sparr: Analyzing Spatial Relative Risk Using Fixed and Adaptive Kernel Density Estimation in R

The estimation of kernel-smoothed relative risk functions is a useful approach to examining the spatial variation of disease risk. Though there exist several options for performing kernel density estimation in statistical software packages, there have been very few contributions to date that have focused on estimation of a relative risk function per se . Use of a variable or adaptive smoothing parameter for estimation of the individual densities has been shown to provide additional benefits in estimating relative risk and specific computational tools for this approach are essentially absent. Furthermore, little attention has been given to providing methods in available software for any kind of subsequent analysis with respect to an estimated risk function. To facilitate analyses in the field, the R package sparr is introduced, providing the ability to construct both fixed and adaptive kernel-smoothed densities and risk functions, identify statistically significant fluctuations in an estimated risk function through the use of asymptotic tolerance contours, and visualize these objects in flexible and attractive ways.

Innovation sustainability in challenging health-care contexts : embedding clinically led change in routine practice

The need for organizational innovation as a means of improving health-care quality and containing costs is widely recognized, but while a growing body of research has improved knowledge of implementation, very little has considered the challenges involved in sustaining change – especially organizational change led ‘bottom-up’ by frontline clinicians. This study addresses this lacuna, taking a longitudinal, qualitative case-study approach to understanding the paths to sustainability of four organizational innovations. It highlights the importance of the interaction between organizational context, nature of the innovation and strategies deployed in achieving sustainability. It discusses how positional influence of service leads, complexity of innovation, networks of support, embedding in existing systems, and proactive responses to changing circumstances can interact to sustain change. In the absence of cast-iron evidence of effectiveness, wider notions of value may be successfully invoked to sustain innovation. Sustainability requires continuing effort through time, rather than representing a final state to be achieved. Our study offers new insights into the process of sustainability of organizational change, and elucidates the complement of strategies needed to make bottom-up change last in challenging contexts replete with competing priorities

Superoxide radicals can act synergistically with hypochlorite to induce damage to proteins

AbstractActivated phagocytes generate both superoxide radicals via a respiratory burst, and HOCl via the concurrent release of the haem enzyme myeloperoxidase. Amine and amide functions on proteins and carbohydrates are major targets for HOCl, generating chloramines (RNHCl) and chloramides (RC(O)NClR′), which can accumulate to high concentrations (>100 μM). Here we show that superoxide radicals catalyse the decomposition of chloramines and chloramides to reactive nitrogen-centred radicals, and increase the extent of protein fragmentation compared to that observed with either superoxide radicals or HOCl, alone. This synergistic action may be of significance at sites of inflammation, where both superoxide radicals and chloramines/chloramides are formed simultaneously

sparr: Analyzing Spatial Relative Risk Using Fixed and Adaptive Kernel Density Estimation in R

The estimation of kernel-smoothed relative risk functions is a useful approach to examining the spatial variation of disease risk. Though there exist several options for performing kernel density estimation in statistical software packages, there have been very few contributions to date that have focused on estimation of a relative risk function per se. Use of a variable or adaptive smoothing parameter for estimation of the individual densities has been shown to provide additional benefits in estimating relative risk and specific computational tools for this approach are essentially absent. Furthermore, little attention has been given to providing methods in available software for any kind of subsequent analysis with respect to an estimated risk function. To facilitate analyses in the field, the R package sparr is introduced, providing the ability to construct both fixed and adaptive kernel-smoothed densities and risk functions, identify statistically significant fluctuations in an estimated risk function through the use of asymptotic tolerance contours, and visualize these objects in flexible and attractive ways

Heparin-stabilised iron oxide for MR applications : a relaxometric study

Superparamagnetic nanoparticles have strong potential in biomedicine and have seen application as clinical magnetic resonance imaging (MRI) contrast agents, though their popularity has plummeted in recent years, due to low efficacy and safety concerns, including haemagglutination. Using an in situ procedure, we have prepared colloids of magnetite nanoparticles, exploiting the clinically approved anti-coagulant, heparin, as a templating stabiliser. These colloids, stable over several days, produce exceptionally strong MRI contrast capabilities particularly at low fields, as demonstrated by relaxometric investigations using nuclear magnetic resonance dispersion (NMRD) techniques and single field r1 and r2 relaxation measurements. This behaviour is due to interparticle interactions, enhanced by the templating effect of heparin, resulting in strong magnetic anisotropic behaviour which closely maps particle size. The nanocomposites have also reliably prevented protein-adsorption triggered thrombosis typical of non-stabilised nanoparticles, showing great potential for in vivo MRI diagnostics

Varenicline and suicidal behaviour: a cohort study based on data from the General Practice Research Database

Objective To determine whether varenicline, a recently licensed smoking cessation product, is associated with an increased risk of suicide and suicidal behaviour compared with alternative treatments bupropion and nicotine replacement therapy