Now showing items 1-20 of 2408

    • When is refraction stable following routine cataract surgery? A systematic review and meta-analysis

      Charlesworth, Emily; Alderson, Alison J.; de Juan, V.; Elliott, David B. (2020-09)
      Purpose: We systematically reviewed the literature to investigate when refraction is stable following routine cataract surgery implanting monofocal intraocular lenses. Current advice recommends obtaining new spectacles 4–6 weeks following surgery. Due to advancements in surgical techniques, we hypothesised that refractive stability would be achieved earlier, which could have major short-term improvements in quality of life for patients. Methods: Medline, CINAHL, AMED, Embase, Web of Science and the Cochrane Library were searched with key words chosen to find articles, which assessed refraction following uncomplicated cataract surgery. Citation chains and the reference lists of all included papers were searched. Unpublished literature was identified using OpenGrey (www.opengrey.eu). The review considered studies that measured refraction at regular intervals following surgery until stability was achieved. Results: The search identified 6,680 papers. Two reviewers independently screened the abstracts and nine papers were found to fit the criteria, of which five were included in the meta-analysis. The quality of the papers was evaluated using the Methodological Index for Non-Randomised Studies (MINORS) instrument. Meta-analysis of 301 patients’ data of spherical, cylindrical and spherical equivalent correction were performed using Review Manager 5 (RevMan 5.3) (https://revman.cochrane.org/). Refraction at 1-week versus the gold standard of 4-weeks showed no significant difference for sphere data (effect size and 95% confidence interval of; ES = 0.00, 95% CI: −0.17, 0.17; p = 1.00), cylindrical data (ES = +0.06; 95% CI: −0.05, 0.17; p = 0.31), and spherical equivalent (ES = −0.01; 95% CI: −0.12, 0.10; p = 0.90). Heterogeneity was non-significant (I2 
    • Experiences following cataract surgery – patient perspectives

      Webber, Kathryn J.; Fylan, F.; Wood, J.M.; Elliott, David B. (2020-09)
      Purpose: Most patients report being highly satisfied with the outcome of cataract surgery but there are variable reports regarding the impact of cataract surgery on some real-world activities, such as fall rates. We hypothesised that adaptations to changed refractive correction and visual function may cause difficulties in undertaking everyday activities for some patients and used a series of focus groups to explore this issue. Method: Qualitative methods were used to explore patients’ experiences of their vision following cataract surgery, including adaptation to vision changes and their post-surgical spectacle prescription. Twenty-six participants took part in five focus groups (Mean age = 68.2 ± 11.4 years), and the data were analysed using thematic analysis. Results: We identified three themes. ‘Changes to Vision’ explores participants’ adaptation following cataract surgery. While several had problems with tasks relying on binocular vision, few found them bothersome and they resolved following second eye surgery. Participants described a trial and error approach to solving these problems rather than applying solutions suggested by their eyecare professionals. ‘Prescription Restrictions’ describes the long-term vision problems that pre-surgery myopic patients experienced as a consequence of becoming emmetropic following surgery and thus needing spectacles for reading and other close work activities, which they did not need before surgery. Very few reported that they had the information or time to make a decision regarding their post-operative correction. ‘Information Needs’ describes participant’s responses to the post-surgical information they were given, and the unmet information need regarding when they can drive following surgery. Conclusion: The findings highlight the need for clinicians to provide information on adaptation effects, assist patients to select the refractive outcome that best suits their lifestyle, and provide clear advice about when patients can start driving again. Patients need to be provided with better guidance from clinicians and prescribing guidelines for clinicians would be beneficial, particularly for the period between first- and second-eye surgery.
    • Clinical procedures in primary eye care

      Elliott, David B. (Elsevier, 2020)
      From the publisher - Well organized and easy to read, Clinical Procedures in Primary Eye Care, 5th Edition, takes an accessible, step-by-step approach to describing the commonly used primary care procedures that facilitate accurate diagnosis and effective patient management. This practical, clinically-focused text offers succinct descriptions of today's most frequently encountered optometric techniques supported by research-based evidence. You’ll find essential instructions for mastering the procedures you need to know, including recent technical advances in the field.
    • Archaeology and contemporary death: Using the past to provoke, challenge and engage

