SummaryFactor VIII is a trace plasma glycoprotein involved as a cofactor in the activation of factor X by factor IXa. Inherited deficiency of factor VIII results in the X-linked bleeding disorder hemophilia A which has been documented in humans, horses, sheep and dogs. In this report, the putative proximal promoter, 5’ untranslated region, complete coding sequence and 3’ untranslated region of the canine factor VIII gene have been characterized. When compared to the human gene, the 5’ flanking region shows conservation of transcription factor binding sites in the 5’ untranslated region. Alignment of the amino acid sequence with that of the previously reported human, mouse and pig proteins demonstrates sequence identity of between 77 and 92% for the A1, A2, A3, C1 and C2 domains but an identity of only between 44 and 62% for the central B domain. The three thrombin cleavage sites are conserved in the canine sequence as are the protein C cleavage sites and the von Wille-brand factor binding region. In addition, all six tyrosine residues that are known to undergo sulfation in the human protein are conserved in the dog. The 3’ untranslated region of the canine gene extends 1.5 kilo-bases. The initial 700 basepairs of this sequence are highly GC rich and the sequence terminates with 2 alternative potential polyadenylation sites. The knowledge of this sequence, in combination with a well described canine model of hemophilia A, provides the necessary starting point for studies addressing the long-term evaluation of factor VIII gene therapy using a homologous transgene.

A B S T R A C TBackground and purpose: Inter-institutional studies highlighted correlation between consistent radiotherapy quality and improved overall patient survival. In treatment planning automation has the potential to address differences due to user-experience and training, promoting standardisation. The aim of this study was to evaluate implementation and clinical effect of a multicentre collaboratively-developed automated planning model for Intensity-Modulated Radiation Therapy/ Volumetric-Modulated Arc Therapy of prostate. The model was built using a variety of public institutions' clinical plans, incorporating different contouring and dose protocols, aiming at minimising their variation. Methods and materials: A model using 110 clinically approved and treated prostate plans provided by different radiotherapy centres was built with RapidPlan (RP), for use on intact and post-prostatectomy prostate cases. The model was validated, distributed and introduced into clinical practice in all institutions. To investigate its impact a total of 126 patients, originally manually inverse planned (OP), were replanned using RP without additional planner manual intervention. Target and organat-risk (OAR) metrics were statistically compared between original and automated plans. Results: For all centres combined and individually, RP provided plans comparable or superior to OP for all dose metrics. Statistically significant reductions with RP were found in bladder (V40Gy) and rectal (V50Gy) low doses (within 2.3% and 3.4% for combined and 4% and 10% individually). No clinically significant changes were seen for the PTV, independently of seminal vesicle inclusion. Conclusion: This project showed it is feasible to develop, share and implement RP models created with plans from different institutions treated with a variety of techniques and dose protocols, with the potential of improving treatment planning results and/or efficiency despite the original variability.

Discourse analysis of interaction in a course on language and literacy development elucidates and exemplifies how preschool teachers constructed new knowledge that can be assumed to contribute to the improved literacy instruction observed in their classrooms. An analytic framework rooted in socio-cultural theory and interactional sociolinguistic methods foregrounds the issues of whose sentiments and knowledge got taken up on the conversational floor and what specific new knowledge was conversationally constructed. We use this framework to explicate a discussion in which the teachers and the instructor assembled a knowledge structure. The group’s emergent response to a question gained propositional content as participants jointly created and used social and informational resources. This approach allows insight into the sociolinguistic processes that contribute to effective professional development experiences.

My first illustration, intended to show some of the problems facing those of us who use statistics to convey information to others, comes not from transport, but involves a giraffe called Victor, whom you may recall some years back becoming the focus of the nation's concern when he fell on his knees after being moved to a new zoo. Giraffes are not designed to be on their knees; they always stand, awake and asleep; and Victor's life was in grave danger. The radio news reporter asked the vet what chance Victor had of surviving the attempt to put him on his feet again. ‘A 50/50 chance’, said the vet. Victor died. The next day the reporter was back and thus accused the vet: ‘You said he had a 50/50 chance and he's dead, so you were wrong, weren't you?’ It is hard to know how to deal with this level of ignorance of what numbers mean, but people's nervousness around statements of probability in particular can be, and frequently are, taken advantage of.

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