Impairment of Methotrexate Transport Is Common in Osteosarcoma Tumor Samples

Osteosarcoma does not respond well to conventional dose methotrexate but does respond to high-dose methotrexate. Previous work has indicated that this resistance may be due to impaired transport of methotrexate across the cell membrane. In this study, the PT430 competitive displacement assay was adapted to evaluate methotrexate transport in 69 high-grade osteosarcoma tumor samples. All samples studied were shown to have relatively impaired methotrexate transport by PT430 assay. Ninety-nine percent of the samples had less than 20% PT430 displacement by methotrexate. Eighty-eight percent exhibited displacement by methotrexate at less than 50% of the displacement by trimetrexate. The high frequency of impaired transport suggests the presence of decreased functionality of the reduced folate carrier protein. The overwhelming presence of impaired transport may explain why methotrexate needs to be given in high doses to be effective in osteosarcoma therapy and suggests that reduced folate carrier-independent antifolates should be explored

Identifying interventions with Gypsies, Roma and Travellers to promote immunisation uptake: methodological approach and findings

Background: In the UK, Gypsy, Roma and Traveller (GRT) communities are generally considered to be at risk of low or variable immunisation uptake. Many strategies to increase uptake for the general population are relevant for GRT communities, however additional approaches may also be required, and importantly one cannot assume that “one size fits all”. Robust methods are needed to identify content and methods of delivery that are likely to be acceptable, feasible, effective and cost effective. In this paper, we describe the approach taken to identify potential interventions to increase uptake of immunisations in six GRT communities in four UK cities; and present the list of prioritised interventions that emerged. / Methods: This work was conducted in three stages: (1) a modified intervention mapping process to identify ideas for potential interventions; (2) a two-step prioritisation activity at workshops with 51 GRTs and 25 Service Providers to agree a prioritised list of potentially feasible and acceptable interventions for each community; (3) cross-community synthesis to produce a final list of interventions. The theoretical framework underpinning the study was the Social Ecological Model. / Results: Five priority interventions were agreed across communities and Service Providers to improve the uptake of immunisation amongst GRTs who are housed or settled on an authorised site. These interventions are all at the Institutional (e.g. cultural competence training) and Policy (e.g. protected funding) levels of the Social Ecological Model. / Conclusions: The “upstream” nature of the five interventions reinforces the key role of GP practices, frontline workers and wider NHS systems on improving immunisation uptake. All five interventions have potentially broader applicability than GRTs. We believe that their impact would be enhanced if delivered as a combined package. The robust intervention development and co-production methods described could usefully be applied to other communities where poor uptake of immunisation is a concern. / Study registration: Current Controlled Trials ISRCTN20019630, Date of registration 01-08-2013, Prospectively registered

Stochasticity and traffic jams in the transcription of ribosomal RNA: Intriguing role of termination and antitermination

In fast growing bacteria, ribosomal RNA (rRNA) is required to be transcribed at very high rates to sustain the high cellular demand on ribosome synthesis. This results in dense traffic of RNA polymerases (RNAP). We developed a stochastic model, integrating results of single-molecule and quantitative in vivo studies of E. coli, to evaluate the quantitative effect of pausing, termination, and antitermination on rRNA transcription. Our calculations reveal that in dense RNAP traffic, spontaneous pausing of RNAP can lead to severe "traffic jams", as manifested in the broad distribution of inter-RNAP distances and can be a major factor limiting transcription and hence growth. Our results suggest the suppression of these pauses by the ribosomal antitermination complex to be essential at fast growth. Moreover, unsuppressed pausing by even a few non-antiterminated RNAPs can already reduce transcription drastically under dense traffic. However, the termination factor Rho can remove the non-antiterminated RNAPs and restore fast transcription. The results thus suggest an intriguing role by Rho to enhance rather than attenuate rRNA transcription.Comment: includes Supporting Informatio

Questioning the rise of gelatinous zooplankton in the World's oceans

During the past several decades, high numbers of gelatinous zooplankton species have been reported in many estuarine and coastal ecosystems. Coupled with media-driven public perception, a paradigm has evolved in which the global ocean ecosystems are thought to be heading toward being dominated by “nuisance” jellyfish. We question this current paradigm by presenting a broad overview of gelatinous zooplankton in a historicalcontext to develop the hypothesis that population changes reflect the human-mediated alteration of global ocean ecosystems. To this end, we synthesize information related to the evolutionary context of contemporary gelatinous zooplankton blooms, the human frame of reference forchanges in gelatinous zooplankton populations, and whether sufficient data are available to have established the paradigm. We conclude that the current paradigm in which it is believed that there has been a global increase in gelatinous zooplankton is unsubstantiated, and we develop a strategy for addressing the critical questions about long-term, human-related changes in the sea as they relate to gelatinous zooplankton blooms

Engaging Gypsy, Roma, and Traveller Communities in Research: Maximizing Opportunities and Overcoming Challenges

Gypsy, Roma, and Traveller people are marginalized worldwide and experience severe health inequalities, even in comparison to other ethnic minority groups. While diverse and hard to categorize, these communities are highly cohesive and members have a strong sense of identity as a group apart from the majority population. Researchers commonly experience challenges in accessing, recruiting, and retaining research participants from these communities, linked to their outsider status, insular nature, and history of discrimination. In this article, the challenges and the opportunities of engaging Gypsies, Roma, and Travellers in a multicenter qualitative research project are discussed. The management of public involvement and community engagement in this U.K.-based project provides insights into conducting research effectively with ethnically and linguistically diverse communities, often considered to be "hard to reach.

