153 research outputs found
Assessing cognitive toxicity in early Phase Trials ‐ what are we missing?
No full textObjectives: novel therapies, such as, small protein molecule inhibitors and immunotherapies are first tested clinically in Phase I trials. Moving on to later phase trials and ultimately standard practice. A key aim of these early clinical trials is to define a toxicity profile; however, the emphasis is often on safety. The concern is cognitive toxicity is poorly studied in this context and may be under-reported. The aim of this review is to map evidence of cognitive assessment, toxicity, and confounding factors within reports from Phase I trials and consider putative mechanisms of impairment aligned with mechanisms of novel therapies. Methods: a scoping review methodology was applied to the search of databases, including Embase, MEDLINE, Clinicaltrials.gov. A [keyword search was conducted, results screened for duplication then inclusion/exclusion criteria applied. Articles were further screened for relevance; data organised into categories and charted in a tabular format]. Evidence was collated and summarised into a narrative synthesis. Results: despite the availability of robust ways to assess cognitive function, these are not routinely included in the conduct of early clinical trials. Reports of cognitive toxicity in early Phase I trials are limited and available evidence on this shows that a proportion of patients experience impaired cognitive function over the course of participating in a Phase I trial. Links are identified between the targeted action of some novel therapies and putative mechanisms of cognitive impairment. Conclusion: the review provides rationale for research investigating cognitive function in this context. A study exploring the cognitive function of patients on Phase I trials and the feasibility of formally assessing this within early clinical trials is currently underway at the Royal Marsden.</p
What is the impact of targeted therapies given within phase I trials on the cognitive function of patients with advanced cancer: a mixed-methods exploratory study conducted in an early clinical trials unit
No full textIntroduction Novel therapies such as small protein molecule inhibitors and immunotherapies are tested in early phase trials before moving to later phase trials and ultimately standard practice. A key aim of these clinical trials is to define a toxicity profile, however, the emphasis is often on safety with measurements of organ toxicity. Other subjective side effects can be under-reported because they are not measured formally within the trial protocols. The concern from clinical practice is that cognitive toxicity is poorly studied and may be under-reported in this context. This could lead to toxicity profiles of new treatments not being fully described and patients with unmet need in terms of acknowledgement and support of symptoms. This protocol outlines a framework of an exploratory study with feasibility aspects to investigate the impact and experience of cognitive changes for patients on phase I trials. Methods and analysis This is a mixed-methods study, combining quantitative and qualitative approaches. The sample is 30 patients with advanced cancer who are participating in phase I trials of novel therapies in the early clinical trials unit of a specialist cancer centre. A test battery of validated cognitive assessments will be taken alongside patient reported outcome measures at three time points from baseline, day eight and day 28 post start of treatment. At day 28, a semi-structured interview will be conducted and the narrative thematically analysed. Results will be integrated to offer a comprehensive description of cognitive function in this patient group. Ethics and dissemination The study has received full HRA and ethical approval. It is the first study to introduce formal cognitive assessments in a cancer phase I trial context. The study has the potential to highlight previously unreported side effects and more importantly unmet need in terms of care for patients who are participating in the trials.</p
Self-consciousness and the image of self in the poetry of Stephen Spender, 1928 to 1934
No full textThe purpose of this thesis is twofold. First, to demonstrate the value and significance of Spender's early poetry in terms of its vision and technique. Through a series of close readings the thesis traces the ways in which Spender's early poetry not only shows itself to be self-conscious but also manipulates images of self. Presenting images of self, Spender achieves a balance between engagement with and distance from the self, and the reader shares in the process of poetic self-awareness. Secondly, to demonstrate the broader value of the poetry. Spender's poetry presents a distinctive exploration of the possibilities of self in relation to the external world. The resolution of Spender’s questioning and selection of both personal and public values, rooted in his contemporary situation and private circumstances, in his poetry takes the form less of historical document than of human record. The period on which I focus, 1928 to 1934, represents Spender’s first, and arguably most significant, poetic phase. The thesis is specifically concerned with four texts: Nine Experiments. Spender's contributions to Oxford Poetry (1929 and 1930), Twenty Poems and Poems (1933 and 1934). Nine Experiments marks the beginning of a particular approach and lyric style which finds its culmination in Poems (1933 and 1934). The earliest poetry is interesting largely insofar as it looks forward to later themes and techniques. In Nine Experiments and Oxford Poetry (1929 and 1930) we see Spender's often successful struggle to achieve effective forms in which to explore issues of self and value. Twenty Poems and Poems (1933 and 1934) concentrate on themes of love and friendship and the pressure on the poet of the contemporary political scene. The poetry does not reconcile the demands of the external, public world with his inner desires and aspirations, but presents a series of fascinatingly unresolved tensions. The thesis explores the way these poems strive for certainty. This striving stems from the tension between Spender's desire to politicize poetry and his tendency to the lyrical, personal statement
“A TRUE AND BROAD SYMPATHY:” THOMAS HUGHES, MEDIEVALISM, AND SOCIAL JUSTICE IN THE NINETEENTH CENTURY
No full textThomas Hughes, author of Tom Brown’s Schooldays (1857), used medievalism to help solve social problems of the Nineteenth Century. This contravenes the traditional view of medievalism, especially Anglo-Saxonism, since others have used it to justify the subjugation of people of lower social status, namely the poor in England, enslaved African Americans in the United States, and Indians under British rule.
