Direct iminization of PEEK

Semi-crystalline poly(ether ketone)s are important high-temperature engineering thermoplastics, but are difficult to characterize at the molecular level because of their insolubility in conventional organic solvents. Here we report that polymers of this type, including PEEK, react cleanly at high temperatures with low-volatility aralkyl amines to afford stable, noncrystalline poly(ether-imine)s, which are readily soluble in solvents such as chloroform, THF and DMF and so characterizable by conventional size-exclusion chromatography

Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo

Purpose: External beam radiotherapy (EBRT) is the principal bladder-preserving monotherapy for muscle-invasive bladder cancer. Seventy percent of muscle-invasive bladder cancers express epidermal growth factor receptor (EGFR), which is associated with poor prognosis. Ionising radiation (IR) stimulates EGFR causing activation of cytoprotective signalling cascades and thus may be an underlying cause of radioresistance in bladder tumours. Materials and methods: We assessed the ability of IR to activate EGFR in bladder cancer cells and the effect of the anti-EGFR therapy, gefitinib on potential radiation-induced activation. Subsequently we assessed the effect of IR on signalling pathways downstream of EGFR. Finally we assessed the activity of gefitinib as a monotherapy, and in combination with IR, using clonogenic assay in vitro, and a murine model in vivo. Results: IR activated EGFR and gefitinib partially inhibited this activation. Radiation-induced activation of EGFR activated the MAPK and Akt pathways. Gefitinib partially inhibited activation of the MAPK pathway but not the Akt pathway. Treatment with combined gefitinib and IR significantly inhibited bladder cancer cell colony formation more than treatment with gefitinib alone (p = 0.001-0.03). J82 xenograft tumours treated with combined gefitinib and IR showed significantly greater growth inhibition than tumours treated with IR alone (p = 0.04). Conclusions: Combining gefitinib and IR results in significantly greater inhibition of invasive bladder cancer cell colony formation in vitro and significantly greater tumour growth inhibition in vivo. Given the high frequency of EGFR expression by bladder tumours and the low toxicity of gefitinib there is justification to translate this work into a clinical trial.Peer-reviewedPublisher Version1721

Entropy Production of Brownian Macromolecules with Inertia

We investigate the nonequilibrium steady-state thermodynamics of single Brownian macromolecules with inertia under feedback control in isothermal ambient fluid. With the control being represented by a velocity-dependent external force, we find such open systems can have a negative entropy production rate and we develop a mesoscopic theory consistent with the second law. We propose an equilibrium condition and define a class of external forces, which includes a transverse Lorentz force, leading to equilibrium.Comment: 10 pages, 1 figur

Reporting and design elements of audit and feedback interventions: a secondary review

BACKGROUND: Audit and feedback (A&F) is a frequently used intervention aiming to support implementation of research evidence into clinical practice with positive, yet variable, effects. Our understanding of effective A&F has been limited by poor reporting and intervention heterogeneity. Our objective was to describe the extent of these issues. METHODS: Using a secondary review of A&F interventions and a consensus-based process to identify modifiable A&F elements, we examined intervention descriptions in 140 trials of A&F to quantify reporting limitations and describe the interventions. RESULTS: We identified 17 modifiable A&F intervention elements; 14 were examined to quantify reporting limitations and all 17 were used to describe the interventions. Clear reporting of the elements ranged from 56% to 97% with a median of 89%. There was considerable variation in A&F interventions with 51% for individual providers only, 92% targeting behaviour change and 79% targeting processes of care, 64% performed by the provider group and 81% reporting aggregate patient data. CONCLUSIONS: Our process identified 17 A&F design elements, demonstrated gaps in reporting and helped understand the degree of variation in A&F interventions

Diffusive hidden Markov model characterization of DNA looping dynamics in tethered particle experiments

In many biochemical processes, proteins bound to DNA at distant sites are brought into close proximity by loops in the underlying DNA. For example, the function of some gene-regulatory proteins depends on such DNA looping interactions. We present a new technique for characterizing the kinetics of loop formation in vitro, as observed using the tethered particle method, and apply it to experimental data on looping induced by lambda repressor. Our method uses a modified (diffusive) hidden Markov analysis that directly incorporates the Brownian motion of the observed tethered bead. We compare looping lifetimes found with our method (which we find are consistent over a range of sampling frequencies) to those obtained via the traditional threshold-crossing analysis (which can vary depending on how the raw data are filtered in the time domain). Our method does not involve any time filtering and can detect sudden changes in looping behavior. For example, we show how our method can identify transitions between long-lived, kinetically distinct states that would otherwise be difficult to discern

