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Synthonic engineering tools, including grid-based searching molecular modelling, are applied to investigate the wetting interactions of the solute and four crystallisation solvents (ethanol, ethyl acetate, acetonitrile and toluene) with the {100}, {001} and {011} forms of RS-ibuprofen. The grid-based methods, in particular the construction of a crystal slab parallel to a given plane in a coordinate system with one axis perpendicular to the surface, are defined in detail. The interaction strengths and nature (dispersive, hydrogen bonding (H-bonding) or coulombic forces) are related to the crystal growth rates and morphologies. The solute is found to interact strongest with the capping {011}, then the side {001} and weakest with the top {100} habit surfaces. The solute interactions with the {100} and {001} surfaces are found to be almost solely dominated by dispersive force contributions, whilst the same with the {011} surfaces are found to have a greater contribution from H-bonding and coulombic forces. The increased surface rugosity, at the molecular level of the {011} surfaces, results in a favourable docking site in a surface 'valley', not present in the {100} and {001} surfaces. The H-bonding solvents ethanol, acetonitrile and ethyl acetate are found to strongly interact with the {011} surfaces and weakly with the {001} surfaces, with the {011} interactions having a much greater contribution from H-bonding and coulombic forces. The interaction energies of the apolar and aprotic solvent toluene, with the {011} and {001} surfaces, are found to be very close. Toluene is found having slightly stronger interactions with the {001} than the {011} surfaces, which are all dominated by dispersive interactions. The ratio of the average energy of the top 100 solvent interactions with the {001} surface divided by the average energy of the top 100 interactions with the {011} surface is compared to the ratio of the experimentally measured growth rates of the same forms. In general, the interaction energy ratio is found to have an inverse ratio with the growth rates, implying that the solvents which are calculated to interact strongly with a particular surface are impeding the growth of that surface and reducing the growth rate, in turn impacting upon the final morphology of the material.

The crystallization of α-p-aminobenzoic acid (pABA) from mixed solutions in ethanol (EtOH) and nitromethane (NMe) is reported. From solutions with compositions >60 wt % NMe, the known α-polymorph of pABA appears. In contrast, crystals prepared from mixed solvent with

The key intermolecular (synthonic) interactions, crystal morphology, and surface interfacial stability of the anti-inflammatory drug RS-ibuprofen are examined in relation to its bulk crystal and surface chemistry, and to rationalize its growth behavior as a function of the crystallization environment. The OH···O H-bonding dimers between adjacent carboxylic acid groups are calculated to be the strongest bulk (intrinsic) synthons, with other important synthons arising due to interactions between the less-polar phenyl ring and aliphatic chain. Morphological prediction, using the attachment energy model, predicts a prismatic faceted shape, in good agreement with the shape of the experimentally grown crystals from the vapor phase. Crystals grown from solution are found to have higher aspect ratios, with those prepared in polar protic solvents (EtOH) producing less needle-like crystals, than those prepared in less polar and aprotic solvents (toluene, acetonitrile, and ethyl acetate). Though the anisotropy factors of the {011} and {002} forms are relatively similar (39.5% and 43.4%, respectively), examination of the surface chemistry reveals that the most important extrinsic (surface-terminated) synthons on the capping {011} surface involve H-bonding interactions, while those on the side {002} surfaces mostly involve van der Waal’s (vdW) interactions. This suggests that a polar, protic solvent is more likely to bind to the capping {011} surface and inhibit growth of the long axis of the needle, compared to apolar and/or aprotic solvents. A previously unreported re-entrant face is found to appear in the external crystal morphology at higher supersaturations (in the range of σ = 0.66–0.79), not due to twinning, which is provisionally identified as being consistent with either the {112} or {012} form. Analysis of the calculated surface entropy α-factors suggest that the capping {011} faces would be expected to be least smooth on the molecular level, with a higher degree of unsaturated extrinsic synthons, in comparison to the {002} and {100} faces. This is consistent with growth mechanism data previously published (Nguyen et al. CrystEngComm 2014, 16, 4568−4586) and with the observed re-entrant morphological instability at the capping surfaces.

Introduction: Incidental irradiation of the heart during radiotherapy can have long-term consequences(1). Deep Inspiration Breath Hold (DIBH) is used for patients receiving radiotherapy for breast cancer to reduce heart doses(2). DIBH can reduce mean heart dose by between 29-67% compared with free breathing(3); differences in dose reduction may be due to patient anatomy or variability in chest expansion achieved at an individual level(4). A survey of a breast cancer special interest group (BRIG) identified patient compliance, ability to hold their breath for the required time, and reproducibility of breath hold as major challenges to implementing DIBH. Between 12-21% of patients are reported to find the technique challenging(5, 6). While coaching has been shown to reduce maximum heart dose compared with non-coached patients(7), formal coaching is not typical in most radiotherapy centres and no standard patient resource exists to support practice prior to radiotherapy planning. Aim: To develop a series of instructional videos to enhance the number of patients that can achieve breath hold, improve patient self-efficacy and patient satisfaction with care. Method: The Medical Research Council (MRC)(8) framework for complex interventions was adopted. A co-design methodology(9) involving patient representatives and health practitioners (HCP) was used to develop a series of instructional videos and podcasts. Co-design workshops were audio recorded and transcribed verbatim. Video scripts were based upon themes identified through framework analysis. To minimise bias member checking was adopted and patient representatives participated in video scripting; to maintain the outputs' authenticity they also appeared as patients in the videos. Results: Key themes from the PPI workshop included: information needs; positioning during radiotherapy; and pre-treatment readiness. Additional themes from the HCP workshop included DIBH service challenges and teaching the DIBH technique. Five videos and two podcasts were developed. Conclusion: This presentation will highlight how participatory co-design facilitated video development to support a more effective DIBH experience. Resource examples will be presented alongside initial feedback from patient representatives and HCPs on suitability and usability. The next stage will assess the resources' effectiveness in supporting breath hold capability.

