A phase II trial of paclitaxel and epirubicin in advanced breast cancer

Initial trials of paclitaxel and doxorubicin in advanced breast cancer yielded high response rates but significant cardiac toxicity was observed. In this phase II trial we investigated the efficacy and safety of paclitaxel combined with epirubicin. Patients with advanced breast cancer, performance status 0–2, measurable disease, and a normal left ventricular ejection fraction, who may have received adjuvant chemotherapy were treated with epirubicin 75 mg m–2followed by a 3-h infusion of paclitaxel 175 mg m–2repeated every 3 weeks. Forty-three eligible patients were treated at six centres. 67% patients received the maximum of six cycles. The response rate was 54% (95% CI 38–69%), 12% CR and 42% PR. Estimated median progression-free survival was 6.9 months (95% CI 5.4–10.0) and estimated median overall survival was 17.9 months (95% CI 14.2–25.7). Four patients had a decrease in the left ventricular ejection fraction (LVEF) of ≥20% of baseline value, and in two patients the LVEF decreased to below the lower limit of normal, but no patient developed clinical evidence of cardiac failure. Grade 4 neutropenia occurred in 56% cycles, but only 4% of cycles were complicated by febrile neutropenia. Grade 3 or 4 non-haematologic toxicity was uncommon. In conclusion, paclitaxel 175 mg m–2and epirubicin 75 mg m–2is a well tolerated, promising regimen for the treatment of advanced breast cancer. © 2000 Cancer Research Campaig

On the shopfloor: exploring the impact of teacher trade unions on school-based industrial relations

Teachers are highly unionised workers and their trade unions exert an important influence on the shaping and implementation of educational policy. Despite this importance there is relatively little analysis of the impact of teacher trade unions in educational management literature. Very little empirical research has sought to establish the impact of teacher unions at school level. In an era of devolved management and quasi-markets this omission is significant. New personnel issues continue to emerge at school level and this may well generate increased trade union activity at the workplace. This article explores the extent to which devolved management is drawing school-based union representation into a more prominent role. It argues that whilst there can be significant differences between individual schools, increased school autonomy is raising the profile of trade union activity in the workplace, and this needs to be better reflected in educational management research

Characterizing HR3549B using SPHERE

Aims. In this work, we characterize the low mass companion of the A0 field star HR3549. Methods. We observed HR3549AB in imaging mode with the the NIR branch (IFS and IRDIS) of SPHERE@VLT, with IFS in YJ mode and IRDIS in the H band. We also acquired a medium resolution spectrum with the IRDIS long slit spectroscopy mode. The data were reduced using the dedicated SPHERE GTO pipeline, purposely designed for this instrument. We employed algorithms such as PCA and TLOCI to reduce the speckle noise. Results. The companion was clearly visible both with IRDIS and IFS.We obtained photometry in four different bands as well as the astrometric position for the companion. Based on our astrometry, we confirm that it is a bound object and put constraints on its orbit. Although several uncertainties are still present, we estimate an age of ~100-150 Myr for this system, yielding a most probable mass for the companion of 40-50MJup and T_eff ~300-2400 K. Comparing with template spectra points to a spectral type between M9 and L0 for the companion, commensurate with its position on the color-magnitude diagram.Comment: Accepted by A&A, 13 pages, 10 Figures (Figures 9 and 10 degraded to reduce the dimension

Isolation and detection of circulating tumour cells from metastatic melanoma patients using a slanted spiral microfluidic device.

Circulating Tumour Cells (CTCs) are promising cancer biomarkers. Several methods have been developed to isolate CTCs from blood samples. However, the isolation of melanoma CTCs is very challenging as a result of their extraordinary heterogeneity, which has hindered their biological and clinical study. Thus, methods that isolate CTCs based on their physical properties, rather than surface marker expression, such as microfluidic devices, are greatly needed in melanoma. Here, we assessed the ability of the slanted spiral microfluidic device to isolate melanoma CTCs via label-free enrichment. We demonstrated that this device yields recovery rates of spiked melanoma cells of over 80% and 55%, after one or two rounds of enrichment, respectively. Concurrently, a two to three log reduction of white blood cells was achieved with one or two rounds of enrichment, respectively. We characterised the isolated CTCs using multimarker flow cytometry, immunocytochemistry and gene expression. The results demonstrated that CTCs from metastatic melanoma patients were highly heterogeneous and commonly expressed stem-like markers such as PAX3 and ABCB5. The implementation of the slanted microfluidic device for melanoma CTC isolation enables further understanding of the biology of melanoma metastasis for biomarker development and to inform future treatment approaches

The beta Pictoris association: Catalog of photometric rotational periods of low-mass members and candidate members

