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Liverpool, United Kingdom

The University of Liverpool is a public university based in the city of Liverpool, England. Founded in 1881 as a university college, it is also one of the six original "red brick" civic universities. It comprises three faculties organised into 35 departments and schools.It is a founding member of the Russell Group of research-intensive universities, the N8 Group for research collaboration and the University Management school is AACSB accredited.The university has produced nine Nobel Prize winners and offers more than 230 first degree courses across 103 subjects. It was the world's first university to establish departments in Oceanography, civic design, architecture, and biochemistry at the Johnston Laboratories.In 2006 the university became the first in the UK to establish an independent university in China making it the world's first Sino-British university.It has an annual turnover of £410 million, including £150 million for research.Graduates of the University are styled with the post-nominal letters Lpool, to indicate the institution. Wikipedia.


Reiterer V.,University of Konstanz | Eyers P.A.,University of Liverpool | Farhan H.,University of Konstanz
Trends in Cell Biology | Year: 2014

Pseudophosphatases and pseudokinases are increasingly viewed as integral elements of signaling pathways, and there is mounting evidence that they have frequently retained the ability to interact with cellular 'substrates', and can exert important roles in different diseases. However, these pseudoenzymes have traditionally received scant attention compared to classical kinases and phosphatases. In this review we explore new findings in the emerging pseudokinase and pseudophosphatase fields, and discuss their different modes of action which include exciting new roles as scaffolds, anchors, spatial modulators, traps, and ligand-driven regulators of canonical kinases and phosphatases. Thus, it is now apparent that pseudokinases and pseudophosphatases both support and drive a panoply of signaling networks. Finally, we highlight recent evidence on their involvement in human pathologies, marking them as potential novel drug targets. © 2014 Elsevier Ltd. Source


Salmonella infection of the chicken is important both as a source of foodborne human salmonellosis and as a source of disease in the chicken itself. Vaccination and other control strategies require an understanding of the immune response and as such have been important in understanding both mucosal immunity and more generally the response to bacterial infection. In this review, we discuss the contribution the study of avian salmonellosis has made to understanding innate immunity including the function of phagocytic cells, pattern recognition receptors, and defensins. The mucosal response to Salmonella infection and its regulation and the contribution this makes in protection against infection and persistence within the gut and future directions in better understanding the role of TH17 and Tregs in this response. Finally, we discuss the role of the immune system and its modulation in persistent infection and infection of the reproductive tract. We also outline key areas of research required to fully understand the interaction between the chicken immune system and Salmonella and how infection is maintained in the absence of substantive gastrointestinal disease. © 2014 Wigley. Source


Bates K.T.,University of Liverpool | Falkingham P.L.,University of Manchester
Biology Letters | Year: 2012

Bite mechanics and feeding behaviour in Tyrannosaurus rex are controversial. Some contend that a modest bite mechanically limited T. rex to scavenging, while others argue that high bite forces facilitated a predatory mode of life. We use dynamic musculoskeletal models to simulate maximal biting in T. rex.Models predict that adult T. rex generated sustained bite forces of 35 000-57 000 N at a single posterior tooth, by far the highest bite forces estimated for any terrestrial animal. Scaling analyses suggest that adult T. rex had a strong bite for its body size, and that bite performance increased allometrically during ontogeny. Positive allometry in bite performance during growth may have facilitated an ontogenetic change in feeding behaviour in T. rex, associated with an expansion of prey range in adults to include the largest contemporaneous animals.This journal is © 2012 The Royal Society. Source


Cooney G.,Royal Edinburgh Hospital | Dwan K.,University of Liverpool | Mead G.,University of Edinburgh
JAMA - Journal of the American Medical Association | Year: 2014

CLINICAL QUESTION: Is exercise an effective treatment for depression? BOTTOM LINE: Exercise is associated with a greater reduction in depression symptoms compared with no treatment, placebo, or active control interventions, such as relaxation or meditation. However, analysis of high-quality studies alone suggests only small benefits. Copyright 2014 American Medical Association. All rights reserved. Source


Background: In 1999, the UK Government launched a strategy to reduce teenage pregnancy and geographical inequalities in teenage conception rates. This study investigates how associations between deprivation and under-18 conceptions, along with subsequent abortions, since changed as teenage pregnancy rates fell. Methods: A data set was constructed from local authority Indices of Multiple Deprivation (IMD) scores and routine data on under-18 conception rates and the proportion of under-18 conceptions leading to abortion from 1998 to 2010. Correlation analysis (Pearson's r) was used to measure the association between each period of conception and abortion data and the relevant version of the IMD. Changes in these correlations over the period were tested for statistical significance. Results: There remained a strong association between IMD and under-18 conception rates from 1998 (r 0.782, P< 0.0001) to 2010 (r 0.817, P< 0.0001) with no statistically significant change. A statistically significant decrease occurred in the inverse association between IMD and the proportion of under-18 conceptions leading to abortion from 1998 (r -0.501, P< 0.0001) to 2010 (r -0.332, P< 0.0001)ConclusionsWhile under-18 conceptions fell from 1998 to 2010, inequalities in rates between the most and least deprived local authorities remained undiminished. At the same time, abortion became an increasingly common outcome of under-18 conceptions. © 2012 The Author 2012, Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. Source


Hancock E.C.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2013

The Lennox-Gastaut syndrome (LGS) is an age-specific disorder, characterised by epileptic seizures, a characteristic electroencephalogram (EEG), psychomotor delay and behavioural disorder. It occurs more frequently in males and onset is usually before the age of eight years, with a peak between three and five years of age. Late cases occurring in adolescence and early adulthood have rarely been reported. Language is frequently affected, with both slowness in ideation and expression in addition to difficulties of motor dysfunction. Severe behavioural disorders (e.g. hyperactivity, aggressiveness and autistic tendencies) and personality disorders are nearly always present. There is also a tendency for psychosis to develop with time. The long-term prognosis is poor; although the epilepsy often improves, complete seizure freedom is rare and conversely the mental and psychiatric disorders tend to worsen with time. To compare the effects of pharmaceutical therapies used to treat LGS in terms of control of seizures and adverse effects. Many people who suffer from this syndrome will already be receiving other antiepileptic medications at the time of their entry into a trial. However, for the purpose of this review we will only consider the effect of the single therapeutic agent being trialled (often as add-on therapy). We searched the Cochrane Epilepsy Group's Specialized Register (18 October 2012), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 10 of 12, 2012) and MEDLINE (1946 to October week 2, 2012). We also searched EMBASE (1980 to March 2003). We imposed no language restrictions. We searched the International Standard Randomised Controlled Trial Number (ISRCTN) register (18 October 2012) for ongoing trials and in addition, we contacted pharmaceutical companies and colleagues in the field to seek any unpublished or ongoing studies. All randomised controlled trials (RCTs) of the administration of drug therapy to patients with LGS. Two review authors independently extracted data. Analysis included assessing study quality, as well as statistical analysis of the effects on overall seizure rates and effects on specific seizure types (e.g. drop attacks), adverse effects and mortality. We found nine RCTs, but were unable to perform any meta-analysis, because each trial looked at different populations, different therapies and considered different outcomes. The optimum treatment for LGS remains uncertain and no study to date has shown any one drug to be highly efficacious; rufinamide, lamotrigine, topiramate and felbamate may be helpful as add-on therapy, clobazam may be helpful for drop seizures. Until further research has been undertaken, clinicians will need to continue to consider each patient individually, taking into account the potential benefit of each therapy weighed against the risk of adverse effects. Source


Richman E.,University of Liverpool
Proceedings of the Nutrition Society | Year: 2012

Coeliac disease is a permanent inflammatory disorder of the small bowel affecting approximately 1% of the population. The only effective treatment that exists is exclusion of gluten from the diet. The present paper aims to review the literature as to whether oats are safe to eat for people with coeliac disease. Much data exist on the restrictive nature that adhering to a gluten-free diet imposes on an individual. If oats could be eaten, this would help reduce the restrictive nature of the diet. This in turn could lead to an increase in the quality of life. Oats are of high-nutritional value, providing a rich source of fibre, vitamins and minerals. The fibre source contains soluble fibre which is believed to help reduce LDL-cholesterol. A systematic review of the literature was conducted. Earlier studies conducted are difficult to compare as they used different methodologies and it is not known whether samples of oats in the studies were contaminated with gluten from other cereals. Many studies reviewed do not state the strain of oat used. Recent research has suggested that it may only be in certain strains of oats which could produce a toxic response to people with coeliac disease. In conclusion, research suggests that the risk from consuming oats may be less harmful than first thought; however, may vary according to the strain of oat. Handling that risk in clinical practice remains controversial. © The Author 2012. Source


Sun L.,Chalmers University of Technology | Diaz-Fernandez Y.A.,Chalmers University of Technology | Diaz-Fernandez Y.A.,University of Liverpool | Gschneidtner T.A.,Chalmers University of Technology | And 3 more authors.
Chemical Society Reviews | Year: 2014

The use of single molecules in electronics represents the next limit of miniaturisation of electronic devices, which would enable us to continue the trend of aggressive downscaling of silicon-based electronic devices. More significantly, the fabrication, understanding and control of fully functional circuits at the single-molecule level could also open up the possibility of using molecules as devices with novel, not-foreseen functionalities beyond complementary metal-oxide semiconductor technology (CMOS). This review aims at highlighting the chemical design and synthesis of single molecule devices as well as their electrical and structural characterization, including a historical overview and the developments during the last 5 years. We discuss experimental techniques for fabrication of single-molecule junctions, the potential application of single-molecule junctions as molecular switches, and general physical phenomena in single-molecule electronic devices. © 2014 the Partner Organisations. Source


Mariani E.,University of Liverpool | Ghassemieh E.,University of Sheffield
Acta Materialia | Year: 2010

6061 O Al alloy foils were welded to form monolithic and SiC fibre-embedded samples using the ultrasonic consolidation (UC) process. Contact pressures of 135, 155 and 175 MPa were investigated at 20 kHz frequency, 50% of the oscillation amplitude, 34.5 mm s-1 sonotrode velocity and 20 °C. Deformed microstructures were analysed using electron backscatter diffraction (EBSD). At all contact pressures deformation occurs by non-steady state dislocation glide. Dynamic recovery is active in the upper and lower foils. Friction at the welding interface, instantaneous internal temperatures (0.5-0.8 of the melting temperature, Tm), contact pressure and fast strain rates result in transient microstructures and grain size reduction by continuous dynamic recrystallization (CDRX) within the bonding zone. Bonding occurs by local grain boundary migration, which allows diffusion and atom interlocking across the contact between two clean surfaces. Textures weaken with increasing contact pressure due to increased strain hardening and different grain rotation rates. High contact pressures enhance dynamic recovery and CDRX. Deformation around the fibre is intense within 50 μm and extends to 450 μm from it. © 2009 Acta Materialia Inc. Source


Greer I.A.,University of Liverpool
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2012

Acute venous thromboembolism poses significant problems in pregnancy, a time when objective diagnosis and prompt treatment are essential. Events can occur at any stage in pregnancy, but the period of greatest risk is in the weeks after delivery. Ultrasound venography remains the diagnostic technique of choice for deep venous thrombosis. For pulmonary thromboembolism, ventilation perfusion lung scan is usually preferred more than computerized tomography pulmonary angiography because of the lower maternal radiation dose and the lower prevalence of coexisting pulmonary problems. Low-molecular-weight heparin is the agent of choice for treatment of venous thromboembolism in pregnancy, and treatment should be provided for a minimum of 3 months and for at least 6 weeks after delivery. New anticoagulant agents such as dabigatran, rivaroxaban, or apixaban are not recommended for use in pregnancy. Source


Bench-Capon T.J.M.,University of Liverpool
Artificial Intelligence and Law | Year: 2012

Modelling reasoning with legal cases has been a central concern of AI and Law since the 1980s. The approach which represents cases as factors and dimensions has been a central part of that work. In this paper I consider how several varieties of the approach can be applied to the interesting case of Popov v Hayashi. After briefly reviewing some of the key landmarks of the approach, the case is represented in terms of factors and dimensions, and further explored using theory construction and argumentation schemes approaches. © 2012 Springer Science+Business Media B.V. Source


Reininghaus U.,Kings College London | Reininghaus U.,University of Cambridge | Priebe S.,Queen Mary, University of London | Bentall R.P.,University of Liverpool
Schizophrenia Bulletin | Year: 2013

Background: Psychiatric taxonomists have sometimes argued for a unitary psychosis syndrome and sometimes for a pentagonal model, including 5 diagnostic constructs of positive symptoms, negative symptoms, cognitive disorganization, mania, and depression. This continues to be debated in preparation for impending revisions of the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases. We aimed to identify general and specific dimensions underlying psychopathological features of psychosis. Methods: The samples comprised 309 patients admitted to psychiatric services in the acute phase of their first or second episode of psychosis and 507 patients with enduring psychosis recruited from community mental health teams. Patients' symptoms were assessed on the Positive and Negative Symptom Scale. Analyses compared unitary, pentagonal, and bifactor models of psychosis. Results: In both samples, a bifactor model including 1 general psychosis factor and, independently, 5 specific factors of positive symptoms, negative symptoms, disorganization, mania, and depression gave the best fit. Scores of general and specific symptom dimensions were differentially associated with phase of illness, diagnosis, social functioning, insight, and neurocognitive functioning. Conclusions: The findings provide strong evidence for a general psychosis dimension in both early and enduring psychosis. Findings further allowed for independent formation of specific symptom dimensions. This may inform the current debate about revised classification systems of psychosis. © The Author 2012. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. Source


Hopkins L.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2012

Prophylactic antibiotics for cesarean section have been shown to reduce the incidence of maternal postoperative infectious morbidity. Many different antibiotic regimens have been reported to be effective. The objective of this review was to determine which antibiotic regimen is most effective in reducing the incidence of infectious morbidity in women undergoing cesarean section. We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. The date of the most recent search was October 1998. Randomized trials that included women undergoing cesarean section were included. Trials were required to compare at least two different antibiotic regimens. Trials that compared placebo with a single antibiotic regimen were not included as these are studies which have been analyzed in another Cochrane review. Data were extracted from each publication independently by the reviewers. Reviewers were not blinded to the authors or sources of the articles. The primary outcome variable was endometritis but data on other infectious complications were collected where provided. Fifty-one trials published between 1979 and 1994 were included in the review and four were excluded from the review. The following results refer to reductions in the incidence of endometritis. Both ampicillin and first generation cephalosporins have similar efficacy with an odds ratio (OR) of 1.27 (95% confidence interval (CI): 0.84-1.93). In comparing ampicillin with second or third generation cephalosporins the odds ratio was 0.83 (95% CI 0.54-1.26) and in comparing a first generation cephalosporin with a second or third generation agent the odds ratio was 1.21 (95% CI 0.97-1.51). A multiple dose regimen for prophylaxis appears to offer no added benefit over a single dose regimen; OR 0.92 (95% CI 0.70-1.23). Systemic and lavage routes of administration appear to have no difference in effect; OR 1.19 (95% CI 0.81-1.73). There was no significant heterogeneity between the trials contained in the various sub-group analyses, although confidence intervals were sometimes wide. Both ampicillin and first generation cephalosporins have similar efficacy in reducing postoperative endometritis. There does not appear to be added benefit in utilizing a more broad spectrum agent or a multiple dose regimen. There is a need for an appropriately designed randomized trial to test the optimal timing of administration (immediately after the cord is clamped versus pre-operative). Source


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

The pain that women experience during labour is affected by multiple physiological and psychosocial factors and its intensity can vary greatly.  Most women in labour require pain relief. Pain management strategies include non-pharmacological interventions (that aim to help women cope with pain in labour) and pharmacological interventions (that aim to relieve the pain of labour). To summarise the evidence from Cochrane systematic reviews on the efficacy and safety of non-pharmacological and pharmacological interventions to manage pain in labour. We considered findings from non-Cochrane systematic reviews if there was no relevant Cochrane review. We searched the Cochrane Database of Systematic Reviews (The Cochrane Library 2011, Issue 5), The Cochrane Database of Abstracts of Reviews of Effects (The Cochrane Library 2011, Issue 2 of 4), MEDLINE (1966 to 31 May 2011) and EMBASE (1974 to 31 May 2011) to identify all relevant systematic reviews of randomised controlled trials of pain management in labour. Each of the contributing Cochrane reviews (nine new, six updated) followed a generic protocol with 13 common primary efficacy and safety outcomes. Each Cochrane review included comparisons with placebo, standard care or with a different intervention according to a predefined hierarchy of interventions. Two review authors extracted data and assessed methodological quality, and data were checked by a third author. This overview is a narrative summary of the results obtained from individual reviews. We identified 15 Cochrane reviews (255 included trials) and three non-Cochrane reviews (55 included trials) for inclusion within this overview. For all interventions, with available data, results are presented as comparisons of: 1. Intervention versus placebo or standard care; 2. Different forms of the same intervention (e.g. one opioid versus another opioid); 3. One type of intervention versus a different type of intervention (e.g. TENS versus opioid). Not all reviews included results for all comparisons. Most reviews compared the intervention with placebo or standard care, but with the exception of opioids and epidural analgesia, there were few direct comparisons between different forms of the same intervention, and even fewer comparisons between different interventions. Based on these three comparisons, we have categorised interventions into: " What works" ,"What may work", and "Insufficient evidence to make a judgement".WHAT WORKSEvidence suggests that epidural, combined spinal epidural (CSE) and inhaled analgesia effectively manage pain in labour, but may give rise to adverse effects. Epidural, and inhaled analgesia effectively relieve pain when compared with placebo or a different type of intervention (epidural versus opioids). Combined-spinal epidurals relieve pain more quickly than traditional or low dose epidurals. Women receiving inhaled analgesia were more likely to experience vomiting, nausea and dizziness.When compared with placebo or opioids, women receiving epidural analgesia had more instrumental vaginal births and caesarean sections for fetal distress, although there was no difference in the rates of caesarean section overall. Women receiving epidural analgesia were more likely to experience hypotension, motor blockade, fever or urinary retention. Less urinary retention was observed in women receiving CSE than in women receiving traditional epidurals. More women receiving CSE than low-dose epidural experienced pruritus.  WHAT MAY WORKThere is some evidence to suggest that immersion in water, relaxation, acupuncture, massage and local anaesthetic nerve blocks or non-opioid drugs may improve management of labour pain, with few adverse effects.  Evidence was mainly limited to single trials. These interventions relieved pain and improved satisfaction with pain relief (immersion, relaxation, acupuncture, local anaesthetic nerve blocks, non-opioids) and childbirth experience (immersion, relaxation, non-opioids) when compared with placebo or standard care. Relaxation was associated with fewer assisted vaginal births and acupuncture was associated with fewer assisted vaginal births and caesarean sections. Source


Brown T.,University of Liverpool
Health technology assessment (Winchester, England) | Year: 2010

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of gefitinib for the first-line treatment of locally advanced or metastatic non-small cell lung cancer, in accordance with the licensed indication, based upon the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The submitted clinical evidence consisted of the IRESSA Pan-ASian Study (IPASS); a phase III open-label randomised controlled trial conducted in 87 centres in East Asia which compared the use of gefitinib with paclitaxel/carboplatin in 1217 chemotherapy (CTX)-naive patients with stage IIIB/IV pulmonary adenocarcinoma. The manufacturer's submission focused on a subgroup of patients in IPASS who were epidermal growth factor receptor (EGFR) gene mutation-positive (M+) (n = 261; 21% of the total IPASS population). The primary clinical outcome was progression-free survival (PFS). Secondary outcomes included overall survival, clinically relevant improvement in quality of life and adverse events (AEs). Cost-effectiveness was measured in terms of incremental cost per quality-adjusted life-year (QALY). In the overall population, PFS was significantly longer in patients treated with gefitinib than in those treated with paclitaxel/carboplatin (hazard ratio 0.74, 95% confidence interval 0.65 to 0.85; p < 0.0001). The manufacturer reported an incremental cost-effectiveness ratio (ICER) of 20,744 pounds per QALY gained for the target population. The probabilistic sensitivity analysis illustrated that for patients who are EGFR M+, gefitinib compared with doublet CTX was not likely to be cost-effective at what would usually be considered standard levels of willingness to pay for an additional QALY; the mean ICER for gefitinib EGFR M+ versus doublet CTX EGFR M+ was reported as 35,700 pounds per QALY. Additional analysis by the ERG included amendments to the base-case analysis, including an alternative approach to projecting survival, inclusion of two important additional comparators, sensitivity to EGFR M+ prevalence, and AE costs and disutilities. The manufacturer's submission provides clinical evidence to support the use of gefitinib in EGFR M+ patients with adenocarcinoma histology only. Before patients can be offered first-line treatment with gefitinib they must undergo EGFR mutation status testing which is currently not routinely available in the NHS. At the time of writing, the guidance document issued by NICE on 28 July 2010 states that 'Gefitinib is recommended as an option for the first-line treatment of people with locally advanced or metastatic non-small-cell lung cancer (NSCLC) if they test positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation and the manufacturer provides gefitinib at the fixed price agreed under the patient access scheme'. Source


Harding S.P.,University of Liverpool
Eye | Year: 2010

Aim To review the decision-making processes and dilemmas in the delivery of services for neovascular age-related macular degeneration (nAMD) and describe its optimal management. Methods Review of literature and presentation of illustrative cases. Results Guidelines are available to aid commissioners and providers of services but with important gaps in advice. Increasing awareness of variants and diseases that mimic nAMD means that clinicians need to carefully assess lesions at presentation, using stereo imaging, fluorescein and indocyanine green angiography, and new generation optical coherence tomography. Current evidence supports the use of ranibizumab as first-line therapy. Evidence is unclear on the most appropriate treatment regime, especially in protocols relying on clinician-determined re-treatment. Current consensus recommends initiation with monthly injections for 3 months followed by maintenance comprising regular monthly visits with clinician-determined re-treatment. Further evidence on treatment protocols and the comparison with bevacizumab is awaited.ConclusionsOwing to incomplete evidence base health professionals face a large number of controversies and dilemmas in care pathways for patients with nAMD. Treatment should be delivered against protocols developed locally in a systematic manner with consensus and a cautious approach to change. © 2010 Macmillan Publishers Limited All rights reserved. Source


Thompson I.,University of Liverpool
ACM Transactions on Mathematical Software | Year: 2013

An algorithm for accurately computing the lower incomplete gamma function γ (a, t) in the case where a = n + 1/2, n ε ℤ and t < 0 is described. Series expansions and analytic continuation are employed to compute the function for certain critical values of n, and these results are used to initiate stable recurrence. The algorithm has been implemented in Fortran 2003, with precompuations carried out in Maple. © 2013 ACM. Source


Fleeman N.,University of Liverpool
Health technology assessment (Winchester, England) | Year: 2010

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of pemetrexed for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in accordance with the licensed indication, based upon the evidence submission from Eli Lilly Ltd to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The majority of the efficacy evidence described in the manufacturer's submission is derived from a phase III open-label randomised controlled trial (RCT) known as the JMDB trial. The trial achieved its primary objective to demonstrate non-inferiority of pemetrexed/cisplatin to gemcitabine/cisplatin for overall survival in all patients with NSCLC. Because no other studies were found comparing pemetrexed/cisplatin with any other relevant comparator, additional efficacy evidence was presented from two phase III RCTs comparing gemcitabine/cisplatin with gemcitabine/carboplatin and docetaxel/cisplatin. The manufacturer's submission reported from its indirect comparisons' analysis that median overall survival and progression-free survival and tumour response rates were more favourable for pemetrexed/cisplatin than for any other comparator. The manufacturer did not identify any published cost-effectiveness analyses of pemetrexed for the first-line treatment of patients with NSCLC. Therefore economic evidence was derived solely from a de novo economic model developed by the manufacturer. A Markov model was developed to evaluate the cost-effectiveness of pemetrexed/cisplatin compared to gemcitabine/cisplatin, docetaxel/cisplatin and gemcitabine/carboplatin. The clinical data used in the economic evaluation were primarily generated from the JMDB trial, with additional data from the two further trials used in the indirect comparisons analysis. The ERG identified a series of problems with this economic model. As a result, three different versions of the model were submitted to NICE and considered by the ERG. The ICERs estimated by this final version of the model ranged from 8056 pounds to 33,065 pounds per QALY, depending on the comparator, the population and the application of a continuation rule. The ERG considered that the model required extensive modification and redesign, and should be subjected to thorough validation against the JMDB trial results. A full quality audit was also required as it was likely that further model inconsistencies may be present that had not yet been identified. The manufacturer subsequently included evidence in the form of three cost effectiveness analyses (two models and an 'in-trial' analysis), stating that a thorough validation process had been followed according to the NICE request. The very short time available to the ERG to consider the new evidence precluded a comprehensive assessment. Instead, the ERG chose to present a simple exploratory analysis combining its own survival projections with key cost estimates obtained from the JMDB trial individual patient data. Compared to gemcitabine, this resulted in ICERs ranging from 17,162 pounds to 30,142 pounds per QALY, depending on the patient population, the maximum number of cycles of chemotherapy and whether a cycle based efficacy adjustment was applied or not. The guidance issued by NICE in September 2009 states that pemetrexed in combination with cisplatin is recommended as an option for the first-line treatment of patients with locally advanced or metastatic NSCLC only if the histology of the tumour has been confirmed as adenocarcinoma or large-cell carcinoma. Source


Hill A.,University of Liverpool
Current Opinion in HIV and AIDS | Year: 2013

PURPOSE OF REVIEW: There are at least seven million people eligible for antiretroviral treatment but not receiving it. An additional 19 million people will need to start treatment in the future, as their HIV disease progresses. Funding for Universal Access to HIV treatment has been restricted by the Global Financial Crisis. RECENT FINDINGS: There are three large randomized trials ongoing, designed to establish the efficacy of lower than approved doses of antiretrovirals. If successful, the results of these trials could lower costs of antiretrovirals and improve the safety profiles. Clinical trials evaluating efavirenz, atazanavir, ritonavir and stavudine are discussed. The costs of these and other antiretrovirals are presented. SUMMARY: The results of these trials could significantly lower the costs of Universal Access. Assuming 15 million people on antiretroviral treatment, the reduction in unit costs of tenofovir (TDF)/3TC/efavirenz from dose optimization of efavirenz to 400mg once daily would save US$16 per person, leading to an overall saving of US$192 million per year. The switch from zidovudine (ZDV)/3TC/atazanavir (ATV)/r 300/100 once daily to dolutegravir along with ATV/r 200/50 once daily would save US$267 per person, leading to an overall saving of US$801 million. The combined saving in costs from first-and second-line treatment would therefore be US$993 million per year. © Lippincott Williams & Wilkins. Source


Flows in ephemeral channels in semiarid areas are only occasional, and channel changes are episodic; but the flash floods can be devastating and have major geomorphological impacts. Data on morphological impacts of flows in semiarid areas are needed to increase understanding of the dynamics and variability of geomorphic responses in such channels. For this purpose nine reaches of river channel in three catchments in SE Spain - the Nogalte, Torrealvilla, and Salada - have been sites for measurement of flows and their effects over the period 1997-2012. The sites encompass a range of channel size, channel morphology, substrate, vegetation, and position within the catchments. A major difference is between schist and marl bedrock areas. Peak flow stage has been recorded and topography surveyed at frequent intervals and after major flow events. Over the 16-year period, an average of 0.5 flow events per year has been recorded at the schist sites, and an average of one per year at the marl sites; but occurrence has been highly variable from year to year. Threshold daily rainfall for channel flow is mostly 15-20 mm, but higher rainfalls do not always produce flow. One to two major floods have occurred in each of the catchments in the period, including the extreme flood event of September 2012 in the Nogalte catchment. Measured morphological changes have occurred between 2 and 10 times at the monitored sites. The same size flow can have differing effects depending on the state of the system. Low flow can mobilise sediment without producing much morphological change. The long-term trajectory of the reaches and the sediment substrate has a major influence on response to events. Channel change is governed by threshold values of hydraulic conditions. The measurements provide an indication of the scale of maximum erosion and deposition that occurs within the channels and on the floodplains over a range of flow magnitudes and the flow impacts that need to be considered in management. © 2015 Elsevier B.V. Source


Konur S.,University of Liverpool
Frontiers of Computer Science | Year: 2013

Over the last two decades, there has been an extensive study of logical formalisms on specifying and verifying real-time systems. Temporal logics have been an important research subject within this direction. Although numerous logics have been introduced for formal specification of real-time and complex systems, an up to date survey of these logics does not exist in the literature. In this paper we analyse various temporal formalisms introduced for specification, including propositional/first-order linear temporal logics, branching temporal logics, interval temporal logics, real-time temporal logics and probabilistic temporal logics. We give decidability, axiomatizability, expressiveness, model checking results for each logic analysed. We also provide a comparison of features of the temporal logics discussed. © 2013 Higher Education Press and Springer-Verlag Berlin Heidelberg. Source


Chen K.,University of Liverpool
International Journal of Computer Mathematics | Year: 2013

Variational image-processing models offer high-quality processing capabilities for imaging. They have been widely developed and used in the last two decades, enriching the fields of mathematics as well as information science. Mathematically, several tools are needed: energy optimization, regularization, partial differential equations, level set functions, and numerical algorithms. This special issue presents readers with nine excellent research papers covering topics from research work into variational image-processing models, algorithms and applications, including image denoising, image deblurring, image segmentation, image reconstruction, restoration of mixed noise types and three-dimensional surface restoration. © 2013 Copyright Taylor and Francis Group, LLC. Source


Kougioumtzoglou I.A.,University of Liverpool | Spanos P.D.,Rice University
Computers and Structures | Year: 2013

An approximate analytical dimension reduction approach is developed for determining the response of a multi-degree-of-freedom (MDOF) nonlinear/hysteretic system subject to a non-stationary stochastic excitation vector. The approach is based on the concepts of statistical linearization and of stochastic averaging. It is readily applicable even for excitations possessing evolutionary in time power spectra. Further, it can be potentially used in conjunction with design spectrum based analyses to obtain peak system response estimates. Numerical examples include MDOF systems comprising the versatile Bouc-Wen (hysteretic) model. The reliability of the approach is demonstrated by pertinent Monte Carlo simulations. © 2012 Elsevier Ltd. Source


Parker G.A.,University of Liverpool
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2013

We give a historic overview and critical perspective of polyandry in the context of sexual selection. Early approaches tended to obfuscate the fact that the total matings (copulations) by the two sexes is equal, neglecting female interests and that females often mate with (or receive ejaculates from) more than one male (polyandry). In recent years, we have gained much more insight into adaptive reasons for polyandry, particularly from the female perspective. However, costs and benefits of multiple mating are unlikely to be equal for males and females. These must be assessed for each partner at each potential mating between male i and female j, and will often be highly asymmetric. Interests of i and j may be in conflict, with (typically, ultimately because of primordial sex differences) i benefitting and j losing from mating, although theoretically the reverse can also obtain. Polyandry reduces the sex difference in Bateman gradients, and the probability of sexual conflict over mating by: (i) reducing the potential expected value of each mating to males in inverse proportion to the number of mates per female per clutch, and also often by (ii) increasing ejaculate costs through increased sperm allocation. It can nevertheless create conflict over fertilization and increase conflict over parental investment. The observed mean mating frequency for the population (and hence the degree of polyandry) is likely, at least in part, to reflect a resolution of sexual conflict. Immense diversity exists across and within taxa in the extent of polyandry, and views on its significance have changed radically, as we illustrate using avian polyandry as a case study. Despite recent criticisms, the contribution of the early pioneers of sexual selection, Darwin and Bateman, remains generally valid, and should not, therefore, be negated; as with much in science, pioneering advances are more often amplified and refined, rather than replaced with entirely new paradigms. Source


Bertamini M.,University of Liverpool
Perception | Year: 2010

The salience of a transformation between a pair of contours depends on the type of transformation (eg a reflection or a translation) and also on figure-ground organisation. Reflection is most salient when both contours belong to the same surface, and translation is most salient when they do not connect a surface. These findings are based on reaction time (RT). Here I replicate and extend them by measuring both RT and sensitivity. The figure-ground relations were changed unambiguously by using stereograms. I compared reflection and translation when they were present within a surface or across surfaces (experiment 1), and within an object or a hole (experiments 2-4). Holes are interesting because they are not objects, but their presence does not increase the number of total objects in the scene. The within-surface advantage for reflection was present in all experiments. There was a between-surface advantage for translation in experiment 1 but there was no hole advantage for translation in experiments 2-4. Thus the effect of context, ie objectness, on detection of regularity is a robust and general phenomenon present in every experiment, but the type of interaction differs for reflection and translation. © 2010 a Pion publication. Source


