Capecitabine and oral cyclophosphamide : a novel oral treatment combination for advanced cancer

Background: This dose escalation study assessed feasibility of a totally oral chemotherapy regimen using cyclophosphamide and capecitabine. The rationale for this combination was based on the observation that preclinical models of cyclophosphamide up-regulated tumor thymidine phosphorylase and increased the activation of capecitabine. Methods: Eligible patients with advanced cancer were treated with oral cyclophosphamide and capecitabine on a 28-day cycle. If no dose limiting toxicities (DLT) were encountered during the first two treatment cycles, the next patient group was assigned to the next highest dose level until the maximum tolerable dose (MTD) was determined. Results: Twenty-seven patients entered treatment. The majority of non-DLT were grades 1 and 2. DLT experienced in the first 8-week observation period were grade 3 diarrhea (one patient, level III) and grade 3 emesis (two patients, level V). MTD was observed at level 5, 1331 mg/m2/day capecitabine days 1–28 with 125 mg/m2/day cyclophosphamide days 1–14 of the 28-day cycle. The recommended phase II dose is therefore 1331 mg/m2/day capecitabine with 100 mg/m2/day cyclophosphamide. The best response evaluation showed four partial responses (breast, colon, ovary and pancreas). Conclusion: Cyclophosphamide and capecitabine can be combined at their full oral single agent dose with promising tolerability and activity.

Differences in primary health care delivery to Australia's Indigenous population : a template for use in economic evaluations

Background Health economics is increasingly used to inform resource allocation decision-making, however, there is comparatively little evidence relevant to minority groups. In part, this is due to lack of cost and effectiveness data specific to these groups upon which economic evaluations can be based. Consequently, resource allocation decisions often rely on mainstream evidence which may not be representative, resulting in inequitable funding decisions. This paper describes a method to overcome this deficiency for Australia’s Indigenous population. A template has been developed which can adapt mainstream health intervention data to the Indigenous setting.

Methods The ‘Indigenous Health Service Delivery Template’ has been constructed using mixed methods, which include literature review, stakeholder discussions and key informant interviews. The template quantifies the differences in intervention delivery between best practice primary health care for the Indigenous population via Aboriginal Community Controlled Health Services (ACCHSs), and mainstream general practitioner (GP) practices. Differences in costs and outcomes have been identified, measured and valued. This template can then be used to adapt mainstream health intervention data to allow its economic evaluation as if delivered from an ACCHS.

Results The template indicates that more resources are required in the delivery of health interventions via ACCHSs, due to their comprehensive nature. As a result, the costs of such interventions are greater, however this is accompanied by greater benefits due to improved health service access. In the example case of the polypill intervention, 58% more costs were involved in delivery via ACCHSs, with 50% more benefits. Cost-effectiveness ratios were also altered accordingly.

Conclusions The Indigenous Health Service Delivery Template reveals significant differences in the way health interventions are delivered from ACCHSs compared to mainstream GP practices. It is important that these differences are included in the conduct of economic evaluations to ensure results are relevant to Indigenous Australians. Similar techniques would be generalisable to other disadvantaged minority populations. This will allow resource allocation decision-makers access to economic evidence that more accurately represents the needs and context of disadvantaged groups, which is particularly important if addressing health inequities is a stated goal.

Creative geeks? Investigating creativity support systems for information technology students

This study investigated creativity and what factors can be conducive to a creative educational milieu. The results of this study highlighted the diverse nature of creativity, and substantiated the need for an audience specific ‘Creativity Support System’. An outcome was a model of creative needs specific for an educational setting

Breastfeeding and infant sleep patterns : an Australian population study

Objective : Our purpose was to determine if babies breastfed at 6 months of age were more likely to wake at night and less likely to sleep alone than formula-fed babies.

Patients and Methods : Data were drawn from the first wave of The Longitudinal Study of Australian Children, an ongoing, nationally representative study of the growth and development of Australia's children. The 4507 participants met the criteria for this study. The measures examined infant sleep problems as the outcome and breastfeeding at 6 months of age as the exposure in addition to the demographic data, maternal mental health, infant birthweight and gestational age at delivery.

