• Capabilities of potential vision test measurements - clinical evaluation in the presence of cataract or macular disease.

      Vianya-Estopa, Marta; Douthwaite, William A.; Noble, B.A.; Elliott, David B. (2007)
      Purpose To determine the usefulness of a battery of potential vision tests (PVTs) including potential acuity meter (PAM), laser interferometer (LI), critical flicker/fusion frequency (CFF), superilluminated pinhole at distance (SPHd) and near (SPHn), and optimal reading speed (ORS) by their independence of the effects of cataracts and sensitivity to macular disease (MD). Setting Department of Optometry, University of Bradford, Bradford and Leeds General Infirmary, Leeds, United Kingdom. Methods Potential vision test measurements were determined in 76 patients with age-related cataract and no other eye disease, 52 patients with MD and clear ocular media, and 28 patients with normal, healthy eyes. Results Potential vision tests were independent of the degrading effects of cataract up to a visual acuity (VA) level of 20/200 or worse (CFF), 20/125 (ORS and SPH), and 20/40 (PAM and LI). A high degree of association was found between PVT scores and distance VA in the MD group for SPHd (r2 = 0.93), SPHn (r2 = 0.89), and PAM (r2 = 0.71). A moderate correlation was found for LI (r2 = 0.55), CFF (r2 = 0.50), and ORS (r2 = 0.45). Conclusions Potential acuity meter and LI showed very limited independence to moderate/dense cataracts and inaccurate predictions in patients with MD. Superilluminated pinhole was relatively unaffected by moderate/dense cataract and yet provided accurate predictions in the presence of MD and clear ocular media. Critical flicker/fusion frequency showed the greatest ability to bypass cataracts, although its ability to predict VA in patients with early MD was limited. The ORS was relatively unaffected by moderate/dense cataract, but its poor ability to predict VA in MD may limit its clinical suitability as a PVT.
    • Capacity building for whole genome sequencing of Mycobacterium tuberculosis and bioinformatics in high TB burden countries.

      Rivière, E.; Heupink, T.H.; Ismail, N.; Dippenaar, A.; Clarke, C.; Abebe, G.; Heusden van, P.; Warren, R.; Meehan, Conor J.; Van Rie, A. (2020-07)
      Whole genome sequencing (WGS) is increasingly used for Mycobacterium tuberculosis (Mtb) research. Countries with the highest tuberculosis (TB) burden face important challenges to integrate WGS into surveillance and research. We assessed the global status of Mtb WGS and developed a 3-week training course coupled with long-term mentoring and WGS infrastructure building. Training focused on genome sequencing, bioinformatics and development of a locally relevant WGS research project. The aim of the long-term mentoring was to support trainees in project implementation and funding acquisition. The focus of WGS infrastructure building was on the DNA extraction process and bioinformatics. Compared to their TB burden, Asia and Africa are grossly underrepresented in Mtb WGS research. Challenges faced resulted in adaptations to the training, mentoring and infrastructure building. Out-of-date laptop hardware and operating systems were overcome by using online tools and a Galaxy WGS analysis pipeline. A case studies approach created a safe atmosphere for students to formulate and defend opinions. Because quality DNA extraction is paramount for WGS, a biosafety level 3 and general laboratory skill training session were added, use of commercial DNA extraction kits was introduced and a 2-week training in a highly equipped laboratory was combined with a 1-week training in the local setting. By developing and sharing the components of and experiences with a sequencing and bioinformatics training program, we hope to stimulate capacity building programs for Mtb WGS and empower high-burden countries to play an important role in WGS-based TB surveillance and research.
    • Capitalist Philanthropy and the New Green Revolution for Food Security

      Morvaridi, Behrooz (2012)
      The aggressive promotion of a neo-liberal form of economic globalization has created super-rich capitalists in the South as well as the North, many of whom choose to invest some of their accumulated wealth in philanthropic ventures targeted at helping to reduce social problems, such as poverty, disease and food insecurity. The rich who have been actively involved in giving to charities and setting up philanthropic foundations – and who have developed a global reputation around this activity – are referred to here as capitalist philanthropists. While capitalist philanthropists’ often-stated rationale for this activity is to help others benefit from their ‘wealth creation’, this form of philanthropy is both politically and ideologically committed to a market approach. In the case of agriculture, this means the modernization of agriculture through market-led forces of production and support for a strategy to restructure agriculture with implementation of new technologies, innovation and management techniques. What has become known as the New Green Revolution is delivered through partnerships between public, private and local institutions and small farmers with a particular focus on sub-Saharan Africa. The article critically examines why capitalist philanthropists give away significant portions of their wealth to projects and programmes that support agrarian change and food security. It considers the motivations for partnerships with private corporations through which they engage in this agenda. What are the political and ideological motivations of capitalist philanthropy? Is this kind of giving altruistic, for the good of society? Or do the origins of capitalist philanthropy determine ‘giving’ as market-led development and expansion of the market as the solution to food security?
    • Capsella bursa-pastoris (L.) Medic. as a biomonitor of heavy metals

