Moving nursing innovation to prime time through the use of creative partnerships.

Nurses are well-positioned to solve many problems in healthcare through engagement in innovation. Support from healthcare organizations to facilitate creative partnerships may accelerate nurses' ability to innovate and improve job satisfaction. The value of creative partnerships is rooted in the diversity of experiences and skillsets of each project team member. While nurses may be content experts and key stakeholders, they often lack experience with project management, information technology, product development, and other important skills. We describe the use of co-creation approaches in creative partnerships with diverse stakeholders to enhance the ability of nurse-led project teams to build valuable and sustainable products or services.

Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors.

The high frequency of activating RAS or BRAF mutations in cancer provides strong rationale for targeting the mitogen-activated protein kinase (MAPK) pathway. Selective BRAF and MAP-ERK kinase (MEK) inhibitors have shown clinical efficacy in patients with melanoma. However, the majority of responses are transient, and resistance is often associated with pathway reactivation of the extracellular signal-regulated kinase (ERK) signaling pathway. Here, we describe the identification and characterization of SCH772984, a novel and selective inhibitor of ERK1/2 that displays behaviors of both type I and type II kinase inhibitors. SCH772984 has nanomolar cellular potency in tumor cells with mutations in BRAF, NRAS, or KRAS and induces tumor regressions in xenograft models at tolerated doses. Importantly, SCH772984 effectively inhibited MAPK signaling and cell proliferation in BRAF or MEK inhibitor-resistant models as well as in tumor cells resistant to concurrent treatment with BRAF and MEK inhibitors. These data support the clinical development of ERK inhibitors for tumors refractory to MAPK inhibitors.

Derivation of motor vehicle tailpipe particle emission factors suitable for modelling urban fleet emissions and air quality assessments.

BACKGROUND, AIM AND SCOPE: Urban motor vehicle fleets are a major source of particulate matter pollution, especially of ultrafine particles (diameters < 0.1 microm), and exposure to particulate matter has known serious health effects. A considerable body of literature is available on vehicle particle emission factors derived using a wide range of different measurement methods for different particle sizes, conducted in different parts of the world. Therefore, the choice as to which are the most suitable particle emission factors to use in transport modelling and health impact assessments presented as a very difficult task. The aim of this study was to derive a comprehensive set of tailpipe particle emission factors for different vehicle and road type combinations, covering the full size range of particles emitted, which are suitable for modelling urban fleet emissions. MATERIALS AND METHODS: A large body of data available in the international literature on particle emission factors for motor vehicles derived from measurement studies was compiled and subjected to advanced statistical analysis, to determine the most suitable emission factors to use in modelling urban fleet emissions. RESULTS: This analysis resulted in the development of five statistical models which explained 86%, 93%, 87%, 65% and 47% of the variation in published emission factors for particle number, particle volume, PM(1), PM(2.5) and PM(10), respectively. A sixth model for total particle mass was proposed but no significant explanatory variables were identified in the analysis. From the outputs of these statistical models, the most suitable particle emission factors were selected. This selection was based on examination of the statistical robustness of the statistical model outputs, including consideration of conservative average particle emission factors with the lowest standard errors, narrowest 95% confidence intervals and largest sample sizes and the explanatory model variables, which were vehicle type (all particle metrics), instrumentation (particle number and PM(2.5)), road type (PM(10)) and size range measured and speed limit on the road (particle volume). DISCUSSION: A multiplicity of factors need to be considered in determining emission factors that are suitable for modelling motor vehicle emissions, and this study derived a set of average emission factors suitable for quantifying motor vehicle tailpipe particle emissions in developed countries. CONCLUSIONS: The comprehensive set of tailpipe particle emission factors presented in this study for different vehicle and road type combinations enable the full size range of particles generated by fleets to be quantified, including ultrafine particles (measured in terms of particle number). These emission factors have particular application for regions which may have a lack of funding to undertake measurements, or insufficient measurement data upon which to derive emission factors for their region. RECOMMENDATIONS AND PERSPECTIVES: In urban areas motor vehicles continue to be a major source of particulate matter pollution and of ultrafine particles. It is critical that in order to manage this major pollution source methods are available to quantify the full size range of particles emitted for transport modelling and health impact assessments.

Discovery of novel orally active ureido NPY Y5 receptor antagonists.

We have derived a novel series of neuropeptide Y (NPY) Y5 receptor antagonists from the biphenylurea 3. Cyclohexylurea 21c, a member of the series, is a potent NPY Y5 receptor antagonist that exhibits excellent pharmacokinetic parameters in rats and dogs. On chronic oral administration to diet-induced obese rats, 21c displayed an anti-obesity profile, causing a modest reduction in food intake, a significant decrease in body weight gain, a decrease in adipose mass, and an increase in lean tissue mass.