Metformin therapy and diabetes in pregnancy

No adverse pregnancy outcomes with metformin use have been reported, except in one unmatched study. Otherwise, the studies are small and non-randomised, with the exception of one prospective, randomised controlled trial, currently under way, comparing metformin with insulin in women with gestational diabetes mellitus (the MiG trial). No long-term follow-up data for offspring of mothers receiving metformin have been published. Any woman with diabetes should be as close to euglycaemia as possible before pregnancy. In some circumstances (eg, severe insulin resistance), metformin therapy during pregnancy may be warranted. When metformin treatment is being considered, the individual risks and benefits need to be discussed with the patient so that an appropriate decision can be reached.

Gene-engineered T cells as a superior adjuvant therapy for metastatic cancer

The major limiting factor in the successful application of adjuvant therapy for metastatic disease is the lack of adjuvant specificity that leads to severe side effects. Reasoning that T cells of the immune system are highly specific, we generated tumor-specific T cells by genetic modification of mouse primary T cells with a chimeric receptor reactive with the human breast cancer-associated Ag erbB-2. These T cells killed breast cancer cells and secreted IFN-gamma in an Ag-specific manner in vitro. We investigated their use against metastatic breast cancer in mice in an adjuvant setting, and compared their effectiveness with the commonly applied adjuvants doxorubicin, 5-fluorouracil, and herceptin. Mice were inoculated orthotopically with the human erbB-2-expressing spontaneously metastatic mouse breast cancer 4T1.2 in mammary tissue, and the primary tumor was surgically removed 8 days later., Significant metastatic disease was demonstrated in lung and liver at the time of surgery on day 8 with increased tumor burden at later time points. T cell adjuvant treatment of day 8 metastatic disease resulted in dramatic increases in survival of mice, and this survival was significantly greater than that afforded by either doxorubicin, 5-fluorouracil, or herceptin.

Cost-effectiveness of cognitive behavioural therapy and selective serotonin reuptake inhibitors for major depression in children and adolescents

Objective: To assess from a health sector perspective the incremental cost-effectiveness of cognitive behavioural therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD) in children and adolescents, compared to 'current practice'. Method: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analysis of randomised controlled trials. An assessment on second stage filter criteria ('equity'; 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are tracked for the duration of a new episode of MDD arising in eligible children (age 6-17 years) in the Australian population in the year 2000. Simulation-modelling techniques are used to present a 95% uncertainty interval (UI) around the cost-effectiveness ratios. Results: Compared to current practice, CBT by public psychologists is the most cost-effective intervention for MDD in children and adolescents at A$9000 per DALY saved (95% UI A$3900 to A$24 000). SSRIs and CBT by other providers are less cost-effective but likely to be less than A$50 000 per DALY saved (> 80% chance). CBT is more effective than SSRIs in children and adolescents, resulting in a greater total health benefit (DALYs saved) than could be achieved with SSRIs. Issues that require attention for the CBT intervention include equity concerns, ensuring an adequate workforce, funding arrangements and acceptability to various stakeholders. Conclusions: Cognitive behavioural therapy provided by a public psychologist is the most effective and cost-effective option for the first-line treatment of MDD in children and adolescents. However, this option is not currently accessible by all patients and will require change in policy to allow more widespread uptake. It will also require 'start-up' costs and attention to ensuring an adequate workforce.

Radiation of the Australian flora: What can comparisons of molecular phylogenies across multiple taxa tell us about the evolution of diversity in present-day communities?

The Australian fossil record shows that from ca. 25 Myr ago, the aseasonal-wet biome (rainforest and wet heath) gave way to the unique Australian sclerophyll biomes dominated by eucalypts, acacias and casuarinas. This transition coincided with tectonic isolation of Australia, leading to cooler, drier, more seasonal climates. From 3 Myr ago, aridification caused rapid opening of the central Australian and zone. Molecular phylogenies with dated nodes have provided new perspectives on how these events could have affected the evolution of the Australian flora. During the Mid-Cenozoic (25-10 Myr ago) period of climatic change, there were rapid radiations in sclerophyll taxa, such as Banksia, eucalypts, pea-flowered legumes and Allocasuarina. At the same time, taxa restricted to the aseasonal-wet biome (Nothofagus, Podocarpaceae and Araucariaceae) did not radiate or were depleted by extinction. During the Pliocene aridification, two Eremean biome taxa (Lepidium and Chenopodiaceae) radiated rapidly after dispersing into Australia from overseas. It is clear that the biomes have different histories. Lineages in the aseasonal-wet biome are species poor, with sister taxa that are species rich, either outside Australia or in the sclerophyll biomes. In conjunction with the fossil record, this indicates depletion of the Australian aseasonal-wet biome from the Mid-Cenozoic. In the sclerophyll biomes, there have been multiple exchanges between the southwest and southeast, rather than single large endemic radiations after a vicariance event. There is need for rigorous molecular phylogenetic studies so that additional questions can be addressed, such as how interactions between biomes may have driven the speciation process during radiations. New studies should include the hither-to neglected monsoonal tropics.

