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Three issues related to good computational fluid dynamics (CFD) practice are discussed. First, adaptive methods are shown to be a simple tool to perform systematic grid refinement studies needed to achieve solutions with controlled accuracy (verification of simulations). Second, it is shown that the sensitivity equation method provides insights about which parameters critically affect the flow response. Finally, flow sensitivities are used to propagate model parameter uncertainties through the CFD code to yield uncertainty estimates of the CFD predictions. This provides a rigorous framework for comparing predictions to measurements (validation of predictions). These combined approaches help to build confidence in CFD predictions and develop good CFD practice. The resulting uncertainty bars put CFD on par with experimental techniques. The approaches are demonstrated on two-dimensional problems: a k-[epsilon] model of the flow in an annular turn-around duct and conjugate free convection with variable fluid properties. Taken together, these approaches offer a good prospect for developing families of computing methods that can be viewed as standards of good practice in CFD, ensuring that verification and validation studies are performed on solid grounds.

Background: People with Alzheimer disease and related dementias often display disruptive behaviors (eg, aggression, wandering, and restlessness), which increase family caregivers' burden of care. However, there are few tools currently available to help these caregivers manage disruptive behaviors. Mobile apps could meet this need, but to date little is known about them., Objective: The aims of our study were to identify existing mobile apps designed to support family caregivers of people with Alzheimer disease and related dementias in managing disruptive behaviors; explore whether family caregivers view these mobile apps as relevant to meeting their needs and as useful in managing disruptive behaviors; and document the types of mobile apps that are of interest and appeal to most family caregivers (with regard to format, ergonomics, and clarity)., Methods: A review of mobile apps initially conducted in February 2018 was updated in March 2019 with 2 platforms (App Store [Apple Inc.] and Google Play [Google]). The selected apps were first analyzed independently by 3 raters (2 students and 1 researcher) for each of the platforms. A focus group discussion was then held with 4 family caregivers to explore their perceptions of the apps according to their needs and interests. The content of the discussion was analyzed., Results: Initially, 7 of 118 apps identified met the inclusion criteria. An eighth app, recommended by one of the knowledge users, was added later. Four family caregivers (women aged between 58 and 78 years) participated in the discussion. Participants expressed a preference for easy-to-understand apps that provide concrete intervention strategies. They reported being most inclined to use two apps, Dementia Advisor and DTA Behaviours., Conclusions: Few mobile apps on the market meet the needs of family caregivers in terms of content and usability. Our results could help to address this gap by identifying what family caregivers deem relevant in a mobile app to help them manage disruptive behaviors., (©Marjorie Désormeaux-Moreau, Charlie-Maude Michel, Mélanie Vallières, Maryse Racine, Myriame Poulin-Paquet, Delphine Lacasse, Pascale Gionet, Melissa Genereux, Wael Lachiheb, Véronique Provencher. Originally published in JMIR Aging (http://aging.jmir.org), 16.04.2021.)

Biologic products encounter various types of interfacial stress during development, manufacturing, and clinical administration. When proteins come in contact with vapor-liquid, solid-liquid, and liquid-liquid surfaces, these interfaces can significantly impact the protein drug product quality attributes, including formation of visible particles, subvisible particles, or soluble aggregates, or changes in target protein concentration due to adsorption of the molecule to various interfaces. Protein aggregation at interfaces is often accompanied by changes in conformation, as proteins modify their higher order structure in response to interfacial stresses such as hydrophobicity, charge, and mechanical stress. Formation of aggregates may elicit immunogenicity concerns; therefore, it is important to minimize opportunities for aggregation by performing a systematic evaluation of interfacial stress throughout the product development cycle and to develop appropriate mitigation strategies. The purpose of this white paper is to provide an understanding of protein interfacial stability, explore methods to understand interfacial behavior of proteins, then describe current industry approaches to address interfacial stability concerns. Specifically, we will discuss interfacial stresses to which proteins are exposed from drug substance manufacture through clinical administration, as well as the analytical techniques used to evaluate the resulting impact on the stability of the protein. A high-level mechanistic understanding of the relationship between interfacial stress and aggregation will be introduced, as well as some novel techniques for measuring and better understanding the interfacial behavior of proteins. Finally, some best practices in the evaluation and minimization of interfacial stress will be recommended.