Scoping studies: advancing the methodology

Abstract Background Scoping studies are an increasingly popular approach to reviewing health research evidence. In 2005, Arksey and O'Malley published the first methodological framework for conducting scoping studies. While this framework provides an excellent foundation for scoping study methodology, further clarifying and enhancing this framework will help support the consistency with which authors undertake and report scoping studies and may encourage researchers and clinicians to engage in this process. Discussion We build upon our experiences conducting three scoping studies using the Arksey and O'Malley methodology to propose recommendations that clarify and enhance each stage of the framework. Recommendations include: clarifying and linking the purpose and research question (stage one); balancing feasibility with breadth and comprehensiveness of the scoping process (stage two); using an iterative team approach to selecting studies (stage three) and extracting data (stage four); incorporating a numerical summary and qualitative thematic analysis, reporting results, and considering the implications of study findings to policy, practice, or research (stage five); and incorporating consultation with stakeholders as a required knowledge translation component of scoping study methodology (stage six). Lastly, we propose additional considerations for scoping study methodology in order to support the advancement, application and relevance of scoping studies in health research. Summary Specific recommendations to clarify and enhance this methodology are outlined for each stage of the Arksey and O'Malley framework. Continued debate and development about scoping study methodology will help to maximize the usefulness and rigor of scoping study findings within healthcare research and practice

Exploring the nature of visual fixations on other pedestrians

How we look at other people may affect conclusions drawn about the effect of changes in lighting when this task needs to be done after dark. This paper reports further analysis of the distance and duration of fixation on other pedestrians, updating a previous review by considering a greater number of fixations and by examining the influence on these of other characteristics such as the relative direction of travel. This analysis provides further support for a tendency to fixate others at a distance of 15 m and for a duration of 500 ms

Effects of dalcetrapib in patients with a recent acute coronary syndrome

In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes

Supramolecular approach to new inkjet printing inks

Electronically complementary, low molecular weight polymers that self-assemble through tunable π−π stacking interactions to form extended supramolecular polymer networks have been developed for inkjet printing applications and successfully deposited using three different printing techniques. Sequential overprinting of the complementary components results in supramolecular network formation through complexation of π-electron rich pyrenyl or perylenyl chain-ends in one component with π-electron deficient naphthalene diimide residues in a chain-folding polyimide. The complementary π−π stacked polymer blends generate strongly colored materials as a result of charge-transfer absorption bands in the visible spectrum, potentially negating the need for pigments or dyes in the ink formulation. Indeed, the final color of the deposited material can be tailored by varying the end-groups of the π-electron rich polymer component. Piezoelectric printing techniques were employed in a proof of concept study to allow characterization of the materials deposited, and a thermal inkjet printer adapted with imaging software enabled in situ analysis of the ink drops as they formed and of their physical properties. Finally, continuous inkjet printing allowed greater volumes of material to be deposited, on a variety of different substrate surfaces, and demonstrated the utility and versatility of this novel type of ink for industrial applications

Pairwise assembly of organopalladium(II) units with cyanurato(3-) and trithiocyanurato(3-) ligands: formation of chiral Pd12, Pd10 and Pd9 cage-molecules

The o-palladated, chloro-bridged dimers [Pd{2-phenylpyridine(-H)}-μ-Cl]2 and [Pd{N,N-dimethylbenzylamine(-H)}-μ-Cl]2 react with cyanuric acid in the presence of base to afford closed, chiral cage-molecules in which twelve organo-Pd(II) centers, located in pairs at the vertices of an octahedron, are linked by four tetrahedrally-arranged cyanurato(3-) ligands. Incomplete (Pd10) cages, having structures derived from the corresponding Pd12 cages by replacing one pair of organopalladium centers with two protons, have also been isolated. Reaction of [Pd{2-phenylpyridine(-H)}-μ-Cl]2 with trithiocyanuric acid gives an entirely different and more open type of cage-complex, comprising only nine organopalladium centers and three thiocyanurato(3-) ligands: cage-closure in this latter system appears to be inhibited by steric crowding of the thiocarbonyl groups