17 research outputs found

    Standardising the collection of patient-reported experience measures to facilitate benchmarking and drive service improvement

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    Patient experience teams in NHS Wales’ Health Boards and Trusts are working across the country to collect patient experience feedback from members of the public who access health care services. Although this work is advanced in many areas, there is currently no way of benchmarking across organisations, reducing opportunities for shared learning. We aimed to work with patients and colleagues across Wales to agree a set of universal Patient Reported Experience Measures (PREMs) questions. Working with patient experience teams, patient groups and Welsh Government, the NHS Wales Patient Reported Outcome Measures (PROMs), Patient Reported Experience Measures (PREMs) and Effectiveness Programme team has agreed a national set of PREMs questions for use across Wales. This process led on from previous work and included patient focus groups, patient experience leads and clinical input. Patients using secondary care services in Wales will be invited to complete the agreed PREMs survey along with patient outcome measures, via an electronic platform. This will provide a consistent method of data collection which will allow us to benchmark across hospitals and organisations in NHS Wales, identifying areas of good practice, as well as areas where patients report poorer experiences. This will allow local patient experience teams to target more in-depth experience gathering initiatives and carry out appropriate improvement programmes, making better use of resources. Identifying and sharing good practice will allow NHS Wales to advance patient experience, while triangulation with patient and clinical outcomes will drive the Prudent Healthcare agenda

    Chalcogenide Glass-on-Graphene Photonics

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    Two-dimensional (2-D) materials are of tremendous interest to integrated photonics given their singular optical characteristics spanning light emission, modulation, saturable absorption, and nonlinear optics. To harness their optical properties, these atomically thin materials are usually attached onto prefabricated devices via a transfer process. In this paper, we present a new route for 2-D material integration with planar photonics. Central to this approach is the use of chalcogenide glass, a multifunctional material which can be directly deposited and patterned on a wide variety of 2-D materials and can simultaneously function as the light guiding medium, a gate dielectric, and a passivation layer for 2-D materials. Besides claiming improved fabrication yield and throughput compared to the traditional transfer process, our technique also enables unconventional multilayer device geometries optimally designed for enhancing light-matter interactions in the 2-D layers. Capitalizing on this facile integration method, we demonstrate a series of high-performance glass-on-graphene devices including ultra-broadband on-chip polarizers, energy-efficient thermo-optic switches, as well as graphene-based mid-infrared (mid-IR) waveguide-integrated photodetectors and modulators

    Thriving under Stress: Selective Translation of HIV-1 Structural Protein mRNA during Vpr-Mediated Impairment of eIF4E Translation Activity

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    Translation is a regulated process and is pivotal to proper cell growth and homeostasis. All retroviruses rely on the host translational machinery for viral protein synthesis and thus may be susceptible to its perturbation in response to stress, co-infection, and/or cell cycle arrest. HIV-1 infection arrests the cell cycle in the G2/M phase, potentially disrupting the regulation of host cell translation. In this study, we present evidence that HIV-1 infection downregulates translation in lymphocytes, attributable to the cell cycle arrest induced by the HIV-1 accessory protein Vpr. The molecular basis of the translation suppression is reduced accumulation of the active form of the translation initiation factor 4E (eIF4E). However, synthesis of viral structural proteins is sustained despite the general suppression of protein production. HIV-1 mRNA translation is sustained due to the distinct composition of the HIV-1 ribonucleoprotein complexes. RNA-coimmunoprecipitation assays determined that the HIV-1 unspliced and singly spliced transcripts are predominantly associated with nuclear cap binding protein 80 (CBP80) in contrast to completely-spliced viral and cellular mRNAs that are associated with eIF4E. The active translation of the nuclear cap binding complex (CBC)-bound viral mRNAs is demonstrated by ribosomal RNA profile analyses. Thus, our findings have uncovered that the maintenance of CBC association is a novel mechanism used by HIV-1 to bypass downregulation of eIF4E activity and sustain viral protein synthesis. We speculate that a subset of CBP80-bound cellular mRNAs contribute to recovery from significant cellular stress, including human retrovirus infection