Virus retentive filters are a key product safety measure for biopharmaceuticals. A simplistic perception is that they function solely based on a size-based particle removal mechanism of mechanical sieving and retention of particles based on their hydrodynamic size. Recent observations have revealed a more nuanced picture, indicating that changes in viral particle retention can result from process pressure and/or flow interruptions. In this study, a mechanistic investigation was performed to help identify a potential mechanism leading to the reported reduced particle retention in small virus filters. Permeate flow rate or permeate driving force were varied and analyzed for their impact on particle retention in three commercially available small virus retentive filters. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:959-970, 2016., (© 2016 American Institute of Chemical Engineers.)

This paper presents for the first time numerical predictions of mechanical blood hemolysis obtained by solving a hyperbolic partial differential equation (PDE) modelling the hemolysis in a Eulerian frame of reference. This provides hemolysis predictions over the entire computational domain as an alternative to the Lagrangian approach consisting in evaluating cell hemolysis along their trajectories. The solution of a PDE over a computational domain, such as in the approach presented herein, yields a unique solution. This is a clear advantage over the Lagrangian approach, which requires the human-made choice of a limited number of trajectories for integration and inevitably results in the incomplete coverage of the computational domain. The hyperbolic hemolysis model is solved with a Discontinuous Galerkin finite element method. The solution algorithm also includes adaptive remeshing to provide high accuracy simulations. Predictions of the modified index of hemolysis (MIH) are presented for flows in dialysis cannulae and sudden contractions. MIH predictions for cannulae differ significantly from those obtained by other authors using the Lagrangian approach. The predictions for flows in sudden contractions are used, along with our own experimental measurements, to assess the value of the threshold shear stress required for hemolysis that is included in the hemolysis model.

In a previous communication, we have proposed a numerical framework for the prediction of in vitro hemolysis indices in the preselection and optimization of medical devices. This numerical methodology is based on a novel interpretation of Giersiepen-Wurzinger blood damage correlation as a volume integration of a damage function over the computational domain. We now propose an improvement of this approach based on a hyperbolic equation of blood damage that is asymptotically consistent. Consequently, while the proposed correction has yet to be proven experimentally, it has the potential to numerically predict more realistic red blood cell destruction in the case of in vitro experiments. We also investigate the appropriate computation of the shear stress scalar of the damage fraction model. Finally, we assess the validity of this consistent approach with an analytical example and with some 3D examples.

Removal of small parvoviruses from highly purified proteins can be performed using normal-flow filters. The entrapment of protein aggregates, denatured proteins and other impurities can cause plugging and a decrease in filter capacity. In the present study a variety of prefilters were investigated for their ability to remove the species that foul Viresolvetrade mark NFP (normal-flow parvovirus) filters. The Viresolvetrade mark Prefilter, which utilizes entrapped diatomaceous earth to hydrophobically bind fouling species, provided a dramatic increase in virus filter capacity for solutions containing human IgG or a variety of monoclonal antibodies. We found that the component of the human IgG stream that bound to the Prefilter, when analysed using SDS/PAGE, isoelectric-focusing, size-exclusion chromatography, CD and ANS (1-anilinonaphthalene-8-sulphonate) titration, consisted of monomeric IgG variants containing more exposed hydrophobic surfaces. The bound component may represent oxidized or otherwise degraded IgG species or a subset of IgG molecules with more hydrophobic antigen-binding surfaces. The results indicate that NFP membranes do not foul solely as a result of entrapment of protein aggregates in the pore structure. The Viresolvetrade mark Prefilter has a high permeability, did not diminish protein yield and provided consistent performance between different media lots, device lots and device scales.

Eight focus groups were conducted with the stakeholders involved in psychiatric foster homes: people with psychiatric disabilities, families, caregivers, and professionals. Four content dimensions emerged as important: 1) foster home environment, 2) caregiver characteristics, 3) community integration, and 4) stakeholder relationships. Findings revealed different perspectives among stakeholders. Caregivers and professionals differed in their views on rehabilitation. Families wanted stricter controls within homes; residents appreciated more autonomy. While residents and caregivers focussed on integration within the foster home, professionals criticized the lack of community integration. These findings demonstrate the need to examine the perspectives of multiple stakeholders in order to present a complete view of psychiatric foster homes.