97 research outputs found

    Detection of ctDNA in plasma of patients with clinically localised prostate cancer is associated with rapid disease progression.

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    BACKGROUND DNA originating from degenerate tumour cells can be detected in the circulation in many tumour types, where it can be used as a marker of disease burden as well as to monitor treatment response. Although circulating tumour DNA (ctDNA) measurement has prognostic/predictive value in metastatic prostate cancer, its utility in localised disease is unknown. METHODS We performed whole-genome sequencing of tumour-normal pairs in eight patients with clinically localised disease undergoing prostatectomy, identifying high confidence genomic aberrations. A bespoke DNA capture and amplification panel against the highest prevalence, highest confidence aberrations for each individual was designed and used to interrogate ctDNA isolated from plasma prospectively obtained pre- and post- (24 h and 6 weeks) surgery. In a separate cohort (n = 189), we identified the presence of ctDNA TP53 mutations in preoperative plasma in a retrospective cohort and determined its association with biochemical- and metastasis-free survival. RESULTS Tumour variants in ctDNA were positively identified pre-treatment in two of eight patients, which in both cases remained detectable postoperatively. Patients with tumour variants in ctDNA had extremely rapid disease recurrence and progression compared to those where variants could not be detected. In terms of aberrations targeted, single nucleotide and structural variants outperformed indels and copy number aberrations. Detection of ctDNA TP53 mutations was associated with a significantly shorter metastasis-free survival (6.2 vs. 9.5 years (HR 2.4; 95% CIs 1.2-4.8, p = 0.014). CONCLUSIONS CtDNA is uncommonly detected in localised prostate cancer, but its presence portends more rapidly progressive disease

    Teaching Writing: a situated dynamic

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    publication-status: Publishedtypes: ArticleThe paper is theoretically grounded in Cultural Historical Activity Theory (CHAT) which holds that human development is founded within participation in social and cultural practices. In particular, the teaching of literacy is shaped not only by the curriculum as designated by policy makers and the institution in which it is located but also by the individuals’ understanding of what literacy and learning involves and how they act to achieve their goals. The paper explores data from a project that investigated the relationship between classroom talk and the teaching of writing in six early years classrooms. Participants’ own understandings of teaching and learning need to be taken into account by researchers and policy makers. CHAT has been used to explore the dynamic relationship between activity at societal, institutional and individual levels. It is argued that researchers and policy makers need to take account of the wider socio-cultural context in planning and evaluating curriculum development initiatives

    A Greater Means to the Greater Good: Ethical Guidelines to Meet Social Movement Organization Advocacy Challenges

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    Existing public relations ethics literature often proves inadequate when applied to social movement campaigns, considering the special communication challenges activists face as marginalized moral visionaries in a commercial public sphere. The communications of counter-hegemonic movements is distinct enough from corporate, nonprofit, and governmental organizations to warrant its own ethical guidelines. The unique communication guidelines most relevant to social movement organizations include promoting asymmetrical advocacy to a greater extent than is required for more powerful organizations and building flexibility into the TARES principles to privilege social responsibility over respect for audience values in activist campaigns serving as ideological critique

    Effectiveness of screening preschool children for amblyopia: a systematic review

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    <p>Abstract</p> <p>Background</p> <p>Amblyopia and amblyogenic factors like strabismus and refractive errors are the most common vision disorders in children. Although different studies suggest that preschool vision screening is associated with a reduced prevalence rate of amblyopia, the value of these programmes is the subject of a continuing scientific and health policy discussion. Therefore, this systematic review focuses on the question of whether screening for amblyopia in children up to the age of six years leads to better vision outcomes.</p> <p>Methods</p> <p>Ten bibliographic databases were searched for randomised controlled trials, non-randomised controlled trials and cohort studies with no limitations to a specific year of publication and language. The searches were supplemented by handsearching the bibliographies of included studies and reviews to identify articles not captured through our main search strategy.</p> <p>Results</p> <p>Five studies met the inclusion criteria. Of these, three studies suggested that screening is associated with an absolute reduction in the prevalence of amblyopia between 0.9% and 1.6% (relative reduction: between 45% and 62%). However, the studies showed weaknesses, limiting the validity and reliability of their findings. The main limitation was that studies with significant results considered only a proportion of the originally recruited children in their analysis. On the other hand, retrospective sample size calculation indicated that the power based on the cohort size was not sufficient to detect small changes between the groups. Outcome parameters such as quality of life or adverse effects of screening have not been adequately investigated in the literature currently available.</p> <p>Conclusion</p> <p>Population based preschool vision screening programmes cannot be sufficiently assessed by the literature currently available. However, it is most likely that the present systematic review contains the most detailed description of the main limitations in current available literature evaluating these programmes. Therefore, future research work should be guided by the findings of this publication.</p

    Doctors under the microscope: the birth of medical audit

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    In 1989 a UK government White Paper introduced medical audit as a comprehensive and statutory system of assessment and improvement in quality of care in hospitals. A considerable body of research has described the evolution of medical audit in terms of a struggle between doctors and National Health Service managers over control of quality assurance. In this paper we examine the emergence of medical audit from 1910 to the early 1950s, with a particular focus on the pioneering work of the American surgeons Codman, MacEachern and Ponton. It is contended that medical professionals initially created medical audit in order to articulate a suitable methodology for assessing individual and organisational performance. Rather than a means of protecting the medical profession from public scrutiny, medical auditing was conceived and operationalised as a managerial tool for fostering the active engagement of senior hospital managers and discharging public accountability. These early debates reveal how accounting was implicated in the development of a system for monitoring and improving the work of medical professionals, advancing the quality of hospital care, and was advocated in ways, which included rather than excluded managers

    A Reaction-Diffusion Model to Capture Disparity Selectivity in Primary Visual Cortex

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    Decades of experimental studies are available on disparity selective cells in visual cortex of macaque and cat. Recently, local disparity map for iso-orientation sites for near-vertical edge preference is reported in area 18 of cat visual cortex. No experiment is yet reported on complete disparity map in V1. Disparity map for layer IV in V1 can provide insight into how disparity selective complex cell receptive field is organized from simple cell subunits. Though substantial amounts of experimental data on disparity selective cells is available, no model on receptive field development of such cells or disparity map development exists in literature. We model disparity selectivity in layer IV of cat V1 using a reaction-diffusion two-eye paradigm. In this model, the wiring between LGN and cortical layer IV is determined by resource an LGN cell has for supporting connections to cortical cells and competition for target space in layer IV. While competing for target space, the same type of LGN cells, irrespective of whether it belongs to left-eye-specific or right-eye-specific LGN layer, cooperate with each other while trying to push off the other type. Our model captures realistic 2D disparity selective simple cell receptive fields, their response properties and disparity map along with orientation and ocular dominance maps. There is lack of correlation between ocular dominance and disparity selectivity at the cell population level. At the map level, disparity selectivity topography is not random but weakly clustered for similar preferred disparities. This is similar to the experimental result reported for macaque. The details of weakly clustered disparity selectivity map in V1 indicate two types of complex cell receptive field organization
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