2,773 research outputs found

    Bright single-photon sources in bottom-up tailored nanowires

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    The ability to achieve near-unity light extraction efficiency is necessary for a truly deterministic single photon source. The most promising method to reach such high efficiencies is based on embedding single photon emitters in tapered photonic waveguides defined by top-down etching techniques. However, light extraction efficiencies in current top-down approaches are limited by fabrication imperfections and etching induced defects. The efficiency is further tempered by randomly positioned off-axis quantum emitters. Here, we present perfectly positioned single quantum dots on the axis of a tailored nanowire waveguide using bottom-up growth. In comparison to quantum dots in nanowires without waveguide, we demonstrate a 24-fold enhancement in the single photon flux, corresponding to a light extraction efficiency of 42 %. Such high efficiencies in one-dimensional nanowires are promising to transfer quantum information over large distances between remote stationary qubits using flying qubits within the same nanowire p-n junction.Comment: 19 pages, 6 figure

    Diagnosing Dementia in the Clinical Setting: Can Amyloid PET Provide Additional Value Over Cerebrospinal Fluid?

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    Cerebrospinal fluid (CSF) measures of amyloid and tau are the first-line Alzheimer's disease biomarkers in many clinical centers. We assessed if and when the addition of amyloid PET following CSF measurements provides added diagnostic value. Twenty patients from a cognitive clinic, who had undergone detailed assessment including CSF measures, went on to have amyloid PET. The treating neurologist's working diagnosis, and degree of diagnostic certainty, was assessed both before and after the PET. Amyloid PET changed the diagnosis in 7/20 cases. Amyloid PET can provide added diagnostic value, particularly in young-onset, atypical dementias, where CSF results are borderline and diagnostic uncertainty remains

    A Multicriteria Decision Analysis Comparing Pharmacotherapy for Chronic Neuropathic Pain, Including Cannabinoids and Cannabis-Based Medical Products

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    BACKGROUND: Pharmacological management of chronic neuropathic pain (CNP) still represents a major clinical challenge. Collective harnessing of both the scientific evidence base and clinical experience (of clinicians and patients) can play a key role in informing treatment pathways and contribute to the debate on specific treatments (e.g., cannabinoids). A group of expert clinicians (pain specialists and psychiatrists), scientists, and patient representatives convened to assess the relative benefit–safety balance of 12 pharmacological treatments, including orally administered cannabinoids/cannabis-based medicinal products, for the treatment of CNP in adults. METHODS: A decision conference provided the process of creating a multicriteria decision analysis (MCDA) model, in which the group collectively scored the drugs on 17 effect criteria relevant to benefits and safety and then weighted the criteria for their clinical relevance. FINDINGS: Cannabis-based medicinal products consisting of tetrahydrocannabinol/cannabidiol (THC/CBD), in a 1:1 ratio, achieved the highest overall score, 79 (out of 100), followed by CBD dominant at 75, then THC dominant at 72. Duloxetine and the gabapentinoids scored in the 60s, amitriptyline, tramadol, and ibuprofen in the 50s, methadone and oxycodone in the 40s, and morphine and fentanyl in the 30s. Sensitivity analyses showed that even if the pain reduction and quality-of-life scores for THC/CBD and THC are halved, their benefit–safety balances remain better than those of the noncannabinoid drugs. INTERPRETATION: The benefit–safety profiles for cannabinoids were higher than for other commonly used medications for CNP largely because they contribute more to quality of life and have a more favorable side effect profile. The results also reflect the shortcomings of alternative pharmacological treatments with respect to safety and mitigation of neuropathic pain symptoms. Further high-quality clinical trials and systematic comprehensive capture of clinical experience with cannabinoids is warranted. These results demonstrate once again the complexity and multimodal mechanisms underlying the clinical experience and impact of chronic pain

    Temporal dynamics of aquatic communities and implications for pond conservation

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    Conservation through the protection of particular habitats is predicated on the assumption that the conservation value of those habitats is stable. We test this assumption for ponds by investigating temporal variation in macroinvertebrate and macrophyte communities over a 10-year period in northwest England. We surveyed 51 ponds in northern England in 1995/6 and again in 2006, identifying all macrophytes (167 species) and all macroinvertebrates (221 species, excluding Diptera) to species. The alpha-diversity, beta-diversity and conservation value of these ponds were compared between surveys. We find that invertebrate species richness increased from an average of 29. 5 species to 39. 8 species between surveys. Invertebrate gamma-diversity also increased between the two surveys from 181 species to 201 species. However, this increase in diversity was accompanied by a decrease in beta-diversity. Plant alpha-, beta and gamma-diversity remained approximately constant between the two periods. However, increased proportions of grass species and a complete loss of charophytes suggests that the communities are undergoing succession. Conservation value was not correlated between sampling periods in either plants or invertebrates. This was confirmed by comparing ponds that had been disturbed with those that had no history of disturbance to demonstrate that levels of correlation between surveys were approximately equal in each group of ponds. This study has three important conservation implications: (i) a pond with high diversity or high conservation value may not remain that way and so it is unwise to base pond conservation measures upon protecting currently-speciose habitats; (ii) maximising pond gamma-diversity requires a combination of late and early succession ponds, especially for invertebrates; and (iii) invertebrate and plant communities in ponds may require different management strategies if succession occurs at varying rates in the two groups

