Development of the Rural Active Living Perceived Environmental Support Scale (RALPESS)

Background: Evidence supports the role of physical and social environments in active living, including perception of environment. However, measurement of perceived environments in rural settings is lacking. This study describes the development of the Rural Active Living Perceived Environmental Support Scale (RALPESS). Methods: Premised on social ecological and cognitive perspectives, 85 initial items were generated through a literature review and a mixed-methods investigation of activity-friendly environments. Items were organized by resource areas town center, indoor and outdoor physical activity areas, schools, churches, and areas around the home/neighborhood-and submitted for expert panel review. In 2009, a revised questionnaire was disseminated to adolescents, parents, public school staff, and older adults in 2 rural southeastern United States counties. Principal component analysis with varimax rotation was used to explore factor structure (n = 542). Results: The final analysis yielded 33 items with 7 factors: 1) church facilities, 2) town center connectivity, 3) indoor areas, 4) around the home/neighborhood, 5) town center physical activity resources, 6) school grounds, and 7) outdoor areas. Conclusions: The RALPESS is a valid, internally consistent, and practically useful instrument to measure perceptions of rural environments in the context of physical activity across the lifespan. Confirmatory factor analysis is recommended to validate factor structure

Contribution of Energetically Reactive Surface Features to the Dissolution of CeO2 and ThO2 Analogues for Spent Nuclear Fuel Microstructures

In the safety case for the geological disposal of nuclear waste, the release of radioactivity from the repository is controlled by the dissolution of the spent fuel in groundwater. There remain several uncertainties associated with understanding spent fuel dissolution, including the contribution of energetically reactive surface sites to the dissolution rate. In this study, we investigate how surface features influence the dissolution rate of synthetic CeO2 and ThO2, spent nuclear fuel analogues that approximate as closely as possible the microstructure characteristics of fuel-grade UO2 but are not sensitive to changes in oxidation state of the cation. The morphology of grain boundaries (natural features) and surface facets (specimen preparation-induced features) was investigated during dissolution. The effects of surface polishing on dissolution rate were also investigated. We show that preferential dissolution occurs at grain boundaries, resulting in grain boundary decohesion and enhanced dissolution rates. A strong crystallographic control was exerted, with high misorientation angle grain boundaries retreating more rapidly than those with low misorientation angles, which may be due to the accommodation of defects in the grain boundary structure. The data from these simplified analogue systems support the hypothesis that grain boundaries play a role in the so-called “instant release fraction” of spent fuel, and should be carefully considered, in conjunction with other chemical effects, in safety performance assessements for the geological disposal of spent fuel. Surface facets formed during the sample annealing process also exhibited a strong crystallographic control and were found to dissolve rapidly on initial contact with dissolution medium. Defects and strain induced during sample polishing caused an overestimation of the dissolution rate, by up to 3 orders of magnitude

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Reducing the uncertainty of nuclear fuel dissolution:An investigation of UO₂ analogue CeO₂

In this investigation, CeO2 analogues, which approximate as closely as possible the characteristics of fuel-grade UO2, were characterised after dissolution under a wide range of conditions. Powdered samples were subject to a range of aggressive and environmentally relevant alteration media with different solubility controls, and reacted at 70°C and 90°C. Dissolution kinetics were monitored through analysis of the coexisting aqueous solution. Monolith samples were monitored for development of surface defects such as pores and dissolution pits, in addition to morphological changes at grain boundaries and surface pores upon dissolution under aggressive conditions. The surfaces were analysed using confocal profilometry, vertical scanning interferometry and scanning electron microscopy. Dissolution rates were found to be greatest in low pH solutions and at higher temperatures. Preferential dissolution appears to occur at grain boundaries and on particular grains, suggesting a crystallographic control on dissolution.</p

Contribution of energetically reactive surface features to the dissolution of CeO₂ and ThO₂ analogues for spent nuclear fuel microstructures

In the safety case for the geological disposal of nuclear waste, the release of radioactivity from the repository is controlled by the dissolution of the spent fuel in groundwater. There remain several uncertainties associated with understanding spent fuel dissolution, including the contribution of energetically reactive surface sites to the dissolution rate. In this study, we investigate how surface features influence the dissolution rate of synthetic CeO2 and ThO2, spent nuclear fuel analogues that approximate as closely as possible the microstructure characteristics of fuel-grade UO2 but are not sensitive to changes in oxidation state of the cation. The morphology of grain boundaries (natural features) and surface facets (specimen preparation-induced features) was investigated during dissolution. The effects of surface polishing on dissolution rate were also investigated. We show that preferential dissolution occurs at grain boundaries, resulting in grain boundary decohesion and enhanced dissolution rates. A strong crystallographic control was exerted, with high misorientation angle grain boundaries retreating more rapidly than those with low misorientation angles, which may be due to the accommodation of defects in the grain boundary structure. The data from these simplified analogue systems support the hypothesis that grain boundaries play a role in the so-called "instant release fraction" of spent fuel, and should be carefully considered, in conjunction with other chemical effects, in safety performance assessements for the geological disposal of spent fuel. Surface facets formed during the sample annealing process also exhibited a strong crystallographic control and were found to dissolve rapidly on initial contact with dissolution medium. Defects and strain induced during sample polishing caused an overestimation of the dissolution rate, by up to 3 orders of magnitude.</p

Dual Pharmacological Targeting of the MAP Kinase and PI3K/mTOR Pathway in Preclinical Models of Colorectal Cancer

<div><p>Background</p><p>The activation of the MAPK and PI3K/AKT/mTOR pathways is implicated in the majority of cancers. Activating mutations in both of these pathways has been described in colorectal cancer (CRC), thus indicating their potential as therapeutic targets. This study evaluated the combination of a PI3K/mTOR inhibitor (PF-04691502/PF-502) in combination with a MEK inhibitor (PD-0325901/PD-901) in CRC cell lines and patient-derived CRC tumor xenograft models (PDTX).</p><p>Materials and Methods</p><p>The anti-proliferative effects of PF-502 and PD-901 were assessed as single agents and in combination against a panel of CRC cell lines with various molecular backgrounds. Synergy was evaluated using the Bliss Additivity method. In selected cell lines, we investigated the combination effects on downstream effectors by immunoblotting. The combination was then evaluated in several fully genetically annotated CRC PDTX models.</p><p>Results</p><p>The <i>in vitro</i> experiments demonstrated a wide range of IC₅₀ values for both agents against a cell line panel. The combination of PF-502 and PD-901 demonstrated synergistic anti-proliferative activity with Bliss values in the additive range. As expected, p-AKT and p-ERK were downregulated by PF-502 and PD-901, respectively. In PDTX models, following a 30-day exposure to PF-502, PD-901 or the combination, the combination demonstrated enhanced reduction in tumor growth as compared to either single agent regardless of KRAS or PI3K mutational status.</p><p>Conclusions</p><p>The combination of a PI3K/mTOR and a MEK inhibitor demonstrated enhanced anti-proliferative effects against CRC cell lines and PDTX models.</p></div

Tumor growth rate analysis on patient-derived tumor xenograft models (PDTX). Tumor growth rates were determined for each individual tumor by fitting tumor volume data over the course of the treatment period to an exponential growth rate equation.

<p>Each point represents a single tumor. Mean tumor growth rate ± standard deviation are represented by the bar and handles. All data presented as mean±SD, ANOVA Tukey’s adjusted p values: *P<0.05 vs. Control; ^†P<0.05 vs. 901; ^‡P<0.05 vs. 502.</p