is dispensable for its anti-apoptotic activity in cancer cells. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

Williams H.C.,University of Nottingham | Dellavalle R.P.,University of Colorado at Denver | Garner S.,Center for the Evaluation of Value and Risk in Health
The Lancet | Year: 2012

Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinisation, inflammation, and bacterial colonisation of hair follicles on the face, neck, chest, and back by Propionibacterium acnes. Although early colonisation with P acnes and family history might have important roles in the disease, exactly what triggers acne and how treatment affects the course of the disease remain unclear. Other factors such as diet have been implicated, but not proven. Facial scarring due to acne affects up to 20 of teenagers. Acne can persist into adulthood, with detrimental effects on self-esteem. There is no ideal treatment for acne, although a suitable regimen for reducing lesions can be found for most patients. Good quality evidence on comparative effectiveness of common topical and systemic acne therapies is scarce. Topical therapies including benzoyl peroxide, retinoids, and antibiotics when used in combination usually improve control of mild to moderate acne. Treatment with combined oral contraceptives can help women with acne. Patients with more severe inflammatory acne usually need oral antibiotics combined with topical benzoyl peroxide to decrease antibiotic-resistant organisms. Oral isotretinoin is the most effective therapy and is used early in severe disease, although its use is limited by teratogenicity and other side-effects. Availability, adverse effects, and cost, limit the use of photodynamic therapy. New research is needed into the therapeutic comparative effectiveness and safety of the many products available, and to better understand the natural history, subtypes, and triggers of acne. © 2012 Elsevier Ltd.

Delahay R.M.,University of Nottingham | Rugge M.,University of Padua
Helicobacter | Year: 2012

Although Helicobacter pylori infection is highly prevalent in the global human population, the majority of infected individuals remain asymptomatic. A complex combination of host, environmental, and bacterial factors are considered to determine susceptibility and severity of outcome in the subset of individuals that develop clinical disease. These factors collectively determine the ability of H. pylori to colonize the gastric mucosa and profoundly influence the nature of the interaction that ensues. Many studies over the last year provide new insight into H. pylori virulence strategies and the activities of critical bacterial determinants that modulate the host environment. These latter include the secreted proteins CagA and VacA and adhesins BabA and OipA, which directly interact with host tissues. Observations from several studies extend the functional repertoire of CagA and the cag type IV secretion system in particular, providing further mechanistic understanding of how these important determinants engage and activate host signalling pathways important in the development of disease. © 2012 Blackwell Publishing Ltd.

Motta S.C.,University of Nottingham
Antipode | Year: 2013

In this article I reflect on introducing critical pedagogy into social justice teaching in an elite UK university as part of the Nottingham Critical Pedagogy Project. I de-essentialise Freire's conceptualisation of the human subject and her desire for transcendence with the introduction of Deleuze and Guattari's politics of desire. This enables an adaption of critical pedagogy from its original context of popular politics to the individualised elite setting of our project. Our pedagogical objectives become the opening of spaces of possibility which decentre the dominant regime of truth of the neoliberal university and enable imagining and becoming "other". This involves disrupting normal patterns of classroom performativity in terms of student as consumer and lecturer as producer of commodities, transgressing dualisms between mind/body, intellectual/emotional and teacher/student. Our pedagogical praxis is therefore inherently political as by radically disturbing commodified subjectivities we foster processes that lead to unanticipated, maybe even unspeakable, transgressions. © 2012 The Author. Antipode © 2012 Antipode Foundation Ltd.

Roy T.,BRAC Health Programme | Lloyd C.E.,Open University Milton Keynes | Lloyd C.E.,University of Nottingham
Journal of Affective Disorders | Year: 2012

Background: Research suggests that co-morbid diabetes and depression is common; however, the implications for clinical practice remain unclear. This paper reviews the current epidemiological evidence on comorbid diabetes and depression, in order to identify the key publications which could both inform practice and identify gaps in knowledge and research. Methods: A systematic review was conducted to identify published literature on the epidemiology of diabetes and depression. In order to review evidence on up-to-date knowledge of recent research and innovations in care literature searches for the last five years (August 2006-August 2011) were conducted. To identify relevant literature, electronic databases MEDLINE, Psych-INFO and EMBASE were searched for English language articles in peer-reviewed journals. Results: High rates of co-morbidity of depression and diabetes have been reported. The prevalence rate of depression is more than three-times higher in people with type 1 diabetes (12, range 5.8-43.3 vs. 3.2, range 2.7-11.4) and nearly twice as high in people with type 2 diabetes (19.1, range 6.5-33 vs. 10.7, range 3.8-19.4) compared to those without. Women with diabetes and also women without diabetes experience a higher prevalence of depression than men. Reviewed studies provide support for a modest relationship between diabetes and depressive symptoms, but the exact direction of this relationship remains unclear. Limitations: Most studies reviewed were cross-sectional and this limits any conclusions about the causal nature and direction of the relationship between diabetes and depression. Variation in measurement methods, lack of longitudinal data and few studies outside Europe and America limit the generalizability of the findings of this review. Conclusions: Current research suggests that the risk of developing depression is increased in people with diabetes; however, further studies are required in order to establish the nature of the relationship between depression, glycaemic control and the development of diabetes complications, and make appropriate recommendations for treatment and to support self-management of diabetes. © 2012 Elsevier B.V.

