Implications of a RAD54L polymorphism (2290C/T) in human meningiomas as a risk factor and/or a genetic marker

BACKGROUND: RAD54L (OMIM 603615, Locus Link 8438) has been proposed as a candidate oncosupressor in tumours bearing a non-random deletion of 1p32, such as breast or colon carcinomas, lymphomas and meningiomas. In a search for RAD54L mutations in 29 menigiomas with allelic deletions in 1p, the only genetic change observed was a silent C/T transition at nucleotide 2290 in exon 18. In this communication the possible association of the 2290C/T polymorphism with the risk of meningiomas was examined. In addition, the usefulness of this polymorphism as a genetic marker within the meningioma consensus deletion region in 1p32 was also verified. The present study comprises 287 blood control samples and 70 meningiomas from Spain and Ecuador. Matched blood samples were only available from Spanish patients. RESULTS: The frequency of the rare allele-T and heterozygotes for the 2290C/T polymorphism in the blood of Spanish meningioma patients and in the Ecuadorian meningioma tumours was higher than in the control population (P < 0.05). Four other rare variants (2290C/G, 2299C/G, 2313G/A, 2344A/G) were found within 50 bp at the 3' end of RAD54L. Frequent loss of heterozygosity for the 2290C/T SNP in meningiomas allowed to further narrow the 1p32 consensus region of deletion in meningiomas to either 2.08 Mbp – within D1S2713 (44.35 Mbp) and RAD54L (46.43 Mbp) – or to 1.47 Mbp – within RAD54L and D1S2134 (47.90 Mbp) – according to recent gene mapping results. CONCLUSION: The statistical analysis of genotypes at the 2290C/T polymorphism suggest an association between the rare T allele and the development of meningeal tumours. This polymorphism can be used as a genetic marker inside the consensus deletion region at 1p32 in meningiomas

Financial control, blame avoidance and Radio Caroline: Talkin’ ‘bout my generation

This research examines the use of financial mechanisms that simultaneously impose controls and facilitate blame avoidance by public office-holders. A qualitative historical examination is used to examine legislation designed to prevent Radio Caroline, a pirate radio station, from broadcasting into Britain in the 1960s. Radio Caroline made a mockery of the British Government’s power to manage radio through a monopolist, the British Broadcasting Corporation. In addition, Radio Caroline played the type of rock music the British Government sought to suppress as representing the undesirable side of youth culture. This research examines the suppression of Radio Caroline through the Marine & Broadcasting (Offences) Act (UK) 1967 and the legislative scapegoating of Radio Caroline by targeting its revenue-earning potential. Inter-generational conflict underpinned the legislative scapegoating of Radio Caroline. This research demonstrates how financial controls can mask scapegoating and blame avoidance strategies by governments

Screening for multi-drug-resistant Gram-negative bacteria: what is effective and justifiable?

Effectiveness is a key criterion in assessing the justification of antibiotic resistance interventions. Depending on an intervention's effectiveness, burdens and costs will be more or less justified, which is especially important for large scale population-level interventions with high running costs and pronounced risks to individuals in terms of wellbeing, integrity and autonomy. In this paper, we assess the case of routine hospital screening for multi-drug-resistant Gram-negative bacteria (MDRGN) from this perspective. Utilizing a comparison to screening programs for Methicillin-Resistant Staphylococcus aureus (MRSA) we argue that current screening programmes for MDRGN in low endemic settings should be reconsidered, as its effectiveness is in doubt, while general downsides to screening programs remain. To accomplish justifiable antibiotic stewardship, MDRGN screening should not be viewed as a separate measure, but rather as part of a comprehensive approach. The program should be redesigned to focus on those at risk of developing symptomatic infections with MDRGN rather than merely detecting those colonised

Prognostic significance of fascin expression in advanced colorectal cancer: an immunohistochemical study of colorectal adenomas and adenocarcinomas

BACKGROUND: Fascin is an actin bundling protein with roles in the formation of cell protrusions and motility of mesenchymal and neuronal cells. Fascin is normally low or absent from epithelia, but is upregulated in several epithelial neoplasms where it may contribute to an invasive phenotype. Here, we report on the prevalence and potential clinical significance of fascin expression in relation to the progression of colorectal adenocarcinoma and to tumor cell proliferation as measured by Ki67 index. METHODS: Conventional tissue sections of 107 colorectal adenomas and 35 adenocarcinomas were analyzed by immunohistochemistry for fascin and Ki67 expression. Fascin expression and Ki67 proliferation index were also investigated by use of a tissue microarray containing cores from a further 158 colorectal adenocarcinomas and 15 adenomas linked to a CCF, IRB-approved database with a mean of 38 months of clinical follow-up. Survival analysis was carried out by the Kaplan-Meier and Cox regression methods. RESULTS: Fascin was not expressed by the normal colonic epithelium. In conventional sections, 16% of adenomas and 26% of adenocarcinomas showed fascin expression in greater than 10% of the tumor cells. In the clinically-annotated tumors, fascin immunoreactivity was more common in tumors located in the proximal colon (p = 0.009), but was not associated with age, gender, or TNM stage. Patients with stage III/IV adenocarcinomas (n = 62) with strong fascin immunoreactivity had a worse prognosis than patients with low or absent fascin, (3-year overall survival of 11% versus 43% for fascin-negative patients; p = 0.023). In adenomas, fascin and Ki67 tended to be inversely correlated at the cellular level; this trend was less apparent in adenocarcinomas. CONCLUSION: Fascin is upregulated in a proportion of adenomas, where its expression is often focal. Strong and diffuse expression was seen in a subset of advanced colorectal adenocarcinomas that correlated with shorter survival in stage III and IV patients. Fascin may have prognostic value as an early biomarker for more aggressive colorectal adenocarcinomas

