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"Mann, Jill"
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Single dose GLP toxicity and biodistribution study of a conditionally replicative adenovirus vector, CRAd-S-pk7, administered by intracerebral injection to Syrian hamsters
Background
CRAd-S-pk7 is a conditionally replicative oncolytic adenoviral vector that contains a survivin promoter and a pk7 fiber modification that confer tumor-specific transcriptional targeting and preferential replication in glioma while sparing the surrounding normal brain parenchyma.
Methods
This IND-enabling study performed under GLP conditions evaluated the toxicity and biodistribution of CRAd-S-pk7 administered as a single intracerebral dose to Syrian hamsters, a permissive model of adenoviral replication. Two hundred and forty animals were stereotactically administered either vehicle (
n
= 60) or CRAd-S-pk7 at 2.5 × 10
7
, 2.5 × 10
8
, or 2.5 × 10
9
viral particles (vp)/animal (each
n
= 60) on day 1. The animals were closely monitored for toxicology evaluation, assessment of viral distribution, and immunogenicity of CRAd-S-pk7.
Results
Changes in hematology, clinical chemistry, and coagulation parameters were minor and transient, and consistent with the inflammatory changes observed microscopically. These changes were considered to be of little toxicological significance. The vector remained localized primarily in the brain and to some degree in the tissues at the incision site. Low levels of vector DNA were detected in other tissues in a few animals suggesting systemic circulation of the virus. Viral DNA was detected in brains of hamsters for up to 62 days. However, microscopic changes and virus-related toxicity to the central nervous system were considered minor and decreased in incidence and severity over time. Such changes are not uncommon in studies using adenoviral vectors.
Conclusion
This study provides safety and toxicology data justifying a clinical trial of CRAd-S-pk7 loaded in FDA-approved HB1.F3.CD neural stem cell carriers administered at the tumor resection bed in humans with recurrent malignant glioma.
Journal Article
Life in Words
This volume collects fifteen landmark essays published over the last three decades by the distinguished medievalist Jill Mann. Bringing together her essays on Chaucer, the Gawain -poet, and Malory, the collection foregrounds the common interest in the semantic implications of key vocabulary such as “authority,” “adventure,” and “price” that links them together.
Mann, one of the finest critics of Middle English literature in her generation, uses the concepts suggested by the language of medieval literature itself as a way into the masterpieces of Middle English, including The Canterbury Tales , Troilus and Criseyde , Sir Gawain and the Green Knight , and the Morte Darthur .
An extended introduction by Mark Rasmussen brings out the nature of the themes that run through the collection, analyses the critical methods in play, and assesses their significance in the context of Middle English studies over the last thirty years.
eBook
O-117 Effective community implementation of advance care planning
Background Barwon Health's community implementation of advance care planning (ACP) supports the belief that conversations regarding a person's values, goals and treatment decisions are best facilitated in the absence of acute illness. Aim To promote an integrated ACP program into the community and primary care, enabling increased awareness, accessibility and participation. Methods Cross-sectorial training and education provided to health professionals to enable promotion of ACP to consumers at multiple intersections of health service delivery. Focussed projects to embed ACP processes. A robust alliance with local General Practices to support ACP from referral to completion in primary care. Results Data demonstrates that introduction to ACP in General Practice effectively initiates conversations in the community. The provision of skilled trained ACP clinicians in General Practice continues to have high referral rates and uptake to document completion (88%) when compared with other referral sources. Clients are predominately referred through the >75 yrs Health Assessment including those with chronic or life limiting illness. Discussion Success is largely dependent on raising community awareness and a multi-pronged approach, with General Practitioners (GP) as major investors. Client satisfaction surveys provide evidence that individuals want to discuss and document their medical treatment and care preferences, and high confidence and trust exists when endorsed by their GP. GP responses are also positive. Conclusion These initiatives have resulted in an increased proportion of patients acutely presenting to Barwon Health who have a pre-existing ACP. These provide a basis for further conversations with patients or families and convey important information to guide treatment decision making.
Journal Article
P-40 Advance care planning - case studies show benefits for the young and healthy aged
Background Barwon Health's community implementation of Advance Care Planning (ACP) works collaboratively with General Practice (GP) conducting patient-centred, facilitator-led clinics. The majority of patients completing ACPs are over 75 years, however a small number are considerably younger, most often in the terminal phase of an illness. Aim To highlight the benefits of ACP in primary care, regardless of age and diagnosis, and evaluate whether expressed wishes matched the actual care received throughout the care continuum. Methods Evaluation of 3 case studies through document audits, including a young woman with metastatic Glioblastoma Multiforme, who was referred by her GP and completed her ACP in the clinic, twenty three days prior to death. Results Documentation at key intersections with a number of health service programs showed references to the ACP and respect for each patient's expressed preferences. Discussion GP's are in a privileged position to identify the needs of patients at different stages of life, and with varying diagnoses, to facilitate timely ACP discussion and completion. This empowers the patient wishing to maintain control over their future health choices and subsequently informs clinicians throughout the care continuum, regardless of where this care occurs. Conclusion Young people with a terminal illness and the healthy aged need access to ACP through primary care. Although initiating discussions and reflecting on death can be profoundly confronting and difficult, GPs are well positioned to initiate these discussions. Follow up by trained ACP Facilitators ensures timely completion of documentation which must be integrated and easily accessible to all treating clinicians.
Journal Article
MAKING IT UP AS YOU GO ALONG
This forum gathers together a set of essays composed in response to the 2011 special issue of Religion & Literature 42.1–2, titled \"Something Fearful\": Medievalist Scholars on the \"Religious Turn\" in Literary Criticism, edited by Kathryn Kerby-Fulton and Jonathan Juilfs. The forum's ten authors reflect both on essays within the original volume and on the broader questions engaged by it and through its very publication; responsive remarks from Kathryn Kerby-Fulton and two contributors to that initiating volume conclude the conversation. Through conversation, response, and critical engagement, the forum's contributors weigh questions of the language of belief in scholarly discourse, of the continuities of religious practice across history, of the assumptions and beliefs undergirding critical work on religion and literature and culture, and of the acknowledgement of the religious convictions of medievalists' scholarly subjects, scholars, and the communities of both.
Journal Article
The Cambridge Companion to Chaucer
The Cambridge Companion to Chaucer is an extensively revised version of the first edition, which has become a classic in the field. This new volume responds to the success of the first edition and to recent debates in Chaucer Studies. Important material has been updated, and new contributions have been commissioned to take into account recent trends in literary theory as well as in studies of Chaucer's works. New chapters cover the literary inheritance traceable in his works to French and Italian sources, his style, as well as new approaches to his work. Other topics covered include the social and literary scene in England in Chaucer's time, and comedy, pathos and romance in the Canterbury Tales. The volume now offers a useful chronology, and the bibliography has been entirely updated to provide an indispensable guide for today's student of Chaucer.
eBook
Reynard the Fox
There are many stories featuring the villainous hero Reynard the Fox in many languages told over many centuries, goingback as far as the early 12th century. All these stories are comic and much of the humour depends on parody and satire resulting in mockery, sometimes the subversion of certain kinds of serious literature, of political and religious institutions and practices, of scholarly argument and moralizing, and of popular beliefs and customs. The contributors to this volume, all of them experts in one or more of the Reynard stories and their backgrounds, focus on the transformation of these tales through various media and to what extent they reflect differences in the cultural, class, and generational background of their tellers.
eBook