      Aksoy, A.; Hale, William H.G.; Dixon, Jean M. (1999)
    • A carbon and nitrogen isotopic investigation of a case of probable infantile scurvy (6th- 4th centuries BC, Slovenia)

      Nicholls, Rebecca A.; Buckberry, Jo; Beaumont, Julia; Črešnar, M.; Mason, P.; Koon, Hannah E.C. (2020-04)
      This paper presents a case study of a young infant, from a larger isotopic and osteological investigation of Bronze/Iron Age (14th-4th century BC) skeletal assemblages from Croatia and Slovenia. The osteological analysis of this infant identified pathological lesions including abnormal porosity and new bone formation consistent with malnutrition and phases of recovery. The distribution and appearance of these pathological lesions (i.e. diffuse micro-porosities and plaques of subperiosteal new bone formation on the skull and long bones) led to the conclusion that this infant probably suffered from scurvy (vitamin C deficiency). The diet and nitrogen balance of this individual were investigated by incremental dentine sampling and stable carbon and nitrogen isotope analysis. This sampling method provided a high resolution record of dietary and metabolic changes from pre-birth to around the time of death. The resulting isotope data exhibited unusually high δ13C values for this region and time period (between -11.3‰ and -12.6‰), while δ15N values were observed to be c. 3‰ above that of rib collagen sampled from contemporary adults recovered from the same site. The isotope profiles generated from the incremental dentine analysis show that δ13C and especially δ15N continue to increase until death. The evidence from the skeletal remains and high resolution isotopic data support the hypothesis that this infant suffered from severe malnutrition and an increasingly negative nitrogen balance. The paper discusses some scenarios which could have resulted in these unusual isotope ratios, whilst considering the diagnosis of possible metabolic disease. The paper also addresses the need for context when interpreting isotopic results. The isotope data should not be viewed in isolation, but rather as part of a multidisciplinary approach, considering the multiple causes of isotopic variability.
    • Cardiology patients' medicines management networks after hospital discharge: A mixed methods analysis of a complex adaptive system

      Fylan, Beth; Tranmer, M.; Armitage, Gerry R.; Blenkinsopp, Alison (2019-05)
      Introduction: The complex healthcare system that provides patients with medicines places them at risk when care is transferred between healthcare organisations, for example discharge from hospital. Consequently, under-standing and improving medicines management, particularly at care transfers, is a priority.Objectives: This study aimed to explore the medicines management system as patients experience it and determine differences in the patient-perceived importance of people in the system.Methods: We used a Social Network Analysis framework, collecting ego-net data about the importance of people patients had contact with concerning their medicines after hospital discharge. Single- and multi-level logistic regression models of patients' networks were constructed, and model residuals were explored at the patient level.This enabled us to identify patients' networks with support tie patterns different from the general patterns suggested by the model results. Qualitative data for those patients were then analysed to understand their differing experiences.Results: Networks comprised clinical and administrative healthcare staff and friends and family members.Networks were highly individual and the perceived importance of alters varied both within and between patients. Ties to spouses were significantly more likely to be rated as highly important and ties to community pharmacy staff (other than pharmacists) and to GP receptionists were less likely to be highly rated. Patients with low-value medicines management networks described having limited information about their medicines and alack of understanding or help. Patients with high-value networks described appreciating support and having confidence in staff.Conclusions: Patients experienced medicines management as individual systems within which they interacted with healthcare staff and informal support to manage their treatment. Multilevel models indicated that there are unexplained variables impacting on patients' assessments of their medicines management networks. Qualitative exploration of the model residuals can offer an understanding of networks that do not have the typical range of support ties.
    • Care homes' use of medicines study: prevalence, causes and potential harm of medication errors in care homes for older people

