Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Bioavailability study of oral and intravenous OGT 719, a novel nucleoside analogue with preferential activity in the liver

Purpose: Although oral fluoropyrimidine pro-drugs are increasingly being administered in preference to intravenous nucleoside analogues in cancer chemotherapy, their activation in malignant liver tissue may be insufficient. OGT 719 (1-galactopyranosyl-5-fluorouracil) is a novel nucleoside analogue, preferentially localized in hepatocytes and hepatoma cells via the asialoglycoprotein receptor. The aim of this study was to assess the systemic bioavailability of this rationally designed drug in 16 patients with advanced solid cancers. Method: Crossover pharmacokinetic study of oral (400 or 800 mg) and intravenous (250 mg/m 2) OGT 719. Results: Linear pharmacokinetics and oral bioavailability of approximately 25% were observed at the dose levels used in this study. Like other 5-FU prodrugs, considerable interpatient variability was observed in bioavailability following oral dosing. The mean half-life for oral doses was 4 h. OGT 719 was well tolerated. No objective tumour responses were demonstrated. Conclusion: The systemic bioavailability and half-life of oral OGT 719 are sufficient to merit dose escalation studies with frequent daily dosing. Subsequent efficacy studies should be performed in patients with primary and secondary liver malignancies.

Facilitating local stories in post-disaster regional communities : evaluation in narrative-driven oral history projects

Cyclone Yasi struck the Cassowary Coast of Northern Queensland, Australia, in the early hours of February 3, 2011, destroying many homes and property, including the destruction of the Cardwell and district historical society’s premises. With their own homes flattened, many residents were forced to live in mobile accommodation, with extended family, or leave the area altogether. The historical society members seemed, however, particularly devastated by their flattened foreshore museum and loss of their precious collection of material. A call for assistance was made through the Oral History Association of Australia’s Queensland branch (OHAA Qld), which along with a Queensland University of Technology (QUT) research team sponsored a trip to best plan how they could start to pick up the pieces to rebuild the museum. This chapter highlights the need for communities to gather, preserve and present their own stories, in a way that is sustainable and meaningful to them – whether that be because of a disaster, or as they go about life in their contemporary communities – the key being that good advice, professional support and embedded evaluation practices at crucial moments along the way can be critically important.

Author response: "NPO practices and preoperative oral carbohydrate intake"

"We thank Dr Marsh for his thoughtful comments and acknowledge the limitations of our study, which we clearly outlined in the article. We also thank Dr Marsh for supporting our call for larger, independent trials to test the effectiveness of preoperative consumption of highcarbohydrate fluids to improve patient outcomes..."

Oral immunization with a novel lipid-based adjuvant protects against genital Chlamydia infection

Oral immunization is attractive as a delivery route because it is needle-free and useful for rapid mass vaccination programs to target pandemics or bioterrorism. This potential has not been realized for human vaccination, due to the requirement of large antigen doses and toxic (to humans) adjuvants to overcome the induction of oral tolerance and potential degradation of antigens in the stomach. To date, only oral vaccines based on live attenuated organisms have been approved for human use. In this study we describe the use of a lipid-based delivery system/adjuvant, Lipid C, for oral immunization to protect mice against genital tract chlamydial infection. Lipid C is formulated from food-grade purified and fractionated triglycerides. Bacterial shedding following vaginal challenge with Chlamydia muridarum was reduced by 50% in female mice orally immunized with the chlamydial major outer membrane protein (MOMP) formulated in Lipid C, protection equivalent to that seen in animals immunized with MOMP admixed with both cholera toxin (CT) and CpG oligodeoxynucleotides (CpG-ODN). Protection was further enhanced when MOMP, CT and CpG were all combined in the Lipid C matrix. Protection correlated with production of gamma interferon (IFN) by splenic T cells, a serum MOMP-specific IgG response and low but detectable levels of MOMP-specific IgA in vaginal lavage.

Constructing subjects and making experts : reading the politics of the psychotherapy novel

This paper examines the ideological and political basis of the practice of psychotherapy in contemporary culture. Psychotherapy is argued to be both inherently political and intimately concerned with the construction of subjectivity. These arguments are examined through interrogating the representation of psychotherapy in the works of Lindner ( The Fifty-Minute Hour , Bantam, New York, 1955) and particularly in Yalom's fictional text Lying on the Couch (HarperPerennial, New York, 1996). The implications within psychotherapy for representing normality, negotiating power, and locating and constructing subjectivity are highlighted through the critical treatment of these texts.

A multilevel investigation into the effects of the philosophical community of inquiry on 6th grade students' reading comprehension, interest in maths, self-esteem, pro-social behaviours and emotional well-being

This investigation measured the effects of a one year participation in an Australian Philosophical Community of Inquiry program on 280 sixth grade students' reading comprehension, interest in maths, self-esteem, social behaviours, and emotional well-being. A multilevel model for change was used to detect differences in the response variables, between a quasi-experimental group and comparison group. Results showed that, for participants, reading comprehension significantly increased while interest in maths decreased. No differences between the groups were found for pro-social behaviour and emotional well-being. Self esteem, however, declined for participants while nonparticipants' self esteem increased.