While the use of medievalism is veiled in Hughes’ work, the subtext of Tom Brown’s Schooldays demonstrated Hughes’ Anglo-Saxonism. Tom Brown and the intertextual material surrounding his narrative exhibit the characteristics of Anglo-Saxonism through cultural primitivism, the concept of allodial, and anti-Norman sentiment.
Beyond this, Hughes viewed American slavery as similar to Anglo-Saxon slavery, which made it the responsibility of every man and government to free the enslaved. Because of this, Hughes was a fervent abolitionist, as can be seen in Hughes’ book on Alfred the Great, indicating that Hughes’s abolitionism was part of a larger period of rapid change in nineteenth-century English, anti-slavery sentiment, and Hughes was at the forefront.
Hughes also used medievalism for the benefit of English people, using it to solve social problems through medieval history. His book, Tom Brown at Oxford, in particular, acts as medievalesque Christian Socialist propaganda. Although his role as a Christian Socialist has been minimized by scholars, Hughes acted to support the working class through literature, popular elections, legislative changes, legal arbitrations for cooperative ventures, and efforts with the Working Men’s College over the 1860s and 1870s, signifying that the Christian Socialist Movement did not collapse in the 1850s.
This Christian Socialist belief travelled to India when Hughes’ friend and fellow Christian Socialist, Lord Ripon, was made Viceroy of India. Hughes viewed Indian subjugation as a form of slavery, though he approved of imperialism. Imperialism allowed men to show their manliness while improving their social station by military service. He argued that military service in India was a sort of righteous fight in which men could find honor. He described English, imperialist heroes in terms of medieval gallantry. He maintained that White men were socially superior to Indian men, while simultaneously believing that Indian men could improve themselves enough for self-rule. Once Ripon went to India, Hughes was bound by friendship and abolitionist zeal to advocate for Indians in Parliament and support Ripon
Remarks on the minimal genus of curves linearly moving on a surface
No full textGiven a smooth, irreducible, projective surface , let be the
minimum geometric genus of an irreducible curve that moves in a linear system
of positive dimension on . We determine the value of this birational
invariant for a general surface of degree in and give a bound
for if is a general polarised K3 or abelian surface. As soon as this
note appeared on the math arxiv, David Stapleton kindly pointed out to the
author a paper by Ein and Lazarsfeld, in which in turn a paper by Konno was
cited. Unfortunately the author was not aware of these two papers which contain
results that strictly include the ones of this note. The author is very
grateful to David Stapleton
Insights into the experiences of patients with cancer in London: framework analysis of free-text data from the National Cancer Patient Experience Survey 2012/2013 from the two London Integrated Cancer Systems
No full textObjectiveTo shed light on experiences of patients with cancer in London National Health Service (NHS) trusts that may not be fully captured in national survey data, to inform improvement action plans by these trusts.DesignFramework analysis of free-text data from 2012/2013 National Cancer Patient Experience Survey (NCPES) from the 2 London Integrated Cancer Systems.Setting and participantsPatients with a cancer diagnosis treated by the NHS across 27 trusts in London.Main outcome measuresFree-text data received from patients categorised into what patients found good about their cancer care and what could be improved.MethodsUsing Framework analysis, a thematic framework was created for 15?403 comments from over 6500 patients. Themes were identified across the London data set, by tumour group and by trust.ResultsTwo-thirds of free-text comments from patients in London were positive and one-third of those related to the good quality of care those patients received. However, the majority of comments for improvement related to quality of care, with a focus on poor care, poor communication and waiting times in outpatient departments. Additionally, 577 patients (9% of those who returned free-text data in London) commented on issues pertaining to the questionnaire itself. Some patients who experienced care from multiple trusts were unclear on how to complete the questionnaire for the single trust whose care they were asked to comment on, others said the questions did not fit their experiences.ConclusionsNCPES free-text analysis can shed light on the experiences of patients that closed questions might not reveal. It further indicates that there are issues with the survey itself, in terms of ambiguities in the questionnaire and difficulties in identifying patients within specific trusts. Both of these issues have the potential to contribute to knowledge and understanding of the uses and limitations of free-text data in improving cancer services
Gender, Faculty Status, and Discipline as Predictors of Teaching in Higher Education during the COVID-19 Pandemic
No full textThe COVID-19 pandemic has significantly changed the way of life for people and businesses around the world. Institutions of higher education and their constituents are no exception. As the pandemic began, colleges and universities moved their operations and teaching modalities online. The emergency shift to remote learning and operating has put a strain on higher education students, faculty, staff, and administrators. The influence of the pandemic has highlighted some vulnerabilities and areas of needed support within specific categories of faculty, which should continue to be explored and better addressed. This quantitative study uses a faculty survey to examine the move to remote teaching from a faculty perspective during the COVID-19 pandemic. The study relies on secondary data analysis of data collected by the Office of Institutional Research at a large, public four-year institution in the mid-Atlantic region of the United States to answer the following research questions:
