Block sequential adriamycin CMF – optimal non-myeloablative chemotherapy for high risk adjuvant breast cancer?

After the publication of the 10-year survival data from Milan on the adjuvant use of the block sequential regimen consisting of four cycles of adriamycin followed by eight cycles of intravenous CMF, many centres adopted this as standard of care for high risk, multiple node-positive breast cancer. For this reason it was identified as the standard arm for the Anglo-Celtic adjuvant high-dose chemotherapy trial. This study reports on the experience of this regimen in 329 women with early breast cancer involving at least four axillary nodes, who were treated outside any adjuvant chemotherapy trial. At a median follow-up of 3 years, the overall 5-year disease-free survival is 61%, and the overall survival is 70%. These data confirm the efficacy of this regimen in non-trial patients, and, for the same high risk subgroup, indicate that this approach offers an outcome at least as good as that seen in the CALGB 9344 AC-Taxol arm, and the NCIC days 1 and 8 CEF

Nitrogen oxides and PAN in plumes from boreal fires during ARCTAS-B and their impact on ozone: an integrated analysis of aircraft and satellite observations

We determine enhancement ratios for NO<sub>x</sub>, PAN, and other NO<sub>y</sub> species from boreal biomass burning using aircraft data obtained during the ARCTAS-B campaign and examine the impact of these emissions on tropospheric ozone in the Arctic. We find an initial emission factor for NO<sub>x</sub> of 1.06 g NO per kg dry matter (DM) burned, much lower than previous observations of boreal plumes, and also one third the value recommended for extratropical fires. Our analysis provides the first observational confirmation of rapid PAN formation in a boreal smoke plume, with 40% of the initial NO<sub>x</sub> emissions being converted to PAN in the first few hours after emission. We find little clear evidence for ozone formation in the boreal smoke plumes during ARCTAS-B in either aircraft or satellite observations, or in model simulations. Only a third of the smoke plumes observed by the NASA DC8 showed a correlation between ozone and CO, and ozone was depleted in the plumes as often as it was enhanced. Special observations from the Tropospheric Emission Spectrometer (TES) also show little evidence for enhanced ozone in boreal smoke plumes between 15 June and 15 July 2008. Of the 22 plumes observed by TES, only 4 showed ozone increasing within the smoke plumes, and even in those cases it was unclear that the increase was caused by fire emissions. Using the GEOS-Chem atmospheric chemistry model, we show that boreal fires during ARCTAS-B had little impact on the median ozone profile measured over Canada, and had little impact on ozone within the smoke plumes observed by TES

Use of oral glucocorticoids and risk of skin cancer and non-Hodgkin's lymphoma: a population-based case–control study

In North Jutland County, Denmark, we investigated whether use of oral glucocorticoids was associated with an increased risk of developing basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM), and non-Hodgkin's lymphoma (NHL). From the Danish Cancer Registry we identified 5422 BCC, 935 SCC, 983 MM, and 481 NHL cases during 1989–2003. Using risk-set sampling we selected four age- and gender-matched population controls for each case from the Civil Registration System. Prescriptions for oral glucocorticoids before diagnosis were obtained from the Prescription Database of North Jutland County on the basis of National Health Service data. We used conditional logistic regression to estimate incidence rate ratios (IRRs), adjusting for chronic medical diseases (information about these were obtained from the National Patient Registry) and use of other immunosuppressants. We found slightly elevated risk estimates for BCC (IRR, 1.15 (95% CI: 1.07–1.25)), SCC (IRR, 1.14 (95% CI: 0.94–1.39)), MM (IRR, 1.15 (95% CI: 0.94–1.41), and NHL (IRR, 1.11 (95% CI: 0.85–1.46)) among users of oral glucocorticoids. Our study supports an overall association between glucocorticoid use and risk of BCC that cannot be explained by the presence of chronic diseases or concomitant use of other immunosuppressants

Homosexual Women Have Less Grey Matter in Perirhinal Cortex than Heterosexual Women

Is sexual orientation associated with structural differences in the brain? To address this question, 80 homosexual and heterosexual men and women (16 homosexual men and 15 homosexual women) underwent structural MRI. We used voxel-based morphometry to test for differences in grey matter concentration associated with gender and sexual orientation. Compared with heterosexual women, homosexual women displayed less grey matter bilaterally in the temporo-basal cortex, ventral cerebellum, and left ventral premotor cortex. The relative decrease in grey matter was most prominent in the left perirhinal cortex. The left perirhinal area also showed less grey matter in heterosexual men than in heterosexual women. Thus, in homosexual women, the perirhinal cortex grey matter displayed a more male-like structural pattern. This is in accordance with previous research that revealed signs of sex-atypical prenatal androgenization in homosexual women, but not in homosexual men. The relevance of the perirhinal area for high order multimodal (olfactory and visual) object, social, and sexual processing is discussed

Templated self-replication in biomimetic systems.

