A 6 year study of mammographic compression force : practitioner variability within and between screening sites

Background The application of compression force in mammography is more heavily influenced by the practitioner rather than the client. This can affect client experience, radiation dose and image quality. This research investigates practitioner compression force variation over a 6 year screening cycle in three different screening units. Methods: Recorded data included: practitioner code, applied compression force(N), breast thickness(mm), BI-RADS® density category. Exclusion criteria included: previous breast surgery, previous/ongoing assessment, breast implants. 975 clients (2925) client visits, 11,700 mammogram images) met inclusion criteria across three sites. Data analysis assessed practitioner variation of compression force and breast thickness. Results: Practitioners across three breast screening sites behave differently in the application of compression force. Two of the three sites demonstrate variability within themselves, though they demonstrated no significant difference in mean, first and third quartile compression force and breast thickness values CC(p>0.5), MLO(p>0.1) between themselves. However, the third site (where mandate dictates a minimum compression force is applied) greater consistency was demonstrated; a significant difference in mean, first and third quartile compression force and breast thickness values(p<0.001) was demonstrated between this site and the other two sites. Conclusion: Stabilisation of variations in compression force may have a positive impact on image quality, radiation dose reduction, re-attendance levels and potentially cancer detection. The large variation in compression forces could negatively impact on client experience between the units and within a unit. Further research is required to establish best practice guidelines for compression force within mammography. Keywords: Compression force, Breast compression, Compression variabilit

Towards a Clinically Relevant Lentiviral Transduction Protocol for Primary Human CD34+ Hematopoietic Stem/Progenitor Cells

Background: Hematopoietic stem cells (HSC), in particular mobilized peripheral blood stem cells, represent an attractive target for cell and gene therapy. Efficient gene delivery into these target cells without compromising self-renewal and multipotency is crucial for the success of gene therapy. We investigated factors involved in the ex vivo transduction of CD34 + HSCs in order to develop a clinically relevant transduction protocol for gene delivery. Specifically sought was a protocol that allows for efficient transduction with minimal ex vivo manipulation without serum or other reagents of animal origin. Methodology/Principal Findings: Using commercially available G-CSF mobilized peripheral blood (PB) CD34 + cells as the most clinically relevant target, we systematically examined factors including the use of serum, cytokine combinations, prestimulation time, multiplicity of infection (MOI), transduction duration and the use of spinoculation and/or retronectin. A self-inactivating lentiviral vector (SIN-LV) carrying enhanced green fluorescent protein (GFP) was used as the gene delivery vehicle. HSCs were monitored for transduction efficiency, surface marker expression and cellular function. We were able to demonstrate that efficient gene transduction can be achieved with minimal ex vivo manipulation while maintaining the cellular function of transduced HSCs without serum or other reagents of animal origin. Conclusions/Significance: This study helps to better define factors relevant towards developing a standard clinical protocol for the delivery of SIN-LV into CD34 + cells

A mammography image set for research purposes using BI-RADS density classification

Purpose Breast density categorization consistency is important when performing research, and minimization of interoperator and intraoperator variability is essential. This research aimed to validate a set of mammography images for visual breast density estimation to achieve consistency in future research projects and to determine observer performance. Methods Using the Breast Imaging Reporting and Data System (BI-RADS) as the visual grading scale, 50 mammography images were scored for density grade by 8 observers. Results Six of 8 observers achieved near-complete intraobserver agreement (kappa 0.81). Strong agreement among observers (kappa 0.61-0.8) was found in 10 of 28 paired observation episodes on the first iteration and 12 of 28 on the second. No observers demonstrated a delta variance above 1. Fleiss’ kappa was used to evaluate concordance among all observers on the first and second iterations (first iteration, 0.64; second iteration, 0.56). Discussion This research illustrates the difficulties of comparing observer visual performance scores because differences can exist when studies are repeated by and among individuals. Conclusion We confirmed that the 50 images were suitable for research purposes. Some variability existed among observers; however, overall density classification agreement was strong. Future research should include repeating this study with digitally acquired images

The 'Walking for Wellbeing in the West' randomised controlled trial of a pedometer-based walking programme in combination with physical activity consultation with 12 month follow-up: rationale and study design

Background: Scotland has a policy aimed at increasing physical activity levels in the population, but evidence on how to achieve this is still developing. Studies that focus on encouraging real world participants to start physical activity in their settings are needed. The Walking for Well-being in theWest study was designed to assess the effectiveness of a pedometer-based walking programme in combination with physical activity consultation. The study was multidisciplinary and based in the community. Walking for Well-being in the West investigated whether Scottish men and women, who were not achieving the current physical activity recommendation, increased and maintainedwalking behaviour over a 12 month period. This paper outlines the rationale and design of this innovative and pragmatic study.Methods: Participants were randomised into two groups: Group 1: Intervention (pedometer-based walking programme combined with a series of physical activity consultations); Group 2: Waiting list control for 12 weeks (followed byminimal pedometer-based intervention). Physical activity (primary outcome) wasmeasured using pedometer step counts (7 day) and the International Physical Activity Questionnaire (long version). Psychological processes were measured using questionnaires relating to the Transtheoretical Model of Behaviour Change, mood (Positive and Negative Affect Schedule) and quality of life (Euroqol EQ-5D instrument). Physiological measures included anthropometric and metabolic outcomes. Environmental influences were assessed subjectively (Neighbourhood Quality of Life Survey) and objectively (neighbourhood audit tool and GIS mapping). The qualitative evaluation employed observation,semi-structured interviews and focus groups. A supplementary study undertook an economic evaluation.Discussion: Data analysis is on-going. Walking for Well-being in the West will demonstrate if a pedometer based walking programme, in combination with physicalactivity consultation results in a sustainable increase in walking behaviour in this sample of Scottish adults over a 12 month period. The study will examine the complex relationships between behavioural change, healthconsequences and the role of the environment, in conjunction with the cost effectiveness of this approach and a detailed insight into the participants' experiences of the intervention.Trial registration: Current Controlled Trials ISRCTN88907382

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Expansion of Pathogen-Specific Mono- and Multifunctional Th1 and Th17 Cells in Multi-Focal Tuberculous Lymphadenitis

BACKGROUND: Th1 and Th17 responses are known to play an important role in immunity to pulmonary tuberculosis (PTB), although little is known about their role in extrapulmonary forms of tuberculosis (TB). METHODS: To identify the role of Th1, Th17, and Th22 cells in multi-focal TB lymphadenitis (TBL), we examined mycobacteria–specific immune responses in the whole blood of individuals with PTB (n = 20) and compared them with those with TBL (n = 25). RESULTS: Elevated frequencies of CD4(+) T cells expressing IFN- γ, TNF-α, and IL-2 were present in individuals with TBL compared with those with PTB at baseline and in response to ESAT-6 and CFP-10. Similarly, increased frequencies of CD4(+) T cells expressing IL-17A, IL-17F, and IFN-γ were also present in individuals with TBL at baseline and following ESAT-6 and CFP-10 stimulation although no significant difference in frequency of Th22 cells was observed. Finally, frequencies of Th1 (but not Th17) cells exhibited a significantly negative correlation with natural regulatory T cell frequencies at baseline. CONCLUSIONS: Multi-focal TB lymphadenitis is therefore characterized by elevated frequencies of Th1 and Th17 cells, indicating that Th1 and Th17 responses in TB disease are probably correlates of disease severity rather than of protective immunity