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The coformulation of monoclonal antibody (mAb) mixtures provides an attractive route to achieving therapeutic efficacy where the targeting of multiple epitopes is necessary. Controlling and predicting the behavior of such mixtures requires elucidating the molecular basis for the self- and cross-protein–protein interactions and how they depend on solution variables. While self-interactions are now beginning to be well understood, systematic studies of cross-interactions between mAbs in solution do not exist. Here, we have used static light scattering to measure the set of self- and cross-osmotic second virial coefficients in a solution containing a mixture of two mAbs, mAbA and mAbB, as a function of ionic strength and pH. mAbB exhibits strong association at a low ionic strength, which is attributed to an electrostatic attraction that is enhanced by the presence of a strong short-ranged attraction of nonelectrostatic origin. Under all solution conditions, the measured cross-interactions are intermediate self-interactions and follow similar patterns of behavior. There is a strong electrostatic attraction at higher pH values, reflecting the behavior of mAbB. Protein–protein interactions become more attractive with an increasing pH due to reducing the overall protein net charges, an effect that is attenuated with an increasing ionic strength due to the screening of electrostatic interactions. Under moderate ionic strength conditions, the reduced cross-virial coefficient, which reflects only the energetic contribution to protein–protein interactions, is given by a geometric average of the corresponding self-coefficients. We show the relationship can be rationalized using a patchy sphere model, where the interaction energy between sites i and j is given by the arithmetic mean of the i–i and j–j interactions. The geometric mean does not necessarily apply to all mAb mixtures and is expected to break down at a lower ionic strength due to the nonadditivity of electrostatic interactions.

Objectives: Drop-foot when incurred as a deficit post-stroke significantly contributes to the development of physical disability and social restriction. The condition is most commonly treated using a custom moulded ankle foot orthosis (AFO) or functional electrical stimulation (FES). No previous systematic review has assessed the evidence for both an orthotic (while the device is still on) and therapeutic (when the device is no longer worn) effect of FES, including all types of methodology and outcome measure. This is certainly a gap in the literature in terms of informing the practising clinician. Methods: A systematic search was conducted to identify all articles published between 1990 and 2008 relating to the effectiveness of FES for the treatment of drop-foot post-stroke using strict inclusion/exclusion criteria. Included literature was quality-appraised according to the Guidelines for Cochrane reviewers. Results: Thirty studies were analysed (264 excluded) and results support the conclusion that FES can have a positive orthotic effect particularly for gait speed and physiological cost index (PCI), in chronic post-stroke patients. Research supporting a therapeutic effect of FES post-stroke is less conclusive. Some support exists for FES in combination with 'conventional rehabilitation' or treadmill training or for increasing the effectiveness of Botulinum toxin injections. Discussion: While more evidence exists to support an orthotic than therapeutic effect of FES, further research is needed to define the extent of a therapeutic effect (particularly in acute patients) and compare the efficacy of FES with an AFO. More standardisation of protocols and a more collaborative approach between engineers, researchers, clinicians and users is required.Post-stroke drop-foot results when the normal interplay between tibialis anterior and triceps surae muscle is disturbed as a result of spasticity in the posterior muscle group (exacerbated by tendon shortening over time) and a weakness of the tibialis anterior and the peroneii muscles. 1 Drop-foot contributes significantly to the residual disabilities incurred as a result of stroke and publications have quoted a conservative estimate of between 18 and 20% as a residual deficit. 2,3 Functional electrical stimulation (FES) is designed to deliver goal-orientated, active repetitive movement training without the constant need for direct therapist input. It is therefore ideally placed to facilitate the neuroscientific principle of motor relearning (in having a carry-over effect) whilst providing an

High-concentration (>100 g/L) solutions of monoclonal antibodies (mAbs) are typically characterized by anomalously large solution viscosity and shear thinning behavior for strain rates ≥10 3 s −1 . Here, the link between protein−protein interactions (PPIs) and the rheology of concentrated solutions of COE-03 and COE-19 mAbs is studied by means of static and dynamic light scattering and microfluidic rheometry. By comparing the experimental data with predictions based on the Baxter sticky hard-sphere model, we surprisingly find a connection between the observed shear thinning and the predicted percolation threshold. The longest shear relaxation time of mAbs was much larger than that of model sticky hard spheres within the same region of the phase diagram, which is attributed to the anisotropy of the mAb PPIs. Our results suggest that not only the strength but also the patchiness of short-range attractive PPIs should be explicitly accounted for by theoretical approaches aimed at predicting the shear rate-dependent viscosity of dense mAb solutions.

Students support inclusion of the module in their training, acknowledging its role in improving their confidence and clinical reasoning, and facilitating continuing professional development. Further studies are required to generalise these findings to a wider population.