A key characteristic of living systems is the storage and replication of information, and as such the development of self-replicating systems capable of heredity is of great importance to the fields of synthetic biology and origin of life research. In this review, the design and implementation of self-replicating systems in the context of bottom-up synthetic biology is discussed, with a particular focus on nucleic acid-based replication including nonenzymatic systems, ribozyme-based systems, and complex in vitro translation coupled RNA and DNA replication. The current state and remaining challenges of the respective fields are discussed, and the potential of individual replicators for synthetic biology applications such as the creation of artificial life capable of Darwinian evolution is also summarized

Integrating mental health into climate change education to inspire climate action while safeguarding mental health

Climate change is the greatest threat humanity faces, and puts at risk the mental health and wellbeing of children and young people. Climate change education must equip children and young people with the knowledge, skills and resilience to live in an uncertain future, sustainably take relevant climate action and work in climate careers. As attention on climate change education grows, this is a critical moment for the mental health community to ensure mental health and wellbeing considerations are embedded. Critically, appropriate integration of mental health can enable these very necessary goals of equipping children and young people to live and work in a future where climate change looms large. This paper explores why promoting good mental health and wellbeing and building psychological resilience can help achieve climate change education outcomes, and why not doing so risks harming children and young people’s mental health. It also explores how integrating discussions about emotions, mental health, and coping strategies within climate change education can be a route into wider discussions about mental health, to support children and young people in the context of rising mental health needs. Learning from an existing approach to promoting good mental health and wellbeing in schools (the ‘whole school approach’) provides the opportunity to explore one avenue through which such an integrated approach could be implemented in practice. Identifying appropriate mechanisms to integrate mental health into climate change education will require co-design and research with educators and young people, and addressing systemic barriers facing the schools sector

Quality of hatchery-reared juveniles for marine fisheries stock enhancement

The potential for stock enhancement by release of hatchery-reared juveniles continues to be a topic of interest to researchers and fisheries managers. While, in many studies, the focus has tended to be on the technology for production of juveniles, the need for a more multidisciplinary approach is now becoming accepted. Ideally, this includes studies of population dynamics and recruitment-limitation of wild stocks, environment–stock interactions, habitat availability, genetic studies of wild and released stocks and integration with appropriate fisheries management. While it may be relatively straightforward to culture large numbers of seed animals, the quality of hatchery-reared juveniles may limit the effectiveness of any release programme. The quality of juveniles may be defined either by their ability to attain the age and size to recruit to a commercial fishery or their fitness to survive to contribute to the spawning stock. Many factors will inevitably influence batch–batch variability in the viability of hatchery-reared juveniles and their ability to recruit and compete in the wild. Some effects of nutrition and environment in the hatchery are well-known or at least recognised and their manipulation offers the potential for improvement of survivorship of juveniles post-release. The choice and utilisation of broodstock also represent a crucial stage in enhancement programmes, and considerations of bottleneck effects arising from reduced effective population size due to skewed parental and family contributions must be given careful consideration. A broodstock design that encompasses sufficient numbers of animals that reflect the genetic, and preferably ecological, identity of the stocks to be enhanced should be adopted. In addition, environmental conditions and husbandry practices within the hatchery as well as broodstock and larval nutrition can all influence the quality of offspring. Further conditioning and/or selection during nursery culture may also be critical in maximising the physiological and behavioural fitness of hatchery juveniles post-release. Although evaluation of long-term performance of individual batches of juveniles requires considerable effort or may be impossible in some cases, this type of quantification is likely to be an important component in the determination of the effectiveness of release programmes. This paper reviews the effects of hatchery and nursery practice on larval and juvenile fitness for stock enhancement and presents examples of comparisons of the quality of wild and hatchery-reared juveniles and the effect of pre-release conditioning on subsequent survival and growth.L. Le Vay, E.T. Quinitio, V.N. Ut and J.H. Lebata acknowledge the support of a European Commission INCO DC grant (contract ECA4-CT-2001-10022). The authors thank Dr. R. Pérez-Dominguez for comments on the manuscript

Compartmentalised RNA catalysis in membrane-free coacervate protocells

Phase separation of mixtures of oppositely charged polymers provides a simple and direct route to compartmentalisation via complex coacervation, which may have been important for driving primitive reactions as part of the RNA world hypothesis. However, to date, RNA catalysis has not been reconciled with coacervation. Here we demonstrate that RNA catalysis is viable within coacervate microdroplets and further show that these membrane-free droplets can selectively retain longer length RNAs while permitting transfer of lower molecular weight oligonucleotides