• Unveiling the prehistoric landscape at Stonehenge through multi-receiver EMI

      De Smedt, P; Van Meirvenne, M.; Saey, T.; Baldwin, E.; Gaffney, Christopher F.; Gaffney, Vincent L. (2014-10)
      Archaeological research at Stonehenge (UK) is increasingly aimed at understanding the dynamic of the wider archaeological landscape. Through the application of state-of-the-art geophysical techniques, unprecedented insight is being gathered into the buried archaeological features of the area. However, applied survey techniques have rarely targeted natural soil variation, and the detailed knowledge of the palaeotopography is consequently less complete. In addition, metallic topsoil debris, scattered over different parts of the Stonehenge landscape, often impacts the interpretation of geophysical datasets. The research presented here demonstrates how a single multi-receiver electromagnetic induction (EMI) survey, conducted over a 22 ha area within the Stonehenge landscape, offers detailed insight into natural and anthropogenic soil variation at Stonehenge. The soil variations that were detected through recording the electrical and magnetic soil variability, shed light on the genesis of the landscape, and allow for a better definition of potential palaeoenvironmental and archaeological sampling locations. Based on the multi-layered dataset, a procedure was developed to remove the influence of topsoil metal from the survey data, which enabled a more straightforward identification of the detected archaeology. The results provide a robust basis for further geoarchaeological research, while potential to differentiate between modern soil disturbances and the underlying sub-surface variations can help in solving conservation and management issues. Through expanding this approach over the wider area, we aim at a fuller understanding of the human–landscape interactions that have shaped the Stonehenge landscape.
    • An update on genomic-guided therapies for pediatric solid tumors

      Tsui, P.C.; Lee, Stephanie; Liu, Z.W.Y.; Ip, L.R.H.; Piao, W.; Chiang, A.K.S.; Lui, V.W.Y. (2017-06)
      Currently, out of the 82 US FDA-approved targeted therapies for adult cancer treatments, only three are approved for use in children irrespective of their genomic status. Apart from leukemia, only a handful of genomic-based trials involving children with solid tumors are ongoing. Emerging genomic data for pediatric solid tumors may facilitate the development of precision medicine in pediatric patients. Here, we provide an up-to-date review of all reported genomic aberrations in the eight most common pediatric solid tumors with whole-exome sequencing or whole-genome sequencing data (from cBioPortal database, Pediatric Cancer Genome Project, Therapeutically Applicable Research to Generate Effective Treatments) and additional non-whole-exome sequencing studies. Potential druggable events are highlighted and discussed so as to facilitate preclinical and clinical research in this area.
    • Uptake of oral anticoagulants for stroke prevention in patients with atrial fibrillation in a single Clinical Commissioning Group in England without restrictions to their use

      Medlinskiene, Kristina; Fay, M.; Petty, Duncan R. (2019-04)
      Background and Objective In England, the uptake of direct oral anticoagulants (DOACs) for stroke prevention in atrial fbrillation has been slow and varied across diferent Clinical Commissioning Groups (CCGs). This study aimed to profle the prescribing of oral anticoagulants for stroke prevention in patients with atrial fbrillation over 3 years in a CCG without restrictions to DOACs use to understand more about organisational and/or individual barriers to the early uptake of DOACs. Methods Data were collected from nine general practices between 1 April 2012 and 31 March 2015 of patients who were initiated on the oral anticoagulant therapy. Data were analysed descriptively and with independent Student’s t test and Chi square test to explore if there was an association between type of oral anticoagulant initiated and sex, age, type of prescriber and prior aspirin use. Results The early uptake of DOACs signifcantly increased over the study period (p<0.0001; medium size efect φc=0.372). There was no statistically signifcant diference between sex or age and type of oral anticoagulant initiated. Primary-care prescribers were responsible for initiating the majority of oral anticoagulants (71%; N=257) and driving the use of DOACs (72%, N=71). Patients switched from aspirin to an oral anticoagulant were more likely to be initiated on warfarin than a DOAC. Conclusions The early use of DOACs, in a CCG without restrictions to their use, was embraced by primary-care prescribers in this particular CCG.
    • Use of a pathway quality improvement care bundle to reduce mortality after emergency laparotomy