      Barber, N.D.; Alldred, David P.; Raynor, D.K.; Dickinson, R.; Garfield, S.; Jesson, B.; Lim, R.; Savage, I.; Standage, C.; Buckle, P.; et al. (2009)
      INTRODUCTION: Care home residents are at particular risk from medication errors, and our objective was to determine the prevalence and potential harm of prescribing, monitoring, dispensing and administration errors in UK care homes, and to identify their causes. METHODS: A prospective study of a random sample of residents within a purposive sample of homes in three areas. Errors were identified by patient interview, note review, observation of practice and examination of dispensed items. Causes were understood by observation and from theoretically framed interviews with home staff, doctors and pharmacists. Potential harm from errors was assessed by expert judgement. RESULTS: The 256 residents recruited in 55 homes were taking a mean of 8.0 medicines. One hundred and seventy-eight (69.5%) of residents had one or more errors. The mean number per resident was 1.9 errors. The mean potential harm from prescribing, monitoring, administration and dispensing errors was 2.6, 3.7, 2.1 and 2.0 (0 = no harm, 10 = death), respectively. Contributing factors from the 89 interviews included doctors who were not accessible, did not know the residents and lacked information in homes when prescribing; home staff's high workload, lack of medicines training and drug round interruptions; lack of team work among home, practice and pharmacy; inefficient ordering systems; inaccurate medicine records and prevalence of verbal communication; and difficult to fill (and check) medication administration systems. CONCLUSIONS: That two thirds of residents were exposed to one or more medication errors is of concern. The will to improve exists, but there is a lack of overall responsibility. Action is required from all concerned.
    • Caring for the dead in late Anglo-Saxon England.

      Hadley, D.M.; Buckberry, Jo (2005)
    • The case for mobile cancer care units: an NHS team's experience

      Booth, C.; Dyminksi, P.; Rattray, Marcus; Quinn, Gemma L.; Nejadhamzeeigilani, Zaynab; Bickley, L.; Seymore, T. (2021-05-07)
      This article reports the use of a mobile cancer care unit (Cancer Van) to provide continuity of care to patients with cancer who utilise the services of Airedale NHS Foundation Trust. The article contains data that shows the resilience of this service during the Covid19 pandemic and provides evidence that this type of service is beneficial for patient care.
    • Caves of Wonder: A Preliminary Analysis of the Faunal Assemblages from the Covesea Caves, NE Scotland

      Fitzpatrick, Alexandra L. (2018-10-13)
      The Covesea Caves are a series of later prehistoric sites located on the Moray Firth in north-east Scotland. Human remains have been recovered from several of these caves: the Sculptor’s Cave, Covesea Cave 1 and Covesea Cave 2 (Benton 1931; Shepherd and Shepherd 1979; Büster and Armit 2016), and display unusual characteristics that may indicate complex ritual and funerary practices (Shepherd 2007; Armit et al. 2011). However, there has been less attention given to the significant number of faunal remains from the Covesea Caves. These faunal assemblages are now the subject of research at the University of Bradford. Focused analysis of the taphonomic and processing characteristics observed on the faunal bones will examine the role of animals in the overarching narrative of the Covesea Caves, as well as further investigate the complex funerary treatments to which the human remains were subject. This paper outlines a method-driven pilot study undertaken on unstratified faunal remains from the ‘Wolf Chamber’ in Covesea Cave 2. Results from this study will be discussed and compared to select stratified remains from the main chamber of Covesea Cave 2; this will be accompanied by data collected from assessments undertaken on the main chamber faunal assemblage. Through this, the taphonomic nature of the cave environment and the role of caves in later prehistoric cosmology will be explored.
    • Cavin-1: caveolae-dependent signalling and cardiovascular disease

      Williams, Jamie J.L.; Palmer, Timothy M. (2014-04-01)
      Caveolae are curved lipid raft regions rich in cholesterol and sphingolipids found abundantly in vascular endothelial cells, adipocytes, smooth muscle cells, and fibroblasts. They are multifunctional organelles with roles in clathrin-independent endocytosis, cholesterol transport, mechanosensing, and signal transduction. Caveolae provide an environment where multiple receptor signalling components are sequestered, clustered, and compartmentalised for efficient signal transduction. Many of these receptors, including cytokine signal transducer gp130, are mediators of chronic inflammation during atherogenesis. Subsequently, disruption of these organelles is associated with a broad-range of disease states including cardiovascular disease and cancer. Cavin-1 is an essential peripheral component of caveolae that stabilises caveolin-1, the main structural/integral membrane protein of caveolae. Caveolin-1 is an essential regulator of endothelial nitric oxide synthase (eNOS) and its disruption leads to endothelial dysfunction which initiates a range of cardiovascular and pulmonary disorders. While dysfunctional cytokine signalling is also a hallmark of cardiovascular disease, knowledge of caveolae-dependent cytokine signalling is lacking as is the role of cavin-1 independent of caveolae. This review will introduce caveolae, its structural components, the caveolins and cavins, their regulation by cAMP, and their potential role in cardiovascular disease.
    • Cbx4 maintains the epithelial lineage identity and cell proliferation in the developing stratified epithelium