Rosenthal R.,University of Basel | Dwan K.,University of Liverpool
Annals of Surgery | Year: 2013

Objective: To evaluate discrepancies between trial registry entries and final reports of randomized controlled trials (RCTs) published in major general surgical journals. Background: Health care decisions are based on published results in peerreviewed journals. Mandatory trial registration was introduced to increase transparency and reduce publication and outcome reporting bias. Methods: The discrepancy rate between trial registry entries and final reports of all RCTs published during 2010 in the Annals of Surgery, Archives of Surgery, and British Journal of Surgery was evaluated. Results: Of 596 identified studies, 545 were excluded because they were not RCTs or interim reports/secondary analysis of RCTs or because of missing trial registry information. In the remaining 51 RCTs, prospective registration was found in 9.8% (n = 5), registration during trial conduct in 33.3% (n = 17), and retrospective registration in 56.9% (n = 29), respectively. For the primary and secondary outcomes, there was no discrepancy in 54.9% and 33.3%, complete omission in 7.8% and 31.3%, new introduction in 7.8% and 39.2%, a change in definition in 9.8% and 5.8%, downgrading from primary to secondary in 21.6%, and upgrading from secondary to primary in 13.7%. There were few discrepancies in randomization, blinding, and intervention and some in targeted sample size and inclusion/exclusion criteria. Conclusions: When interpreting the results of surgical RCTs, the possibility of selective reporting, and thus outcome reporting bias, has to be kept in mind. For future trials, prospective registration should be strictly respected with the ultimate goal to increase transparency and contribute to high-level evidence reports for optimal patient care in surgery. Copyright © 2013 by Lippincott Williams and Wilkins. Source


Ram Y.M.,Louisiana State University | Mottershead J.E.,University of Liverpool
Mechanical Systems and Signal Processing | Year: 2013

The paper addresses the problem of suppressing vibrations by active control. Conventional methods use a mathematical model, e.g. finite elements, as the foundations for the computations of the control gains. Such a model is known to contain inaccuracies and assumptions that may hinder the calculations. An alternative approach, advocated previously by the authors, is to design a controller using vibration measurements, in the form of receptances, typically available from a modal test. The methodology as originally formulated was limited to single-input control. In this paper new theory is described that is applicable to both single-input and multiple-input-multiple-output vibration control of practical engineering structures. The theory is supplemented by a series of illustrative numerical examples. © 2013 Elsevier Ltd. Source


Pirmohamed M.,University of Liverpool
Annual Review of Genomics and Human Genetics | Year: 2014

Drug response varies between individuals owing to disease heterogeneity, environmental factors, and genetic factors. Genetic factors can affect both the pharmacokinetics and pharmacodynamics of a drug, leading to changes in local and systemic drug exposure and/or changes in the function of the drug target, altering drug response. Several pharmacogenetic biomarkers are already utilized in clinical practice and have been shown to improve clinical outcomes. However, a large number of other biomarkers have never made it beyond the discovery stage. Concerted effort is needed to improve the translation of pharmacogenetic biomarkers into clinical practice, and this will involve the use of standardized phenotyping and genotyping strategies, collaborative work, multidisciplinary approaches to identifying and replicating associations, and cooperation with industry to facilitate translation and commercialization. Acceptance of these approaches by clinicians, regulators, patients, and the public will be important in determining future success. Copyright © 2014 by Annual Reviews. All rights reserved. Source


Lehtonen J.,University of Basel | Parker G.A.,University of Liverpool
Molecular Human Reproduction | Year: 2014

Males and females are a fundamental aspect of human reproduction, yet procreation is perfectly possible without this division into two sexes. Biologically, males are defined as the sex that produces the smaller gametes (e.g. sperm), implying that the male and female sexes only exist in species with gamete dimorphism (anisogamy). Our ancestors were isogamous, meaning that only one gamete size was produced. The question of the evolutionary origin of males and females is then synonymous to asking what evolutionary pressures caused gamete sizes to diverge. Studying the ancestral evolutionary divergence of males and females relies largely on mathematical modelling. Here, we review two classes of models explaining the evolutionary origin of males and females: gamete competition and gamete limitation. These seemingly alternative explanations are not mutually exclusive, but two aspects of a single evolutionary process. Once evolved, anisogamy and the two sexes are evolutionarily very stable. This explains the maintenance of anisogamy in organisms with internal fertilization, which can cause large decreases in both gamete competition and gamete limitation. The ancestral divergence and maintenance of gamete sizes subsequently led to manyother differences we now observe between the two sexes, sowing the seeds for what we have become. © The Author 2014. Source


Serra A.,Polytechnic University of Catalonia | Bacon D.J.,University of Liverpool | Pond R.C.,University of Exeter
Physical Review Letters | Year: 2010

A Comment on the Letter by B. Li and E. Ma, Phys. Rev. Lett.PRLTAO0031-9007 103, 035503 (2009)10.1103/PhysRevLett.103.035503. The authors of the Letter offer a Reply. © 2010 The American Physical Society. Source


Johnson E.K.,University of Bath | Adams D.J.,University of Liverpool | Cameron P.J.,University of Bath
Journal of the American Chemical Society | Year: 2010

The dipeptide amphiphile Fmoc-Leu-Gly-OH has been induced to self-assemble into thin surface-supported hydrogel gel films and gap-spanning hydrogel membranes. The thickness can be closely controlled, giving films/membranes from tens of nanometers to millimeters thick. SEM and TEM have confirmed that the dipeptides self-assemble to form fibers, with the membranes resembling a dense "mat" of entangled fibers. The films and membranes were stable once formed. The films could be reversibly dried and collapsed, then reswollen to regain the gel structure. © 2010 American Chemical Society. Source


Parry G.,University of Liverpool
Journal of Experimental Botany | Year: 2014

The nuclear pore complex (NPC) is a multisubunit protein conglomerate that facilitates movement of RNA and protein between the nucleus and cytoplasm. Relatively little is known regarding the influence of the Arabidopsis NPC on growth and development. Seedling development, flowering time, nuclear morphology, mRNA accumulation, and gene expression changes in Arabidopsis nucleoporin mutants were investigated. Nuclear export of mRNA is differentially affected in plants with defects in nucleoporins that lie in different NPC subcomplexes. This study reveals differences in the manner by which nucleoporins alter molecular and plant growth phenotypes, suggesting that nuclear pore subcomplexes play distinct roles in nuclear transport and reveal a possible feedback relationship between the expression of genes involved in nuclear transport. © 2014 The Author. Published by Oxford University Press on behalf of the Society for Experimental Biology. Source


Husein A.B.,University of Liverpool
Primary dental care : journal of the Faculty of General Dental Practitioners (UK) | Year: 2011

The aim of this survey was to investigate the views of general dental practitioners (GDPs) on their perceived roles and the barriers regarding dental care of patients following head and neck radio-therapy. From a total of 1163 GDPs on the Mersey Postgraduate Dental Deanery mailing list, 369 were selected at random. Questionnaires were sent out in February 2010 followed by reminders a month later. A study-specific questionnaire was piloted prior to the survey. One hundred and ninety-eight of the potential 336 respondents returned valid questionnaires, a response rate of 59%. They did not respond to all questions. Of those who responded, 99/188 (53%) were either 'not at all' or 'little' happy about managing these patients and 118/183 (64%) and 100/173 (58%), respectively, perceived that complex management and the new General Dental Services (nGDS) contract introduced in 2006 were 'quite a bit' or 'very much' barriers to treatment. The majority of the respondents felt that they were 'quite a bit' or 'very much' happy to carry out routine fillings (177/195; 90%), periodontal treatment (166/195; 85%), removable dentures (161/195; 83%), crown and bridge work (123/192; 64%), and root canal therapy (114/195; 58%) but only 53/191 (28%) to perform dental extractions. Over half of the respondents felt that they had 'quite a bit' or a 'main role' in managing radiotherapy caries, xerostomia, detecting recurrence and offering smoking-cessation advice. The majority of the GDPs who responded had been involved in the management of patients who had undergone radio-therapy to the head and neck. A substantial number perceived barriers to care, such as the complexity of the treatment and the nGDS contract. These findings need further investigation. Continuing professional development would be helpful to improve GDPs' confidence in dealing with this group of patients. Source


Trayhurn P.,University of Liverpool | Trayhurn P.,The University of Buckingham
Physiological Reviews | Year: 2013

The rise in the incidence of obesity has led to a major interest in the biology of white adipose tissue. The tissue is a major endocrine and signaling organ, with adipocytes, the characteristic cell type, secreting a multiplicity of protein factors, the adipokines. Increases in the secretion of a number of adipokines occur in obesity, underpinning inflammation in white adipose tissue and the development of obesity-associated diseases. There is substantial evidence, particularly from animal studies, that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in PO2 is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of >1,000 genes. The secretion of a number of inflammation-related adipokines is upregulated by hypoxia, and there is a switch from oxidative metabolism to anaerobic glycolysis. Glucose utilization is increased in hypoxic adipocytes with corresponding increases in lactate production. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Many of the responses of adipocytes to hypoxia are initiated at PO2 levels above the normal physiological range for adipose tissue. The other cell types within the tissue also respond to hypoxia, with the differentiation of preadipocytes to adipocytes being inhibited and preadipocytes being transformed into leptin-secreting cells. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity. © 2013 the American Physiological Society. Source


Field J.K.,University of Liverpool | Hansell D.M.,Royal Brompton Hospital | Duffy S.W.,Queen Mary, University of London | Baldwin D.R.,University of Nottingham
The Lancet Oncology | Year: 2013

Implementation of lung cancer CT screening is currently the subject of a major policy decision within the USA. Findings of the US National Lung Screening Trial showed a 20% reduction in lung cancer mortality and a 6·7% decrease in all-cause mortality; subsequently, five US professional and clinical organisations and the US Preventive Services Task Force recommended that screening should be implemented. Should national health services in Europe follow suit? The European community awaits mortality and cost-effectiveness data from the NELSON trial in 2015-16 and pooled findings of European trials. In the intervening years, a recommendation is proposed that a demonstration trial is done in the UK. In this Review, we summarise the existing evidence and identify questions that remain to be answered before the implementation of international lung cancer screening programmes. © 2013 Elsevier Ltd. Source


Danjuma M.I.,University of Liverpool
Current hypertension reports | Year: 2014

The converging clinical effectiveness of mineralocorticoid receptor antagonists (MRAs) Spironolactone and Eplerenone has made their safety profiles/cost-effectiveness key determinants of "agents of choice" across a broad range of clinical indications. The clinical biology of the aldosterone molecule and its range of effects in varied organ systems have been well elucidated from recent mechanistic and systematic studies. Clinical experience with Spironolactone is well established, as is its adverse effects profile. The range of adverse effects experienced with Spironolactone subsequently led to its modification and synthesis of Eplerenone. Recent published reports have confirmed lower prevalence rates of sex-related adverse effects attributable to Eplerenone compared to Spironolactone. There is, however, not much to choose between these agents in regards to other adverse effects including hyperkalemia and kidney failure. As was the experience with Spironolactone, as more robust observational data on Eplerenone accrues, it is possible that the real-life experience of its adverse profile may be discordant with that reported by randomized controlled clinical trials (RCTs). In addition, its metabolism by the vulnerable and highly polymorphic cytochrome dependent pathway also makes it susceptible to various drug interactions. The potential implication of the latter (including morbidity and mortality) may take years to evolve. Source


Aziz N.,University of Liverpool
Clinics | Year: 2013

Azoospermia is a descriptive term referring to ejaculates that lack spermatozoa without implying a specific underlying cause. The traditional definition of azoospermia is ambiguous, which has ramifications on the diagnostic criteria. This issue is further compounded by the apparent overlap between the definitions of oligospermia and azoospermia. The reliable diagnosis of the absence of spermatozoa in a semen sample is an important criterion not only for diagnosing male infertility but also for ascertaining the success of a vasectomy and for determining the efficacy of hormonal contraception. There appears to be different levels of rigor in diagnosing azoospermia in different clinical situations, which highlights the conflict between scientific research and clinical practice in defining azoospermia. © 2013 CLINICS. Source


Pearson M.,University of Liverpool
COPD: Journal of Chronic Obstructive Pulmonary Disease | Year: 2013

The mechanisms underlying the majority of COPD cases have remained ill-defined. Cigarette smoke contains many toxic chemicals that certainly cause some inflammatory responses, but this article advances a hypothesis that the nicotine and similar compounds within the smoke acting as vasoconstrictors of bronchiolar arterioles may be more important via multiple small infarcts that eventually destroy lung tissue. The hypothesis can explain many of the known features of COPD and if accepted would significantly alter the approach to this condition. © 2013 Informa Healthcare USA, Inc. Source


Weeks A.,University of Liverpool
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2015

Postpartum haemorrhage (PPH) remains a major cause of maternal deaths worldwide, and is estimated to cause the death of a woman every 10 minutes. This review presents the latest clinical advice, including new evidence on controlled cord traction, misoprostol, and oxytocin. The controversy around the diagnosis of PPH, the limitations of universal prophylaxis, and novel ways to provide obstetric first aid are also presented. It ends with a call to develop high-quality front-line obstetric services that can deal rapidly with unexpected haemorrhages as well as minimising blood loss at critical times: major abruption, placenta praevia, and caesarean for prolonged labour. © 2014 Royal College of Obstetricians and Gynaecologists. Source


De Magalhaes J.P.,University of Liverpool
EMBO Reports | Year: 2015

Animal models have advanced biomedical research, but they have important limits. The tools of comparative genomics should now allow us to expand our bestiary to study non-model organisms and how they deal with aging and cancer, eventually applying this knowledge to human health. © 2015 The Author. Source


Davies E.V.,University of Liverpool
ISME Journal | Year: 2016

The Liverpool Epidemic Strain (LES) is a polylysogenic, transmissible strain of Pseudomonas aeruginosa, capable of superinfecting existing P. aeruginosa respiratory infections in individuals with cystic fibrosis (CF). The LES phages are highly active in the CF lung and may have a role in the competitiveness of the LES in vivo. In this study, we tested this by competing isogenic PAO1 strains that differed only by the presence or absence of LES prophages in a rat model of chronic lung infection. Lysogens invaded phage-susceptible populations, both in head-to-head competition and when invading from rare, in the spatially structured, heterogeneous lung environment. Appreciable densities of free phages in lung tissue confirmed active phage lysis in vivo. Moreover, we observed lysogenic conversion of the phage-susceptible competitor. These results suggest that temperate phages may have an important role in the competitiveness of the LES in chronic lung infection by acting as anti-competitor weapons.The ISME Journal advance online publication, 12 April 2016; doi:10.1038/ismej.2016.51. © 2016 International Society for Microbial Ecology Source


Powell A.K.,University of Liverpool
Nature protocols | Year: 2010

Natural and semi-synthetic heparan sulfate (HS) saccharide libraries are a valuable resource for investigating HS structure-function relationships, enabling high-throughput glycomics studies. Owing to the difficulty of chemical or in vitro enzymatic synthesis of HS saccharides, the structural diversity displayed in saccharides from tissue or cell sources cannot be readily accessed. In contrast, saccharide libraries can be generated by partial digestion of tissue-derived HS polysaccharide chains and chromatographic fractionation of the resulting saccharide mixtures. Fractionation is initially on the basis of hydrodynamic volume, using size exclusion chromatography. Further fractionation, on the basis of charge using strong anion exchange, can subsequently be applied. Desalting and sample concentration follows each fractionation step. Chromatographic fractions are generated that contain purified, or partially purified, saccharides. Here we describe a comprehensive protocol for generation of structurally diverse natural saccharide libraries from HS variants that is fast (approximately 3 weeks) and reproducible. Source


Doyle T.,University College London | Geretti A.M.,University College London | Geretti A.M.,University of Liverpool
Current Opinion in Infectious Diseases | Year: 2012

PURPOSE OF REVIEW: The source, significance and optimal management of low-level viraemia during highly active antiretroviral therapy (HAART) are poorly defined. This review highlights recent observations that have implications for clinical practice. RECENT FINDINGS: The definition of low-level viraemia remains elusive. Whereas evidence obtained with second-generation viral load assays indicates that confirmed detection of plasma HIV-1 RNA above 50=copies/ml predicts negative outcomes, third-generation assays detect HIV-1 RNA below this threshold. In patients monitored with the Abbott RealTime assay, the cutoff that should trigger confirmation of viraemia and clinical review can be revised to 40=copies/ml. Further data are needed on the cost-effectiveness of intervening when RNA detection is observed below this cutoff. Discrepancies among viral load assays prevent generalization of these observations. To further compound the issue, most patients on stably suppressive HAART show residual viraemia at around 1-10=copies/ml using research-based ultrasensitive assays. The source of residual viraemia remains controversial, but neither short nor long-term HAART intensification with antiretrovirals such as raltegravir reduces the viraemia. A transient effect of intravenous immunoglobulin has been reported, and different regimens may vary in their propensity to allow HIV-1 RNA persistence. Further studies are required to clarify the relationship between low-level viraemia and the size of proviral DNA reservoirs, and the contribution of cellular and tissue compartments and cell-to-cell spread to ongoing virus replication during HAART. SUMMARY: Understanding the source and clinical significance of HIV-1 RNA persistence in plasma during HAART is required to guide patient care and inform the design of HIV eradication strategies. Copyright © Lippincott Williams & Wilkins. Source


Alfirevic Z.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: One of the main aims of routine antenatal care is to identify the 'at risk' fetus in order to apply clinical interventions which could result in reduced perinatal morbidity and mortality. Doppler ultrasound study of umbilical artery waveforms helps to identify the compromised fetus in 'high-risk' pregnancies and, therefore, deserves assessment as a screening test in 'low-risk' pregnancies. OBJECTIVES: To assess the effects on obstetric practice and pregnancy outcome of routine fetal and umbilical Doppler ultrasound in unselected and low-risk pregnancies. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (May 2010). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in unselected pregnancies compared to no Doppler ultrasound. Studies where uterine vessels have been assessed together with fetal and umbilical vessels have been included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. MAIN RESULTS: We included five trials involving 14,185 women. The methodological quality of the trials was generally unclear because of insufficient data included in the reports.Routine fetal and umbilical Doppler ultrasound examination in low-risk or unselected populations did not result in increased antenatal, obstetric and neonatal interventions, and no overall differences were detected for substantive short term clinical outcomes such as perinatal mortality. There is no available evidence to assess the effect on substantive long term outcomes such as childhood neurodevelopment and no data to assess maternal outcomes, particularly psychological effects. AUTHORS' CONCLUSIONS: Existing evidence does not provide conclusive evidence that the use of routine umbilical artery Doppler ultrasound, or combination of umbilical and uterine artery Doppler ultrasound in low-risk or unselected populations benefits either mother or baby. Future studies should be designed to address small changes in perinatal outcome, and should focus on potentially preventable deaths. Source


Dwan K.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2011

Publication of complete trial results is essential if people are to be able to make well-informed decisions about health care. Selective reporting of randomised controlled trials (RCTs) is a common problem. To systematically review studies of cohorts of RCTs to compare the content of trial reports with the information contained in their protocols, or entries in a trial registry. We conducted electronic searches in Ovid MEDLINE (1950 to August 2010); Ovid EMBASE (1980 to August 2010); ISI Web of Science (1900 to August 2010) and the Cochrane Methodology Register (Issue 3, 2010), checked reference lists, and asked authors of eligible studies to identify further studies. Studies were not excluded based on language of publication or our assessment of their quality. Published or unpublished cohort studies comparing the content of protocols or trial registry entries with published trial reports. Data were extracted by two authors independently. Risk of bias in the cohort studies was assessed in relation to follow up and selective reporting of outcomes. Results are presented separately for the comparison of published reports to protocols and trial registry entries. We included 16 studies assessing a median of 54 RCTs (range: 2 to 362). Twelve studies compared protocols to published reports and four compared trial registry entries to published reports. In two studies, eligibility criteria differed between the protocol and publication in 19% and 100% RCTs. In one study, 16% (9/58) of the reports included the same sample size calculation as the protocol. In one study, 6% (4/63) of protocol-report pairs gave conflicting information regarding the method of allocation concealment, and 67% (49/73) of blinded studies reported discrepant information on who was blinded. In one study unacknowledged discrepancies were found for methods of handling protocol deviations (44%; 19/43), missing data (80%; 39/49), primary outcome analyses (60%; 25/42) and adjusted analyses (82%; 23/28). One study found that of 13 protocols specifying subgroup analyses, 12 of these 13 trials reported only some, or none, of these. Two studies found that statistically significant outcomes had a higher odds of being fully reported compared to nonsignificant outcomes (range of odds ratios: 2.4 to 4.7). Across the studies, at least one primary outcome was changed, introduced, or omitted in 4-50% of trial reports. Discrepancies between protocols or trial registry entries and trial reports were common, although reasons for these were not discussed in the reports. Full transparency will be possible only when protocols are made publicly available or the quality and extent of information included in trial registries is improved, and trialists explain substantial changes in their reports. Source


Ford E.S.,Centers for Disease Control and Prevention | Capewell S.,University of Liverpool
Annual Review of Public Health | Year: 2011

Mortality rates from coronary heart disease (CHD), which had risen during the twentieth century in many countries, started declining in some countries during the 1960s. Once initial skepticism about the validity of the observed trends dissipated, researchers attempted to generate explanations about the events that had transpired using a variety of techniques, including ecological examinations of the trends in risk factors for CHD and changes in management of CHD, multivariate risk equations, and increasingly sophisticated modeling techniques. Improvements in risk factors as well as changes in cardiac treatments have both contributed to the reductions in CHD mortality, although estimates of their contributions have varied among countries. Models suggest that additional large reductions in CHD mortality are feasible by either improving the distribution of risk factors in the population or raising the percentage of patients receiving evidence-based treatments. © 2011 by Annual Reviews. rights reserved. Source


Biktasheva I.V.,University of Liverpool | Dierckx H.,Ghent University | Biktashev V.N.,University of Exeter
Physical Review Letters | Year: 2015

A scroll wave in a very thin layer of excitable medium is similar to a spiral wave, but its behavior is affected by the layer geometry. We identify the effect of sharp variations of the layer thickness, which is separate from filament tension and curvature-induced drifts described earlier. We outline a two-step asymptotic theory describing this effect, including asymptotics in the layer thickness and calculation of the drift of so-perturbed spiral waves using response functions. As specific examples, we consider drift of scrolls along thickness steps, ridges, ditches, and disk-shaped thickness variations. Asymptotic predictions agree with numerical simulations. © 2015 American Physical Society. Source


Arendrup M.C.,Statens Serum Institute | Cuenca-Estrella M.,Institute Salud Carlos III | Lass-Florl C.,Innsbruck Medical University | Hope W.W.,University of Liverpool
Drug Resistance Updates | Year: 2013

Candida and Aspergillus infections have emerged as significant pathogens in recent decades. During this same time, broad spectrum triazole and echinocandin antifungal agents have been developed and increasingly used. One consequence of widespread use is leading to the emergence of mutants with acquired resistance mutations. Therefore, accurate susceptibility testing and appropriate clinical breakpoints for the interpretation of susceptibility results have become increasingly important. Here we review the underlying methodology by which breakpoints have been selected by EUCAST (European Committee on Antimicrobial Susceptibility Testing). Five parameters are evaluated: dosing regimens used; EUCAST MIC distributions from multiple laboratories, species and compound specific epidemiological cut off values (upper MIC limits of wild type isolates or ECOFFs), pharmacokinetic/pharmacodynamic relationships and targets associated with outcome and finally clinical data by species and MIC when available. The general principles are reviewed followed by a detailed review of the individual aspects for Candida species and the three echinocandins and for Aspergillus and the three mould-active azoles. This review provides an update of the subcommittee on antifungal susceptibility testing (AFST) of the EUCAST methodology and summarises the current EUCAST breakpoints for Candida and Aspergillus. Recommendations about applicability of antifungal susceptibility testing in the routine setting are also included. © 2014 Elsevier Ltd. Source


Greer I.A.,University of Liverpool
Journal of Thrombosis and Haemostasis | Year: 2011

Background: Recurrent pregnancy loss (RPL) is a major issue for women's health. Acquired and heritable thrombophilias are associated with RPL, this association could reflect a general prothrombotic phenotype rather than a specific thrombophilia. Antithrombotic intervention has therefore been assessed for RPL. Results: Two large randomised trials with untreated control groups showed no benefit from antithrombotic treatment with LMWH and low dose aspirin in women with RPL. These trials had insufficient power to exclude an effect in women with underlying thrombophilia, ≥3 losses, or late losses. Conclusions: Antithrombotic intervention should not be recommended for unexplained RPL in general. There may be specific groups such as those with an heritable thrombophilia, or with three or more losses, or second trimester losses that might benefit and where further trials are required. Further there is a need to consider the benefits of LMWH on implantation such as in women undergoing assisted conception therapy. © 2011 International Society on Thrombosis and Haemostasis. Source


Uetrecht J.,University of Toronto | Naisbitt D.J.,University of Liverpool
Pharmacological Reviews | Year: 2013

Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. The major targets are skin, liver, and bone marrow. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. However, rigorous mechanistic studies are very difficult to perform, especially in the absence of valid animal models. Models to explain how drugs or reactive metabolites interact with the MHC/T-cell receptor complex include the hapten and P-I models, and most recently it was found that abacavir can interact reversibly with MHC to alter the endogenous peptides that are presented to T cells. The discovery of HLA molecules as important risk factors for some IDRs has also significantly contributed to our understanding of these adverse reactions, but it is not yet clear what fraction of IDRs have a strong HLA dependence. In addition, with the exception of abacavir, most patients who have the HLA that confers a higher IDR risk with a specific drug will not have an IDR when treated with that drug. Interindividual differences in T-cell receptors and other factors also presumably play a role in determining which patients will have an IDR. The immune response represents a delicate balance, and immune tolerance may be the dominant response to a drug that can cause IDRs. © 2013 by The American Society for Pharmacology and Experimental Therapeutics. Source


Dockray G.J.,University of Liverpool
Journal of Physiology | Year: 2014

The landmark discovery by Bayliss and Starling in 1902 of the first hormone, secretin, emerged from earlier observations that a response (pancreatic secretion) following a stimulus (intestinal acidification) occurred after section of the relevant afferent nerve pathway. Nearly 80 years elapsed before it became clear that visceral afferent neurons could themselves also be targets for gut and other hormones. The action of gut hormones on vagal afferent neurons is now recognised to be an early step in controlling nutrient delivery to the intestine by regulating food intake and gastric emptying. Interest in these mechanisms has grown rapidly in view of the alarming global increase in obesity. Several of the gut hormones (cholecystokinin (CCK); peptide YY3-36 (PYY3-36); glucagon-like peptide-1 (GLP-1)) excite vagal afferent neurons to activate an ascending pathway leading to inhibition of food intake. Conversely others, e.g. ghrelin, that are released in the inter-digestive period, inhibit vagal afferent neurons leading to increased food intake. Nutrient status determines the neurochemical phenotype of vagal afferent neurons by regulating a switch between states that promote orexigenic or anorexigenic signalling through mechanisms mediated, at least partly, by CCK. Gut-brain signalling is also influenced by leptin, by gut inflammation and by shifts in the gut microbiota including those that occur in obesity. Moreover, there is emerging evidence that diet-induced obesity locks the phenotype of vagal afferent neurons in a state similar to that normally occurring during fasting. Vagal afferent neurons are therefore early integrators of peripheral signals underling homeostatic mechanisms controlling nutrient intake. They may also provide new targets in developing treatments for obesity and feeding disorders. © 2014 The Physiological Society. Source


Whiteford M.,University of Liverpool
Housing Studies | Year: 2013

This article offers a critical appraisal of the 'New Labour' governments' (1997-2010) much vaunted commitment to confronting and combating the spectre of visible rough sleeping and its associated street culture. It reviews the trajectory of policy initiatives and welfare practices concerned with engendering the social inclusion of homeless people. It subsequently interrogates attempts to shape the behaviour of people experiencing homelessness through the imposition of greater conditionality and invocation of an ethic of self-responsibility. It stresses the importance of considering the role of actively engaged local communities in governing homeless people and regulating homeless service providers. It does this using an ethnographic case study of homelessness and housing need in a small market town in the south-west of England. © 2013 Copyright Taylor and Francis Group, LLC. Source


Cook L.M.,University of Manchester | Saccheri I.J.,University of Liverpool
Heredity | Year: 2013

From the outset multiple causes have been suggested for changes in melanic gene frequency in the peppered moth Biston betularia and other industrial melanic moths. These have included higher intrinsic fitness of melanic forms and selective predation for camouflage. The possible existence and origin of heterozygote advantage has been debated. From the 1950s, as a result of experimental evidence, selective predation became the favoured explanation and is undoubtedly the major factor driving the frequency change. However, modelling and monitoring of declining melanic frequencies since the 1970s indicate either that migration rates are much higher than existing direct estimates suggested or else, or in addition, non-visual selection has a role. Recent molecular work on genetics has revealed that the melanic (carbonaria) allele had a single origin in Britain, and that the locus is orthologous to a major wing patterning locus in Heliconius butterflies. New methods of analysis should supply further information on the melanic system and on migration that will complete our understanding of this important example of rapid evolution. © 2013 Macmillan Publishers Limited All rights reserved. Source


Wilson R.,University of Liverpool
Expert Review of Proteomics | Year: 2013

A major ambition of proteomics is the provision of assays that can diagnose disease and monitor therapies. These assays are required to be sensitive and specific for individual proteins, and in most cases to quantify more than one protein in the same sample. The two main technologies currently used for proteomics assays are based on mass spectrometry and panels of affinity molecules such as antibodies. In the first part of this review the most sensitive existing assays based on these technologies are described and compared with the gold standard of ELISA. Analytical sensitivity is defined and related to the limit of detection, and analytical specificity is defined and shown to depend on molecular proofreading steps, similar to those applied in living systems whenever there is a need for high fidelity. It is shown that at present neither mass spectrometry nor panels of affinity molecules offer the necessary combination of sensitivity and specificity required for multiplexed assays. In the second part of this review the growing numbers of assays that use additional proofreading steps to combine sensitivity with specificity are described. These include assays based on proximity ligation and slow off-rate modified aptamers. Finally the review considers what improvements might be possible in the near future, and concludes that further development of proteomics assays incorporating advanced proofreading steps are most likely to provide the necessary combination of sensitivity and specificity, without incurring high development costs. © 2013 Expert Reviews Ltd. Source


Smith D.A.,University of Liverpool | Smith D.A.,University of Cape Town
Molecular Pharmaceutics | Year: 2013

The commentary describes progress in modeling and simulation in ADME science and focuses on lipoidal permeability as a central driver of drug molecule disposition. The tension between screening and in silico is outlined with practical suggestions on how to improve multiparameter models. The limitations on modeling drug metabolism and its enzymes are highlighted together with key features in molecules that lead to drug transport. Reservations about the quality of data and the imprecise classification of drug molecules are explained. Encouragement to move modeling and simulation to the forefront of project start-up is provided after examining the complexity of macromolecule-small molecule conjugate prodrugs. © 2013 American Chemical Society. Source


Jackson M.J.,University of Liverpool
Antioxidants and Redox Signaling | Year: 2013

Significance: Aging leads to a loss of skeletal muscle mass and function that causes instability, increased risk of falls, and need for residential care. This is due to a reduction in the muscle mass and strength that is primarily due caused by a decrease in the number of muscle fibers, particularly, type II fibers, and atrophy and weakening of those remaining. Recent Advances: Although increased oxidative damage was originally thought to be the key to the aging process, data now indicate that reactive oxygen species (ROS) may be one of the several components of the degenerative processes in aging. The skeletal muscle shows important rapid adaptations to the ROS generated by contractions that are attenuated in aged organisms and transgenic studies have indicated that overcoming these attenuated responses can prevent the age-related loss of muscle mass and function. Critical Issues: Elucidation of the mechanisms by which the skeletal muscle adapts to the ROS generated to contractions and the way in which these processes are attenuated by aging is critical to the development of logical approaches to prevent age-related loss of muscle mass and function. Future Directions: Future studies are likely to focus on the redox regulation of adaptive pathways and their maintenance during aging as an approach to maintain and improve muscle function. Antioxid. Redox Signal. 19, 804-812. © 2013, Mary Ann Liebert, Inc. Source