      Croucher, Karina T.; Büster, L.; Dayes, J.; Green, L.; Raynsford, J.; Comerford Boyes, Louise; Faull, C. (2021)
      While death is universal, reactions to death and ways of dealing with the dead body are hugely diverse, and archaeological research reveals numerous ways of dealing with the dead through time and across the world. In this paper, findings are presented which not only demonstrate the power of archaeology to promote and aid discussion around this difficult and challenging topic, but also how our approach resulted in personal growth and professional development impacts for participants. In this interdisciplinary pilot study, archaeological case studies were used in 31 structured workshops with 187 participants from health and social care backgrounds in the UK, to explore their reactions to a diverse range of materials which documented wide and varied approaches to death and the dead. Our study supports the hypothesis that the past is a powerful instigator of conversation around challenging aspects of death, and after death care and practices: 93% of participants agreed with this. That exposure to archaeological case studies and artefacts stimulates multifaceted discourse, some of it difficult, is a theme that also emerges in our data from pre, post and follow-up questionnaires, and semi-structured interviews. The material prompted participants to reflect on their biases, expectations and norms around both treatment of the dead, and of bereavement, impacting on their values, attitudes and beliefs. Moreover, 87% of participants believed the workshop would have a personal effect through thinking differently about death and bereavement, and 57% thought it would impact on how they approached death and bereavement in their professional practice. This has huge implications today, where talk of death remains troublesome, and for some, has a near-taboo status – ‘taboo’ being a theme evident in some participants’ own words. The findings have an important role to play in facilitating and normalising discussions around dying and bereavement and in equipping professionals in their work with people with advanced illness.
    • Concomitant Control of Mechanical Properties and Degradation in Resorbable Elastomer-like Materials Using Stereochemistry and Stoichiometry for Soft Tissue Engineering

      Wandel, M.B.; Bell, C.A.; Yu, J.; Arno, M.C.; Dreger, N.Z.; Hsu, Y.-H.; Pitto-Barry, Anaïs; Worch, J.C.; Dove, A.P.; Becker, M.L. (2020)
      Complex biological tissues are highly viscoelastic and dynamic. Efforts to repair or replace cartilage, tendon, muscle, and vasculature using materials that facilitate repair and regeneration have been ongoing for decades. However, materials that possess the mechanical, chemical and resorption characteristics necessary to recapitulate these tissues have been difficult to mimic using synthetic resorbable biomaterials. Herein, we report a series of resorbable elastomer-like materials that are compositionally identical and possess varying ratios of cis:trans double bonds in the backbone. These features afford concomitant control over the mechanical and surface eroding degradation properties of these materials. We show the materials can be functionalized post-polymerization with bioactive species and enhance cell adhesion. Furthermore, an in vivo rat model demonstrates that degradation and resorption are dependent on succinate stoichiometry in the elastomers and the results show limited inflammation highlighting their potential for use in soft tissue regeneration and drug delivery.
    • Scottish soldiers from the Battle of Dunbar 1650: a prosopographical approach to a skeletal assemblage