      Mardaryev, Andrei N.; Liu, B.; Rapisarda, Valentina; Poterlowicz, Krzysztof; Malashchuk, Igor; Rudolf, Jana; Sharov, A.A.; Jahoda, C.J.; Fessing, Michael Y.; Benitah, S.; et al. (2016-01-01)
      During development, multipotent progenitor cells establish lineage-specific programmers of gene activation and silencing underlying their differentiation into specialized cell types. We show that the Polycomb component Cbx4 serves as a critical determinant that maintains the epithelial identity in the developing epidermis by repressing nonepidermal gene expression programs. Cbx4 ablation in mice results in a marked decrease of the epidermal thickness and keratinocyte (KC) proliferation associated with activation of numerous neuronal genes and genes encoding cyclin-dependent kinase inhibitors (p16/p19 and p57). Furthermore, the chromodomain- and SUMO E3 ligase-dependent Cbx4 activities differentially regulate proliferation, differentiation, and expression of nonepidermal genes in KCs. Finally, Cbx4 expression in KCs is directly regulated by p63 transcription factor, whereas Cbx4 overexpression is capable of partially rescuing the effects of p63 ablation on epidermal development. These data demonstrate that Cbx4 plays a crucial role in the p63-regulated program of epidermal differentiation, maintaining the epithelial identity and proliferative activity in KCs via repression of the selected nonepidermal lineage and cell cycle inhibitor genes.
    • Cbx4 regulates the proliferation of thymic epithelial cells and thymus function.

      Liu, B.; Liu, Y.F.; Du, Y.R.; Mardaryev, Andrei N.; Yang, W.; Chen, H.; Xu, Z.M.; Xu, C.Q.; Zhang, X.R.; Botchkarev, Vladimir A.; et al. (2013)
      Thymic epithelial cells (TECs) are the main component of the thymic stroma, which supports T-cell proliferation and repertoire selection. Here, we demonstrate that Cbx4, a Polycomb protein that is highly expressed in the thymic epithelium, has an essential and non-redundant role in thymic organogenesis. Targeted disruption of Cbx4 causes severe hypoplasia of the fetal thymus as a result of reduced thymocyte proliferation. Cell-specific deletion of Cbx4 shows that the compromised thymopoiesis is rooted in a defective epithelial compartment. Cbx4-deficient TECs exhibit impaired proliferative capacity, and the limited thymic epithelial architecture quickly deteriorates in postnatal mutant mice, leading to an almost complete blockade of T-cell development shortly after birth and markedly reduced peripheral T-cell populations in adult mice. Furthermore, we show that Cbx4 physically interacts and functionally correlates with p63, which is a transcriptional regulator that is proposed to be important for the maintenance of the stemness of epithelial progenitors. Together, these data establish Cbx4 as a crucial regulator for the generation and maintenance of the thymic epithelium and, hence, for thymocyte development.
    • CCR7 as a therapeutic target in Cancer

      Salem, Anwar; Alotaibi, Mashael; Mroueh, Rima; Basheer, H.A.; Afarinkia, Kamyar (2021-01)
      The CCR7 chemokine axis is comprised of chemokine ligand 21 (CCL21) and chemokine ligand 19 (CCL19) acting on chemokine receptor 7 (CCR7). This axis plays two important but apparently opposing roles in cancer. On the one hand, this axis is significantly engaged in the trafficking of a number of effecter cells involved in mounting an immune response to a growing tumour. This suggests therapeutic strategies which involve potentiation of this axis can be used to combat the spread of cancer. On the other hand, the CCR7 axis plays a significant role in controlling the migration of tumour cells towards the lymphatic system and metastasis and can thus contribute to the expansion of cancer. This implies that therapeutic strategies which involve decreasing signaling through the CCR7 axis would have a beneficial effect in preventing dissemination of cancer. This dichotomy has partly been the reason why this axis has not yet been exploited, as other chemokine axes have, as a therapeutic target in cancer. Recent report of a crystal structure for CCR7 provides opportunities to exploit this axis in developing new cancer therapies. However, it remains unclear which of these two strategies, potentiation or antagonism of the CCR7 axis, is more appropriate for cancer therapy. This review brings together the evidence supporting both roles of the CCR7 axis in cancer and examines the future potential of each of the two different therapeutic approaches involving the CCR7 axis in cancer.
    • A Cdc42- and Rac-interactive binding (CRIB) domain mediates functions of coronin

