The experience of conducting collaborative and intensive pragmatic qualitative (CLIP-Q) research to support rapid public health and healthcare innovation

A key challenge for qualitative methods in applied health research is the fast pace that can characterize the public health and health and care service landscape, where there is a need for research informed by immediate pragmatic questions and relevant findings are required quickly to inform decision-making. The COVID-19 pandemic accelerated the pace at which evidence was needed to inform urgent public health and healthcare decision-making. This required qualitative researchers to step up to the challenge of conducting research at speed whilst maintaining rigor and ensuring the findings are credible. This article illustrates how working with multidisciplinary, collaborative teams and the tailoring of qualitative methods to be more pragmatic and efficient can provide timely and credible results. Using time-limited case studies of applied qualitative health research drawn from the work of the Behavioral and Qualitative Science Team from the National Institute for Health and Care Research Applied Research Collaboration West (NIHR ARC West), we illustrate our collaborative and intensive pragmatic qualitative (CLIP-Q) approach. CLIP-Q involves (i) collaboration at all stages of the design, conduct and implementation of projects and, where possible, co-production with people with lived experience, (ii) an intensive team-based approach to data collection and analysis at pace, and (iii) pragmatic study design and efficient strategies at each stage of the research process. The case studies include projects conducted pre COVID-19 and during the first wave of the pandemic, where urgent evidence was required in weeks rather than months to inform rapid public health and healthcare decision making

Interactions between metabolic, reward and cognitive processes in appetite control:Implications for novel weight management therapies

Traditional models of appetite control have emphasised the role of parallel homeostatic and hedonic systems, but more recently the distinction between independent homeostatic and hedonic systems has been abandoned in favour of a framework that emphasises the cross talk between the neurochemical substrates of the two systems. In addition, evidence has emerged more recently, that higher level cognitive functions such as learning, memory and attention play an important role in everyday appetite control and that homeostatic signals also play a role in cognition. Here, we review this evidence and present a comprehensive model of the control of appetite that integrates cognitive, homeostatic and reward mechanisms. We discuss the implications of this model for understanding the factors that may contribute to disordered patterns of eating and suggest opportunities for developing more effective treatment approaches for eating disorders and weight management

Structure of the γ-D-glutamyl-L-diamino acid endopeptidase YkfC from Bacillus cereus in complex with L-Ala-γ-D-Glu: insights into substrate recognition by NlpC/P60 cysteine peptidases.

Dipeptidyl-peptidase VI from Bacillus sphaericus and YkfC from Bacillus subtilis have both previously been characterized as highly specific γ-D-glutamyl-L-diamino acid endopeptidases. The crystal structure of a YkfC ortholog from Bacillus cereus (BcYkfC) at 1.8 Å resolution revealed that it contains two N-terminal bacterial SH3 (SH3b) domains in addition to the C-terminal catalytic NlpC/P60 domain that is ubiquitous in the very large family of cell-wall-related cysteine peptidases. A bound reaction product (L-Ala-γ-D-Glu) enabled the identification of conserved sequence and structural signatures for recognition of L-Ala and γ-D-Glu and, therefore, provides a clear framework for understanding the substrate specificity observed in dipeptidyl-peptidase VI, YkfC and other NlpC/P60 domains in general. The first SH3b domain plays an important role in defining substrate specificity by contributing to the formation of the active site, such that only murein peptides with a free N-terminal alanine are allowed. A conserved tyrosine in the SH3b domain of the YkfC subfamily is correlated with the presence of a conserved acidic residue in the NlpC/P60 domain and both residues interact with the free amine group of the alanine. This structural feature allows the definition of a subfamily of NlpC/P60 enzymes with the same N-terminal substrate requirements, including a previously characterized cyanobacterial L-alanine-γ-D-glutamate endopeptidase that contains the two key components (an NlpC/P60 domain attached to an SH3b domain) for assembly of a YkfC-like active site

The structure of BVU2987 from Bacteroides vulgatus reveals a superfamily of bacterial periplasmic proteins with possible inhibitory function.

Proteins that contain the DUF2874 domain constitute a new Pfam family PF11396. Members of this family have predominantly been identified in microbes found in the human gut and oral cavity. The crystal structure of one member of this family, BVU2987 from Bacteroides vulgatus, has been determined, revealing a β-lactamase inhibitor protein-like structure with a tandem repeat of domains. Sequence analysis and structural comparisons reveal that BVU2987 and other DUF2874 proteins are related to β-lactamase inhibitor protein, PepSY and SmpA_OmlA proteins and hence are likely to function as inhibitory proteins

Atypical Haemolytic Uraemic Syndrome Associated with a Hybrid Complement Gene

BACKGROUND: Sequence analysis of the regulators of complement activation (RCA) cluster of genes at chromosome position 1q32 shows evidence of several large genomic duplications. These duplications have resulted in a high degree of sequence identity between the gene for factor H (CFH) and the genes for the five factor H-related proteins (CFHL1–5; aliases CFHR1–5). CFH mutations have been described in association with atypical haemolytic uraemic syndrome (aHUS). The majority of the mutations are missense changes that cluster in the C-terminal region and impair the ability of factor H to regulate surface-bound C3b. Some have arisen as a result of gene conversion between CFH and CFHL1. In this study we tested the hypothesis that nonallelic homologous recombination between low-copy repeats in the RCA cluster could result in the formation of a hybrid CFH/CFHL1 gene that predisposes to the development of aHUS. METHODS AND FINDINGS: In a family with many cases of aHUS that segregate with the RCA cluster we used cDNA analysis, gene sequencing, and Southern blotting to show that affected individuals carry a heterozygous CFH/CFHL1 hybrid gene in which exons 1–21 are derived from CFH and exons 22/23 from CFHL1. This hybrid encodes a protein product identical to a functionally significant CFH mutant (c.3572C>T, S1191L and c.3590T>C, V1197A) that has been previously described in association with aHUS. CONCLUSIONS: CFH mutation screening is recommended in all aHUS patients prior to renal transplantation because of the high risk of disease recurrence post-transplant in those known to have a CFH mutation. Because of our finding it will be necessary to implement additional screening strategies that will detect a hybrid CFH/CFHL1 gene

Embracing complexity and uncertainty to create impact: Exploring the processes and transformative potential of co-produced research through development of a social impact model

© 2018 The Author(s). The potential use, influence and impact of health research is seldom fully realised. This stubborn problem has caused burgeoning global interest in research aiming to address the implementation 'gap' and factors inhibiting the uptake of scientific evidence. Scholars and practitioners have questioned the nature of evidence used and required for healthcare, highlighting the complex ways in which knowledge is formed, shared and modified in practice and policy. This has led to rapid expansion, expertise and innovation in the field of knowledge mobilisation and funding for experimentation into the effectiveness of different knowledge mobilisation models. One approach gaining prominence involves stakeholders (e.g. researchers, practitioners, service users, policy-makers, managers and carers) in the co-production, and application, of knowledge for practice, policy and research (frequently termed integrated knowledge translation in Canada). Its popularity stems largely from its potential to address dilemmas inherent in the implementation of knowledge generated using more reductionist methods. However, despite increasing recognition, demands for co-produced research to illustrate its worth are becoming pressing while the means to do so remain challenging. This is due not only to the diversity of approaches to co-production and their application, but also to the ways through which different stakeholders conceptualise, measure, reward and use research. While research co-production can lead to demonstrable benefits such as policy or practice change, it may also have more diffuse and subtle impact on relationships, knowledge sharing, and in engendering culture shifts and research capacity-building. These relatively intangible outcomes are harder to measure and require new emphases and tools. This opinion paper uses six Canadian and United Kingdom case studies to explore the principles and practice of co-production and illustrate how it can influence interactions between research, policy and practice, and benefit diverse stakeholders. In doing so, we identify a continuum of co-production processes. We propose and illustrate the use of a new 'social model of impact' and framework to capture multi-layered and potentially transformative impacts of co-produced research. We make recommendations for future directions in research co-production and impact measurement

A conserved fold for fimbrial components revealed by the crystal structure of a putative fimbrial assembly protein (BT1062) from Bacteroides thetaiotaomicron at 2.2 Å resolution

The crystal structure of BT1062 from Bacteroides thetaiotaomicron revealed a conserved fold that is widely adopted by fimbrial components

Structure of Bacteroides thetaiotaomicron BT2081 at 2.05 Å resolution: the first structural representative of a new protein family that may play a role in carbohydrate metabolism

The crystal structure of BT2081 from B. thetaiotaomicron reveals a two-domain protein with a putative carbohydrate-binding site in the C-­terminal domain