Patient perspectives on delays in diagnosis and treatment of cancer: a qualitative analysis of free-text data

Background: Earlier cancer diagnosis is crucial in improving cancer survival. The International Cancer Benchmarking Partnership Module 4 (ICBP4) is a quantitative survey study that explores the reasons for delays in diagnosis and treatment of breast, colorectal, lung, and ovarian cancer. To further understand the associated diagnostic processes, it is also important to explore the patient perspectives expressed in the free-text comments. Aim: To use the free-text data provided by patients completing the ICBP4 survey to augment the understanding of patients’ perspectives of their diagnostic journey. Design and setting: Qualitative analysis of the free-text data collected in Wales between October 2013 and December 2014 as part of the ICBP4 survey. Newly-diagnosed patients with either breast, ovarian, colorectal, or lung cancer were identified from registry data and then invited by their GPs to participate in the survey. Method: A thematic framework was used to analyse the free-text comments provided at the end of the ICBP4 survey. Of the 905 patients who returned a questionnaire, 530 included comments. Results: The free-text data provided information about patients’ perspectives of the diagnostic journey. Analysis identified factors that acted as either barriers or facilitators at different stages of the diagnostic process. Some factors, such as screening, doctor–patient familiarity, and private treatment, acted as both barriers and facilitators depending on the context. Conclusion: Factors identified in this study help to explain how existing models of cancer diagnosis (for example, the Pathways to Treatment Model) work in practice. It is important that clinicians are aware of how these factors may interact with individual clinical cases and either facilitate, or act as a barrier to, subsequent cancer diagnosis. Understanding and implementing this knowledge into clinical practice may result in quicker cancer diagnoses

Counting Complex Disordered States by Efficient Pattern Matching: Chromatic Polynomials and Potts Partition Functions

Counting problems, determining the number of possible states of a large system under certain constraints, play an important role in many areas of science. They naturally arise for complex disordered systems in physics and chemistry, in mathematical graph theory, and in computer science. Counting problems, however, are among the hardest problems to access computationally. Here, we suggest a novel method to access a benchmark counting problem, finding chromatic polynomials of graphs. We develop a vertex-oriented symbolic pattern matching algorithm that exploits the equivalence between the chromatic polynomial and the zero-temperature partition function of the Potts antiferromagnet on the same graph. Implementing this bottom-up algorithm using appropriate computer algebra, the new method outperforms standard top-down methods by several orders of magnitude, already for moderately sized graphs. As a first application, we compute chromatic polynomials of samples of the simple cubic lattice, for the first time computationally accessing three-dimensional lattices of physical relevance. The method offers straightforward generalizations to several other counting problems.Comment: 7 pages, 4 figure

Assessment of the 2016 National Institute for Health and Care Excellence high-sensitivity troponin rule-out strategy.

OBJECTIVE: We aimed to evaluate the limit of detection of high-sensitivity troponin (hs-cTn) and Thrombolysis In Myocardial Infarction (TIMI) score combination rule-out strategy suggested within the 2016 National Institute for Health and Care Excellence (NICE) Chest Pain of Recent Onset guidelines and establish the optimal TIMI score threshold for clinical use. METHODS: A pooled analysis of adult patients presenting to the emergency department with chest pain and a non-ischaemic ECG, recruited into six prospective studies, from Australia, New Zealand and the UK. We evaluated the sensitivity of TIMI score thresholds from 0 to 2 alongside hs-cTnT or hs-cTnI for the primary outcome of major adverse cardiac events within 30 days. RESULTS: Data were available for 3159 patients for hs-cTnT and 4532 for hs-cTnI, of these 376 (11.9%) and 445 (9.8%) had major adverse cardiac events, respectively. Using a TIMI score of 0, the sensitivity for the primary outcome was 99.5% (95% CI 98.1% to 99.9%) alongside hs-cTnT and 98.9% (97.4% to 99.6%)%) alongside hs-cTnI, identifying 17.9% and 21.0% of patients as low risk, respectively. For a TIMI score ≤1 sensitivity was 98.9% (97.3% to 99.7%)%) alongside hs-cTnT and 98.4% (96.8% to 99.4%)%) alongside hs-cTnI, identifying 28.1% and 35.7% as low risk, respectively. For TIMI≤2, meta-sensitivity was <98% with either assay. CONCLUSIONS: Our findings support the rule-out strategy suggested by NICE. The TIMI score threshold suggested for clinical use is 0. The proportion of patients identified as low risk (18%-21%) and suitable for early discharge using this threshold may be sufficient to encourage change of practice. TRIAL REGISTRATION NUMBERS: ADAPT observational study/IMPACT intervention trial ACTRN12611001069943.ADAPT-ADP randomised controlled trial ACTRN12610000766011.EDACS-ADP randomised controlled trial ACTRN12613000745741.TRUST observational study ISRCTN no. 21109279

