1,002 research outputs found
Acceptability of orodispersible films for delivery of medicines to infants and preschool children
Orodispersible films (ODFs) possess potential to facilitate oral drug delivery to children; however, documentation
of their acceptability in this age group is lacking. This study is the first to explore the initial
perceptions, acceptability and ease of use of ODFs for infants and preschool children, and their caregivers
through observed administration of the type of dosage form. Placebo ODFs were administered
to children stratified into aged 6 to 12 months, 1 year, 2 years, 3 years, 4 years and 5 years old and into
those with an acute illness or long-term stable condition in hospital setting. Acceptability of the dosage
form and end-user views were assessed by (a) direct observation of administration, (b) questionnaires
to caregivers and nurses, and (c) age-adapted questionnaires for children aged 3 years and over.
The majority of children (78%) aged 3 years and over gave the ODF a positive rating both on verbal
and non-verbal scales. Despite little prior experience, 78% of caregivers expressed positive opinion
about ODFs before administration. After the ODFs were taken, 79% of infant caregivers and 86% caregivers
of preschool children positively rated their child’s acceptance of the ODF. The intraclass correlation
coefficient value was 0.92 showing good agreement between ratings of caregivers and nurses.
ODFs showed a high degree of acceptability among young children and their caregivers. If drug loading
permits, pharmaceutical companies should consider developing pediatric medicines in this format.
The methodology described here is useful in assessing the acceptability of active ODF preparations
and other dosage forms to children
FIC/FEM formulation with matrix stabilizing terms for incompressible flows at low and high Reynolds numbers
The final publication is available at Springer via http://dx.doi.org/10.1007/s00466-006-0060-yWe present a general formulation for incompressible fluid flow analysis using the finite element method. The necessary stabilization for dealing with convective effects and the incompressibility condition are introduced via the Finite Calculus method using a matrix form of the stabilization parameters. This allows to model a wide range of fluid flow problems for low and high Reynolds numbers flows without introducing a turbulence model. Examples of application to the analysis of incompressible flows with moderate and large Reynolds numbers are presented.Peer ReviewedPostprint (author's final draft
Non-Fermi-liquid d-wave metal phase of strongly interacting electrons
Developing a theoretical framework for conducting electronic fluids
qualitatively distinct from those described by Landau's Fermi-liquid theory is
of central importance to many outstanding problems in condensed matter physics.
One such problem is that, above the transition temperature and near optimal
doping, high-transition-temperature copper-oxide superconductors exhibit
`strange metal' behaviour that is inconsistent with being a traditional Landau
Fermi liquid. Indeed, a microscopic theory of a strange-metal quantum phase
could shed new light on the interesting low-temperature behaviour in the
pseudogap regime and on the d-wave superconductor itself. Here we present a
theory for a specific example of a strange metal---the 'd-wave metal'. Using
variational wavefunctions, gauge theoretic arguments, and ultimately
large-scale density matrix renormalization group calculations, we show that
this remarkable quantum phase is the ground state of a reasonable microscopic
Hamiltonian---the usual t-J model with electron kinetic energy and two-spin
exchange supplemented with a frustrated electron `ring-exchange' term,
which we here examine extensively on the square lattice two-leg ladder. These
findings constitute an explicit theoretical example of a genuine
non-Fermi-liquid metal existing as the ground state of a realistic model.Comment: 22 pages, 12 figures: 6 pages, 7 figures of main text + 16 pages, 5
figures of Supplementary Information; this is approximately the version
published in Nature, minus various subedits in the main tex
Berkovich Nanoindentation on AlN Thin Films
Berkovich nanoindentation-induced mechanical deformation mechanisms of AlN thin films have been investigated by using atomic force microscopy (AFM) and cross-sectional transmission electron microscopy (XTEM) techniques. AlN thin films are deposited on the metal-organic chemical-vapor deposition (MOCVD) derived Si-doped (2 × 1017 cm−3) GaN template by using the helicon sputtering system. The XTEM samples were prepared by means of focused ion beam (FIB) milling to accurately position the cross-section of the nanoindented area. The hardness and Young’s modulus of AlN thin films were measured by a Berkovich nanoindenter operated with the continuous contact stiffness measurements (CSM) option. The obtained values of the hardness and Young’s modulus are 22 and 332 GPa, respectively. The XTEM images taken in the vicinity regions just underneath the indenter tip revealed that the multiple “pop-ins” observed in the load–displacement curve during loading are due primarily to the activities of dislocation nucleation and propagation. The absence of discontinuities in the unloading segments of load–displacement curve suggests that no pressure-induced phase transition was involved. Results obtained in this study may also have technological implications for estimating possible mechanical damages induced by the fabrication processes of making the AlN-based devices
Daily life stress and the cortisol awakening response : testing the anticipation hypothesis
Acknowledgments We thank Paul Stewart for his contribution to data collection and Dr Matthew Jones for programming the handheld computers. Author Contributions Conceived and designed the experiments: WS DJP. Performed the experiments: DJP. Analyzed the data: WS. Wrote the paper: WS DJP.Peer reviewedPublisher PD
Modulation of emotional appraisal by false physiological feedback during fMRI
BACKGROUND
James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined.
METHODOLOGY/PRINCIPAL FINDINGS
We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level.
