Supercooled-liquid and plastic-crystalline state in succinonitrile-glutaronitrile mixtures

We report a thorough characterization of the glassy phases of mixtures of succinonitrile and glutaronitrile via dielectric spectroscopy and differential scanning calorimetry. This system is revealed to be one of the rare examples where both glassy states of matter, a structurally disordered supercooled liquid and an orientationally disordered plastic crystal, can be prepared in the same material. Both disordered states can be easily supercooled, finally arriving at a structural-glass or a glassy-crystal state. Detailed investigations using broadband dielectric spectroscopy enable a comparison of the glassy dynamics in both phases. Just as previously demonstrated for supercooled-liquid and plastic-crystalline ethanol, our experiments reveal very similar relaxational behavior and glass temperatures of both disordered states. Thus the prominent role of orientational degrees of freedom in the glass transition, suggested on the basis of the findings for ethanol, is fully corroborated by the present work. Moreover, the fragilities of both phases are determined and compared for different mixtures. The findings can be well understood within an energy-landscape based explanation of fragility.Comment: 8 pages, 7 figure

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

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

Temperature development of glassy alpha-relaxation dynamics determined by broadband dielectric spectroscopy

We present the temperature dependence of alpha-relaxation times of 13 glass formers determined from broadband dielectric spectroscopy, also including data from aging measurements. The data sets partly cover relaxation-time ranges of up to 16 decades enabling a critical test of the validity of model predictions. For this purpose, the data are provided for electronic download. Here we employ these results to test the applicability of the Vogel-Fulcher-Tammann equation and a recently proposed new approach that was demonstrated to provide superior fits of a vast collection of viscosity data.Comment: 6 pages, 5 figures, final version with minor revisions according to referee demands. The relaxation time data published in the present work can be downloaded at http://link.aps.org/supplemental/10.1103/PhysRevE.81.05150

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

Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis ( RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines ( e. g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-gamma at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA

Pragmatic methods for reviewing exceptionally large bodies of evidence: systematic mapping review and overview of systematic reviews using lung cancer survival as an exemplar.

INTRODUCTION:Lung cancer (LC) is the most common cause of cancer death in the world and associated with significant economic burden. We conducted a review of published literature to identify prognostic factors associated with LC survival and determine which may be modifiable and could be targeted to improve outcomes. METHODS:The exceptionally large volume of LC prognostic research required a new staged approach to reviewing the literature. This comprised an initial mapping review of existing reviews or meta-analyses, based on titles and abstracts, followed by an overview of systematic reviews evaluating factors that independently contribute to lung cancer survival. The overview of reviews was based on full text papers and incorporated a more in-depth assessment of reviews evaluating modifiable factors. RESULTS:A large volume of published systematic reviews and meta-analyses were identified, but very few focused on modifiable factors for LC survival. Several modifiable factors were identified, which are potential candidates for targeted interventions aiming to improve cancer outcomes. The mapping review included 398 reviews, of which 207 investigated the independent effect of prognostic factors on lung cancer survival. The most frequently evaluated factors were novel biomarkers (86 biomarkers in 138 reviews). Only 15 modifiable factors were investigated in 20 reviews. Those associated with significant survival improvement included normal BMI/less weight loss, good performance status, not smoking/quitting after diagnosis, good pre-treatment quality of life, small gross volume tumour, early-stage tumour, lung resection undertaken by a thoracic/cardiothoracic surgeon, care being discussed by a multidisciplinary team, and timeliness of care. CONCLUSIONS:The study utilised a novel approach for reviewing an extensive and complicated body of research evidence. It enabled us to address a broad research question and focus on a specific area of priority. The staged approach ensured the review remained relevant to the stakeholders throughout, whilst maintaining the use of objective and transparent methods. It also provided important information on the needs of future research. However, it required extensive planning, management, and ongoing reviewer training

Human Leukocyte Antigen (HLA) A*1101-restricted Epstein-Barr virus-specific T-cell receptor gene transfer to target Nasopharyngeal carcinoma

