Now showing items 1-20 of 2525

    • Preservation of Smooth Muscle Cell Integrity and Function: A Target for Limiting Abdominal Aortic Aneurysm Expansion?

      Clark, E.R.; Helliwell, R.J.; Bailey, M.A.; Hemmings, K.E.; Bridge, K.I.; Griffin, K.J.; Scott, D.J.A.; Jennings, L.M.; Riches-Suman, Kirsten; Porter, K.E. (2022-03)
      (1) Abdominal aortic aneurysm (AAA) is a silent, progressive disease with significant mortality from rupture. Whilst screening programmes are now able to detect this pathology early in its development, no therapeutic intervention has yet been identified to halt or retard aortic expansion. The inability to obtain aortic tissue from humans at early stages has created a necessity for laboratory models, yet it is essential to create a timeline of events from EARLY to END stage AAA progression. (2) We used a previously validated ex vivo porcine bioreactor model pre-treated with protease enzyme to create "aneurysm" tissue. Mechanical properties, histological changes in the intact vessel wall, and phenotype/function of vascular smooth muscle cells (SMC) cultured from the same vessels were investigated. (3) The principal finding was significant hyperproliferation of SMC from EARLY stage vessels, but without obvious histological or SMC aberrancies. END stage tissue exhibited histological loss of α-smooth muscle actin and elastin; mechanical impairment; and, in SMC, multiple indications of senescence. (4) Aortic SMC may offer a therapeutic target for intervention, although detailed studies incorporating intervening time points between EARLY and END stage are required. Such investigations may reveal mechanisms of SMC dysfunction in AAA development and hence a therapeutic window during which SMC differentiation could be preserved or reinstated.
    • Construction of Ternary Phase Diagrams: Application of Quantitative NMR

      Telford, Richard; Obule, Whitney; Seaton, Colin C. (2022-02)
      The growth of cocrystalline phases continues to expand as a key area of crystal engineering research. Understanding the phase behavior of the material and controlling the crystalline form of the material from a solution-based route can be aided by the construction of a ternary phase diagram for the system. A range of methods exist for this process which display a variety of costs and time to achieve the final diagram. The application of quantitative NMR (qNMR) to this problem offers a fast analysis method to directly determine the solution composition of all species (coformers and solvent) and is demonstrated to successfully allow the construction of ternary diagrams with and without a cocrystal phase being formed for systems with high and low solubility.
    • Error Bred in the Bone

      Thompson, K.; Manchester, Keith; Buckberry, Jo; Sparrow, Thomas; Holland, Andrew D.; Wilson, Andrew S. (Springer Nature, 2022-04)
      This chapter describes a collaborative project funded by Grants for All, Arts Council England, led by artist Karina Thompson, together with researchers from the Biological Anthropology Research Centre (BARC), School of Archaeological and Forensic Sciences, University of Bradford. The artworks took digitised historic clinical radiographs and digitised human skeletal pathological data from the landmark Digitised Diseases, and From Cemetery to Clinic digital bioarchaeology resources developed by colleagues from Visualising Heritage as a starting point. In addition to a series of small-scale installations displayed alongside the Biological Anthropology Research Centre teaching collection, large-scale exhibition pieces were displayed as part of national and international exhibitions. Collectively these works draw attention to the potential of digital bioarchaeology, whilst ensuring the importance of humanising the documentation of disease through time.
    • Expansion of the 4-(Diethylamino)benzaldehyde Scaffold to Explore the Impact on Aldehyde Dehydrogenase Activity and Antiproliferative Activity in Prostate Cancer

