• Pandoraea sp. strain E26: discovery of its quorum-sensing properties via whole-genome sequence analysis

      Chan, K; Yin, W.; Tee, K.K.; Chang, Chien-Yi; Priya, K. (2015-05)
      We report the draft genome sequence of Pandoraea sp. strain E26 isolated from a former landfill site, sequenced by the Illumina MiSeq platform. This genome sequence will be useful to further understand the quorum-sensing system of this isolate.
    • Papain-catalysed mechanochemical synthesis of oligopeptides by milling and twin-screw extrusion: application in the Juliá-Colonna enantioselective epoxidation

      Ardila-Fierro, K.; Crawford, Deborah E.; Körner, A.; James, S.L.; Bolm, C.; Hernández, J.G. (2018-01)
      The oligomerisation of L-amino acids by papain was studied in a mixer ball mill and in a planetary ball mill. The biocatalyst proved stable under the ball milling conditions providing the corresponding oligopeptides in good to excellent yields and with a variable degree of polymerisation. Both parameters were found to be dependent on the reaction conditions and on the nature of the amino acid (specifically on its side-chain size and hydrophobicity). In addition, the chemoenzymatic oligomerisation was demonstrated by utilising twin-screw extrusion technology, which allowed for a scalable continuous process. Finally, the synthesised oligo(L-Leu) 2b proved to be active as a catalyst in the Juliá–Colonna enantioselective epoxidation of chalcone derivatives.
    • Parallel evaluation of Doxorubicin inducing Genetic damage in human lymphocytes and sperm using the Comet assay and spectral karyotyping

      Anderson, Diana; Baumgartner, Adolf; Cemeli, Eduardo; Schmid, Thomas E. (2004)
      In recent years, two techniques for detecting genetic damage in the whole genome have gained importance: the alkaline comet assay, to detect DNA damage such as strand breaks and alkali-labile sites, and a multicolour FISH method, spectral karyotyping (SKY), to identify chromosomal aberrations simultaneously in all metaphase chromosomes. In the present study, the induction of DNA damage in human sperm and lymphocytes in vitro has been studied employing an anticancer drug, doxorubicin (DX). An increase in DNA damage was observed with the comet assay as the median per cent head DNA of sperm significantly decreased from 82.07 and 85.14% in the untreated control groups to 63.48 and 72.52% at doses of 0.8 µM DX. At 1.6 µM the percentage declined to 60.96% (the corresponding tail moment increased from 4.42 to 12.19). In stimulated lymphocytes, a significant increase was observed in tail moment, from 0.72 and 0.53 in controls to 15.17 and 12.10 at 0.2 µM DX, continuing at the same level to a final concentration of 1.6 µM. Structural aberrations found in the parallel SKY study in stimulated lymphocytes at 0.2 µM DX consisted of 14% chromatid-type and 2% chromosome-type aberrations; none were found in controls. The SKY results correlate very well with the findings of the comet assay in lymphocytes where DNA damage was observed at similar doses. This study is the first reporting use of the comet assay and SKY analysis in parallel after chemical treatment. The potential of the two techniques together is evident, as they represent a set of assays feasible for evaluating damage in human somatic and germ cells after chemical treatment (i) by direct observation of two different end-points, detecting general DNA damage and chromosomal aberrations and (ii) by extrapolation from lymphocytes to sperm, which provides a `parallelogram¿ approach in human cells.
    • Parallel RNA interference screens identify EGFR activation as an escape mechanism in FGFR3-mutant cancer

      Herrera-Abreu, M.T.; Pearson, A.; Campbell, J.; Shnyder, Steven D.; Knowles, M.A.; Ashworth, A.; Turner, N.C. (2013)
      Activation of fibroblast growth factor receptors (FGFR) is a common oncogenic event. Little is known about the determinants of sensitivity to FGFR inhibition and how these may vary between different oncogenic FGFRs. Using parallel RNA interference (RNAi) genetic screens, we show that the EGF receptor (EGFR) limits sensitivity to FGFR inhibition in FGFR3-mutant and -translocated cell lines, but not in other FGFR-driven cell lines. We also identify two distinct mechanisms through which EGFR limits sensitivity. In partially FGFR3-dependent lines, inhibition of FGFR3 results in transient downregulation of mitogen-activated protein kinase signaling that is rescued by rapid upregulation of EGFR signaling. In cell lines that are intrinsically resistant to FGFR inhibition, EGFR dominates signaling via repression of FGFR3, with EGFR inhibition rescued by delayed upregulation of FGFR3 expression. Importantly, combinations of FGFR and EGFR inhibitors overcome these resistance mechanisms in vitro and in vivo. Our results illustrate the power of parallel RNAi screens in identifying common resistance mechanisms to targeted therapies. SIGNIFICANCE: Our data identify a novel therapeutic approach to the treatment of FGFR3-mutant cancer, emphasizing the potential of combination approaches targeting both FGFR3 and EGFR. Our data extend the role of EGFR in mediating resistance to inhibitors targeting a mutant oncogene, showing that EGFR signaling can repress mutant FGFR3 to induce intrinsic resistance to FGFR targeting.
    • Part-time versus full-time occlusion therapy for treatment of amblyopia: A meta-analysis