Results : After adjustment for covariates, reports by mothers of infants that breastfed at 6 months of age suggested infants were 66% more likely to wake during the night and 72% more likely to report difficulty sleeping alone. However, breastfeeding had a strongly protective effect on wheezing, coughing, snoring and breathing problems, and it was not associated with restless sleep or problems getting to sleep for the infant.

Conclusions : Breastfeeding was found to be associated with increased night waking and this is consistent with other studies. There are biological reasons why this might be required to ensure breastfeeding continues to 6 months and beyond. The current low rates of sustained breastfeeding in many Western countries needs to be reconsidered in relation to parental and public health practices promoting prolonged nocturnal infant sleep patterns.

Limited population structure, genetic drift and bottlenecks characterise an endangered bird species in a dynamic, fire-prone ecosystem

Fire is a major disturbance process in many ecosystems world-wide, resulting in spatially and temporally dynamic landscapes. For populations occupying such environments, fire-induced landscape change is likely to influence population processes, and genetic patterns and structure among populations. The Mallee Emu-wren Stipiturus mallee is an endangered passerine whose global distribution is confined to fire-prone, semi-arid mallee shrublands in south-eastern Australia. This species, with poor capacity for dispersal, has undergone a precipitous reduction in distribution and numbers in recent decades. We used genetic analyses of 11 length-variable, nuclear loci to examine population structure and processes within this species, across its global range. Populations of the Mallee Emu-wren exhibited a low to moderate level of genetic diversity, and evidence of bottlenecks and genetic drift. Bayesian clustering methods revealed weak genetic population structure across the species' range. The direct effects of large fires, together with associated changes in the spatial and temporal patterns of suitable habitat, have the potential to cause population bottlenecks, serial local extinctions and subsequent recolonisation, all of which may interact to erode and homogenise genetic diversity in this species. Movement among temporally and spatially shifting habitat, appears to maintain long-term genetic connectivity. A plausible explanation for the observed genetic patterns is that, following extensive fires, recolonisation exceeds in-situ survival as the primary driver of population recovery in this species. These findings suggest that dynamic, fire-dominated landscapes can drive genetic homogenisation of populations of species with low-mobility and specialised habitat that otherwise would be expected to show strongly structured populations. Such effects must be considered when formulating management actions to conserve species in fire-prone systems.

Localization of copper and copper transporters in the human brain

Disturbances in brain copper result in rare and severe neurological disorders and may play a role in the pathogenesis and progression of multiple neurodegenerative diseases. Our current understanding of mammalian brain copper transport is based on model systems outside the central nervous system and no data are available regarding copper transport systems in the human brain. To address this deficit, we quantified regional copper concentrations and examined the distribution and cellular localization of the copper transport proteins Copper transporter 1, Atox1, ATP7A, and ATP7B in multiple regions of the human brain using inductively coupled plasma-mass spectrometry, Western blot and immunohistochemistry. We identified significant relationships between copper transporter levels and brain copper concentrations, supporting a role for these proteins in copper transport in the human brain. Interestingly, the substantia nigra contained twice as much copper than that in other brain regions, suggesting an important role for copper in this brain region. Furthermore, ATP7A levels were significantly greater in the cerebellum, compared with other brain regions, supporting an important role for ATP7A in cerebellar neuronal health. This study provides novel data regarding copper regulation in the human brain, critical to understand the mechanisms by which brain copper levels can be altered, leading to neurological disease.

Silencing host genes using RNAi to impact virus growth in vitro

Using short interfering RNAs to silence individual human host genes we were able to demonstrate that alpha coatamer protein (COPA) is important for the replication of highly pathogenic Avian Influenza A/chicken/Vietnam/008/2004 H5N1 in vitro and may therefore hold potential as a target for novel antiviral therapeutics.