Reflecting photonics: reaching new audiences through new partnerships – IYL 2015 and the Royal Horticultural Society Flower Show

The ‘Reflecting Photonics’ show garden was exhibited at the 2015 Royal Horticultural Society (RHS) Flower Show in Tatton Park, UK, to celebrate the International Year of Light and Light-based Technologies. Elks-Smith Garden Design alongside landscapers ‘Turf N’ Earth’ collaborated with researchers, marketing and outreach professionals from the University of Southampton to design, construct and exhibit a photonics-themed garden. The garden and supporting exhibition united science and art to reach new audiences – particularly family groups alongside other key influencers to the young – and showcased the world-leading research in optical fibers at the university in an accessible manner. Researchers and a publicity professional, funded by the EPSRC Centre for Innovative Manufacturing in Photonics, developed an integrated approach to the event’s public engagement and marketing. The overarching aim was to influence a positive change in the attitude of the garden visitors towards physics and photonics, with additional focus on promoting careers for women in STEM. The show garden won an RHS Gold Medal award and the coveted ‘People’s Choice Award’ for the best large garden. The project subsequently won the South East England Physics Network Public Engagement Innovation Project Award. Approximately 80,000 visitors saw the garden, with a further three million television viewers on a popular British gardening show. There were also over 75,400 Tweet impressions on social media. This paper discusses the project aims, explores the design of the garden and its relationship with the research, describes the work of the public engagement team, and outlines the impact of the event

Differential expression, function and response to inflammatory stimuli of 11β-hydroxysteroid dehydrogenase type 1 in human fibroblasts: a mechanism for tissue-specific regulation of inflammation

Stromal cells such as fibroblasts play an important role in defining tissue-specific responses during the resolution of inflammation. We hypothesized that this involves tissue-specific regulation of glucocorticoids, mediated via differential regulation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Expression, activity and function of 11β-HSD1 was assessed in matched fibroblasts derived from various tissues (synovium, bone marrow and skin) obtained from patients with rheumatoid arthritis or osteoarthritis. 11β-HSD1 was expressed in fibroblasts from all tissues but mRNA levels and enzyme activity were higher in synovial fibroblasts (2-fold and 13-fold higher mRNA levels in dermal and synovial fibroblasts, respectively, relative to bone marrow). Expression and activity of the enzyme increased in all fibroblasts following treatment with tumour necrosis factor-α or IL-1β (bone marrow: 8-fold and 37-fold, respectively, compared to vehicle; dermal fibroblasts: 4-fold and 14-fold; synovial fibroblasts: 7-fold and 31-fold; all P < 0.01 compared with vehicle). Treatment with IL-4 or interferon-γ was without effect, and there was no difference in 11β-HSD1 expression between fibroblasts (from any site) obtained from patients with rheumatoid arthritis or osteoarthritis. In the presence of 100 nmol/l cortisone, IL-6 production – a characteristic feature of synovial derived fibroblasts – was significantly reduced in synovial but not dermal or bone marrow fibroblasts. This was prevented by co-treatment with an 11β-HSD inhibitor, emphasizing the potential for autocrine activation of glucocorticoids in synovial fibroblasts. These data indicate that differences in fibroblast-derived glucocorticoid production (via the enzyme 11β-HSD1) between cells from distinct anatomical locations may play a key role in the predeliction of certain tissues to develop persistent inflammation

