PROPEL: implementation of an evidence based pelvic floor muscle training intervention for women with pelvic organ prolapse: a realist evaluation and outcomes study protocol

Abstract Background Pelvic Organ Prolapse (POP) is estimated to affect 41%–50% of women aged over 40. Findings from the multi-centre randomised controlled “Pelvic Organ Prolapse PhysiotherapY” (POPPY) trial showed that individualised pelvic floor muscle training (PFMT) was effective in reducing symptoms of prolapse, improved quality of life and showed clear potential to be cost-effective. However, provision of PFMT for prolapse continues to vary across the UK, with limited numbers of women’s health physiotherapists specialising in its delivery. Implementation of this robust evidence from the POPPY trial will require attention to different models of delivery (e.g. staff skill mix) to fit with differing care environments. Methods A Realist Evaluation (RE) of implementation and outcomes of PFMT delivery in contrasting NHS settings will be conducted using multiple case study sites. Involving substantial local stakeholder engagement will permit a detailed exploration of how local sites make decisions on how to deliver PFMT and how these lead to service change. The RE will track how implementation is working; identify what influences outcomes; and, guided by the RE-AIM framework, will collect robust outcomes data. This will require mixed methods data collection and analysis. Qualitative data will be collected at four time-points across each site to understand local contexts and decisions regarding options for intervention delivery and to monitor implementation, uptake, adherence and outcomes. Patient outcome data will be collected at baseline, six months and one year follow-up for 120 women. Primary outcome will be the Pelvic Organ Prolapse Symptom Score (POP-SS). An economic evaluation will assess the costs and benefits associated with different delivery models taking account of further health care resource use by the women. Cost data will be combined with the primary outcome in a cost effectiveness analysis, and the EQ-5D-5L data in a cost utility analysis for each of the different models of delivery. Discussion Study of the implementation of varying models of service delivery of PFMT across contrasting sites combined with outcomes data and a cost effectiveness analysis will provide insight into the implementation and value of different models of PFMT service delivery and the cost benefits to the NHS in the longer term

Applications of a non-interferometric x-ray phase contrast imaging method with both synchrotron and conventional sources

We have developed a totally incoherent, non-interferometric x-ray phase contrast imaging (XPCI) method. This is based on the edge illumination (EI) concept developed at the ELETTRA synchrotron in Italy in the late ‘90s. The method was subsequently adapted to the divergent beam generated by a conventional source, by replicating it for every detector line through suitable masks. The method was modelled both with the simplified ray-tracing and with the more rigorous wave-optics approach, and in both cases excellent agreement with the experimental results was found. The wave-optics model enabled assessing the methods’ coherence requirements, showing that they are at least an order of magnitude more relaxed than in other methods, without this having negative consequences on the phase sensitivity. Our masks have large pitches (up to 50 times larger than in grating interferometry, for example), which allows for manufacturing through standard lithography, scalability, cost-effectiveness and easiness to align. When applied to a polychromatic and divergent beam generated by a conventional source, the method enables the detection of strong phase effects also with uncollimated, unapertured sources with focal spots of up to 100 mm, compatible with the state-of-the-art in mammography. When used at synchrotrons, it enables a contrast increase of orders of magnitude over other methods. Robust phase retrieval was proven for both coherent and incoherent sources, and additional advantages are compatibility with high x-ray energies and easy implementation of phase sensitivity in two directions simultaneously. This paper briefly summarizes these achievements and reviews some of the key results

Edge illumination and coded-aperture X-ray phase-contrast imaging: Increased sensitivity at synchrotrons and lab-based translations into medicine, biology and materials science

The edge illumination principle was first proposed at Elettra (Italy) in the late nineties, as an alternative method for achieving high phase sensitivity with a very simple and flexible set-up, and has since been under continuous development in the radiation physics group at UCL. Edge illumination allows overcoming most of the limitations of other phase-contrast techniques, enabling their translation into a laboratory environment. It is relatively insensitive to mechanical and thermal instabilities and it can be adapted to the divergent and polychromatic beams provided by X-ray tubes. This method has been demonstrated to work efficiently with source sizes up to 100m, compatible with state-of-the-art mammography sources. Two full prototypes have been built and are operational at UCL. Recent activity focused on applications such as breast and cartilage imaging, homeland security and detection of defects in composite materials. New methods such as phase retrieval, tomosynthesis and computed tomography algorithms are currently being theoretically and experimentally investigated. These results strongly indicate the technique as an extremely powerful and versatile tool for X-ray imaging in a wide range of applications