      Huddart, S.; Peden, C.J.; Swart, M.; McCormick, B.; Dickinson, M.; Mohammed, Mohammed A.; Quiney, N. (2015)
      Emergency laparotomies in the U.K., U.S.A. and Denmark are known to have a high risk of death, with accompanying evidence of suboptimal care. The emergency laparotomy pathway quality improvement care (ELPQuiC) bundle is an evidence-based care bundle for patients undergoing emergency laparotomy, consisting of: initial assessment with early warning scores, early antibiotics, interval between decision and operation less than 6 h, goal-directed fluid therapy and postoperative intensive care. The ELPQuiC bundle was implemented in four hospitals, using locally identified strategies to assess the impact on risk-adjusted mortality. Comparison of case mix-adjusted 30-day mortality rates before and after care-bundle implementation was made using risk-adjusted cumulative sum (CUSUM) plots and a logistic regression model. Risk-adjusted CUSUM plots showed an increase in the numbers of lives saved per 100 patients treated in all hospitals, from 6.47 in the baseline interval (299 patients included) to 12.44 after implementation (427 patients included) (P < 0.001). The overall case mix-adjusted risk of death decreased from 15.6 to 9.6 per cent (risk ratio 0.614, 95 per cent c.i. 0.451 to 0.836; P = 0.002). There was an increase in the uptake of the ELPQuiC processes but no significant difference in the patient case-mix profile as determined by the mean Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity risk (0.197 and 0.223 before and after implementation respectively; P = 0.395). Use of the ELPQuiC bundle was associated with a significant reduction in the risk of death following emergency laparotomy.
    • Use of batch mixing to investigate the continuous solvent-free mechanical synthesis of OLED materials by twin-screw extrusion (TSE)

      Crawford, Deborah E.; James, S.L.; McNally, T. (2018-01)
      Mechanochemical synthesis has the potential to change the way in which chemistry is conducted, particularly with regard to removing or dramatically reducing the need for solvents. Recently, it has been demonstrated that mechanochemistry can be carried out continuously and on large scale through the use of twin-screw extrusion (TSE). TSE has successfully been applied to the synthesis of cocrystals, metal organic frameworks (MOFs), deep eutectic solvents (DESs), metal complexes, and organic condensation reactions. However, while TSE provides a route for mechanochemical synthesis to be developed into a continuous, high-volume manufacturing process, little is currently understood about how to best optimize the various process parameters involved. Herein, we investigate the use of a batch mixer that has been previously used in polymer processing, to optimize mechanochemical reactions performed by extrusion. In particular, reactions between 8-hydroxyquinoline (Hq) and metal acetate salts of zinc or aluminum to give quinolinate complexes Znq2·AcOH and Alq3·AcOH, which are of interest for organic light-emitting diode (OLED) applications, have been investigated. The manner in which the progress of the reaction correlates with the machine torque, temperature, and specific mechanical energy (SME) imparted by the batch mixer has been elucidated. Significantly, this knowledge enabled optimization of the mechanochemical reactions by TSE through the key parameters of screw speed, feed rate, temperature, and particle size.
    • Use of complementary nucleobase-containing synthetic polymers to prepare complex self-assembled morphologies in water

