1,805 research outputs found

    Biofilm-forming capability of highly virulent, multidrug-resistant Candida auris

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    The emerging multidrug-resistant yeast pathogen Candida auris has attracted considerable attention as a source of healthcare–associated infections. We report that this highly virulent yeast has the capacity to form antifungal resistant biofilms sensitive to the disinfectant chlorhexidine in vitro

    Objective functions for comparing simulations with insect trap catch data

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    Targeted surveillance of high risk invasion sites using insect traps is becoming an important tool in border biosecurity, aiding in early detection and subsequent monitoring of eradication attempts. The mark-release-recapture technique is widely used to study the dispersal of insects, and to generate unbiased estimates of population density. It may also be used in the biosecurity context to quantify the efficacy of surveillance and eradication monitoring systems. Marked painted apple moths were released at three different locations in Auckland, New Zealand over six weeks during a recent eradication campaign. The results of the mark-release-recapture experiment were used to parameterise a process-based mechanistic dispersal model in order to understand the moth dispersal pattern in relation to wind patterns, and to provide biosecurity agencies with an ability to predict moth dispersal patterns. A genetic algorithm was used to fit some model parameters. Different objective functions were tested: 1) Cohen’s Kappa test, 2) the sum of squared difference on trap catches, 3) the sum of squared difference weighted by distance from the release site, 4) the sum of squared difference weighted on distance between best-fit paired data. The genetic algorithm proved to be a powerful fitting method, but the model results were highly dependant on the objective function used. Objective functions for fitting spatial data need to characterise spatial patterns as well as density (ie. recapture rate). For fitting stochastic models to datasets derived from stochastic spatial processes, objective functions need to accommodate the fact that a perfect fit is practically impossible, even if the models are the same. Applied on mark-release-recapture data, the Cohen’s Kappa test and the sum of squared difference on trap catches captured respectively the distance component of the spatial pattern and the density component adequately but failed to capture both requirements whereas the sum of squared difference weighted by distance from the release site did. However, in order to integrate the stochastic error generated by the model underlying stochastic process, only the sum of squared difference weighted on distance between best-fit paired data was adequate. The relevance of each of the fitting methods is detailed, and their respective strengths and weaknesses are discussed in relation to their ability to capture the spatial patterns of insect recaptures

    Exosomal αvβ6 integrin is required for monocyte M2 polarization in prostate cancer

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    Therapeutic approaches aimed at curing prostate cancer are only partially successful given the occurrence of highly metastatic resistant phenotypes that frequently develop in response to therapies. Recently, we have described αvβ6, a surface receptor of the integrin family as a novel therapeutic target for prostate cancer; this epithelial-specific molecule is an ideal target since, unlike other integrins, it is found in different types of cancer but not in normal tissues. We describe a novel αvβ6-mediated signaling pathway that has profound effects on the microenvironment. We show that αvβ6 is transferred from cancer cells to monocytes, including β6-null monocytes, by exosomes and that monocytes from prostate cancer patients, but not from healthy volunteers, express αvβ6. Cancer cell exosomes, purified via density gradients, promote M2 polarization, whereas αvβ6 down-regulation in exosomes inhibits M2 polarization in recipient monocytes. Also, as evaluated by our proteomic analysis, αvβ6 down-regulation causes a significant increase in donor cancer cells, and their exosomes, of two molecules that have a tumor suppressive role, STAT1 and MX1/2. Finally, using the Ptenpc−/− prostate cancer mouse model, which carries a prostate epithelial-specific Pten deletion, we demonstrate that αvβ6 inhibition in vivo causes up-regulation of STAT1 in cancer cells. Our results provide evidence of a novel mechanism that regulates M2 polarization and prostate cancer progression through transfer of αvβ6 from cancer cells to monocytes through exosomes

    Burgers velocity fields and dynamical transport processes

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    We explore a connection of the forced Burgers equation with the Schr\"{o}dinger (diffusive) interpolating dynamics in the presence of deterministic external forces. This entails an exploration of the consistency conditions that allow to interpret dispersion of passive contaminants in the Burgers flow as a Markovian diffusion process. In general, the usage of a continuity equation tρ=(vρ)\partial_t\rho =-\nabla (\vec{v}\rho), where v=v(x,t)\vec{v}=\vec{v}(\vec{x},t) stands for the Burgers field and ρ\rho is the density of transported matter, is at variance with the explicit diffusion scenario. Under these circumstances, we give a complete characterisation of the diffusive matter transport that is governed by Burgers velocity fields. The result extends both to the approximate description of the transport driven by an incompressible fluid and to motions in an infinitely compressible medium.Comment: Latex fil