    Can programme theory be used as a 'translational tool’ to optimise health service delivery in a national early years’ initiative in Scotland: a case study

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    Background Theory-based evaluation (TBE) approaches are heralded as supporting formative evaluation by facilitating increased use of evaluative findings to guide programme improvement. It is essential that learning from programme implementation is better used to improve delivery and to inform other initiatives, if interventions are to be as effective as they have the potential to be. Nonetheless, few studies describe formative feedback methods, or report direct instrumental use of findings resulting from TBE. This paper uses the case of Scotland’s, National Health Service, early years’, oral health improvement initiative (Childsmile) to describe the use of TBE as a framework for providing feedback on delivery to programme staff and to assess its impact on programmatic action.<p></p> Methods In-depth, semi-structured interviews and focus groups with key stakeholders explored perceived deviations between the Childsmile programme 'as delivered’ and its Programme Theory (PT). The data was thematically analysed using constant comparative methods. Findings were shared with key programme stakeholders and discussions around likely impact and necessary actions were facilitated by the authors. Documentary review and ongoing observations of programme meetings were undertaken to assess the extent to which learning was acted upon.<p></p> Results On the whole, the activities documented in Childsmile’s PT were implemented as intended. This paper purposefully focuses on those activities where variation in delivery was evident. Differences resulted from the stage of roll-out reached and the flexibility given to individual NHS boards to tailor local implementation. Some adaptations were thought to have diverged from the central features of Childsmile’s PT, to the extent that there was a risk to achieving outcomes. The methods employed prompted national service improvement action, and proposals for local action by individual NHS boards to address this.<p></p> Conclusions The TBE approach provided a platform, to direct attention to areas of risk within a national health initiative, and to agree which intervention components were 'core’ to its hypothesised success. The study demonstrates that PT can be used as a 'translational tool’ to facilitate instrumental use of evaluative findings to optimise implementation within a complex health improvement programme.<p></p&gt

    Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

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    <p>Abstract</p> <p>Background</p> <p>Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry.</p> <p>Methods</p> <p>A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders – Fourth Edition (DSM-IV).</p> <p>Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD.</p> <p>Results</p> <p>The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia.</p> <p>Conclusion</p> <p>The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.</p

    A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

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    Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

    The shear viscosity of carbon fibre suspension and its application for fibre length measurement

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    The viscosity of short carbon fibre suspensions in glycerol aqueous solution was measured using a bespoke vane-in-cup viscometer, where the carbon fibre has an aspect ratio from 450 to 2209. In the semi-concentrated regime, nL3 ranging from 20 to 4400, the suspensions demonstrated strong shear-thinning characteristics particularly at higher concentrations. The shear-thinning characteristic is strongly related to the crowding factor proposed by Kerekes, indicating that non-hydrodynamic interactions occur in the suspensions. The influence of fibre bending on viscosity emerges when the bending ratio is lower than 0.0028. An empirical model based on transient network formation and rupture was proposed and used to correlate the relative viscosity with fibre concentration nL3 and shear rate. Based on the model, a viscosity method is established to analyse the fibre length by measuring the viscosity of the fibre suspension using a bespoke vane-in-cup viscometer

    Pharmacology of airways and vessels in lung slices in situ: role of endogenous dilator hormones

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    Small airway and vessels play a critical role in chronic airway and pulmonary vascular diseases, but their pharmacology has not been well characterised. We have studied airway and vascular responses in rat lung slices and separately in vitro using myography. In lung slices, under basal conditions, acetylcholine contracted airways, but had no vascular effect. The thromboxane mimetic, U46619 contracted both vessels and airways. In the presence of U46619, acetylcholine dilated vessels, but further contracted airways, an effect that was blocked by the nitric oxide synthase inhibitor L-N(G)-nitro-L-arginine or apamin plus charybdotoxin, which inhibit endothelial-derived hyperpolarising factor. Airway responses in lung slices were unaffected by L-N(G)nitro-L-arginine methyl ester, indomethacin or apamin plus charybdotoxin. By contrast, apamin plus charybdotoxin contracted bronchi studied in isolation. Our observations are the first to identify mechanisms of endothelium dependent dilations in precision cut lung slices and the potential for transverse hormonal communication between airways and vessels
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