      Ibrahim, Ali I.M.; Battle, Elisabet; Sneha, Smarakan; Jimenez, R.; Pequerul, R.; Pares, X.; Rüngeler, T.; Jha, V.; Tuccinardi, T.; Sadiq, Maria; et al. (2022-03-10)
      Aldehyde dehydrogenases (ALDHs) are overexpressed in various tumor types including prostate cancer and considered a potential target for therapeutic intervention. 4-(Diethylamino)benzaldehyde (DEAB) has been extensively reported as a pan-inhibitor of ALDH isoforms, and here, we report on the synthesis, ALDH isoform selectivity, and cellular potencies in prostate cancer cells of 40 DEAB analogues; three analogues (14, 15, and 16) showed potent inhibitory activity against ALDH1A3, and two analogues (18 and 19) showed potent inhibitory activity against ALDH3A1. Significantly, 16 analogues displayed increased cytotoxicity (IC50 = 10-200 μM) compared with DEAB (>200 μM) against three different prostate cancer cell lines. Analogues 14 and 18 were more potent than DEAB against patient-derived primary prostate tumor epithelial cells, as single agents or in combination treatment with docetaxel. In conclusion, our study supports the use of DEAB as an ALDH inhibitor but also reveals closely related analogues with increased selectivity and potency.
    • Semi-Synthetic Analogues of Cryptolepine as a Potential Source of Sustainable Drugs for the Treatment of Malaria, Human African Trypanosomiasis and Cancer

      Abacha, Yabalu Z.; Forkuo, A.D.; Gbedema, S.Y.; Mittal, N.; Ottilie, S.; Rocamora, F.; Winzeler, E.A.; van Schalkwyk, D.A.; Kelly, J.M.; Taylor, M.C.; et al. (2022-04)
      The prospect of eradicating malaria continues to be challenging in the face of increasing parasite resistance to antimalarial drugs so that novel antimalarials active against asexual, sexual, and liver-stage malaria parasites are urgently needed. In addition, new antimalarials need to be affordable and available to those most in need and, bearing in mind climate change, should ideally be sustainable. The West African climbing shrub Cryptolepis sanguinolenta is used traditionally for the treatment of malaria; its principal alkaloid, cryptolepine (1), has been shown to have antimalarial properties, and the synthetic analogue 2,7-dibromocryptolepine (2) is of interest as a lead toward new antimalarial agents. Cryptolepine (1) was isolated using a two-step Soxhlet extraction of C. sanguinolenta roots, followed by crystallization (yield 0.8% calculated as a base with respect to the dried roots). Semi-synthetic 7-bromo- (3), 7, 9-dibromo- (4), 7-iodo- (5), and 7, 9-dibromocryptolepine (6) were obtained in excellent yields by reaction of 1 with N-bromo- or N-iodosuccinimide in trifluoroacetic acid as a solvent. All compounds were active against Plasmodia in vitro, but 6 showed the most selective profile with respect to Hep G2 cells: P. falciparum (chloroquine-resistant strain K1), IC50 = 0.25 µM, SI = 113; late stage, gametocytes, IC50 = 2.2 µM, SI = 13; liver stage, P. berghei sporozoites IC50 = 6.13 µM, SI = 4.6. Compounds 3–6 were also active against the emerging zoonotic species P. knowlesi with 5 being the most potent (IC50 = 0.11 µM). In addition, 3–6 potently inhibited T. brucei in vitro at nM concentrations and good selectivity with 6 again being the most selective (IC50 = 59 nM, SI = 478). These compounds were also cytotoxic to wild-type ovarian cancer cells as well as adriamycin-resistant and, except for 5, cisplatin-resistant ovarian cancer cells. In an acute oral toxicity test in mice, 3–6 did not exhibit toxic effects at doses of up to 100 mg/kg/dose × 3 consecutive days. This study demonstrates that C. sanguinolenta may be utilized as a sustainable source of novel compounds that may lead to the development of novel agents for the treatment of malaria, African trypanosomiasis, and cancer.
    • The Europe’s Lost Frontiers Augmented Reality sandbox: Explaining a 2.5 million Euro project using play sand

      Murgatroyd, Philip; Butler, Micheál; Gaffney, Vincent L. (Springer, 2022-04-06)
      The subject area of the Europe's Lost Frontiers project, the submerged landscape of Doggerland, is inaccessible and the data by which we can understand it is complex and hard for the non-specialist to understand. In order to be able to present the project at public events, an Augmented Reality sandbox was constructed, which records the shape of sand in a box, interprets it as a landscape inhabited by humans, animals and plants, and projects this simulated land back on to the sand. Different software packages can be used to highlight the effects of climate change or provide examples of the different types of evidence available to archaeologists researching submerged landscapes. The end result is an interactive, accessible display which attracts all ages and can be used as a starting point to conversation regarding the project's archaeological, scientific and technological aspects.
    • Development of a novel micro-bead force spectroscopy approach to measure the ability of a thermo-active polymer to remove bacteria from a corneal model

