A framework to support the design and cultivation of embedded research initiatives

This work was supported by the National Institute of Health Research (NIHR) Health Services & Delivery Research (HS&DR) programme under grant number 16/52/21.Background: Embedded research involves co-locating researchers within non-academic organisations to better link research and practice. Embedded research initiatives are often complex and emergent with a range of underlying intents, structures and processes. This can create tensions within initiatives and contributes to ongoing uncertainty about the most suitable designs and the effectiveness of different approaches. Aims and objectives: We aimed to devise a practical framework to support those designing and cultivating embedded research by operationalising findings from an extensive study of existing initiatives. Key conclusions: The underpinning research on embedded initiatives – a literature review and scoping exercise of initiatives in health settings across the UK – showed that such initiatives share ten common sets of concerns in relation to their intent, structure and processes. We used these insights during a co-production workshop with embedded researchers and their managers that made use of a range of creative activities. The workshop resulted in a practical framework (and associated web-based tools) that draw on the metaphor of a garden to represent the growing, emergent nature of embedded research initiatives and the active work which individuals and organisations need to put into planning and maintaining such initiatives. Each of the aspects is represented as a separate area within the garden using relevant visual metaphors. Building on this, we also present a series of reflective questions designed to facilitate discussion and debate about design features, and we link these to the wider literature, thereby helping those involved to articulate and discuss their preferences and expectations.Publisher PDFPeer reviewe

A New Model for Void Coalescence by Internal Necking

A micromechanical model for predicting the strain increment required to bring a damaged material element from the onset of void coalescence up to final fracture is developed based on simple kinematics arguments. This strain increment controls the unloading slope and the energy dissipated during the final step of material failure. Proper prediction of the final drop of the load carrying capacity is an important ingredient of any ductile fracture model, especially at high stress triaxiality. The model has been motivated and verified by comparison to a large set of finite element void cell calculations.

The effects of rate sensitivity and plastic potential surface curvature on plastic flow localization in porous solids

Plastic flow localization in porous elastic-viscoplastic solids is analyzed with an emphasis on the effects of material rate sensitivity and plastic potential surface curvature. The effect of rate sensitivity is included in a material model that accounts for a change of yield surface curvature in a rate-insensitive porous ductile solid. Shear band formation under plane strain and axisymmetric tension, and localized necking in biaxially stretched sheets are analyzed by using the present material model. The results illustrate the interactions of the effects of void nucleation and growth, material rate sensitivity and plastic potential surface curvature on plastic flow localization. The effects of nonproportional straining paths on localized necking in thin sheets are also demonstrated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42772/1/10704_2004_Article_BF00015862.pd

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond.

Cells have a number of mechanisms to maintain protein homeostasis, including proteasome-mediated degradation of ubiquitinated proteins and autophagy, a regulated process of ‘self-eating’ where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by toll-like receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses. Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis

Recent advances in ankylosing spondylitis: understanding the disease and management

The term spondyloarthritis refers to a group of immune-mediated diseases characterised by inflammation of the axial skeleton, peripheral joints, and entheses. Ankylosing spondylitis (AS) is the most common and characteristic of these entities and even though it was first described over two centuries ago, the understanding of the underlying disease mechanism remains incomplete. It is known that around 40% of patients with AS have subclinical bowel inflammation, suggesting that the origin of the disease could be in the gut. Also, more genes and new molecules have demonstrated a role in the pathogenesis of AS. In this review, we analyse the latest therapies for spondyloarthritis and the most relevant discoveries over the last three years, together with their implications for different aspects of the disease