      Kang, Y.; Pitto-Barry, Anaïs; Rolph, M.S.; Hua, Z.; Hands-Portman, I.; Kirby, N.; O'Reilly, R.K. (2016-04-28)
      Amphiphilic nucleobase-containing block copolymers with poly(oligo(ethylene glycol) methyl ether methacrylate) as the hydrophilic block and nucleobase-containing blocks as the hydrophobic segments were successfully synthesized using RAFT polymerization and then self-assembled via solvent switch in aqueous solutions. Effects of the common solvent on the resultant morphologies of the adenine (A) and thymine (T) homopolymers, and A/T copolymer blocks and blends were investigated. These studies highlighted that depending on the identity of the common solvent, DMF or DMSO, spherical micelles or bicontinuous micelles were obtained. We propose that this is due to the presence of A–T interactions playing a key role in the morphology and stability of the resultant nanoparticles, which resulted in a distinct system compared to individual adenine or thymine polymers. Finally, the effects of annealing on the self-assemblies were explored. It was found that annealing could lead to better-defined spherical micelles and induce a morphology transition from bicontinuous micelles to onion-like vesicles, which was considered to occur due to a structural rearrangement of complementary nucleobase interactions resulting from the annealing process.
    • The use of corsetry to treat Pott’s disease of the spine from 19th Century Wolverhampton, England

      Moore, Joanna; Buckberry, Jo (2016-09)
      Corsets have been used both to create a fashionable silhouette and as an orthopaedic treatment for spinal conditions, but skeletal changes associated with the use of corsetry are rarely reported on in the palaeopathological literature. Here, we report on a 19th-century adult male with Pott’s disease of the vertebral column and related vertebral compression deformities, which probably result from the use of a corset. Wolverhampton HB40 presented destruction of the vertebral bodies of T6 to L4, ankylosis of the apophyseal joints of L1 and L2 and an angular kyphosis of the lumbar region, the result of tuberculosis. The presence of flattened spinous processes and bilateral acute angulation of multiple ribs in the lower thoracic region is indicative of plastic deformation caused by the use of the corset. The presence of both of these changes in an adult male, at a time when the use of cosmetic corsets by men was in decline, suggests that the compression trauma was the result of an orthopaedic corset used to correct the defective posture resulting from tubercular kyphosis, although corset use to obtain a fashionable silhouette cannot be ruled out.
    • The use of isolated peripheral lymphocytes and human whole blood in the comet assay

      Najafzadeh, Mojgan; Anderson, Diana (2016-10-27)
      The comet assay is a sensitive method used to detect DNA damage, measuring DNA breaks and alkali labile lesions in eukaryotic cells. Here, the use of whole blood in the alkaline gel electrophoresis method is described. Two hundred and seventy blood samples from individuals were examined: 120 healthy individuals, 65 suspected or pre-cancerous individuals and 85 cancer patients. Each sample was divided into two identical volumes in different falcon tubes. The blood was prepared and stored by adding the same amount of RPMI medium and 10% DMSO. Using the Student’s t-Test, the data showed a p value = 0.59 for Olive tail moment (OTM) and 0.16 for % tail DNA, and no statistically significant differences between the two methods, with or without treatment. In conclusion, using whole blood instead of isolated lymphocytes saves time, is still very sensitive and requires less than 20 µL of blood from each individual.
    • Use of Methylmalonyl-CoA Epimerase in Enhancing Crotonase Stereoselectivity

      Hamed, Refaat B.; Gomez-Castellanos, J.R.; Sean Froese, D.; Krysztofinska, E.; Yue, W.W.; Schofield, C.J. (2016-03-15)
      The use of methylmalonyl-CoA epimerase (MCEE) to improve stereoselectivity in crotonase-mediated biocatalysis is exemplified by the coupling of MCEE, crotonyl-CoA carboxylase reductase and carboxymethylproline synthase in a three-enzyme one-pot sequential synthesis of functionalised C-5 carboxyalkylprolines starting from crotonyl-CoA and carbon dioxide.
    • The use of pharmacokinetic and pharmacodynamic end points to determine the dose of AQ4N, a novel hypoxic cell cytotoxin, given with fractionated radiotherapy in a phase I study.