Tischler V.,University of Nottingham
BMC medical education | Year: 2014

BACKGROUND: Peer teaching is now used in medical education with its value increasingly being recognised. It is not yet established whether students differ in their satisfaction with teaching by peer-teachers compared to those taught by academic or clinical staff. This study aimed to establish satisfaction with communication skills teaching between these three teaching groups.METHODS: Students participated in a role-play practical facilitated either by clinicians, peer-teachers or non-clinical staff. A questionnaire was administered to first-year medical students after participating in a communication skills role-play session asking students to evaluate their satisfaction with the session. Data were analysed in SPSS 20.RESULTS: One hundred and ninety eight students out of 239 (83%) responded. Students were highly satisfied with the teaching session with no difference in satisfaction scores found between those sessions taught by peers, clinical and non-clinical staff members. 158 (80%) considered the session useful and 139 (69%) strongly agreed tutors facilitated their development. There was no significant difference in satisfaction scores based on tutor background.CONCLUSIONS: Satisfaction is as high when tutored by peer-teachers compared to clinicians or non-clinical staff. Constructive feedback is welcomed from a range of personnel. Final-year students could play an increasing role in the teaching of pre-clinical medical students.

Thomas A.G.,University of Manchester | Syres K.L.,University of Nottingham
Chemical Society Reviews | Year: 2012

The interaction of organic molecules with titanium dioxide surfaces has been the subject of many studies over the last few decades. Numerous surface science techniques have been utilised to understand the often complex nature of these systems. The reasons for studying these systems are hugely diverse given that titanium dioxide has many technological and medical applications. Although surface science experiments investigating the adsorption of organic molecules on titanium dioxide surfaces is not a new area of research, the field continues to change and evolve as new potential applications are discovered and new techniques to study the systems are developed. This tutorial review aims to update previous reviews on the subject. It describes experimental and theoretical work on the adsorption of carboxylic acids, dye molecules, amino acids, alcohols, catechols and nitrogen containing compounds on single crystal TiO 2 surfaces. © 2012 The Royal Society of Chemistry.

Duggan C.,University of Nottingham
British Journal of Psychiatry | Year: 2011

The Dangerous and Severe Personality Disorder (DSPD) initiative was introduced a decade ago against overwhelming opposition from psychiatrists and others concerned with the implications of extending the public protection agenda through the use of a questionable medical 'diagnosis'. As this initiative is now being scaled down, it offers an opportunity to consider the positive and negative aspects of the initiative together with its longer-term legacy. © 2011 The Royal College of Psychiatrists.

Weisel O.,University of Nottingham | Shalvi S.,Ben - Gurion University of the Negev | Shalvi S.,University of Amsterdam
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Cooperation is essential for completing tasks that individuals cannot accomplish alone. Whereas the benefits of cooperation are clear, little is known about its possible negative aspects. Introducing a novel sequential dyadic die-rolling paradigm, we show that collaborative settings provide fertile ground for the emergence of corruption. In the main experimental treatment the outcomes of the two players are perfectly aligned. Player A privately rolls a die, reports the result to player B, who then privately rolls and reports the result as well. Both players are paid the value of the reports if, and only if, they are identical (e.g., if both report 6, each earns €6). Because rolls are truly private, players can inflate their profit by misreporting the actual outcomes. Indeed, the proportion of reported doubles was 489% higher than the expected proportion assuming honesty, 48% higher than when individuals rolled and reported alone, and 96% higher than when lies only benefited the other player. Breaking the alignment in payoffs between player A and player B reduced the extent of brazen lying. Despite player Bs central role in determining whether a double was reported, modifying the incentive structure of either player A or player B had nearly identical effects on the frequency of reported doubles. Our results highlight the role of collaboration-particularly on equal terms-in shaping corruption. These findings fit a functional perspective on morality.When facing opposing moral sentiments-to be honest vs. to join forces in collaboration-people often opt for engaging in corrupt collaboration.

