Patterns of symptoms possibly indicative of cancer and associated help-seeking behaviour in a large sample of United Kingdom residents - the USEFUL study

Background.Cancer awareness campaigns aim to increase awareness of the potential seriousness of signs and symptoms of cancer, and encourage their timely presentation to healthcare services. Enhanced understanding of the prevalence of symptoms possibly indicative of cancer in different population subgroups, and associated general practitioner (GP) help-seeking behaviour, will help to target cancer awareness campaigns more effectively.Aim.To determine: i) the prevalence of 21 symptoms possibly indicative of breast, colorectal, lung or upper gastrointestinal cancer in the United Kingdom (UK), including six ‘red flag’ symptoms; ii) whether the prevalence varies among population subgroups; iii) the proportion of symptoms self-reported as presented to GPs; iv) whether GP help-seeking behaviour varies within population subgroups.Methods.Self-completed questionnaire about experience of, and response to, 25 symptoms (including 21 possibly indicative of the four cancers of interest) in the previous month and year; sent to 50,000 adults aged 50 years or more and registered with 21 general practices in Staffordshire, England or across Scotland. Results.Completed questionnaires were received from 16,778 respondents (corrected response rate 34.2%). Almost half (45.8%) of respondents had experienced at least one symptom possibly indicative of cancer in the last month, and 58.5% in the last year. The prevalence of individual symptoms varied widely (e.g. in the last year between near zero% (vomiting up blood) and 15.0% (tired all the time). Red flag symptoms were uncommon. Female gender, inability to work because of illness, smoking, a history of a specified medical diagnosis, low social support and lower household income were consistently associated with experiencing at least one symptom possibly indicative of cancer in both the last month and year. The proportion of people who had contacted their GP about a symptom experienced in the last month varied between 8.1% (persistent cough) and 39.9% (unexplained weight loss); in the last year between 32.8% (hoarseness) and 85.4% (lump in breast). Nearly half of respondents experiencing at least one red flag symptom in the last year did not contact their GP about it. Females, those aged 80+ years, those unable to work because of illness, ex-smokers and those previously diagnosed with a specified condition were more likely to report a symptom possibly indicative of cancer to their GP; and those on high household income less likely.Conclusion.Symptoms possibly indicative of cancer are common among adults aged 50+ years in the UK, although they are not evenly distributed. Help-seeking responses to different symptoms also vary. Our results suggest important opportunities to provide more nuanced messaging and targeting of symptom-based cancer awareness campaigns

DOES NEURAL RESPONSE TO PARENTAL CRITICISM MEDIATE THE ASSOCIATION BETWEEN PARENTAL WARMTH AND ADOLESCENT DEPRESSION?

The risk for depression rises during adolescence, particularly in adolescents with a history of anxiety. Prior studies have shown that parenting factors, including warmth, indirectly affect depressive outcomes through their influence on adolescent development of emotion processing and regulation. Yet, it is not known whether the influences of parental warmth on depression are attributed to the effects of warmth on the functioning of underlying neural networks implicated in emotion processing and depression. Using a longitudinal and ecologically valid design, this study assessed whether the functioning of neural emotion processing and regulation networks in response to personalized parental criticism mediates the relationship between parental warmth and depressive symptoms in adolescents with a history of clinical anxiety. Parental criticism is considered a salient negative and socially relevant stimulus for adolescents, given the increased parent-child conflict during this period. 47 adolescents (M=13.43, SD=1.37) participated in a study assessing the effects of child anxiety treatment on the subsequent development of depressive symptoms. Immediately following anxiety treatment, adolescents and their parent participated in a worry discussion task. Observed positive and supportive parental affect was coded by trained observers. Adolescents also reported on perceptions of parental acceptance. Two years later, adolescents completed a functional neuroimaging assessment. During the neuroimaging task, adolescents were presented with auditory stimuli of pre-recorded parental criticism. Neutral, non-personalized statements were also presented. One year later, adolescents reported on depressive symptoms. Neither parental warmth assessed behaviorally nor using self-report were related to adolescent depressive symptoms three years later. After controlling for multiple comparisons, higher adolescent-reported perceptions of parental warmth predicted lower neural activation in response to criticism, compared to neutral statements, in the left amygdala, bilateral insula, subgenual anterior cingulate, dorsal anterior cingulate, and right ventrolateral prefrontal cortex. Mediation hypotheses were not supported. Findings suggest that when adolescents perceive their parents as warmer, their brains are less activated in response to criticism two years later, in both affective salience and emotion regulation networks. These results may indicate that warm and accepting parenting behavior plays a key role in shaping how the adolescent brain perceives threat within interpersonal contexts and regulates associated emotion

