Centres and limit cycles for an extended Kukles system

We present conditions for the origin to be a centre for a class of cubic systems. Some of the centre conditions are determined by finding complicated invariant functions. We also investigate the coexistence of fine foci and the simultaneous bifurcation of limit cycles from them

Limit cycles of a predator-prey model with intratrophic predation

AbstractWe present some properties of a differential system that can be used to model intratrophic predation in simple predator–prey models. In particular, for the model we determine the maximum number of limit cycles that can exist around the only fine focus in the first quadrant and show that this critical point cannot be a centre

Desperately seeking niches: Grassroots innovations and niche development in the community currency field

The sustainability transitions literature seeks to explain the conditions under which technological innovations can diffuse and disrupt existing socio-technical systems through the successful scaling up of experimental ‘niches’; but recent research on ‘grassroots innovations’ argues that civil society is a promising but under-researched site of innovation for sustainability, albeit one with very different characteristics to the market-based innovation normally considered in the literature. This paper aims to address that research gap by exploring the relevance of niche development theories in a civil society context. To do this, we examine a growing grassroots innovation – the international field of community currencies – which comprises a range of new socio-technical configurations of systems of exchange which have emerged from civil society over the last 30 years, intended to provide more environmentally and socially sustainable forms of money and finance. We draw on new empirical research from an international study of these initiatives comprising primary and secondary data and documentary sources, elite interviews and participant observation in the field. We describe the global diffusion of community currencies, and then conduct a niche analysis to evaluate the utility of niche theories for explaining the development of the community currency movement. We find that some niche-building processes identified in the existing literature are relevant in a grassroots context: the importance of building networks, managing expectations and the significance of external ‘landscape’ pressures, particularly at the level of national-type. However, our findings suggest that existing theories do not fully capture the complexity of this type of innovation: we find a diverse field addressing a range of societal systems (money, welfare, education, health, consumerism), and showing increasing fragmentation (as opposed to consolidation and standardisation); furthermore, there is little evidence of formalised learning taking place but this has not hampered movement growth. We conclude that grassroots innovations develop and diffuse in quite different ways to conventional innovations, and that niche theories require adaptation to the civil society context

Gene expression profiling in NOD mice reveals that B cells are highly educated by the pancreatic environment during autoimmune diabetes

Aims/hypothesis: B cells play an important role in driving the development of type 1 diabetes; however, it remains unclear how they contribute to local beta cell destruction during disease progression. Here, we use gene expression profiling of B cell subsets identified in inflamed pancreatic tissue to explore their primary functional role during the progression of autoimmune diabetes. Methods: Transcriptional profiling was performed on FACS-sorted B cell subsets isolated from pancreatic islets and the pancreatic lymph nodes of NOD mice. Results: B cells are highly modified by the inflamed pancreatic tissue and can be distinguished by their transcriptional profile from those in the lymph nodes. We identified both a discrete and a core shared gene expression profile in islet CD19+CD138– and CD19+CD138+ B cell subsets, the latter of which is known to have enriched autoreactivity during diabetes development. On localisation to pancreatic islets, compared with CD138– B cells, CD138+ B cells overexpress genes associated with adhesion molecules and growth factors. Their shared signature consists of gene expression changes related to the differentiation of antibody-secreting cells and gene regulatory networks associated with IFN signalling pathways, proinflammatory cytokines and Toll-like receptor (TLR) activation. Finally, abundant TLR7 expression was detected in islet B cells and was enhanced specifically in CD138+ B cells. Conclusions/interpretation: Our study provides a detailed transcriptional analysis of islet B cells. Specific gene signatures and interaction networks have been identified that point towards a functional role for B cells in driving autoimmune diabetes. Graphical abstract

Collaborative action for person-centred coordinated care (P3C): an approach to support the development of a comprehensive system-wide solution to fragmented care