Seymour J.,University of Nottingham
Current Opinion in Supportive and Palliative Care | Year: 2012

Purpose of review Mixed methods research designs have been recognized as important in addressing complexity and are recommended particularly in the development and evaluation of complex interventions. This article reports a review of studies in palliative care published between 2010 and March 2012 that combine qualitative and quantitative approaches. Recent findings A synthesis of approaches to mixed methods research taken in 28 examples of published research studies of relevance to palliative and supportive care is provided, using a typology based on a classic categorization put forward in 1992. Summary Mixed-method studies are becoming more frequently employed in palliative care research and resonate with the complexity of the palliative care endeavour. Undertaking mixed methods research requires a sophisticated understanding of the research process and recognition of some of the underlying complexities encountered when working with different traditions and perspectives on issues of: sampling, validity, reliability and rigour, different sources of data and different data collection and analysis techniques. © 2012 Wolters Kluwer Health | Lippincott Williams &Wilkins.

Danielsson N.A.,University of Nottingham
Proceedings of the ACM SIGPLAN International Conference on Functional Programming, ICFP | Year: 2010

A monadic parser combinator library which guarantees termination of parsing, while still allowing many forms of left recursion, is described. The library's interface is similar to those of many other parser combinator libraries, with two important differences: one is that the interface clearly specifies which parts of the constructed parsers may be infinite, and which parts have to be finite, using dependent types and a combination of induction and coinduction; and the other is that the parser type is unusually informative. The library comes with a formal semantics, using which it is proved that the parser combinators are as expressive as possible. The implementation is supported by a machine-checked correctness proof. © 2010 ACM.

Tan J.K.L.,University of Western Ontario | Bhate K.,University of Nottingham
British Journal of Dermatology | Year: 2015

Summary Acne is estimated to affect 9·4% of the global population, making it the eighth most prevalent disease worldwide. Epidemiological studies have demonstrated that acne is most common in postpubescent teens, with boys most frequently affected, particularly with more severe forms of the disease. This paper aims to provide an update on the epidemiology of acne worldwide. Recent general and institutional studies from around the world have shown that the prevalence of acne is broadly consistent globally (with the exception of specific populations, which are discussed). However, this review highlights that there is a wide range of disparate outcome measures being applied in epidemiology studies, and we emphasize the need to develop a widely accepted, credible, standard assessment scale to address this in the future. In addition we discuss special populations, such as those devoid of acne, as well as the impact of potential determinants of acne on disease epidemiology. © 2015 British Association of Dermatologists.

Heffernan M.,University of Nottingham
Transactions of the Institute of British Geographers | Year: 2014

This essay considers the politics and patronage of geography in early-modern France. It examines how the Paris Academy of Sciences, widely acknowledged as the 18th century's pre-eminent scientific society, came to recognise geography as an independent science in 1730, a century before the establishment of the first geographical societies. Although the Academy was centrally concerned with cartography from its inception in 1666, it initially afforded no official status to geography, which was viewed either as a specialised form of historical inquiry or as a minor component within the hegemonic science of astronomy. The rise of Newtonian mathematics and the associated controversy about the shape of the earth challenged the Academy's epistemological foundations and prompted a debate about the educational and political significance of geography as a scientific practice. The death in 1726 of Guillaume Delisle, a prominent Academy astronomer-cartographer and a popular geography tutor to the young Louis XV, led to a spirited campaign to elect Philippe Buache, Delisle's protégé, to a new Academy position as a geographer rather than an astronomer. The campaign emphasised the social and political utility of geography, though the Academy's decision to recognise this new and distinctively modern science was ultimately facilitated by traditional networks of patronage within the French Royal Court. © 2013 The Author. Transactions of the Institute of British Geographers © 2013 Royal Geographical Society (with the Institute of British Geographers).

Lewis N.M.,University of Nottingham
Annals of the Association of American Geographers | Year: 2014

Research in the field of sexuality and space has begun to explore the relationships between gay and queer sexual subjectivities and migration. Much of this research examines the regulation and policing of queer international migrants or identity formation processes among younger queer people migrating within countries. This study, although located partially within the second category, broadens and deepens existing accounts of gay men's migrations within countries by focusing on life circumstances and events beyond an initial coming-out process and considering the migration experiences of gay men at multiple points in the life course. This study uses life course theory to contextualize the migration narratives of 48 self-identified gay men in Ottawa, Ontario, Canada, and Washington, DC. The findings lend credence to recent claims that migration is central in the lives of gay men and other queer people but extends the concept of gay migration to include more than just the disclosure or initial development of a gay identity. They reframe migration as a tool used to negotiate a variety of life circumstances and transitions (e.g., establishing careers, creating meaningful community identities) rendered challenging by variegated landscapes of stigma and inclusion in North America. © 2014 Copyright Taylor & Francis Group, LLC.