Medicine, material science and security: the versatility of the coded-aperture approach

The principal limitation to the widespread deployment of X-ray phase imaging in a variety of applications is probably versatility. A versatile X-ray phase imaging system must be able to work with polychromatic and non-microfocus sources (for example, those currently used in medical and industrial applications), have physical dimensions sufficiently large to accommodate samples of interest, be insensitive to environmental disturbances (such as vibrations and temperature variations), require only simple system set-up and maintenance, and be able to perform quantitative imaging. The coded-aperture technique, based upon the edge illumination principle, satisfies each of these criteria. To date, we have applied the technique to mammography, materials science, small-animal imaging, non-destructive testing and security. In this paper, we outline the theory of coded-aperture phase imaging and show an example of how the technique may be applied to imaging samples with a practically important scale

Impact of Solitary Involved Lymph Node on Outcome in Localized Cancer of the Esophagus and Esophagogastric Junction

Node-positive esophageal cancer is associated with a dismal prognosis. The impact of a solitary involved node, however, is unclear, and this study examined the implications of a solitary node compared with greater nodal involvement and node-negative disease. The clinical and pathologic details of 604 patients were entered prospectively into a database from1993 and 2005. Four pathologic groups were analyzed: node-negative, one lymph node positive, two or three lymph nodes positive, and greater than three lymph nodes positive. Three hundred and fifteen patients (52%) were node-positive and 289 were node-negative. The median survival was 26 months in the node-negative group. Patients (n = 84) who had one node positive had a median survival of 16 months (p = 0.03 vs node-negative). Eighty-four patients who had two or three nodes positive had a median survival of 11 months compared with a median survival of 8 months in the 146 patients who had greater than three nodes positive (p = 0.01). The survival of patients with one node positive [number of nodes (N) = 1] was also significantly greater than the survival of patients with 2–3 nodes positive (N = 2–3) (p = 0.049) and greater than three nodes positive (p < 0001). The presence of a solitary involved lymph node has a negative impact on survival compared with node-negative disease, but it is associated with significantly improved overall survival compared with all other nodal groups

Modulation of the immune response by nematode secreted acetylcholinesterase revealed by heterologous expression in Trypanosoma musculi

Nematode parasites secrete molecules which regulate the mammalian immune system, but their genetic intractability is a major impediment to identifying and characterising the biological effects of these molecules. We describe here a novel system for heterologous expression of helminth secreted proteins in the natural parasite of mice, Trypanosoma musculi, which can be used to analyse putative immunomodulatory functions. Trypanosomes were engineered to express a secreted acetylcholinesterase from Nippostrongylus brasiliensis. Infection of mice with transgenic parasites expressing acetylcholinesterase resulted in truncated infection, with trypanosomes cleared early from the circulation. Analysis of cellular phenotypes indicated that exposure to acetylcholinesterase in vivo promoted classical activation of macrophages (M1), with elevated production of nitric oxide and lowered arginase activity. This most likely occurred due to the altered cytokine environment, as splenocytes from mice infected with T. musculi expressing acetylcholinesterase showed enhanced production of IFNγ and TNFα, with diminished IL-4, IL-13 and IL-5. These results suggest that one of the functions of nematode secreted acetylcholinesterase may be to alter the cytokine environment in order to inhibit development of M2 macrophages which are deleterious to parasite survival. Transgenic T. musculi represents a valuable new vehicle to screen for novel immunoregulatory proteins by extracellular delivery in vivo to the murine host

Mapping biomass with remote sensing: a comparison of methods for the case study of Uganda