Yang H.,Feinstein Institute for Medical Research | Antoine D.J.,University of Liverpool | Andersson U.,Karolinska University Hospital | Tracey K.J.,Feinstein Institute for Medical Research
Journal of Leukocyte Biology | Year: 2013

HMGB1 is a ubiquitous nuclear protein present in almost all cell types. In addition to its intracellular functions, HMGB1 can be extracellularly released, where it mediates activation of innate immune responses, including chemotaxis and cytokine release. HMGB1 contains three conserved redox-sensitive cysteines (C23, C45, and C106); modification of these cysteines determines the bioactivity of extracellular HMGB1. Firstly, the cytokine-stimulating activity of HMGB1 requires C23 and C45 to be in a disulfide linkage, at the same time that C106 must remain in its reduced form as a thiol. This distinctive molecular conformation enables HMGB1 to bind and signal via the TLR4/MD-2 complex to induce cytokine release in macrophages. Secondly, for HMGB1 to act as a chemotactic mediator, all three cysteines must be in the reduced form. This all-thiol HMGB1 exerts its chemotactic activity to initiate inflammation by forming a heterocomplex with CXCL12; that complex binds exclusively to CXCR4 to initiate chemotaxis. Thirdly, binding of the HMGB1 to CXCR4 or to TLR4 is completely prevented by all-cysteine oxidation. Also, the initial post-translational redox modifications of HMGB1 are reversible processes, enabling HMGB1 to shift from acting as a chemotactic factor to acting as a cytokine and vice versa. Lastly, post-translational acetylation of key lysine residues within NLSs of HMGB1 affects HMGB1 to promote inflammation; hyperacetylation of HMGB1 shifts its equilibrium from a predominant nuclear location toward a cytosolic and subsequent extracellular presence. Hence, post-translational modifications of HMGB1 determine its role in inflammation and immunity. © Society for Leukocyte Biology. Source


Mitchell T.M.,Italian National Institute of Geophysics and Volcanology | Faulkner D.R.,University of Liverpool
Earth and Planetary Science Letters | Year: 2012

In nature, permeability is enhanced in the damage zone of faults in crystalline rocks, where fracturing occurs on a wide range of scales. Understanding this permeability structure is paramount for predicting crustal fluid flow. We combine quantitative field and laboratory measurements to predict microfracture damage zone permeability in low-porosity granitic rocks as a function of distance from the fault core and displacement. Microfracture controlled matrix permeability exerts an increasingly dominant role on fluid flow with increasing depth. In the field we analysed the scaling relationships of microfracture densities surrounding strike-slip faults developed in granodiorite within the Atacama fault system in northern Chile. Displacements ranging over 5 orders of magnitude (~0.012-5000. m), allow the variation of microfracture damage with increasing distance from faults to be determined empirically as a function of displacement. We reproduce microfracture damage in the laboratory in a suite of triaxial deformation experiments by inducing cyclic damage in initially intact samples while continuously measuring permeability. Combining field and laboratory datasets through the microfracture density allows the permeability profile with distance from the fault to be predicted from fault displacement. © 2012 Elsevier B.V.. Source


Bro-Jorgensen J.,University of Liverpool
PLoS ONE | Year: 2012

Selection on intrinsic lifespan depends on both external factors affecting mortality and inherent tradeoffs in resource allocation between viability traits and other fitness-related traits. Longevity is therefore likely to vary between species in a sex-specific manner due to interspecific and intersexual differences in behavioural ecology. Here I focus on the bovid family to test two central hypotheses on longevity selection using the comparative method: firstly, that a reduction of extrinsic mortality in social species strengthens selection on intrinsic lifespan, and secondly, that mortality costs associated with intense sexual selection lead to shorter intrinsic lifespan. The results show that longevity (i) increases with sociality in both sexes and (ii) decreases with male-biased sexual size-dimorphism, but in males only. These discoveries suggest that sociality, a key ungulate strategy to reduce predation-related mortality, selects for inherently longer-lived organisms, and that strong sexual selection, which is known to compromise survival rates in the wild, can constrain also intrinsic lifespan. The contrasting results for males and females indicate that selection on longevity in the two sexes is partly uncoupled. © 2012 Jakob Bro-Jørgensen. Source


Cooper A.I.,University of Liverpool
Angewandte Chemie - International Edition | Year: 2011

Molecular solids go porous: An imine-linked organic cage exhibits exceptional surface area (SABET=1375 m2ag-1) and selective gas sorption, suggesting that porous molecular organic solids could compete in the future with porous networks such as polymers and metal-organic frameworks. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Assa H.,University of Liverpool
Agricultural Finance Review | Year: 2016

Purpose – The purpose of this paper is twofold. First, the author proposes a financial engineering framework to model commodity prices based on market demand processes and demand functions. This framework explains the relation between demand, volatility and the leverage effect of commodities. It is also shown how the proposed framework can be used to price derivatives on commodity prices. Second, the author estimates the model parameters for agricultural commodities and discuss the implications of the results on derivative prices. In particular, the author see how leverage effect (or inverse leverage effect) is related to market demand. Design/methodology/approach – This paper uses a power demand function along with the Cox, Ingersoll and Ross mean-reverting process to find the price process of commodities. Then by using the Ito theorem the constant elastic volatility (CEV) model is derived for the market prices. The partial differential equation that the dynamics of derivative prices satisfy is found and, by the Feynman-Kac theorem, the market derivative prices are provided within a Monte-Carlo simulation framework. Finally, by using a maximum likelihood estimator, the parameters of the CEV model for the agricultural commodity prices are found. Findings – The results of this paper show that derivative prices on commodities are heavily affected by the elasticity of volatility and, consequently, by market demand elasticity. The empirical results show that different groups of agricultural commodities have different values of demand and volatility elasticity. Practical implications – The results of this paper can be used by practitioners to price derivatives on commodity prices and by insurance companies to better price insurance contracts. As in many countries agricultural insurances are subsidised by the government, the results of this paper are useful for setting more efficient policies. Originality/value – Approaches that use the methodology of financial engineering to model agricultural prices and compute the derivative prices are rather new within the literature and still need to be developed for further applications. © 2016, © Emerald Group Publishing Limited. Source


Bagust A.,University of Liverpool
Health and Quality of Life Outcomes | Year: 2013

Background: The original valuation exercise which formed the basis of the UK EQ-5D time trade-off social tariff of health states, employed a sampling scheme involving 43 health states. Neither that study, nor other published international valuations studies have used explicit quantifiable criteria to justify the choice of sampled states. New criteria are proposed and methods described to aid researchers in designing improved sampling schemes for future EQ-5D sampling exercises.Method: Four such criteria are described, and applied to assess the merits of four sampling schemes previously reported, using three large observational databases to quantify relative performance. An alternative sampling design conforming to these criteria is described, which aims to generate improved performance.Results: Previous published approaches are shown to perform poorly against the measured criteria. The alternative sampling design is demonstrated to provide superior performance on all measures.Conclusion: Future valuation exercises using sampled health states based on this approach may be expected to offer benefits in terms of greater precision, avoidance of bias in favour of less severe states, and a higher proportion of research observations valued directly rather than dependent on extrapolation modelling. © 2013 Bagust; licensee BioMed Central Ltd. Source


Whittington R.,University of Liverpool
International Journal of Law and Psychiatry | Year: 2013

Background: Psychiatry is characterised by bio-psycho-social approaches and therapies. Thus there should be an interest in comprehensive theoretical models for didactic purposes. Methods: A narrative synthesis of key themes in the current literature on psychiatric aspects of violence was conducted with the aim of integrating biological, psychological and sociological ideas in this area. Results: Two didactical models are proposed for 1) individual disposition and for 2) acting in specific situations, each including available evidence-based knowledge. Conclusions: The proposed models may be helpful for a comprehensive understanding of all relevant influencing factors in violent mentally ill people and for didactical purposes. © 2013 Elsevier Ltd. Source


Vora J.,University of Liverpool
Diabetes Care | Year: 2013

In conclusion, combining incretin-based therapies with basal insulin provides complementary actions, lowering both PPG and FPG, to improve glycemic control in type 2 diabetes. Theoretically, incretin-based therapies are an alternative to bolus insulin for certain groups of patients, such as the elderly, where meeting A1C targets must be balanced against the risk of hypoglycemia; however, studies evaluating any potential benefit in the elderly have not been conducted. Additionally, the weight-sparing effect of GLP-1RAs makes them well suited for use in patients with concerns about insulininduced weight gain. The improvements in glycemic control may reduce the incidence of diabetes-related complications, and taken together with the reduced risk of hypoglycemia, an incretin plus basal insulin regimen could provide significant health-economic advantages. Further research is needed to establish the longterm benefits of insulin plus incretin therapy. © 2013 by the American Diabetes Association. Source


Zhou J.G.,University of Liverpool
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2010

A set of rectangular lattice Boltzmann methods for fluid flows is developed. It is shown that reformulating local equilibrium distribution functions can result in the rectangular lattice Boltzmann models without the aid of an interpolation for shallow water equations, Navier-Stokes equations, and axisymmetric flow equations. In addition, schemes for correct incorporation of force terms into the models are proposed for simulations of flows involving forces in practice. The methods completely retain the innate kinetic features and the simple procedure of the standard lattice Boltzmann method with an additional benefit of being suitable for rectangular lattices at little extra computational cost. The methodology is illustrated and validated through its application to different flow problems, demonstrating the potential power of the models. © 2010 The American Physical Society. Source


Neilson J.P.,University of Liverpool
The Cochrane database of systematic reviews | Year: 2013

Miscarriage occurs in 10% to 15% of pregnancies. The traditional treatment, after miscarriage, has been to perform surgery to remove any remaining placental tissues in the uterus ('evacuation of uterus'). However, medical treatments, or expectant care (no treatment), may also be effective, safe and acceptable. To assess the effectiveness, safety and acceptability of any medical treatment for incomplete miscarriage (before 24 weeks). We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2012) and reference lists of retrieved papers. Randomised controlled trials comparing medical treatment with expectant care or surgery or alternative methods of medical treatment. Quasi-randomised trials were excluded. Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked. Twenty studies (4208 women) were included. There were no trials specifically of miscarriage treatment after 13 weeks' gestation.Three trials involving 335 women compared misoprostol treatment (all vaginally administered) with expectant care. There was no statistically significant difference in complete miscarriage (average risk ratio (RR) 1.23, 95% confidence interval (CI) 0.72 to 2.10; two studies, 150 women, random-effects), or in the need for surgical evacuation (average RR 0.62, 95% CI 0.17 to 2.26; two studies, 308 women, random-effects). There were few data on 'deaths or serious complications'.Twelve studies involving 2894 women addressed the comparison of misoprostol (six studies used oral administration, four studies used vaginal, one study sub-lingual, one study combined vaginal + oral) with surgical evacuation. There was a slightly lower incidence of complete miscarriage with misoprostol (average RR 0.97, 95% CI 0.95 to 0.99, 11 studies, 2493 women, random-effects) but with success rate high for both methods. Overall, there were fewer surgical evacuations with misoprostol (average RR 0.06, 95% CI 0.02 to 0.13; 11 studies, 2654 women, random-effects) but more unplanned procedures (average RR 5.82, 95% CI 2.93 to 11.56; nine studies, 2274 women, random-effects). There were few data on 'deaths or serious complications'. Nausea was more common with misoprostol (average RR 2.41, 95% CI 1.44 to 4.03; nine studies, 2179 women, random-effects).Five trials compared different routes of administration and/or doses of misoprostol. There was no clear evidence of one regimen being superior to another. Limited evidence suggests that women generally seem satisfied with their care. Long-term follow-up from one included study identified no difference in subsequent fertility between the three approaches. The available evidence suggests that medical treatment, with misoprostol, and expectant care are both acceptable alternatives to routine surgical evacuation given the availability of health service resources to support all three approaches. Women experiencing miscarriage at less than 13 weeks should be offered an informed choice. Future studies should include long-term follow-up. Source


North P.,University of Liverpool
Environment and Planning A | Year: 2011

This paper uses social movement theory (SMT) as a theoretical 'gymnasium' to explore the limits and possibilities of climate activism in the UK. The core SMT concepts are used to explore why climate activism emerged when it did, and how conceptions of there being a problem were translated into arguments about what should be done. If something should be done, is contentious politics or policy change the most appropriate strategy? At what scale should action take place: a local politics of prefiguration, through direct action, or in more visible mass mobilisations? It is argued that climate activism takes place in a diverse range of political spaces and scales and works actively to produce knowledges about the dangers of anthropogenic climate change and responsibilities for it, but it is unclear that it has the motive power to move to more sustainable ways of organising human society. © 2011 Pion Ltd and its Licensors. Source


During recent years, a rapid expansion in large-scale mining activity has generated a host of protests in Peru, as rural populations have attempted to defend their livelihood and environment. This article examines the genesis and trajectory of one such mobilization that emerged in the province of San Marcos and neighbouring Condebamba Valley, located in the northern Andean department of Cajamarca. The social movement's internal organization, strategy, tactics and repertoires of struggle are analyzed. Practices inherited from the rondas campesinas (nightwatch patrols) are seen to have exercised an important influence in shaping its modus operandi, which contrasts in key respects with the behaviour of other anti-mining protests in Peru, such as Majaz. The article concludes with an assessment of how shifting power relations within the state might influence the chances of successful collective action in the countryside. © 2011 Blackwell Publishing Ltd. Source


Background: Some important research questions in medical education and health services research need 'mixed methods research' (particularly synthesizing quantitative and qualitative findings). The approach is not new, but should be more explicitly reported. Aim: The broad search question here, of a disjointed literature, was thus: What is mixed methods research - how should it relate to medical education research?, focused on explicit acknowledgement of 'mixing'. Methods: Literature searching focused on Web of Knowledge supplemented by other databases across disciplines. Findings: Five main messages emerged: - Thinking quantitative and qualitative, not quantitative versus qualitative - Appreciating that mixed methods research blends different knowledge claims, enquiry strategies, and methods - Using a 'horses for courses' [whatever works] approach to the question, and clarifying the mix - Appreciating how medical education research competes with the 'evidence-based' movement, health services research, and the 'RCT' - Being more explicit about the role of mixed methods in medical education research, and the required expertise Conclusion: Mixed methods research is valuable, yet the literature relevant to medical education is fragmented and poorly indexed. The required time, effort, expertise, and techniques deserve better recognition. More write-ups should explicitly discuss the 'mixing' (particularly of findings), rather than report separate components. © 2011 Informa UK Ltd All rights reserved. Source


Gowlett J.A.J.,University of Liverpool
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2016

Numbers of animal species react to the natural phenomenon of fire, but only humans have learnt to control it and to make it at will. Natural fires caused overwhelmingly by lightning are highly evident on many landscapes. Birds such as hawks, and some other predators, are alert to opportunities to catch animals including invertebrates disturbed by such fires and similar benefits are likely to underlie the first human involvements with fires. Early hominins would undoubtedly have been aware of such fires, as are savanna chimpanzees in the present. Rather than as an event, the discovery of fire use may be seen as a set of processes happening over the long term. Eventually, fire became embedded in human behaviour, so that it is involved in almost all advanced technologies. Fire has also influenced human biology, assisting in providing the high-quality diet which has fuelled the increase in brain size through the Pleistocene. Direct evidence of early fire in archaeology remains rare, but from 1.5 Ma onward surprising numbers of sites preserve some evidence of burnt material. By the Middle Pleistocene, recognizable hearths demonstrate a social and economic focus on many sites. The evidence of archaeological sites has to be evaluated against postulates of biological models such as the ‘cooking hypothesis’ or the ‘social brain’, and questions of social cooperation and the origins of language. Although much remains to be worked out, it is plain that fire control has had a major impact in the course of human evolution. © 2016 The Authors. Source


Cook I.R.,University of Liverpool | Ward K.,University of Manchester
Urban Studies | Year: 2011

This paper argues for a rethinking of our understanding of what and where go into the 'urban' in the New Urban Politics (NUP). It contends that these issues have always been more complex, complicated and, most importantly, contested than has sometimes appeared to be the case in the literature. Using the example of one trans-urban policy learning network-that around the city of Manchester's bids for the Olympic and Commonwealth Games-the paper makes the case for taking seriously the politics around comparison and referencing in making possible the NUP. It argues that there is a need to study the circuits, networks and webs in and through which urban knowledge and learning are constituted and moved around, and that often underpin the territorial outcomes that have been the traditional focus of scholars working on the NUP.© 2011 Urban Studies Journal Limited. Source


Kaye S.B.,University of Liverpool
Journal of Cataract and Refractive Surgery | Year: 2010

Purpose: To provide a method to allow calculation of the average focal length and power of a lens through a specified meridian of any defined surface, not limited to the paraxial approximations. Setting: University of Liverpool, Liverpool, United Kingdom. Method: Functions were derived to model back-vertex focal length and representative power through a meridian containing any defined surface. Average back-vertex focal length was based on the definition of the average of a function, using the angle of incidence as an independent variable. Results: Univariate functions allowed determination of average focal length and power through a section of any defined or topographically measured surface of a known refractive index. These functions incorporated aberrations confined to the section. Conclusions: The proposed method closely approximates the average focal length, and by inference power, of a section (meridian) of a surface to a single or scalar value. It is not dependent on the paraxial and other nonconstant approximations and includes aberrations confined to that meridian. A generalization of this method to include all orthogonal and oblique meridians is needed before a comparison with measured wavefront values can be made. Financial Disclosure: The author has a no financial or proprietary interest in any material or method mentioned. © 2010 ASCRS and ESCRS. Source


Posas P.J.,University of Liverpool
Environmental Impact Assessment Review | Year: 2011

The Protocol on Strategic Environmental Assessment (SEA) to the United Nations Economic Commission for Europe (UNECE) Espoo Convention came into force on 11 July 2010. This Protocol, to which the European Union is party, gives a legal basis for enhanced attention to human health in the SEA process. In this context, the United Kingdom's (UK's) 2007 Draft Guidance on Health in Strategic Environmental Assessment represents an important early government-led effort to bring health issues and public health considerations more significantly into the SEA process. Since the UK is a worldwide leader in environmental and various other types of impact assessment, and since other countries may eventually consider its example in efforts to meet UNECE SEA Protocol requirements, scrutiny of its outputs is warranted. This paper thus examines the UK's Draft Guidance from both HIA academic and practitioner perspectives. First it assesses the extent to which the Draft Guidance reflects recent issues and lessons learned in the academic literature. In order to make the assessment, a meta-analysis of 70 HIA-related peer-reviewed articles was undertaken to extract authors' priority recommendations. These recommendations were subsequently compared with the contents of the Draft Guidance. Secondly, the Draft Guidance was assessed for its accordance with recommendations of the UNECE SEA Protocol background paper written by two HIA practitioners. Overall, the Draft Guidance's accordance with both sets of recommendations was found to be high, with only a few easily-remedied gaps. This evaluation suggests that the UK's Draft Guidance can be a useful starting point in the creation of future guidance on health in SEA in both the UK and other countries. © 2011 Elsevier Inc. Source


Gavin N.T.,University of Liverpool | Marshall T.,Aberystwyth University
Global Environmental Change | Year: 2011

Copenhagen 2009 was a major moment in the development of climate change as an issue. But climate sceptics before and during this event, sought to influence the nature of debate, and for this reason, the way Copenhagen was covered in the mass media was particularly important. This paper outlines the contours of contrarian arguments and claims, and assesses their reflection in the coverage at Copenhagen. The focus is on television, and extends to the assessment of internet - both modes of mass communication underrepresented in the existing literature. The results suggest a higher profile for contrarians and scepticism than is perhaps healthy, and speak to the role of these mass media, now and in the future, particularly with regard to the issue of public comprehension of the issues involved. © 2011. Source


Gowlett J.A.J.,University of Liverpool
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2015

Percussion makes a vital link between the activities of early human ancestors and other animals in tool-use and tool-making. Far more of the early human actions are preserved as archaeology, since the percussion was largely used for making hard tools of stone, rather than for direct access to food. Both primate tools and early hominin tools, however, offer a means to exploring variability in material culture, a strong focus of interest in recent primate studies. This paper charts such variability in the Acheulean, the longestlasting tool tradition, extant form about 1.7 to about 0.1 Ma, and well known for its characteristic handaxes. The paper concentrates on the African record, although the Acheulean was also known in Europe and Asia. It uses principal components and discriminant analysis to examine the measurements from 66 assemblages (whole toolkits), and from 18 sets of handaxes. Its review of evidence confirms that there is deep-seated pattern in the variation, with variability within a site complex often matching or exceeding that between sites far distant in space and time. Current techniques of study allow comparisons of handaxes far more easily than for other components, stressing a need to develop common practice in measurement and analysis. The data suggest, however, that a higher proportion of traits recurs widely in Acheulean toolkits than in the chimpanzee record. © 2015 The Author(s) Published by the Royal Society. All rights reserved. Source


The heparan sulfate (HS) chains of proteoglycans are a key regulatory component of the extracellular matrices of animal cells, including the pericellular matrix around the plasma membrane. In these matrices they regulate transport, gradient formation, and effector functions of over 400 proteins central to cell communication. HS from different matrices differs in its selectivity for its protein partners. However, there has been no direct test of how HS in the matrix regulates the transport of its partner proteins. We address this issue by single molecule imaging and tracking in fibroblast pericellular matrix of fibroblast growth factor 2 (FGF2), stoichiometrically labelled with small gold nanoparticles. Transmission electron microscopy and photothermal heterodyne imaging (PHI) show that the spatial distribution of the HS-binding sites for FGF2 in the pericellular matrix is heterogeneous over length scales ranging from 22 nm to several μm. Tracking of individual FGF2 by PHI in the pericellular matrix of living cells demonstrates that they undergo five distinct types of motion. They spend much of their time in confined motion (∼110 nm diameter), but they are not trapped and can escape by simple diffusion, which may be slow, fast, or directed. These substantial translocations (μm) cover distances far greater than the length of a single HS chain. Similar molecular motion persists in fixed cells, where the movement of membrane PGs is impeded. We conclude that FGF2 moves within the pericellular matrix by translocating from one HS-binding site to another. The binding sites on HS chains form non-random, heterogeneous networks. These promote FGF2 confinement or substantial translocation depending on their spatial organisation. We propose that this spatial organisation, coupled to the relative selectivity and the availability of HS-binding sites, determines the transport of FGF2 in matrices. Similar mechanisms are likely to underpin the movement of many other HS-binding effectors. Source


Forster J.,Queen Mary, University of London | Hirst A.G.,Queen Mary, University of London | Atkinson D.,University of Liverpool
Proceedings of the National Academy of Sciences of the United States of America | Year: 2012

Most ectothermic organisms mature at smaller body sizes when reared in warmer conditions. This phenotypically plastic response, known as the "temperature-size rule" (TSR), is one of the most taxonomically widespread patterns in biology. However, the TSR remains a longstanding life-history puzzle for which no dominant driver has been found. We propose that oxygen supply plays a central role in explaining the magnitude of ectothermic temperature-size responses. Given themuch lower oxygen availability and greater effort required to increase uptake in water vs. air, we predict that the TSR in aquatic organisms, especially larger species with lower surface area-body mass ratios, will be stronger than in terrestrial organisms. We performed ameta-analysis of 1,890 body mass responses to temperature in controlled experiments on 169 terrestrial, freshwater, and marine species. This reveals that the strength of the temperature-size response is greater in aquatic than terrestrial species. In animal species of ∼100 mg dry mass, thetemperature-size response of aquatic organisms is 10 times greater than in terrestrial organisms (-5.0% °C-1 vs. -0.5% °C-1). Moreover, although the size response of small (<0.1mg drymass) aquatic and terrestrial species is similar, increases in species size cause the response to become increasingly negative in aquatic species, as predicted, but on average less negative in terrestrial species. These results support oxygen as a major driver of temperaturesize responses in aquatic organisms. Further, the environment-dependent differences parallel latitudinal body size clines, and will influence predicted impacts of climate warming on food production, community structure, and food-web dynamics. Source


China provides a unique social-economic and political context for urban conservation and regeneration within the current trend of modernisation and globalisation. This paper investigates 4 urban regeneration projects conducted in four most internationalised historical Chinese cities from 1989 to 2005, in order to understand how traditional architectural elements are manipulated in these projects. It also examines the roles local governments, developers, designers and local residents played in these projects in the intensification process of the market oriented economy over time. The paper argues that socio-cultural sustainable regeneration of historical urban environments must make places for local people, rather than preserve certain traditional forms as cultural symbols. Tradition must evolve by the collective and traditional forms must be widely used in architectural and urban design with community involvement, in order to achieve real cultural identity and social cohesion. © 2010 Elsevier Ltd. Source


Thachil J.,University of Liverpool
European Journal of Internal Medicine | Year: 2010

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by heparin administration. It is caused by the formation of pathogenic antibodies to complexes of platelet factor-4 (PF4) and heparin on platelet surfaces that cause platelet activation, aggregation and thrombosis. There has been intense research on this intriguing, drug-related thrombocytopenia explaining several characteristic aspects of this condition. However, prothrombotic potential of the key player, PF4 has not been investigated in many studies although it has been shown to be critical in monocyte chemotaxis, monocyte-platelet interaction, and megakaryocyte suppression, all of which can contribute to the pathophysiology of HIT. This article explains the important role of PF4 released during platelet activation with the administration of heparin in the pathogenesis of thrombocytopenia and thrombosis in HIT. © 2009 Elsevier B.V. All rights reserved. Source


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

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


Gracey J.A.,University of Liverpool
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We renormalize six-dimensional φ3 theory in the modified minimal subtraction (MS¯) scheme at four loops. From the resulting β-function, anomalous dimension, and mass anomalous dimension, we compute four loop critical exponents relevant to the Lee-Yang edge singularity and percolation problems. Using resummation methods and information on the exponents of the relevant two-dimensional conformal field theory, we obtain estimates for exponents in dimensions 3, 4, and 5 which are in reasonable agreement with other techniques for these two problems. The renormalization group functions for the more general theory with an O(N) symmetry are also computed in order to obtain estimates of exponents at various fixed points in five dimensions. Included in this O(N) analysis is the full evaluation of the mass operator mixing matrix of anomalous dimensions at four loops. We show that its eigenexponents are in agreement with the mass exponents computed at O(1/N2) in the nonperturbative large N expansion. © 2015 American Physical Society. Source


Kemp G.J.,University of Liverpool | Brindle K.M.,University of Cambridge
Diabetes | Year: 2012

Magnetic resonance spectroscopy (MRS) methods offer a potentially valuable window into cellular metabolism. Measurement of flux between inorganic phosphate (Pi) and ATP using 31P MRS magnetization transfer has been used in resting muscle to assess what is claimed to be mitochondrial ATP synthesis and has been particularly popular in the study of insulin effects and insulin resistance. However, the measured Pi→ATP flux in resting skeletal muscle is far higher than the true rate of oxidative ATP synthesis, being dominated by a glycolytically mediated Pi↔ATP exchange reaction that is unrelated to mitochondrial function. Furthermore, even if measured accurately, the ATP production rate in resting muscle has no simple relationship to mitochondrial capacity as measured either ex vivo or in vivo. We summarize the published measurements of Pi→ATP flux, concentrating on work relevant to diabetes and insulin, relate it to current understanding of the physiology of mitochondrial ATP synthesis and glycolytic Pi↔ATP exchange, and discuss some possible implications of recently reported correlations between Pi→ATP flux and other physiological measures. © 2012 by the American Diabetes Association. Source


Watson A.J.M.,University of East Anglia | Collins P.D.,University of Liverpool
Digestive Diseases | Year: 2011

Colorectal cancer arises in individuals with acquired or inherited genetic predisposition who are exposed to a range of risk factors. Many of these risk factors are associated with affluent Western societies. More than 95% of colorectal cancers are sporadic, arising in individuals without a significant hereditary risk. Geographic variation in the incidence of colorectal cancer is considerable with a higher incidence observed in the West. Environmental factors contribute substantially to this variation. A number of these risk factors are associated with a Western lifestyle and could be considered a product of 'civilization'. Recently, smoking has been recognized as a risk factor. Energy consumption also influences colorectal cancer risk, with obesity increasing risk and exercise reducing risk. However, the strongest contribution to environmental risk for colorectal cancer is dietary. Consumption of fat, alcohol and red meat is associated with an increased risk. Fresh fruit and vegetables and dietary fibre may be protective. Much has been learnt recently about the molecular pathogenesis of colorectal cancer. Colorectal cancer always arises in the context of genomic instability. There is inactivation of the tumour suppressor genes adenomatous polyposis coli, p53, transforming growth factor-β, activation of oncogene pathways including K-ras, and activation of the cyclooxygenase-2, epidermal growth factor receptor and vascular endothelial growth factor pathways. The mechanisms by which some environmental factors modify the mutation risk in these pathways have been described. Copyright © 2011 S. Karger AG, Basel. Source


Bray G.A.,Pennington Biomedical Research Center | Fruhbeck G.,University of Navarra | Ryan D.H.,Pennington Biomedical Research Center | Wilding J.P.H.,University of Liverpool
The Lancet | Year: 2016

A modern approach to obesity acknowledges the multifactorial determinants of weight gain and the health benefits to be derived from weight loss. Foundational to any weight loss effort is lifestyle change, diet, and increased physical activity. The approach should be a high quality diet to which patients will adhere accompanied by an exercise prescription describing frequency, intensity, type, and time with a minimum of 150 min moderate weekly activity. For patients who struggle with weight loss and who would receive health benefit from weight loss, management of medications that are contributing to weight gain and use of approved medications for chronic weight management along with lifestyle changes are appropriate. Medications approved in the USA or European Union are orlistat, naltrexone/bupropion, and liraglutide; in the USA, lorcaserin and phentermine/topiramate are also available. Surgical management (gastric banding, sleeve gastrectomy, and Roux-en Y gastric bypass) can produce remarkable health improvement and reduce mortality for patients with severe obesity. © 2016 Elsevier Ltd. Source


Marine Spatial Planning (MSP) is emerging as key tool in the delivery of more effective sea use management and the integration ambitions of MSP are central to its rise to prominence. This paper reviews three key strands of thinking (integrated coastal and ocean management; integrated water resource management; and terrestrial spatial planning) that are informing the development of MSP and sets out a framework encompassing different dimensions of integration that those engaged in MSP might find it helpful to consider. The paper then explores how this framework can inform MSP development and related activity by using it to structure reflections on experience in the Irish Sea. Here the paper draws upon the outputs of a project that was funded by the UK's Economic and Social Research Council concerning Transnational Partnership Working in Support of Marine Spatial Planning in the Irish Sea. The analysis highlights the integration strengths and weaknesses associated with the emerging MSP structures in the Irish Sea and areas where further attention may be beneficial. The paper concludes by reflecting upon the value of the integration framework proposed, how it could be developed, and on key issues that those engaged in MSP in other contexts might need to address in rising to the integration ambitions of MSP. © 2012 Elsevier Ltd. Source


Morrissey K.,University of Liverpool | O'Donoghue C.,Teagasc
Marine Policy | Year: 2013

Recent research in Ireland has estimated both the national and regional economic value of the marine sector. However, economic activity does not exist in a vacuum. Activities in the marine sector not only directly affect the industries in the sector but also influence other sectors through inter-sectoral linkages. This paper uses an input-output (IO) methodology to examine the linkages and production effects of the Irish marine sector on the national economy. Disaggregating the Irish IO table for 2007 to include 10 additional marine sectors, this paper represents the first effort to quantify the inter-industry linkage effects, production-inducing effects and employment multipliers in the marine sector. This analysis found that a number of marine sectors, notably the maritime transportation sector, have an important economic role within the wider Irish economy. © 2012 Elsevier Ltd. Source


Weindling A.M.,University of Liverpool
Seminars in Fetal and Neonatal Medicine | Year: 2010

The mechanisms for the adequate provision of oxygen to the peripheral tissues are complex. They involve control of the microcirculation and peripheral blood flow, the position of the oxygen dissociation curve including the proportion of fetal and adult haemoglobin, blood gases and viscosity. Systemic blood pressure appears to have little effect, at least in the non-shocked state. The adequate delivery of oxygen (DO2) depends on consumption (VO2), which is variable. The balance between VO2 and DO2 is given by fractional oxygen extraction (FOE=VO2/DO2). FOE varies from organ to organ and with levels of activity. Measurements of FOE for the whole body produce a range of about 0.15-0.33, i.e. the body consumes 15-33% of oxygen transported. © 2010 Elsevier Ltd. Source