      Millard, A.R.; Annis, R.G.; Caffell, A.C.; Dodd, L.L.; Fischer, R.; Gerrard, C.M.; Graves, C.P.; Hendy, J.; Mackenzie, L.; Montgomery, J.; et al. (2020)
      After the Battle Dunbar between English and Scottish forces in 1650, captured Scottish soldiers were imprisoned in Durham and many hundreds died there within a few weeks. The partial skeletal remains of 28 of these men were discovered in 2013. Building on previous osteological work, here we report wide-ranging scientific studies of the remains to address the following questions: Did they have comparable diet, health and disease throughout their lives? Did they have common histories of movement (or lack of movement) during their childhoods? Can we create a collective biography of these men? Strontium and oxygen isotope analysis of tooth enamel investigated childhood movement. Carbon and nitrogen isotope analysis of incrementally sampled dentine addressed childhood diet and nutrition. Metaproteomic analysis of dental calculus investigated oral microbiomes and food residues; this was complemented by microscopic analysis of debris in calculus from ingested materials. Selected individuals were examined for dental microwear. The extent of hydroxylation of proline in collagen was examined as a potential biomarker for scurvy. An osteobiography for each man was created using the full range of data generated about him, and these were synthesised using an approach based on the historical method for a collective biography or prosopography. The childhood residences of the men were primarily within the Midland Valley of Scotland, though some spent parts of their childhood outside the British Isles. This is concordant with the known recruitment areas of the Scottish army in 1650. Their diets included oats, brassicas and milk but little seafood, as expected for lowland rather than highland diets of the period. Childhood periods of starvation or illness were almost ubiquitous, but not simultaneous, suggesting regionally variable food shortages in the 1620s and 1630s. It is likely there was widespread low-level scurvy, ameliorating in later years of life, which suggests historically unrecorded shortages of fruit and vegetables in the early 1640s. Almost all men were exposed to burnt plant matter, probably as inhaled soot, and this may relate to the high proportion of them with of sinusitis. Interpersonal violence causing skeletal trauma was rare. Based on commonalities in their osteobiographies, we argue that these men were drawn from the same stratum of society. This study is perhaps the most extensive to date of individuals from 17th century Scotland. Combined with a precise historical context it allows the lives of these men to be investigated and compared to the historical record with unprecedented precision. It illustrates the power of archaeological science methods to confirm, challenge and complement historical evidence.
    • Pilot cluster randomised trial of an evidence-based intervention to reduce avoidable hospital admissions in nursing home residents (Better Health in Residents of Care Homes with Nursing - BHiRCH-NH Study)

      Sampson, E.L.; Feast, A.; Blighe, Alan; Froggatt, K.; Hunter, R.; Marston, L.; McCormack, B.; Nurock, S.; Panca, M.; Powell, Catherine; et al. (2020-12)
      Objectives To pilot a complex intervention to support healthcare and improve early detection and treatment for common health conditions experienced by nursing home (NH) residents. Design Pilot cluster randomised controlled trial. Setting 14 NHs (7 intervention, 7 control) in London and West Yorkshire. Participants NH residents, their family carers and staff. Intervention Complex intervention to support healthcare and improve early detection and treatment of urinary tract and respiratory infections, chronic heart failure and dehydration, comprising: (1) ‘Stop and Watch (S&W)’ early warning tool for changes in physical health, (2) condition-specific care pathway and (3) Situation, Background, Assessment and Recommendation tool to enhance communication with primary care. Implementation was supported by Practice Development Champions, a Practice Development Support Group and regular telephone coaching with external facilitators. Outcome measures Data on NH (quality ratings, size, ownership), residents, family carers and staff demographics during the month prior to intervention and subsequently, numbers of admissions, accident and emergency visits, and unscheduled general practitioner visits monthly for 6 months during intervention. We collected data on how the intervention was used, healthcare resource use and quality of life data for economic evaluation. We assessed recruitment and retention, and whether a full trial was warranted. Results We recruited 14 NHs, 148 staff, 95 family carers and 245 residents. We retained the majority of participants recruited (95%). 15% of residents had an unplanned hospital admission for one of the four study conditions. We were able to collect sufficient questionnaire data (all over 96% complete). No NH implemented intervention tools as planned. Only 16 S&W forms and 8 care pathways were completed. There was no evidence of harm. Conclusions Recruitment, retention and data collection processes were effective but the intervention not implemented. A full trial is not warranted.
    • Aldehyde Dehydrogenases and Prostate Cancer: Shedding Light on Isoform Distribution to Reveal Druggable Target

      Quattrini, L.; Sadiq, Maria; Petrarolo, G.; Maitland, N.J.; Frame, F.M.; Pors, Klaus; La Motta, C. (2020-12-04)
      Prostate cancer represents the most common malignancy diagnosed in men, and is the second-leading cause of cancer death in this population. In spite of dedicated efforts, the current therapies are rarely curative, requiring the development of novel approaches based on innovative molecular targets. In this work, we validated aldehyde dehydrogenase 1A1 and 1A3 isoform expressions in different prostatic tissue-derived cell lines (normal, benign and malignant) and patient-derived primary prostate tumor epithelial cells, demonstrating their potential for therapeutic intervention using a small library of aldehyde dehydrogenase inhibitors. Compound 3b, 6-(4-fluorophenyl)-2-phenylimidazo [1,2-a]pyridine exhibited not only antiproliferative activity in the nanomolar range against the P4E6 cell line, derived from localized prostate cancer, and PC3 cell lines, derived from prostate cancer bone metastasis, but also inhibitory efficacy against PC3 colony-forming efficiency. Considering its concomitant reduced activity against normal prostate cells, 3b has the potential as a lead compound to treat prostate cancer by means of a still untapped molecular target.
    • Saturated with meaning: peatlands, heritage and folklore