Infusing virus-specific T-cells is effective treatment for rare Epstein-Barr virus (EBV)-associated post-transplant lymphomas and more limited success has been reported using this approach to treat a far more common EBV-associated malignancy, Nasopharyngeal carcinoma (NPC). However, current approaches using EBV-transformed lymphoblastoid cell lines to reactivate EBV-specific T-cells for infusion take 2-3 months of in vitro culture and favour outgrowth of T-cells targeting viral antigens expressed within EBV+ lymphomas but not NPC. Here we explore T-cell receptor (TCR) gene transfer to rapidly and reliably generate T-cells specific for the NPC-associated viral protein LMP2. We cloned a HLA A*1101-restricted TCR, which would be widely applicable since 40% of NPC patients carry this HLA allele. Studying both wild-type and modified forms we have optimised expression of the TCR and demonstrated high avidity antigen-specific function (proliferation, cytotoxicity, cytokine release) in both CD8+ and CD4+ T-cells. The engineered T-cells also inhibited LMP2+ epithelial tumour growth in a mouse model. Furthermore, transduced T-cells from patients with advanced NPC lysed LMP2-expressing NPC cell lines. Therefore, using this approach, within a few days large numbers of high avidity LMP2-specific T-cells can be reliably generated to treat NPC, providing an ideal clinical setting to test TCR gene transfer without the risk of autoimmunity through targeting self-antigens

Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and disease and identify disease specific pathways

Synovial fibroblasts in persistent inflammatory arthritis have been suggested to have parallels with cancer growth and wound healing, both of which involve a stereotypical serum response programme. We tested the hypothesis that a serum response programme can be used to classify diseased tissues, and investigated the serum response programme in fibroblasts from multiple anatomical sites and two diseases. To test our hypothesis we utilized a bioinformatics approach to explore a publicly available microarray dataset including rheumatoid arthritis (RA), osteoarthritis (OA) and normal synovial tissue, then extended those findings in a new microarray dataset representing matched synovial, bone marrow and skin fibroblasts cultured from RA and OA patients undergoing arthroplasty. The classical fibroblast serum response programme discretely classified RA, OA and normal synovial tissues. Analysis of low and high serum treated fibroblast microarray data revealed a hierarchy of control, with anatomical site the most powerful classifier followed by response to serum and then disease. In contrast to skin and bone marrow fibroblasts, exposure of synovial fibroblasts to serum led to convergence of RA and OA expression profiles. Pathway analysis revealed three inter-linked gene networks characterising OA synovial fibroblasts: Cell remodelling through insulin-like growth factors, differentiation and angiogenesis through -3 integrin, and regulation of apoptosis through CD44. We have demonstrated that Fibroblast serum response signatures define disease at the tissue level, and that an OA specific, serum dependent repression of genes involved in cell adhesion, extracellular matrix remodelling and apoptosis is a critical discriminator between cultured OA and RA synovial fibroblasts

A programme theory for liaison mental health services in England

Background: Mechanisms by which liaison mental health services (LMHS) may bring about improved patient and organisational outcomes are poorly understood. A small number of logic models have been developed, but they fail to capture the complexity of clinical practice. Method: We synthesised data from a variety of sources including a large national survey, 73 in-depth interviews with acute and liaison staff working in hospitals with different types of liaison mental health services, and relevant local, national and international literature. We generated logic models for two common performance indicators used to assess organisational outcomes for LMHS: response times in the emergency department and hospital length of stay for people with mental health problems. Results: We identified 8 areas of complexity that influence performance, and 6 trade-offs which drove the models in different directions depending upon the balance of the trade-off. The logic models we developed could only be captured by consideration of more than one pass through the system, the complexity in which they operated, and the trade-offs that occurred. Conclusions: Our findings are important for commissioners of liaison services. Reliance on simple target setting may result in services that are unbalanced and not patient-centred. Targets need to be reviewed on a regular basis, together with other data that reflect the wider impact of the service, and any external changes in the system that affect the performance of LMHS, which are beyond their control