Exploring attitudes towards a randomised controlled trial of venous access devices – a nested pre-trial qualitative study

Purpose: This pre-trial qualitative research study was carried out to explore patient and clinical staff attitudes to central venous access devices (CVADs). In addition, views about participation in a randomised controlled trial (RCT) were explored with the aim of maximising recruitment to an imminent RCT of three CVADs. Methods: Three patient focus groups (each comprising three patients) and 23 interviews with clinical staff were conducted. Interviews and focus group discussions were digitally recorded, transcribed verbatim, anonymised, uploaded to the QSR NVivo10 qualitative software programme and thematically analysed. Results: Analysis of focus group interviews revealed the added challenges that a CVAD poses to patients with cancer. Four key themes emerged: continuity of daily life, pain and discomfort, stigma (a mark of disgrace associated with certain conditions) and self-preservation. The findings show the impact of a CVAD on patients’ ability to manage their condition. Clinical staff interviews highlighted several potential barriers to recruitment; a lack of equipoise (genuine clinical uncertainty as to which intervention is the most beneficial), concerns about the logistics of device insertion and a perceived requirement for education and training. Conclusions: This qualitative study raises awareness of key areas of concern to patients who need a CVAD for chemotherapy delivery. It was identified that there is a need for clearer patient information around CVADs. Additionally it allows investigators to identify barriers to recruitment in a timely manner in order to minimise the potential for conflict between the roles of carer and researcher and consequently, maximise recruitment to the RCT

50 Functions for the E.S.L. Classroom

This is a materials development project designed for ESL students who need to know what to say and how to say it in everyday situations of American life. Using a variety of- native and non-native speakers, a videotape was used to record 50 short scenes of functions performed in English. All the functions on the videotape are titled, with a brief pause in between each one for easy reference. The dialogues are also typed to clarify what was said and can be used to make copies for the students. The written section also includes suggested activities for the benefit of the teacher using the videotape

Adenovirus vector-specific T cells demonstrate a unique memory phenotype with high proliferative potential and coexpression of CCR5 and integrin α4_4β7_7

Background: The Step Study was a randomized trial to reduce HIV infection through vaccination with an adenovirus type 5-based gag/pol/nef construct; analysis following early cessation of the trial revealed an excess of HIV seroconversion in Ad5 seropositive men. This led to the suggestion that the Ad based vector may boost the number of CD4$^+$ CCR5$^+$ T-cells, target cells for HIV infection. Objectives: We sought to determine the immunophenotype and proliferative capacity of Ad5-specific T cells in the peripheral blood of adult donors to determine whether stimulation with replication defective Ad5 vectors could result in the significant expansion of a CD4$^+$ CCR5$^+$ T cell subset. Methods: Ad5 specific T cells were identified in the peripheral blood of healthy donors by IFN-$_y$ secretion assay and proliferative response was measured by CFSE labelling. Cells were analysed by flow cytometry to determine T cell differentiation marker, CCR5 and α$_4$β$_7$ expression on memory and proliferated cells. Results: Ad5-specific CD4$^+$ T cells within healthy adult donors exhibit a unique minimally differentiated memory phenotype with co-expression of CD45RA, CD45RO and CCR7. Stimulation with Ad vector leads to rapid expansion in vitro and a switch to an effector memory phenotype. Both short-term reactivated and proliferating Ad5-specific CD4+ T-cells express the HIV co-receptor CCR5 and the HIV gp120-binding integrin α$_4$β$_7$. Conclusion: Ad5-specific T cells demonstrate a phenotype and proliferative potential that would support HIV infection; these results are pertinent to the findings of the Step Study and future use of Ad5 as a vaccine vector

Effective Actions for Heterotic M-Theory

We discuss the moduli space approximation for heterotic M-theory, both for the minimal case of two boundary branes only, and when a bulk brane is included. The resulting effective actions may be used to describe the cosmological dynamics in the regime where the branes are moving slowly, away from singularities. We make use of the recently derived colliding branes solution to determine the global structure of moduli space, finding a boundary at which the trajectories undergo a hard wall reflection. This has important consequences for the allowed moduli space trajectories, and for the behaviour of cosmological perturbations in the model.Comment: 21 pages, 4 figures. References added and some discussions clarifie

A pilot randomised controlled trial of an internet-based cognitive behavioural therapy self-management programme (MS Invigor8) for multiple sclerosis fatigue

The majority of people affected by Multiple Sclerosis (PaMS) experience severe and disabling fatigue. MS Fatigue is poorly understood and most existing treatments have limited effectiveness. However, a recent randomised controlled trial (RCT) showed that cognitive-behaviour therapy with a clinical psychologist was effective in reducing MS fatigue severity and impact. The current study developed an Internet-based version of this intervention to make it available to a wider group of PaMS and conducted preliminary investigations of its efficacy, feasibility and cost-effectiveness in a pilot RCT. The ‘MS Invigor8’ website was developed using agile design and substantial input from PaMS. The programme includes eight online tailored and interactive sessions along with homework tasks, intended to be accessed weekly. In the pilot trial, 40 patients were randomised to MS Invigor8 (n=23) or standard care (n=17). The MS Invigor8 group accessed sessions over 8-10 weeks and received up to three 30-50 minute telephone support sessions. Participants completed online questionnaires assessing fatigue, mood and quality of life at baseline and 10 weeks follow-up. Large between group treatment effects were found for the primary outcomes of fatigue severity (d=1.19) and impact (d =1.22). The MS Invigor8 group also reported significantly greater improvements in anxiety and depression. Analysis suggested that the intervention may be cost-effective. Qualitative feedback suggested that participants considered this treatment approach acceptable and helpful. Technical website problems negatively affected some users’ experiences and need to be resolved. Given the promising results a larger RCT with longer term follow-up is warranted. <br/

Identification of the underlying factor structure of the Derriford Appearance Scale 24

Background. The Derriford Appearance Scale24 (DAS24) is a widely used measure of distress and dysfunction in relation to self-consciousness of appearance. It has been used in clinical and research settings, and translated into numerous European and Asian languages. Hitherto, no study has conducted an analysis to determine the underlying factor structure of the scale. Methods. A large (n=1265) sample of community and hospital patients with a visible difference were recruited face to face or by post, and completed the DAS24. Results. A two factor solution was found to be the best fit to the data. A main factor, general self consciousness (GSC), was represented by 18 items. Six items comprised a second factor, sexual and body self-consciousness (SBSC). The SBSC scale demonstrated greater sensitivity and specificity in identifying distress for sexually significant areas of the body. Discussion. The factor structure of the DAS24 facilitates a more nuanced interpretation of scores using this scale. Two conceptually and statistically coherent sub-scales were identified. The SBSC subscale offers a means of identifying distress and dysfunction around sexually significant areas of the body not previously possible with this scale

BOSH:Bayesian Optimization by Sampling Hierarchically

Deployments of Bayesian Optimization (BO) for functions with stochastic evaluations, such as parameter tuning via cross validation and simulation optimization, typically optimize an average of a fixed set of noisy realizations of the objective function. However, disregarding the true objective function in this manner finds a high-precision optimum of the wrong function. To solve this problem, we propose Bayesian Optimization by Sampling Hierarchically (BOSH), a novel BO routine pairing a hierarchical Gaussian process with an information-theoretic framework to generate a growing pool of realizations as the optimization progresses. We demonstrate that BOSH provides more efficient and higher-precision optimization than standard BO across synthetic benchmarks, simulation optimization, reinforcement learning and hyper-parameter tuning tasks

Development and validation of an LC-MS/MS assay for the quantification of efavirenz in different biological matrices

Aim: The non-nucleoside reverse transcriptase inhibitor efavirenz is one of the most prescribed antiretroviral therapeutics. Efavirenz-containing therapy has become associated with the occurrence of CNS side effects, including sleep disturbances, depression and even psychosis. Results: The investigation of efavirenz distribution required the development of a versatile and sensitive method. In addition to plasma, quantification was required in brain tissue and phosphate-buffered saline. The assay presented here was linear from 1.9 to 500 ng/ml. Accuracy and precision ranged between 93.7 and 99.5%, and 1.5 and 5.6%, respectively. Discussion: The method developed here represents a versatile, sensitive and easy-to-use assay. The assay has been applied to in vitro and in vivo samples demonstrating reliable efavirenz quantification in multiple matrices