Cancer symptom awareness and barriers to symptomatic presentation in England – Are we clear on cancer?

Background: Low cancer awareness may contribute to delayed diagnosis and poor cancer survival. We aimed to quantify socio-demographic differences in cancer symptom awareness and barriers to symptomatic presentation in the English population. Methods: Using a uniquely large data set (n=49?270), we examined the association of cancer symptom awareness and barriers to presentation with age, gender, marital status and socio-economic position (SEP), using logistic regression models to control for confounders. Results: The youngest and oldest, the single and participants with the lowest SEP recognised the fewest cancer symptoms, and reported most barriers to presentation. Recognition of nine common cancer symptoms was significantly lower, and embarrassment, fear and difficulties in arranging transport to the doctor’s surgery were significantly more common in participants living in the most deprived areas than in the most affluent areas. Women were significantly more likely than men to both recognise common cancer symptoms and to report barriers. Women were much more likely compared with men to report that fear would put them off from going to the doctor. Conclusions: Large and robust socio-demographic differences in recognition of some cancer symptoms, and perception of some barriers to presentation, highlight the need for targeted campaigns to encourage early presentation and improve cancer outcomes

Complex circular subsidence structures in tephra deposited on large blocks of ice: Varða tuff cone, Öræfajökull, Iceland

Several broadly circular structures up to 16 m in diameter, into which higher strata have sagged and locally collapsed, are present in a tephra outcrop on southwest Öræfajökull, southern Iceland. The tephra was sourced in a nearby basaltic tuff cone at Varða. The structures have not previously been described in tuff cones, and they probably formed by the melting out of large buried blocks of ice emplaced during a preceding jökulhlaup that may have been triggered by a subglacial eruption within the Öræfajökull ice cap. They are named ice-melt subsidence structures, and they are analogous to kettle holes that are commonly found in proglacial sandurs and some lahars sourced in ice-clad volcanoes. The internal structure is better exposed in the Varða examples because of an absence of fluvial infilling and reworking, and erosion of the outcrop to reveal the deeper geometry. The ice-melt subsidence structures at Varða are a proxy for buried ice. They are the only known evidence for a subglacial eruption and associated jökulhlaup that created the ice blocks. The recognition of such structures elsewhere will be useful in reconstructing more complete regional volcanic histories as well as for identifying ice-proximal settings during palaeoenvironmental investigations

Which symptoms are linked to a delayed presentation among melanoma patients? A retrospective study

Background: The incidence of melanoma is rising. Early detection is associated with a more favourable outcome. The factors that influence the timing of a patient’s presentation for medical assessment are not fully understood. The aims of the study were to measure the nature and duration of melanoma symptoms in a group of patients diagnosed with melanoma within the preceding 18 months and to identify the symptoms and barriers associated with a delay in presentation. Methods: A questionnaire was distributed to a random sample of 200 of the 963 melanoma patients who had participated in the Cancer Patient Experience Survey 2010 and were known to be alive 1 year later. Data were collected on symptoms, duration of symptoms prior to presentation and the reasons for not attending a doctor sooner. Results: A total of 159 patients responded to the questionnaire; 74 (47%) were men; mean age was 62 (range 24–90) years. Of the 149 patients who reported a symptom, 40 (27%) had a delayed presentation (i.e. >3 months). A mole growing bigger was the most common symptom and reporting this symptom was significantly associated with a delayed presentation (odds ratio (OR) 2.04, 95% confidence interval (95% CI) 1.14–5.08). Patients aged ≥65 years were less likely to report a barrier to presentation and were less likely to delay than those under 40, although this was of borderline statistical significance (OR 0.28, 95% CI 0.08–1.00). Conclusions: This study highlights that an enlarging mole is a significant symptom influencing the timing of presentation. Increasing public awareness of the signs of melanoma and of the importance of early presentation is desirable. Health professionals should take advantage of the opportunity to educate patients on such symptoms and signs where feasible. Further exploration of the barriers to presentation in younger people should be considered