Engaging Gypsy, Roma, and Traveller Communities in research: Maximizing opportunities and overcoming challenges

Gypsy, Roma, and Traveller people are marginalized worldwide and experience severe health inequalities, even in comparison to other ethnic minority groups. While diverse and hard to categorize, these communities are highly cohesive and members have a strong sense of identity as a group apart from the majority population. Researchers commonly experience challenges in accessing, recruiting, and retaining research participants from these communities, linked to their outsider status, insular nature, and history of discrimination. In this article, the challenges and the opportunities of engaging Gypsies, Roma, and Travellers in a multicenter qualitative research project are discussed. The management of public involvement and community engagement in this U.K.-based project provides insights into conducting research effectively with ethnically and linguistically diverse communities, often considered to be “hard to reach.”

Shifts between gelatinous and crustacean plankton in a coastal upwellin region

proyectos RADIALES (IEO) y EURO-BASIN (Ref. 264933, 7FP)Variability in the dominance of copepods vs. gelatinous plankton was analysed using monthly time-series covering the last 55 years and related to changes in climatic, oceanographic, and fishery conditions in the upwelling region of Galicia (NW Spain). Seasonality was generally the main component of variability in all groups, both along the coast and in the nearby ocean, but no common long-term trend was found. Coastal copepods increased since the early 1990s, and gelatinous plankton increased in the ocean during the 1980s. Different trends were found for gelatinous plankton in two coastal sites, characterized by increases in either medusae or tunicates. In all series, multiyear periods of relative dominance of gelatinous vs. copepod plankton were evident. In general, copepod periods were observed in positive phases of the main modes of regional climatic variability. Conversely, gelatinous periods occurred during negative climatic phases. However, the low correlations between gelatinous plankton and climatic, oceanographic, or fishery variables suggest that local factors play a major role in their proliferations.7FP, IEOPreprin

Identifying interventions with Gypsies, Roma and Travellers to promote immunisation uptake: methodological approach and findings

Background: In the UK, Gypsy, Roma and Traveller (GRT) communities are generally considered to be at risk of low or variable immunisation uptake. Many strategies to increase uptake for the general population are relevant for GRT communities, however additional approaches may also be required, and importantly one cannot assume that “one size fits all”. Robust methods are needed to identify content and methods of delivery that are likely to be acceptable, feasible, effective and cost effective. In this paper, we describe the approach taken to identify potential interventions to increase uptake of immunisations in six GRT communities in four UK cities; and present the list of prioritised interventions that emerged.Methods: This work was conducted in three stages: (1) a modified intervention mapping process to identify ideas for potential interventions; (2) a two-step prioritisation activity at workshops with 51 GRTs and 25 Service Providers to agree a prioritised list of potentially feasible and acceptable interventions for each community; (3) crosscommunity synthesis to produce a final list of interventions. The theoretical framework underpinning the study was the Social Ecological Model.Results: Five priority interventions were agreed across communities and Service Providers to improve the uptake of immunisation amongst GRTs who are housed or settled on an authorised site. These interventions are all at the Institutional (e.g. cultural competence training) and Policy (e.g. protected funding) levels of the Social Ecological Model.Conclusions: The “upstream” nature of the five interventions reinforces the key role of GP practices, frontline workers and wider NHS systems on improving immunisation uptake. All five interventions have potentially broader applicability than GRTs. We believe that their impact would be enhanced if delivered as a combined package. The robust intervention development and co production methods described could usefully be applied to other communities where poor uptake of immunisation is a concern

The Type la Supernova 2001V in NGC 3987

CCD photometry of the type Ia SN 2001V occured in the edge-on spiral galaxy NGC 3987 is presented. The observations made through Johnson-Cousins BVRI filters were collected from Feb. 24 (t = -8 days, with respect to B-maximum), up to May 5 (t = +62 days). The light curves are analyzed with the revised Multi-Colour Light Curve Shape (MLCS) method by fitting template vectors to the observed light curves simultaneously. The reddening of SN 2001V is estimated to be E(B-V)=0.05 mag, while the galactic component is E(B-V) = 0.02 mag, suggesting that part of the reddening may be due to the ISM in the host galaxy. The Delta parameter in MLCS converged to -0.47 mag, indicating that this SN was overluminous relative to the majority of Type Ia SNe. The inferred distance to its host galaxy, NGC 3987, is 74.5 \pm 5 Mpc, which is in good agreement with recently determined kinematic distances, based on radial velocity corrected for Virgo-infall and Hubble constant H_0 = 65 km/s/Mpc.Comment: 6 pages, 4 figures, accepted in Astronomy and Astrophysic