Spatial audio in small display screen devices

Our work addresses the problem of (visual) clutter in mobile device interfaces. The solution we propose involves the translation of technique-from the graphical to the audio domain-for expliting space in information representation. This article presents an illustrative example in the form of a spatialisedaudio progress bar. In usability tests, participants performed background monitoring tasks significantly more accurately using this spatialised audio (a compared with a conventional visual) progress bar. Moreover, their performance in a simultaneously running, visually demanding foreground task was significantly improved in the eye-free monitoring condition. These results have important implications for the design of multi-tasking interfaces for mobile devices

Drawing Trees with Perfect Angular Resolution and Polynomial Area

We study methods for drawing trees with perfect angular resolution, i.e., with angles at each node v equal to 2{\pi}/d(v). We show: 1. Any unordered tree has a crossing-free straight-line drawing with perfect angular resolution and polynomial area. 2. There are ordered trees that require exponential area for any crossing-free straight-line drawing having perfect angular resolution. 3. Any ordered tree has a crossing-free Lombardi-style drawing (where each edge is represented by a circular arc) with perfect angular resolution and polynomial area. Thus, our results explore what is achievable with straight-line drawings and what more is achievable with Lombardi-style drawings, with respect to drawings of trees with perfect angular resolution.Comment: 30 pages, 17 figure

Ectopic A-lattice seams destabilize microtubules

Natural microtubules typically include one A-lattice seam within an otherwise helically symmetric B-lattice tube. It is currently unclear how A-lattice seams influence microtubule dynamic instability. Here we find that including extra A-lattice seams in GMPCPP microtubules, structural analogues of the GTP caps of dynamic microtubules, destabilizes them, enhancing their median shrinkage rate by >20-fold. Dynamic microtubules nucleated by seeds containing extra A-lattice seams have growth rates similar to microtubules nucleated by B-lattice seeds, yet have increased catastrophe frequencies at both ends. Furthermore, binding B-lattice GDP microtubules to a rigor kinesin surface stabilizes them against shrinkage, whereas microtubules with extra A-lattice seams are stabilized only slightly. Our data suggest that introducing extra A-lattice seams into dynamic microtubules destabilizes them by destabilizing their GTP caps. On this basis, we propose that the single A-lattice seam of natural B-lattice MTs may act as a trigger point, and potentially a regulation point, for catastrophe

Investigation of the Relationship between CGMP Signalling and Calcium Mobilisation in Plasmodium Falciparum with a Focus on the Role of Phosphodiesterases in Sexual Development

Malaria kills almost half a million people every year and is a huge public health burden particularly in Sub-Saharan Africa. The current first line treatment is very effective but is threatened by the drug resistance that has been seen in the many effective compounds that have come before it. Consequently, there is a real need to develop new and novel compounds that target multiple stages of the parasite life cycle, as failure of our first line treatment could be devastating. Cell signalling pathways regulate essential events in the parasite lifecycle and as such, components of these pathways are potential targets for parasite disruption. The cyclic nucleotide and Ca2+ signalling cascades have essential functions at multiple stages in the parasite life cycle and often show overlap in their roles. This means that inhibition of one such pathway may disrupt the other. The relationship between 3’-5’-cyclic guanosine monophosphate and Ca2+ signalling is investigated here using Ca2+ assays on both schizont and gametocyte stages using a combination of genetic and pharmacological approaches. Results indicate that zaprinast-induced Ca2+ release through PDE inhibition is dependent upon PKG and in schizonts occurs via inositol triphosphate. Gametogenesis is an essential lifecycle event leading to transmission. The PDE PfPDEδ has been implicated in this event, however little is known about this enzyme. Using a PfPDEδ-ko line and the generation of a HA-tagged PfPDEδ line using the CRISPRCas9 gene editing system, this project seeks to confirm whether PfPDEδ is essential for gametogenesis and to understand more about the role that this protein plays in this event. This includes its cellular localisation, cyclic nucleotide specificity and its role in Ca2+ mobilisation, an event essential to the later stages of gametogenesis. The role of PfPDEδ in erythrocyte-infected gametocyte deformability is also investigated and the phenotype of a PfPDEδ-ko line is dissected. This information will eventually aim to determine whether PfPDEδ would be a good transmission-blocking target. Of particular interest to this thesis are compounds that would prevent transmission because currently the only licenced antimalarial to target transmission stages is Primaquine. A combination of a transmission-blocking agent with one that will inhibit asexual replicating stages would both alleviate clinical symptoms while preventing transmission. PDEs have already been identified and used as effective drug targets in humans. A small panel of Pfizer PDE inhibiters that have shown good activity in asexual blood stages has been tested against the gametocyte stages and this has led to the identification of a human PDE inhibitor that not only kills asexual blood stages in the low nM range, but also one that can kill gametocyte stages at similar concentrations. In addition to this, the mode of action of this compound has been determined