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

    The Acceptability of Faecal Microbiota Transplant for Anterior Resection Syndrome (AFFINITY) Study

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    Low anterior resection syndrome (LARS) is recognised as disordered bowel function after rectal resection. Temporary ileostomy is associated with LARS and with reduced colonic bacteria. Faecal microbiota transplant (FMT) is the introduction of enteric bacteria from healthy donors into a patient&rsquo;s gut. We hypothesise that FMT could improve bowel function after ileostomy reversal. We aim to determine whether FMT would be acceptable to patients. Patients who had undergone anterior resection in the previous two years across four sites were sent questionnaires. A group of patients were invited to a focus group to explore their views further. There were 98 eligible patients, of whom 40 responded (41%); 67% were male, median age was 67 (range 31&ndash;83) years, and 11 still had a stoma. Of those who had their stoma reversed, 52% had major LARS symptoms. Sixty-five percent thought the concept of FMT sounded effective and 70% were willing to try it. A healthy anonymous donor and FMT via enema were the most acceptable options to the respondents. Seven patients attended the focus group; 2 female, 5 male, mean age 66 (range 45&ndash;75) years. All patients thought FMT was acceptable but the word &ldquo;faecal&rdquo; made it less acceptable. All participants would consider entering a trial with FMT as a treatment option. The main concerns were safety and efficacy. The majority of patients who responded thought FMT was acceptable and were willing to try it as a potential treatment option

    Standardising the collection of patient-reported experience measures to facilitate benchmarking and drive service improvement

    No full text
    Patient experience teams in NHS Wales’ Health Boards and Trusts are working across the country to collect patient experience feedback from members of the public who access health care services. Although this work is advanced in many areas, there is currently no way of benchmarking across organisations, reducing opportunities for shared learning. We aimed to work with patients and colleagues across Wales to agree a set of universal Patient Reported Experience Measures (PREMs) questions. Working with patient experience teams, patient groups and Welsh Government, the NHS Wales Patient Reported Outcome Measures (PROMs), Patient Reported Experience Measures (PREMs) and Effectiveness Programme team has agreed a national set of PREMs questions for use across Wales. This process led on from previous work and included patient focus groups, patient experience leads and clinical input. Patients using secondary care services in Wales will be invited to complete the agreed PREMs survey along with patient outcome measures, via an electronic platform. This will provide a consistent method of data collection which will allow us to benchmark across hospitals and organisations in NHS Wales, identifying areas of good practice, as well as areas where patients report poorer experiences. This will allow local patient experience teams to target more in-depth experience gathering initiatives and carry out appropriate improvement programmes, making better use of resources. Identifying and sharing good practice will allow NHS Wales to advance patient experience, while triangulation with patient and clinical outcomes will drive the Prudent Healthcare agenda

    Quality of Life Benefits from Arrhythmia Ablation: A longitudinal study using the C-CAP questionnaire and EQ5D.

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    AIMS To investigate long term efficacy of cardiac ablation for symptomatic arrhythmia by gathering generic and arrhythmia related quality of life data using patient reported outcome measures before and after ablation. METHODS Consecutive patients undergoing cardiac ablation procedures at three sites in the UK were enrolled (n = 561). Data were collected at baseline, at 8-16 weeks and 12 months after the ablation with responses from 390 patients received at all three time points. Non-parametric tests were used to identify any changes in patient outcomes due to non-normal data. RESULTS There were significant improvements in symptom severity, impact on life scores, EQ-5D-5L indices and VAS scores at pre- versus three months and at pre-ablation versus 1 year. Impact on life score showed additional improvement at 1 year versus three months, while improvements in symptom severity, EQ-5D-5L indices and VAS scores continued to be maintained between 3 months and 1 year. CONCLUSION Cardiac ablation provides patients with arrhythmias relief from symptoms, and results in an improvement in quality of life. Improvements observed at 3 months are maintained at 1 year follow up. This article is protected by copyright. All rights reserved
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