Literary prosumers : young people’s reading and writing in a new media landscape

The production of culture is today a matter of ‘user generated content’ and young people are vital participants as ‘prosumers’, i.e. both producers and consumers, of cultural products. Among other things, they are busy creating fan works (stories, pictures, films) based on already published material. Using the genre fan fiction as a point of departure, this article explores the drivers behind net communities organised around fan culture and argues that fan fiction sites can in many aspects be regarded as informal learning settings. By turning to the rhetoric principle of imitatio, the article shows how in the collective interactive processes between readers and writers such fans develop literacies and construct gendered identities.

Comparative susceptibility of mosquito populations in North Queensland, Australia to oral infection with dengue virus

Dengue is the most prevalent arthropod-borne virus, with at least 40% of the world’s population at risk of infection each year. In Australia, dengue is not endemic, but viremic travelers trigger outbreaks involving hundreds of cases. We compared the susceptibility of Aedes aegypti mosquitoes from two geographically isolated populations with two strains of dengue virus serotype 2. We found, interestingly, that mosquitoes from a city with no history of dengue were more susceptible to virus than mosquitoes from an outbreak-prone region, particularly with respect to one dengue strain. These findings suggest recent evolution of population-based differences in vector competence or different historical origins. Future genomic comparisons of these populations could reveal the genetic basis of vector competence and the relative role of selection and stochastic processes in shaping their differences. Lastly, we show the novel finding of a correlation between midgut dengue titer and titer in tissues colonized after dissemination.

Re-reading the reading lesson : episodes in the history of reading pedagogy

Reading pedagogy is constantly an object of discussion and debate in contemporary policy and practice but is rarely a matter for historical inquiry. This paper reports from a recent study of the history of reading pedagogy in Australia and beyond. It focuses on a recurring figure in the historical record—the ‘reading lesson’. Presented as a distinctive trope, the reading lesson is traced in its regularity in and through the discourse of reading pedagogy, starting in 1930s Australia and moving back into 19th-century Europe, and with specific reference to the UK and the USA. Teaching reading is expressly identified as a moral project—something that, it can be argued, clearly continues into the present.

ShARe/CLEF eHealth Evaluation Lab 2013, Task 3: Information retrieval to address patients' questions when reading clinical reports

This paper presents the results of task 3 of the ShARe/CLEF eHealth Evaluation Lab 2013. This evaluation lab focuses on improving access to medical information on the web. The task objective was to investigate the effect of using additional information such as the discharge summaries and external resources such as medical ontologies on the IR effectiveness. The participants were allowed to submit up to seven runs, one mandatory run using no additional information or external resources, and three each using or not using discharge summaries.

A 5- versus 3-day course of oral corticosteroids for children with asthma exacerbations who are not hospitalised : a randomised controlled trial

Objective To determine whether a 5-day course of oral prednisolone is superior to a 3-day course in reducing the 2-week morbidity of children with asthma exacerbations who are not hospitalised. Design, setting and participants Double-blind randomised controlled trial of asthma outcomes following a 5-day course of oral prednisolone (1 mg/kg) compared with a 3-day course of prednisolone plus placebo for 2 days. Participants were children aged 2–15 years who presented to the emergency departments of three Queensland hospitals between March 2004 and February 2007 with an acute exacerbation of asthma, but were not hospitalised. Sample size was defined a priori for a study power of 90%. Main outcome measures Difference in proportion of children who were symptom-free at Day 7, as measured by intention-to-treat (ITT) and per-protocol analysis; quality of life (QOL) on Days 7 and 14. Results 201 children were enrolled, and there was an 82% completion rate. There was no difference between groups in the proportion of children who were symptom-free (observed difference, 0.04 [95% CI, − 0.09 to 0.18] by ITT analysis; 0.04 [95% CI, − 0.17 to 0.09] by per-protocol analysis). There was also no difference between groups in QOL (P = 0.42). The difference between groups for the primary outcome was within the equivalence range calculated post priori. Conclusion A 5-day course of oral prednisolone confers no advantage over a 3-day course for children with asthma exacerbations who are not hospitalised.

A visual profile of Queensland indigenous and non-indigenous school children, and the association between vision and reading

This research investigated the prevalence of vision disorders in Queensland Indigenous primary school children, creating the first comprehensive visual profile of Indigenous children. Findings showed reduced convergence ability and reduced visual information processing skills were more common in Indigenous compared to non-Indigenous children. Reduced visual information processing skills were also associated with reduced reading outcomes in both groups of children. As early detection of visual disorders is important, the research also reviewed the delivery of screening programs across Queensland and proposed a model for improved coordination and service delivery of vision screening to Queensland school children.