      Pattem, J.; Swift, Thomas; Rimmer, Stephen; Holmes, T.; MacNeil, S.; Shepherd, J. (2021-07)
      Microbial keratitis occurs from the infection of the cornea by fungi and or bacteria. It remains one of the most common global causes of irreversible blindness accounting for 3.5% (36 million) of blind people as of 2015. This paper looks at the use of a bacteria binding polymer designed to bind Staphylococcus aureus and remove it from the corneal surface. Mechanical unbinding measurements were used to probe the interactions of a thermo-active bacteria-binding polymer, highly-branched poly(N-isopropyl acrylamide), functionalised with modified vancomycin end groups (HB-PNIPAM-Van) to bacteria placed on rabbit corneal surfaces studied ex-vivo. This was conducted during sequential temperature phase transitions of HB-PNIPAM-Van-S. aureus below, above and below the lower critical solution temperature (LCST) in 3 stages, in-vitro, using a novel micro-bead force spectroscopy (MBFS) approach via atomic force microscopy (AFM). The effect of temperature on the functionality of HB-PNIPAM-Van-S. aureus showed that the polymer-bacteria complex reduced the work done in removing bacterial aggregates at T > LCST (p < 0.05), exhibiting reversibility at T < LCST (p < 0.05). At T < LCST, the breaking force, number of unbinding events, percentage fitted segments in the short and long range, and the percentage of unbinding events occurring in the long range (> 2.5 µm) increased (p < 0.05). Furthermore, the LCST phase transition temperature showed 100 × more unbinding events in the long-range z-length (> 2.5 µm) compared to S. aureus aggregates only. Here, we present the first study using AFM to assess the reversible mechanical impact of a thermo-active polymer-binding bacteria on a natural corneal surface.
    • Semi-interpenetrating Polyurethane Network Foams Containing Highly Branched Poly(N-isopropyl acrylamide) with Vancomycin Functionality

      Swift, Thomas; Hoskins, Richard; Hicks, J.; Dyson, Edward N.; Daignault, M.; Buckle, Dorothy; Douglas, C.W.I.; MacNeil, S.; Rimmer, Stephen (2021-05-17)
      Highly branched poly(N-isopropylacrylamide) (HB-PNIPAM), functionalized with vancomycin at the chain ends, acted as a bacterial adhesive and was incorporated into polyurethane foams to form semi-interpenetrating networks. The poly(N-isopropylacrylamide) was labelled with a solvatochromic dye, Nile red. It was found that the thermal response of the polymer was dependent on architecture and temperature dependent color changes were observed within the foam. The foams had open pore structures and the presence of the HB-PNIPAM substantially reduced the shrinkage of the foam as the temperature was increased upto 20 °C. The foams were selectively adhesive for Staphylococcus aureus (Gram-positive bacteria) compared to Pseudomonas aeruginosa (Gram-negative bacteria) and the presence of S. aureus was indicated by increased fluorescence intensity (590 to 800 nm).
    • Evaluation of ligand modified poly (N-Isopropyl acrylamide) hydrogel for etiological diagnosis of corneal infection

      Shivshetty, N.; Swift, Thomas; Pinnock, A.; Pownall, D.; MacNeil, S.; Douglas, I.; Garg, P.; Rimmer, Stephen (2022-01)
      Corneal ulcers, a leading cause of blindness in the developing world are treated inappropriately without prior microbiology assessment because of issues related to availability or cost of accessing these services. In this work we aimed to develop a device for identifying the presence of Gram-positive or Gram-negative bacteria or fungi that can be used by someone without the need for a microbiology laboratory. Working with branched poly (N-isopropyl acrylamide) (PNIPAM) tagged with Vancomycin, Polymyxin B, or Amphotericin B to bind Gram-positive bacteria, Gram-negative bacteria and fungi respectively, grafted onto a single hydrogel we demonstrated specific binding of the organisms. The limit of detection of the microbes by these polymers was between 10 and 4 organisms per high power field (100X) for bacteria and fungi binding polymers respectively. Using ex vivo and animal cornea infection models infected with bacteria, fungi or both we than demonstrated that the triple functionalised hydrogel could pick up all 3 organisms after being in place for 30 min. To confirm the presence of bacteria and fungi we used conventional microbiology techniques and fluorescently labelled ligands or dyes. While we need to develop an easy-to-use either a colorimetric or an imaging system to detect the fluorescent signals, this study presents for the first time a simple to use hydrogel system, which can be applied to infected eyes and specifically binds different classes of infecting agents within a short space of time. Ultimately this diagnostic system will not require trained microbiologists for its use and will be used at the point-of-care.
    • Gesturing Beyond Bones: Proposing a Decolonised Zooarchaeology