R-process enrichment from a single event in an ancient dwarf galaxy

Elements heavier than zinc are synthesized through the (r)apid and (s)low neutron-capture processes. The main site of production of the r-process elements (such as europium) has been debated for nearly 60 years. Initial studies of chemical abundance trends in old Milky Way halo stars suggested continual r-process production, in sites like core-collapse supernovae. But evidence from the local Universe favors r-process production mainly during rare events, such as neutron star mergers. The appearance of a europium abundance plateau in some dwarf spheroidal galaxies has been suggested as evidence for rare r-process enrichment in the early Universe, but only under the assumption of no gas accretion into the dwarf galaxies. Cosmologically motivated gas accretion favors continual r-process enrichment in these systems. Furthermore, the universal r-process pattern has not been cleanly identified in dwarf spheroidals. The smaller, chemically simpler, and more ancient ultra-faint dwarf galaxies assembled shortly after the first stars formed, and are ideal systems with which to study nucleosynthesis events such as the r-process. Reticulum II is one such galaxy. The abundances of non-neutron-capture elements in this galaxy (and others like it) are similar to those of other old stars. Here, we report that seven of nine stars in Reticulum II observed with high-resolution spectroscopy show strong enhancements in heavy neutron-capture elements, with abundances that follow the universal r-process pattern above barium. The enhancement in this "r-process galaxy" is 2-3 orders of magnitude higher than that detected in any other ultra-faint dwarf galaxy. This implies that a single rare event produced the r-process material in Reticulum II. The r-process yield and event rate are incompatible with ordinary core-collapse supernovae, but consistent with other possible sites, such as neutron star mergers.Comment: Published in Nature, 21 Mar 2016: http://dx.doi.org/10.1038/nature1742

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

IMPLEmenting a clinical practice guideline for acute low back pain evidence-based manageMENT in general practice (IMPLEMENT) : cluster randomised controlled trial study protocol

Background: Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidencebased clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim: This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design: This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access to the guideline using the existing dissemination strategy. Practitioners in the intervention arm will be invited to participate in facilitated face-to-face workshops that have been underpinned by behavioural theory. Investigators (not involved in the delivery of the intervention), patients, outcome assessors and the study statistician will be blinded to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012606000098538 (date registered 14/03/2006).The trial is funded by the NHMRC by way of a Primary Health Care Project Grant (334060). JF has 50% of her time funded by the Chief Scientist Office3/2006). of the Scottish Government Health Directorate and 50% by the University of Aberdeen. PK is supported by a NHMRC Health Professional Fellowship (384366) and RB by a NHMRC Practitioner Fellowship (334010). JG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors are funded by their own institutions

Translating clinicians' beliefs into implementation interventions (TRACII) : a protocol for an intervention modeling experiment to change clinicians' intentions to implement evidence-based practice

Background: Biomedical research constantly produces new findings, but these are not routinely incorporated into health care practice. Currently, a range of interventions to promote the uptake of emerging evidence are available. While their effectiveness has been tested in pragmatic trials, these do not form a basis from which to generalise to routine care settings. Implementation research is the scientific study of methods to promote the uptake of research findings, and hence to reduce inappropriate care. As clinical practice is a form of human behaviour, theories of human behaviour that have proved to be useful in other settings offer a basis for developing a scientific rationale for the choice of interventions. Aims: The aims of this protocol are 1) to develop interventions to change beliefs that have already been identified as antecedents to antibiotic prescribing for sore throats, and 2) to experimentally evaluate these interventions to identify those that have the largest impact on behavioural intention and behavioural simulation. Design: The clinical focus for this work will be the management of uncomplicated sore throat in general practice. Symptoms of upper respiratory tract infections are common presenting features in primary care. They are frequently treated with antibiotics, and research evidence is clear that antibiotic treatment offers little or no benefit to otherwise healthy adult patients. Reducing antibiotic prescribing in the community by the "prudent" use of antibiotics is seen as one way to slow the rise in antibiotic resistance, and appears safe, at least in children. However, our understanding of how to do this is limited. Participants will be general medical practitioners. Two theory-based interventions will be designed to address the discriminant beliefs in the prescribing of antibiotics for sore throat, using empirically derived resources. The interventions will be evaluated in a 2 × 2 factorial randomised controlled trial delivered in a postal questionnaire survey. Two outcome measures will be assessed: behavioural intention and behavioural simulation.This study is funded by the European Commission Research Directorate as part of a multi-partner program: Research Based Education and Quality Improvement (ReBEQI): A Framework and tools to develop effective quality improvement programs in European healthcare. (Proposal No: QLRT-2001-00657)

The size-brightness correspondence:evidence for crosstalk among aligned conceptual feature dimensions

The same core set of cross-sensory correspondences connecting stimulus features across different sensory channels are observed regardless of the modality of the stimulus with which the correspondences are probed. This observation suggests that correspondences involve modality-independent representations of aligned conceptual feature dimensions, and predicts a size-brightness correspondence, in which smaller is aligned with brighter. This suggestion accommodates cross-sensory congruity effects where contrasting feature values are specified verbally rather than perceptually (e.g., where the words WHITE and BLACK interact with the classification of high and low pitch sounds). Experiment 1 brings these two issues together in assessing a conceptual basis for correspondences. The names of bright/white and dark/black substances were presented in a speeded brightness classification task in which the two alternative response keys differed in size. A size-brightness congruity effect was confirmed, with substance names classified more quickly when the relative size of the response key needing to be pressed was congruent with the brightness of the named substance (e.g., when yoghurt was classified as a bright substance by pressing the smaller of two keys). Experiment 2 assesses the proposed conceptual basis for this congruity effect by requiring the same named substances to be classified according to their edibility (with all of the bright/dark substances having been selected for their edibility/inedibility, respectively). The predicted absence of a size-brightness congruity effect, along with other aspects of the results, supports the proposed conceptual basis for correspondences and speaks against accounts in which modality-specific perceptuomotor representations are entirely responsible for correspondence-induced congruity effects