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Fragmented care results in poor outcomes for individuals with complexity of need. Person-centred coordinated care (P3C) is perceived to be a potential solution, but an absence of accessible evidence and the lack of a scalable 'blue print' mean that services are 'experimenting' with new models of care with little guidance and support. This paper presents an approach to the implementation of P3C using collaborative action, providing examples of early developments across this programme of work, the core aim of which is to accelerate the spread and adoption of P3C in United Kingdom primary care settings. METHODS: Two centrally funded United Kingdom organisations (South West Collaboration for Leadership in Applied Health Research and Care and South West Academic Health Science Network) are leading this initiative to narrow the gap between research and practice in this urgent area of improvement through a programme of service change, evaluation and research. Multi-stakeholder engagement and co-design are core to the approach. A whole system measurement framework combines outcomes of importance to patients, practitioners and health organisations. Iterative and multi-level feedback helps to shape service change while collecting practice-based data to generate implementation knowledge for the delivery of P3C. The role of the research team is proving vital to support informed change and challenge organisational practice. The bidirectional flow of knowledge and evidence relies on the transitional positioning of researchers and research organisations. RESULTS: Extensive engagement and embedded researchers have led to strong collaborations across the region. Practice is beginning to show signs of change and data flow and exchange is taking place. However, working in this way is not without its challenges; progress has been slow in the development of a linked data set to allow us to assess impact innovations from a cost perspective. Trust is vital, takes time to establish and is dependent on the exchange of services and interactions. If collaborative action can foster P3C it will require sustained commitment from both research and practice. This approach is a radical departure from how policy, research and practice traditionally work, but one that we argue is now necessary to deal with the most complex health and social problems.This research was supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. TS’s current post at the University of Oxford is funded by the NIHR Collaboration for Leadership in Applied Health Research and Care Oxford at Oxford Health NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. This research was also funded by the South West Academic health Science Network (AHSN). The views expressed are those of the authors and not necessarily those of the AHSN.The NIHR CLAHRC Programme fund the substantive posts of HML, RB, NB, HW, TPS and MP as members of the South West Peninsula CLARHC. All other co-authors are members of the wider collaboration and are substantially employed by their respective organisations

Operation Moonshot: rapid translation of a SARS-CoV-2 targeted peptide immunoaffinity liquid chromatography-tandem mass spectrometry test from research into routine clinical use

OBJECTIVES: During 2020, the UK's Department of Health and Social Care (DHSC) established the Moonshot programme to fund various diagnostic approaches for the detection of SARS-CoV-2, the pathogen behind the COVID-19 pandemic. Mass spectrometry was one of the technologies proposed to increase testing capacity. METHODS: Moonshot funded a multi-phase development programme, bringing together experts from academia, industry and the NHS to develop a state-of-the-art targeted protein assay utilising enrichment and liquid chromatography tandem mass spectrometry (LC-MS/MS) to capture and detect low levels of tryptic peptides derived from SARS-CoV-2 virus. The assay relies on detection of target peptides, ADETQALPQRK (ADE) and AYNVTQAFGR (AYN), derived from the nucleocapsid protein of SARS-CoV-2, measurement of which allowed the specific, sensitive, and robust detection of the virus from nasopharyngeal (NP) swabs. The diagnostic sensitivity and specificity of LC-MS/MS was compared with reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) via a prospective study. RESULTS: Analysis of NP swabs (n=361) with a median RT-qPCR quantification cycle (Cq) of 27 (range 16.7-39.1) demonstrated diagnostic sensitivity of 92.4% (87.4-95.5), specificity of 97.4% (94.0-98.9) and near total concordance with RT-qPCR (Cohen's Kappa 0.90). Excluding Cq>32 samples, sensitivity was 97.9% (94.1-99.3), specificity 97.4% (94.0-98.9) and Cohen's Kappa 0.95. CONCLUSIONS: This unique collaboration between academia, industry and the NHS enabled development, translation, and validation of a SARS-CoV-2 method in NP swabs to be achieved in 5 months. This pilot provides a model and pipeline for future accelerated development and implementation of LC-MS/MS protein/peptide assays into the routine clinical laboratory

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]