      Fitzpatrick, Alexandra L. (2022-02-08)
      This is paper represents a long process of self-reflection and critique of prior work I have presented on decolonising zooarchaeology. Engaging with current discourse on the misuse and appropriation of decolonial theory, I instead propose a framework which promotes movement towards decolonisation without co-opting the terminology. Through this, I also propose some alterations and considerations to my original proposal from 2019.
    • You Will Never Be Indiana Jones: How Toxic Masculinity Spurs Sexism and Ableism in Archaeology

      Fitzpatrick, Alexandra L. (Lady Science, 2020)
      There’s much to unpack regarding the legacy of Indiana Jones and the rest of the archaeological adventure genre, particularly regarding the way these stories perpetuate colonialist and Orientalist thought. But popular culture has also presented a view of archaeology steeped in toxic masculinity, a view that bolsters both sexism and ableism within the discipline.
    • A Brief Consideration of the Later Prehistoric Appearance and Possible Significance of the Great Auk (Pinguinus impennis) in the Covesea Caves of North-East Scotland

      Fitzpatrick, Alexandra L.; Bond, Julie M.; Büster, Lindsey S.; Armit, Ian (2020-01)
      This Short Note describes the distribution and composition of the great auk assemblage found within the Covesea Caves, and discusses its significance.
    • Archaeology Decolonized Yet?

      Fitzpatrick, Alexandra L. (2021-07)
      Tuck and Yang famously wrote that “decolonization is not a metaphor”…but are archaeologists still thinking metaphorically? The origins of archaeology as a discipline can be traced to colonial endeavours and the pursuit of instilling and maintaining racist hierarchies; as such, colonialist attitudes and approaches have become entrenched in the very foundation of archaeology. Fortunately, the past decades have seen a movement towards rectifying these past injustices, with more recent actions aligned with the broader decolonial movement that can be seen throughout academia. But has any part of archaeology been “decolonized” yet? In this article, I will examine the current state of decolonizing archaeology, with reference to actions occurring in adjacent disciplines, such as heritage and museum studies. Particular attention will be paid to projects that have attempted a decolonial approach, and the results of said project. This will be framed by an honest and critical self-reflection of my own attempts to “decolonise” my research, placing both its successes and failures in context with the broader literature on postcolonial archaeology today. This framework will also delve into the ways in which my identity as a Chinese American migrant working in Britain colours my perspective on decolonising archaeology.
    • Policy Statement: Mental Well-being among Anthropologists at Universities: A Call for System Transformation

      Fletcher, E.H.; Backe, E.L.; Brykalski, T.; Fitzpatrick, Alexandra L.; Gonzalez, M.; Ginzburg, S.L.; Meeker, R.; Riendeau, R.P.; Thies-Sauder, M.; Reyes-Foster, B.M. (2022-03-07)
      The Anthropology of Mental Health Interest Group affirms that the state of mental health in Academic Anthropology needs serious attention and transformation. We respond to structural inequities in academia that exacerbate mental distress among graduate students and other anthropologists who experience oppression, by putting forward a policy statement with recommendations to create more equitable learning and working environments.
    • The prevalence of diffuse idiopathic skeletal hyperostosis in England and Catalonia from the Roman to the post-medieval periods

