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Whilst patient engagement (PE) activities have become increasingly prevalent in medicines development, collaborating actors have different perspectives of its goals and its added value. In the development of PE standards and frameworks, the significance of these differences tends to be minimized. Boundary objects have been shown to mediate knowledge exchange between multiple social worlds, thereby playing an important role in participatory technology governance processes. In this paper, we draw on boundary objects to learn from the process of co-designing a PE monitoring and evaluation (M&E) framework within the IMI-PARADIGM consortium (2018 – 2020). As facilitators of PARADIGM’s co-design process, we report on the challenges encountered in designing a practicable M&E framework that serves different needs and interests. We argue these challenges of co-design reflect a negotiation of different frames throughout, thereby providing insight into how such work may contribute to addressing the challenge of knowledge integration in institutional medicines development settings.

The 2010 Alcohol Hangover Research Group consensus paper defined a cutoff blood alcohol concentration (BAC) of 0.11% as a toxicological threshold indicating that sufficient alcohol had been consumed to develop a hangover. The cutoff was based on previous research and applied mostly in studies comprising student samples. Previously, we showed that sensitivity to hangovers depends on (estimated) BAC during acute intoxication, with a greater percentage of drinkers reporting hangovers at higher BAC levels. However, a substantial number of participants also reported hangovers at comparatively lower BAC levels. This calls the suitability of the 0.11% threshold into question. Recent research has shown that subjective intoxication, i.e., the level of severity of reported drunkenness, and not BAC, is the most important determinant of hangover severity. Non-student samples often have a much lower alcohol intake compared to student samples, and overall BACs often remain below 0.11%. Despite these lower BACs, many non-student participants report having a hangover, especially when their subjective intoxication levels are high. This may be the case when alcohol consumption on the drinking occasion that results in a hangover significantly exceeds their “normal” drinking level, irrespective of whether they meet the 0.11% threshold in any of these conditions. Whereas consumers may have relative tolerance to the adverse effects at their “regular” drinking level, considerably higher alcohol intake—irrespective of the absolute amount—may consequentially result in a next-day hangover. Taken together, these findings suggest that the 0.11% threshold value as a criterion for having a hangover should be abandoned.

Molten globules are compact intermediates in the protein folding process which retain native- like secondary structure, but have a fluctuating ensemble of tertiary folds. Human alpha-lactalbumin is a Ca2+ binding protein which forms a molten globule at pH 2. Although much is known about the secondary structure of the alpha-lactalbumin molten globule, the tertiary structure has so far not been elucidated. Presented in Chapter 2 is a double electron-electron resonance study of alpha-lactalbumin. The C-helix was found to be fully folded in the molten globule, in agreement with previous studies. Furthermore, it is also shown that both the N- and C-termini are in close proximity to the C-helix, forming part of the hydrophobic core of the protein. Data collected in the presence of 8M urea show that the protein is unfolded under these conditions, and distinguishes the molten globule state from this. These data provide quantitative information about the tertiary structure of the alpha-lactalbumin molten globule, and may provide important insight into the protein folding process. Although a wide variety of chemical and biological systems are known to be sensitive to the strength of an applied magnetic field, no biological systems, such as the cryptochrome proteins believed to be the magnetoreceptors in migratory birds, have yet been shown to be sensitive to the field direction. Traditionally, the anisotropic response of such systems to the magnetic field has been probed using photoselection or alignment with liquid crystals. The experimental sensitivity to anisotropy could, however, be improved by increasing the degree of molecular alignment, such as by crystallisation. Presented in Chapter 3 is a study of hen egg white lysozyme crystals doped with FMN, which together form a magnetically sensitive system. The crystals were studied using confocal microscopy, with the magnetic field effect being spatially resolved. The diffusion of FMN through the crystals was also studied, with the spatial variation of the magnetic field effect being explained with reference to the diffusion of FMN. Although no anisotropy of the magnetic field effect was observed in this system, the use of crystallisation as a method of controlling molecular orientation is potentially useful in systems which are expected to show anisotropy (such as cryptochrome). The behaviour of many chemical systems differs between the bulk solution and at the interface. These interfacial processes can be difficult to probe using conventional absorption spectroscopy due to the relatively low absorbance of species at the interface as compared to the bulk. Cavity ring down and cavity enhanced absorption spectroscopy are two techniques which increase the sensitivity of absorption measurements, and evanescent wave variants of both have been applied to interfacial studies. Presented in Chapter 4 is a polarisation sensitive, broad band, evanescent wave cavity enhanced absorption experiment, which allows the study of the spectra of species at the silica/solvent interface across the visible region. A variety of systems which show interesting inter- facial behaviour have been studied, including crystal violet at the silica/water interface, and with polyelectrolyte films. The data could be fitted to extract spectra, kinetics, and average orientations of three individual species. These studies demonstrate the power of the polarisation sensitive, broad band nature of this experiment in determining complex interfacial behaviour involving more than one species.