      Flint, Abbi; Jennings, Benjamin R. (2020)
      Peatlands have often been represented in cultural material as being dangerous and inhospitable places, partly based on post-medieval influences, but also partly based on elements of folklore which emphasise the ‘other-worldly’ and liminal nature of these environments. Using Ilkley Moor, West Yorkshire, as a case study, the role of heritage, folklore and cultural media in guiding perceptions of the landscape is explored. Contemporary society is more diversified than historic situations, and our review indicates that perceptions of heritage landscapes reflect this complexity. The use of the peatland by different groups is explored, before addressing the interconnected roles of folklore and archaeology in past, present and future engagement with this landscape.
    • Can We Create a Circular Pharmaceutical Supply Chain (CPSC) to Reduce Medicines Waste?

      Alshemari, Abdullah; Breen, Liz; Quinn, Gemma; Sivarajah, Uthayasankar (2020-11-18)
      The increase in pharmaceutical waste medicines is a global phenomenon and financial burden. The Circular Economy, as a philosophy within the pharmaceutical supply chain, aims to promote waste reduction, maximise medicines value, and enable sustainability within this supply chain (increasing circularity). Circularity strategies for pharmaceuticals are not currently implemented in many countries, due to quality and safety barriers. The aim of this study was to determine whether the application of circular economy principles can minimise pharmaceutical waste and support sustainability in the pharmaceutical supply chain; Methods: a detailed narrative literature review was conducted in order to examine pharmaceutical waste creation, management, disposal, and the application of circular economy principles; Results: the literature scrutinised revealed that pharmaceutical waste is created by multiple routes, each of which need to be addressed by pharmacists and healthcare bodies through the Circular Economy 9R principles. These principles act as a binding mechanism for disparate waste management initiatives. Medicines, or elements of a pharmaceutical product, can be better managed to reduce waste, cost, and reduce negative environmental impacts through unsafe disposal. the study findings outline a Circular Pharmaceutical Supply Chain and suggests that it should be considered and tested as a sustainable supply chain proposition.
    • A great wave: the Storegga tsunami and the end of Doggerland?

      Walker, James; Gaffney, Vincent L.; Fitch, Simon; Muru, Merle; Fraser, Andy; Bates, M.; Bates, R. (Cambridge University Press, 2020-12)
      Around 8150 BP, the Storegga tsunami struck North-west Europe. The size of this wave has led many to assume that it had a devastating impact upon contemporaneous Mesolithic communities, including the final inundation of Doggerland, the now submerged Mesolithic North Sea landscape. Here, the authors present the first evidence of the tsunami from the southern North Sea, and suggest that traditional notions of a catastrophically destructive event may need rethinking. In providing a more nuanced interpretation by incorporating the role of local topographic variation within the study of the Storegga event, we are better placed to understand the impact of such dramatic occurrences and their larger significance in settlement studies.
    • Improving the Safety and Continuity Of Medicines management at Transitions of care (ISCOMAT): protocol for a process evaluation of a cluster randomised control trial