Individual and contextual covariates of burnout: a cross-sectional nationwide study of French teachers

<p>Abstract</p> <p>Background</p> <p>Limited information on the covariates of burnout syndrome in French teachers is available. The aim of this study was to evaluate the relative contributions of individual and contextual factors on the three burnout dimensions: emotional exhaustion, depersonalization, and reduced personal accomplishment.</p> <p>Methods</p> <p>The source data come from an epidemiological postal survey on physical and mental health conducted in 2005 among 20,099 education workers (in activity or retired) selected at random from the health plan records of the national education system. The response rate was 52.4%. Teachers in activity currently giving classes to students who participated in the survey (n = 3,940) were invited to complete a self-administered questionnaire including the Maslach Burnout Inventory. 2,558 teachers provided complete data (64.9%). Variables associated with high emotional exhaustion (highest quartile of score), high depersonalization (highest quartile), and reduced personal accomplishment (lowest quartile) were evaluated using multivariate logistic regression. Studied variables referred to demographic characteristics, socio-professional environment, job dissatisfaction, experienced difficulties at work, and teaching motivations.</p> <p>Results</p> <p>Different variables were associated with each burnout dimension. Female teachers were more susceptible to high emotional exhaustion and reduced personal accomplishment, whereas male teachers were more susceptible to high depersonalization. Elementary school teachers were more susceptible to high emotional exhaustion, but less susceptible to high depersonalization and reduced personal accomplishment than their higher school level counterparts. Experienced difficulties with pupils were associated with all three dimensions. A socio-economically underprivileged school neighbourhood was also related to high emotional exhaustion and high depersonalization.</p> <p>Conclusion</p> <p>Programs to enhance teaching environment might be an interesting approach to try to prevent burnout. It would be useful to take the different dimensions into account in planning the intervention.</p

Inspired or foolhardy: sensemaking, confidence and entrepreneurs' decision-making.

The purpose of this paper is to investigate the role of confidence in how both new and experienced entrepreneurs interpret and make sense of their business environment to inform decision-making. We illustrate our conceptual arguments with descriptive results from a large-scale (n = 6289) survey on entrepreneurs' perception of business performance and their decisions taken at a time of uncertainty in an economic downturn. Quantitative findings are stratified along experiential lines to explore heterogeneity in entrepreneurial decision-making and directly inform our conceptual arguments, while qualitative data from open questions are used to explain the role of confidence. Newer entrepreneurs are found to be more optimistic in the face of environmental risk, which impacts on their decision-making and innovative capabilities. However, the more experienced entrepreneurs warily maintain margin and restructure to adapt to environmental changes. Instead of looking directly at the confidence of individuals, we show how confidence impacts sensemaking, and ultimately, decision-making. These insights inform research on the behaviour of novice and experienced entrepreneurs in relation to innovative business activities. Specifically, blanket assumptions on the role of confidence may be misplaced as its impact changes with experience to alter how entrepreneurs make sense of their environment

Prevalence, associated factors and predictors of anxiety: a community survey in Selangor, Malaysia

Background: Anxiety is the most common mental health disorders in the general population. This study aimed to determine the prevalence of anxiety, its associated factors and the predictors of anxiety among adults in the community of Selangor, Malaysia. Methods: A cross sectional study was carried out in three districts in Selangor, Malaysia. The inclusion criteria of this study were Malaysian citizens, adults aged 18 years and above, and living in the selected living quarters based on the list provided by the Department of Statistics Malaysia (DOS). Participants completed a set of questionnaires, including the validated Malay version of Generalized Anxiety Disorder 7 (GAD 7) to detect anxiety. Results: Of the 2512 participants who were approached, 1556 of them participated in the study (61.90 %). Based on the cut-off point of 8 and above in the GAD-7, the prevalence of anxiety was 8.2 %. Based on the initial multiple logistic regression analysis, the predictors of anxiety were depression, serious problems at work, domestic violence and high perceived stress. When reanalyzed again after removing depression, low self-esteem and high perceived stress, six predictors that were identified are cancer, serious problems at work, domestic violence, unhappy relationship with family, non-organizational religious activity and intrinsic religiosity. Conclusion: This study reports the prevalence of anxiety among adults in the community of Selangor, Malaysia and also the magnitude of the associations between various factors and anxiety

Genome-wide association studies of cancer: current insights and future perspectives.

Genome-wide association studies (GWAS) provide an agnostic approach for investigating the genetic basis of complex diseases. In oncology, GWAS of nearly all common malignancies have been performed, and over 450 genetic variants associated with increased risks have been identified. As well as revealing novel pathways important in carcinogenesis, these studies have shown that common genetic variation contributes substantially to the heritable risk of many common cancers. The clinical application of GWAS is starting to provide opportunities for drug discovery and repositioning as well as for cancer prevention. However, deciphering the functional and biological basis of associations is challenging and is in part a barrier to fully unlocking the potential of GWAS