      Yazdani, N.; Sadeghi, R.; Momeni-Moghaddam, H.; Zarifmahmoudi, L.; Ehsaei, Asieh; Barrett, Brendan T. (2017)
      Purpose: To compare full-time occlusion (FTO) and part-time occlusion (PTO) therapy in the treatment of amblyopia, with the secondary aim of evaluating the minimum number of hours of part-time patching required for maximal effect from occlusion. Methods: A literature search was performed in PubMed, Scopus, Science Direct, Ovid, Web of Science and Cochrane library. Methodological quality of the literature was evaluated according to the Oxford Center for Evidence Based Medicine and modified Newcastle-Ottawa scale. Statistical analyses were performed using Comprehensive Meta-Analysis (version 2, Biostat Inc., USA). Results: The present meta-analysis included six studies (three randomized controlled trials [RCTs] and three non-RCTs). Pooled standardized difference in the mean changes in the visual acuity was 0.337 [lower and upper limits: 0.009, 0.683] higher in the FTO as compared to the PTO group; however, this difference was not statistically significant (P ¼ 0.056, Cochrane Q value ¼ 20.4 (P ¼ 0.001), I2 ¼ 75.49%). Egger's regression intercept was 5.46 (P ¼ 0.04). The pooled standardized difference in means of visual acuity changes was 1.097 [lower and upper limits: 0.68, 1.513] higher in the FTO arm (P < 0.001), and 0.7 [lower and upper limits: 0.315, 1.085] higher in the PTO arm (P < 0.001) compared to PTO less than two hours. Conclusions: This meta-analysis shows no statistically significant difference between PTO and FTO in treatment of amblyopia. However, our results suggest that the minimum effective PTO duration, to observe maximal improvement in visual acuity is six hours per day.
    • Particle formation by mixing with supercritical antisolvent at high Reynolds numbers.

      Shekunov, Boris Yu.; Baldyga, J.; York, Peter (2001)
      A precipitation process is considered in which completely miscible solution and supercritical antisolvent are passed through premixing and diluting zones of a turbulent flow. The influence of flow velocity on particle size and nuclei concentration is discussed in terms of mixing and precipitation time constants and their supersaturation dependencies. The proposed model allowed the major process parameters such as supersaturation profile, mixed fluid fraction and mean particle size to be calculated and compared with experimental data. For the crystallization system paracetamol/ethanol/CO2 studied, the supersaturation profile becomes established at Re104. The particle size and shape are defined, firstly, by increase of supersaturation and relative volume of mixed (on molecular scale) fluid with increase of flow velocity and, secondly, by decrease of residence time available for nucleation with increase of flow velocity. These competitive processes can result in minimum particle size at a defined flow rate.
    • Partition of neutral molecules and ions from water to o-nitrophenyl octyl ether and of neutral molecules from the gas phase to o-nitrophenyl octyl ether

      Abraham, M.H.; Acree Jr, W.E.; Liu, Xiangli (2018-02)
      We have set out an equation for partition of 87 neutral molecules from water to o-nitrophenyl octyl ether, NPOE, an equation for partition of the 87 neutral molecules and 21 ionic species from water to NPOE, and an equation for partition of 87 neutral molecules from the gas phase to NPOE. Comparison with equations for partition into other solvents shows that, as regards partition of neutral (nonelectrolyte) compounds, NPOE would be a good model for 1,2-dichloroethane and for nitrobenzene. In terms of partition of ions and ionic species, NPOE is quite similar to 1,2-dichloroethane and not far away from other aprotic solvents such as nitrobenzene.
    • Paternal smoking as a cause for transgenerational damage in the offspring