      Swaminathan, Karthic; Müller-Taubenberger, A.; Faix, J.; Rivero, F.; Noegel, A.A. (2014-01)
      The Cdc42- and Rac-interactive binding motif (CRIB) of coronin binds to Rho GTPases with a preference for GDP-loaded Rac. Mutation of the Cdc42- and Rac-interactive binding motif abrogates Rac binding. This results in increased 1evels of activated Rac in coronin-deficient Dictyostelium cells (corA−), which impacts myosin II assembly. corA− cells show increased accumulation of myosin II in the cortex of growth-phase cells. Myosin II assembly is regulated by myosin heavy chain kinase–mediated phosphorylation of its tail. Kinase activity depends on the activation state of the p21-activated kinase a. The myosin II defect of corA− mutant is alleviated by dominant-negative p21-activated kinase a. It is rescued by wild-type coronin, whereas coronin carrying a mutated Cdc42- and Rac-interactive binding motif failed to rescue the myosin defect in corA− mutant cells. Ectopically expressed myosin heavy chain kinases affinity purified from corA− cells show reduced kinase activity. We propose that coronin through its affinity for GDP–Rac regulates the availability of GTP–Rac for activation of downstream effectors.
    • The cell biology of human hair follicle pigmentation.

      Tobin, Desmond J. (2011-02)
      Although we have made significant progress in understanding the regulation of the UVR-exposed epidermal-melanin unit, we know relatively little about how human hair follicle pigmentation is regulated. Progress has been hampered by gaps in our knowledge of the hair growth cycle’s controls, to which hair pigmentation appears tightly coupled. However, pigment cell researchers may have overly focused on the follicular melanocytes of the nocturnal and UVR-shy mouse as a proxy for human epidermal melanocytes. Here, I emphasize the epidermis-follicular melanocyte pluralism of human skin, as research models for vitiligo, alopecia areata and melanoma, personal care/cosmetics innovation. Further motivation could be in finding answers to why hair follicle and epidermal pigmentary units remain broadly distinct? Why melanomas tend to originate from epidermal rather than follicular melanocytes? Why multiple follicular melanocyte sub-populations exist? Why follicular melanocytes are more sensitive to aging influences? In this perspective, I attempt to raise the status of the human hair follicle melanocyte and highlight some species-specific issues involved which the general reader of the pigmentation literature (with its substantial mouse-based data) may not fully appreciate.
    • Cell Traction Force Mapping in MG63 and HaCaTs

      Soon, Chin Fhong; Genedy, Mohamed A.; Youseffi, Mansour; Denyer, Morgan C.T. (2013)
      The ability of a cell to adhere and transmit traction forces to a surface reveals the cytoskeleton integrity of a cell. Shear sensitive liquid crystals were discovered with new function in sensing cell traction force recently. This liquid crystal has been previously shown to be non-toxic, linear viscoelastic and sensitive to localized exerted forces. This paper reports the possibility of extending the application of the proposed liquid crystal based cell force sensor in sensing traction forces of osteoblast-like (MG-63) and human keratinocyte (HaCaT) cell lines exerted to the liquid crystal sensor. Incorporated with cell force measurement software, force distributions of both cell types were represented in force maps. For these lowly contractile cells, chondrocytes expressed regular forces (10 – 90 nN, N = 200) around the circular cell body whereas HaCaT projected forces (0 – 200 nN, N = 200) around the perimeter of poly-hedral shaped body. These forces are associated with the organisation of the focal adhesion expressions and stiffness of the LC substrate. From the results, liquid crystal based cell force sensor system is shown to be feasible in detecting forces of both MG63 and HaCaT.
    • Cell vs. bacterial viability in the presence of host defence peptides and RGD

      Katsikogianni, Maria G.; Hancock, R.E.W.; Devine, D.A.; Wood, David J. (2015)
      More than 2 million people/year suffer a bone fracture in the UK1. Reconstruction of bone defects represents a major clinical challenge and is addressed using a number of medical devices. Although medical device compositions and applications may differ widely, all attract microorganisms and represent niches for medical device associated infections. For open fractures, the risk of infection can be 55%2. These infections are often resistant to many of the currently available antibiotics and represent a huge and growing financial and healthcare burden. The aim of this study was a fundamental understanding of how the presence of host defence peptides (HDPs)3 and/or RGD can influence the outcome of cell vs. bacterial viability and proliferation.