430 research outputs found

    An exploration of the accentuation effect: errors in memory for voice fundamental frequency (F0) and speech rate

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    The accentuation effect demonstrates how memory often reflects category typical representations rather than the specific features of learned items. The present study investigated the impact of manipulating fundamental frequency (F0) and speech rate (syllables per second) on immediate target matching performance (selecting a voice from a pair to match a previously heard target voice) for a range of synthesised voices. It was predicted that when participants were presented with high or low frequency target voices, voices even higher or lower in frequency would be selected. The same pattern was also predicted for speech rate. Inconsistent with the accentuation account, the results showed a general bias to select voices higher in frequency for high, moderate, and low frequency target voices. For speech rate, listeners selected voices faster in rate for slow rate target voices. Overall it seems doubtful that listeners rely solely on categorical information about voices during recognition

    Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

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    Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

    Organisational barriers to the facilitation of overseas volunteering and training placements in the NHS

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    Background Undertaking a period of voluntary work or a professional placement overseas has long been a feature of medical training in the UK. There are now a number of high profile National Health Service (NHS) initiatives aimed at increasing access to such opportunities for staff at all levels. We present findings from a qualitative study involving a range of NHS staff and other stakeholders which explored barriers to participation in these activities. Methods A grounded theory methodology was drawn upon to conduct thematic based analysis. Our data included in-depth, semi-structured interviews with a range of returned volunteers, non-volunteers and other stakeholders (n=51) who were, or had been, employed by the NHS. Results There are significant barriers to placement and volunteering activity stemming from structural and organisational shortcomings within the NHS. Difficulties in filling clinical roles has a significant impact on the ability of staff to plan and undertake independent placements. There is currently no clearly defined pathway within the NHS by which the majority of grades can apply for, or organise, a period of overseas voluntary or professional placement activity. There were divergent views on the relevance and usefulness of overseas professional placements. Conclusions We argue that in the context of current UK policy initiatives aimed at facilitating overseas volunteer and professional placement activity, urgent attention needs to be given to the structural and organisational framework within which such initiatives will be required to work

    Do Meio- and Macrobenthic Nematodes Differ in Community Composition and Body Weight Trends with Depth?

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    Nematodes occur regularly in macrobenthic samples but are rarely identified from them and are thus considered exclusively a part of the meiobenthos. Our study compares the generic composition of nematode communities and their individual body weight trends with water depth in macrobenthic (>250/300 µm) samples from the deep Arctic (Canada Basin), Gulf of Mexico (GOM) and the Bermuda slope with meiobenthic samples (<45 µm) from GOM. The dry weight per individual (µg) of all macrobenthic nematodes combined showed an increasing trend with increasing water depth, while the dry weight per individual of the meiobenthic GOM nematodes showed a trend to decrease with increasing depth. Multivariate analyses showed that the macrobenthic nematode community in the GOM was more similar to the macrobenthic nematodes of the Canada Basin than to the GOM meiobenthic nematodes. In particular, the genera Enoploides, Crenopharynx, Micoletzkyia, Phanodermella were dominant in the macrobenthos and accounted for most of the difference. Relative abundance of non-selective deposit feeders (1B) significantly decreased with depth in macrobenthos but remained dominant in the meiobenthic community. The occurrence of a distinct assemblage of bigger nematodes of high dry weight per individual in the macrobenthos suggests the need to include nematodes in macrobenthic studies

    Randomised phase II study of ASA404 combined with carboplatin and paclitaxel in previously untreated advanced non-small cell lung cancer

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    ASA404 (5,6-dimethylxanthenone-4-acetic acid or DMXAA) is a small-molecule tumour-vascular disrupting agent (Tumour-VDA). This randomised phase II study evaluated ASA404 plus standard therapy of carboplatin and paclitaxel in patients with histologically confirmed stage IIIb or IV non-small cell lung cancer (NSCLC) not previously treated with chemotherapy. Patients were randomised to receive ⩽6 cycles of carboplatin area under the plasma concentration–time curve 6 mg ml−1 min and paclitaxel 175 mg m−2 (CP, n=36) or standard therapy plus ASA404 1200 mg m−2 (ASA404-CP, n=37). There was little change in the systemic exposure of either total or free carboplatin or paclitaxel on addition of ASA404. Safety profiles were similar and manageable in both groups, with most adverse effects attributed to standard therapy. Tumour response rate (31 vs 22%), median time to tumour progression (5.4 vs 4.4 months) and median survival (14.0 vs 8.8 months, hazard ratio 0.73, 95% CI 0.39, 1.38) were improved in the ASA404 combination group compared with the standard therapy group. In conclusion, this study establishes the feasibility of combining ASA404 with carboplatin and paclitaxel in patients with previously untreated, advanced NSCLC, demonstrating a manageable safety profile and lack of adverse pharmacokinetic interactions. The results indicate that there may be a benefit associated with ASA404, but this needs to be evaluated in a larger trial

    Four reasons to prefer Bayesian analyses over significance testing

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    Inference using significance testing and Bayes factors is compared and contrasted in five case studies based on real research. The first study illustrates that the methods will often agree, both in motivating researchers to conclude that H1 is supported better than H0, and the other way round, that H0 is better supported than H1. The next four, however, show that the methods will also often disagree. In these cases, the aim of the paper will be to motivate the sensible evidential conclusion, and then see which approach matches those intuitions. Specifically, it is shown that a high-powered non-significant result is consistent with no evidence for H0 over H1 worth mentioning, which a Bayes factor can show, and, conversely, that a low-powered non-significant result is consistent with substantial evidence for H0 over H1, again indicated by Bayesian analyses. The fourth study illustrates that a high-powered significant result may not amount to any evidence for H1 over H0, matching the Bayesian conclusion. Finally, the fifth study illustrates that different theories can be evidentially supported to different degrees by the same data; a fact that P-values cannot reflect but Bayes factors can. It is argued that appropriate conclusions match the Bayesian inferences, but not those based on significance testing, where they disagree
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