The Protopangaea-Palaeopangaea model for the Precambrian continental crust predicts quasi-integrity reflecting a dominant Lid Tectonics defined by a palaeomagnetic record showing prolonged near-static polar behaviour during very long time intervals (~2.7-2.2, 1.5-1.2, and 0.75-0.6 Ga). Intervening times show polar loops radiating from the geometric centre of the crust explaining the anomalous Precambrian magnetic inclination bias. The crustal lid was a symmetrical crescent-shaped body confined to a single hemisphere on the globe comparable in form to the Phanerozoic supercontinent (Neo)Pangaea. There were two major transitions in the tectonic regime when prolonged near-static motion was succeeded by widespread tectonic-magmatic activity, and each coincided with the major isotopic/geochemical signatures in the Precambrian record. The first comprised a ~90° reconfiguration of crust and mantle at ~2.2 Ga terminating the long 2.7-2.2 Ga static interval; the second was the largest continental break-up event in geological history and is constrained to the Ediacaran Period at ~0.6 Ga by multiple isotopic and geochemical signatures and the subsidence history of marine passive margins. Break-up of the lid at ~0.6 Ga defines a transition from dominant Lid Tectonics to dominant Plate Tectonics and is the primary cause of contrasts between the Precambrian and Phanerozoic aeons of geological times. The long interval of minimal continental motion in the mid-Proterozoic correlates with extensive emplacement of anorogenic anorthosite-rapakivi plutons unique to these times, and high-level emplacement was probably caused by blanketing of the mantle and comprehensive thermal weakening of the crust. Continental velocities were low during the two Proterozoic intervals characterized by profound glaciation (~2.4-2.2 and ~0.75-0.6 Ga) when partial or complete magmatic shutdown is likely to have reduced volcanic greenhouse gas production. Specific implications of Protopangaea-Palaeopangaea include: (i) support for recent evidence that 60-70% of the present continental crust had accreted by ~2.5 Ga; (ii) recognition from spatially constrained mineral provinces that sub-crustal lithosphere was already chemically differentiated by mid-Archaean times; (iii) strong axial alignment of younger greenstone belts, major Palaeoproterozoic shear zones, and later Meso-Neoproterozoic mobile/orogenic belts; (iv) concentration of anorogenic magmatism and progressive contraction of activity towards the orogenic margin subsequently to become the focus of Grenville (~1.1 Ga) orogenesis; and (v) late Neoproterozoic arc magmatism/tectonics at the instep margin of the continental crescent persisting until the Ediacaran continental break-up. © 2014 © 2014 Taylor & Francis. Source


Jones G.D.,University of Liverpool
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2015

Experimentally measured Legendre polynomial coefficients (a2 and a4) obtained from (α-γ) angular correlations for the (JP=0+) α(J1=2+) γ(J2=0+) spin sequence can vary markedly depending on the half-life of the 2+ state and on the source/backing combination. Three simple equations have been derived to determine each of the substate populations of the spin-relaxed 2+ state involving only the measured a2 and a4 coefficients. By the same methodology, three equations have been derived for each of the substates of spin-relaxed 5/2 states in terms of the statistical tensors, or population alignment coefficients, B2 and B4, of Rose and Brink. These B2 and B4 coefficients are directly proportional to the corresponding a2 and a4 coefficients. More simply, two equations have been derived for spin-relaxed spin 1 or 3/2 states in terms of the parameter B2, since a4=0 for these states. The orthogonality of the Legendre polynomial coefficients, a2 and a4, has enabled error equations to be deduced for each of the substate populations, in terms of the measured experimental errors in a2 and a4. © 2015 Elsevier B.V. All rights reserved. Source


Faraggi A.E.,University of Liverpool | Rizos J.,University of Ioannina
Nuclear Physics B | Year: 2015

The existence of an extra Z' inspired from heterotic-string theory at accessible energy scales attracted considerable interest in the particle physics literature. Surprisingly, however, the construction of heterotic-string derived models that allow for an extra Z' to remain unbroken down to low scales has proven to be very difficult. The main reason being that the U(1) symmetries that are typically discussed in the literature are either anomalous or have to be broken at a high scale to generate light neutrino masses. In this paper we use for that purpose the self-duality property under the spinor vector duality, which was discovered in free fermionic heterotic string models. The chiral massless states in the self-dual models fill complete 27 representations of E6. The anomaly free gauge symmetry in the effective low energy field theory of our string model is SU(4)C×SU(2)L×SU(2)R×U(1)ζ, where U(1)ζ is the family universal U(1) symmetry that descends from E6, and is typically anomalous in other free fermionic heterotic-string models. Our model therefore allows for the existence of a low scale Z', which is a combination of B-L, U(1)ζ and T3R. The string model is free of exotic fractionally charged states in the massless spectrum. It contains exotic SO(10) singlet states that carry fractional, non-E6 charge, with respect to U(1)ζ. These non-E6 string states arise in the model due to the breaking of the E6 symmetry by discrete Wilson lines. They represent a distinct signature of the string vacua. They may provide viable dark matter candidates. © 2015 The Authors. Source


Tatar R.,University of Liverpool
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We consider the field theories on multiple stacks of D5-branes wrapped on four cycles of resolved/deformed conifold geometries fibered over a two-torus. The central charges of the D5-branes are slightly misaligned when the branes are wrapped on various rigid holomorphic two-cycles or when they have different charges with respect to a magnetic flux turned on the two-torus. The wrapped D5-branes preserve (0, 2) supersymmetry in two dimensions if the Kahler moduli and the magnetic flux are related. Our geometries are T-dual to the brane configurations considered by Kutasov-Lin, and we provide a geometric interpretation for their equality between the field theory D-terms and the magnetic fluxes. We also consider the geometric transitions for rigid holomorphic two-cycles fibered over a two-torus with magnetic flux and discuss the partial breaking of supersymmetry after the geometric transition. © 2015 American Physical Society. © 2015 American Physical Society. Source


In this article, I examine a defining feature of the 'new public health': the (re)construction of health-related phenomena in behavioural terms. While the 'behavioural turn' within epidemiology has had far-reaching implications for the way in which public health problems as a whole are conceptualised, including, significantly, obesity and alcohol (mis)use, here I explore how the new public health works up its behavioural objects using the example of tobacco use. Beginning with the work of counting smokers, I trace the emergence and consolidation of a standard model for identifying and measuring tobacco-related harm, a model, I argue, that has been extended so that tobacco use itself can be treated in disease terms. As I show with reference to an example of contemporary public health research practice in the UK, this extension is problematic because it establishes a depoliticised view of the public's health that concentrates on individuals, recast as bundles of problem behaviours, at the expense of any examination of the social, cultural and economic circumstances in which those individuals live. Epidemiological research of this kind, with its core message that behavioural problems require behavioural solutions, relies on close alliances between the health sector and decision-makers more broadly. Under these conditions, the point at which research ends and government begins is often difficult to locate. I conclude by arguing that we should pay greater attention to the epidemiological practices used to transform the behaviour of the tobacco user, like that of the eater or drinker, into a site of governmental intervention. © 2011 Taylor & Francis. Source


Tagliabue A.,University of Liverpool | Aumont O.,Center Ird Of Bretagne | Bopp L.,CEA Saclay Nuclear Research Center
Geophysical Research Letters | Year: 2014

Variable supply of iron to the ocean is often invoked to explain part of past changes in atmospheric CO2 (CO2atm). Using model simulations, we find that CO2atm is sensitive on the order of 15, 2, and 1 ppm to sedimentary, dust, and hydrothermal iron input. CO2atm is insensitive to dust because it is not the major iron input to the Southern Ocean. Modifications to the relative export of Si(OH)4 to low latitudes are opposite to those predicted previously. Although hydrothermalism is the major control on the iron inventory in ∼25% of the ocean, it remains restricted to the deep ocean, with minor effects on CO2atm. Nevertheless, uncertainties regarding the iron-binding ligand pool can have significant impacts on CO2atm. Ongoing expansion of iron observations as part of GEOTRACES will be invaluable in refining these results. Key Points Atmospheric CO2 is relatively insensitive to changes to dust supply of iron Hydrothermal Fe is key to the iron inventory, but has a small effect on CO2 There are unexpected changes to Si cycling due to changes in Fe input ©2014. American Geophysical Union. All Rights Reserved. Source


Johnson E.K.,University of Bath | Adams D.J.,University of Liverpool | Cameron P.J.,University of Bath
Journal of Materials Chemistry | Year: 2011

Over the last 12 months a number of papers have been published which shed light on the processes that control the self-assembly of peptides into fibrous hydrogel networks. A number of new properties of dipeptide hydrogels have also been reported. This article highlights recent activity in the area of peptide self-assembly, with a particular focus on tri-peptides, di-peptides and protected amino acids. © The Royal Society of Chemistry. Source


Connor V.,University of Liverpool
Rheumatology International | Year: 2011

Knowledge and understanding about the immunosuppressive properties of anti-TNF therapies and the adverse effects these causes have advanced over the last 10 years since the first of these drugs was approved. These drugs work by inhibiting tumour necrosis factor (TNF) in the body, which plays an essential role in the immune response to invading pathogens. Anti-TNF drugs have therapeutic value because high levels of TNF are thought to be part of the pathophysiology of many chronic inflammatory disorders such as rheumatoid arthritis and Crohn's disease. Anti-TNF drugs are usually well-tolerated, however, there have been reports of many potentially serious adverse effects. This article will comprehensively analyse these adverse effects; the incidence, symptoms and mechanisms will be discussed. In addition, the contraindications of this class of drugs will be explored and the detection and prevention methods that should be put in place by health care professionals who treat patients on these drugs will be described. © 2009 Springer-Verlag. Source


Jones N.,University of Liverpool
International Journal of Impact Engineering | Year: 2010

A study is reported on the energy-absorbing effectiveness factor which was introduced recently. The factor is defined as the quotient of the total energy, which can be absorbed in a system, to the maximum energy up to failure in a normal tensile specimen, which is made from the same volume of material. This dimensionless parameter allows comparisons to be made of the effectiveness of various geometrical shapes and of energy absorbers made from different materials. The influence of material properties and various geometrical parameters on the value of the dimensionless parameter has been examined for the static and dynamic axial crushing behaviours of thin-walled sections. The influence of foam fillings and the stiffening of circular and square tubes is examined. It transpires that, according to the energy-absorbing effectiveness factor, an axially crushed circular tube is the most effective structural shape. Moreover multi-cellular cross-sections, and axial stiffening, increases the effectiveness of thin-walled sections. In these latter two cases, the energy absorbed by the additional material in a tensile test is included in the denominator of the energy-absorbing effectiveness factor. The influence of foam filling was found to increase the energy-absorbing effectiveness factor even though the additional energy absorbed by the foam is retained in the denominator. It was also noted that a circular tube, crushed axially either statically or dynamically, and made from an aluminium alloy, had a larger energy-absorbing effectiveness factor than a similar one made from a stainless steel, because the steel had a larger rupture strain which was not required during the deformation of the particular geometry examined. © 2008. Source


Vora J.,University of Liverpool | Heise T.,Profil Institute For Stoffwechselforschung
Diabetes, Obesity and Metabolism | Year: 2013

Lowering blood glucose with insulin therapy towards beneficial target levels while also avoiding hypoglycaemia is a challenging task. An important confounding factor, which might be under-appreciated in this scenario, is that of variable glucose readings causing difficulties with dose adjustment. Furthermore, this glucose variability is, to some extent, a reflection of variability in the glucose-lowering action of the insulin therapy itself. Not only is glucose variability a major confounding factor in disease management but it is possibly also of direct prognostic consequence and is increasingly recognized as an informative measurement in diabetes management. The scope for insulin-induced glucose variability is particularly great with basal insulins because of their prolonged absorption from high-dose depots. Pharmacodynamic (PD) variability manifests as both fluctuations in the level of glucose-lowering effect over time, and as inconsistencies in the response from one injection to another. Well-controlled pharmacokinetic (PK)/PD studies using repeated isoglycaemic clamp methodology clearly how that many injected basal insulin products have high variable absorption with correspondingly variable action. Incomplete resuspension and precipitation appear to be important issues with regard to unpredictability in this action, while an inadequate duration of action relative to the dosing interval results in a fluctuating action profile. There are some ultra-long-acting basal insulins with novel protraction mechanisms currently in clinical development for which clamp studies show markedly improved PK/PD profiles. © 2013 Blackwell Publishing Ltd. Source


De Magalhaes J.P.,University of Liverpool
Nature Reviews Cancer | Year: 2013

The ageing of populations worldwide is leading to an unprecedented increase in cancer cases and fatalities. Understanding the links between cancer and ageing is therefore more important than ever. How the interplay of ageing-associated changes affects cancer initiation and progression is complex, however, and some ageing processes probably foster cancer development whereas others hinder it, possibly in a tissue-specific manner. In the emerging age of cancer, how can our growing understanding of the biology of ageing inform cancer biology? © 2013 Macmillan Publishers Limited. All rights reserved. Source


Najafian G.,University of Liverpool
Applied Ocean Research | Year: 2010

Offshore structures are exposed to random wave loading in the ocean environment and hence the probability distribution of their response to wave loading is a minimum requirement for the efficient probabilistic analysis of these structures. Even if the structural system can be assumed to be linear, due to nonlinearity of the wave loading mechanism and also due to the intermittency of wave loading on members in the splash zone, the response is often non-Gaussian. The (conventional) method of moments is one of the methods which is frequently used to determine the parameters of the adopted probability model from a simulated or measured record of response. However, when higher order moments (e.g. 3rd or 4th order moments) are required for the derivation of distribution parameters, the parameter values obtained from this method show considerable scatter due to sampling variability. The purpose of this investigation was to compare the efficiency of the conventional form of the method of moments with two alternative forms of the method, i.e. with linear and the (new) low-order methods of moments. As a method of demonstration, the three different methods of moments have been applied to symmetric Pierson-Holmes distributions. The results show that in most cases the sampling variability of the parameter values determined from the two alternative forms of the method of moments is much smaller than their corresponding values derived from the conventional method of moments. © 2010 Elsevier Ltd. Source


Walker G.J.A.,University of Liverpool | Gunasekera P.,UNFPA
International Urogynecology Journal and Pelvic Floor Dysfunction | Year: 2011

Introduction and hypothesis: Information on the prevalence, risk factors and social consequences of pelvic floor dysfunction (PFD) affecting women in 16 low-income and lower middle-income countries is reviewed. Methods: Medline searches were performed for articles dealing with prevalence of PFD. Results: Thirty studies were identified. The mean prevalence for pelvic organ prolapse was 19.7% (range 3.4-56.4%), urinary incontinence (UI) was 28.7% (range 5.2-70.8%) and faecal incontinence (FI) was 6.9% (range 5.3-41.0%). Risk factors for PFD are similar to those in more affluent countries particularly increased age and parity, but additionally, PFD is associated with other factors including poor nutrition and heavy work. The social consequences of PFD conditions can be devastating. Conclusions: Pelvic organ prolapse and urinary and faecal incontinence are significant problems in developing countries. Access to health care to manage these conditions is often limited, and women usually have to live with the consequences for the rest of their lives. © 2010 The International Urogynecological Association. Source


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

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


Coupland S.E.,University of Liverpool
Histopathology | Year: 2011

B-cell non-Hodgkin lymphomas (B-NHL) represent the most common malignant lymphoid neoplasms, with the majority of these arising from germinal centre or post-germinal centre B cells, due to (at least) a disruption of the different phases of normal B-cell development. The most common B-cell lymphoma subtypes include follicular lymphoma, diffuse large B-cell lymphoma, marginal zone lymphoma and mantle cell lymphoma. As with other malignancies, it has been demonstrated that the development and progression of B-cell lymphomas involves complex interactions between the neoplastic B-cells and the surrounding microenvironment, including stromal cells, the intratumoral vasculature, the various types of macrophages, as well as T-cells, including regulatory T-cells (also termed T-regs). The complex communications between the cell populations involves interplay between chemokines, chemokine receptors and adhesion molecules, and the balance between these determines whether there is a tumour cell growth promotion or inhibition. The demonstration of the importance of the microenvironment in B-NHL has been shown recently using methodologies such as gene expression profiling, and has been validated in some B-NHL lymphoma subtypes using other techniques, such as immunohistochemistry. This is particularly in the case of follicular lymphomas, in which both T-regs and macrophages have been demonstrated to have prognostic value. As such, the microenvironment of B-cell lymphomas represents a challenge to the development of therapeutic agents, requiring re-direction and inclusion of these non-neoplastic supportive cells into future treatment strategies. © 2011 Blackwell Publishing Limited. Source


Bodger K.,University of Liverpool
PharmacoEconomics | Year: 2011

Traditionally, half of the direct costs associated with chronic inflammatory bowel diseases (IBD) Crohns disease (CD) and ulcerative colitis (UC) have related to hospital inpatient treatment for a sub-group of more severely affected, often therapy-resistant individuals. The advent of effective but relatively expensive biological agents has increased the contribution of drugs to overall medical care costs. This has focussed interest on the relative cost effectiveness of rival therapies for IBD and, in particular, on the affordability of long-term biological therapy. The purpose of this article is to review the available literature on this topic and to identify areas for future research.Head-to-head trials of competing treatment options are uncommon and clinical trials have seldom addressed cost effectiveness. In UC, models have explored the cost utility of 'high-' versus 'standard-' dose 5-aminosalicylic acid (5-ASA) therapy and the theoretical impact of improved adherence with once-daily formulations. In CD, cost-utility models for anti-tumour necrosis factor (TNF) drugs versus standard care have suggested consistently that incremental benefits are achieved at increased overall cost. However, studies of varying design have produced a wide spectrum of incremental cost-effectiveness ratio estimates, which highlights the challenges and limitations of existing modelling techniques. © 2011 Adis Data Information BV. All rights reserved. Source


Jones A.,University of Liverpool
Experimental and clinical psychopharmacology | Year: 2013

Training social drinkers to exercise motor inhibitory control leads to a reduction in alcohol consumption. However, it is unclear if participants should attempt to exercise inhibitory control in the presence of alcohol-related cues or if nonspecific inhibition training is equally effective. It is also unclear if comparable effects can be demonstrated by training oculomotor inhibitory control. We trained motor inhibition in the context of a modified stop-signal task (experiment 1) and oculomotor inhibition in the context of a modified antisaccade task (experiment 2) before investigating the influence of these manipulations on alcohol consumption. Results from experiment 1 demonstrated that training motor inhibition in the presence of alcohol-related cues led to reduced ad libitum alcohol consumption in the laboratory but not self-reported drinking in the week after training. These effects were seen in contrast to a control group that received no inhibition training and another control group that was trained to inhibit only in the presence of neutral cues; alcohol consumption did not differ between the latter two groups. In experiment 2, training of oculomotor inhibition in the presence of alcohol-related cues led to slowed eye movements toward target cues on catch trials, but it did not influence the proportion of inhibitory failures and had no influence on alcohol consumption in the laboratory. We conclude that training participants to exercise inhibitory control in the presence of alcohol-related cues can reduce alcohol consumption, but the effects are transient and are only seen when motor, but not oculomotor, inhibition is trained. (c) 2013 APA, all rights reserved. Source


Moss B.,University of Liverpool
Freshwater Biology | Year: 2010

The legend of Dr Faustus crops up repeatedly in European literature, drama and music, suggesting that it has profound meaning. In our relationship with the biosphere we have perhaps made a Faustian bargain. In return for unrestrained use of the Earth's resources, we may have mortgaged a long-term future. Currently we are hoping to renegotiate the bargain, but there is detail in the small-print-clauses about climate change, destruction of ecosystems and consequent release of nutrients to waterways that we have ignored. Natural biomes determine that the biosphere is maintained in a state favourable to our particular biochemistry. Part of the mechanism is regulation of atmospheric gas composition through storage of carbon as biological deposits. 2. Shallow lakes and wetlands, and the tundras and forests of wet soil, store carbon at a much greater rate than the global ocean. The influence, on shallow lake systems, of warming coupled with degrees of eutrophication has been studied in replicated experimental ponds. The first experiment used modest nutrient addition and a 3 °C rise in temperature. Such warming led to some increase in phosphorus availability, takeover by an introduced warm-water species, Lagarosiphon major of the submerged plant community, and an increase in the frequency of severe deoxygenation, with occasional fish kills. 3. The second experiment used a rise of 4 °C against a similar ambient background to that of the first experiment, but a nutrient environment much closer to that of lowland eutrophicated waters. Especially with moderate nitrogen loading, floating duckweeds became very abundant, though submerged plants persisted. Oxygen concentrations fell markedly. Final fish biomass fell by 60% on warming and 80% at the highest nutrient loading used, but the combination of warming and even modest nutrients brought oxygen frequently to zero overnight and killed all the fish. Because the fish used (Gasterosteus aculeatus) were extremely resilient, there are severe implications for many other European fish species. 4. Analysis of oxygen curves allowed calculation of metabolic parameters of the tank systems. Both warming and nutrient addition substantially increased community respiration compared with photosynthesis. Extrapolation suggests that if this phenomenon is widespread, an increase of about 1.8 Gt over the 1990's net annual atmospheric accumulation rate of 3.2 Gt might result. Since the IPCC models of future climate change do not include such biological feedbacks, they may thus seriously underestimate the future rise in temperature and its consequences. 5. Thematic implications: we do not know if our Faustian bargain can be renegotiated; our political and social institutions are poorly equipped in knowledge and barely accept the importance of biosphere processes, and our scientific establishment is reductionist and conforms to the values of the rest of society. Current approaches to mitigation of climate change attend only to carbon release from human institutions, with little or no reference to natural systems. The future is exceptionally uncertain. © 2010 Blackwell Publishing Ltd. Source


Kougioumtzoglou I.A.,University of Liverpool | Spanos P.D.,Rice University
Mechanical Systems and Signal Processing | Year: 2013

A novel identification approach for linear and nonlinear time-variant systems subject to non-stationary excitations based on the localization properties of the harmonic wavelet transform is developed. Specifically, a single-input/single-output (SISO) structural system model is transformed into an equivalent multiple-input/single-output (MISO) system in the wavelet domain. Next, time and frequency dependent generalized harmonic wavelet based frequency response functions (GHW-FRFs) are appropriately defined. Finally, measured (non-stationary) input-output (excitation-response) data are utilized to identify the unknown GHW-FRFs and related system parameters. The developed approach can be viewed as a generalization of the well established reverse MISO spectral identification approach to account for non-stationary inputs and time-varying system parameters. Several linear and nonlinear time-variant systems are used to demonstrate the reliability of the approach. The approach is found to perform satisfactorily even in the case of noise-corrupted data. © 2013 Elsevier Ltd. Source


Korte M.,Helmholtz Center Potsdam | Constable C.,University of California at San Diego | Donadini F.,ETH Zurich | Holme R.,University of Liverpool
Earth and Planetary Science Letters | Year: 2011

Knowledge of the Holocene evolution of Earth's magnetic field is important for understanding geodynamo processes in the core, is necessary for studying long-term solar-terrestrial relationships, and can provide useful age constraints for archeologicaland stratigraphic applications. Continuous time-varying global field models based on archeo- and paleomagnetic data are useful tools in this regard. We use a comprehensive data compilation and recently refined modelling strategies to produce CALS10k.1b, the first time-varying spherical harmonic geomagnetic field model spanning 10. ky. The model is an average obtained from bootstrap sampling to take account of uncertainties in magnetic components and ages in the data (and hence has version number 1b instead of 1). This model shows less spatial and temporal resolution than earlier versions for 0-3. ka, and particularly aims to provide a robust representation of the large-scale field at the core-mantle boundary (CMB). We discuss the geomagnetic dipole evolution and changes in Holocene magnetic field morphology at the CMB as shown by the new reconstruction. The results are compatible with earlier models (CALS3k.3 and CALS3k.4) for 0-3. ka, but reveal some clear deficiencies in the 0-7. ka CALS7K.2 model prior to 3. ka. CALS10k.1b is able to resolve mobile and structurally-evolving high latitude radial field flux lobes at the CMB in both hemispheres, as well as persistent non-zonal structure, in the 10. ky average. Contributions to the average field from time-varying structures in the equatorial Indonesian-Australian region are particularly striking. © 2011 Elsevier B.V. Source


Jones N.,University of Liverpool
International Journal of Impact Engineering | Year: 2014

The pseudo-shakedown phenomenon for the repeated and identical mass impact loadings on circular and rectangular plates, is studied using a rigid-plastic method of analysis. Comparisons are made with experimental data which has been published on the response of circular and square plates subjected to repeated mass impacts. Previous studies have explored the effect of only the current impact mass and ignored the accumulation of any masses from earlier impacts on a plate. This has led to a steady growth of the transverse displacements without the achievement of pseudo-shakedown. The effect of allowing the masses to accumulate on a plate surface, as, for example, in the loading of cargo in a hold, is shown to have an important influence on the behaviour. The asymptotic values of the associated expressions reveal that a pseudo-shakedown state is achieved for this case and has an associated modest value of the maximum permanent transverse displacement. The phenomenon of pseudo-shakedown is clarified and the equations are useful design tools for an estimate of the pseudo-shakedown behaviour of plating, which is loaded repeatedly with cargo and other masses in various practical situations. © 2013 Elsevier Ltd. All rights reserved. Source


Mottershead J.E.,University of Liverpool | Link M.,University of Kassel | Friswell M.I.,University of Swansea
Mechanical Systems and Signal Processing | Year: 2011

The sensitivity method is probably the most successful of the many approaches to the problem of updating finite element models of engineering structures based on vibration test data. It has been applied successfully to large-scale industrial problems and proprietary codes are available based on the techniques explained in simple terms in this article. A basic introduction to the most important procedures of computational model updating is provided, including tutorial examples to reinforce the reader's understanding and a large scale model updating example of a helicopter airframe. © 2010 Elsevier Ltd. All rights reserved. Source


Vogt A.,University of Liverpool
Journal of High Energy Physics | Year: 2011

We have derived the coefficients of the highest three 1/x -enhanced small-x logarithms of all timelike splitting functions and the coefficient functions for the transverse fragmentation function in one-particle inclusive e+e- annihilation at (in principle) all orders in massless perturbative QCD. For the longitudinal fragmentation function we present the respective two highest contributions. These results have been obtained from KLN-related decompositions of the unfactorized fragmentation functions in dimensional regularization and their structure imposed by the mass-factorization theorem. The resummation is found to completely remove the huge small-x spikes present in the fixed-order results, allowing for stable results down to very small values of the momentum fraction and scaling variable x. Our calculations can be extended to (at least) the corresponding αn s ln2nx contributions to the above quantities and their counterparts in deep-inelastic scattering. © 2011 SISSA. Source


Page R.D.,University of Liverpool
Physical Review C - Nuclear Physics | Year: 2011

The regular systematic behavior of Qp values is analyzed to provide a basis for estimating Q values for as yet unknown proton and α decays. These estimates are used in predicting partial half-lives for proton and α-particle emission from states in Ta, Re, Ir, and Au nuclei beyond the proton drip line. The implications of these predictions for further experimental study in this region are discussed. © 2011 The American Physical Society. Source


Prior I.A.,University of Liverpool | Hancock J.F.,University of Houston
Seminars in Cell and Developmental Biology | Year: 2012

Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions. Recent work has revealed how differences between the Ras isoforms in their trafficking, localization and protein-membrane orientation enable signalling specificity to be determined. We review the various strategies used to characterize compartmentalized Ras localization and signalling. Localization is an important contextual modifier of signalling networks and insights from the Ras system are of widespread relevance for researchers interested in signalling initiated from membranes. © 2011. Source


Gracey J.A.,University of Liverpool
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

We present the full expressions for the QCD β-function in the MOMggg, MOMq and MOMh renormalization schemes at three loops for an arbitrary colour group in the Landau gauge. The results for all three schemes are in very good agreement with the SU(3) numerical estimates provided by Chetyrkin and Seidensticker. © 2011 Elsevier B.V. Source


Gracey J.A.,University of Liverpool
Journal of High Energy Physics | Year: 2011

We compute the anomalous dimensions of the flavour non-singlet twist-2 Wilson operators in the RI'/SMOM scheme at two loops in an arbitrary linear covariant gauge. In addition we provide the full Green's function for these operators inserted in a quark 2-point function at the symmetric subtraction point. The three loop anomalous dimensions in the Landau gauge are also derived. © SISSA 2011. Source


Wieshmann U.C.,Walton Center for Neurology and Neurosurgery | Baker G.A.,University of Liverpool
BMJ Open | Year: 2013

Objectives: To ascertain the frequency of self-reported anger and depression in levetiracetam (LEV). Design: We compared patients with epilepsy (PWE) taking LEV with PWE taking other antiepileptic drugs (AEDs). Setting: All PWE and controls submitted information to the UK AED register. Participants: We analysed the data of 418 PWE and 41 control participants. 158 participants took LEV in monotherapy or as part of polypharmacotherapy, 260 PWE took other AED. Primary and secondary outcome measures: All PWE and controls completed the Liverpool Adverse Event Profile (LAEP) which includes items on anger and depression quantified on a four-point Likert scale, with 1 indicating that there was never a problem; 2, rarely a problem; 3, sometimes a problem and 4, always or often a problem. Results: 49% of PWE on LEV and 39% on AED other than LEV reported anger as sometimes or always being a problem ( p=0.042). 48% of PWE on LEV and 45% on AED other than LEV reported depression as sometimes or always being a problem ( p=0.584). 7% of control participants reported anger as sometimes being a problem and 93% reported anger as never or rarely being a problem. Depression was never a problem in 75% of controls and rarely a problem in 25%. Conclusions: Anger and depression were more frequently reported as a problem by PWE than by control participants. Our observational register of self-reported symptoms suggested anger being more often a problem in patients taking LEV than in PWE taking other AED. PWE should be informed about this potential problem of LEV. Source


Ouyang H.,University of Liverpool
Mechanical Systems and Signal Processing | Year: 2011

Structural modification in the form of adding mass and stiffness (and sometime damping) as a means of passive control to assign desirable poles and zeros for symmetric systems has been extensively studied. Pole and zero assignment by means of active control has also attracted much research. Assignment of poles to stabilise second-order damped asymmetric dynamic systems using structural modifications and state-feedback control, respectively, was carried out recently. It was found that the former is often incapable of assigning complex poles with negative real parts for asymmetric systems while the latter is nearly always capable of doing that. However, the gains required to assign poles with negative real parts using active control can be high. This paper presents a two-stage passive (structural modification) and active (state-feedback) combined control approach to assign complex poles with negative real parts to damped asymmetric dynamic systems to suppress flutter instability. This hybrid approach is motivated by possible restriction to gains of actuators and cost of sole active control. Simulated numerical examples show its effectiveness over the individual control strategies of passive control and active control. © 2010 Elsevier Ltd. All rights reserved. Source


Michael C.,University of Liverpool | Ottnad K.,University of Bonn | Urbach C.,University of Bonn
Physical Review Letters | Year: 2013

We present a lattice QCD computation of η and η′ masses and mixing angles, for the first time controlling continuum and quark mass extrapolations. The results for Mη=551(8)stat(6) syst MeV and Mη′=1006(54)stat(38) syst(+61)ex MeV are in excellent agreement with experiment. Our data show that the mixing in the quark flavor basis can be described by a single mixing angle of φ=46(1)stat(3) syst indicating that the η′ is mainly a flavor singlet state. © 2013 American Physical Society. Source


Gibbs B.M.,University of Liverpool
Journal of the Acoustical Society of America | Year: 2013

There has been a steady development of methods of measurement and prediction of structure-borne noise in buildings, particularly over the last two decades. In proposing and evaluating these methods, a major consideration has been the likely trade-off between accuracy and simplicity. Structure-borne sound transmission is a more complicated process than airborne sound transmission, but practitioners seek methods of prediction for the former, which are as straightforward as for the latter. In this paper a description is given of a study of multi-contact sources in buildings. The study concentrates on measurement and calculation procedures for sources and calculation procedures for receiver structures, particularly lightweight building elements. Although the study is not exhaustive, the findings point to the limitations of simplified methods, specifically the uncertainties likely as a result of reducing the data sets and computational effort, and the discrepancies resulting from simplifying assumptions. © 2013 Acoustical Society of America. Source


Dockray G.J.,University of Liverpool
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2012

