Older adults do not show enhanced benefits from multisensory information on speeded perceptual discrimination tasks

Some research has shown that older adults benefit more from multisensory information than do young adults. However, more recent evidence has shown that the multisensory age benefit varies considerably across tasks. In the current study, older (65 – 80) and young (18 – 30) adults (N = 191) completed a speeded perceptual discrimination task either online or face-to-face to assess task response speed. We examined whether presenting stimuli in multiple sensory modalities (audio-visual) instead of one (audio-only or visual-only) benefits older adults more than young adults. Across all three experiments, a consistent speeding of response was found in the multisensory condition compared to the unisensory conditions for both young and older adults. Furthermore, race model analysis showed a significant multisensory benefit across a broad temporal interval. Critically, there were no significant differences between young and older adults. Taken together, these findings provide strong evidence in favour of a multisensory benefit that does not differ across age groups, contrasting with prior research

Does audio-visual information result in improved health-related decision-making compared with audio-only or visual-only information? Protocol for a systematic review and meta-analysis

Introduction: Making health-related decisions can be difficult due to the amount and complexity of information available. Audio-visual information may improve memory for health information but whether audio-visual information can enhance health-related decisions has not been explored using quantitative methods. The objective of this systematic review is to understand how effective audio-visual information is for informing health-related decision-making compared with audio-only or visual-only information. Methods and analysis: Randomised controlled trials (RCTs) will be included if they include audio-visual and either audio-only or visual-only information provision and decision-making in a health setting. Studies will be excluded if they are not reported in English. Twelve databases will be searched including: Ovid MEDLINE, PubMed and PsychINFO. The Cochrane Risk of Bias tool (V.7) will be used to assess risk of bias in included RCTs. Results will be synthesised primarily using a meta-analysis; where quantitative data are not reported, a narrative synthesis will be used. Ethics and dissemination: No ethical issues are foreseen. Data will be disseminated via academic publication and conference presentations. Findings may also be published in scientific newsletters and magazines. This review is funded by the Economic and Social Research Council

Micrositing variability and mean flow scaling for marine turbulence in Ramsey Sound

We present turbulence results from two acoustic Doppler current profiler measurement campaigns carried out in Ramsey Sound at two locations within 50mof one another. The first measurements were taken in 2009 and the second in 2011; both include a complete spring–neap cycle. In this paper we characterise turbulence through turbulent kinetic energy (TKE) density and integral lengthscales and their relationships with one another and with mean flow parameters. We briefly describe the methods used to calculate these parameters. We find that a flood–ebb asymmetry is present in the data from both measurement campaigns, but although the flood tides are similar at both locations, the ebb tides are much more energetic in the 2011 data than the 2009 data. We suggest that this may be due to differences in seabed features between the two measurement locations. Dimensional analysis is employed to investigate how TKE scales with mean flow velocity; we find that the expected quadratic scaling is not well supported by the data at either measurement location. As a consequence, flows that have more energetic turbulence may instead appear to be less turbulent if judged by turbulence intensity. We investigate the correlation between lengthscales and TKE density and find that it is highly site-specific: it should not be assumed that for a given measurement location highly energetic turbulence is associated with larger flow structures or vice versa

Interleukin-17D and Nrf2 mediate initial innate immune cell recruitment and restrict MCMV infection.

Innate immune cells quickly infiltrate the site of pathogen entry and not only stave off infection but also initiate antigen presentation and promote adaptive immunity. The recruitment of innate leukocytes has been well studied in the context of extracellular bacterial and fungal infection but less during viral infections. We have recently shown that the understudied cytokine Interleukin (IL)-17D can mediate neutrophil, natural killer (NK) cell and monocyte infiltration in sterile inflammation and cancer. Herein, we show that early immune cell accumulation at the peritoneal site of infection by mouse cytomegalovirus (MCMV) is mediated by IL-17D. Mice deficient in IL-17D or the transcription factor Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an inducer of IL-17D, featured an early decreased number of innate immune cells at the point of viral entry and were more susceptible to MCMV infection. Interestingly, we were able to artificially induce innate leukocyte infiltration by applying the Nrf2 activator tert-butylhydroquinone (tBHQ), which rendered mice less susceptible to MCMV infection. Our results implicate the Nrf2/IL-17D axis as a sensor of viral infection and suggest therapeutic benefit in boosting this pathway to promote innate antiviral responses

Mathematical model of a telomerase transcriptional regulatory network developed by cell-based screening: analysis of inhibitor effects and telomerase expression mechanisms