Theory of Distinct Crystal Structures of Polymerized Fullerides AC60, A=K, Rb, Cs: the Specific Role of Alkalis

The polymer phases of AC60 form distinct crystal structures characterized by the mutual orientations of the (C60-)n chains. We show that the direct electric quadrupole interaction between chains always favors the orthorhombic structure Pmnn with alternating chain orientations. However the specific quadrupolar polarizability of the alkali metal ions leads to an indirect interchain coupling which favors the monoclinic structure I2/m with equal chain orientations. The competition between direct and indirect interactions explains the structural difference between KC60 and RbC60, CsC60.Comment: 4 pages, 2 figures, 1 tabl

Lower Bounds and Series for the Ground State Entropy of the Potts Antiferromagnet on Archimedean Lattices and their Duals

We prove a general rigorous lower bound for $W(\Lambda,q)=\exp(S_0(\Lambda,q)/k_B)$, the exponent of the ground state entropy of the $q$-state Potts antiferromagnet, on an arbitrary Archimedean lattice $\Lambda$. We calculate large-$q$ series expansions for the exact $W_r(\Lambda,q)=q^{-1}W(\Lambda,q)$ and compare these with our lower bounds on this function on the various Archimedean lattices. It is shown that the lower bounds coincide with a number of terms in the large-$q$ expansions and hence serve not just as bounds but also as very good approximations to the respective exact functions $W_r(\Lambda,q)$ for large $q$ on the various lattices $\Lambda$. Plots of $W_r(\Lambda,q)$ are given, and the general dependence on lattice coordination number is noted. Lower bounds and series are also presented for the duals of Archimedean lattices. As part of the study, the chromatic number is determined for all Archimedean lattices and their duals. Finally, we report calculations of chromatic zeros for several lattices; these provide further support for our earlier conjecture that a sufficient condition for $W_r(\Lambda,q)$ to be analytic at $1/q=0$ is that $\Lambda$ is a regular lattice.Comment: 39 pages, Revtex, 9 encapsulated postscript figures, to appear in Phys. Rev.

Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression

Introduction\ud Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity. \ud \ud Methods\ud Flow cytometry was used to analyse the phenotype and cytokine production of mononuclear cells isolated from peripheral blood (PBMC) (n = 44), synovial fluid (SFMC) (n = 14) and synovium (SVMC) (n = 10) of RA patients and PBMC of healthy controls (n = 13). \ud \ud Results\ud The frequency of IL-17-producing CD4 T cells was elevated in RA SFMC compared with RA PBMC (P = 0.04). However, the frequency of this population in RA SVMC was comparable to that in paired RA PBMC. The percentage of IL-17-producing CD4 T cells coexpressing tumor necrosis factor alpha (TNFα) was significantly increased in SFMC (P = 0.0068). The frequency of IFNγ-producing CD4 T cells was also significantly higher in SFMC than paired PBMC (P = 0.042). The majority of IL-17-producing CD4 T cells coexpressed IFNγ. IL-17-producing CD4 T cells in RA PBMC and SFMC exhibited very little IL-22 or IL-23R coexpression. \ud \ud Conclusions\ud These findings demonstrate a modest enrichment of IL-17-producing CD4 T cells in RA SFMC compared to PBMC. Th17 cells in SFMC produce more TNFα than their PBMC counterparts, but are not a significant source of IL-22 and do not express IL-23R. However, the percentage of CD4 T cells which produce IL-17 in the rheumatoid joint is low, suggesting that other cells may be alternative sources of IL-17 within the joints of RA patients. \ud \u