      Steward, W.P.; Middleton, M.; Benghiat, A.; Loadman, Paul M.; Hayward, C.; Walter, S.; Ford, S.; Halbert, G.; Patterson, Laurence H.; Talbot, D. (2009-11-25)
      Background: AQ4N (1,4-bis[[2-(dimethylamino)ethyl] amino]-5,8-dihydroxyanthracene-9, 10-dione bis-N-oxide dihydrochloride) is a prodrug which is selectively activated within hypoxic tissues to AQ4, a topoisomerase II inhibitor and DNA intercalator. Patients and methods: In the phase I study, 22 patients with oesophageal carcinoma received an i.v. infusion of AQ4N (22.5¿447 mg/m2) followed, 2 weeks later, by further infusion and radiotherapy. Pharmacokinetics and lymphocyte AQ4N and AQ4 levels were measured after the first dose. At 447 mg/m2, biopsies of tumour and normal tissue were taken after AQ4N administration. Results: Drug-related adverse events were blue discolouration of skin and urine, grade 2¿3 lymphopenia, grade 1¿3 fatigue, grade 1¿2 anaemia, leucopenia and nausea. There were no drug-related serious adverse events (SAEs). Three patients had reductions in tumour volume >50%, nine had stable disease. Pharmacokinetics indicated predictable clearance. Plasma area under the curve (AUC) at 447 mg/m2 exceeded AQ4N concentrations in mice at therapeutic doses and tumour biopsies contained concentrations of AQ4 greater than those in normal tissue. Tumour concentrations of AQ4 exceeded in vitro IC50 values for most cell lines investigated. Conclusions: No dose-limiting toxic effects were observed and a maximum tolerated dose was not established. Tumour AQ4 concentrations and plasma AUC at 447 mg/m2 exceeded active levels in preclinical models. This dose was chosen for future studies with radiotherapy.
    • Use of single-vision distance spectacles improves landing control during step descent in well-adapted multifocal lens-wearers

      Timmis, Matthew A.; Johnson, Louise; Elliott, David B.; Buckley, John G. (2010)
      PURPOSE: Epidemiologic research has shown that multifocal spectacle wearers (bifocal and progressive addition lenses [PALs]) are more than twice as likely to fall than are nonmultifocal spectacle wearers, with this risk further increasing when negotiating stairs. The present study investigated whether step and stair descent safety is improved by using single-vision distance lenses. METHODS: From a stationary standing position on top of a block, 20 long-term multifocal wearers stepped down (from different block heights) onto a lower level wearing bifocal, progressive addition, or single-vision distance lenses. RESULTS: Use of single-vision distance spectacles led to an increased single-limb support time, a reduced ankle and knee angle and vertical center-of-mass velocity at contact with the lower level, and a reduced ankle angular velocity and vertical center-of-mass velocity during initial landing (P < 0.03). These findings indicate that landing occurred in a more controlled manner when the subjects wore single-vision distance spectacles, rather than tending to "drop" onto the lower level as occurred when wearing bifocals or PALs. CONCLUSIONS: Use of single-vision distance spectacles led to improvements in landing control, consistent with individuals' being more certain regarding the precise height of the lower floor level. This enhanced control was attributed to having a view of the foot, step edge, and immediate floor area that was not blurred, magnified, or doubled and that did not suffer from image jump or peripheral distortions. These findings provide further evidence that use of single-vision distance lenses in everyday locomotion may be advantageous for elderly multifocal wearers who have a high risk of falling.
    • The Use of Stable Light Isotopes as a Method of Exploring the Homogeneity and Heterogeneity of diet in Late Bronze Age and Early Iron Age Temperate Europe: A Preliminary Study