Evaluation of an Inexpensive Growth Medium for Direct Detection of Escherichia coli in Temperate and Sub-Tropical Waters

The cost and complexity of traditional methods for the detection of faecal indicator bacteria, including E. coli, hinder widespread monitoring of drinking water quality, especially in lowincome countries and outside controlled laboratory settings. In these settings the problem is exacerbated by the lack of inexpensive media for the detection of E. coli in drinking water. We developed a new low-cost growth medium, aquatest (AT), and validated its use for the direct detection of E. coli in temperate and sub-tropical drinking waters using IDEXX QuantiTray1. AT was compared with IDEXX Colilert-181 and either EC-MUG or MLSB for detecting low levels of E. coli from water samples from temperate (n = 140; Bristol, UK) and subtropical regions (n = 50, Pretoria/Tshwane, South Africa). Confirmatory testing (n = 418 and 588, respectively) and the comparison of quantitative results were used to assess performance. Sensitivity of AT was higher than Colilert-181 for water samples in the UK [98.0% vs. 86.9%; p<0.0001] and South Africa [99.5% vs. 93.2%; p = 0.0030]. There was no significant difference in specificity, which was high for both media (>95% in both settings). Quantitative results were comparable and within expected limits. AT is reliable and accurate for the detection of E. coli in temperate and subtropical drinking water. The composition of the new medium is reported herein and can be used freely

Secretome protein signature of human pancreatic cancer stem-like cells

Emerging research has demonstrated that pancreatic ductal adenocarcinoma (PDAC) contains a sub-population of cancer stem cells (CSCs) characterized by self-renewal, anchorage-independent-growth, long-term proliferation and chemoresistance. The secretome analysis of pancreatic CSCs has not yet been performed, although it may provide insight into tumour/microenvironment interactions and intracellular processes, as well as to identify potential biomarkers. To characterize the secreted proteins of pancreatic CSCs, we performed an iTRAQ-based proteomic analysis to compare the secretomes of Panc1 cancer stem-like cells (Panc1 CSCs) and parental cell line. A total of 72 proteins were found up-/down-regulated in the conditioned medium of Panc1 CSCs. The pathway analysis revealed modulation of vital physiological pathways including glycolysis, gluconeogenesis and pentose phosphate. Through ELISA immunoassays we analysed the presence of the three proteins most highly secreted by Panc1 CSCs (ceruloplasmin, galectin-3, and MARCKS) in sera of PDAC patient. ROC curve analysis suggests ceruloplasmin as promising marker for patients negative for CA19-9.Overall, our study provides a systemic secretome analysis of pancreatic CSCs revealing a number of secreted proteins which participate in pathological conditions including cancer differentiation, invasion and metastasis. They may serve as a valuable pool of proteins from which biomarkers and therapeutic targets can be identified. Biological significance: The secretome of CSCs is a rich reservoir of biomarkers of cancer progression and molecular therapeutic targets, and thus is a topic of great interest for cancer research. The secretome analysis of pancreatic CSCs has not yet been performed. Recently, our group has demonstrated that Panc-CSCs isolated from parental cell line by using the CSC selective medium, represent a model of great importance to deepen the understanding of the biology of pancreatic adenocarcinoma. To our knowledge, this is the first proteomic study of pancreatic CSC secretome. We performed an iTRAQ-based analysis to compare the secretomes of Panc1 CSCs and Panc1 parental cell line and identified a total of 43 proteins secreted at higher level by pancreatic cancer stem cells. We found modulation of different vital physiological pathways (such as glycolysis and gluconeogenesis, pentose phosphate pathway) and the involvement of CSC secreted proteins (for example 72 kDa type IV collagenase, galectin-3, alpha-actinin-4, and MARCKS) in pathological conditions including cancer differentiation, invasion and metastasis. By ELISA verification we found that MARCKS and ceruloplasmin discriminate between controls and PDAC patients; in addition ROC curve analyses indicate that MARCKS does not have diagnostic accuracy, while ceruloplasmin could be a promising marker only for patients negative for CA19-9.We think that the findings reported in our manuscript advance the understanding of the pathways implicated in tumourigenesis, metastasis and chemoresistance of pancreatic cancer, and also identify a pool of proteins from which novel candidate diagnostic and therapeutic biomarkers could be discovered

Narrative analysis of paradata from the Poverty in the UK survey: a worked example