<p>Abstract</p> <p>Background</p> <p>Assessing biomass is gaining increasing interest mainly for bioenergy, climate change research and mitigation activities, such as reducing emissions from deforestation and forest degradation and the role of conservation, sustainable management of forests and enhancement of forest carbon stocks in developing countries (REDD+). In response to these needs, a number of biomass/carbon maps have been recently produced using different approaches but the lack of comparable reference data limits their proper validation. The objectives of this study are to compare the available maps for Uganda and to understand the sources of variability in the estimation. Uganda was chosen as a case-study because it presents a reliable national biomass reference dataset.</p> <p>Results</p> <p>The comparison of the biomass/carbon maps show strong disagreement between the products, with estimates of total aboveground biomass of Uganda ranging from 343 to 2201 Tg and different spatial distribution patterns. Compared to the reference map based on country-specific field data and a national Land Cover (LC) dataset (estimating 468 Tg), maps based on biome-average biomass values, such as the Intergovernmental Panel on Climate Change (IPCC) default values, and global LC datasets tend to strongly overestimate biomass availability of Uganda (ranging from 578 to 2201 Tg), while maps based on satellite data and regression models provide conservative estimates (ranging from 343 to 443 Tg). The comparison of the maps predictions with field data, upscaled to map resolution using LC data, is in accordance with the above findings. This study also demonstrates that the biomass estimates are primarily driven by the biomass reference data while the type of spatial maps used for their stratification has a smaller, but not negligible, impact. The differences in format, resolution and biomass definition used by the maps, as well as the fact that some datasets are not independent from the reference data to which they are compared, are considered in the interpretation of the results.</p> <p>Conclusions</p> <p>The strong disagreement between existing products and the large impact of biomass reference data on the estimates indicate that the first, critical step to improve the accuracy of the biomass maps consists of the collection of accurate biomass field data for all relevant vegetation types. However, detailed and accurate spatial datasets are crucial to obtain accurate estimates at specific locations.</p

Sensitivity to change of the Neck Pain and Disability Scale

The Neck Pain and Disability Scale (NPAD) is a 20-item instrument to measure neck pain and related disability. The aim of this study was to assess sensitivity to change of the NPAD. A total of 411 participants from 15 general practices in the middle of Germany completed a multidimensional questionnaire including the German version of the NPAD and self-reported demographic and clinical information. Sensitivity to change was analysed by linear regression analysis of the NPAD at follow-up and educational level, age class, depression, anxiety, and deficits in social support, respectively, and by Pearson’s correlation analyses between mean change in NPAD at follow-up and mean change in prognostic markers. Those having more than basic education (regression coefficient −7.2, p < 0.001) and/or being in a younger age class (−2.9, p = 0.020) consistently reported significantly lower average NPAD scores at follow-up compared to those with basic education and/or a older age class. In contrast, those who were classified to be depressed (regression coefficient 2.1, p < 0.001), anxious (1.9, p < 0.001), or having deficits in social support (5.5, p = 0.004) reported significantly higher NPAD scores. Change in depression, anxiety, and social support scale between baseline and follow-up was significantly correlated with change in the NPAD score. Hence, these data are in the direction anticipated across all baseline factors investigated. In conclusion, the NPAD seems to be a sensitive measure for use in clinical practice and future studies of neck pain and related disability

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Obesity and Gastroesophageal Reflux: Quantifying the Association Between Body Mass Index, Esophageal Acid Exposure, and Lower Esophageal Sphincter Status in a Large Series of Patients with Reflux Symptoms

Obesity and gastroesophageal reflux disease (GERD) are increasingly important health problems. Previous studies of the relationship between obesity and GERD focus on indirect manifestations of GERD. Little is known about the association between obesity and objectively measured esophageal acid exposure. The aim of this study is to quantify the relationship between body mass index (BMI) and 24-h esophageal pH measurements and the status of the lower esophageal sphincter (LES) in patients with reflux symptoms. Data of 1,659 patients (50% male, mean age 51 ± 14) referred for assessment of GERD symptoms between 1998 and 2008 were analyzed. These subjects underwent 24-h pH monitoring off medication and esophageal manometry. The relationship of BMI to 24-h esophageal pH measurements and LES status was studied using linear regression and multiple regression analysis. The difference of each acid exposure component was also assessed among four BMI subgroups (underweight, normal weight, overweight, and obese) using analysis of variance and covariance. Increasing BMI was positively correlated with increasing esophageal acid exposure (adjusted R 2 = 0.13 for the composite pH score). The prevalence of a defective LES was higher in patients with higher BMI (p &lt; 0.0001). Compared to patients with normal weight, obese patients are more than twice as likely to have a mechanically defective LES [OR = 2.12(1.63–2.75)]. An increase in body mass index is associated with an increase in esophageal acid exposure, whether BMI was examined as a continuous or as a categorical variable; 13% of the variation in esophageal acid exposure may be attributable to variation in BMI