Cancer cells depend on transcription of telomerase reverse transcriptase (TERT). Many transcription factors affect TERT, though regulation occurs in context of a broader network. Network effects on telomerase regulation have not been investigated, though deeper understanding of TERT transcription requires a systems view. However, control over individual interactions in complex networks is not easily achievable. Mathematical modelling provides an attractive approach for analysis of complex systems and some models may prove useful in systems pharmacology approaches to drug discovery. In this report, we used transfection screening to test interactions among 14 TERT regulatory transcription factors and their respective promoters in ovarian cancer cells. The results were used to generate a network model of TERT transcription and to implement a dynamic Boolean model whose steady states were analysed. Modelled effects of signal transduction inhibitors successfully predicted TERT repression by Src-family inhibitor SU6656 and lack of repression by ERK inhibitor FR180204, results confirmed by RT-QPCR analysis of endogenous TERT expression in treated cells. Modelled effects of GSK3 inhibitor 6-bromoindirubin-3′-oxime (BIO) predicted unstable TERT repression dependent on noise and expression of JUN, corresponding with observations from a previous study. MYC expression is critical in TERT activation in the model, consistent with its well known function in endogenous TERT regulation. Loss of MYC caused complete TERT suppression in our model, substantially rescued only by co-suppression of AR. Interestingly expression was easily rescued under modelled Ets-factor gain of function, as occurs in TERT promoter mutation. RNAi targeting AR, JUN, MXD1, SP3, or TP53, showed that AR suppression does rescue endogenous TERT expression following MYC knockdown in these cells and SP3 or TP53 siRNA also cause partial recovery. The model therefore successfully predicted several aspects of TERT regulation including previously unknown mechanisms. An extrapolation suggests that a dominant stimulatory system may programme TERT for transcriptional stability

Academic doctors' views of complementary and alternative medicine (CAM) and its role within the NHS: an exploratory qualitative study

<p>Abstract</p> <p>Background</p> <p>There has been a marked increase in the use of complementary and alternative medicine (CAM) in the UK population in recent years. Surveys of doctors' perspectives on CAM have identified a variety of views and potential information needs. While these are useful for describing the proportions of doctors who hold particular attitudes towards CAM, they are less helpful for understanding why. In addition, while the views of non-academic doctors have begun to be studied, the perspective and rationales of academic doctors remains under-researched. It seems important to investigate the views of those with a research-orientation, given the emphasis on the need for more scientific evidence in recent debates on CAM.</p> <p>Methods</p> <p>This exploratory study used qualitative methods to explore academic doctors' views of CAM and the rationales they provided for their views. A purposeful sampling strategy was used to identify doctors with a dual clinical and academic role in the Bristol area, with an anticipated variety of views on CAM. Semi-structured interviews were conducted with nine doctors. The data were analysed thematically, drawing on the Framework Approach.</p> <p>Results</p> <p>The doctors expressed a spectrum of views on CAM, falling into three broad groups: the 'enthusiasts', the 'sceptics' and the 'undecided'. Scepticism or uncertainty about the value of CAM was prominent, except among those practising a form of CAM. A variety of rationales underpinned their perspectives on CAM, a key recurring rationale being their perspective on the scientific evidence base. The main themes arising included: the role of doctors' professional experiences of conventional medicine and CAM in shaping their attitudes towards CAM, doctor-patient communication about CAM and patient disclosure, whether there is a need for training and education in CAM for doctors, a hierarchy of acceptability of CAM and the nature of evidence; and the role of CAM within the NHS.</p> <p>Conclusion</p> <p>Despite the caution or scepticism towards CAM expressed by doctors in this study, more open doctor-patient communication about CAM may enable doctors' potential concerns about CAM to be addressed, or at least enhance their knowledge of what treatments or therapies their patients are using. Offering CAM to patients may serve to enhance patients' treatment choices and even increase doctors' fulfilment in their practice. However, given the recurring concerns about lack of scientific evidence expressed by the doctors in this study, perceptions of the evidence base may remain a significant barrier to greater integration of CAM within the NHS.</p

Disease surveillance using a hidden Markov model

<p>Abstract</p> <p>Background</p> <p>Routine surveillance of disease notification data can enable the early detection of localised disease outbreaks. Although hidden Markov models (HMMs) have been recognised as an appropriate method to model disease surveillance data, they have been rarely applied in public health practice. We aimed to develop and evaluate a simple flexible HMM for disease surveillance which is suitable for use with sparse small area count data and requires little baseline data.</p> <p>Methods</p> <p>A Bayesian HMM was designed to monitor routinely collected notifiable disease data that are aggregated by residential postcode. Semi-synthetic data were used to evaluate the algorithm and compare outbreak detection performance with the established Early Aberration Reporting System (EARS) algorithms and a negative binomial cusum.</p> <p>Results</p> <p>Algorithm performance varied according to the desired false alarm rate for surveillance. At false alarm rates around 0.05, the cusum-based algorithms provided the best overall outbreak detection performance, having similar sensitivity to the HMMs and a shorter average time to detection. At false alarm rates around 0.01, the HMM algorithms provided the best overall outbreak detection performance, having higher sensitivity than the cusum-based Methods and a generally shorter time to detection for larger outbreaks. Overall, the 14-day HMM had a significantly greater area under the receiver operator characteristic curve than the EARS C3 and 7-day negative binomial cusum algorithms.</p> <p>Conclusion</p> <p>Our findings suggest that the HMM provides an effective method for the surveillance of sparse small area notifiable disease data at low false alarm rates. Further investigations are required to evaluation algorithm performance across other diseases and surveillance contexts.</p