      Nicholls, R.; Koon, Hannah E.C. (2016)
      This paper introduces stable light isotope analysis as a method of investigating the homogeneity and heterogeneity of communities inhabiting areas of the East Alpine region during the Late Bronze Age and Early Iron Age. It will present a short review on the use of carbon and nitrogen light isotope values, and discuss how they provide insight into the diet and health of past populations. A pilot study of results obtained from the bone collagen of 14 individuals, from 6 sites located in modern-day Slovenia and northern Croatia, will also be presented. This small dataset provides an example of the values that will be collected throughout the ENTRANS Project, and how they can be used as a tool to investigate the lives of people in the past.
    • The use of thermographic imaging to evaluate therapeutic response in human tumour xenograft models

      Hussain, Nosheen; Connah, David; Ugail, Hassan; Cooper, Patricia A.; Falconer, Robert A.; Patterson, Laurence H.; Shnyder, Steven D. (2016-08-05)
      Non-invasive methods to monitor tumour growth are an important goal in cancer drug development. Thermographic imaging systems offer potential in this area, since a change in temperature is known to be induced due to changes within the tumour microenvironment. This study demonstrates that this imaging modality can be applied to a broad range of tumour xenografts and also, for the first time, the methodology’s suitability to assess anti-cancer agent efficacy. Mice bearing subcutaneously implanted H460 lung cancer xenografts were treated with a novel vascular disrupting agent, ICT-2552, and the cytotoxin doxorubicin. The effects on tumour temperature were assessed using thermographic imaging over the first 6 hours post-administration and subsequently a further 7 days. For ICT-2552 a significant initial temperature drop was observed, whilst for both agents a significant temperature drop was seen compared to controls over the longer time period. Thus thermographic imaging can detect functional differences (manifesting as temperature reductions) in the tumour response to these anti-cancer agents compared to controls. Importantly, these effects can be detected in the first few hours following treatment and therefore the tumour is observable non-invasively. As discussed, this technique will have considerable 3Rs benefits in terms of reduction and refinement of animal use.
    • User interactions in strategic research: The example of two UK 'Integrated Urban Drainage Pilots'

      Sharp, Liz (2008)
      According to Lowe and Phillipson (2006) the traditional binary division into `basic¿ and `applied¿ research, have recently been extended to a new category called `strategic¿ research, signifying research which is both inter-disciplinary and interacts with research users. Sharp and Dixon (2007) have argued that there are different level of strategic research, signifying different levels of interaction, resource sharing, and joint development of outputs. Drawing on this understanding, this paper considers two user-oriented `Integrated Urban Drainage¿ pilot projects conducted during 2006-7, in order to consider what insights these `not-quite¿ research projects can yield about the nature of strategic research. The paper finds that the pilots were similar to other inter-disciplinary research projects ¿ except that they were commissioned and partly managed by practitioners. Common dilemmas, for example about the inter-linkages between work packages and about the extent of stakeholder interaction, highlight the increasingly fluid boundaries between the categories of `policy evaluation¿, `policy pilot¿ and `research project¿. The paper concludes that the concepts of `researcher¿ and `research user¿ might be replaced with a more flexible idea about `research stakeholders¿ whose varied interests in projects require a flexible communication strategy to fulfil a range of needs.
    • Using a Modified Lymphocyte Genome Sensitivity (LGS) Test or TumorScan Test to Detect Cancer at an Early Stage in Each Individual