      Powell, Catherine; Breen, Liz; Fylan, Beth; Ismail, Hanif; Alderson, S.L.; Gale, C.P.; Gardner, Peter H.; Farrin, A.J.; Alldred, D.P.; ISCOMAT Programme Management Team (2020-11)
      Introduction A key priority for the UK National Health Service and patients is to ensure that medicines are used safely and effectively. However, medication changes are not always optimally communicated and implemented when patients transfer from hospital into community settings. Heart failure is a common reason for admission to hospital. Patients with heart failure have a high burden of morbidity, mortality and complex pharmacotherapeutic regimens. The Improving the Safety and Continuity Of Medicines management at Transitions of care programme comprises a cluster randomised controlled trial which will test the effectiveness of a complex behavioural intervention aimed at improving medications management at the interface between hospitals discharge and community care. We will conduct a rigorous process evaluation to inform interpretation of the trial findings, inform implementation of the intervention on a wider scale and aid dissemination of the intervention. Methods and analysis The process evaluation will be conducted in six purposively selected intervention sites (ie, hospital trusts and associated community pharmacies) using a mixed-methods design. Fidelity and barriers/enablers of implementation of the Medicines at Transitions Intervention (MaTI) will be explored using observation, interviews (20 patients, 40 healthcare professionals), surveys and routine trial data collection on adherence to MaTI. A parallel mixed analysis will be applied. Qualitative data will be thematically analysed using Framework analysis and survey data will be analysed descriptively. Data will be synthesised, triangulated and mapped to the Consolidated Framework for Implementation Research where appropriate. The process evaluation commenced on June 2018 and is due to end on February 2021. Ethics and dissemination Approved by Research Ethics Committee and the UK Health Research Authority REC: 18/YH/0017/IRAS: 231 431. Findings will be disseminated via academic and policy conferences, peer-reviewed publications and social media. Trial registration number ISRCTN66212970.
    • Glycosyl disulfides: importance, synthesis and application to chemical and biological systems

      Ribeiro Morais, Goreti; Falconer, Robert A. (2020)
      The disulfide bond plays an important role in the formation and stabilisation of higher order structures of peptides and proteins, while in recent years interest in this functional group has been extended to carbohydrate chemistry. Rarely found in nature, glycosyl disulfides have attracted significant attention as glycomimetics, with wide biological applications including lectin binding, as key components of dynamic libraries to study carbohydrate structures, the study of metabolic and enzymatic studies, and even as potential drug molecules. This interest has been accompanied and fuelled by the continuous development of new methods to construct the disulfide bond at the anomeric centre. Glycosyl disulfides have also been exploited as versatile intermediates in carbohydrate synthesis, particularly as glycosyl donors. This review focuses on the importance of the disulfide bond in glycobiology and in chemistry, evaluating the different methods available to synthesise glycosyl disulfides. Furthermore, we review the role of glycosyl disulfides as intermediates and/or glycosyl donors for the synthesis of neoglycoproteins and oligosaccharides, before finally considering examples of how this important class of carbohydrates have made an impact in biological and therapeutic contexts.
    • Depth-resolved variations in visibility of retinal nerve fibre bundles across the retina in enface OCT images of healthy eyes.

      Cheloni, Riccardo; Denniss, Jonathan (2021-1)
      Recent developments in optical coherence tomography (OCT) technology enable direct enface visualisation of retinal nerve fibre bundle (RNFB) loss in glaucoma. However, the optimum depth at which to visualise RNFBs across the retina is unknown. We aimed to evaluate the range of depths and optimum depth at which RNFBs can be visualised across the retina in healthy eyes. The central ± 25° retina of 10 healthy eyes from 10 people aged 57–75 years (median 68.5 years) were imaged with spectral domain OCT. Slab images of maximum axial resolution (4 μm) containing depth‐resolved attenuation coefficients were extracted from 0 to 193.5 μm below the inner limiting membrane (ILM). Bundle visibility within 10 regions of a superimposed grid was assessed subjectively by trained optometrists (n = 8), according to written instructions. Anterior and posterior limits of RNFB visibility and depth of best visibility were identified for each grid sector. Effects of retinal location and individual eye on RNFB visibility were explored using linear mixed modelling with likelihood ratio tests. Intraclass correlation coefficient (ICC) was used to measure overall agreement and repeatability of grading. Spearman’s correlation was used to measure correlation between depth range of visible RNFBs and retinal nerve fibre layer thickness (RNFLT). Retinal location and individual eye affected anterior limit of visibility (χ2(9) = 58.6 and 60.5, both p < 0.0001), but none of the differences exceeded instrument resolution, making anterior limit consistent across the retina and different eyes. Greater differences were observed in the posterior limit of visibility across retinal areas (χ2(9) = 1671.1, p < 0.0001) and different eyes (χ2(9) = 88.7, p < 0.0001). Optimal depth for visualisation of RNFBs was around 20 µm below the ILM in most regions. It varied slightly with retinal location (χ2(9) = 58.8, p < 0.0001), but it was not affected by individual eye (χ2(9) = 10.7, p = 0.29). RNFB visibility showed good agreement between graders (ICC 0.89, 95%CI 0.87–0.91), and excellent repeatability (ICC 0.96–0.99). Depth range of visible RNFBs was highly correlated with RNFLT (ρ = 0.9, 95%CI: 0.86–0.95). The range of depths with visible RNFBs varies markedly across the healthy retina, consistently with RNFLT. To extract all RNFB information consistently across the retina, slab properties should account for differences across retinal locations and between individual eyes.
    • Doggerland and the Lost Frontiers Project (2015–2020)