Soultanas P.,University of Nottingham
Transcription | Year: 2011

In response to environmental and nutritional stimuli, a whole array of proteins remodel genome architecture, activate or transcribe genes, suppress genes, repair lesions and base-modifications, faithfully replicate and safely separate the parental and daughter genomes during cell division. Negotiating and resolving conflicts of genome trafficking is essential for genome stability. © 2011 Landes Bioscience.

Ebling F.J.P.,University of Nottingham
Frontiers in Neuroendocrinology | Year: 2015

Seasonal cycles of fattening and body weight reflecting changes in both food intake and energy expenditure are a core aspect of the biology of mammals that have evolved in temperate and arctic latitudes. Identifying the neuroendocrine mechanisms that underlie these cycles has provided new insights into the hypothalamic control of appetite and fuel oxidation. Surprisingly, seasonal cycles do not result from changes in the leptin-responsive and homeostatic pathways located in the mediobasal and lateral hypothalamus that regulate meal timing and compensatory responses to starvation or caloric restriction. Rather, they result from changes in tanycyte function, which locally regulates transport and metabolism of thyroid hormone and retinoic acid. These signals are crucial for the initial development of the brain, so it is hypothesized that seasonal neuroendocrine cycles reflect developmental mechanisms in the adult hypothalamus, manifest as changes in neurogenesis and plasticity of connections. © 2014 Elsevier Inc.

Walsh D.J.,University of Nottingham
Sociology of Health and Illness | Year: 2010

The experience of childbirth is one of the most corporeal of the human condition. Against a backdrop of profound change in the milieu of birthing over the past 30 years, especially in the developed world, a number of discourses now compete for the status of the safest, most fulfilling birth experience. Supporters of biomedical and 'natural' approaches make their respective claims to those, with obstetricians broadly aligning their professional interests with the former and midwives with the latter. There is mounting evidence that childbearing women's experiences of birth are often shaped in the uneasy space between the two. Within sociological discourse in health, embodiment is a dominant theme but, to date, research has concentrated mainly on new reproductive technologies, and there is a dearth of recent research and theorising around the act of parturition itself. This paper argues that because of this, there has been a polarising tendency in current discourses which is having a largely negative impact on women, professionals and the maternity services. A call is made for an integration of traditional childbirth embodiment theories, mediated through compassionate, relationally focused maternity care, especially when labour complications develop. © 2009 The Author. Journal compilation © 2009 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd.

Foody G.M.,University of Nottingham
Global Ecology and Biogeography | Year: 2011

Aim To explore the impacts of imperfect reference data on the accuracy of species distribution model predictions. The main focus is on impacts of the quality of reference data (labelling accuracy) and, to a lesser degree, data quantity (sample size) on species presence-absence modelling. Innovation The paper challenges the common assumption that some popular measures of model accuracy and model predictions are prevalence independent. It highlights how imperfect reference data may impact on a study and the actions that may be taken to address problems. Main conclusions The theoretical independence of prevalence of popular accuracy measures, such as sensitivity, specificity, true skills statistics (TSS) and area under the receiver operating characteristic curve (AUC), is unlikely to occur in practice due to reference data error; all of these measures of accuracy, together with estimates of species occurrence, showed prevalence dependency arising through the use of a non-gold-standard reference. The number of cases used also had implications for the ability of a study to meet its objectives. Means to reduce the negative effects of imperfect reference data in study design and interpretation are suggested. © 2010 Blackwell Publishing Ltd.

Background: In recent years there has been an exponential growth in the number of people accessing online discussion forums for information, advice and support in relation to a range of both acute and chronic health issues. However, there has been little attention given to exploring the role of alcohol-related forums in the United Kingdom. Methods: A total of 758 messages, retrieved from three public UK-based alcohol discussion forums were qualitatively analysed using thematic analysis. Results: An insight into the online experience of members was captured through three inter-related themes. The first theme "sharing" describes the process of disclosure and aspects of problem drinking, which were discussed by members. Second, the theme "supporting" identifies the ways through which members of the group engaged in mutually supportive communication. Thirdly, "sobriety" describes the collective goal for forum members and describes the challenges of achieving and maintaining this state. Conclusions: Participation in alcohol-related online discussion forums may confer some practical and emotional benefit for those living with alcohol-related problems. Future research is required to fully explore the nature and impact of peer support for this specific problem behaviour. © 2014 Informa UK Ltd.