      Navarro, L.C.; Buckberry, Jo (2022-06)
      Objective: Evaluate the prevalence of DISH through time from the Roman to the post-Medieval period in England and Catalonia. Material: 281 individuals from England and 247 from Catalonia were analyzed. Methods: Adult individuals with at least three well-preserved lower thoracic vertebral bodies were analyzed. DISH was assessed considering the early stages of development. Diachronic and geographical dietary shifts were investigated using reported light isotope data, archaeological reports and historical documentation. Results: Males and older individuals showed consistently higher prevalence of DISH, however, only the English sample showed a significant difference between males and females in the prevalence of DISH. No significant difference was found in the prevalence of DISH though time (from Roman to post medieval periods) nor across regions (England and Catalonia). Conclusion: The development of DISH is probably influenced by a combination of factors including increasing age and sex. Significance: This is the first exhaustive analysis of DISH in ancient Catalan populations and the first that considers the early stages of DISH. Limitations: Reduced sample size, particularly in post-medieval samples, as a result of the available excavated samples and the inclusion criteria adopted. Future Research: Include rural, religious and high-status samples in the analysis of DISH. Re-assess the prevalence of DISH in post-medieval populations.
    • An isotope signature for diffuse idiopathic skeletal hyperostosis?

      Castells Navarro, Laura; Buckberry, Jo; Beaumont, Julia (2022)
      Objectives: Diffuse idiopathic skeletal hyperostosis (DISH) has recurrently been associated with a rich diet (high in protein and higher trophic level foods); however, very few studies have investigated this link using carbon and nitrogen (δ13C and δ15N) stable isotope analysis. This paper explores the relationship between DISH and diet in two Roman urban communities by analyzing individuals with and without DISH. Materials and methods: δ13C and δ15N analysis carried out on collagen from 33 rib samples (No DISH: 27; early DISH: 4; DISH: 2) selected from individuals buried at the Romano-British site of Baldock (UK), 41 rib samples (No DISH: 38; early DISH: 3) from individuals from the Catalan Roman site of Santa Caterina (Barcelona, Spain). Additionally, six faunal samples from Baldock and seven from Santa Caterina were analyzed. Results: Standardized human isotope data from Santa Caterina show high δ15N probably associated to a diet combining terrestrial resources and freshwater fish. In contrast, isotope results from Baldock suggest a terrestrial-based diet. Individuals with DISH do not show isotopic ratios indicative of rich diet and there is no correlation between stage of DISH development and δ13C and δ15N. Conclusion: The results of this study suggest that individuals with DISH followed a similar or isotopically similar diet as those individuals without DISH in Baldock and in Santa Caterina and therefore, while DISH may have been influenced by individual's dietary habits, this is not reflected in their isotopic signature.
    • Repeatability of quantitative MRI in patients with rheumatoid arthritis

      Bertham, D.P.; Tan, A.L.; Booth, A.; Paton, L.; Emery, P.; Bigkands, J.; Farrow, Matthew (2022)
      Introduction : Rheumatoid arthritis (RA) affects 1% of the population and is principally associated with joint inflammation. It is suggested however that muscle involvement may be one of the earliest clinical features of RA. It is therefore important that techniques exist to accurately assess muscle health in those with RA to enable successful treatment. This study assesses the inter-rater and intra-rater repeatability of Diffusion Tensor MRI (DTI), 2-Point Dixon fat fraction, and T2 relaxation of the thigh muscle in patients with RA using manual regions of interest (ROI). Methods: Nineteen patients (10/19 males; mean age 59; range 18-85) diagnosed with RA had an MRI scan of their hamstrings and quadriceps muscles to obtain fat fraction (FF), mean diffusivity (MD), fractional anisotropy (FA), and T2 quantitative measurements. Two raters (R#1 & R#2) (initials removed for review) independently contoured ROIs for each patient. R#1 repeated the ROI for the same 19 patients after a 6-month hiatus to assess intra-rater repeatability. Inter-rater and intra-rater repeatability for the ROI measurements were compared using Inter Class Correlation (ICC) and Bland-Altman plots. Results: There was excellent agreement for both inter-rater and intra-rater repeatability. ICC results ranged from 0.900-0.998 (P<0.001), and intra-rater ICC results ranged from 0.977-0.999 (P<0.001). Bland-Altman plots also showed excellent agreement. Conclusions: ICC measurements and Bland-Altman plots showed excellent repeatability and agreement with no statistically significant differences when assessing the inter-rater and intra-rater repeatability of FF, MD, FA, and T2 relaxation of the thigh muscle using manual regions of interest in patients with RA. Implications for practice: Manual ROI drawing does not introduce significant errors obtaining FF, MD, FA, and T2 MRI measurements in an RA population.
    • A prospective evaluation of the clinical safety and effectiveness of a COVID-19 Urgent Eyecare Service across five areas in England