      Anderson, Diana; Najafzadeh, Mojgan; Scally, Andy J.; Jacob, B.K.; Griffith, John; Chaha, R.; Linforth, R.; Soussaline, M.; Soussaline, F. (2019-01-03)
      Our previous case-control study observed isolated lymphocytes from 208 individuals and determined the differences in the sensitivity to genomic damage of lymphocytes derived from cancer patients, pre/suspect cancer patients and healthy volunteers using the Comet assay (Anderson et al, 2014). We adapted the LGS technique using a slightly different method and examined 700 more blood samples from 598 patients with cancer or suspected cancer and 102 healthy individuals. To help increase the sensitivity of the test and detect cancer at the level of each individual, we joined with the IMSTAR team who analysed our cells with their fully automated Pathfinder™ cell reader-analyser system. With this reading and analysis system 4,000 to 10,000 cells were able to be read per slide. The new test which is called TumorScan is a highly sensitive test to detect any cancer at an early stage through the response of the white blood cells to UV treatment. These patient blood samples have also been collected at the stage before confirming diagnosis and treatment. There were four of these individuals with cancer who had received anti-cancer treatment. The results from these patients showed a reverse pattern compared to non-treated cancer patients and followed the pattern seen in healthy individuals. The results are consistent with the early results as reported in the above 2014 paper. Given the results from these samples were in a particularly challenging subgroup, whose cancer status was difficult to distinguish, the data suggest that the technique using the TumorScan system could exceed the area under the ROC curve >93% obtained in the earlier study on a group basis, whereas this present study was to detect cancer at an early stage in each individual.
    • Using a smartphone on the move: do visual constraints explain why we slow walking speed?

      Rubio Barañano, Alejandro; Faisal, Muhammad; Barrett, Brendan T.; Buckley, John G. (Springer Nature, 2021)
      Viewing one’s smartphone whilst walking commonly leads to a slowing of walking. Slowing walking-speed may occur because of safety concerns or because of visual constraints. We determine how walking-induced phone motion affects the ability to read on-screen information. Phone-reading performance (PRP) was assessed whilst participants walked on a treadmill at various speeds. The fastest speed was repeated, wearing an elbow-brace (Braced) or with the phone mounted stationary (Fixed). An audible cue (‘text-alert’), indicated participants had 2 seconds to lift/view the phone and read aloud a series of digits. PRP was the number of digits read correctly. Each condition was repeated 5 times. 3D-motion analyses determined phone-motion relative to the head, from which the variability in acceleration in viewing distance, and in the gaze angles in the up-down and right-left directions were assessed. A main-effect of condition indicated PRP decreased with walking speed; particularly so for the Braced and Fixed conditions (p=0.022). Walking condition also affected the phone’s relative motion (p
    • Using avatars in weight management settings: a systematic review

      Horne, M.; Hill, A.; Murells, T.; Ugail, Hassan; Irving; Chinnadorai, R.; Hardy, Maryann L. (2020-03)
      Background: Obesity interventions rely predominantly on managing dietary intake and/or increasing physical activity but sustained adherence to behavioural regimens is often poor. Avatar technology is well established within the computer gaming industry and evidence suggests that virtual representations of self may impact real-world behaviour, acting as a catalyst for sustained weight loss behaviour modification. However, the effectiveness of avatar technology in promoting weight loss is unclear. Aims: We aimed to assess the quantity and quality of empirical support for the use of avatar technologies in adult weight loss interventions. Method: A systematic review of empirical studies was undertaken. The key objectives were to determine if: (i) the inclusion of avatar technology leads to greater weight loss achievement compared to routine intervention; and (ii) whether weight loss achievement is improved by avatar personalisation (avatar visually reflects self). Results: We identified 6 papers that reported weight loss data. Avatar-based interventions for weight loss management were found to be effective in the short (4–6 weeks) and medium (3–6 months) term and improved weight loss maintenance in the long term (12 months). Only 2 papers included avatar personalisation, but results suggested there may be some added motivational benefit. Conclusions: The current evidence supports that avatars may positively impact weight loss achievement and improve motivation. However, with only 6 papers identified the evidence base is limited and therefore findings need to be interpreted with caution.
    • Using Discourse Analysis in Social Psychology

      Budds, K.; Locke, Abigail; Burr, V. (2017-04)
      Discourse analytic approaches are increasingly used in psychological research. In this chapter, we will briefly introduce the key discourse analytic approaches used within psychological research. Then, using an example from some work carried out by the first author on ‘older motherhood’, we will guide you through the practical steps associated with an approach to discourse analysis called critical discursive psychology and consider how this approach is successfully applied to qualitative data. Finally, we will consider some of the practical applications of the approach.