      Anderson, Diana; Schmid, Thomas E.; Baumgartner, Adolf (2015)
      In 2013, the World Health Organization referred to tobacco smoking as an epidemic and a great threat to human health. Despite the obvious exposures from first- and secondhand smoking contributing to illnesses, an increased cancer risk, and death, there is a hidden risk to the next generation(s) from transgenerational mutations. In human populations, paternal preconceptional germ cell damage leading to genomic instability in offspring has always been difficult to evaluate as preconceptional and gestational exposures usually cannot be analyzed independently. Clear indications have been found that the effect of pre- and periconceptional paternal smoking may have been transmitted to the offspring via the spermatozoal genome and epigenome. Hence, cigarette smoke has to be considered a human germ cell mutagen due to its potential of inducing transgenerational DNA alterations in the unexposed F1 offspring of smoking-exposed fathers. For cohort studies, the practice of almost exclusively employing mother–childbirth pairs for the evaluation of lifestyle factors, such as smoking, while excluding the fathers’ contribution has to be reconsidered. Evidence now strongly points to the necessity of including the fathers in order not to miss paternal transgenerational damage in the offspring. This applies for genetic, epigenetic, and other transmissible effects.
    • Pathobiology of chemotherapy-induced hair loss.

      Paus, R.; Haslam, I.S.; Sharov, A.A.; Botchkarev, Vladimir A. (2013)
      Hair loss can be a psychologically devastating adverse effect of chemotherapy, but satisfactory management strategies for chemotherapy-induced alopecia remain elusive. In this Review we focus on the complex pathobiology of this side-effect. We discuss the clinical features and current management approaches, then draw upon evidence from mouse models and human hair-follicle organ-culture studies to explore the main pathobiology principles and explain why chemotherapy-induced alopecia is so challenging to manage. P53-dependent apoptosis of hair-matrix keratinocytes and chemotherapy-induced hair-cycle abnormalities, driven by the dystrophic anagen or dystrophic catagen pathway, play important parts in the degree of hair-follicle damage, alopecia phenotype, and hair-regrowth pattern. Additionally, the degree of hair-follicle stem-cell damage determines whether chemotherapy-induced alopecia is reversible. We highlight the need for carefully designed preclinical research models to generate novel, clinically relevant pointers to how this condition may be overcome.
    • Pathogens

      Lazenby, J.; Chang, Chien-Yi (2014)
    • Pathway-dependent gold nanoparticle formation by biocatalytic self-assembly

      Sahoo, J.K.; Roy, S.; Javid, Nadeem; Duncan, K.; Aitken, L.; Ulijn, R.V. (2017-09)
      We report on the use of non-equillibrium biocatalytic self-assembly and gelation to guide the reductive synthesis of gold nanoparticles. We show that biocatalytic rates simultaneously dictate supramolecular order and presentation of reductive phenols which in turn results in size control of nanoparticles that are formed.
    • Patient and public involvement in designing and conducting doctoral research: the whys and the hows

      Tomlinson, Justine; Medlinskiene, Kristina; Cheong, V-Lin; Khan, Sarah; Fylan, Beth (2019-08)
      Public and patient involvement (PPI) has been shown to have a positive impact on health and social care research. However, adequate examples describing how to operationalise effective PPI, especially in doctoral studies, are lacking. Hence, doctoral researchers new to research, or those with limited experience, can be discouraged from facilitating PPI in their research. This paper aims to describe and discuss in detail the approaches used by four doctoral researchers to incorporate PPI at different stages of their research studies from study design to disseminating findings. We aim to inform other doctoral researchers about the challenges and limitations relating to PPI that we faced. Through these, we share pragmatic recommendations for facilitating PPI during doctoral studies. The description of four case studies demonstrated that PPI could be incorporated at various stages during doctoral research. This has had a beneficial impact on our research study progression, researcher self-esteem and lastly, helped alleviate researcher isolation during doctoral studies.
    • Patient experience and physiological response to two commercially available daily disposable myopia control contact lenses

      Ghorbani Mojarrad, Neema; Cargill, C.; Collard, S.; Terry, L. (2022)
      Background: A range of myopia management (MM) contact lenses are becoming available to practitioners. These lenses are designed to slow myopia progression and axial elongation. This study explored the initial experience of participants wearing daily disposable MM contact lenses to investigate established factors previously associated with successful lens wear. Methods: This was a prospective, double-masked, crossover study. Twenty participants aged 18–30 years old were assigned to wear two daily disposable MM lenses in a randomised order. Visual acuity, contrast sensitivity, and amplitude/lag of accommodation were assessed at baseline, post-insertion, and after 2 and 6 h of lens wear. Self-reported lens comfort and vision quality were recorded at the same timepoints, and at 10 h post-insertion. Pairwise comparisons were performed between the two lenses at each timepoint, as well as assessing changes throughout wear. The relationship of the measured parameters to overall lens satisfaction was also assessed. Results: There were no significant differences between the two MM lenses at any timepoint for any of the participant-reported parameters, including overall satisfaction. A small difference in visual acuity was noted at 6 h post-insertion, although this is unlikely to be clinically significant. Comfort decreased throughout the day, most notably at 10 h post-insertion. A moderate positive correlation was observed between participant-reported visual quality and overall satisfaction. A similar pattern was seen for comfort and overall satisfaction. Self-reported vision quality and measured visual acuity were poorly correlated, highlighting the benefit of subjectively assessing the quality of vision with these lenses. Conclusions: The participants demonstrated comparable measures across a range of measures between the two MM lenses. Notably, half of the participants demonstrated a clear lens preference, although the preferred lens varied between individuals. Candidates for MM may benefit from trialling more than one MM lens design, to maximise initial wearing satisfaction.
    • Patient Perspectives on Factors Affecting Direct Oral Anticoagulant Use for Stroke Prevention in Atrial Fibrillation

      Medlinskiene, Kristina; Richardson, S.; Fylan, Beth; Stirling, K.; Rattray, Marcus; Petty, Duncan R. (2021-05-10)
      Introduction: Oral anticoagulant therapy choices for patients with atrial fibrillation (AF) expanded in the last decade with the introduction of direct oral anticoagulants (DOAC). However, the implementation of DOACs was slow and varied across different health economies in England. There is limited evidence on the patient role in the uptake of new medicines, including DOACs, apart from considering their demographic and clinical characteristics. Hence, this study aimed to address the gap by exploring the view of patients with AF on factors affecting DOAC use. Methods: A qualitative study using semi-structured interviews was conducted in three health economies in the North of England. Adult patients (>18 years) diagnosed with non-valvular AF, prescribed an oral anticoagulant (vitamin K antagonist or DOAC), and able to give written consent were recruited. Data were collected between August 2018 and April 2019. Audio recorded interviews were transcribed verbatim and analyzed using the framework method. Results: Four themes with eleven subthemes discussed identified factors affecting the use of DOACs. They were linked to limited healthcare financial and workforce resources, patient involvement in decision-making, patient knowledge about DOACs, safety concerns about oral anticoagulants, and oral anticoagulant therapy impact on patients' daily lives. Lack of a) opportunities to voice patient preferences and b) information on available therapy options resulted in some patients experiencing difficulties with the prescribed therapy. This was reported to cause negative impact on their daily lives, adherence, and overall satisfaction with the therapy. Conclusion: Greater patient involvement in decision-making could prevent and resolve difficulties encountered by some patients and potentially improve outcomes plus increase the uptake of DOACs.
    • Patients' hands and healthcare-associated infection

      Kerr, Kevin G.; Banfield, Kathleen R.; Jones, K.A.; Snelling, Anna M. (2007)
      Not available
    • Patients' knowledge of new medicines after discharge from hospital: What are the effects of hospital-based discharge counseling and community-based medicines use reviews (MURs)?

      Elson, Rachel; Cook, Helen; Blenkinsopp, Alison (2017-05)
      Background Interventions to reduce medicines discontinuity at transitions during and reinforced after discharge are effective. However, few studies have linked hospital-based counseling with onward referral for community pharmacy-based follow-up to support patients' medicines use. Objective To determine the effects of targeted hospital pharmacist counseling on discharge or targeted community pharmacy medicines reviews post-discharge on patients' knowledge of newly started medication. Methods The study was a controlled trial of targeted medicines discharge counseling provided by hospital pharmacists or follow-up post-discharge medicines review provided by community pharmacists compared with usual care (nurse counseling). Outcomes measured using a structured telephone survey conducted at two and four weeks after patients were discharged from hospital. Results Patients who received hospital pharmacist counseling were significantly more likely to report being told the purpose of their new medicine and how to take it versus those receiving usual care. Fewer than half of the patients who were allocated to receive a community pharmacy medicines review received one. Conclusions Patient knowledge of medicines newly prescribed in the hospital was increased by targeted counseling of hospital pharmacists. The findings suggest the need to improve the consistency of the information covered when providing counseling, perhaps by the implementation of a counseling checklist for use by all disciplines of staff involved in patient counseling. The potential of community pharmacy follow-up medicines review is currently undermined by several barriers to uptake.
    • Patients' views of visual field testing and priorities for research development and translation into practice