      Gaffney, Vincent L.; Allaby, R.; Bates, R.; Bates, M.; Ch'ng, E.; Fitch, Simon; Garwood, P.; Momber, G.; Murgatroyd, Philip; Pallen, M.; et al. (2017-05)
      As this volume, the final monograph of the SPLASHCOS network, was being finalised, the European Research Council agreed to fund a major new project relating to the marine palaeolandscapes of the southern North Sea. Emerging from the earlier work of the North Sea Palaeolandscapes Project (NSPP), the Lost Frontiers project seeks to go beyond the maps generated by that ground-breaking research. Led by researchers in the fields of archaeogeophysics, molecular biology and computer simulation, the project seeks to develop a new paradigm for the study of past environments, ecological change and the transition between hunter gathering societies and farming in North West Europe. Following from earlier work, the project will seek to release the full potential of the available seismic reflectance data sets to generate topographical maps of the whole of early Holocene Doggerland that are as accurate and complete as possible. Using these data, the study will then reconstruct and simulate the emerging palaeoenvironments of Doggerland using conventional palaeoenvironmental data, as well as ancient DNA extracted directly from sediment cores along the routes of two submerged river valleys. Using this base data, the project aims to transform our understanding of the colonisation and development of floral, faunal and human life, to explore the Mesolithic landscapes and to identify incipient Neolithic signals indicating early contact and development within the region of Doggerland.
    • Evaluation of the toxicity of two electron-deficient half-sandwich complexes against human lymphocytes from healthy individuals

      Habas, Khaled S.A.; Soldevila Barreda, Joan J.; Azmanova, Maria; Rafols, Laia; Pitto-Barry, Anaïs; Anderson, Diana; Barry, Nicolas P.E. (2020)
      Electron‐deficient half‐sandwich complexes are a class of under‐studied organometallics with demonstrated potential as metallodrug candidates. The present study investigates the effect of two 16‐electron organoruthenium complexes ([( p‐ cym)Ru(benzene‐1,2‐dithiolato)] ( 1 ) and [( p ‐cym)Ru(maleonitriledithiolate)] ( 2 )) on the cell viability of non‐immortalised human lymphocytes from healthy individuals. The genotoxic effects of 1 and 2 in lymphocytes using the Comet and cytokinesis‐block micronucleus assays is also investigated. Gene expression studies were carried out on a panel of genes involved in apoptosis and DNA damage repair response. Results show that the two 16‐electron complexes do not have significant effect on the cell viability of human lymphocytes from healthy individuals. However, an increase in DNA damage is induced by both compounds, presumably through oxidative stress production.
    • Application of small molecule FPR1 antagonists in the treatment of cancers

      Ahmet, Djevdet S.; Basheer, H.A.; Salem, Anwar; Lu, Di; Aghamohammadi, Amin; Weyerhäuser, P.; Bordiga, A.; Almeniawi, J.; Rashid, S.; Cooper, Patricia A.; et al. (Nature, 2020-10)
      The formylpeptide receptor-1 (FPR1) is a member of the chemotactic GPCR-7TM formyl peptide receptor family, whose principle function is in trafficking of various leukocytes into sites of bacterial infection and inflammation. More recently, FPR1 has been shown to be expressed in different types of cancer and in this context, plays a significant role in their expansion, resistance and recurrence. ICT12035 is a selective and potent (30 nM in calcium mobilisation assay) small molecule FPR1 antagonist. Here, we demonstrate the efficacy of ICT12035, in a number of 2D and 3D proliferation and invasion in vitro assays and an in vivo model. Our results demonstrate that targeting FPR1 by a selective small molecule antagonist, such as ICT12035, can provide a new avenue for the treatment of cancers.
    • Effect of polymerisation by microwave on the physical properties of molecularly imprinted polymers (MIPs) specific for caffeine

