Phase II Study of Paclitaxel in Patients With Soft Tissue Sarcomas

Purpose. Patients with soft tissue sarcoma (STS) who have previously received standard chemotherapy including adriamycin (doxorubicin), ifosfamide, cyclophosphamide and DTIC (dacarbazine) have very limited therapeutic options. It is important to identify new drugs with some activity in this disease and we therefore undertook this trial to determine the antitumor activity of paclitaxel (Taxol)

The feasibility and effectiveness of a web-based personalised feedback and social norms alcohol intervention in UK university students: A randomised control trial

OBJECTIVE Alcohol misuse amongst University students is a serious concern, and research has started to investigate the feasibility of using e-health interventions. This study aimed to establish the effectiveness of an electronic web-based personalised feedback intervention through the use of a randomised control trial (RCT). METHODS 506 participants were stratified by gender, age group, year of study, self-reported weekly consumption of alcohol and randomly assigned to either a control or intervention condition. Intervention participants received electronic personalised feedback and social norms information on their drinking behaviour which they could access by logging onto the website at any time during the 12-week period. CAGE score, average number of alcoholic drinks consumed per drinking occasion, and alcohol consumption over the last week were collected from participants at pre- and post-survey. RESULTS A significant difference in pre- to post-survey mean difference of alcohol consumed per occasion was found, with those in the intervention condition displaying a larger mean decrease when compared to controls. No intervention effect was found for units of alcohol consumed per week or for CAGE scores. Sixty-three percent of intervention participants agreed that the feedback provided was useful. Those intervention participants who were above the CAGE cut off were more likely to report that the website would make them think more about the amount they drank. CONCLUSIONS Delivering an electronic personalised feedback intervention to students via the World Wide Web is a feasible and potentially effective method of reducing student alcohol intake. Further research is needed to replicate this outcome, evaluate maintenance of any changes, and investigate the process of interaction with web-based interventions

The effectiveness of web-based interventions designed to decrease alcohol consumption – a systematic review

OBJECTIVE To review the published literature on the effectiveness of web-based interventions designed to decrease consumption of alcohol and/or prevent alcohol abuse. METHOD Relevant articles published up to, and including, May 2006 were identified through electronic searches of Medline, PsycInfo, Embase, Cochrane Library, ASSIA, Web of Science and Science Direct. Reference lists of all articles identified for inclusion were checked for articles of relevance. An article was included if its stated or implied purpose was to evaluate a web-based intervention designed to decrease consumption of alcohol and/or to prevent alcohol abuse. Studies were reliably selected and quality-assessed, and data were independently extracted and interpreted by two authors. RESULTS Initial searches identified 191 articles of which 10 were eligible for inclusion. Of these, five provided a process evaluation only, with the remaining five providing some pre-to post-intervention measure of effectiveness. In general the percentage quality criteria met was relatively low and only one of the 10 articles selected was a randomized control trial. CONCLUSION The current review provides inconsistent evidence on the effectiveness of eIectronic screening and brief intervention (eSBI) for alcohol use. Process research suggests that web-based interventions are generally well received. However further controlled trials are needed to fully investigate their efficacy, to determine which elements are keys to outcome and to understand if different elements are required in order to engage low- and high-risk drinkers

KiDS+VIKING+GAMA:Testing semi-analytic models of galaxy evolution with galaxy-galaxy-galaxy lensing