Purpose of review: Cholecystokinin (CCK) controls nutrient delivery to the small intestine by inhibiting food intake and gastric emptying. This review deals with recent work shedding new light on how and when. Recent findings: Intestinal I-cells release CCK in response to dietary lipid and protein through mechanisms involving the G-protein-coupled receptors GPR40 and calcium-sensing receptor. Vagal afferent neurons are a primary target of CCK and are now recognized as an important site of integration of peripheral signals regulating ingestion. In addition to regulating vagal afferent nerve discharge, CCK also controls the expression of receptors and peptide neurotransmitters by these neurons; these actions are potentiated by leptin and inhibited by ghrelin. The responses of vagal afferent neurons to CCK are attenuated in obesity. Studies of human central nervous system responses using functional magnetic resonance imaging indicate activation of brainstem, hypothalamus and motor cortex by ingested fatty acid that is inhibited by a CCK-1 receptor antagonist. CCK may also play a role in adaptive responses in pancreatic islets by maintaining β-cell mass and acting as an incretin in certain circumstances. Summary: CCK mediates inhibition of food intake in response to ingested lipid and protein; resistance to CCK occurs in obesity and may contribute to altered mechanisms regulating food intake. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Prior I.A.,University of Liverpool | Lewis P.D.,University of Swansea | Mattos C.,Northeastern University
Cancer Research | Year: 2012

All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61. Although there is a high degree of similarity among the isoforms, K-Ras mutations are far more frequently observed in cancer, and each isoform displays preferential coupling to particular cancer types. We examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases. These findings were unexpected given that these mutations occur in regions that share 100% amino-acid sequence identity among the 3 isoforms. Of importance, many of these mutational biases were not due to differences in exposure to mutagens, because the patterns were still evident when compared within specific cancer types. We discuss potential genetic and epigenetic mechanisms, as well as isoform-specific differences in protein structure and signaling, that may promote these distinct mutation patterns and differential coupling to specific cancers. ©2012 AACR. Source


Robledo L.M.,Autonomous University of Madrid | Butler P.A.,University of Liverpool
Physical Review C - Nuclear Physics | Year: 2013

The relevance of coupling of quadrupole and octupole collective degrees of freedom in physical observables is explored in calculations with the Gogny force for the light radon, radium, and thorium isotopes. The results of the generator coordinate method calculations for the properties of negative parity states show an improvement over the traditional ones that consider just the octupole moment. © 2013 American Physical Society. Source


Casse G.,University of Liverpool
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2013

Silicon detectors have risen to a predominant role in high energy physics experiments since their introduction just over thirty years ago. Their outstanding capabilities of high resolution, low mass and fast response to ionising radiation have given silicon detectors the role of device of choice for the inner regions of collider experiments. Their evolution over the years has been notable, and it is possibly accelerating in the present times with the impulse coming from stringent requirements of future experiments and from developments in the microelectronics industry. Recent advancements of silicon detectors are reviewed and reported from the perspective of future challenges. © 2013 Elsevier B.V. © 2013 Elsevier Ltd. All rights reserved. Source


Tu X.,University of Manchester | Tu X.,University of Liverpool | Whitehead J.C.,University of Manchester
Applied Catalysis B: Environmental | Year: 2012

A coaxial dielectric barrier discharge (DBD) reactor has been developed for plasma-catalytic dry reforming of CH 4 into syngas over different Ni/γ-Al 2O 3 catalysts. Three different packing methods are introduced into the single-stage plasma-catalysis system to investigate the influence of catalysts packed into the plasma area on the physical properties of the DBD and determine consequent synergistic effects in the plasma-catalytic dry reforming reactions. Compared to the fully packed reactor, which strongly changes the discharge mode due to a significant reduction in the discharge volume, partially packing the Ni/γ-Al 2O 3 catalyst either in a radial or axial direction into the discharge gap still shows strong filamentary discharge and significantly enhances the physical and chemical interactions between the plasma and catalyst. Optical emission spectra of the discharge demonstrate the presence of reactive species (CO, CH, C 2, CO 2 + and N 2 +) in the plasma dry reforming of methane. We also find the presence of the Ni/γ-Al 2O 3 catalyst in the plasma has a weak effect on the gas temperature of the CH 4/CO 2 discharge. The synergistic effect resulting from the integration of the plasma and catalyst is clearly observed when the 10wt% Ni/γ-Al 2O 3 catalyst in flake form calcined at 300°C is partially packed in the plasma, showing both the CH 4 conversion (56.4%) and H 2 yield (17.5%) are almost doubled. The synergy of plasma-catalysis also contributes to a significant enhancement in the energy efficiency for greenhouse gas conversion. This synergistic effect from the combination of low temperature plasma and solid catalyst can be attributed to both strong plasma-catalyst interactions and high activity of the Ni/γ-Al 2O 3 catalyst calcined at a low temperature. © 2012 Elsevier B.V. Source


We aimed to determine the effects of variations in dietary composition on equine gut microbiota and their fermentation products, and proposed that dietary modifications profoundly affect microbial ecosystems and their metabolites. Bacterial communities within the large intestine of three groups of horses were compared using oligonucleotide-RNA hybridisation methodology. Each group consisting of six horses was maintained on (1) a grass-only diet, (2) a concentrate diet (i.e. supplemented with hydrolysable carbohydrates) and (3) a concentrate diet but horses were affected by simple colonic obstruction and distension (SCOD), a prevalent form of dietary-induced intestinal disease. We show that in response to dietary change and intestinal disease, there is a progressive and significant increase in Lachnospiraceae, the Bacteroidetes assemblage and the lactic acid-producing, Bacillus-Lactobacillus-Streptococcus (BLS) group. In contrast, there is a corresponding decrease in the proportion of obligate fibrolytic, acid-intolerant bacteria, Fibrobacter and Ruminococcaceae. Assessment of monocarboxylic acids indicated that there are significantly higher concentrations of lactic acid in the colonic contents of horses maintained on a concentrate diet and those suffering from SCOD, correlating with the observed increase in the population abundance of the BLS group. However, the population size of the Veillonellaceae (lactate utilisers) remained constant in each study group. The inability of this group to respond to increased lactic acid may be a contributory factor to the build-up of lactic acid observed in horses fed a concentrate diet and those suffering from SCOD. Source


Schewe S.,University of Liverpool
Information Processing Letters | Year: 2014

The distributed synthesis problem of safety and reachability languages is known to be undecidable. In this article, we establish that this is the case for very simple languages, namely for safety and reachability specifications in the intersection of LTL and ACTL. © 2013 The Author. Source


Controversy continues over how best to capture "sterilizing activity" of anti-tuberculosis regimens in early clinical development. Selecting surrogate endpoints capable of providing proof-of-concept, finding the optimal dose and identifying the best combination of companion drugs for new agents currently depends on an empirical balance of favourable biological, logistical and statistical properties. While more flexible rate-based measures of treatment response are better suited to these tasks, their interpretation depends critically on understanding the laboratory techniques on which they are based. In order to reduce the costly uncertainties of Phase II and III development, more extensive evaluation of such surrogate endpoints will be required in broader-based collaborative studies which make better use of our emerging scientific knowledge of the underlying mechanisms of sterilization in a clinical context. © 2010 Elsevier Ltd. All rights reserved. Source


SUMMARY Parasitic helminths are ubiquitous in most host, including human, populations. Helminths often alter the likelihood of infection and disease progression of coinfecting microparasitic pathogens (viruses, bacteria, protozoa), and there is great interest in incorporating deworming into control programmes for many major diseases (e.g. HIV, tuberculosis, malaria). However, such calls are controversial; studies show the consequences of deworming for the severity and spread of pathogens to be highly variable. Hence, the benefits of deworming, although clear for reducing the morbidity due to helminth infection per se, are unclear regarding the outcome of coinfections and comorbidities. I develop a theoretical framework to explore how helminth coinfection with other pathogens affects host mortality and pathogen spread and evolution under different interspecific parasite interactions. In all cases the outcomes of coinfection are highly context-dependent, depending on the mechanism of helminth-pathogen interaction and the quantitative level of helminth infection, with the effects of deworming potentially switching from beneficial to detrimental depending on helminth burden. Such context-dependency may explain some of the variation in the benefits of deworming seen between studies, and highlights the need for obtaining a quantitative understanding of parasite interactions across realistic helminth infection ranges. However, despite this complexity, this framework reveals predictable patterns in the effects of helminths that may aid the development of more effective, integrated management strategies to combat pathogens in this coinfected world. © Cambridge University Press 2013. Source


Jack I.,University of Liverpool | Osborn H.,Wilberforce Road
Nuclear Physics B | Year: 2014

The response of four dimensional quantum field theories to a Weyl rescaling of the metric in the presence of local couplings and which involve a, the coefficient of the Euler density in the energy momentum tensor trace on curved space, is reconsidered. Previous consistency conditions for the anomalous terms, which implicitly define a metric G on the space of couplings and give rise to gradient flow like equations for a, are derived taking into account the role of lower dimension operators. The results for infinitesimal Weyl rescaling are integrated to finite rescalings e2σ to a form which involves running couplings and which interpolates between IR and UV fixed points. The results are also restricted to flat space where they give rise to broken conformal Ward identities.Expressions for the three loop Yukawa β-functions for a general scalar/fermion theory are obtained and the three loop contribution to the metric G for this theory is also calculated. These results are used to check the gradient flow equations to higher order than previously. It is shown that these are only valid when β→. B, a modified β-function, and that the equations provide strong constraints on the detailed form of the three loop Yukawa β-function. N=1 supersymmetric Wess-Zumino theories are also considered as a special case. It is shown that the metric for the complex couplings in such theories may be restricted to a hermitian form. © 2014 The Authors. Source


Hopkins C.,University of Liverpool
Acta Acustica united with Acustica | Year: 2014

Airborne and impact sound insulation in buildings can be predicted according to the International Standard, ISO 15712 and the identical European Standard, EN 12354. Calculation of the flanking transmission requires knowledge of the vibration reduction index for which these standards contain empirical data. This paper investigates the vibration reduction index for the specific case of heavyweight buildings built from solid masonry/concrete walls and floors by using wave theory to calculate data for L-, T-and X-junctions. Calculations are carried out assuming only bending wave transmission at the junction as well as bending and in-plane wave transmission at the junction. The results show that the frequency-invariant empirical data in the standards is likely to give rise to errors in the mid-and high-frequency ranges due to the importance of in-plane wave generation at the junction. Regression analysis is used to identify new relationships that are specific to junctions of solid heavyweight walls and floors. For future work these give the potential to re-assess the existence of any bias error using the model in the standards and allow greater insight into the uncertainty associated with the model. © S. Hirzel Verlag • EAA. Source


Hasan M.,University of Liverpool
The Cochrane database of systematic reviews | Year: 2013

This is an updated version of the original Cochrane review published in The Cochrane Library 2001, Issue 4.Nearly a third of people with epilepsy do not have their seizures controlled with current treatments. Continuous attempts have been made to find new antiepileptic drugs based on increasing knowledge of the cellular and molecular biology involved in the genesis of epilepsy and seizures. Therefore, calcium antagonists that can alter the effects of calcium on brain cells have been investigated for their effect on epileptic seizures. To evaluate the effects of calcium antagonists when used as an add-on therapy for people with drug-resistant epilepsy. We searched the Cochrane Epilepsy Group Specialized Register (29 January 2013), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12), MEDLINE (1948 to 29 January 2013) and SCOPUS (all years to 29 January 2013). Randomised placebo-controlled or active-controlled add-on trials of any calcium antagonist in people with drug-resistant epilepsy. Two review authors (MH and JP) independently selected trials for inclusion and extracted data. Outcomes investigated included 50% or greater reduction in seizure frequency, treatment withdrawal, adverse effects, cognition and quality of life. Analyses were by intention to treat. Eleven trials were included with a total of 424 participants, one parallel-group and seven cross-over trials of flunarizine, two cross-over trials of nimodipine and one cross-over trial of nifedipine.For flunarizine, the risk ratio (RR) with 95% confidence interval (CI) for a 50% or greater reduction in seizure frequency in a single parallel trial was 1.53 (95% CI 0.59 to 3.96) indicating a non-significant advantage of flunarizine. We were unable to acquire data for this outcome from the other seven cross-over trials. The overall RR for treatment withdrawal of flunarizine was 7.11 (95% CI 1.73 to 29.30) indicating individuals were significantly more likely to have flunarizine withdrawn than placebo. No adverse effects were associated statistically with flunarizine.For nifedipine, we were unable to acquire the data we required for our specified outcomes.For nimodipine, we had data only from the first treatment period from one of the two cross-over trials (17 participants). The RR for a 50% or greater reduction in seizure frequency was 7.78 (99% CI 0.46 to 130.88) and for treatment withdrawal the RR was 2.25 (99% CI 0.25 to 20.38). Flunarizine may have a weak effect on seizure frequency but had a significant withdrawal rate, probably due to adverse effects, and should not be recommended for use as an add-on treatment. Similarly, there is no convincing evidence to support the use of nifedipine or nimodipine as add-on treatments for epilepsy. Source


Alfirevic Z.,University of Liverpool
The Cochrane database of systematic reviews | Year: 2013

Planned caesarean delivery for women thought be in preterm labour may be protective for baby, but could also be quite traumatic for both mother and baby. The optimal mode of delivery of preterm babies for both cephalic and breech presentation remains, therefore, controversial. To assess the effects of a policy of planned immediate caesarean delivery versus planned vaginal birth for women in preterm labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (5 August 2013). Randomised trials comparing a policy of planned immediate caesarean delivery versus planned vaginal delivery for preterm birth. Two review authors independently assessed trials for inclusion. Two review authors independently extracted data and assessed risk of bias. Data were checked for accuracy. We included six studies (involving 122 women) but only four studies (involving only 116 women) contributed data to the analyses. INFANT: There were very little data of relevance to the three main (primary) outcomes considered in this review: There was no significant difference between planned immediate caesarean section and planned vaginal delivery with respect to birth injury to infant (risk ratio (RR) 0.56, 95%, confidence interval (CI) 0.05 to 5.62; one trial, 38 women) or birth asphyxia (RR 1.63, 95% CI 0.84 to 3.14; one trial, 12 women). The only cases of birth trauma were a laceration of the buttock in a baby who was delivered by caesarean section and mild bruising in another allocated to the group delivered vaginally.The difference between the two groups with regard to perinatal deaths was not significant (0.29, 95% CI 0.07 to 1.14; three trials, 89 women) and there were no data specifically relating to neonatal admission to special care and/or intensive care unit.There was also no difference between the caesarean or vaginal delivery groups in terms of markers of possible birth asphyxia (RR 1.63, 95% CI 0.84 to 3.14; one trial, 12 women) or Apgar score less than seven at five minutes (RR 0.83, 95% CI 0.43 to 1.60; four trials, 115 women) and no difference in attempts at breastfeeding (RR 1.40, 95% 0.11 to 17.45; one trial, 12 women). There was also no difference in neonatal fitting/seizures (RR 0.22, 95% CI 0.01 to 4.32; three trials, 77 women), hypoxic ischaemic encephalopathy (RR 4.00, 95% CI 0.20 to 82.01;one trial, 12 women) or respiratory distress syndrome (RR 0.55, 95% CI 0.27 to 1.10; three trials, 103 women). There were no data reported in the trials specifically relating to meconium aspiration. There was also no significant difference between the two groups for abnormal follow-up in childhood (RR 0.65, 95% CI 0.19 to 2.22; one trial, 38 women) or delivery less than seven days after entry (RR 0.95, 95% CI 0.73 to 1.24; two trials, 51 women). MOTHER: There were no data reported on maternal admissions to intensive care. However, there were seven cases of major maternal postpartum complications in the group allocated to planned immediate caesarean section and none in the group randomised to vaginal delivery (RR 7.21, 95% CI 1.37 to 38.08; four trials, 116 women).There were no data reported in the trials specifically relating to maternal satisfaction (postnatal). There was no significant difference between the two groups with regard to postpartum haemorrhage. A number of non-prespecified secondary outcomes were also considered in the analyses. There was a significant advantage for women in the vaginal delivery group with respect to maternal puerperal pyrexia (RR 2.98, 95% CI 1.18 to 7.53; three trials, 89 women) and other maternal infection (RR 2.63, 95% CI 1.02 to 6.78; three trials, 103 women), but no significant differences in wound infection (RR 1.16, 95% CI 0.18 to 7.70; three trials, 103 women), maternal stay more than 10 days (RR 1.27, 95% CI 0.35 to 4.65; three trials, 78 women) or the need for blood transfusion (results not estimable). There is not enough evidence to evaluate the use of a policy of planned immediate caesarean delivery for preterm babies. Further studies are needed in this area, but recruitment is proving difficult. Source


Alfirevic Z.,University of Liverpool
The Cochrane database of systematic reviews | Year: 2013

Cardiotocography (known also as electronic fetal monitoring), records changes in the fetal heart rate and their temporal relationship to uterine contractions. The aim is to identify babies who may be short of oxygen (hypoxic), so additional assessments of fetal well-being may be used, or the baby delivered by caesarean section or instrumental vaginal birth. To evaluate the effectiveness of continuous cardiotocography during labour. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (31 December 2012) and reference lists of retrieved studies. Randomised and quasi-randomised controlled trials involving a comparison of continuous cardiotocography (with and without fetal blood sampling) with (a) no fetal monitoring, (b) intermittent auscultation (c) intermittent cardiotocography. Two review authors independently assessed study eligibility, quality and extracted data from included studies. Thirteen trials were included with over 37,000 women; only two were judged to be of high quality.Compared with intermittent auscultation, continuous cardiotocography showed no significant improvement in overall perinatal death rate (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.59 to 1.23, n = 33,513, 11 trials), but was associated with a halving of neonatal seizures (RR 0.50, 95% CI 0.31 to 0.80, n = 32,386, nine trials). There was no significant difference in cerebral palsy rates (RR 1.75, 95% CI 0.84 to 3.63, n = 13,252, two trials). There was a significant increase in caesarean sections associated with continuous cardiotocography (RR 1.63, 95% CI 1.29 to 2.07, n = 18,861, 11 trials). Women were also more likely to have an instrumental vaginal birth (RR 1.15, 95% CI 1.01 to 1.33, n = 18,615, 10 trials).Data for subgroups of low-risk, high-risk, preterm pregnancies and high-quality trials were consistent with overall results. Access to fetal blood sampling did not appear to influence the difference in neonatal seizures nor any other prespecified outcome. Continuous cardiotocography during labour is associated with a reduction in neonatal seizures, but no significant differences in cerebral palsy, infant mortality or other standard measures of neonatal well-being. However, continuous cardiotocography was associated with an increase in caesarean sections and instrumental vaginal births. The challenge is how best to convey these results to women to enable them to make an informed choice without compromising the normality of labour. Source


Nolan S.J.,University of Liverpool
The Cochrane database of systematic reviews | Year: 2013

This is an updated version of the previously published Cochrane review (Issue 4, 2009)Worldwide, phenytoin and valproate are commonly used antiepileptic drugs. It is generally believed that phenytoin is more effective for partial onset seizures, and that valproate is more effective for generalised onset tonic-clonic seizures with or without other generalised seizure types. To review the best evidence comparing phenytoin and valproate when used as monotherapy in individuals with partial onset seizures or generalised onset tonic-clonic seizures with or without other generalised seizure types. We searched the Cochrane Epilepsy Group's Specialised Register (19 February 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, The Cochrane Library, January 2013), MEDLINE (1946 to 18 February 2013), SCOPUS (19 February 2013), ClinicalTrials.gov (19 February 2013), and WHO International Clinical Trials Registry Platform ICTRP (19 February 2013). We handsearched relevant journals, contacted pharmaceutical companies, original trial investigators and experts in the field. Randomised controlled trials in children or adults with partial onset seizures or generalised onset tonic-clonic seizures with a comparison of valproate monotherapy versus phenytoin monotherapy. This was an individual patient data review. Outcomes were time to (a) treatment withdrawal (b) 12-month remission (c) six-month remission and (d) first seizure post randomisation. Cox proportional hazards regression models were used to obtain study-specific estimates of hazard ratios (HRs) with 95% confidence intervals (CIs) with the generic inverse variance method used to obtain the overall pooled HR and 95% CI. Individual patient data were available for 669 individuals out of 1119 eligible individuals from five out of 11 trials, 60% of the potential data. Results apply to generalised tonic-clonic seizures, but not absence or myoclonus seizure types. For remission outcomes, HR > 1 indicates an advantage for phenytoin and for first seizure and withdrawal outcomes HR > 1 indicates an advantage for valproateThe main overall results (pooled HR adjusted for seizure type, 95% CI) were time to (a) withdrawal of allocated treatment 1.09 (0.76 to 1.55); (b) 12-month remission 0.98 (0.78 to 1.23); (c) six-month remission 0.95 (0.78 to 1.15) and (d) first seizure 0.93 (0.75 to 1.14). The results suggest no overall difference between the drugs for these outcomes. No statistical interaction between treatment and seizure type (partial versus generalised) was found, but misclassification of seizure type may have confounded the results of this review. We have not found evidence that a significant difference exists between phenytoin and valproate for the outcomes examined in this review. However misclassification of seizure type may have confounded the results of this review. Results do not apply to absence or myoclonus seizure types. No outright evidence was found to support or refute current treatment policies. Source


Remmington T.,University of Liverpool
The Cochrane database of systematic reviews | Year: 2013

Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with CF and appropriate antibiotic therapy is vital. Antibiotics for pulmonary exacerbations are usually given intravenously, and for long-term treatment, via a nebuliser. Oral anti-pseudomonal antibiotics with the same efficacy and safety as intravenous or nebulised antibiotics would benefit people with CF due to ease of treatment and avoidance of hospitalisation. To determine the benefit or harm of oral anti-pseudomonal antibiotic therapy for people with CF, colonised with Pseudomonas aeruginosa, in the:1. treatment of a pulmonary exacerbation; and 2. long-term treatment of chronic infection. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We contacted pharmaceutical companies and checked reference lists of identified trials.Date of last search: 28 June 2013. Randomised or quasi-randomised controlled trials comparing any dose of oral anti-pseudomonal antibiotics, to other combinations of inhaled, oral or intravenous antibiotics, or to placebo or usual treatment for pulmonary exacerbations and long-term treatment. Two authors independently selected the trials, extracted data and assessed quality. We contacted trial authors to obtain missing information. We included three trials examining pulmonary exacerbations (171 participants) and two trials examining long-term therapy (85 participants). We regarded the most important outcomes as quality of life and lung function. The analysis did not identify any statistically significant difference between oral anti-pseudomonal antibiotics and other treatments for these outcome measures for either pulmonary exacerbations or long-term treatment. One of the included trials reported significantly better lung function when treating a pulmonary exacerbation with ciprofloxacin when compared with intravenous treatment; however, our analysis did not confirm this finding. We found no evidence of difference between oral anti-pseudomonal antibiotics and other treatments regarding adverse events or development of antibiotic resistance, but trials were not adequately powered to detect this. None of the studies had a low risk of bias from blinding which may have an impact particularly on subjective outcomes such as quality of life. The risk of bias for other criteria could not be clearly stated across the studies. We found no conclusive evidence that an oral anti-pseudomonal antibiotic regimen is more or less effective than an alternative treatment for either pulmonary exacerbations or long-term treatment of chronic infection with P. aeruginosa. Until results of adequately-powered future trials are available, treatment needs to be selected on a pragmatic basis, based upon any available non-RCT evidence, the clinical circumstances of the individual, the known effectiveness of drugs against local strains and upon individual preference. Source


Hancock E.C.,University of Liverpool
The Cochrane database of systematic reviews | Year: 2013

Infantile spasms (West's Syndrome) is a syndrome that includes a peculiar type of epileptic seizure-the spasms-and an electroencephalographic (EEG) abnormality often called hypsarrhythmia. Psychomotor retardation is frequently found at follow-up. Approximately two-thirds of affected infants will have a detectable underlying neurological abnormality, but still little is known about the pathophysiological basis for infantile spasms, and treatment remains problematic. To compare the effects of single pharmaceutical therapies used to treat infantile spasms in terms of control of the spasms, resolution of the EEG, relapse rates, psychomotor development, subsequent epilepsy, side effects, and mortality. To identify published data, we searched the Cochrane Epilepsy Group Specialised Register (October 2012), CENTRAL (The Cochrane Library 2012, Issue 9), MEDLINE (1946 to September Week 4, 2012), EMBASE (1980 to March 2003), and the reference lists of all retrieved articles.To identify unpublished data, we searched the ISRCTN Register (www.controlled-trials.com), corresponded with colleagues and drug companies, and made requests at international conferences. All randomised controlled trials (RCTs) of the administration of drug therapy to patients with infantile spasms. Data collection from all relevant publications was independently undertaken by three review authors (before 2010) or by two review authors using a standard proforma. Analysis included assessment of study quality and a search for sources of heterogeneity. We found 16 small RCTs (fewer than 100 patients enrolled) and 2 larger RCTs (more than 100 patients enrolled). These 18 studies looked at a total of 916 patients treated with a total of 12 different pharmaceutical agents. Overall methodology of the studies was poor, in part because of ethical dilemmas such as giving placebo injections to children. Two studies showed that placebo was not as good as active treatment in resolving the spasms. The strongest evidence suggested that hormonal treatment (prednisolone or tetracosactide depot) leads to resolution of spasms faster and in more infants than does vigabatrin. Responses without subsequent relapse may be no different. The same study suggests that hormonal treatments might improve the long-term developmental outcome compared with vigabatrin in infants not found to have an underlying cause for their infantile spasms. To date, few well-designed RCTs have considered the treatment of infantile spasms, and the numbers of patients enrolled have been small. In the majority, methodology has been poor, hence it is not clear which treatment is optimal in the treatment of this epilepsy syndrome. Hormonal treatment resolves spasms in more infants than vigabatrin, but this may or may not translate into better long-term outcomes. If prednisolone or vigabatrin is used, high dosage is recommended. Vigabatrin may be the treatment of choice in tuberous sclerosis. Resolution of the EEG features may be important, but this has not been proven. Further research using large studies with robust methodology is required. Source


Neilson J.P.,University of Liverpool
The Cochrane database of systematic reviews | Year: 2013

Hypoxaemia during labour can alter the shape of the fetal electrocardiogram (ECG) waveform, notably the relation of the PR to RR intervals, and elevation or depression of the ST segment. Technical systems have therefore been developed to monitor the fetal ECG during labour as an adjunct to continuous electronic fetal heart rate monitoring with the aim of improving fetal outcome and minimising unnecessary obstetric interference. To compare the effects of analysis of fetal ECG waveforms during labour with alternative methods of fetal monitoring. The Cochrane Pregnancy and Childbirth Group's Trials Register (latest search 12 February 2013). Randomised trials comparing fetal ECG waveform analysis with alternative methods of fetal monitoring during labour. Trial quality assessment and data extraction were performed by one review author, without blinding. Six trials (16,295 women) were included: five trials of ST waveform analysis (15,338 women) and one trial of PR interval analysis (957 women). In comparison to continuous electronic fetal heart rate monitoring alone, the use of adjunctive ST waveform analysis made no significant difference to primary outcomes: births by caesarean section (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.91 to 1.08), the number of babies with severe metabolic acidosis at birth (cord arterial pH less than 7.05 and base deficit greater than 12 mmol/L) (RR 0.78, 95% CI 0.44 to 1.37, data from 14,574 babies), or babies with neonatal encephalopathy (RR 0.54, 95% CI 0.24 to 1.25). There were, however, on average fewer fetal scalp samples taken during labour (RR 0.61, 95% CI 0.41 to 0.91) although the findings were heterogeneous; there were fewer operative vaginal deliveries (RR 0.89, 95% CI 0.81 to 0.98) and admissions to special care unit (RR 0.89, 95% CI 0.81 to 0.99); there was no statistically significant difference in the number of babies with low Apgar scores at five minutes or babies requiring neonatal intubation. There was little evidence that monitoring by PR interval analysis conveyed any benefit. These findings provide some modest support for the use of fetal ST waveform analysis when a decision has been made to undertake continuous electronic fetal heart rate monitoring during labour. However, the advantages need to be considered along with the disadvantages of needing to use an internal scalp electrode, after membrane rupture, for ECG waveform recordings. Source


Maltby E.,University of Liverpool | Acreman M.C.,UK Center for Ecology and Hydrology
Hydrological Sciences Journal | Year: 2011

Ecosystem services are natural assets produced by the environment and utilized by humans - such as clean air, water, food and materials - and contribute to social and cultural well-being. This concept, arguably, has been developed further in wetlands than any other ecosystem. Wetlands were historically important in producing the extensive coal deposits of the Carboniferous period; key steps in human development took place in communities occupying the wetland margins of rivers, lakes and the sea; and wetlands play a key role in the hydrological cycle influencing floods and river droughts. In this paper we examine three pillars that support the wetland research agenda: hydrology, wetland origins and development, and linkages to society. We investigate these through an overview of the evolution of wetland science and assessment of the wide range of topics relating to ecosystem services covered in this Special Issue. We explain the seminal change in how modern society values the benefits of natural ecosystems and highlight the pathfinder role that wetland research has played in the paradigm shift. © 2011 Copyright 2011 IAHS Press. Source


Alfirevic Z.,University of Liverpool
The Cochrane database of systematic reviews | Year: 2013

Abnormal blood flow patterns in fetal circulation detected by Doppler ultrasound may indicate poor fetal prognosis. It is also possible false positive Doppler ultrasound findings could encourage inappropriate early delivery. The objective of this review was to assess the effects of Doppler ultrasound used to assess fetal well-being in high-risk pregnancies on obstetric care and fetal outcomes. We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 30 September 2013. Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in high-risk pregnancies compared with no Doppler ultrasound. Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked. Eighteen completed studies involving just over 10,000 women were included. The trials were generally of unclear quality with some evidence of possible publication bias. The use of Doppler ultrasound in high-risk pregnancy was associated with a reduction in perinatal deaths (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52 to 0.98, 16 studies, 10,225 babies, 1.2% versus 1.7 %, number needed to treat (NNT) = 203; 95% CI 103 to 4352). There were also fewer inductions of labour (average RR 0.89, 95% CI 0.80 to 0.99, 10 studies, 5633 women, random-effects) and fewer caesarean sections (RR 0.90, 95% CI 0.84 to 0.97, 14 studies, 7918 women). No difference was found in operative vaginal births (RR 0.95, 95% CI 0.80 to 1.14, four studies, 2813 women), nor in Apgar scores less than seven at five minutes (RR 0.92, 95% CI 0.69 to 1.24, seven studies, 6321 babies). Current evidence suggests that the use of Doppler ultrasound in high-risk pregnancies reduced the risk of perinatal deaths and resulted in less obstetric interventions. The quality of the current evidence was not of high quality, therefore, the results should be interpreted with some caution. Studies of high quality with follow-up studies on neurological development are needed. Source


Ahmad S.,University of Liverpool
Stem Cells Translational Medicine | Year: 2012

The cornea is the clear tissue at the front of the eye that transmits light to the retina at the back of the eye. The cornea is covered by an epithelium and surrounded by a narrow band of tissue known as the limbus. The limbus has two important roles in maintaining a healthy corneal epithelium. First, stem cells for the corneal epithelium reside at the limbus and not in the cornea. Second, the limbus acts as a barrier separating the clear avascular corneal epithelium from the surrounding vascular conjunctival tissue. A failure of these limbal functions can result in the painful and blinding disease of limbal stem cell deficiency. In this disease, the corneal epithelium cannot be maintained by the stem cells, and the corneal surface becomes replaced by hazy conjunctival tissue. There are many causes of limbal stem cell deficiency, such as burns to the eye, inflammatory diseases, and hereditary diseases. Current understanding of the pathophysiology of the disease is discussed here. In particular, understanding whether the limbal stem cells are lost or become dysfunctional or indeed whether the limbal microenvironment is disturbed is important when developing appropriate management strategies for the disease. ©AlphaMed Press. Source


Wilding J.P.H.,University of Liverpool
Diabetes, Obesity and Metabolism | Year: 2012