We intended to compile the most complete catalog of bona fide members and candidate members of the beta Pictoris association, and to measure their rotation periods and basic properties from our own observations, public archives, and exploring the literature. We carried out a multi-observatories campaign to get our own photometric time series and collected all archived public photometric data time series for the stars in our catalog. Each time series was analyzed with the Lomb-Scargle and CLEAN periodograms to search for the stellar rotation periods. We complemented the measured rotational properties with detailed information on multiplicity, membership, and projected rotational velocity available in the literature and discussed star by star. We measured the rotation periods of 112 out of 117 among bona fide members and candidate members of the beta Pictoris association and, whenever possible, we also measured the luminosity, radius, and inclination of the stellar rotation axis. This represents to date the largest catalog of rotation periods of any young loose stellar association. We provided an extensive catalog of rotation periods together with other relevant basic properties useful to explore a number of open issues, such as the causes of spread of rotation periods among coeval stars, evolution of angular momentum, and lithium-rotation connection.Comment: Forthcoming article, Received: 20 June 2016 / Accepted: 09 September 2016; 40 pages, 2 figures. The online figures A1-A73 are available at CD

Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

Understanding the impact of diet and nutrition on symptoms of Tourette Syndrome: A Scoping Review

This document is the accepted manuscript version. The final, definitive version of this paper has been published in Journal of Child Health Care, December 2017, published by SAGE Publishing, doi:https://doi.org/10.1177/1367493517748373.Anecdotal reports frequently suggest some dietary involvement in the maintenance of tics in children with Tourette syndrome (TS). This scoping review aimed to (1) understand the possible influence of diet as a trigger of tics and (2) map out the existing studies documenting dietary interventions in children with TS. Current evidence suggests no single diet to benefit individuals with TS. However, reports from parents of children with TS suggest that certain allergens in food may exacerbate tic-related symptoms. For example, an increase in tics has been related to the consumption of caffeine and refined sugar. Moreover, oligoantigenic diets and sugar-free diets have been identified as significantly reducing tics. More research is urgently needed to develop more accurate guidance for parents and children with TS, as many have reported using dietary and nutritional supplements, despite the lack of evidence detailing any benefits, side effects and recommended doses.Peer reviewedFinal Accepted Versio

Palaeozoic petroleum systems of the Orcadian Basin to Forth Approaches, Quadrants 6 - 21, UK

This report synthesises the results of the 21CXRM Palaeozoic project to describe the Carboniferous and Devonian petroleum systems of the Orcadian Basin to Forth Approaches area (Quadrants 6 – 21). Petroleum systems of the Orcadian study area that involve significant Palaeozoic elements are not wholly contained within Devonian, Carboniferous and Permian strata. A number of producing fields attest to two main proven petroleum systems; i. Co-sourced Devonian oil (with Jurassic oil) within a Jurassic reservoir: the Beatrice, Jacky and Lybster fields; ii. Jurassic-sourced oil in a Devonian and/or Carboniferous reservoir: the Buchan, Stirling, Claymore, Highlander fields. (Jurassic-sourced oil in a Permian (Zechstein) reservoir is also proven in the Carnoustie, Ettrick and Claymore fields, and in a Rotliegend reservoir in the Dee discovery). A number of additional unproven petroleum system elements are considered in this report; i. Possibilities for Devonian and Carboniferous sourcing or co-sourcing (with Jurassic oil) of Devonian, Carboniferous and Permian (Rotliegend) reservoirs in those areas underlain by proven Palaeozoic source rock; ii. Possibilities for migrated Jurassic and/or Devonian and/or Carboniferous hydrocarbons onto horst blocks and the regional Grampian High, into basement, Palaeozoic or younger reservoirs. Focusing on frontier areas north and east of the Inner Moray Firth and from the north-eastern Forth Approaches to Grampian High, integration of a large volume of seismic, well, geophysical, organic geochemistry, maturity and reservoir property data at regional scale has established: Source rocks A wide extent of potential Devonian lacustrine source rocks mapped seismically from the Inner Moray Firth to the East Orkney Basin and north of the Halibut Horst. Geochemically-typed Devonian-sourced oil shows, oil seep data outside the area of mature Kimmeridge Clay Formation, burial depth and a limited organic geochemistry/maturity dataset indicative of Devonian source rocks that are potentially mature for oil generation outside the Inner Moray Firth. Good quality gas- and oil-prone Carboniferous source rocks are mapped from the Witch Ground Graben to north eastern end of the Forth Approaches. Wells drilled on highs indicate oil-window thermal maturity levels. Oil and gas shows and basin modelling indicate Carboniferous strata buried more deeply in adjacent basins may reach gas maturity levels, with Cenozoic maturation. Key source rock intervals are: o Lower Devonian, lacustrine Struie Formation (Quadrants 11, 12), oil prone. o Middle Devonian, lacustine Orcadia Formation and Eday Group (Quadrants 11- 15 and possibly Quadrants 19, 20), oil prone. o Visean – Namurian (lower-mid Carboniferous) fluvio-deltaic Firth Coal Formation, gas and oil prone. (This unit is age-equivalent of the Scremerston and Yoredale Formations, Cleveland Group source rocks in Quadrants 25-44