Several semi-analytic models (SAMs) try to explain how galaxies form, evolve and interact inside the dark matter large-scale structure. These SAMs can be tested by comparing their predictions for galaxy-galaxy-galaxy-lensing (G3L), which is weak gravitational lensing around galaxy pairs, with observations. We evaluate the SAMs by Henriques et al. (2015; H15) and by Lagos et al. (2012; L12), implemented in the Millennium Run, by comparing their predictions for G3L to observations at smaller scales than previous studies and also for pairs of lens galaxies from different populations. We compare the G3L signal predicted by the SAMs to measurements in the overlap of the Galaxy And Mass Assembly survey (GAMA), the Kilo-Degree Survey (KiDS), and the VISTA Kilo-degree Infrared Galaxy survey (VIKING), splitting lens galaxies into two colour and five stellar-mass samples. Using an improved G3L estimator, we measure the three-point correlation of the matter distribution for mixed lens pairs with galaxies from different samples, and unmixed lens pairs with galaxies from the same sample. Predictions by the H15 SAM agree with the observations for all colour-selected and all but one stellar-mass-selected sample with 95% confidence. Deviations occur for lenses with stellar masses below $9.5h^{-2}\mathrm{M}_\odot$ at scales below $0.2h^{-1}\mathrm{Mpc}$. Predictions by the L12 SAM for stellar-mass selected samples and red galaxies are significantly higher than observed, while the predicted signal for blue galaxy pairs is too low. The L12 SAM predicts more pairs of small stellar-mass and red galaxies than the H15 SAM and the observations, as well as fewer pairs of blue galaxies. Likely explanations are different treatments of environmental effects by the SAMs and different models of the initial mass function. We conclude that G3L provides a stringent test for models of galaxy formation and evolution.Comment: 14 pages, 8 figures, replaced with version accepted to Astronomy & Astrophysics after considering referees comment

Multivalent helix mimetics for PPI-inhibition.

The exploitation of multivalent ligands for the inhibition of protein-protein interactions has not yet been explored as a supramolecular design strategy. This is despite the fact that protein-protein interactions typically occur within the context of multi-protein complexes and frequently exploit avidity effects or co-operative binding interactions to achieve high affinity interactions. In this paper we describe preliminary studies on the use of a multivalent N-alkylated aromatic oligoamide helix mimetic for inhibition of p53/hDM2 and establish that protein dimerisation is promoted, rather than enhanced binding resulting from a higher effective concentration of the ligand. This journal i

The Subsystems Approach to Genome Annotation and its Use in the Project to Annotate 1000 Genomes

The release of the 1000(th) complete microbial genome will occur in the next two to three years. In anticipation of this milestone, the Fellowship for Interpretation of Genomes (FIG) launched the Project to Annotate 1000 Genomes. The project is built around the principle that the key to improved accuracy in high-throughput annotation technology is to have experts annotate single subsystems over the complete collection of genomes, rather than having an annotation expert attempt to annotate all of the genes in a single genome. Using the subsystems approach, all of the genes implementing the subsystem are analyzed by an expert in that subsystem. An annotation environment was created where populated subsystems are curated and projected to new genomes. A portable notion of a populated subsystem was defined, and tools developed for exchanging and curating these objects. Tools were also developed to resolve conflicts between populated subsystems. The SEED is the first annotation environment that supports this model of annotation. Here, we describe the subsystem approach, and offer the first release of our growing library of populated subsystems. The initial release of data includes 180 177 distinct proteins with 2133 distinct functional roles. This data comes from 173 subsystems and 383 different organisms

c-kitpos GATA-4 High Rat Cardiac Stem Cells Foster Adult Cardiomyocyte Survival through IGF-1 Paracrine Signalling

Resident c-kit positive (c-kitpos) cardiac stem cells (CSCs) could be considered the most appropriate cell type for myocardial regeneration therapies. However, much is still unknown regarding their biological properties and potential.We produced clones of high and low expressing GATA-4 CSCs from long-term bulk-cultured c-kitpos CSCs isolated from adult rat hearts. When c-kitpos GATA-4 high expressing clonal CSCs (cCSCs) were co-cultured with adult rat ventricular cardiomyocytes, we observed increased survival and contractility of the cardiomyocytes, compared to cardiomyocytes cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low expressing cCSCs. When analysed by ELISA, the concentration of IGF-1 was significantly increased in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-cultures and there was a significant correlation between IGF-1 concentration and cardiomyocyte survival. We showed the activation of the IGF-1 receptor and its downstream molecular targets in cardiomyocytes co-cultured with c-kitpos GATA-4 high cCSCs but not in cardiomyocytes that were cultured alone, co-cultured with fibroblasts or c-kitpos GATA-4 low cCSCs. Addition of a blocking antibody specific to the IGF-1 receptor inhibited the survival of cardiomyocytes and prevented the activation of its signalling in cardiomyocytes in the c-kitpos GATA-4 high cCSC/cardiomyocyte co-culture system. IGF-1 supplementation or IGF-1 high conditioned medium taken from the co-culture of c-kitpos GATA-4 high cCSCs plus cardiomyocytes did extend the survival and contractility of cardiomyocytes cultured alone and cardiomyocytes co-cultured with c-kitpos GATA-4 low cCSCs.c-kitpos GATA-4 high cCSCs exert a paracrine survival effect on cardiomyocytes through induction of the IGF-1R and signalling pathway