    General duality for abelian-group-valued statistical-mechanics models

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    We introduce a general class of statistical-mechanics models, taking values in an abelian group, which includes examples of both spin and gauge models, both ordered and disordered. The model is described by a set of ``variables'' and a set of ``interactions''. A Gibbs factor is associated to each variable and to each interaction. We introduce a duality transformation for systems in this class. The duality exchanges the abelian group with its dual, the Gibbs factors with their Fourier transforms, and the interactions with the variables. High (low) couplings in the interaction terms are mapped into low (high) couplings in the one-body terms. The idea is that our class of systems extends the one for which the classical procedure 'a la Kramers and Wannier holds, up to include randomness into the pattern of interaction. We introduce and study some physical examples: a random Gaussian Model, a random Potts-like model, and a random variant of discrete scalar QED. We shortly describe the consequence of duality for each example.Comment: 26 pages, 2 Postscript figure

    The effects of changes in the order of verbal labels and numerical values on children's scores on attitude and rating scales

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    Research with adults has shown that variations in verbal labels and numerical scale values on rating scales can affect the responses given. However, few studies have been conducted with children. The study aimed to examine potential differences in children’s responses to Likert-type rating scales according to their anchor points and scale direction, and to see whether or not such differences were stable over time. 130 British children, aged 9 to 11, completed six sets of Likert-type rating scales, presented in four different ways varying the position of positive labels and numerical values. The results showed, both initially and 8-12 weeks later, that presenting a positive label or a high score on the left of a scale led to significantly higher mean scores than did the other variations. These findings indicate that different arrangements of rating scales can produce different results which has clear implications for the administration of scales with children

    Knee joint kinetics in response to multiple three-dimensional printed, customised foot orthoses for the treatment of medial compartment knee osteoarthritis

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    The knee adduction moment is consistently used as a surrogate measure of medial compartment loading. Foot orthoses are designed to reduce knee adduction moment via lateral wedging. The 'dose' of wedging required to optimally unload the affected compartment is unknown and variable between individuals. This study explores a personalised approach via three-dimensional printed foot orthotics to assess the biomechanical response when two design variables are altered: orthotic length and lateral wedging. Foot orthoses were created for 10 individuals with symptomatic medial knee osteoarthritis and 10 controls. Computer-aided design software was used to design four full and four three-quarter-length foot orthoses per participant each with lateral posting of 0° 'neutral', 5° rearfoot, 10° rearfoot and 5° forefoot/10° rearfoot. Three-dimensional printers were used to manufacture all foot orthoses. Three-dimensional gait analyses were performed and selected knee kinetics were analysed: first peak knee adduction moment, second peak knee adduction moment, first knee flexion moment and knee adduction moment impulse. Full-length foot orthoses provided greater reductions in first peak knee adduction moment (p = 0.038), second peak knee adduction moment (p = 0.018) and knee adduction moment impulse (p = 0.022) compared to three-quarter-length foot orthoses. Dose effect of lateral wedging was found for first peak knee adduction moment (p < 0.001), second peak knee adduction moment (p < 0.001) and knee adduction moment impulse (p < 0.001) indicating greater unloading for higher wedging angles. Significant interaction effects were found for foot orthosis length and participant group in second peak knee adduction moment (p = 0.028) and knee adduction moment impulse (p = 0.036). Significant interaction effects were found between orthotic length and wedging condition for second peak knee adduction moment (p = 0.002). No significant changes in first knee flexion moment were found. Individual heterogeneous responses to foot orthosis conditions were observed for first peak knee adduction moment, second peak knee adduction moment and knee adduction moment impulse. Biomechanical response is highly variable with personalised foot orthoses. Findings indicate that the tailoring of a personalised intervention could provide an additional benefit over standard interventions and that a three-dimensional printing approach to foot orthosis manufacturing is a viable alternative to the standard methods.Full Tex

    Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST).

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    Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects &lt;50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Clinicaltrials.gov NCT01660126 ; registered 8th June 2012

    ‘Emptying the cage, changing the birds’: state rescaling, path-dependency and the politics of economic restructuring in post-crisis Guangdong

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    This paper evaluates how economic restructuring in Guangdong is entwined with the politicization of state rescaling during and after the global financial crisis of 2008. It shows how a key industrial policy known as ‘double relocation’ generated tensions between the Guangdong government, then led by Party Secretary Wang Yang, and the senior echelon of the Communist Party of China in Beijing. The contestations and negotiations that ensued illustrate the dynamic entwinement between state rescaling and institutional path-dependency: the Wang administration launched this industrial policy in spite of potentially destabilizing effects on the prevailing national structure of capital accumulation. This foregrounds, in turn, the constitutive and constraining effects of established, national-level policies on local, territorially-specific restructuring policies
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