Generic delimitation and phylogenetic uncertainty: An example from a group that has undergone an explosive radiation

Phylogenetic trees can provide a stable basis for a higher-level classification of organisms that reflects evolutionary relationships. However, some lineages have a complex evolutionary history that involves explosive radiation or hybridisation. Such histories have become increasingly apparent with the use of DNA sequence data for phylogeny estimation and explain, in part, past difficulties in producing stable morphology-based classifications for some groups. We illustrate this situation by using the example of tribe Mirbelieae (Fabaceae), whose generic classification has been fraught for decades. In particular, we discuss a recent proposal to combine 19 of the 25 Mirbelieae genera into a single genus, Pultenaea sens. lat., and how we might find stable and consistent ways to squeeze something as complex as life into little boxes for our own convenience. © CSIRO.

Cognitive behavioral therapy for older adults: Practical guidelines for the use of homework assignments

There is emerging evidence to support the effectiveness of cognitive behavior therapy (CBT) for older adults. However, there are a number of clinical difficulties that practitioners often encounter when using homework assignments with the older adult population. In this article, we provide a brief summary of the research findings on homework in CBT, review common obstacles to the use of homework, and provide concrete suggestions for the adaptation of homework assignments to increase their potential effectiveness with older adults. We also describe several types of homework assignments that may be most helpful, augmenting these suggestions with clinical examples.

Bush peas: a rapid radiation with no support for monophyly of Pultenaea (Fabaceae : Mirbelieae)

Phylogenetic hypotheses are presented for Pultenaea based on cpDNA (trnL-F and ndhF) and nrDNA ( ITS) sequence data. Pultenaea, as it is currently circumscribed, comprises six strongly supported lineages whose relationships with each other and 18 closely related genera are weak or conflicting among datasets. The lack of resolution among the six Pultenaea clades and their relatives appears to be the result of a rapid radiation, which is evident in molecular data from both the chloroplast and nuclear genomes. The molecular data provide no support for the monophyly of Pultenaea as it currently stands. Given these results, Pultenaea could split into many smaller genera. We prefer the taxonomically stable alternative of subsuming all 19 genera currently recognised in Pultenaea sensu lato (= the Mirbelia group) into an expanded concept of Pultenaea that would comprise similar to 470 species.

The states, diffusion, and concentration distribution of water in radiation-formed PVA/PVP hydrogels

Hydrogels with various compositions of polyvinyl alcohol (PVA) and poly(1-vinyl-2-pyrrolidinone) (PVP) were prepared by irradiating mixtures of PVA and PVP in aqueous solutions with gamma-rays from Co-60 sources at room temperature. The states of water in the hydrogels were characterized using DSC and NMR T-2 relaxation measurements and the kinetics of water diffusion in the hydrogels were studied by sorption experiments and NMR imaging. The DSC endothermic peaks in the temperature range -10 to +10 degrees C implied that there are at least two kinds of freezable water present in the matrix. The difference between the total water content and the freezable water content was refer-red to as bound water, which is not freezable. The weight fraction of water at which only nonfreezable water is present in a hydrogel with F-VP = 0.19 has been estimated to be g(H2O)/g(Polymer) = 0.375. From water sorption experiments, it was demonstrated that the early stage of the diffusion of water into the hydrogels was Fickian. A curve-fit of the early-stage experimental data to the Fickian model allowed determination of the water diffusion coefficient, which was found to lie between 1.5 x 10(-11) m(2) s(-1) and 4.5 x 10(-11) m(2) s(-1), depending on the polymer composition, the cross-link density, and the temperature. It was also found that the energy barrier for diffusion of water molecules into PVA/PVP hydrogels was approximate to 24 kJ mol(-1). Additionally, the diffusion coefficients determined from NMR imaging of the volumetric swelling of the gels agreed well with the results obtained by the mass sorption method.

Hormone replacement therapy and breast cancer: estimate of risk: Education debate

The risk of breast cancer arises from a combination of genetic susceptibility and environmental factors. Recent studies show that type and duration of use of hormone replacement therapy affect a women's risk of developing breast cancer.1-7 The women's health initiative trial was stopped early because of excess adverse cardiovascular events and invasive breast cancer with oestrogen and progestogen.6 The publicity increased public awareness of the risks of hormone replacement therapy, and this was heightened by the publication of the million women study.2 However, the recently published oestrogen only arm of the women's health initiative trial suggests that this formulation may reduce the risk of breast cancer.8 To help make sense of the often confusing information,9 women and clinicians need individual rather than population risk data. We have produced estimates that can be used to calculate individual risk for women living up to the age of 79 and suggest the risk