Isolation and characterization of resident endogenous c-Kit⁺ cardiac stem cells from the adult mouse and rat heart

This protocol describes the isolation of endogenous c-Kit (also known as CD117)-positive (c-Kit⁺), CD45-negative (CD45⁻) cardiac stem cells (eCSCs) from whole adult mouse and rat hearts. The heart is enzymatically digested via retrograde perfusion of the coronary circulation, resulting in rapid and extensive breakdown of the whole heart. Next, the tissue is mechanically dissociated further and cell fractions are separated by centrifugation. The c-Kit⁺ CD45⁻ eCSC population is isolated by magnetic-activated cell sorting technology and purity and cell numbers are assessed by flow cytometry. This process takes ∼4 h for mouse eCSCs or 4.5 h for rat eCSCs. We also describe how to characterize c-Kit⁺ CD45⁻ eCSCs. The c-Kit⁺ CD45⁻eCSCs exhibit the defining characteristics of stem cells: they are self-renewing, clonogenic and multipotent. This protocol also describes how to differentiate eCSCs into three main cardiac lineages: functional, beating cardiomyocytes, smooth muscle, and endothelial cells. These processes take 17-20 d

Quantification of dissolved CO2 plumes at the Goldeneye CO2-release experiment

According to many prognostic scenarios by the Intergovernmental Panel on Climate Change (IPCC), a scaling-up of carbon dioxide (CO2) capture and storage (CCS) by several orders-of-magnitude is necessary to meet the target of ≤2 °C global warming by 2100 relative to preindustrial levels. Since a large fraction of the predicted CO2 storage capacity lies offshore, there is a pressing need to develop field-tested methods to detect and quantify potential leaks in the marine environment. Here, we combine field measurements with numerical models to determine the flow rate of a controlled release of CO2 in a shallow marine setting at about 119 m water depth in the North Sea. In this experiment, CO2 was injected into the sediment at 3 m depth at 143 kg d-1. The new leakage monitoring tool predicts that 91 kg d-1 of CO2 escaped across the seafloor, and that 51 kg d-1 of CO2 were retained in the sediment, in agreement with independent field estimates. The new approach relies mostly on field data collected from ship-deployed technology (towed sensors, Acoustic Doppler current profiler—ADCP), which makes it a promising tool to monitor existing and upcoming offshore CO2 storage sites and to detect and quantify potential CO2 leakage

Population, behavioural and environmental drivers of malaria prevalence in the Democratic Republic of Congo

<p>Abstract</p> <p>Background</p> <p>Malaria is highly endemic in the Democratic Republic of Congo (DRC), but the limits and intensity of transmission within the country are unknown. It is important to discern these patterns as well as the drivers which may underlie them in order for effective prevention measures to be carried out.</p> <p>Methods</p> <p>By applying high-throughput PCR analyses on leftover dried blood spots from the 2007 Demographic and Health Survey (DHS) for the DRC, prevalence estimates were generated and ecological drivers of malaria were explored using spatial statistical analyses and multilevel modelling.</p> <p>Results</p> <p>Of the 7,746 respondents, 2268 (29.3%) were parasitaemic; prevalence ranged from 0-82% within geographically-defined survey clusters. Regional variation in these rates was mapped using the inverse-distance weighting spatial interpolation technique. Males were more likely to be parasitaemic than older people or females (p < 0.0001), while wealthier people were at a lower risk (p < 0.001). Increased community use of bed nets (p = 0.001) and community wealth (p < 0.05) were protective against malaria at the community level but not at the individual level. Paradoxically, the number of battle events since 1994 surrounding one's community was negatively associated with malaria risk (p < 0.0001).</p> <p>Conclusions</p> <p>This research demonstrates the feasibility of using population-based behavioural and molecular surveillance in conjunction with DHS data and geographic methods to study endemic infectious diseases. This study provides the most accurate population-based estimates to date of where illness from malaria occurs in the DRC and what factors contribute to the estimated spatial patterns. This study suggests that spatial information and analyses can enable the DRC government to focus its control efforts against malaria.</p