Experiences of non-progressive and augmented labour among nulliparous women: a qualitative interview study in a Grounded Theory approach

<p>Abstract</p> <p>Background</p> <p>Non-progressive labour is the most common complication in nulliparas and is primarily treated by augmentation. Augmented labour is often terminated by instrumental delivery. Little qualitative research has addressed experiences of non-progressive and augmented deliveries. The aim of this study was to gain a deeper understanding of the experience of non-progressive and augmented labour among nulliparas and their experience of the care they received.</p> <p>Methods</p> <p>A qualitative study was conducted using individual interviews. Data was collected and analysed according to the Grounded Theory method. The participants were a purposive sample of ten women. The interviews were conducted 4–15 weeks after delivery.</p> <p>Results</p> <p>The women had contrasting experiences during the birth process. During labour there was a conflict between the expectation of having a natural delivery and actually having a medical delivery. The women experienced a feeling of separation between mind and body. Interacting with the midwife had a major influence on feelings of losing and regaining control. Reconciliation between the contrasting feelings during labour was achieved. The core category was named Dialectical Birth Process and comprised three categories: Balancing natural and medical delivery, Interacting, Losing and regaining control.</p> <p>Conclusion</p> <p>A dialectical process was identified in these women's experiences of non-progressive labour. The process is susceptible to interaction with the midwife; especially her support to the woman's feeling of being in control. Midwives should secure that the woman's recognition of the fact that the labour is non-progressive and augmentation is required is handled with respect for the dialectical process. Augmentation of labour should be managed as close to the course of natural labour and delivery as possible.</p

TDAG51 is an ERK signaling target that opposes ERK-mediated HME16C mammary epithelial cell transformation

<p>Abstract</p> <p>Introduction</p> <p>Signaling downstream of Ras is mediated by three major pathways, Raf/ERK, phosphatidylinositol 3 kinase (PI3K), and Ral guanine nucleotide exchange factor (RalGEF). Ras signal transduction pathways play an important role in breast cancer progression, as evidenced by the frequent over-expression of the Ras-activating epidermal growth factor receptors EGFR and ErbB2. Here we investigated which signal transduction pathways downstream of Ras contribute to EGFR-dependent transformation of telomerase-immortalized mammary epithelial cells HME16C. Furthermore, we examined whether a highly transcriptionally regulated ERK pathway target, PHLDA1 (TDAG51), suggested to be a tumor suppressor in breast cancer and melanoma, might modulate the transformation process.</p> <p>Methods</p> <p>Cellular transformation of human mammary epithelial cells by downstream Ras signal transduction pathways was examined using anchorage-independent growth assays in the presence and absence of EGFR inhibition. TDAG51 protein expression was down-regulated by interfering small hairpin RNA (shRNA), and the effects on cell proliferation and death were examined in Ras pathway-transformed breast epithelial cells.</p> <p>Results</p> <p>Activation of both the ERK and PI3K signaling pathways was sufficient to induce cellular transformation, which was accompanied by up-regulation of EGFR ligands, suggesting autocrine EGFR stimulation during the transformation process. Only activation of the ERK pathway was sufficient to transform cells in the presence of EGFR inhibition and was sufficient for tumorigenesis in xenografts. Up-regulation of the PHLDA1 gene product, TDAG51, was found to correlate with persistent ERK activation and anchorage-independent growth in the absence or presence of EGFR inhibition. Knockdown of this putative breast cancer tumor-suppressor gene resulted in increased ERK pathway activation and enhanced matrix-detached cellular proliferation of Ras/Raf transformed cells.</p> <p>Conclusion</p> <p>Our results suggest that multiple Ras signal transduction pathways contribute to mammary epithelial cell transformation, but that the ERK signaling pathway may be a crucial component downstream of EGFR activation during tumorigenesis. Furthermore, persistent activation of ERK signaling up-regulates TDAG51. This event serves as a negative regulator of both Erk activation as well as matrix-detached cellular proliferation and suggests that TDAG51 opposes ERK-mediated transformation in breast epithelial cells.</p