1. How has COVID-19 changed the usage of technology, various teaching methods, and adjustments to course expectations?
2. Are there age, faculty status, and/or discipline differences in usage of technology, various teaching methods, and adjustments to course assignments?
3. Post-COVID-19, how do faculty status/rank and gender influence maintaining work-life balance?Policy, Organizational and Leadership Studie
Association of the serotonin transporter gene, neuroticism and smoking behaviours
No full textCigarette consumption and smoking cessation are influenced in part by genes. Personality traits have also been implicated in the aetiology of smoking. Neuroticism, a personality trait with a heritable component, correlates well with anxiety and depression, increasing the risk of being a smoker and decreasing the chance of smoking cessation. Several prior studies in non-British populations have given conflicting results as to whether some genetic polymorphisms affect the relationship between smoking and neuroticism. This study investigated the influence of serotonin transporter (5HTTLPR) genotypes on a composite measure of neuroticism and cigarette consumption/smoking cessation in a British population. Although neuroticism was significantly associated with cigarette consumption and smoking cessation, genotype did not affect this relationship. Our results do not support initial interest in utilising 5HTTLPR genotypes in combination with neuroticism ratings for predicting outcome in smoking cessation clinical settings.Colin O'Gara, Jo Knight, John Stapleton, Jason Luty, Ben Neale, Matt Nash, Patricia Heuzo-Diaz, Farzana Hoda, Sarah Cohen, Gay Sutherland, David Collier, Pak Sham, David Ball, Peter McGuffin and Ian Crai
Sequent calculus for euler diagrams
No full textProof systems play a major role in the formal study of diagrammatic logical systems. Typically, the style of inference is not directly comparable to traditional sentential systems, to study the diagrammatic aspects of inference. In this work, we present a proof system for Euler diagrams with shading in the style of sequent calculus. We prove it to be sound and complete. Furthermore we outline how this system can be extended to incorporate heterogeneous logical descriptions. Finally, we explain how small changes allow for reasoning with intuitionistic logic
Aspects of the history of the Catholic gentry of Yorkshire from the Pilgrimage of Grace to the First Civil War
No full textThis study looks at the responses of the Yorkshire Catholic gentry to the immense
changes to their religious landscape in the early modem period, between 1536 and
1642. It examines how they continued to adhere to the Catholic religion, despite all
attempts first to induce and then compel conformity and highlights the ways in which
they managed to survive and prosper throughout the period, demonstrating that
previously neglected groups such as women and younger sons had a crucial role to
play in this process. The overwhelming theme to their actions was one of pragmatism,
rather than the heroic and self-destructive behaviour that was much admired by earlier
historians who wanted to identify martyrs to the Catholic cause.
The areas that are to be examined reflect both public and private gentry activities. In
the public sphere the Yorkshire gentry's part in the rebellions of the Tudor and Stuart
eras are studied along with their rejection of plots. The importance of marriage as an
early modem tool for building alliances and social advancement is acknowledged and
the impact that a continuing adherence to Catholicism had on this is considered. The
gentry and the church are examined through a study of the Catholic gentry's
involvement with their local parishes, their reaction to the dissolution and their
continuing adherence to monasticism, as shown through their devotion to English
orders on the continent. To reflect the changes that were occurring in this period
Catholic involvement in education, the law and medicine are also explored showing
that the Catholic community was not isolated from the wider society. Lastly the role
of Catholic women is given specific consideration in order both to redress the
imbalance in previous studies and due to the crucial role that women played in the
continuation of the Catholic community within Yorkshire
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