      Muthusamy, V.; Turpin, A.; Nguyen, B.N.; Denniss, Jonathan; McKendrick, A.M. (2021-10)
      There is limited information regarding the views of patients, as healthcare consumers, on visual field testing, and no information regarding their preferences for future test developments. This study aimed to increase knowledge of patients' subjective experience of visual field assessment and to explore their opinions and priorities regarding current active areas of research and development. Online questionnaire with purposive sampling design. Adults who regularly perform visual field tests in Australia who report having glaucoma or being at risk of glaucoma. An anonymous survey, implemented using the Qualtrics webtool, with both closed and open ended questions designed to explore opinions regarding visual field testing, visit attendance for perimetry, as well as priorities for developments. The survey assessed three domains: 1) opinions regarding visual field test duration and visit frequency; 2) subjective experience; and 3) perspectives on future developments for perimetry. 152 complete survey responses were obtained. The median (IQR) age of participants was 66 (60-72) years. Most participants (70%) had experience of performing more than 11 visual field tests. Participants recalled that they completed visual field tests in median of 6 minutes (IQR: 5-8 minutes) and were willing to accept additional time (median: 5, IQR: 3-6 minutes) to obtain more information. Participants were prepared to increase both the number of visual field tests per eye and the frequency of visual field tests (median: 3, IQR: 2-4 visits per year), in order to gain more information about their visual status. Regarding future developments, the most preferred option was "similar test times but an increase in the level of information about my visual field", which ranked significantly higher than all other options including "shorter test times that maintain the currently available level of information about my visual field." Our study confirms, in a different population and healthcare system, previous research reporting patient perspectives on visual field assessment. We further reveal that healthcare consumers show a strong preference for accurate information about their vision and report being prepared to undergo longer visual field tests or more visual field tests to achieve that outcome.
    • Patients’ experiences with home parental nutrition: A grounded theory study

      Wong, C.; Lucas, Beverley J.; Wood, Diana (2018-04)
      Background & aims Parenteral nutrition (PN) provides nourishment and hydration as an intravenous infusion to patients with intestinal failure (IF). The aim of the study is to generate theory that explains the experiences of adult patients living with home parenteral nutrition (HPN) and complex medication regimens. Methods A grounded theory methodology was used to explore the experiences of twelve patients receiving HPN. A semi-structured interview was conducted and recorded in each participant's home setting. Each interview was transcribed verbatim. The simultaneous process of data collection and analysis was followed reflecting the principles of the constant comparative approach. Results A total of 15 patients gave written consent, with 12 of them agreeing to be interviewed. All the participants had previously undergone surgery as a result of chronic ill health or sudden illness. Analysis revealed two core categories: stoma and HPN, and these were supported by the subcategories: maintaining stoma output, access to toilets, managing dietary changes, maintaining the HPN infusion routine, access to technical help to set up an HPN infusion, mobility with HPN equipment and general health changes. The strategy of living with loss was demonstrated by all the participants, and this was supported by the action strategies of maintaining daily activities and social interactions. Conclusions This study generates new understanding and insight into the views and experiences of patients receiving HPN in the UK. The findings from these participants have been shown to resonate with the Kubler-Ross Model [1] of the five stages of grief. The theory of living with loss was generated by the use of a grounded theory methodology. This small scale exploratory study reveals opportunities for improvements in practice to be considered by the nutrition support team (NST) and other healthcare professionals involved in the patient's hospital stay prior to discharge on HPN.
    • Patients’ experiences with home parenteral nutrition: a literature review

      Wong, C.; Lucas, Beverley J.; Wood, Diana (2015)
      Aim The aim of this review is to summarise the literature relating to patients’ experiences with home parenteral nutrition (HPN). Method This literature review is based on searches of CINAHL, PubMed, Web of Knowledge and Web of Science for articles published between 1970 and 2013. Additional studies were included from Department of Health publications, NICE clinical guidance, UK patient support group with interests in HPN or intestinal failure (IF). Results Patients with severe IF have been successfully treated with HPN since the 1970s. Early published studies evaluated clinical outcomes such as catheter-related infections, metabolic complications, thrombosis of the catheterised vein and liver impairment. Since the 1980s questionnaire studies were used to evaluate the quality of life (QoL) of patients treated with HPN. These early studies used QoL assessment tools which were not validated for patients treated with HPN. Internationally, there were published qualitative research studies which explored the experiences of patients treated with HPN. Conclusions The long-term outcome of patients treated with HPN continues to attract research interest. The review of the literature did not identify any published qualitative studies on the experiences of patients treated with HPN in the UK, suggesting a gap in the research. The UK National Health Service advocates a patient-centred approach for service design and delivery in primary and secondary care. This literature review has highlighted opportunities for qualitative research into the experiences of patients living with HPN to achieve better understanding and awareness of the rehabilitation of these patients