Deriving a mutation index of carcinogenicity using protein structure and protein interfaces

With the advent of Next Generation Sequencing the identification of mutations in the genomes of healthy and diseased tissues has become commonplace. While much progress has been made to elucidate the aetiology of disease processes in cancer, the contributions to disease that many individual mutations make remain to be characterised and their downstream consequences on cancer phenotypes remain to be understood. Missense mutations commonly occur in cancers and their consequences remain challenging to predict. However, this knowledge is becoming more vital, for both assessing disease progression and for stratifying drug treatment regimes. Coupled with structural data, comprehensive genomic databases of mutations such as the 1000 Genomes project and COSMIC give an opportunity to investigate general principles of how cancer mutations disrupt proteins and their interactions at the molecular and network level. We describe a comprehensive comparison of cancer and neutral missense mutations; by combining features derived from structural and interface properties we have developed a carcinogenicity predictor, InCa (Index of Carcinogenicity). Upon comparison with other methods, we observe that InCa can predict mutations that might not be detected by other methods. We also discuss general limitations shared by all predictors that attempt to predict driver mutations and discuss how this could impact high-throughput predictions. A web interface to a server implementation is publicly available at http://inca.icr.ac.uk/

Magnetic resonance imaging protocols for paediatric neuroradiology

Increasingly, radiologists are encouraged to have protocols for all imaging studies and to include imaging guidelines in care pathways set up by the referring clinicians. This is particularly advantageous in MRI where magnet time is limited and a radiologist’s review of each patient’s images often results in additional sequences and longer scanning times without the advantage of improvement in diagnostic ability. The difficulties of imaging small children and the challenges presented to the radiologist as the brain develops are discussed. We present our protocols for imaging the brain and spine of children based on 20 years experience of paediatric neurological MRI. The protocols are adapted to suit children under the age of 2 years, small body parts and paediatric clinical scenarios

COSMIC 2005

The Catalogue Of Somatic Mutations In Cancer (COSMIC) database and web site was developed to preserve somatic mutation data and share it with the community. Over the past 25 years, approximately 350 cancer genes have been identified, of which 311 are somatically mutated. COSMIC has been expanded and now holds data previously reported in the scientific literature for 28 known cancer genes. In addition, there is data from the systematic sequencing of 518 protein kinase genes. The total gene count in COSMIC stands at 538; 25 have a mutation frequency above 5% in one or more tumour type, no mutations were found in 333 genes and 180 are rarely mutated with frequencies <5% in any tumour set. The COSMIC web site has been expanded to give more views and summaries of the data and provide faster query routes and downloads. In addition, there is a new section describing mutations found through a screen of known cancer genes in 728 cancer cell lines including the NCI-60 set of cancer cell lines

Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

Maternal Psychosocial Stress during Pregnancy and Placenta Weight: Evidence from a National Cohort Study

To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming.; We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N?=?78,017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0-18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10(-3); B, 14.33; CI, 10.12-18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth.; Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Management practices for control of ragwort species

The ragwort species common or tansy ragwort (Jacobaea vulgaris, formerly Senecio jacobaea), marsh ragwort (S. aquaticus), Oxford ragwort (S. squalidus) and hoary ragwort (S. erucifolius) are native in Europe, but invaded North America, Australia and New Zealand as weeds. The abundance of ragwort species is increasing in west-and central Europe. Ragwort species contain different groups of secondary plant compounds defending them against generalist herbivores, contributing to their success as weeds. They are mainly known for containing pyrrolizidine alkaloids, which are toxic to grazing cattle and other livestock causing considerable losses to agricultural revenue. Consequently, control of ragwort is obligatory by law in the UK, Ireland and Australia. Commonly used management practices to control ragwort include mechanical removal, grazing, pasture management, biological control and chemical control. In this review the biology of ragwort species is shortly described and the different management practices are discussed