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

Smoking in pregnancy is a substantial public health problem. When used by non-pregnant smokers, pharmacotherapies [nicotine replacement therapy (NRT), bupropion and varenicline] are effective treatments for smoking cessation, however, their efficacy and safety in pregnancy remains unknown. To determine the efficacy and safety of smoking cessation pharmacotherapies, including NRT, varenicline and bupropion (or any other medications) when used to support smoking cessation in pregnancy. We searched the Pregnancy and Childbirth Group's Trials Register (5 March 2012), checked references of retrieved studies and contacted authors in the field. Randomised controlled trials (RCTs) with designs that permit the independent effects of any type of NRT (e.g. patch, gum etc.) or any other pharmacotherapy on smoking cessation to be ascertained were eligible for inclusion. Trials must provide very similar (ideally identical) levels of behavioural support or cognitive behaviour therapy (CBT) to participants in active drug and comparator trial arms.The following RCT designs are considered acceptable.Placebo RCTs: any form of NRT or other pharmacotherapy, with or without behavioural support/CBT, or brief advice compared with placebo NRT and additional support of similar intensity.RCTs providing a comparison between i) behavioural support/CBT or brief advice and ii) any form of NRT or other pharmacotherapy added to behavioural support of similar (ideally identical) intensity.Parallel- or cluster-randomised design trials are eligible for inclusion. However, quasi-randomised, cross-over and within-participant designs are not eligible for inclusion due to the potential biases associated with these designs. Two review authors independently assessed trials for inclusion and risk of bias and extracted data. Two assessors independently extracted data and cross checked individual outcomes of this process to ensure accuracy. The primary efficacy outcome was smoking cessation in later pregnancy (in all but one trial, at or around delivery); safety was assessed by seven birth outcomes that indicated neonatal well being and we also collated data on adherence. Six trials of NRT enrolling 1745 pregnant smokers were included; we found no trials of varenicline or bupropion. No statistically significant difference was seen for smoking cessation in later pregnancy after using NRT as compared to control (risk ratio (RR) 1.33, 95% confidence interval (CI) 0.93 to 1.91, six studies, 1745 women). Subgroup analysis comparing placebo-RCTs with those which did not use placebos found that efficacy estimates for cessation varied with trial design (placebo RCTs, RR 1.20, 95% CI 0.93 to 1.56, four studies, 1524 women; non-placebo RCTs, RR 7.81, 95% CI 1.51 to 40.35, two studies, 221 women; P value for random-effects subgroup interaction test = 0.03). There were no statistically significant differences in rates of miscarriage, stillbirth, premature birth, birthweight, low birthweight, admissions to neonatal intensive care or neonatal death between NRT or control groups. Nicotine replacement therapy is the only pharmacotherapy for smoking cessation that has been tested in RCTs conducted in pregnancy. There is insufficient evidence to determine whether or not NRT is effective or safe when used to promote smoking cessation in pregnancy or to determine whether or not using NRT has positive or negative impacts on birth outcomes. Further research evidence of efficacy and safety is needed, ideally from placebo-controlled RCTs that investigate higher doses of NRT than were tested in the included studies.

Polarized Raman microspectroscopy and atomic force microscopy were used to obtain quantitative information regarding the molecular structure of individual diphenylalanine (FF) nano- and microtubes. The frequencies of the Raman spectral bands corresponding to the amide I (1690 cm(-1)) and amide III (1249 cm(-1)) indicated that the FF-molecules interact by hydrogen bonding at the N-H and not at the C{box drawing double horizontal}O sites. The calculated mean orientation angles of the principal axes of the Raman tensors (PARTs) obtained from the polarized Raman spectral measurements were 41 ± 4° for the amide I and 59 ± 5° for amide III. On the basis of the orientation of the PART for the amide I mode, it was found that the C{box drawing double horizontal}O bond is oriented at an angle of 8 ± 4° to the tube axis. These values did not vary significantly with the diameter of the tubes (range 400-1700 nm) and were in agreement with the molecular structure proposed previously for larger crystalline specimens.

Sivanesan V.,University of Nottingham
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2012

We give a detailed calculation for the Hamiltonian of single Galileon field theory, keeping track of all the surface terms. We calculate the energy of static, spherically symmetric configuration of the single Galileon field at cubic order coupled to a point source and show that the 2-branches of the solution possess energy of equal magnitude and opposite sign, the sign