Introduction: Conventional radiotherapy has been planned with a full bladder based on the rationale that it will move the small bowel out of the treatment field and result in greater sparing of the bladder itself[1]. Our department has moved from a ‘comfortably full’ bladder to a strict drinking protocol of emptying the bladder, drinking three cups of water and waiting 30 minutes prior to treatment for our prostate cancer patients. A service evaluation was carried out to determine if this change in practice results in a more consistent bladder volume from CT panning to treatment. Method and Materials: Based on 233 prostate patients treated per year a sample size of 146 was determined to result in a 95% confidence level with a 5% margin of error[2]. The last 73 patients on the comfortably full protocol and the first 73 patients on the new bladder protocol were compared. Their bladder volume from CT and on their CBCT fraction one was outlined by one observer to ascertain the difference in bladder volume and assess consistency. Results: The bladder filling protocol does not result in a statistically significant difference in bladder volume from CT to CBCT fraction one compared to comfortably full; the results prove that there is statistically no benefit from moving from comfortably full to the strict drinking protocol in terms of consistency of bladder volume achieved. Conclusion and Discussion: In the UK there are currently no official guidelines on what is the optimal volume of bladder for prostate cancer patients[3]. To attend a busy regional cancer centre patients may have had to travel a long distance. This coupled with any unintended delays can result in patients having to empty or be taken of the treatment couch, therefore a strict drinking protocol may not be feasible .The results of this well powered study that there is no statistically significant difference in consistency gained from employing a strict drinking protocol compared to maintaining a comfortably full bladder.

Single crystals of salmeterol xinafoate (form I), prepared from slow cooled supersaturated propan-2-ol solutions, crystallize in a triclinic P1¯ symmetry with 2 closely related independent salt pairs within the asymmetric unit, with an approximately double-unit cell volume compared with the previously published crystal structure. Synthonic analysis of the bulk intermolecular packing confirms the similarity in packing energetics between the 2 salt pairs. The strongest synthons, as expected, are dominated by coulombic interactions. Morphologic prediction reveals a plate-like morphology, dominated by the {001}, {010}, and {100} surfaces, consistent with experimentally grown crystals. Although surface chemistry of the slow-growing {001} face comprises large sterically hindering phenyl groups, although weaker coulombic interactions still prevail from the alcohol group present on the phenyl and hydroxymethyl groups. The surface chemistry of the faster growing {010} and {100} faces are dominated by the significantly stronger cation/anion interactions occurring between the carboxylate and protonated secondary ammonium ion groups. The importance of understanding the cohesive and adhesive nature of the crystal surfaces of an active pharmaceutical ingredient, with respect to their interaction with other active pharmaceutical ingredient crystals and how that may affect formulation design, is highlighted.

Internet and web-based tools are essential in eLearning. They can also act as a supplement to learning in campus-based environments. Such tools can bring great benefits to a teacher, or they can generate considerable overhead work resulting in a loss of efficiency and effectiveness. We identify some principles, and some practices, for enhancing the efficiency and effectiveness of teachers using webbased, e-Learning and e-Administration tools in a mostly campus-based learning environment. The key principles we seek in e-Learning and eAdministration tools are simplicity, versatility and a decentralized, but collaborative, mode of operation which we illustrate through case studies of our own work and that of others. We review relevant learning and assessment models, explicate the key principles for supporting the teacher's role with web-based tools, and provide numerous illustrative examples.

Organoamino phosphonium cations of formula [P(NHR)4]+ offer four hydrogen bonding sites that are arranged in tetrahedral fashion around the central phosphorus atom. This arrangement generates novel supramolecular building blocks that are distinct from the commonly planar NH donor systems, such as urea and guanidine. The supramolecular aggregation of these cations in the presence of chloride and several carboxylate anions is described. The carboxylate salts are obtained either by anion exchange reactions with phosphonium chlorides or by protonation reaction of the neutral phosphine imine P(NPh)(NHPh)3. X-ray structure analyses of the title compounds show that they form hierarchical structures ranging from 1D chains to 2D sheets and 3D networks. Control over the dimensionality of the supramolecular structure can be achieved by modulating the steric bulk of the phosphonium cation.