Diabetes is a complex disease defined by hyperglycaemia; however, strong associations with abdominal obesity, hypertension and dyslipidaemia contribute to the high risk of cardiovascular disease. Although aggressive glycaemic control reduces microvascular complications, the evidence for macrovascular complications is less certain. The theoretical benefits of the mode of action of peroxisome proliferator-activated receptor (PPAR) agonists are clear. In clinical practice, PPAR-α agonists such as fibrates improve dyslipidaemia, while PPAR-γ agonists such as thiazolidinediones improve insulin resistance and diabetes control. However, although these agents are traditionally classed according to their target, they have different and sometimes conflicting clinical benefit and adverse event profiles. It is speculated that this is because of differing properties and specificities for the PPAR receptors (each of which targets specific genes). This is most obvious in the impact on cardiovascular outcomes-in clinical trials pioglitazone appeared to reduce cardiovascular events, whereas rosiglitazone potentially increased the risk of myocardial infarction. The development of a dual PPAR-α/γ agonist may prove beneficial in effectively managing glycaemic control and improving dyslipidaemia in patients with type 2 diabetes. Yet, development of agents such as muraglitazar and tesaglitazar has been hindered by various serious adverse events. Aleglitazar, a balanced dual PPAR-α/γ agonist, is currently the most advanced in clinical development and has shown promising results in phase II clinical trials with beneficial effects on glucose and lipid variables. A phase III study, ALECARDIO, is ongoing and will establish whether improvements in laboratory test profiles translate into an improvement in cardiovascular outcomes. © 2012 Blackwell Publishing Ltd. Source


De Magalhaes J.P.,University of Liverpool
FASEB Journal | Year: 2012

The idea that aging follows a predetermined sequence of events, a program, has been discredited by most contemporary authors. Instead, aging is largely thought to occur due to the accumulation of various forms of molecular damage. Recent work employing functional genomics now suggests that, indeed, certain facets of mammalian aging may follow predetermined patterns encoded in the genome as part of developmental processes. It appears that genetic programs coordinating some aspects of growth and development persist into adulthood and may become detrimental. This link between development and aging may occur due to regulated processes, including through the action of microRNAs and epigenetic mechanisms. Taken together with other results, in particular from worms, these findings provide evidence that some aging changes are not primarily a result of a build-up of stochastic damage but are rather a product of regulated processes. These processes are interpreted as forms of antagonistic pleiotropy, the product of a "shortsighted watchmaker," and thus do not assume aging evolved for a purpose. Overall, it appears that the genome does, indeed, contain specific instructions that drive aging in animals, a radical shift in our perception of the aging process. © The Author(s). Source


Grove M.,University of Liverpool
Mathematical Biosciences | Year: 2013

Models of foraging behaviour often assume either that animals are searching for resources, and therefore have no prior knowledge of resource locations, or that they are effectively omniscient, with a comprehensive knowledge of their habitat. By contrast, few attempts have been made to examine the actual conditions under which spatial memory will provide net benefits to foragers. To redress this balance, a model is developed that relates the sensory acuity of the forager and key indices of resource structure to the expected foraging efficiency via calculation of inter-patch distances. Efficiencies of 'ignorant' and 'prescient' foragers are examined in order to derive sets of conditions under which natural selection will favour the evolution of spatial memory capabilities. Results suggest that when resources are densely distributed or sensory acuity is high, spatial memory for resource locations provides no increase in efficiency over that of an 'ignorant' forager encountering resources at random. © 2012 Elsevier Inc. Source


Wile D.,University of Liverpool
Annals of Clinical Biochemistry | Year: 2012

Diuretics, in one form or another, have been around for centuries and this review sets out to chart their development and clinical use. Starting with the physiology of the kidney, it progresses to explain how diuretics actually work, via symports on the inside of the renal tubules. The different classes of diuretics are characterized, along with their mode of action. The clinical use of diuretics in conditions like congestive cardiac failure and hypertension, as well as some rarer, but clinically important, conditions is then examined. An account is given of the adverse effects of diuretics and how they come about. Common adverse effects like hypokalaemia and hyponatraemia are examined in some detail, and other electrolyte disturbances like hypomagnesaemia also gain a mention. Diuretic use in chronic kidney disease is examined and new guidelines that have been introduced are presented. A section on diuretic abuse is included as this is becoming an all too common clinical scenario, and the sometimes tragic consequences of this abuse are emphasized. Diuretics also find a role in the diagnosis of forms of renal tubular acidosis and this role is explored. Finally, a selection of some of the newer approaches to diuretic therapy are presented, often the consequence of the increasing development of molecular biology, and some of the novel compounds - which may be in drug formularies of the future - are revealed. Source


Weightman P.,University of Liverpool
Physical Biology | Year: 2012

The emergence of intense sources of terahertz radiation based on lasers and electron accelerators has considerable potential for research on biological systems. This perspective gives a brief survey of theoretical work and the results of experiments on biological molecules and more complex biological systems. Evidence is accumulating that terahertz radiation influences biological systems and this needs to be clarified in order to establish safe levels of human exposure to this radiation. The use of strong sources of terahertz radiation may contribute to the resolution of controversies over the mechanism of biological organization. However the potential of these sources will only be realized if they are accompanied by the development of sophisticated pump-probe and multidimensional experimental techniques and by the study of biological systems in the controlled environments necessary for their maintenance and viability. © 2012 IOP Publishing Ltd. Source


Heparan sulfate (HS) is present on the surface of virtually all mammalian cells and is a major component of the extracellular matrix (ECM), where it plays a pivotal role in cell-cell and cell-matrix cross-talk through its large interactome. Disruption of HS biosynthesis in mice results in neonatal death as a consequence of malformed lungs, indicating that HS is crucial for airway morphogenesis. Neonatal mortality (~50%) in newborns with congenital diaphragmatic hernia (CDH) is principally associated with lung hypoplasia and pulmonary hypertension. Given the importance of HS for lung morphogenesis, we investigated developmental changes in HS structure in normal and hypoplastic lungs using the nitrofen rat model of CDH and semi-synthetic bacteriophage ('phage) display antibodies, which identify distinct HS structures. The pulmonary pattern of elaborated HS structures is developmentally regulated. For example, the HS4E4V epitope is highly expressed in sub-epithelial mesenchyme of E15.5 - E17.5 lungs and at a lower level in more distal mesenchyme. However, by E19.5, this epitope is expressed similarly throughout the lung mesenchyme.We also reveal abnormalities in HS fine structure and spatiotemporal distribution of HS epitopes in hypoplastic CDH lungs. These changes involve structures recognised by key growth factors, FGF2 and FGF9. For example, the EV3C3V epitope, which was abnormally distributed in the mesenchyme of hypoplastic lungs, is recognised by FGF2. The observed spatiotemporal changes in HS structure during normal lung development will likely reflect altered activities of many HS-binding proteins regulating lung morphogenesis. Abnormalities in HS structure and distribution in hypoplastic lungs can be expected to perturb HS:protein interactions, ECM microenvironments and crucial epithelial-mesenchyme communication, which may contribute to lung dysmorphogenesis. Indeed, a number of epitopes correlate with structures recognised by FGFs, suggesting a functional consequence of the observed changes in HS in these lungs. These results identify a novel, significant molecular defect in hypoplastic lungs and reveals HS as a potential contributor to hypoplastic lung development in CDH. Finally, these results afford the prospect that HS-mimetic therapeutics could repair defective signalling in hypoplastic lungs, improve lung growth, and reduce CDH mortality. Source


Bakewell D.J.,University of Liverpool
Journal of Physics D: Applied Physics | Year: 2011

A Fourier-Bessel (FB) series solution is derived that describes the dielectrophoretic-driven transport of nanoparticles in a microdevice. The solution assumes that the nanoparticles do not interact and is based on a linear Fokker-Planck equation that includes the effects of thermal diffusion. The solution is applicable for a dielectrophoretic force that varies exponentially in the microdevice, such as in the far field of planar interdigitated arrays. Important applications of the FB solution are demonstrated that include simulation and system classification of nanoparticle movement under the action of weak and strong dielectrophoretic forces. Methods are demonstrated for the inverse process of estimating model parameters, such as the dielectrophoretic force, based on nanoparticle concentration data obtained experimentally. Data decomposition into separate spatial and temporal modes is demonstrated and Fourier transformation of the series solution yields a representation in the frequency domain. The frequency response predicted by transforming the time-dependent FB solution indicates the presence of a dielectrophoresis modulation bandwidth that concurs with observations of preliminary experiments. © 2011 IOP Publishing Ltd. Source


Jones N.,University of Liverpool
International Journal of Impact Engineering | Year: 2014

This article studies the significant amount of literature that has been published recently on the dynamic response of plating subjected to large dynamic loadings. A theoretical method of analysis for mass impacts, dynamic pressure pulses and impulsive velocity or blast loadings on circular, square and rectangular plates is presented for the idealisation of a rigid, perfectly plastic material. This theoretical analysis caters for the influence of finite-displacements and is developed further to predict the response for plates made from a strain rate sensitive material. Relatively simple equations are presented for the maximum permanent transverse displacements which give good agreement with the corresponding experimental data, and therefore, can be used for design purposes, safety calculations, security studies, hazard assessments and forensic investigations. © 2013 Elsevier Ltd. All rights reserved. Source


Hofer W.A.,University of Liverpool
Foundations of Physics | Year: 2011

An equation proposed by Levy, Perdew and Sahni (Phys. Rev. A 30:2745, 1984) is an orbital-free formulation of density functional theory. However, this equation describes a bosonic system. Here, we analyze on a very fundamental level, how this equation could be extended to yield a formulation for a general fermionic distribution of charge and spin. This analysis starts at the level of single electrons and with the question, how spin actually comes into a charge distribution in a non-relativistic model. To this end we present a space-time model of extended electrons, which is formulated in terms of geometric algebra. Wave properties of the electron are referred to mass density oscillations. We provide a comprehensive and non-statistical interpretation of wavefunctions, referring them to mass density components and internal field components. It is shown that these wavefunctions comply with the Schrödinger equation, for the free electron as well as for the electron in electrostatic and vector potentials. Spin-properties of the electron are referred to intrinsic field components and it is established that a measurement of spin in an external field yields exactly two possible results. However, it is also established that the spin of free electrons is isotropic, and that spin-dynamics of single electrons can be described by a modified Landau-Lifshitz equation. The model agrees with the results of standard theory concerning the hydrogen atom. Finally, we analyze many-electron systems and derive a set of coupled equations suitable to characterize the system without any reference to single electron states. The model is expected to have the greatest impact in condensed matter theory, where it allows to describe an N-electron system by a many-electron wavefunction Ψ of four, instead of 3N variables. The many-body aspect of a system is in this case encoded in a bivector potential. © 2010 Springer Science+Business Media, LLC. Source


Walsh J.L.,University of Liverpool | Kong M.G.,Loughborough University
Applied Physics Letters | Year: 2011

Lowerature atmospheric pressure plasmas are of great importance in many emerging biomedical and materials processing applications. The redundancy of a vacuum system opens the gateway for highly portable plasma systems, for which air ideally becomes the plasma-forming gas and remote plasma processing is preferred to ensure electrical safety. Typically, the gas temperature observed in air plasma greatly exceeds that suitable for the processing of thermally liable materials; a large plasma-sample distance offers a potential solution but suffers from a diluted downstream plasma chemistry. This Letter reports a highly portable air plasma jet system which delivers enhanced downstream chemistry without compromising the low temperature nature of the discharge, thus forming the basis of a powerful tool for emerging mobile plasma applications. © 2011 American Institute of Physics. Source


Quasi-integrity of continental crust between Mid-Archaean and Ediacaran times is demonstrated by conformity of palaeomagnetic poles to near-static positions between ∼2.7-2.2 Ga, ∼1.5-1.2 Ga and ∼0.75-0.6 Ga. Intervening data accord to coherent APW loops turning at "hairpins" focused near a continental-centric location. Although peripheral adjustments occurred during Early Proterozoic (∼2.2 Ga) and Grenville (∼1.1 Ga) times, the crust retained a low order symmetrical crescent-shaped form constrained to a single global hemisphere until break-up in Ediacaran times. Conformity of palaeomagnetic data to specific Eulerian parameters enables definition of a master Precambrian APW path used to estimate the root mean square velocity (vRMS) of continental crust between 2.8 and 0.6 Ga. A long interval of little polar movement between ∼2.7 and 2.2 Ga correlates with global magmatic shutdown between ∼2.45 and 2.2 Ga, whilst this interval and later slowdown at ∼0.75-0.6 Ga to velocities of <2 cm/year correlate with episodes of widespread glaciation implying that these prolonged climatic anomalies had an internal origin; the reduced input of volcanically-derived atmospheric greenhouse gases is inferred to have permitted freeze-over conditions with active ice sheets extending into equatorial latitudes as established by low magnetic inclinations in glaciogenic deposits. v RMS variations through Precambrian times correspond to the distribution of U-Pb ages in orogenic granitoids and detrital zircons and demonstrate that mobility of continental crust has been closely related to crustal tectonism and incrementation. Both periods of near-stillstand were followed by rapid vRMS recording massive heat release from beneath the continental lid at ∼2.2 and 0.6 Ga. The first coincided with the Lomagundi-Jatuli isotopic event and led to prolonged orogenesis accompanied by continental flooding and reconfiguration of the crust on the Earth's surface; the second led to continental break-up and instigated the comprehensive Plate Tectonics that has characterised Phanerozoic times. The Mesoproterozoic interval characterised by anorogenic magmatism correlates with low vRMS between ∼1.5 and 1.1 Ga. Insulation of the sub-continental mantle evidently permitted high temperature melting and weakening of the crustal lid to enable buoyant emplacement of large plutons at high crustal levels during this magmatic event unique to Mesoproterozoic and early Neoproterozoic times. © 2012, China University of Geosciences (Beijing) and Peking University. Production and hosting by Elsevier B.V. All rights reserved. Source


Gray J.M.N.T.,University of Manchester | Kokelaar B.P.,University of Liverpool
Journal of Fluid Mechanics | Year: 2010

Particle size segregation can have a significant feedback on the motion of many hazardous geophysical mass flows such as debris flows, dense pyroclastic flows and snow avalanches. This paper develops a new depth-averaged theory for segregation that can easily be incorporated into the existing depth-averaged structure of typical models of geophysical mass flows. The theory is derived by depth-averaging the segregation-remixing equation for a bi-disperse mixture of large and small particles and assuming that (i) the avalanche is always inversely graded and (ii) there is a linear downslope velocity profile through the avalanche depth. Remarkably, the resulting large particle transport equation is very closely related to the segregation equation from which it is derived. Large particles are preferentially transported towards the avalanche front and then accumulate there. This is important, because when this is combined with mobility feedback effects, the larger less mobile particles at the front can be continuously shouldered aside to spontaneously form lateral levees that channelize the flow and enhance run-out. The theory provides a general framework that will enable segregation-mobility feedback effects to be studied in detail for the first time. While the large particle transport equation has a very simple representation of the particle size distribution, it does a surprisingly good job of capturing solutions to the full theory once the grains have segregated into inversely graded layers. In particular, we show that provided the inversely graded interface does not break it has precisely the same solution as the full theory. When the interface does break, a concentration shock forms instead of a breaking size segregation wave, but the net transport of large particles towards the flow front is exactly the same. The theory can also model more complex effects in small-scale stratification experiments, where particles may either be brought to rest by basal deposition or by the upslope propagation of a granular bore. In the former case the resulting deposit is normally graded, while in the latter case it is inversely graded. These completely opposite gradings in the deposit arise from a parent flow that is inversely graded, which raises many questions about how to interpret geological deposits. © 2010 Cambridge University Press. Source


Gracey J.A.,University of Liverpool
European Physical Journal C | Year: 2010

The three dimensional Gribov-Zwanziger Lagrangian is analysed at one and two loops. Specifically, the two loop gap equation is evaluated and the Gribov mass is expressed in terms of the coupling constant. The one loop corrections to the propagators of all the fields are determined. It is shown that when the gap equation is satisfied the Faddeev-Popov ghost and both Bose and Grassmann localizing ghosts all enhance in the infrared limit at one loop. This verifies that the Kugo-Ojima confinement criterion holds to this order and we also show that both Grassmann ghosts are enhanced at two loops. For the Bose ghost we determine the full form of the propagator in the zero momentum limit for both the transverse and longitudinal pieces and confirm Zwanziger's recent general analysis for the low energy behaviour. We provide an alternative but equivalent version of the horizon condition expressing it as the vacuum expectation value of an operator involving only the localizing Bose ghost field. The one loop static potential is also determined. © 2010 Springer-Verlag / Società Italiana di Fisica. Source


Irving G.J.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2012

In many parts of the world, hepatitis A infection represents a significant cause of morbidity and socio-economic loss. Whilst hepatitis A vaccines have the potential to prevent disease, the degree of protection afforded against clinical outcomes and within different populations remains uncertain. There are two types of hepatitis A virus (HAV) vaccine, inactivated and live attenuated. It is important to determine the efficacy and safety for both vaccine types. To determine the clinical protective efficacy, sero-protective efficacy, and safety and harms of hepatitis A vaccination in persons not previously exposed to hepatitis A. We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, Science Citation Index Expanded, and China National Knowledge Infrastructure (CNKI) up to November 2011. Randomised clinical trials comparing HAV vaccine with placebo, no intervention, or appropriate control vaccines in participants of all ages. Data extraction and risk of bias assessment were undertaken by two authors and verified by a third author. Where required, authors contacted investigators to obtain missing data. The primary outcome was the occurrence of clinically apparent hepatitis A (infectious hepatitis). The secondary outcomes were lack of sero-protective anti-HAV immunoglobulin G (IgG), and number and types of adverse events. Results were presented as relative risks (RR) with 95% confidence intervals (CI). Dichotomous outcomes were reported as risk ratio (RR) with 95% confidence interval (CI), using intention-to-treat analysis. We conducted assessment of risk of bias to evaluate the risk of systematic errors (bias) and trial sequential analyses to estimate the risk of random errors (the play of chance). We included a total of 11 clinical studies, of which only three were considered to have low risk of bias; two were quasi-randomised studies in which we only addressed harms. Nine randomised trials with 732,380 participants addressed the primary outcome of clinically confirmed hepatitis A. Of these, four trials assessed the inactivated hepatitis A vaccine (41,690 participants) and five trials assessed the live attenuated hepatitis A vaccine (690,690 participants). In the three randomised trials with low risk of bias (all assessing inactivated vaccine), clinically apparent hepatitis A occurred in 9/20,684 (0.04%) versus 92/20,746 (0.44%) participants in the HAV vaccine and control groups respectively (RR 0.09, 95% CI 0.03 to 0.30). In all nine randomised trials, clinically apparent hepatitis A occurred in 31/375,726 (0.01%) versus 505/356,654 (0.18%) participants in the HAV vaccine and control groups respectively (RR 0.09, 95% CI 0.05 to 0.17). These results were supported by trial sequential analyses. Subgroup analyses confirmed the clinical effectiveness of both inactivated hepatitis A vaccines (RR 0.09, 95% CI 0.03 to 0.30) and live attenuated hepatitis A vaccines (RR 0.07, 95% CI 0.03 to 0.17) on clinically confirmed hepatitis A. Inactivated hepatitis A vaccines had a significant effect on reducing the lack of sero-protection (less than 20 mIU/L) (RR 0.01, 95% CI 0.00 to 0.03). No trial reported on a sero-protective threshold less than 10 mIU/L. The risk of both non-serious local and systemic adverse events was comparable to placebo for the inactivated HAV vaccines. There were insufficient data to draw conclusions on adverse events for the live attenuated HAV vaccine. Hepatitis A vaccines are effective for pre-exposure prophylaxis of hepatitis A in susceptible individuals. This review demonstrated significant protection for at least two years with the inactivated HAV vaccine and at least five years with the live attenuated HAV vaccine. There was evidence to support the safety of the inactivated hepatitis A vaccine. More high quality evidence is required to determine the safety of live attenuated vaccines. Source


Newsham D.,University of Liverpool
British Journal of Ophthalmology | Year: 2010

Background/aims: Several studies have recently provided insights into how amblyopia may be most effectively managed. Despite the new evidence, a US study reported that a recent randomised controlled trial had made little influence on clinical practice. The aims of this research are to assess current practice of amblyopia management in the UK and to determine the comparability with the evidence-based recommendations. Methods: A questionnaire was constructed to assess current amblyopia management practice, particularly in relation to areas investigated by recent research and emailed to every head orthoptist within the UK. Results: There was a great deal of variability in the amount of occlusion that was prescribed for moderate and severe amblyopia. Sixty per cent of clinicians indicated that the maximum they would prescribe was in excess of the 6 h recommended by research. Atropine was rarely recommended as a first-line treatment, with occlusion generally being considered to be more effective. Despite recommendations regarding education as a means of reducing non-compliance, only 39% of clinicians always gave written information, although various other methods of enhancing compliance were used. A period of refractive adaptation was allowed by most clinicians but often far less than recommended. Conclusion: The uptake of recent research evidence into clinical practice is sporadic and incomplete with one-third of respondents indicating that following the studies, they had made no changes whatsoever to their practice. This is similar to other areas of medicine; the reasons are likely to be varied, and is an area that would benefit from greater attention. Source


Alldred S.K.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2012

Down's syndrome occurs when a person has three copies of chromosome 21 - or the specific area of chromosome 21 implicated in causing Down's syndrome - rather than two. It is the commonest congenital cause of mental retardation. Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing.   To estimate and compare the accuracy of second trimester serum markers for the detection of Down's syndrome. We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to May 2007), EMBASE (1980 to 18 May 2007), BIOSIS via EDINA (1985 to 18 May 2007), CINAHL via OVID (1982 to 18 May 2007), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2007, Issue 1), MEDION (May 2007), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (May 2007), The National Research Register (May 2007), Health Services Research Projects in Progress database (May 2007). We studied reference lists and published review articles.   Studies evaluating tests of maternal serum in women at 14-24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection. Data were extracted as test positive/test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses. Fifty-nine studies involving 341,261 pregnancies (including 1,994 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Seventeen studies made direct comparisons between tests. Fifty-four test combinations were evaluated formed from combinations of 12 different tests and maternal age; alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free beta human chorionic gonadotrophin (βhCG), free alpha human chorionic gonadotrophin (αhCG), Inhibin A, SP2, CA125, troponin, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PGF) and proform of eosinophil major basic protein (ProMBP).Meta-analysis of 12 best performing or frequently evaluated test combinations showed double and triple tests (involving AFP, uE3, total hCG, free βhCG) significantly outperform individual markers, detecting six to seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate. Tests additionally involving inhibin performed best (eight out of every 10 Down's syndrome pregnancies) but were not shown to be significantly better than standard triple tests in direct comparisons. Significantly lower sensitivity occurred in women over the age of 35 years. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting the accuracy of the sensitivity. Tests involving two or more markers in combination with maternal age are significantly more sensitive than those involving one marker. The value of combining four or more tests or including inhibin have not been proven to show statistically significant improvement. Further study is required to investigate reduced test performance in women aged over 35 and the impact of differential pregnancy loss on study findings. Source


Cheng K.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2012

Cystic fibrosis-related liver disease peaks in adolescence with up to 20% of people with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies.Date of the most recent search of the Group's trials register: 10 July 2012. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. Ten trials have been identified, of which three trials involving 118 participants were included. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30 participants from two trials. Improvement in biliary excretion was reported in only one trial and no significant change after treatment was shown. Long-term outcomes such as death or need for liver transplantation were not reported. There are few trials assessing the effectiveness of ursodeoxycholic acid. There is insufficient evidence to justify its routine use in cystic fibrosis. Source


Smyth R.L.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2012

Poor nutrition occurs frequently in people with cystic fibrosis (CF) and is associated with other adverse outcomes. Oral calorie supplements are used to increase total daily calorie intake and improve weight gain. However, they are expensive and there are concerns they may reduce the amount of food eaten and not improve overall energy intake. To establish whether in people with CF, oral calorie supplements: increase daily calorie intake; and improve overall nutritional intake, nutritional indices, lung function, survival and quality of life. To assess adverse effects associated with using these supplements. We searched the Cochrane CF Trials Register comprising references from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We contacted companies marketing oral calorie supplements.Last search: 19 July 2012. Randomised or quasi-randomised controlled trials comparing use of oral calorie supplements for at least one month to increase calorie intake with no specific intervention or additional nutritional advice in people with CF. We independently selected the included trials, assessed risk of bias and extracted data. We contacted the authors of included trials and obtained additional information for two trials. We identified 21 trials and included three, reporting results from 131 participants. There were no significant differences between people receiving supplements or dietary advice alone for change in weight, height, body mass index, z score or other indices of nutrition or growth. Changes in weight (kg) at three, six and twelve months respectively were: MD 0.32 (95% CI -0.09 to 0.72); MD 0.47 (95% CI -0.07 to 1.02 ); and MD 0.16 (-0.68 to 1.00). Total calorie intake was greater in people taking supplements at 12 months, MD 265.70 (95% CI 42.94 to 488.46). There were no significant differences between the groups for anthropometric measures of body composition, lung function, gastrointestinal adverse effects or activity levels. Oral calorie supplements do not confer any additional benefit in the nutritional management of moderately malnourished children with CF over and above the use of dietary advice and monitoring alone. While nutritional supplements may be used, they should not be regarded as essential. Further randomised controlled trials are needed to establish the role of short-term oral protein energy supplements in people with CF and acute weight loss and also for the long-term nutritional management of adults with CF or advanced lung disease, or both. Source


Mbizvo G.K.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2012

Epilepsy is an important neurological condition and drug resistance in epilepsy is particularly common in individuals with focal seizures. In this review, we summarise the current evidence regarding a new antiepileptic drug, levetiracetam, when used as add-on treatment for controlling drug-resistant focal epilepsy. This is an update to a Cochrane Review that was originally published in 2001. To evaluate the effectiveness of levetiracetam, added on to usual care, in treating drug-resistant focal epilepsy. We searched the Cochrane Epilepsy Group's Specialized Register (August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 7, 2012), and MEDLINE (1946 to August week 1, 2012). We also contacted the manufacturers of levetiracetam and researchers in the field to seek any ongoing or unpublished trials. Randomised, placebo-controlled trials of add-on levetiracetam treatment in people with drug-resistant focal epilepsy. Two review authors independently selected trials for inclusion, assessed trials for bias, extracted data, and evaluated the overall quality of evidence. Outcomes investigated included 50% or greater reduction in focal seizure frequency (response); less than 50% reduction in focal seizure frequency (non-response); treatment withdrawal; adverse effects (including a specific analysis of changes in behaviour); cognitive effects and quality of life (QoL). Risk ratios (RR) with 95% confidence intervals (CIs) were used as measures of effect (99% CIs for adverse effects). Primary analyses were Intention-to-Treat (ITT). Dose response and inter-trial heterogeneity were evaluated in regression models. Eleven trials (1861 participants) were included. They predominantly possessed low risks of bias. Participants were adults in nine trials (1565 participants) and children in the remaining two trials (296 participants). The dose of levetiracetam tested was 1000 to 4000 mg/day in adults, and 60 mg/kg/day in children. Treatment ranged from 12 to 24 weeks. For the 50% or greater reduction in focal seizure frequency outcome, the RR was significantly in favour of levetiracetam at all doses. The naive estimates, ignoring dose, showed children (52% responded) as better responders than adults (39% responded) on levetiracetam. 25% of children and 16% of adults responded to placebo. The Number Needed to Treat for an additional beneficial outcome for children and adults was four (95% CI three to seven) and five (95% CI four to six), respectively. The significant levels of statistical heterogeneity between trials on adults precluded valid provision of an overall RR (ignoring dose). Results for the two trials that tested levetiracetam 2000 mg on adults were sufficiently similar to be combined to give an RR for 50% or greater reduction in focal seizure frequency of 4.91 (95% CI 2.75 to 8.77), with an RR of 0.68 (95% CI 0.60 to 0.77) for non-response. At this dose, 37% and 8% of adults were responders in the levetiracetam and placebo groups, respectively. Regression analysis demonstrated that much of the heterogeneity between adult trials was likely to be explained by different doses of levetiracetam tested and different years of trial publication. There was no evidence of statistical heterogeneity between trials on children. For these trials, the RR for 50% or greater reduction in focal seizure frequency was 1.91 (95% CI 1.38 to 2.63), with an RR of 0.68 (95% CI 0.56 to 0.81) for non-response. 27% of children responded. Participants were not significantly more likely to have levetiracetam withdrawn (RR 0.98; 95% CI 0.73 to 1.32 and RR 0.80; 95% CI 0.43 to 1.46 for adults and children, respectively). For adults, somnolence (RR 1.51; 99% CI 1.06 to 2.17) and infection (RR 1.76; 99% CI 1.03 to 3.02) were significantly associated with levetiracetam. Accidental injury was significantly associated with placebo (RR 0.60; 99% CI 0.39 to 0.92). No individual adverse effect was significantly associated with levetiracetam in children. Changes in behaviour were negligible in adults (1% affected; RR 1.79; 99% CI 0.59 to 5.41) but significant in children (23% affected; RR 1.90; 99% CI 1.16 to 3.11). Source


Southern K.W.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2012

Macrolide antibiotics may have a modifying role in diseases which involve airway infection and inflammation, like cystic fibrosis. To test the hypotheses that, in people with cystic fibrosis, macrolide antibiotics: 1. improve clinical status compared to placebo or another antibiotic; 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, dose and duration of macrolide therapy. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching relevant journals and abstract books of conference proceedings.We contacted investigators known to work in the field, previous authors and pharmaceutical companies manufacturing macrolide antibiotics for unpublished or follow-up data (May 2010).Latest search of the Group's Cystic Fibrosis Trials Register: 29 February 2012. Randomised controlled trials of macrolide antibiotics compared to: placebo; another class of antibiotic; another macrolide antibiotic; or the same macrolide antibiotic at a different dose. Two authors independently extracted data and assessed risk of bias. Seven groups were contacted and provided additional data which were incorporated into the review. Ten of 31 studies identified were included (959 patients). Five studies with a low risk of bias examined azithromycin versus placebo and demonstrated consistent improvement in forced expiratory volume in one second over six months (mean difference at six months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four studies)). Patients treated with azithromycin were approximately twice as likely to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95% confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was a significant reduction in need for oral antibiotics and greater weight gain in those taking azithromycin. Adverse events were uncommon and not obviously associated with azithromycin, although a once-weekly high dose regimen was associated with more frequent gastrointestinal adverse events. Treatment with azithromycin was associated with reduced identification of Staphylococcus aureus on respiratory culture, but also a significant increase in macrolide resistance. This review provides evidence of improved respiratory function after six months of azithromycin. Data beyond six months were less clear, although reduction in pulmonary exacerbation was sustained. Treatment appeared safe over a six-month period; however, emergence of macrolide resistance was a concern. A multi-centre trial examining long-term effects of this antibiotic treatment is needed, especially for infants recognised through newborn screening. Source


Casse G.,University of Liverpool
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2010

Finely segmented silicon detectors made with n-side readout on p-type substrate have emerged as the most promising choice for the replacement of the tracker systems for the CERN LHC upgrade to higher luminosity. They have practically assumed the status of baseline devices for the silicon microstrip layers of the upgrades, and are now also being considered as possible candidates even for the innermost pixel layers. A review of the reasons for the success of the p-type bulk devices is presented here. © 2009 Elsevier B.V. All rights reserved. Source


Turner L.,University of Liverpool
Safer Communities | Year: 2014

Purpose - This paper aims to explore the recent introduction of directly elected police and crime commissioners (PCCs) in England and Wales, and to consider to what extent this new innovation should be considered as a positive contribution to the achievement of democratic policing. Design/methodology/ approach - The paper draws on a range of key sources of academic literature on police accountability and the sociology of policing, as well as considering the content of government pronouncements and legislation. Findings - The central argument of the paper is that the introduction of PCCs needs to be examined within the context of the hegemony of neo-liberal logic in public services reform. It is argued that some enduring myths of policing, including the myth that the police impartially uphold an impartial law, lend themselves to the depoliticisation of policing which is necessary in order to facilitate neo-liberal colonisation of the service, which is inimical to democratic policing. Originality/value - The paper builds upon and contests some of the early critiques of the introduction of PCCs which have emerged and proposes a new direction for the development of critique in this area. It will be of interest to policing scholars as well as anyone concerned about the relationship between democracy and policing under current conditions of deep public service cuts and the colonisation of service provision by neo-liberal values. Copyright © 2014 Emerald Group Publishing Limited. All rights reserved. Source