      Brahmbhatt, H.A.; Surtees, Alexander P.H.; Tierney, C.; Ige, O.A.; Piletska, E.V.; Swift, Thomas; Turner, N.W. (Royal Society of Chemistry, 2020-08)
      Molecularly Imprinted Polymers (MIPs) are a class of polymeric materials that exhibit highly specific recognition properties towards a chosen target. These “smart materials” offer robustness to work in extreme environmental conditions and cost effectiveness; and have shown themselves capable of the affinities/specificities observed of their biomolecular counterparts. Despite this, in many MIP systems heterogeneity generated in the polymerisation process is known to affect the performance. Microwave reactors have been extensively studied in organic chemistry because they can afford fast and well-controlled reactions, and have been used for polymerisation reactions; however, their use for creating MIPs is limited. Here we report a case study of a model MIP system imprinted for caffeine, using microwave initiation. Experimental parameters such as polymerisation time, temperature and applied microwave power have been investigated and compared with polymers prepared by oven and UV irradiation. MIPs have been characterised by BET, SEM, DSC, TGA, NMR, and HPLC for their physical properties and analyte recognition performance. The results suggest that the performance of these polymers correlates to their physical characteristics. These characteristics were significantly influenced by changes in the experimental polymerisation parameters, and the complexity of the component mixture. A series of trends were observed as each parameter was altered, suggesting that the performance of a generated polymer could be possible to predict. As expected, component selection is shown to be a major factor in the success of an imprint using this method, but this also has a significant effect on the quality of resultant polymers suggesting that only certain types of MIPs can be made using microwave irradiation. This work also indicates that the controlled polymerisation conditions offered by microwave reactors could open a promising future in the development of MIPs with more predictable analyte recognition performance, assuming material selection lends itself to this type of initiation.
    • Model-based integration analysis revealed presence of novel prognostic miRNA targets and important cancer driver genes in triple-negative breast cancers

      Zaka, M.; Sutton, Chris W.; Peng, Y.; Konur, Savas (2020-03)
      Background: miRNAs (microRNAs) play a key role in triple-negative breast cancer (TNBC) progression, and its heterogeneity at the expression, pathological and clinical levels. Stratification of breast cancer subtypes on the basis of genomics and transcriptomics profiling, along with the known biomarkers’ receptor status, has revealed the existence of subgroups known to have diverse clinical outcomes. Recently, several studies have analysed expression profiles of matched mRNA and miRNA to investigate the underlying heterogeneity of TNBC and the potential role of miRNA as a biomarker within cancers. However, the miRNA-mRNA regulatory network within TNBC has yet to be understood. Results and Findings: We performed model-based integrated analysis of miRNA and mRNA expression profiles on breast cancer, primarily focusing on triple-negative, to identify subtype-specific signatures involved in oncogenic pathways and their potential role in patient survival outcome. Using univariate and multivariate Cox analysis, we identified 25 unique miRNAs associated with the prognosis of overall survival (OS) and distant metastases-free survival (DMFS) with “risky” and “protective” outcomes. The association of these prognostic miRNAs with subtype-specific mRNA genes was established to investigate their potential regulatory role in the canonical pathways using anti-correlation analysis. The analysis showed that miRNAs contribute to the positive regulation of known breast cancer driver genes as well as the activation of respective oncogenic pathway during disease formation. Further analysis on the “risk associated” miRNAs group revealed significant regulation of critical pathways such as cell growth, voltage-gated ion channel function, ion transport and cell-to-cell signalling. Conclusion: The study findings provide new insights into the potential role of miRNAs in TNBC disease progression through the activation of key oncogenic pathways. The results showed previously unreported subtype-specific prognostic miRNAs associated with clinical outcome that may be used for further clinical evaluation.