      Swystun, Alexander G.; Davey, Christopher J. (2022-01)
      Although urgent primary eye care schemes exist in some areas of England, their current safety is unknown. Accordingly, the aim of the present study was to quantify the clinical safety and effectiveness of a COVID-19 Urgent Eyecare Service (CUES) across Luton, Bedford, Hull, East Riding of Yorkshire and Harrogate. Consenting patients with acute onset eye problems who had accessed the service were contacted to ascertain what the optometrist's recommendation was, whether this worked, if they had to present elsewhere and how satisfied they were with the CUES. A total of 27% (170/629) and 6.3% (28/445) of patients managed virtually and in person, respectively, did not have their acute eye problem resolved. Regression analysis revealed that patients who attended a face-to-face consultation were 4.66 times more likely to be correctly managed [Exp (β) = 5.66], relative to those solely managed virtually. Optometrists' phone consultations failed to detect conditions such as stroke, intracranial hypertension, suspected space occupying lesions, orbital cellulitis, scleritis, corneal ulcer, wet macular degeneration, uveitis with macular oedema and retinal detachment. Of referrals to hospital ophthalmology departments, in total, 19% were false-positives. Patients, however, were typically very satisfied with the service. Uptake was associated with socioeconomic status. The present study found that a virtual assessment service providing optometrist tele-consultations was not effective at resolving patients' acute-onset eye problems. The range and number of pathologies missed by tele-consultations suggests that the service model in the present study was detrimental to patient safety. To improve this, optometrists should follow evidence based guidance when attempting to manage patients virtually, or in person. For example, patients presenting with acute-onset symptoms of flashing lights and/or floaters require an urgent dilated fundus examination. Robust data collection on service safety is required on an ongoing basis.
    • Author's Reply

      Swystun, Alexander G.; Davey, Christopher J. (2022-05)
    • Barriers and facilitators to the uptake of new medicines into clinical practice: a systematic review

      Medlinskiene, Kristina; Tomlinson, Justine; Marques, Iuri; Richardson, S.; Stirling, K.; Petty, Duncan R. (2021-11)
      Implementation and uptake of novel and cost-effective medicines can improve patient health outcomes and healthcare efficiency. However, the uptake of new medicines into practice faces a wide range of obstacles. Earlier reviews provided insights into determinants for new medicine uptake (such as medicine, prescriber, patient, organization, and external environment factors). However, the methodological approaches used had limitations (e.g., single author, narrative review, narrow search, no quality assessment of reviewed evidence). This systematic review aims to identify barriers and facilitators affecting the uptake of new medicines into clinical practice and identify areas for future research. A systematic search of literature was undertaken within seven databases: Medline, EMBASE, Web of Science, CINAHL, Cochrane Library, SCOPUS, and PsychINFO. Included in the review were qualitative, quantitative, and mixed-methods studies focused on adult participants (18 years and older) requiring or taking new medicine(s) for any condition, in the context of healthcare organizations and which identified factors affecting the uptake of new medicines. The methodological quality was assessed using QATSDD tool. A narrative synthesis of reported factors was conducted using framework analysis and a conceptual framework was utilised to group them. A total of 66 studies were included. Most studies (n = 62) were quantitative and used secondary data (n = 46) from various databases, e.g., insurance databases. The identified factors had a varied impact on the uptake of the different studied new medicines. Differently from earlier reviews, patient factors (patient education, engagement with treatment, therapy preferences), cost of new medicine, reimbursement and formulary conditions, and guidelines were suggested to influence the uptake. Also, the review highlighted that health economics, wider organizational factors, and underlying behaviours of adopters were not or under explored. This systematic review has identified a broad range of factors affecting the uptake of new medicines within healthcare organizations, which were grouped into patient, prescriber, medicine, organizational, and external environment factors. This systematic review also identifies additional factors affecting new medicine use not reported in earlier reviews, which included patient influence and education level, cost of new medicines, formulary and reimbursement restrictions, and guidelines. PROSPERO database (CRD42018108536).