Is it feasible to screen women with idiopathic recurrent miscarriage (RM) for high uterine natural killer (uNK) cell density and then randomize them to prednisolone or placebo when pregnant? It was feasible to recruit women with idiopathic RM into a 'screen and treat' trial despite their desire for active medication. Clinical trials of immunotherapy in women with idiopathic RM have failed to substantiate efficacy in preventing miscarriage. Preimplantation uNK cell density is higher in women with RM and can be reduced with prednisolone. In a pilot RCT, 160 eligible women were screened with an endometrial biopsy and those with high uNK cell density were invited to return when pregnant for randomization to prednisolone (20 mg for 6 weeks, 10 mg for 1 week, 5 mg for 1 week) or identical placebo tablets. Randomization was by random number generation and patients, clinicians and outcome assessors were blinded to allocation. The study size and duration was determined by funding, which was for a feasibility trial, for 2 years, sufficient to screen 150 women and randomize 40 women. The outcome measures were recruitment rate, women's perspectives, compliance, live birth and miscarriage rates and pregnancy complications. The trial was advertised nationally in the UK. Women who attended research clinics run by one consultant (SQ) with three or more consecutive idiopathic miscarriages were included. Women's perspectives of the trial were sought through a questionnaire. The endometrium was sampled 5-9 days after the LH surge, stained using immunohistochemistry for CD56 and the sub-epithelial region analysed with image analysis. Women with a high uNK cell density (>5%) were invited to contact the clinic at 4-6 weeks gestation for randomization. Compliance with medication was assessed using a daily log, and side effects recorded by the women in a diary and on a structured proforma completed in the clinic at the end of the first trimester. All women had ultrasound scans every 2 weeks until 14 weeks' gestation and growth scans at 28 and 34 weeks' gestation in addition to routine antenatal care and a follow-up in person or by telephone 6 weeks after delivery. Despite the fact that 85% of women said they would prefer the active treatment, the trial recruitment occurred at the planned rate. Eligible women (n = 160) attended the research clinics and had the uNK test, 72 were screen positive and 40 returned when pregnant for randomization. Compliance with medication was reported to be 100%. The active treatment was associated with side effects of insomnia and flushing. The live birth rate was 12/20 (60%) with prednisolone and 8/20 (40%) with placebo (Risk Ratio 1.5, 95% confidence interval (CI) 0.79-2.86, absolute difference 20% CI-10%, +50%), and hence, this was not significant. There were no pregnancy complications or serious adverse fetal outcomes. This was a feasibility trial so of insufficient size to assess efficacy or safety. There was inconsistency in the start date of the trial medication and this may have affected the outcome in the active treatment group. It was feasible to recruit women with idiopathic RM into a 'screen and treat' trial despite their desire for active medication. Our data also suggest that in future trials the primary outcome measure is live birth rate after 24 weeks gestation. Source


The response of periodic microstructures to deformation can be analysed rigorously and this provides guidance in understanding more complex microstructures. When deforming by diffusion creep accompanied by sliding, irregular hexagons are shown to be anisotropic in their rheology. Analytic solutions are derived in which grain rotation is a key aspect of the deformation. If grain boundaries cannot support shear stress, the polycrystal viscosity is extremely anisotropic. There are two orthogonal directions of zero strength: sliding and rotation cooperate to allow strain parallel to these directions to be accomplished without any dissolution or plating. When a linear velocity/shear stress relationship is introduced for grain boundaries, the anisotropy is less extreme, but two weak directions still exist along which polycrystal strength is controlled only by the grain boundary "viscosity". Irregular hexagons are characterised by four parameters. A particular subset of hexagons defined by two parameters, which includes regular hexagons as well as some elongate shapes, shows singular behaviour. Grain shapes that are close to that of the subset may exhibit large grain rotation rates and have no well-defined rheology unless there is a finite grain boundary viscosity. This new analysis explains why microstructures based on irregular but near equiaxed grains show high rotation rates during diffusion creep and it provides a framework for understanding strength anisotropy during diffusion creep. © 2010 Taylor & Francis. Source


Gracey J.A.,University of Liverpool
Journal of High Energy Physics | Year: 2010

We compute the static potential in the Gribov-Zwanziger Lagrangian as a function of the Gribov mass, γ, in the MS scheme in the Landau gauge at one loop. The usual gauge independent one loop perturbative static potential is recovered in the limit as γ → 0. By contrast the Gribov-Zwanziger static potential contains the term γ 2/(p 2) 2. However, the linearly rising potential in coordinate space as a function of the radial variable r does not emerge due to a compensating behaviour as r →∞. Though in the short distance limit a dipole behaviour is present. We also demonstrate enhancement in the propagator of the bosonic localizing Zwanziger ghost field when the one loop Gribov gap equation is satisfied. The explicit form of the one loop gap equation for the Gribov mass parameter is also computed in the MOM scheme and the zero momentum value of the renormalization group invariant effective coupling constant is shown to be the same value as that in the MS scheme. © 2010 SISSA. Source


Ouyang H.,University of Liverpool
Journal of Sound and Vibration | Year: 2010

Friction-induced self-excited linear vibration is often governed by a second-order matrix differential equation of motion with an asymmetric stiffness matrix. The asymmetric terms are product of friction coefficient and the normal stiffness at the contact interface. When the friction coefficient becomes high enough, the resultant vibration becomes unstable as frequencies of two conjugate pairs of complex eigenvalues (poles) coalesce (when viscous damping is low). This short paper presents a receptance-based inverse method for assigning complex poles to second-order asymmetric systems through (active) state-feedback control of a combination of active stiffness, active damping and active mass, which is capable of assigning negative real parts to stabilise an unstable system. © 2009 Elsevier Ltd. All rights reserved. Source


Liu L.-N.,University of Liverpool
Biochimica et Biophysica Acta - Bioenergetics | Year: 2016

The cyanobacterial thylakoid membrane represents a system that can carry out both oxygenic photosynthesis and respiration simultaneously. The organization, interactions and mobility of components of these two electron transport pathways are indispensable to the biosynthesis of thylakoid membrane modules and the optimization of bioenergetic electron flow in response to environmental changes. These are of fundamental importance to the metabolic robustness and plasticity of cyanobacteria. This review summarizes our current knowledge about the distribution and dynamics of electron transport components in cyanobacterial thylakoid membranes. Global understanding of the principles that govern the dynamic regulation of electron transport pathways in nature will provide a framework for the design and synthetic engineering of new bioenergetic machinery to improve photosynthesis and biofuel production. This article is part of a Special Issue entitled: Organization and dynamics of bioenergetic systems in bacteria, edited by Conrad Mullineaux. © 2015 The Author. Published by Elsevier B.V. Source


Vogt A.,University of Liverpool
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2010

We analyze the iterative structure of unfactorized partonic structure functions in the large- x limit, and derive all-order expressions for the leading-logarithmic off-diagonal splitting functions Pgq and Pqg and the corresponding coefficient functions CΦ,q and C2,g in Higgs- and gauge-boson exchange deep-inelastic scattering. The splitting functions are given in terms of a new function not encountered in perturbative QCD so far, and vanish maximally in the supersymmetric limit CA-CF→0. The coefficient functions do not vanish in this limit, and are given by simple expressions in terms of the above new function and the well-known leading-logarithmic threshold exponential. Our results also apply to the evolution of parton fragmentation functions and semi-inclusive e+e- annihilation. © 2010 Elsevier B.V. Source


Bowers R.G.,University of Liverpool
Journal of Mathematical Biology | Year: 2011

In order to determine the possible evolutionary behaviour of an ecological system using adaptive dynamics, it is necessary in an ab initio calculation to find the fitness and its derivatives at a singular point. It has been suggested that the possible evolutionary behaviour can be predicted directly from the resident population dynamics, without the need for calculation, by applying three criteria-one based on the form of the density dependent rates and two on the role played by the evolving parameters. The existing arguments for these criteria are rather limited: they apply to systems in which individuals enter an initial class and can then move through any number of other population classes sequentially. (Extensions are included but only apply for systems of two and three classes.) Additionally, many of the arguments depend on the use of a phenomenologically motivated fitness (shown equivalent to the standard form but in a rather long and indirect manner). The present paper removes all these flaws-the criteria are established directly from the standard definition of fitness and individuals can enter any class and move through the classes non-sequentially without restriction on their number. The criteria thus established underlie a geometric description of the singular behaviour in adaptive dynamics which allows direct inferences to be made from population dynamics to the possible singular behaviour depending on which of the criteria apply and on the nature of the trade-off between evolving parameters. The method has the great advantage of leaving the trade-off explicit but unspecified. © 2010 Springer-Verlag. Source


Wong S.,University of Liverpool
Energy Policy | Year: 2012

Basing on our devised World Bank's 'Design Principles' for effective renewable energy projects in developing countries and an in-depth analysis of our two solar lighting projects in Bangladesh and India, this paper explores three key obstacles that constrain poor people from obtaining solar lighting: financial exclusion, weak governance, and passive NGO and customer participation. The low take-up rate has a social and psychological impact. This paper recommends creating easy access to credit, establishing a robust complaint system, and developing strategic partnership to overcome the obstacles. © 2010 Elsevier Ltd. Source


Read J.,University of Auckland | Bentall R.P.,University of Liverpool
British Journal of Psychiatry | Year: 2012

After decades of ignoring or minimising the prevalence and effects of negative events in childhood, researchers have recently established that a broad range of adverse childhood events are significant risk factors for most mental health problems, including psychosis. Researchers are now investigating the biological and psychological mechanisms involved. In addition to the development of a traumagenic neurodevelopmental model for psychosis, the exploration of a range of psychological processes, including attachment and dissociation, is shedding light on the specific aetiologies of discrete phenomena such as hallucinations and delusions. It is argued that the theoretical, clinical and primary prevention implications of our belated focus on childhood are profound. Source


Walklate S.,University of Liverpool
Theoretical Criminology | Year: 2011

The purpose of this article is to examine the ways in which studies of criminal victimization have contributed to this presumption of human vulnerability, and to examine the potential in understandings of resilience for overcoming this presumption. In order to do this the argument falls into three parts. In the first part I shall consider the different ways in which victimization and vulnerability have been linked together. In the second I shall examine the concept of resilience and its relationship, if any, with vulnerability and victimization. Throughout this discussion I shall draw on feminist informed work as a way of suggesting a differently oriented approach to both of these concepts: presented here as thinking otherwise. In the final and concluding part of this article the implications of contemporary understandings of these concepts will be situated within the broader policy context characterized by Aradau (2004) as informed by a 'politics of pity'. © The Author(s) 2011. Source


Lemaitre J.F.,University of Liverpool
Proceedings. Biological sciences / The Royal Society | Year: 2011

Theory predicts that males should increase overall investment in ejaculate expenditure with increasing levels of sperm competition. Since ejaculate production is costly, we may expect males to tailor their reproductive investment according to anticipated levels of sperm competition. Here, we investigate plasticity in ejaculate investment in response to cues of population average levels of sperm competition in a promiscuous mammal, the bank vole (Myodes glareolus). We manipulated the social experience of experimental subjects during sexual development via differential exposure to the odour of rival males, to simulate conditions associated with relatively high or low average levels of sperm competition. Males exposed to a high level of competition developed larger major accessory reproductive glands (seminal vesicles) than those that experienced a low level of competition, suggesting that an increased investment in the production of copulatory plugs and/or mating rate may be beneficial at relatively high sperm competition levels. However, investment in sperm production, testis size and sperm motility were not altered according to social experience. Our findings emphasize the importance of non-sperm components of the ejaculate in mammalian postcopulatory sexual selection, and add to the growing evidence linking plasticity in reproductive traits to social cues of sperm competition. Source


Oldfield F.,University of Liverpool
Journal of Paleolimnology | Year: 2013

The paper presents a personal summary of the role of magnetic measurements in lake sediment studies. Examples are used to illustrate the main variations in lake sediment magnetic properties and the processes controlling their variations. These are considered in terms of sediment sequences: (1) that are virtually devoid of magnetic minerals; (2) the magnetic properties of which are dominated by input of magnetic minerals from 'primary', unweathered catchment sources (3) with magnetic properties indicative of erosion of weathered material, mainly magnetically enhanced topsoil; (4) that have received minimal input of terrigenous ferrimagnetic minerals but are rich in biogenic magnetite (5) parts of which have experienced dissolution diagenesis (6) in which signals from erosion, biogenic magnetite and dissolution can all be detected and (7) that are dominated by the presence of authigenic greigite. Additional issues, including the importance of particle size variations as a control of magnetic properties, the under-representation of haematite and goethite in the magnetic record and the significance of atmospheric deposition are also considered. A concluding section briefly outlines the present status of environmental magnetism and its role in palaeoenvironmental research based on lake sediment studies. © 2013 Springer Science+Business Media Dordrecht. Source


Mukaka M.M.,University of Malawi | Mukaka M.M.,University of Liverpool
Malawi Medical Journal | Year: 2012

Correlation is a statistical method used to assess a possible linear association between two continuous variables. It is simple both to calculate and to interpret. However, misuse of correlation is so common among researchers that some statisticians have wished that the method had never been devised at all. The aim of this article is to provide a guide to appropriate use of correlation in medical research and to highlight some misuse. Examples of the applications of the correlation coefficient have been provided using data from statistical simulations as well as real data. Rule of thumb for interpreting size of a correlation coefficient has been provided. Source


Pilgrim D.,University of Liverpool
Sociology of Health and Illness | Year: 2012

It is now over thirty years since Claus Offe theorised the crisis tendencies of the welfare state in late capitalism. As part of that work he explored ongoing and irresolvable forms of crisis management in parliamentary democracies: capitalism cannot live with the welfare state but also cannot live without it. This article examines the continued relevance of this analysis by Offe, by applying its basic assumptions to the response of the British welfare state to mental health problems, at the turn of the twenty first century. His general theoretical abstractions are tested against the empirical picture of mental health service priorities, evident since the 1980s, in sections dealing with: re-commodification tendencies; the ambiguity of wage labour in the mental health workforce; the emergence of new social movements; and the limits of legalism. © 2012 The Author. Sociology of Health & Illness © 2012 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd. Source


Behnsen J.,University of Manchester | Faulkner D.R.,University of Liverpool
Journal of Geophysical Research: Solid Earth | Year: 2013

Smectites, such as montmorillonite, are abundant throughout the upper crust and are commonly found in fault gouge. They are known for their weak frictional strength and low permeability. Smectites are swellable clays in which the interlayer cation can easily be exchanged. In this study, we measure permeability and frictional strength of montmorillonite exchanged with Na +, K+, Ca2+, and Mg2+ using a triaxial shear apparatus. We find that the interlayer cation influences both permeability and the friction coefficient. K-montmorillonite is significantly stronger (μ=0.26) than Na-montmorillonite (μ=0.15) and Ca- or Mg-montmorillonite (μ=0.11). Permeability for all four clays is between 10-21 and 10-23 m2 in the pressure range between 10 MPa and 100 MPa, with K-montmorillonite the most permeable clay gouge. Mg-, Ca-, and Na-montmorillonite show relative similar permeabilities of which Na-montmorillonite is least permeable. We relate the higher frictional strength and permeability of K-montmorillonite to reduce interlayer water content caused by differences in cation hydration and adsorption. The results show that the rapid cation exchange process in montmorillonite can influence macroscale parameters, such as permeability and strength, which can contribute to changes in local pressure conditions and frictional strength of shallow fault zones. © 2013. American Geophysical Union. All Rights Reserved. Source


Mitchison D.,St. Georges Hospital Medical School | Davies G.,University of Liverpool
International Journal of Tuberculosis and Lung Disease | Year: 2012

The history of the development of modern chemotherapy for tuberculosis (TB), largely due to the British Medical Research Council, is first described. There is a current need to shorten the duration of treatment and to prevent and cure drug-resistant disease. These aims will only be achieved if the way in which multidrug treatment prevents resistance from emerging and the reasons for the very slow response to chemotherapy are understood. Consideration of mutation rates to resistance and the size of bacterial populations in lesions makes it very unlikely that resistance would emerge spontaneously, leaving irregularity in drug taking and inadequate dosage as the main reasons for its occurrence. Slow response to treatment seems due to the presence of persister populations whose natural history is only partly known. In the future, we need to explore the persister state in patients and in experimental murine TB, and to take it into account in the design of future mouse experiments. The activity of rifamycins and pyrazinamide is being increased by a rise in rifamycin dosage and the inhalation of pyrazinoic acid. New drugs are gradually being brought into use, initially TMC207 and the nitroimadazoles, PA824 and OPC67683. They will need to be tested in new combination regimens for drug-susceptible and multi- and extensively drug-resistant disease. © 2012 The Union. Source


Gumruk R.,Karadeniz Technical University | Mines R.A.W.,University of Liverpool
International Journal of Mechanical Sciences | Year: 2013

This paper focuses on investigating the mechanical static compression behaviour of 316L stainless steel micro-lattice materials manufactured using selective laser melting method. In theoretical and numerical approaches, the material overlapping effects in the vicinity of strut connection points is taken into consideration to give reasonable predictions corresponding to the initial stiffness and strength values. In theoretical studies, Timoshenko beam model is used to consider the shear effect in calculation of initial stiffness. In addition, to include work hardening of micro struts in calculation of collapse strength a model is developed. Experiments have shown that mechanical response of micro lattice structures is governed by their aspect ratio. The theoretical predictions are quite close to experiments. Finite element models simulate the initial stiffness and strength values related to experimental tests, although there are some small differences in loading history, resulting from the complex strut joint geometry and variable diameter. Also, within the scope of this paper, the stress-strain curves of an individual defected micro strut manufactured using selective laser melting method are measured using an efficient method and the elasticity modulus for the defected micro strut is found as 97 GPa, which is 60% lower than bulk material. As a result, the findings show that in the micro scaled structures, the geometry of connection points and material overlapping should be taken into account to find the proper results in terms of mechanical responses in theoretical studies as well as finite element models. © 2013 Elsevier Ltd. Source


Li G.L.,Max Planck Institute of Colloids and Interfaces | Zheng Z.,Max Planck Institute of Colloids and Interfaces | Mohwald H.,Max Planck Institute of Colloids and Interfaces | Shchukin D.G.,Max Planck Institute of Colloids and Interfaces | Shchukin D.G.,University of Liverpool
ACS Nano | Year: 2013

We report the development of silica/polymer double-walled hybrid nanotubes, which consist of a hollow cavity, a porous silica inner wall, and a stimuli-responsive (pH, temperature, and redox) polymeric outer wall, as a novel nanocontainer system. The length, diameter, wall thickness, and aspect ratio of the hybrid nanotubes are precisely controlled in the range of 48-506 nm, 41-68 nm, 3-24 nm, and 1.2-7.6, respectively. The hybrid nanotubes loaded with active molecules exhibit morphology-dependent release and pH-, temperature-, redox-responsive release, which enable a wide range of applications from energy storage to drug delivery and self-healing coatings for metal corrosion protection. © 2013 American Chemical Society. Source


Piper J.D.A.,University of Liverpool
Tectonophysics | Year: 2013

Plate Tectonics requires a specific range of thermal, fluid and compositional conditions before it will operate to mobilise planetary lithospheres. The response to interior heat dispersion ranges from mobile lids in constant motion able to generate zones of subduction and spreading (Plate Tectonics), through styles of Lid Tectonics expressed by stagnant lids punctured by volcanism, to lids alternating between static and mobile. The palaeomagnetic record through Earth history provides a test for tectonic style because a mobile Earth of multiple continents is recorded by diverse apparent polar wander paths, whilst Lid Tectonics is recorded by conformity to a single position. The former is difficult to isolate without extreme selection whereas the latter is a demanding requirement and easily recognised. In the event, the Precambrian palaeomagnetic database closely conforms to this latter property over very long periods of time (~. 2.7-2.2. Ga, 1.5-1.3. Ga and 0.75-0.6. Ga); intervening intervals are characterised by focussed loops compatible with episodes of true polar wander stimulated by disturbances to the planetary figure. Because of this singular property, the Precambrian palaeomagnetic record is highly effective in showing that a dominant Lid Tectonics operated throughout most of Earth history. A continental lid comprising at least 60% of the present continental area and volume had achieved quasi-integrity by 2.7. Ga. Reconfiguration of mantle and continental lid at ~. 2.2. Ga correlates with isotopic signatures and the Great Oxygenation Event and is the closest analogy in Earth history to the resurfacing of Venus. Change from Lid Tectonics to Plate Tectonics is transitional and the geological record identifies incipient development of Plate Tectonics on an orogenic scale especially after 1.1. Ga, but only following break-up of the continental lid (Palaeopangaea) in Ediacaran times beginning at ~. 0.6. Ga has it become comprehensive in the style evident during the Phanerozoic Eon (<. 0.54. Ga). © 2013 Elsevier B.V. Source


Fielding S.R.,University of Liverpool
Limnology and Oceanography | Year: 2013

A revised estimate of the relationship between the maximum growth rate (μmax, d-1) of Emiliania huxleyi and temperature (T, °C) was made using quantile regression and literature data from culture experiments (n = 1415). For modeling E. huxleyi bloom formation and coccolithophore functional group growth rate, this relationship is commonly assumed to follow an exponential relationship, as is the case for photosynthetic algal species in general. However, data specific to E. huxleyi show that this relationship is better described by a power function. Direct comparison with growth rate-temperature relationships used to model E. huxleyi from the literature shows that they overestimate growth rate by up to 250% over a wide range of temperatures. It is recommended that the revised relationship of μmax = 0.1419T 0.8151 be used in future models incorporating temperature-dependent maximum growth rate estimates of E. huxleyi and of coccolithophores as a functional group. © 2013, by the Association for the Sciences of Limnology and Oceanography, Inc. Source


Brust M.,University of Liverpool | Gordillo G.J.,University of Buenos Aires
Journal of the American Chemical Society | Year: 2012

Electrocatalytic proton reduction leading to the formation of adsorbed molecular hydrogen on gold nanoparticles of 1-3 and 14-16 nm diameter stabilized by 1-mercapto-undecane-11-tetra(ethyleneglycol) has been demonstrated by cyclic voltammetry using a hanging mercury drop electrode. The nanoparticles were adsorbed to the electrode from aqueous dispersion and formed robust surface layers transferrable to fresh base electrolyte solutions. Unique electrocatalytic proton redox chemistry was observed that has no comparable counterpart in the electrochemistry of bulk gold electrodes. Depending on size, the nanoparticles have a discrete number of electrocatalytically active sites for the two-electron/two-proton reduction process. The adsorbed hydrogen formed is oxidized with the reverse potential sweep. These findings represent a new example of qualitative different behavior of nanoparticles in comparison with the corresponding bulk material. © 2012 American Chemical Society. Source


Jones N.,University of Liverpool | Paik J.K.,Pusan National University
International Journal of Impact Engineering | Year: 2012

The perforation of aluminium alloy plates subjected to impacts characterised as low-velocity (up to about 20 m/s) and moderate-velocity (20-300 m/s, approximately) are examined in this paper, wherein recent experimental data and some empirical equations have been compared. The threshold velocity for the normal perforation of metal plates focuses on cylindrical projectiles with various shaped impact faces, principally flat. A criterion is suggested in order to distinquish between low-velocity and moderate-velocity impacts. Several new empirical equations have been developed in this paper. Recommendations are made for the use of particular empirical equations that are suitable for estimating the perforation energy of plates in the two impact velocity regimes which have been examined in this article. There is a paucity of experimental data which hinders the development of empirical equations, though surprisingly accurate predictions for perforation velocities are possible to achieve for some practical problems. Nevertheless, numerical studies are required to remove many of the restrictions on the validity of empirical equations, but these methods require a considerable amount of accurate experimental data on the dynamic material properties and failure criteria. © 2011 Elsevier Ltd. All rights reserved. Source


Volker C.,Alfred Wegener Institute for Polar and Marine Research | Tagliabue A.,University of Liverpool
Marine Chemistry | Year: 2015

Most dissolved iron in the ocean is bound to organic molecules with strong conditional stability constants, known as ligands that are found at concentrations ranging from 0.2 to more than 10nmolL-1. In this work we report the first mechanistic description of ligand dynamics in two three-dimensional models of ocean biogeochemistry and circulation. The model for ligands is based on the concept that ligands are produced both from organic matter remineralization and phytoplankton processes, and that they are lost through bacterial and photochemical degradation, as well as aggregation and to some extent in the process of phytoplankton uptake of ligand-bound iron.A comparison with a compilation of in-situ measurements shows that the model is able to reproduce some large-scale features of the observations, such as a decrease in ligand concentrations along the conveyor belt circulation in the deep ocean, lower surface and subsurface values in the Southern Ocean, or higher values in the mesopelagic than in the abyssal ocean.Modeling ligands prognostically (as opposed to assuming a uniform ligand concentration) leads to a more nutrient-like profile of iron that is more in accordance with data. It however, also leads to higher surface concentrations of dissolved iron and negative excess ligand L* in some ocean regions. This is probably an indication that with more realistic and higher ligand concentrations near the surface, as opposed to the traditionally chosen low uniform concentration, iron modelers will have to re-evaluate their assumption of low scavenging rates for iron. Given their sensitivity to environmental conditions, spatio-temporal variations in ligand concentrations have the potential to impact primary production via changes in iron limitation. © 2014. Source


Kougioumtzoglou I.A.,University of Liverpool
Journal of Sound and Vibration | Year: 2013

A novel approximate analytical approach for determining the response evolutionary power spectrum (EPS) of nonlinear/hysteretic structural systems subject to stochastic excitation is developed. Specifically, relying on the theory of locally stationary processes and utilizing a recently proposed representation of non-stationary stochastic processes via wavelets, a versatile formula for determining the nonlinear system response EPS is derived; this is done in conjunction with a stochastic averaging treatment of the problem and by resorting to the orthogonality properties of harmonic wavelets. Further, the nonlinear system non-stationary response amplitude probability density function (PDF), which is required as input for the developed approach, is determined either by utilizing a numerical path integral scheme, or by employing a time-dependent Rayleigh PDF approximation technique. A significant advantage of the approach relates to the fact that it is readily applicable for treating not only separable but non-separable in time and frequency EPS as well. The hardening Duffing and the versatile Preisach (hysteretic) oscillators are considered in the numerical examples section. Comparisons with pertinent Monte Carlo simulations demonstrate the reliability of the approach. © 2013 Elsevier Ltd. Source


Grove M.,University of Liverpool
Quaternary International | Year: 2015

The origin and initial dispersal of Homo sapiens out of East Africa and into the Levant remains a major research focus in evolutionary anthropology. There is little doubt that climatic changes played a role in facilitating this dispersal, but the specific dynamics remain poorly understood. This contribution surveys the fossil and genetic evidence for the origin and dispersal of modern humans, and situates this evidence within the context of biological theories of plasticity and dispersal. It is shown that certain climatic and environmental conditions are expected to lead to the evolution of plastic strategies, and that such strategies are characteristic of successfully dispersing species. A model is formulated that allows for the identification of features in climatic records that are conducive to the evolution of plasticity, and thus to the development of dispersal capabilities. Using as an example a palaeoclimatic record from Lake Tana, Ethiopia, the model is used to pinpoint the chronology of likely periods of dispersal from East Africa. Results indicate the presence of a dispersal phase c.97-105ka, a date that fits well with the initial modern human colonisation of the Levant shortly after 100ka. Implications of recent genetic chronologies for the origin of non-African modern humans and the archaeological evidence for possible routes out of Africa are discussed in this context. © 2014 Elsevier Ltd and INQUA. Source


Sharples S.,University of Liverpool | Radhi H.,Global Engineering Bureau
Renewable Energy | Year: 2013

This paper assesses the technical and economic performance of PV technology integrated into residential buildings in the Gulf Cooperation Council (GCC) countries. It highlights the value of PV electricity for the GCC society from the perspective of consumers, utilities and environment. Through a systematic modelling analysis it is shown that the efficiency of PV system drops by 4-6% due to high range of module temperature and also a change in power output due to high ambient temperatures. Consequently, the outputs of horizontal and vertical PV modules are found to be less than estimates based on standard test conditions. Economically, this study shows that building integrated photovoltaic (BIPV) systems are not viable in GCC countries and cannot compete with conventional electricity sources on a unit cost basis. From a society point of view, however, the integration of PV technology into buildings would have several benefits for the GCC countries, including: first, savings in capital cost due to central power plants and transmission and distribution processes; second, an increase in the exported oil and natural gas used for electricity generation; and third, a reduction in the CO2 emissions from conventional power plants. When these considerations are taken into account then BIPV should become a feasible technology in GCC countries. © 2012 Elsevier Ltd. Source


Lloyd C.D.,University of Liverpool
Transactions of the Institute of British Geographers | Year: 2015

Areas within England and Wales have population profiles that make them distinct from other locales; some areas have lower unemployment rates than others, while, in some places, there is a greater mix of ethnic groups than elsewhere. Thus, the degree of difference between areas differs geographically and between population sub-groups. Being able to measure change in these differences is crucial in assessing whether the population has become more or less similar over time. The spatial distribution of the population by, for example, ethnicity or employment status can be characterised and the resulting measures show how the population is geographically organised, and how this changes through time. For example, spatial concentrations of the population by age may be less obvious locally (e.g. within a town or city) or regionally (e.g. the north west of England) than by housing tenure. This paper makes two key contributions: (i) it introduces methods for the analysis of spatial distributions of population sub-groups and (ii) enhances our understanding of the characteristics of population sub-groups in England and Wales and how they have changed over time. Based on Census data for Output Areas, the analysis uses the index of dissimilarity, Moran's I autocorrelation coefficient and the variogram to measure (spatial) variation in variables representing population sub-groups by age, ethnic group, housing tenure, car or van ownership, qualifications, employment, limiting long term illness and National Statistics Socio-economic Classification. The analysis shows that, between 2001 and 2011, unevenness in most population sub-groups reduced and the populations in individual Census zones across England and Wales became more similar. Neighbouring Census zones also became more similar (more 'clustered'). The findings suggest that there were decreased differences both within and between regions for many population variables between 2001 and 2011. © 2014 Royal Geographical Society (with the Institute of British Geographers). Source


Christley R.M.,University of Liverpool
Open Epidemiology Journal | Year: 2010

It is well recognised that low statistical power increases the probability of type II error, that is it reduces the probability of detecting a difference between groups, where a difference exists. Paradoxically, low statistical power also increases the likelihood that a statistically significant finding is actually falsely positive (for a given p-value). Hence, ethical concerns regarding studies with low statistical power should include the increased risk of type I error in such studies reporting statistically significant effects. This paper illustrates the effect of low statistical power by comparing hypothesis testing with diagnostic test evaluation using concepts familiar to clinicians, such as positive and negative predicative values. We also note that, where there is a high probability that the null hypothesis is true, statistically significant findings are even more likely to be falsely positive. © R.M. Christley; Licensee Bentham Open. Source


Iturriza-Gomara M.,University of Liverpool | Lopman B.,Centers for Disease Control and Prevention
Current Opinion in Infectious Diseases | Year: 2014

PURPOSE OF REVIEW: To provide an overview of the burden of norovirus disease in healthcare settings and the factors responsible for outbreaks in these institutions; to assess progress on interventions aimed at reducing the burden of norovirus disease. RECENT FINDINGS: Norovirus outbreaks in healthcare settings are driven by confluence of viral diversity, the built environment, and host factors. Some of these characteristics may be modifiable and the target of successful interventions. SUMMARY: Most norovirus outbreaks in hospital and residential care institutions are associated with a particular genotype, known as GII.4. The persistence of norovirus is associated with strain diversity, which is driven by immune evasion and viral adaptation to interaction with a variety of human histo-blood group antigens. The healthcare environment presents serious challenges for control, both because of the physical structure of the built space and the high levels of contact among patient populations who may have compromised hygiene. Increased vulnerability among the populations in healthcare institutions is likely to be multifactorial and may include the following: nutritional status, immunodeficiency or senescence, chronic inflammation, and microbiome alterations. Current control measures are based on general infection control principles, and treatment is mainly supportive and nonspecific. Vaccines and antiviral agents are being developed with promising results, but none are currently available. © 2014 Wolters kluwer Health. Source


Kougioumtzoglou I.A.,University of Liverpool | Spanos P.D.,Rice University
Probabilistic Engineering Mechanics | Year: 2012