This paper describes how a narrative analysis of survey paradata from Peter Townsend’s groundbreaking Poverty in the UK: A Survey of Household Resources and Standards of Living 1967-69 (PinUK) enabled us to address the following issues: • How the story of one household emerges from paradata in the PinUK survey. • How the story of the research relationship emerges through paradata. • How paradata reveal research practices

Malignant middle cerebral artery infarct: A clinical case report

Background:Ischaemic stroke accounts for 87% of strokes and occurs when a clot or a thrombus blocks a blood vessel, cutting off blood flow to a part of the brain. If large areas of brain are affected, space-occupying oedema may result, leading to rapid neurological deterioration, coma and death. Malignant middle cerebral artery infarction (MMCAI) is a life-threating ischaemic stroke involving the whole middle cerebral artery (MCA) territory and comprises up to 10% of MCA infarctions.Methods:We report the case of a 62 year old female ‘Mary’ who presented with a MMCAI together with a summary of the most recent and relevant evidence for treatment options in terms of survival and quality of life for her. We also focus on the vital role of the nurse in Mary’s care and treatment.Results:Intravenous thrombolysis and endovascular clot retrieval (ECR) during the hyperacute phase have been shown to improve outcomes but Mary did not meet the criteria for thrombolysis and received unsuccessful ECR. Her neurological condition deteriorated so she underwent surgical decompression, which is one of the major advances for MMCAI treatment together with expert neuro critical care nursing. Mary made a good functional recovery, returning home to live independently.Conclusion:This case highlights the need to consider all contextual and patient preferences in relation to treatment options. In addition the case emphases the vital role the neuro critical care nurse specialist plays in the complex assessment and treatment of this patient who experienced a MMCAI and underwent complex interventions

Relationship between symptoms, sociodemographic factors, and general practice help-seeking in 10 904 adults aged 50 and over

Symptoms are a common reason for contact with primary care. This study investigated associations between symptom-related, demographic, social, and economic factors on general practice (GP) help-seeking. Secondary analysis of responses to a 25-symptom questionnaire, from 10 904 adults aged ≥50 years reporting at least one symptom in the preceding year. Cluster analysis and univariable and multivariable logistic regressions explored associations between self-reported GP help-seeking, symptom-related factors, and respondent characteristics. Most respondents, 7638 (70%), reported more than one symptom in the preceding year. Ten symptom clusters were identified. Most included common symptoms like headache and back or joint pain. There were increased odds of help-seeking in females, those with poorer health status and those unable to work due to illness/disability when multiple symptoms were reported, but not when single symptoms were reported. Age and sex had variable effects on help-seeking, depending on the symptom. Reporting poorer health status, more comorbidities, and being unable to work due to illness or disability increased odds of help-seeking across a diverse variety of symptoms. Single people and those reporting lower social contact had lower odds of help-seeking for some symptoms. Being a current smoker reduced odds of help-seeking for persistent indigestion/heartburn, persistent cough, coughing up phlegm, and shortness of breath. Factors associated with self-reported help-seeking vary for different symptoms. Poorer health and adverse economic and social factors are associated with increased GP help-seeking. These wider determinants of health interact with symptom experiences and will influence GP workload.</p

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD

How does social context influence appraisal and help-seeking for potential cancer symptoms in adults aged 50 and over? A qualitative interview study

Objective: To investigate how social context and social network activation influence appraisal and help-seeking for symptoms potentially indicative of cancer. Methods: Semi-structured telephone interview study. Community dwelling adults who had experienced at least one symptom potentially indicative of cancer within the last month were sampled from a national symptom survey. Results: Thirty-four interviews were conducted. Participants looked to peers and wider society to judge whether symptoms might be normal for their age. Involvement of others in symptom appraisal promoted an active management strategy, such as contacting a healthcare professional or trying a medication. There were practical, emotional, attitudinal, normative and moral barriers to involving others. Cancer narratives from significant others, public health campaigns and the media influenced symptom appraisal. Participants held mental representations of types of people who get cancer, for example, smokers and unfit people. This had two consequences. First, participants did not identify themselves as a candidate for cancer; impeding help-seeking. Second, social judgements about lifestyle introduced stigma. Conclusion: Involving friends/family in symptom appraisal facilitates help-seeking but barriers exist to involving others. Campaigns to promote earlier cancer diagnosis should incorporate age-appropriate narratives, address misconceptions about ‘types’ of people who get cancer and tackle stigma about lifestyle factors.</p

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio