Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains

<p>Abstract</p> <p>Background</p> <p>There is currently a requirement for antiviral therapies capable of protecting against infection with Venezuelan equine encephalitis virus (VEEV), as a licensed vaccine is not available for general human use. Monoclonal antibodies are increasingly being developed as therapeutics and are potential treatments for VEEV as they have been shown to be protective in the mouse model of disease. However, to be truly effective, the antibody should recognise multiple strains of VEEV and broadly reactive monoclonal antibodies are rarely and only coincidentally isolated using classical hybridoma technology.</p> <p>Results</p> <p>In this work, methods were developed to reliably derive broadly reactive murine antibodies. A phage library was created that expressed single chain variable fragments (scFv) isolated from mice immunised with multiple strains of VEEV. A broadly reactive scFv was identified and incorporated into a murine IgG2a framework. This novel antibody retained the broad reactivity exhibited by the scFv but did not possess virus neutralising activity. However, the antibody was still able to protect mice against VEEV disease induced by strain TrD when administered 24 h prior to challenge.</p> <p>Conclusion</p> <p>A monoclonal antibody possessing reactivity to a wide range of VEEV strains may be of benefit as a generic antiviral therapy. However, humanisation of the murine antibody will be required before it can be tested in humans.</p> <p>Crown Copyright © 2009</p

Cancer specialist nurses’ perspectives of physical activity promotion and the potential role of physical activity apps in cancer care

Purpose: The purpose of this study was to understand breast, prostate and colorectal cancer Clinical Nurse Specialists’ (CNSs) perspectives on physical activity (PA) promotion and the role of smartphone apps to support PA promotion in cancer care. Methods: CNSs working in breast, prostate or colorectal cancer were recruited via advertisements distributed by professional organisations. In-depth semi-structured telephone interviews were conducted and analysed using thematic analysis. Results: 19 CNSs participated. The analysis resulted in 4 themes regarding CNSs’ perspectives of PA promotion within cancer care: i) policy changes in survivorship care have influenced CNSs’ promotion of PA; ii) CNSs recognise their role in supporting PA but sit within a wider system necessary for effective PA promotion; iii) CNSs use several techniques to promote PA within their consultations; iv) remaining challenges in PA promotion. The analysis resulted in 3 themes regarding CNSs’ perspectives on the use of apps to promote PA within cancer care: i) the influence of apps on access to PA support; ii) the role of apps in self-directed PA; iii) implementing apps in cancer care. Conclusions: The results of this study provide valuable insight into the CNS role and provide a number of important considerations for the development and implementation of PA interventions within cancer care, with a specific focus on smartphone-based interventions. Implications for cancer survivors: CNSs play an important role in PA promotion in cancer care and this research can inform the development of PA interventions delivered via smartphone app for people affected by cancer

Statistical design and analysis in trials of proportionate interventions: a systematic review

Background: In proportionate or adaptive interventions, the dose or intensity can be adjusted based on individual need at predefined decision stages during the delivery of the intervention. The development of such interventions may require an evaluation of the effectiveness of the individual stages in addition to the whole intervention. However, evaluating individual stages of an intervention has various challenges, particularly the statistical design and analysis. This review aimed to identify the use of trials of proportionate interventions and how they are being designed and analysed in current practice. Methods: We searched MEDLINE, Web of Science and PsycINFO for articles published between 2010 and 2015 inclusive. We considered trials of proportionate interventions in all fields of research. For each trial, its aims, design and analysis were extracted. The data synthesis was conducted using summary statistics and a narrative format. Results: Our review identified 44 proportionate intervention trials, comprising 28 trial results, 13 protocols and three secondary analyses. These were mostly described as stepped care (n=37) and mainly focussed on mental health research (n=30). The other studies were aimed at finding an optimal adaptive treatment strategy (n=7) in a variety of therapeutic areas. Further terminology used included adaptive intervention, staged intervention, sequentially multiple assignment trial or a two-phase design. The median number of decision stages in the interventions was two and only one study explicitly evaluated the effect of the individual stages. Conclusions: Trials of proportionate staged interventions are being used predominantly within the mental health field. However, few studies consider the different stages of the interventions, either at the design or the analysis phase, and how they may interact with one another. There is a need for further guidance on the design, analyses and reporting across trials of proportionate interventions

Accelerometer-assessed physical activity and sedentary time among colon cancer survivors: associations with psychological health outcomes

Purpose: The purpose of this study was to determine associations of objectively assessed moderate-to-vigorous intensity physical activity (MVPA) and sedentary time with psychological health outcomes including depression symptoms, anxiety symptoms, and overall satisfaction with life in colon cancer survivors. Methods: Colon cancer survivors (N = 180) from Alberta, Canada (n = 91), and Western Australia (n  = 89) completed a mailed survey that assessed depression symptom severity, state anxiety, and satisfaction with life (SWL). Sedentary time and MVPA were assessed using the Actigraph® GT3X+ accelerometer (60-s epochs) via a 7-day monitoring protocol. MVPA and sedentary time were corrected for wear time and then examined as quartiles (Q). Multivariate analysis of variance was used to examine associations of MVPA and sedentary time with psychological health. Results: There was a significant association between psychological health outcomes and objectively assessed MVPA [Wilks’ λ = 0.886, F(3382.2) = 2.156, p = 0.024] that suggested a small and significant association between MVPA and SWL (p = 0.032). A significant multivariate analysis of variance (MANOVA) [Wilks’ λ = 0.945, F(3159) = 3.1, p = 0.028] suggested participants meeting guidelines reported significantly fewer anxiety symptoms (M diff = −1.23, p = 0.027) and higher perceptions of SWL (M diff = 3.0, p = 0.008). No significant associations emerged for sedentary time [Wilks’ λ = 0.956, F(9382.3) = 0.788, p = 0.628].Conclusions: Contrary to previously published research using self-reports, objectively assessed MVPA and sedentary time were not associated with depression symptoms. Objectively assessed MVPA was associated with SWL and anxiety outcomes in colon cancer survivors. Implications for Cancer Survivors: Colon cancer survivors should continue to engage in regular and sustained MVPA for the accrual of psychological health benefits