A novel approximate analytical technique for determining the non-stationary response probability density function (PDF) of a class of randomly excited nonlinear oscillators is developed. Specifically, combining the concepts of statistical linearization and of stochastic averaging the evolution of the response amplitude of oscillators with nonlinear damping is captured by a first-order stochastic differential equation (SDE). This equation has nonlinear drift but constant diffusion coefficients. This convenient feature of the SDE along with the concept of the Wiener path integral is utilized in conjunction with a variational formulation to derive an approximate closed form solution for the response amplitude PDF. Notably, the determination of the non-stationary response PDF is accomplished without the need to advance the solution in short time steps as it is required by the existing alternative numerical path integral solution schemes. In this manner, an analytical Wiener path integral based technique is developed for treating certain stochastic dynamics problems for the first time. Further, the technique can be used as a convenient tool for assessing the accuracy of alternative, more general, approximate solution methods. The accuracy of the technique is demonstrated by pertinent Monte Carlo simulations. © 2011 Elsevier Ltd. All rights reserved. Source


Van Der Poel W.H.,Wageningen University | Van Der Poel W.H.,University of Liverpool
Current Opinion in Virology | Year: 2014

Hepatitis E virus (HEV), genus Hepevirus, family hepeviridae is a main cause of epidemic hepatitis in developing countries and single cases of hepatitis in higher income countries. There are at least four HEV genotypes which have different epidemiologic and clinical features. Hepatitis E viruses are often transmitted via food and environmental routes. The actual role of these transmission routes in the spread of HEV can depend on the virus genotype, the environmental conditions, the hygienic conditions and the types of foods consumed. In this review food and environmental routes of HEV transmission are discussed to raise the awareness regarding the focal points for the development of accurate prevention and control strategies of HEV infection, food safety and public health protection © 2014 Elsevier B.V. Source


Taylor M.L.,University of Exeter | Price T.A.R.,University of Liverpool | Wedell N.,University of Exeter
Trends in Ecology and Evolution | Year: 2014

A popular notion in sexual selection is that females are polyandrous and their offspring are commonly sired by more than a single male. We now have large-scale evidence from natural populations to be able to verify this assumption. Although we concur that polyandry is a generally common and ubiquitous phenomenon, we emphasise that it remains variable. In particular, the persistence of single paternity, both within and between populations, requires more careful consideration. We also explore an intriguing relation of polyandry with latitude. Several recent large-scale analyses of the relations between key population fitness variables, such as heterozygosity, effective population size (Ne), and inbreeding coefficients, make it possible to examine the global effects of polyandry on population fitness for the first time. © 2014 The Authors. Source


An increasingly sophisticated array of approaches are now available for the study of the activities of reactive oxygen species and oxidative modifications in skeletal muscle, but the most up-to-date techniques are not readily available to many researchers in this field due to their requirement for sophisticated mass spectrometry, imaging or other high cost technologies. Most papers published therefore rely on a number of established approaches although the choice of approach is also clearly dependent upon the experimental model and access to skeletal muscle that is available to the investigator, how much detail is required and the overall question to be addressed. Numerous reports have described the problems associated with some of the popular approaches that are widely followed, including measurement of thiobarbituric acid substances and the sole use of fluorescence-based probes such as dichlorodihydrofluorescein. This brief review reports the areas in which methods are improving to allow valid assessments to made in this area and indicates some of the more recent developments that provide alternative ways to assess the activity of individual species and endpoints in the various experimental models that may be examined. © 2016 The Physiological Society. Source


Wheeler J.,University of Liverpool
Geology | Year: 2014

Thermodynamic calculations predict mineralogy from temperature and pressure and vice versa. Such calculations assume that stress is isotropic despite the fact that differential stresses prevail in Earth, resulting from large-scale tectonics and/or differences between fluid and rock pressures in porous rocks. New calculations show that differential stress can have significant effects on thresholds for metamorphic reactions, depending on the grain-scale reaction pathways. A differential stress may, depending on the reaction pathway, have an effect equivalent to a pressure difference on the order of (assemblage volume)/(reaction volume change) × (differential stress). The multiplying factor is typically 10 or more. For example, the onset of a garnet + clinopyroxene breakdown reaction may be offset, up or down, by the equivalent of 500 MPa in pressure for a 50 MPa differential stress. The effect is equivalent to a temperature difference on the order of (assemblage volume)/(reaction entropy change) × (differential stress). For example, the onset of muscovite + quartz breakdown may be offset, up or down, by the equivalent of 130 °C for a 50 MPa differential stress. Much of Earth is under differential stress, so the new calculations invite a reappraisal of metamorphic mineralogy and microstructure, indicating that new insights into stresses and fluid pressures on Earth can be gained. © 2014 Geological Society of America. Source


Smith H.G.,University of Liverpool | Blake W.H.,University of Plymouth
Geomorphology | Year: 2014

Fine sediment source fingerprinting techniques have been widely applied in agricultural river catchments. Successful source discrimination in agricultural environments depends on the key assumption that land-use source signatures imprinted on catchment soils are decipherable from those due to other landscape factors affecting soil and sediment properties. In this study, we re-examine this critical assumption by investigating (i) the physical and chemical basis for source discrimination and (ii) potential factors that may confound source un-mixing in agricultural catchments, including particle size and organic matter effects on tracer properties. The study is situated in the River Tamar, a predominantly agricultural catchment (920km2) in south-west England that has also been affected by mining. Source discrimination focused on pasture and cultivated land uses and channel banks. Monthly, time-integrated suspended sediment samples were collected across seven catchments for a 12-month period. Physical and chemical properties measured in source soils and sediment included fallout radionuclides (137Cs, excess 210Pb), major and minor element geochemical constituents, total organic carbon and particle size. Source discrimination was entirely dependent on differences in tracer property concentrations between surface and sub-surface soils. This is based on fallout radionuclide concentrations that are surface-elevated, while many geochemical properties are surface-depleted due to weathering and pedogenetic effects, although surface soil contamination can reverse this trend. However, source discrimination in the study catchments was limited by (i) rotation of cultivated and pasture fields resulting in reduced differences between these two sources, and (ii) the cultivated source signature resembling a mix of the pasture and channel bank sources for many tracer properties. Furthermore, a combination of metal pollution from abandoned historic mines and organic enrichment of sediment from upland areas of peaty soils resulted in the non-conservative behaviour of some tracer properties in several catchments. Differences in the particle size and organic carbon content of source soils could explain much of the variation in these properties in downstream sediment, rather than selective transport effects. Inconsistent relationships between particle size, organic carbon and tracer property concentrations further undermined the basis for the use of widely applied corrections to tracer datasets. Sensitivity analysis showed that correcting source tracer data for differences in organic matter can produce large changes to source contribution estimates that cannot be justified, and such corrections should not be used. Confounding factors related to poor source discrimination and non-conservative behaviour are highly likely to affect sediment fingerprinting studies in many agricultural catchments. As a result, estimates of source contributions in many fingerprinting studies may contain significant unquantified errors. © 2013 Elsevier B.V. Source


Turner M.A.,University of Liverpool
Early Human Development | Year: 2011

Drug development is crucial to improving the care given to neonates through new and existing medicines. Pressure from regulatory agencies has improved the way in which pharmaceutical companies work with neonates. This provides new opportunities for the neonatal community. This paper describes the issues that arise during the development of new drugs and considers how the contemporary approach to new drugs can inform research on existing drugs. © 2011 Elsevier Ireland Ltd. Source


Tu X.,University of Liverpool | Whitehead J.C.,University of Manchester
International Journal of Hydrogen Energy | Year: 2014

An alternating-current (AC) gliding arc reactor has been developed offering a new route for the co-generation of syngas and value-added carbon nanomaterials by plasma dry reforming of methane. Different carbon nanostructures including spherical carbon nanoparticles, multi-wall carbon nanotubes and amorphous carbon have been obtained as by-products of syngas generation in the plasma system. Optical emission spectra of the discharge demonstrate the formation of different reactive species (Al, CO, CH, C 2, Hα, Hβ and O) in the plasma dry reforming reaction. The effect of different operating parameters (feed flow rate, input power and CH4/CO2 molar ratio) on the performance of the plasma process has been evaluated in terms of the conversion of feed gas, product selectivity and energy conversion efficiency. It is interesting to note that gliding arc plasma can be used to generate much cleaner gas products of which syngas is the main one. The results also show that the energy efficiency of dry reforming using gliding arc plasma is an order of magnitude higher than that for processing using dielectric barrier or corona discharges. Both of these can be attributed to the higher electron density in the order of 1023 m-3 generated in the gliding arc plasma. Copyright © 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved. Source


The impact of dilute polymer solution drops (equilibrium diameter: ~3. mm) on a hot surface in the Leidenfrost regime is studied experimentally by high-speed imaging, in the range of impact Weber numbers between 10 and 200, and compared with the impact of water drops in the same conditions. Dilute solutions of polyethylene oxide (PEO) in de-ionised water were used as model viscoelastic fluids, with polymer mass concentrations in the range 100-400. ppm. Results confirm previous findings showing that polymer additives cause a reduction of the maximum spreading diameter and an increase of the maximum bouncing height of drops already at low polymer concentrations. This suggests a different distribution of the initial impact kinetic energy with respect to drops of pure water. The analysis of drop oscillations does not show significant effects of the polymer concentration on the drop dynamic behaviour which is similar in Newtonian and in viscoelastic drops. © 2013 Elsevier Inc. Source


Vallabhaneni S.R.,University of Liverpool
Circulation | Year: 2012

Background-Fenestrated endovascular repair of abdominal aortic aneurysms has been proposed as an alternative to open surgery for juxtarenal and pararenal abdominal aortic aneurysms. At present, the evidence base for this procedure is predominantly limited to single-center or single-operator series. The aim of this study was to present nationwide early results of fenestrated endovascular repair in the United Kingdom. Methods and Results-All patients who underwent fenestrated endovascular repair between January 2007 and December 2010 at experienced institutions in the United Kingdom(>10 procedures) were retrospectively studied by use of the GLOBALSTAR database. Site-reported data relating to patient demographics, aneurysm morphology, procedural details, and outcome were recorded. Data from 318 patients were obtained from 14 centers. Primary procedural success was achieved in 99% (316/318); perioperative mortality was 4.1%, and intraoperative target vessel loss was observed in 5 of 889 target vessels (0.6%). The early reintervention (<30 days) rate was 7% (22/318). There were 11 deaths during follow-up; none were aneurysm-related. Survival by Kaplan-Meier analysis was 94% (SE 0.01), 91% (0.02), and 89% (0.02) at 1, 2, and 3 years, respectively. Freedom from target vessel loss was 93% (0.02), 91% (0.02), and 85% (0.06), and freedom from late secondary intervention (>30 days) was 90% (0.02), 86% (0.03), and 70% (0.08) at 1, 2, and 3 years. Conclusions-In this national sample, fenestrated endovascular repair has been performed with a high degree of technical and clinical success. Late survival and target vessel patency are satisfactory. These results support continued use and evaluation of this technique for juxtarenal aneurysms, but illustrate the need for a more robust evidence base. © 2012 American Heart Association, Inc. Source


Luo Y.,University of Edinburgh | Carnell A.J.,University of Liverpool | Lam H.W.,University of Edinburgh
Angewandte Chemie - International Edition | Year: 2012

Fixed: Cyclic imines, in which the C=N bond is constrained in the Z geometry, have been identified as highly effective substrates for enantioselective rhodium-catalyzed additions of potassium alkenyltrifluoroborates. Not only is the alkene in the products a useful functional handle for subsequent manipulations, products containing aryl sulfamates may be employed in nickel-catalyzed Suzuki-Miyaura and Kumada coupling reactions to generate further compounds of interest. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Cooper A.I.,University of Liverpool
Angewandte Chemie - International Edition | Year: 2012

Holey suitable crystals: A trisbenzimidazolone molecule self-assembles by hydrogen bonding to form a permanently porous crystal with an apparent surface area, SA BET, of 2796 m 2 g -1 (see scheme), demonstrating that extrinsic, intermolecular porosity is a viable strategy for highly porous materials. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Stanistreet I.G.,University of Liverpool
Journal of Human Evolution | Year: 2012

Reconstructing paleoenvironments and landscapes within lake-centered, hominin-yielding basinal sequences requires a resolution of time-rock units finer than but complementary to that provided by the present tephrostratigraphy. Although indispensable in providing an absolute time frame at Olduvai, the average 15,000-20,000 year intervals between successive tuff units lack the time resolution to construct a sufficiently contemporary paleolandscape within sedimentary intervals away from the interleaved tuffs. Such control is essential to construct valid paleogeographies in which to contextualize contemporaneous paleoanthropological sites and the traces of hominin land use they contain. Within Beds I and II of the Olduvai Basin a Sequence Stratigraphic analysis has achieved a relative time framework in which time-rock units, "lake-parasequences," each generated by a major advance and withdrawal of the lake system, are recognizable for average periods of about 4000 years duration. Within each of these time slices at least two paleogeographic landscapes are identifiable, reducing the time constraints of an individual landscape reconstruction to a few thousand years. Within the sedimentary succession both highly incised and less incised unconformities are identifiable to provide sequence boundaries. Within each sequence the higher frequency lake-parasequences can be identified by (1) a disconformable base, (2) accretion of sediment during lake transgression and at maximum, (3) a disconformable top caused by lake withdrawal, and (4) a soil profile generated beneath that disconformable land surface. Individual lake-parasequences can be recognized in lake marginal and fan settings, and their imprint can also be seen in the lake setting where, for example, maximum flooding might be marked by a layer of dolomite. Lower Bed II parasequences represent time intervals of <5000 years, while parasequential periods between Tuffs IB and IC in Bed I are <4300 years. Analogous Holocene lake-level changes of the same order in East Africa have a period close to 4200 years. The estimated period is close to that defined by Stadial/Interstadial Dansgaard-Oeschger Events recorded in the Greenland Ice record, which force cycles of period similar to lake-parasequences, both in the Arabian Sea and Lake Malawi. Lake-parasequences not only aid construction of landscapes, they also allow contextualization of individual paleoanthropological occurrences. For instance, a parasequence lies between Leakey's Level 1 and her butchered Deinotherium occurrence at FLK N. However, elephantid and giraffid skeletons associated with stone artifacts at VEK, uncovered by OLAPP excavations, are situated on the same land surface as a possibly butchered rhinocerid at KK. To complement the existing absolute radiometric time framework, relative Sequence Stratigraphic techniques might be applied to any lake-centered, hominin-yielding basinal sequence, not only those found within East Africa. Because they are climatically controlled, and might plausibly be related to globally driven Dansgaard-Oeschger Events, lake-parasequences and their associated sequences might be correlatable between various East African basins in the Plio-Pleistocene in the same way as they presently are for the Holocene. © 2012 Elsevier Ltd. Source


Stollhofen H.,Friedrich - Alexander - University, Erlangen - Nuremberg | Stanistreet I.G.,University of Liverpool
Journal of Human Evolution | Year: 2012

Normal faults displacing Upper Bed I and Lower Bed II strata of the Plio-Pleistocene Lake Olduvai were studied on the basis of facies and thickness changes as well as diversion of transport directions across them in order to establish criteria for their synsedimentary activity. Decompacted differential thicknesses across faults were then used to calculate average fault slip rates of 0.05-0.47 mm/yr for the Tuff IE/IF interval (Upper Bed I) and 0.01-0.13 mm/yr for the Tuff IF/IIA section (Lower Bed II). Considering fault recurrence intervals of ∼1000 years, fault scarp heights potentially achieved average values of 0.05-0.47 m and a maximum value of 5.4 m during Upper Bed I, which dropped to average values of 0.01-0.13 m and a localized maximum of 0.72 m during Lower Bed II deposition. Synsedimentary faults were of importance to the form and paleoecology of landscapes utilized by early hominins, most traceably and provably Homo habilis as illustrated by the recurrent density and compositional pattern of Oldowan stone artifact assemblage variation across them. Two potential relationship factors are: (1) fault scarp topographies controlled sediment distribution, surface, and subsurface hydrology, and thus vegetation, so that a resulting mosaic of microenvironments and paleoecologies provided a variety of opportunities for omnivorous hominins; and (2) they ensured that the most voluminous and violent pyroclastic flows from the Mt. Olmoti volcano were dammed and conduited away from the Olduvai Basin depocenter, when otherwise a single or set of ignimbrite flows might have filled and devastated the topography that contained the central lake body. In addition, hydraulically active faults may have conduited groundwater, supporting freshwater springs and wetlands and favoring growth of trees. © 2011 Elsevier Ltd. Source


Turner P.,University of Liverpool
Proceedings of the Nutrition Society | Year: 2010

Many patients in the intensive care unit are malnourished or unable to eat. Feeding them correctly has the potential to reduce morbidity and even mortality but is a very complex procedure. The inflammatory response induced by surgery, trauma or sepsis will alter metabolism, change the ability to utilise nutrients and can lead to rapid loss of lean mass. Both overfeeding and underfeeding macronutrients can be harmful but generally it would seem optimal to give less during metabolic stress and immobility and increase in recovery. Physical intolerance of feeding such as diarrhoea or delayed gastric emptying is common in the intensive care unit. Diarrhoea can be treated with fibre or peptide feeds and anti-diarrhoeal drugs; however, the use of probiotics is controversial. Gastric dysfunction problems can often be overcome with prokinetic drugs or small bowel feeding tubes. New feeds with nutrients such as n-3 fatty acids that have the potential to attenuate excessive inflammatory responses show great promise in favourably improving metabolism and substrate utilisation. The importance of changing nutrient provision according to metabolic and physical tolerance cannot be understated and although expert groups have produced many guidelines on nutritional support of the critically ill, correct interpretation and implementation can be difficult without a dedicated nutrition health care professional such as a dietitian or a multidisciplinary nutritional support team. © 2010 The Author. Source


This paper examines the professionalising of geriatric medicine in the UK roughly between the 1940s and the 1970s and locates it in terms of the broader context of the relationship between the professions and the state. It looks at how this relationship shaped geriatric medicine's professional jurisdiction, including the discourses of expertise on the one hand and the constituting of the 'subjects' of such expertise on the other. In contrast to other sociological approaches to the professions, which highlight the negative impact of state encroachment on professional territory, this paper contends that without the backing of the Ministry of Health the specialty may never have established itself in the face of prolonged opposition from rival specialists. However, such support was predicated on the specialty's highlighting particular legitimating discourses and practices at the expense of others, and in framing this in terms of specific policy concerns around an ageing population. Whilst this imprinted the profession with the stamp of governmentality, it also contributed to the broader problematising of old age in the twentieth century. The paper concludes by considering the legacy of this context of professionalisation for the profession today. © 2010 The Author. Sociology of Health & Illness © 2010 Foundation for the Sociology of Health & Illness/Blackwell Publishing Ltd. Source


Wuerger S.,University of Liverpool
PLoS ONE | Year: 2013

It is well known that the peripheral visual system declines with age: the yellowing of the lens causes a selective reduction of short-wavelength light and sensitivity losses occur in the cone receptor mechanisms. At the same time, our subjective experience of colour does not change with age. The main purpose of this large-scale study (n = 185) covering a wide age range of colour-normal observers (18-75 years of age) was to assess the extent to which the human visual system is able to compensate for the changes in the optical media and at which level of processing this compensation is likely to occur. We report two main results: (1) Supra-threshold parafoveal colour perception remains largely unaffected by the age-related changes in the optical media (yellowing of the lens) whereas our ability to discriminate between small colour differences is compromised with an increase in age. (2) Significant changes in colour appearance are only found for unique green settings under daylight viewing condition which is consistent with the idea that the yellow-blue mechanism is most affected by an increase in age due to selective attenuation of short-wavelength light. The data on the invariance of hue perception, in conjunction with the age-related decline in chromatic sensitivity, provides evidence for compensatory mechanisms that enable colour-normal human observers a large degree of colour constancy across the life span. These compensatory mechanisms are likely to originate at cortical sites. © 2013 Sophie Wuerger. Source


Gowlett J.A.J.,University of Liverpool
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2013

Elongation is a commonly found feature in artefacts made and used by humans and other animals and can be analysed in comparative study. Whether made for use in hand or beak, the artefacts have some common properties of length, breadth, thickness and balance point, and elongation can be studied as a factor relating to construction or use of a long axis. In human artefacts, elongation can be traced through the archaeological record, for example in stone blades of the Upper Palaeolithic (traditionally regarded as more sophisticated than earlier artefacts), and in earlier blades of the Middle Palaeolithic. It is now recognized that elongation extends to earlier Palaeolithic artefacts, being found in the repertoire of both Neanderthals and more archaic humans. Artefacts used by non-human animals, including chimpanzees, capuchin monkeys and New Caledonian crows show selection for diameter and length, and consistent interventions of modification. Both chimpanzees and capuchins trim side branches from stems, and appropriate lengths of stave are selected or cut. In human artefacts, occasional organic finds show elongation back to about 0.5 million years. A record of elongation achieved in stone tools survives to at least 1.75 Ma (million years ago) in the Acheulean tradition. Throughout this tradition, some Acheulean handaxes are highly elongated, usually found with others that are less elongated. Finds from the million-year-old site of Kilombe and Kenya are given as an example. These findings argue that the elongation need not be integral to a design, but that artefacts may be the outcome of adjustments to individual variables. Such individual adjustments are seen in animal artefacts. In the case of a handaxe, the maker must balance the adjustments to achieve a satisfactory outcome in the artefact as a whole. It is argued that the need to make decisions about individual variables within multivariate objects provides an essential continuity across artefacts made by different species. © 2013 The Author(s) Published by the Royal Society. All rights reserved. Source


Pettitt A.,University of Liverpool
British Journal of Cancer | Year: 2016

Background:Anti-apoptotic BCL-2 family members antagonise apoptosis by sequestering their pro-apoptotic counterparts. The balance between the different BCL-2 family members forms the basis of BH3 profiling, a peptide-based technique used to predict chemosensitivity of cancer cells. Recent identification of cell-permeable, selective inhibitors of BCL-2, BCL-XL and MCL-1, further facilitates the determination of the BCL-2 family dependency of cancer cells.Methods:We use BH3 profiling in combination with cell death analyses using a chemical inhibitor toolkit to assess chemosensitivity of cancer cells.Results:Both BH3 profiling and the inhibitor toolkit effectively predict chemosensitivity of cells addicted to a single anti-apoptotic protein but a combination of both techniques is more instructive when cell survival depends on more than one anti-apoptotic protein.Conclusions:The inhibitor toolkit provides a rapid, inexpensive and simple means to assess the chemosensitivity of tumour cells and in conjunction with BH3 profiling offers much potential in personalising cancer therapy.British Journal of Cancer advance online publication, 8 March 2016; doi:10.1038/bjc.2016.49 www.bjcancer.com. © 2016 Cancer Research UK Source


Criddle D.N.,University of Liverpool
Pancreatology | Year: 2015

Excessive alcohol consumption is a major trigger for severe acute pancreatitis which may lead to multi-organ dysfunction and premature death of the individual. Hyperlipidaemia is a risk factor for both acute and chronic pancreatitis and the role of fatty acids in mediating damage has received increasing attention in recent years. In the pancreas ethanol is metabolised by both oxidative and non-oxidative pathways. The latter, predominant route generates fatty acid ethyl esters (FAEEs) from fatty acid substrates via the action of diverse enzymes called FAEE synthases, including carboxylester lipase an enzyme synthesized and secreted by the acinar cells. Inhibition of the oxidative pathway promotes formation of FAEEs which induce sustained elevations of cytosolic calcium leading to inhibition of mitochondrial function, loss of ATP and necrosis of isolated pancreatic acinar cells. Furthermore, FAEEs undergo hydrolysis in the mitochondria releasing free fatty acids that exert toxic effects. Our recent work has shown that pharmacological inhibition of carboxylester lipase ameliorated detrimental effects of non-oxidative ethanol metabolism in isolated pancreatic acinar cells invitro and in a new invivo experimental model of alcoholic acute pancreatitis, revealing a specific enzyme target for ethanol-induced injury. Strategies that prevent FAEE synthesis, protect mitochondria, reduce calcium overload or sustain calcium homeostasis by ATP provision may provide promising therapeutic avenues for the treatment of alcoholic acute pancreatitis. © 2015 IAP and EPC. Source


Goebel A.,University of Liverpool | Goebel A.,Walton Center
Autoimmunity Reviews | Year: 2013

Complex regional pain syndrome (CRPS) is a painful condition, which arises in a limb after trauma. CRPS can profoundly affect patients' quality of life, and there is no cure. CRPS is associated with limb-confined sensory, motor, skin, bone and autonomic abnormalities. Recent research has shown that some patients respond to treatment with immunoglobulins, and that a majority have IgG serum-autoantibodies directed against, and activating autonomic receptors. CRPS serum-IgG, when transferred to mice elicits abnormal behaviour. These results suggest that CRPS is associated with an autoantibody-mediated autoimmune process in some cases. CRPS has unusual features, including a non-destructive, and regionally-confined course. We propose that CRPS constitutes a prototype of a new kind of autoimmunity, which we term 'IRAM' (injury-triggered, regionally-restricted autoantibody-mediated autoimmune disorder with minimally-destructive course). Understanding autoimmune contribution to CRPS should allow the exploration of novel treatment modalities in the future. Additional 'functional' disorders, painful or painless may be autoimmune in nature. © 2013 Elsevier B.V. Source


Blachut J.,University of Liverpool
Thin-Walled Structures | Year: 2011

The paper considers the buckling of short, and relatively thick, mild steel conical shells subjected to the combined action of external pressure and axial compression. Past results on axially compressed cones and on cones subjected to hydrostatic external pressure are compared with fresh test results on equivalent, axially compressed cylinder and with the equivalent cylinder subjected to external hydrostatic pressure. The paper contains both numerical and experimental results. Details about experiments, numerical modelling and computed estimates of the load carrying capacity of analyzed shells are given. Results of this study suggest that the concept of equivalent cylinders is not applicable to short master-cones. Combined stability plots have also been derived for the master-cone and equivalent cylinders. They provide not only the failure envelopes but also the yield envelopes and spread of plastic zones. The paper also brings into the light a useful design tool proposed by Esslinger and van Impe [8], and applicable to elasticplastic buckling of cones subjected to external hydrostatic pressure. © 2010 Elsevier Ltd. Source


Hornik T.,University of Liverpool | Zhong Q.-C.,Loughborough University
IEEE Transactions on Power Electronics | Year: 2011

In this paper, a current-control strategy is proposed for voltage-source inverters in microgrids. The main objective of the proposed controller is to inject a clean sinusoidal current to the grid, even in the presence of nonlinear/unbalanced loads and/or grid-voltage distortions. The repetitive control technique is adopted because it can deal with a very large number of harmonics simultaneously. The proposed current controller consists of an internal model and a stabilizing compensator, which is designed by using the H ∞ control theory. It turns out that the stabilizing compensator may be simply an inductor. This leads to a very low total harmonic distortion (THD) and improved tracking performance. In order to demonstrate the improvement of performance, the proposed controller is compared with the traditional proportional-resonant, proportional-integral, and predictive deadbeat controllers. The control strategies are evaluated in the grid-connected mode with experiments under different scenarios: steady-state and transient responses without local loads, and steady-state responses with unbalanced resistive and nonlinear local loads. The proposed controller significantly outperforms the other control schemes in terms of the THD level, with the price of slightly slower dynamic responses. © 2010 IEEE. Source


Patel V.,London School of Hygiene and Tropical Medicine | Rahman A.,University of Liverpool | Verdeli H.,Columbia University
Behaviour Research and Therapy | Year: 2011

Even though psychological treatments have been advocated as treatments for a range of mental disorders by the WHO for scaling up through primary care globally, the vast majority of potential beneficiaries are unable to access these treatments. Two major barriers impede the path between evidence based treatments and improved access: the lack of skilled human resources and the acceptability of treatments across cultures. This essay synthesizes the experiences of programs which developed and evaluated psychological treatments for depression in three resource poor developing countries. These programs addressed the human resource barrier by training lay or community health workers to deliver the treatments and addressed the acceptability barrier by systematically adapting the treatment to contextual factors. All programs demonstrated significant benefits in recovery rates when compared with usual care demonstrating the effectiveness of the approach. The implications for these experiences to improving access to psychological treatments in the global context are discussed. © 2011 Elsevier Ltd. Source


Rowe F.J.,University of Liverpool
Cochrane database of systematic reviews (Online) | Year: 2012

The use of botulinum toxin as an investigative and treatment modality for strabismus is well reported in the medical literature. However it is unclear how effective its use is in comparison to other treatment options for strabismus. To evaluate the efficacy of botulinum toxin in the treatment of strabismus compared with alternative treatment options, to investigate dose effect and complication rates. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 11), MEDLINE (January 1950 to December 2011), EMBASE (January 1980 to December 2011), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to December 2011), 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). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 5 December 2011. We manually searched the Australian Orthoptic Journal and British and Irish Orthoptic Journal and ESA, ISA and IOA conference proceedings. We attempted to contact researchers who are active in this field for information about further published or unpublished studies. We included randomised controlled trials (RCTS) of any use of botulinum toxin treatment for strabismus. Each review author independently assessed study abstracts identified from the electronic and manual searches. Author analysis was then compared and full papers for appropriate studies were obtained. We found four RCTs that were eligible for inclusion. Two trials found that there was no difference between the use of botulinum toxin and surgery for patients requiring retreatment for acquired esotropia or infantile esotropia. There was no evidence for a prophylactic effect of botulinum toxin in a treatment trial of acute onset sixth nerve palsy. Botulinum toxin had a poorer response than surgery in a trial of patients requiring treatment for horizontal strabismus in the absence of binocular vision. Reported complications included ptosis and vertical deviation and ranged from 24% in a trial using Dysport™ to 52.17% and 55.54% in trials using Botox™. The majority of published literature on the use of botulinum toxin in the treatment of strabismus consists of retrospective studies, cohort studies or case reviews. Although these provide useful descriptive information, clarification is required as to the effective use of botulinum toxin as an independent treatment modality. Four RCTs on the therapeutic use of botulinum toxin in strabismus have shown varying responses ranging from a lack of evidence for prophylactic effect of botulinum toxin in acute sixth nerve palsy, to poor response in patients with horizontal strabismus without binocular vision, to no difference in response in patients that required retreatment for acquired esotropia or infantile esotropia. It was not possible to establish dose effect information. Complication rates for use of Botox™ or Dysport™ ranged from 24% to 55.54%. Source


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


Speed M.P.,University of Liverpool | Ruxton G.D.,University of Glasgow
American Naturalist | Year: 2010

We apply signal detection methodology to make predictions about the evolution of Batesian mimicry. Our approach is novel in three ways. First, we applied a deterministic evolutionary modeling system that allows a large number of alternative mimetic morphs to coexist and compete. Second, we considered that there may be natural boundaries to phenotypic expression. Finally, we allowed increasing conspicuousness to impose an increasing detection cost on mimics. In some instances, the model predicts widespread variation in mimetic forms at evolutionary stability. In other situations, rather than a polymorphism the model predicts dimorphisms in which some prey were maximally cryptic and had minimal resemblance to the model, whereas many others were more conspicuous than the model. The biological implications of these results, particularly for our understanding of imperfect mimicry, are discussed. © 2010 by The University of Chicago. Source


Pervasive negative thoughts about the self are central to the experience of depression. Brain imaging studies in the general population have localised self-related cognitive processing to areas of the medial pre-frontal cortex. To use fMRI to compare the neural correlates of self-referential processing in depressed and non-depressed participants. Cross-sectional comparison of regional activation using Blood Oxygen Level Dependent (BOLD) fMRI in 13 non-medicated participants with major depressive episode and 14 comparison participants, whilst carrying out a self-referential cognitive task. Both groups showed significant activation of the dorsomedial pre-frontal cortex and posterior cingulate cortex in the 'self-referent' condition. The depressed group showed significantly greater activation in the medial superior frontal cortex during the self-referent task. No difference was observed between groups in the 'other-referent' condition. Major depressive episode is associated with specific neurofunctional changes related to self-referential processing. Source


Weedall G.D.,University of Liverpool | Conway D.J.,London School of Hygiene and Tropical Medicine
Trends in Parasitology | Year: 2010

Parasite antigen genes might evolve under frequency-dependent immune selection. The distinctive patterns of polymorphism that result can be detected using population genetic methods that test for signatures of balancing selection, allowing genes encoding important targets of immunity to be identified. Analyses can be complicated by population structures, histories and features of a parasite's genome. However, new sequencing technologies facilitate scans of polymorphism throughout parasite genomes to identify the most exceptional gene specific signatures. We focus on malaria parasites to illustrate challenges and opportunities for detecting targets of frequency-dependent immune selection to discover new potential vaccine candidates. © 2010 Elsevier Ltd. Source


Rynkiewicz E.C.,University of Edinburgh | Pedersen A.B.,University of Edinburgh | Fenton A.,University of Liverpool