Full evaluation report â includes the full primary data set for the project. (DOCX 10152 kb)

Showing examples from each of the identified domains and stakeholder groups which illustrate transitions from red to green (August 2013-August 2014). (DOCX 17 kb)

Background Health services face the challenges created by complex problems, and so need complex intervention solutions. However they also experience ongoing difficulties in translating findings from research in this area in to quality improvement changes on the ground. BounceBack was a service development innovation project which sought to examine this issue through the implementation and evaluation in a primary care setting of a novel complex intervention. Methods The project was a collaboration between a local mental health charity, an academic unit, and GP practices. The aim was to translate the charity’s model of care into practice-based evidence describing delivery and impact. Normalisation Process Theory (NPT) was used to support the implementation of the new model of primary mental health care into six GP practices. An integrated process evaluation evaluated the process and impact of care. Results Implementation quickly stalled as we identified problems with the described model of care when applied in a changing and variable primary care context. The team therefore switched to using the NPT framework to support the systematic identification and modification of the components of the complex intervention: including the core components that made it distinct (the consultation approach) and the variable components (organisational issues) that made it work in practice. The extra work significantly reduced the time available for outcome evaluation. However findings demonstrated moderately successful implementation of the model and a suggestion of hypothesised changes in outcomes. Conclusions The BounceBack project demonstrates the development of a complex intervention from practice. It highlights the use of Normalisation Process Theory to support development, and not just implementation, of a complex intervention; and describes the use of the research process in the generation of practice-based evidence. Implications for future translational complex intervention research supporting practice change through scholarship are discussed. Electronic supplementary material The online version of this article (doi:10.1186/s12913-016-1726-6) contains supplementary material, which is available to authorized users.

Empirical force-field calculations utilising the atom-atom method were used to examine the strength, directionality and chemical state of the intermolecular interactions (synthons) present in the polymorphic forms (α and β) of p-aminobenzoic acid (pABA). This is set within the context of predicting the morphology of both forms in terms of the unsatisfied synthons at each growth surface. The α lattice energy was calculated to be -24.54 kcal mol-1 with the dominant intermolecular interactions found to consist of OH⋯O carboxylic acid H-bonding dimers and head to head π-π stacking interactions. The β lattice energy was calculated to be -22.73 kcal mol-1 and the dominant interactions found to consist of a 4-membered H-bonding ring made up of two identical NH⋯O and OH⋯N interactions, plus strong head to tail π-π stacking interactions. The NH2 group was calculated to contribute more to the β lattice energy than to the α, as it acts as a H-bonding donor and acceptor in the β structure, whilst acting solely as a donor in α. Conversely, the COOH group was found to contribute more strongly to the α lattice energy due to the formation of the OH⋯O H-bonds and also NH⋯O H-bonds, while the COOH group in the β structure forms only weaker O⋯HN and OH⋯N interactions. Morphological prediction of the β form gave greater resemblance to the experimental morphology compared to α. Surface chemistry analysis revealed that the strength, character and directionality of the synthons present varies in terms of their anisotropy between these two polymorphs. The strength and character of the unsaturated synthons exposed at the major surfaces of the α crystal were found to significantly vary, which results in a needle-like morphology. In contrast, the strength and character of the synthons exposed at the major surfaces of the β morphology were found to be much more similar, which results in the more equant morphology. Overall, this paper presents a synthonic, analytical approach which holistically links the molecular properties with the bulk and surface synthons, and through this rationalises their contributions to the growth and morphology of this organic crystalline system.

The molecular assembly and subsequent nucleation of para-amino benzoic acid (PABA) from ethanolic solutions is probed using a multi-scale and multi-technique approach. This is applied by examining and interrelating information regarding the molecular, solution-state, cluster, solid-state and surface structures to understand why the alpha form of PABA is crystallised in preference to its low temperature beta form. Calculations suggest that conformational changes within the solute molecule play little or no role in directing the nucleation of either the alpha or beta crystal forms. Combined ab initio and molecular dynamics calculations of the stability of small clusters in solution suggests that the hydrogen-bonded carboxylic acid dimers, present in the alpha structure, are the most stable in solution and play a major role in the self-assembly and polymorphic expression of the alpha form in ethanol in preference to the beta form. These calculations are in good agreement with X-ray small-angle scattering analysis which reveals the presence of PABA clusters in ethanol which are consistent with the size and shape of a carboxylic acid dimer. SAXS studies also reveal the presence of larger cluster structures in a size range 10–40 nm which appear to grow, perhaps reflecting a change in the balance between monomers and dimers within the solution during the nucleation process. The results of crystallisation-kinetics experiments indicate an instantaneous nucleation mechanism where the number of instantaneously nucleated crystallites is calculated to be 1360–660 nuclei per ml and the subsequent growth is found to be only rate limited by diffusion of the growth unit to the crystallite surface. A linear dependence of growth rate with respect to supersaturation is observed for the (0 1 −1) capping face, which is associated with strong π–π stacking interactions. This is consistent with a solid-on-solid mechanism associated with surface roughened growth and concomitant poor lattice-perfection. Conversely, the side (1 0 −1) surface has a growth mechanism consistent with a 2D nucleation birth and spread mechanism. Hence, these mechanisms result in very fast growth along the b-axis and the needle-like morphology that is observed for alpha-PABA.