302 research outputs found

    Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

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    INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

    Novel genetic loci associated with hippocampal volume

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    The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg =-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness

    Pneumoconiosis from Agricultural Dust Exposure among Young California Farmworkers

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    BackgroundAgricultural workers are exposed to airborne pollutants, including organic and inorganic (mineral) dusts.ObjectivesLung autopsy specimens from consecutive coroner's cases of Hispanic males in Fresno County, California, (n = 112) were obtained to determine whether mineral dust exposure in agricultural work leads to pneumoconiosis.MethodsThe left lung was fixed by inflation. We evaluated airway and parenchymal pathology using standardized diagnostic criteria and semiquantitative grading schemata, including the grading of small airways for fibrosis and birefringent mineral dust particles. We analyzed lung dust burden on a subset of 37 lungs following bleach digestion, using scanning electron microscopy (SEM), X-ray spectrometry (XRS) and image analysis, and by X-ray diffraction for crystalline silica (CSi). Farmworkers comprised 51.5% and nonfarmworkers 48.5% of the samples.ResultsProximal airways demonstrated little mineral dust accumulation, but membranous and respiratory bronchioles had wall thickening, remodeling, and inflammation associated with carbonaceous and mineral dust deposition. These changes were independently associated with agricultural work, cigarette smoking, and increased age. Mineral dust small airways disease, pneumoconiosis (macules and nodules), and pathologic changes consistent with chronic bronchitis, emphysema, and interstitial fibrosis predominated in farmworkers compared with nonfarmworkers. CSi, determined gravimetrically, and aluminum silicate particles, determined by SEM/XRS, were increased in the lungs of farmworkers compared with nonfarmworkers and were significantly (p < 0.05) associated with small airway disease and pneumoconiosis.ConclusionMineral dust exposure is associated with increased small airway disease and pneumoconiosis among California farmworkers; however, the clinical significance and natural history of these changes remains to be determined

    Mobile Selves: Gender, ethnicity and mobile phones in the everyday lives of young Pakistani-British women and men

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    This paper focuses on mobile phone use by a young minority ethnic group as a medium through which to explore diversity and technology use in everyday life. Recent research with young people has shown that mobile phones are instrumentally, socially and emotionally important but few have problematized the homogeneous concept of 'youth'. This paper argues for increased recognition of the intersections of social categories such as youth, gender and ethnicity with technologies, specifically mobile phones, in order to understand complexity of use. Drawing on new empirical, qualitative data from an urban area in the North East of England we explore the focus group narratives of young Pakistani-British Muslim women and men focusing on the notion of 'shifting' gendered and cultural identities and social practices, developed and reworked in relation to the use of mobile phones. We look at the gendered dynamics of mobile use, including gender talk and text, and ask whether the young women and men experience mobiles differently in everyday life. We also explore the ways in which mobiles are used to create 'space of one's own' and the gendered dynamics of remaining connected, especially to key peer groups. The paper concludes with the assertion that in order to fully explore the mutability of youth cultures across space and time, we need to develop a more dynamic concept of 'mobile selves' by exploring the place and meaning of technologies such as mobile phones in the rich tapestries of young people's lives

    The perceived impact of location privacy: A web-based survey of public health perspectives and requirements in the UK and Canada

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    <p>Abstract</p> <p>Background</p> <p>The "place-consciousness" of public health professionals is on the rise as spatial analyses and Geographic Information Systems (GIS) are rapidly becoming key components of their toolbox. However, "place" is most useful at its most precise, granular scale – which increases identification risks, thereby clashing with privacy issues. This paper describes the views and requirements of public health professionals in Canada and the UK on privacy issues and spatial data, as collected through a web-based survey.</p> <p>Methods</p> <p>Perceptions on the impact of privacy were collected through a web-based survey administered between November 2006 and January 2007. The survey targeted government, non-government and academic GIS labs and research groups involved in public health, as well as public health units (Canada), ministries, and observatories (UK). Potential participants were invited to participate through personally addressed, standardised emails.</p> <p>Results</p> <p>Of 112 invitees in Canada and 75 in the UK, 66 and 28 participated in the survey, respectively. The completion proportion for Canada was 91%, and 86% for the UK. No response differences were observed between the two countries. Ninety three percent of participants indicated a requirement for personally identifiable data (PID) in their public health activities, including geographic information. Privacy was identified as an obstacle to public health practice by 71% of respondents. The overall self-rated median score for knowledge of privacy legislation and policies was 7 out of 10. Those who rated their knowledge of privacy as high (at the median or above) also rated it significantly more severe as an obstacle to research (<it>P </it>< 0.001). The most critical cause cited by participants in both countries was bureaucracy.</p> <p>Conclusion</p> <p>The clash between PID requirements – including granular geography – and limitations imposed by privacy and its associated bureaucracy require immediate attention and solutions, particularly given the increasing utilisation of GIS in public health. Solutions include harmonization of privacy legislation with public health requirements, bureaucratic simplification, increased multidisciplinary discourse, education, and development of toolsets, algorithms and guidelines for using and reporting on disaggregate data.</p

    Risky Bodies at Leisure: Young Women Negotiating Space and Place

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    This article explores constructions of risk and safety in the leisure lives of young women. Drawing upon qualitative data from two action research projects based in the north-east of England, we analyse the risk narratives of two groups of young women, one white and one South Asian, in order to ground theoretical perspectives on risk. Adopting an interdisciplinary approach, we address the ways in which risk emotions, risk calculations and management strategies are perceived as embodied, temporal and spatially located, arguing that risk is also deeply embedded in social and cultural discourses around female ‘respectability’. Young women share some common risk perceptions and experiences, in particular linked to male violence, many choosing to inhabit inside ‘safe’ spaces for leisure. What is also clear is that taking a risk can be a fun and desirable aspect of leisurely activity, ‘risky’ behaviour providing a way for young women to negotiate and contest dominant discourses around feminine, cultural identities
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