Now showing items 1-20 of 2673

    • In situ monitoring of competitive coformer exchange reaction by 1H MAS Solid-state NMR

      Hareendran, C.; Alsirawan, B.; Paradkar, Anant R; Ajithku, T.G.am (American Chemical Society, 2024-03)
      In a competitive coformer exchange reaction, a recent topic of interest in pharmaceutical research, the coformer in a pharmaceutical cocrystal is exchanged with another coformer which is expected to form a cocrystal that is more stable. There will be a competition between coformers to form the most stable product through formation of hydrogen bonds. Thus, to monitor each and every step of such reactions, employing a very sensitive technique is crucial. 1H nuclear magnetic resonance (NMR) is a very powerful technique that is very sensitive to the hydrogen bond interactions. In this study, an in situ monitoring of a coformer exchange reaction is carried out by 1H magic angle spinning (MAS) solid-state NMR (SSNMR) at a spinning frequency of 60 KHz. The changes in caffeine maleic acid cocrystals on addition of glutaric acid, and caffeine glutaric cocrystal on addition of maleic acid were monitored. In all the reactions, it has been observed that caffeine glutaric acid Form I is formed. When glutaric acid was added to 2:1 caffeine maleic acid, the formation of metastable 1:1 caffeine glutaric acid Form I was observed, at the start of the experiment, indicating that the centrifugal pressure is enough for the formation. The difference in the end product of the reactions with similar reaction pathway of 1:1 and 2:1 reactant stoichiometry indicate that a complete replacement of maleic acid has only occurred only in the 1:1 stoichiometry of the reactants. The polymorphic transition of caffeine glutaric acid Form II to Form I at higher temperature was crucial reason which triggers the exchange of glutaric acid with maleic acid in the reaction of caffeine glutaric acid and maleic acid. Based on these results, new reaction pathways in competitive coformer exchange reactions could be distinguished, and the remarkable role of stoichiometry, polymorphism, temperature and centrifugal pressure could be established.
    • Assembling Wellbeing in Archaeological Teaching and Learning

      Cobb, H.; Croucher, Karina (Routledge, 2022)
      Wellbeing is a growing concern for educators and students alike and is especially significant in the light of the Covid-19 pandemic, which has brought the importance of wellbeing into sharp focus. Elsewhere, the authors (Cobb and Croucher) have written about a new pedagogic approach they have developed, specifically related to archaeology, although applicable across higher education. In this approach, they draw on relational theories and archaeology's “material turn” to focus on “Inclusive Learning Assemblages”. They explore the material and social assemblages that students encounter, both in different learning contexts and outwith learning, arguing that if we foreground learning assemblages, then student diversity and the student learning experience will be enhanced. In this paper, the authors take a step further by exploring the value of this approach for student wellbeing. They argue that taking an assemblage approach to teaching and learning in archaeology, and foregrounding diversity, actively improves student wellbeing too. This paper brings into dialogue mental health issues, with the diversity of student experiences, and the broad material engagements of an archaeology degree, in order to suggest a series of concrete steps that practitioners can implement to enhance student wellbeing.
    • Daily Negotiations with Materiality: Re–Assembling Halaf Ornamentation

      Belcher, E.; Croucher, Karina (Sidestone Press, 2023-11)
      In this paper we consider the making, daily use and deposition of ornaments in the Halaf period. We seek to move beyond rigid ‘craft production’ interpretive frameworks intersecting symbolism, complexity and social inequality. Instead, we seek different ways of knowing prehistoric ornaments, through their materiality, assemblage and visuality as evidence of ambiguous mutable person-object relationships and experiences. Making and decoration of/with ornaments offers insights into social concepts of embodiment, personhood, identity and belonging, and should be interpreted as having ambiguous, multiple uses and meanings. Using six case studies of ornament types from excavated assemblages, we critically examine existing methods of small finds’ presentation and suggest more dynamic ways of artefact analysis, interpretation and publication. We present this interpretative model as a methodology applicable broadly to small find studies in all archaeological contexts. In our analysis we re-orient towards considering assemblages of dynamic communities of makers, users and identities embedded in these objects’ life histories.
    • Dying 2 Talk: Generating a more compassion community for young people

      Booth, J.; Croucher, Karina; Walters, Elizabeth R.; Sutton-Butler, Aoife; Booth-Boniface, E.; Coe, Mia (Springer, 2023-12)
      People in the Global North often have a problem talking about — and processing — the inevitability of death. This can be because death and care of the dying has been professionalised, with encounters of death within our families and communities no longer being ‘normal and routine’ (Kellehear 2005). Young people are particularly excluded from these conversations, with implications for future mental health and wellbeing (Ainsley-Green 2017). Working in Wolverhampton and Bradford, the Dying 2 Talk (D2T) project aimed to build young people’s future resilience around this challenging topic. We recruited over 20 young people as project ambassadors to co-produce resources that would encourage talk about death, dying and bereavement. The resources were used as the basis of ‘Festivals of the Dead’ which were taken to schools to engage wider audiences of young people (aged 11 +). The project aimed to use alternative ‘ways in’ to open discussion, beginning with archaeology, and ultimately using gaming, dance, creative writing and other creative outputs to facilitate discussion, encourage compassionate relationships and build resilience. The resources succeeded in engaging young people from ages 11–19 years, facilitating a comfortable and supportive environment for these vital conversations. Project evaluations and observations revealed that the Festivals, and the activities co-created by the young ambassadors helped to facilitate spontaneous conversations about death, dying and bereavement amongst young people by providing a comfortable and supportive environment. The project was funded by the Arts and Humanities Research Council (AH/V008609/1), building on a pilot project funded by the Higher Education Innovation Fund at the University of Bradford.
    • Etiquette in the context of death and dying: Communication and conversation

      Dayes, J.; Keenan, J.; Sadza, M.; Croucher, Karina (Sage Journals, 2024)
      Death, bereavement, and grief are experiences suffused with conflict and disenfranchisement. Intricately connected is ‘etiquette’ – the sense of ‘should’ ‘must’ ‘right’ ‘wrong’ ‘appropriate’ and ‘inappropriate’ individuals feel in death and bereavement situations. This paper is the first of two answering the question, ‘where does etiquette arise in death and bereavement situations and what does this ‘look like?’’ The theme The etiquette of communication and conversation is described, highlighting the importance of early communication for resolving conflict, what is considered ‘appropriate’ communication and support, and the social values underpinning these. Data highlighted how the CBT concept of ‘shoulding and musting’ manifests in death and bereavement situations, gave insight into etiquette’s role in disenfranchising grief through shaping conversations, and offered suggestions for bereavement support. Though the term ‘etiquette’ may be misleading out of context, the concept resonated with the bereaved community and provided language to discuss the nuances of their experiences.
    • A proteomic investigation to discover candidate proteins involved in novel mechanisms of 5-fluorouracil resistance in colorectal cancer

      Duran, M. Ortega; Shaheed, Sadr-ul; Sutton, Chris W.; Shnyder, Steven (MDPI, 2024-02)
      One of the main obstacles to therapeutic success in colorectal cancer (CRC) is the development of acquired resistance to treatment with drugs such as 5-fluorouracil (5-FU). Whilst some resistance mechanisms are well known, it is clear from the stasis in therapy success rate that much is still unknown. Here, a proteomics approach is taken towards identification of candidate proteins using 5-FU-resistant sublines of human CRC cell lines generated in house. Using a multiplexed stable isotope labelling with amino acids in cell culture (SILAC) strategy, 5-FU-resistant and equivalently passaged sensitive cell lines were compared to parent cell lines by growing in Heavy medium with 2D liquid chromatography and Orbitrap Fusion™ Tribrid™ Mass Spectrometry analysis. Among 3003 commonly quantified proteins, six (CD44, APP, NAGLU, CORO7, AGR2, PLSCR1) were found up-regulated, and six (VPS45, RBMS2, RIOK1, RAP1GDS1, POLR3D, CD55) down-regulated. A total of 11 of the 12 proteins have a known association with drug resistance mechanisms or role in CRC oncogenesis. Validation through immunodetection techniques confirmed high expression of CD44 and CD63, two known drug resistance mediators with elevated proteomics expression results. The information revealed by the sensitivity of this method warrants it as an important tool for elaborating the complexity of acquired drug resistance in CRC.
    • Oncology Activity

      Gill, J.H.; Shnyder, Steven (Springer, 2015-01-15)
      The development of therapeutics to treat cancer is conceptually more difficult than for nonlife-threatening diseases for several reasons, including its complex pathophysiological nature, the molecular individuality of each tumor, and the robustness and predictability of preclinical models toward determining efficacy and safety. A major limitation to development of a “blockbuster” therapeutic strategy is the infinite combination of cellular and molecular perturbations and associated heterogeneity of causative genetic factors driving disease progression. Although challenging, the diversity of drug targets, coupled with the lethality of the disease, has encouraged studies of a vast array of approaches and opportunities for disease treatment over the years.
    • The 2021 Campus Dig

      George, Sarah; Jennings, Benjamin R. (Unknown, 2023-12)
    • Apigenin cocrystals: from computational pre-screening to physicochemical property characterisation

      Makadia, J.; Seaton, Colin C.; Li, M. (2023-05)
      Apigenin (4′,5,7-trihydroxyflavone, APG) has many potential therapeutic benefits; however, its poor aqueous solubility has limited its clinical applications. In this work, a large scale cocrystal screening has been conducted, aiming to discover potential APG cocrystals for enhancement of its solubility and dissolution rate. In order to reduce the number of the experimental screening tests, three computational prescreening tools, i.e., molecular complementarity (MC), hydrogen bond propensity (HBP), and hydrogen bond energy (HBE), were used to provide an initial selection of 47 coformer candidates, leading to the discovery of seven APG cocrystals. Among them, six APG cocrystal structures have been determined by successful growth of single crystals, i.e., apigenin-carbamazepine hydrate 1:1:1 cocrystal, apigenin-1,2-di(pyridin-4-yl)ethane hydrate 1:1:1 cocrystal, apigenin-valerolactam 1:2 cocrystal, apigenin-(dl) proline 1:2 cocrystal, apigenin-(d) proline/(l) proline 1:1 cocrystal. All of the APG cocrystals showed improved dissolution performances with the potential to be formulated into drug products.
    • High-fat diet effects on contractile performance of isolated mouse soleus and extensor digitorum longus when supplemented with high dose vitamin D

      Shelley, S.P.; James, Rob S.; Eustace, S.J.; Eyre, E.L.J.; Tallis, J. (2024-02)
      Evidence suggests vitamin D3 (VD) supplementation can reduce accumulation of adipose tissue and inflammation and promote myogenesis in obese individuals, and thus could mitigate obesity-induced reductions in skeletal muscle (SkM) contractility. However, this is yet to be directly investigated. This study, using the work-loop technique, examined effects of VD (cholecalciferol) supplementation on isolated SkM contractility. Female mice (n = 37) consumed standard low-fat diet (SLD) or high-fat diet (HFD), with or without VD (20,000 IU/kg-1 ) for 12 weeks. Soleus and EDL (n = 8-10 per muscle per group) were isolated and absolute and normalized (to muscle size and body mass) isometric force and power output (PO) were measured, and fatigue resistance determined. Absolute and normalized isometric force and PO of soleus were unaffected by diet (P > 0.087). However, PO normalized to body mass was reduced in HFD groups (P  0.588). HFD reduced EDL isometric stress (P = 0.048) and absolute and normalized PO (P  0.493). Cumulative work during fatiguing contractions was lower in HFD groups (P  0.060). This study uniquely demonstrated that high-dose VD had limited effects on SkM contractility and did not offset demonstrated adverse effects of HFD. However, small and moderate effect sizes suggest improvement in EDL muscle performance and animal morphology in HFD VD groups. Given effect sizes observed, coupled with proposed inverted U-shaped dose-effect curve, future investigations are needed to determine dose/duration specific responses to VD, which may culminate in improved function of HFD SkM. NEW FINDINGS: What is the central question of this study? Can vitamin D supplementation alleviate detrimental effects of high-fat diet (HFD) consumption on contractile performance of isolated skeletal muscles? What is the main finding and its importance? The present study is the first to examine the synergistic effects of HFD consumption and vitamin D supplementation on the contractile performance of isolated skeletal muscle. These findings suggest high dose vitamin D has limited effects on force, power or fatigue resistance of isolated mouse soleus and extensor digitorum longus.
    • Evaluating the irritant factors of silicone and hydrocolloid skin contact adhesives using trans-epidermal water loss, protein stripping, erythema, and ease of removal

      Dyson, Edward; Sikkink, Stephen; Nocita, Davide; Twigg, Peter C.; Westgate, Gillian E.; Swift, Thomas (ACS, 2024-01)
      A composite silicone skin adhesive material was designed to improve its water vapor permeability to offer advantages to wearer comfort compared to existing skin adhesive dressings available (including perforated silicone and hydrocolloid products). The chemical and mechanical properties of this novel dressing were analyzed to show that it has a high creep compliance, offering anisotropic elasticity that is likely to place less stress on the skin. A participant study was carried out in which 31 participants wore a novel silicone skin adhesive (Sil2) and a hydrocolloid competitor and were monitored for physiological response to the dressings. Trans-epidermal water loss (TEWL) was measured pre- and postwear to determine impairment of skin barrier function. Sil2 exhibited a higher vapor permeability than the hydrocolloid dressings during wear. Peel strength measurements and dye counter staining of the removed dressings showed that the hydrocolloid had a higher adhesion to the participants’ skin, resulting in a greater removal of proteins from the stratum corneum and a higher pain rating from participants on removal. Once the dressings were removed, TEWL of the participants skin beneath the Sil2 was close to normal in comparison to the hydrocolloid dressings that showed an increase in skin TEWL, indicating that the skin had been highly occluded. Analysis of the skin immediately after removal showed a higher incidence of erythema following application of hydrocolloid dressings (>60%) compared to Sil2, (
    • Germ cell determination and the developmental origin of germ cell tumors

      Nicholls, Peter; Page, D.C. (2021-04)
      In each generation, the germline is tasked with producing somatic lineages that form the body, and segregating a population of cells for gametogenesis. During animal development, when do cells of the germline irreversibly commit to producing gametes? Integrating findings from diverse species, we conclude that the final commitment of the germline to gametogenesis - the process of germ cell determination - occurs after primordial germ cells (PGCs) colonize the gonads. Combining this understanding with medical findings, we present a model whereby germ cell tumors arise from cells that failed to undertake germ cell determination, regardless of their having colonized the gonads. We propose that the diversity of cell types present in these tumors reflects the broad developmental potential of migratory PGCs.
    • Advancing clinical and translational research in germ cell tumours (GCT): recommendations from the Malignant Germ Cell International Consortium

      Fonseca, A.; Lobo, J.; Hazard, F.K.; Gell, J.; Nicholls, Peter; Weiss, R.S.; Klosterkemper, L.; Volchenboum, S.L.; Nicholson, J.C.; Frazier, A.L.; et al. (2022-11)
      Germ cell tumours (GCTs) are a heterogeneous group of rare neoplasms that present in different anatomical sites and across a wide spectrum of patient ages from birth through to adulthood. Once these strata are applied, cohort numbers become modest, hindering inferences regarding management and therapeutic advances. Moreover, patients with GCTs are treated by different medical professionals including paediatric oncologists, neuro-oncologists, medical oncologists, neurosurgeons, gynaecological oncologists, surgeons, and urologists. Silos of care have thus formed, further hampering knowledge dissemination between specialists. Dedicated biobank specimen collection is therefore critical to foster continuous growth in our understanding of similarities and differences by age, gender, and site, particularly for rare cancers such as GCTs. Here, the Malignant Germ Cell International Consortium provides a framework to create a sustainable, global research infrastructure that facilitates acquisition of tissue and liquid biopsies together with matched clinical data sets that reflect the diversity of GCTs. Such an effort would create an invaluable repository of clinical and biological data which can underpin international collaborations that span professional boundaries, translate into clinical practice, and ultimately impact patient outcomes.
    • Effect of myopia management contact lens design on accommodative microfluctuations and eye movements during reading

      Ghorbani Mojarrad, Neema; Hussain, M.; Mankowska, Aleksandra; Mallen, Edward A.H.; Cufflin, Matthew P. (2024-02)
      Background: Soft contact lenses have been developed and licensed for reducing myopia progression. These lenses have different designs, such as extended depth of focus (EDOF) and dual focus (DF). In this prospective, doublemasked, cross-over study, different lens designs were investigated to see whether these had impact on accommodative microfluctuations and eye movements during reading. Methods: Participants were fitted with three lenses in a randomised order; a single vision (SV) design (Omafilcon A2; Proclear), a DF design (Omafilcon A2; MiSight), and an EDOF lens design (Etafilcon A; NaturalVue),. Accommodative microfluctuations were measured at 25 cm for at least 60s in each lens, using a Shin-Nippon SRW-5000 autorefractor adapted to continuously record accommodation at 22Hz. Eye movement data was collected with the Thomson Clinical Eye Tracker incorporating a Tobii Eye bar. Eye movements include fixations per row, fixations per minute, mean regressions per row, total number of regressions, and total rightward saccades. Accommodation data was analysed using power spectrum analysis. Differences between the lenses were compared using a related sample two-way Friedman test. Results: Twenty-three participants (18–29 years) were recruited to take part. The average mean spherical error was − 2.65D ± 1.42DS, with an average age of 23.4 ± 3.5 years. No significant difference for accommodative microfluctuations was found. Significant differences were found for fixations per row (P = 0.03), fixations per minute (P = 0.008), mean regressions per row (P = 0.002), and total number of regressions (P = 0.002), but not total rightward saccades (P = 0.10). Post-hoc analysis indicated the EDOF lens results were significantly different from the other lenses, with more regressive eye movements observed. Conclusions: Regressive saccades appear to increase when wearing EDOF lens designs, which may impact visual comfort. Further studies in children, over a longer period of adaptation are necessary to assess the potential impact of this finding on daily reading activities in children.
    • Adiponectin negatively regulates pigmentation, Wnt/β-catenin and HGF/c-Met signalling within human scalp hair follicles ex vivo

      Nicu, C.; Jackson, J.; Shahmalak, A.; Pople, J.; Ansell, David; Paus, R. (2023-04)
      Adiponectin reportedly stimulates proliferation and elongation of human scalp hair follicles (HFs) ex vivo. In the current study, we investigated how adiponectin oligomers produced by perifollicular dermal white adipose tissue (dWAT), a potent source of adiponectin isoforms, influence human HF proliferation and pigmentation. To do so, we treated microdissected, organ-cultured HFs in the presence or absence of dWAT with a recombinant human adiponectin oligomer mix, or inhibited dWAT-derived adiponectin using a neutralizing antibody. Multiplex qPCR (Fluidigm) revealed that adiponectin oligomers downregulated pigmentation genes KITLG, PMEL and TYRP1 and Wnt genes AXIN2, LEF1 and WNT10B. In situ hybridization showed that adiponectin downregulated AXIN2 and LEF1, and up-regulated DKK1 within the dermal papilla (DP), a highly unusual transcriptional profile for a putative hair growth-promoting agent. Adiponectin oligomers also downregulated protein expression of the HGF receptor c-Met within the matrix and DP. However, adiponectin did not alter hair matrix keratinocyte proliferation within 48 h ex vivo, irrespective of the presence/absence of dWAT; HF pigmentation (Masson-Fontana histochemistry, tyrosinase activity) was also unchanged. In contrast, neutralizing adiponectin isoforms within HF + dWAT increased proliferation, melanin content and tyrosinase activity but resulted in fewer melanocytes and melanocytic dendrites, as assessed by gp100 immunostaining. These seemingly contradictory effects suggest that adiponectin exerts complex effects upon human HF biology, likely in parallel with the pro-pigmentation effects of dWAT- and DP-derived HGF. Our data suggest that dWAT-derived ratios of adiponectin isoforms and the cleaved, globular version of adiponectin may in fact determine how adiponectin impacts upon follicular pigmentation and growth.
    • Supramolecular chemistry enables vat photopolymerization 3D printing of novel water-soluble tablets

      Ong, J.J.; Chow, Y.L.; Gaisford, S.; Cook, M.T.; Swift, Thomas; Telford, Richard; Rimmer, Stephen; Qin, Y.; Mai, Y.; Goyanes, A.; et al. (2023-08-25)
      Vat photopolymerization has garnered interest from pharmaceutical researchers for the fabrication of personalised medicines, especially for drugs that require high precision dosing or are heat labile. However, the 3D printed structures created thus far have been insoluble, limiting printable dosage forms to sustained-release systems or drug-eluting medical devices which do not require dissolution of the printed matrix. Resins that produce water-soluble structures will enable more versatile drug release profiles and expand potential applications. To achieve this, instead of employing cross-linking chemistry to fabricate matrices, supramolecular chemistry may be used to impart dynamic interaction between polymer chains. In this study, water-soluble drug-loaded printlets (3D printed tablets) are fabricated via digital light processing (DLP) 3DP for the first time. Six formulations with varying ratios of an electrolyte acrylate …
    • Cytochrome P450 isoforms 1A1, 1B1 AND 2W1 as targets for therapeutic intervention in head and neck cancer

      Presa, Daniela; Khurram, S.A.; Zubir, A.Z.A.; Swaroop, Sneha; Cooper, Patricia A.; Morais, Goreti R.; Sadiq, Maria; Sutherland, Mark; Loadman, Paul; McCaul, Jim; et al. (2021-09)
      Epidemiological studies have shown that head and neck cancer (HNC) is a complex multistage process that in part involves exposure to a combination of carcinogens and the capacity of certain drug-metabolising enzymes including cytochrome P450 (CYP) to detoxify or activate such carcinogens. In this study, CYP1A1, CYP1B1 and CYP2W1 expression in HNC was correlated with potential as target for duocarmycin prodrug activation and selective therapy. In the HNC cell lines, elevated expression was shown at the gene level for CYP1A1 and CYP1B1 whereas CYP2W1 was hardly detected. However, CYP2W1 was expressed in FaDu and Detroit-562 xenografts and in a cohort of human HNC samples. Functional activity was measured in Fadu and Detroit-562 cells using P450-Glo™ assay. Antiproliferative results of duocarmycin prodrugs ICT2700 and ICT2706 revealed FaDu and Detroit-562 as the most sensitive HNC cell lines. Administration of ICT2700 in vivo using a single dose of ICT2700 (150 mg/kg) showed preferential inhibition of small tumour growth (mean size of 60 mm3) in mice bearing FaDu xenografts. Significantly, our findings suggest a potential targeted therapeutic approach to manage HNCs by exploiting intratumoural CYP expression for metabolic activation of duocarmycin-based prodrugs such as ICT2700.
    • Exploring Radio Frequency Techniques for Bone Fracture Detection: A Comprehensive Review of Low Frequency and Microwave Approaches

      Ahmad, Aldelemy; Ebenezer, Adjei; Prince, Siaw; Buckley, John; Hardy, Maryann; Qahwaji, Rami S.R.; Abd-Alhameed, Raed; Bastos, J.; Barbosa, C.; Elfergani, I.; et al. (2023-09-13)
      This comprehensive review paper examines bone fracture detection techniques based on time-domain low-frequency and microwave radiofrequency (RF). Early and accurate diagnosis of bone fractures remains critical in healthcare, as it can significantly improve patient outcomes. This review focuses on the potential of low-frequency and microwave RF methods, particularly their combination and application of time-domain analysis for enhanced fracture detection. We begin by providing an overview of the fundamental concepts of RF techniques and then by examining biological tissues' dielectric properties. We then compare the advantages and limitations of various bone fracture detection techniques, such as low-frequency RF methods, microwave RF methods, ultrasonography, X-ray, and CT scans. The discussion then shifts to hybrid approaches that combine low-frequency and microwave techniques, emphasising the advantages of such combinations in fracture detection. Machine learning techniques, their applications in bone fracture detection, and the role of time-domain analysis in hybrid approaches are also investigated. Finally, we examine the accuracy and reliability of simulated models for bone fracture detection. We discuss recent advancements and future directions, such as novel sensor technologies, improved signal processing techniques, integration with medical imaging modalities, and personalised fracture detection approaches. This review aims to comprehensively understand the landscape and future potential of time-domain analysis in low-frequency and microwave RF techniques for bone fracture detection.
    • Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol

      Hull, M.A.; Ow, P.L.; Ruddock, S.; Brend, T.; Smith, A.F.; Marshall, H.; Song, M.; Chan, A.T.; Garrett, W.S.; Yilmaz, O.; et al. (BMJ, 2023-11)
      There remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory as well as antineoplastic properties. A phase 2 randomised trial of preoperative EPA free fatty acid 2 g daily in patients undergoing surgery for CRC liver metastasis showed no difference in the primary endpoint (histological tumour proliferation index) compared with placebo. However, the trial demonstrated possible benefit for the prespecified exploratory endpoint of postoperative disease-free survival. Therefore, we tested the hypothesis that EPA treatment, started before liver resection surgery (and continued postoperatively), improves CRC outcomes in patients with CRC liver metastasis. Methods and analysis: The EPA for Metastasis Trial 2 trial is a randomised, double-blind, placebo-controlled, phase 3 trial of 4 g EPA ethyl ester (icosapent ethyl (IPE; Vascepa)) daily in patients undergoing liver resection surgery for CRC liver metastasis with curative intent. Trial treatment continues for a minimum of 2 years and maximum of 4 years, with 6monthly assessments, including quality of life outcomes, as well as annual clinical record review after the trial intervention. The primary endpoint is CRC progression-free survival. Key secondary endpoints are overall survival, as well as the safety and tolerability of IPE. A minimum 388 participants are estimated to provide 247 CRC progression events during minimum 2-year follow-up, allowing detection of an HR of 0.7 in favour of IPE, with a power of 80% at the 5% (two sided) level of significance, assuming drop-out of 15%. Ethics and dissemination: Ethical and health research authority approval was obtained in January 2018. All data will be collected by 2025. Full trial results will be published in 2026. Secondary analyses of health economic data, biomarker studies and other translational work will be published subsequently. Trial registration number NCT03428477.
    • Current approaches to soft contact lens handling training - Global perspectives

      Vianya-Estopa, M.; Ghorbani Mojarrad, Neema; Huntjens, B.; Garcia-Porta, N.; Pinero, D.P.; Nagra, M.; Terry, L.; Dutta, D.; Wolffsohn, J.; Joshi, M.; et al. (2023-12)
      All neophyte contact lens wearers require training on how to handle contact lenses. Currently, almost no published information exists describing the most common approaches used by those involved in such training in soft contact lens wearers. This study aimed to gather information on the approaches taken by those conducting this training worldwide. An online survey was created in English and translated to Spanish and distributed internationally via social media, conference attendees, and professional contacts. The anonymous survey included information on workplace setting of respondents, information about the typical approaches used for application and removal of soft contact lenses, length of the appointment, and success rate with their approach. Survey responses were received between May 2021 and April 2022. A total of 511 individuals completed the survey and responses were received from 31 countries with 48.7% from the UK. The most common approach taught for application was to have the patient hold the upper eyelashes (84.7%) and to hold the lower eyelid with the same hand as the lens (89.4%). Lenses were applied directly to the cornea by 57.7% of the respondents. The most common approach taught for lens removal was to drag the lens inferiorly from the cornea prior to removal (49.3%). Most respondents did not use videos to aid the teaching appointment (62.0%); however, they felt that their approach was successful in most cases (90). Application and removal training sessions lasted a median of 30 min and contact lenses were typically dispensed after the instructor witnessing successful application and removal three times. Various methods are adopted globally for training of application and removal of soft contact lenses, with many advising a patient-specific approach is required for success. The results of this survey provide novel insights into soft contact lens handling training in clinical practice.