CONCLUSIONS/SIGNIFICANCE
Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state
Modulation of emotional appraisal by false physiological feedback during fMRI
BACKGROUND
James and Lange proposed that emotions are the perception of physiological reactions. Two-level theories of emotion extend this model to suggest that cognitive interpretations of physiological changes shape self-reported emotions. Correspondingly false physiological feedback of evoked or tonic bodily responses can alter emotional attributions. Moreover, anxiety states are proposed to arise from detection of mismatch between actual and anticipated states of physiological arousal. However, the neural underpinnings of these phenomena previously have not been examined.
METHODOLOGY/PRINCIPAL FINDINGS
We undertook a functional brain imaging (fMRI) experiment to investigate how both primary and second-order levels of physiological (viscerosensory) representation impact on the processing of external emotional cues. 12 participants were scanned while judging face stimuli during both exercise and non-exercise conditions in the context of true and false auditory feedback of tonic heart rate. We observed that the perceived emotional intensity/salience of neutral faces was enhanced by false feedback of increased heart rate. Regional changes in neural activity corresponding to this behavioural interaction were observed within included right anterior insula, bilateral mid insula, and amygdala. In addition, right anterior insula activity was enhanced during by asynchronous relative to synchronous cardiac feedback even with no change in perceived or actual heart rate suggesting this region serves as a comparator to detect physiological mismatches. Finally, BOLD activity within right anterior insula and amygdala predicted the corresponding changes in perceived intensity ratings at both a group and an individual level.
CONCLUSIONS/SIGNIFICANCE
Our findings identify the neural substrates supporting behavioural effects of false physiological feedback, and highlight mechanisms that underlie subjective anxiety states, including the importance of the right anterior insula in guiding second-order "cognitive" representations of bodily arousal state
Comparison of Functional Proteomic Analyses of Human Breast Cancer Cell Lines T47D and MCF7
T47D and MCF7 are two human hormone-dependent breast cancer cell lines which are widely used as experimental models for in vitro and in vivo (tumor xenografts) breast cancer studies. Several proteins involved in cancer development were identified in these cell lines by proteomic analyses. Although these studies reported the proteomic profiles of each cell line, until now, their differential protein expression profiles have not been established. Here, we used two-dimensional gel and mass spectrometry analyses to compare the proteomic profiles of the two cell lines, T47D and MCF7. Our data revealed that more than 164 proteins are differentially expressed between them. According to their biological functions, the results showed that proteins involved in cell growth stimulation, anti-apoptosis mechanisms and cancerogenesis are more strongly expressed in T47D than in MCF7. These proteins include G1/S-specific cyclin-D3 and prohibitin. Proteins implicated in transcription repression and apoptosis regulation, including transcriptional repressor NF-X1, nitrilase homolog 2 and interleukin-10, are, on the contrary, more strongly expressed in MCF7 as compared to T47D. Five proteins that were previously described as breast cancer biomarkers, namely cathepsin D, cathepsin B, protein S100-A14, heat shock protein beta-1 (HSP27) and proliferating cell nuclear antigen (PCNA), are found to be differentially expressed in the two cell lines. A list of differentially expressed proteins between T47D and MCF7 was generated, providing useful information for further studies of breast cancer mechanisms with these cell lines as models
Spatially Resolved Distribution Function and the Medium-Range Order in Metallic Liquid and Glass
The structural description of disordered systems has been a longstanding challenge in physical science. We propose an atomic cluster alignment method to reveal the development of three-dimensional topological ordering in a metallic liquid as it undercools to form a glass. By analyzing molecular dynamic (MD) simulation trajectories of a Cu64.5Zr35.5 alloy, we show that medium-range order (MRO) develops in the liquid as it approaches the glass transition. Specifically, around Cu sites, we observe “Bergman triacontahedron” packing (icosahedron, dodecahedron and icosahedron) that extends out to the fourth shell, forming an interpenetrating backbone network in the glass. The discovery of Bergman-type MRO from our order-mining technique provides unique insights into the topological ordering near the glass transition and the relationship between metallic glasses and quasicrystals
Room for Improvement in Conducting and Reporting Non-Inferiority Randomized Controlled Trials on Drugs: A Systematic Review
BACKGROUND: A non-inferiority (NI) trial is intended to show that the effect of a new treatment is not worse than the comparator. We conducted a review to identify how NI trials were conducted and reported, and whether the standard requirements from the guidelines were followed. METHODOLOGY AND PRINCIPAL FINDINGS: From 300 randomly selected articles on NI trials registered in PubMed at 5 February 2009, we included 227 NI articles that referred to 232 trials. We excluded studies on bioequivalence, trials on healthy volunteers, non-drug trials, and articles of which the full-text version could not be retrieved. A large proportion of trials (34.0%) did not use blinding. The NI margin was reported in 97.8% of the trials, but only 45.7% of the trials reported the method to determine the margin. Most of the trials used either intention to treat (ITT) (34.9%) or per-protocol (PP) analysis (19.4%), while 41.8% of the trials used both methods. Less than 10% of the trials included a placebo arm to confirm the efficacy of the new drug and active comparator against placebo, and less than 5.0% were reporting the similarity of the current trial with the previous comparator's trials. In general, no difference was seen in the quality of reporting before and after the release of the CONSORT statement extension 2006 or between the high-impact and low-impact journals. CONCLUSION: The conduct and reporting of NI trials can be improved, particularly in terms of maximizing the use of blinding, the use of both ITT and PP analysis, reporting the similarity with the previous comparator's trials to guarantee a valid constancy assumption, and most importantly reporting the method to determine the NI margin
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