371 research outputs found

    Save Money or Feel Cozy?: A Field Experiment Evaluation of a Smart Thermostat that Learns Heating Preferences

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    We present the design of a fully autonomous smart thermostat that supports end-users in managing their heating preferences in a realtime pricing regime. The thermostat uses a machine learning algorithm to learn how a user wants to trade off comfort versus cost. We evaluate the thermostat in a field experiment in the UK involving 30 users over a period of 30 days. We make two main contributions. First, we study whether our smart thermostat enables end-users to handle real-time prices, and in particular, whether machine learning can help them. We find that the users trust the system and that they can successfully express their preferences; overall, the smart thermostat enables the users to manage their heating given real-time prices. Moreover, our machine learning-based thermostats outperform a baseline without machine learning in terms of usability. Second, we present a quantitative analysis of the users’ economic behavior, including their reaction to price changes, their price sensitivity, and their comfort-cost trade-offs. We find a wide variety regarding the users’ willingness to make trade-offs. But in aggregate, the users’ settings enabled a large amount of demand response, reducing the average energy consumption during peak hours by 38%

    Enzymatic- and temperature-sensitive controlled release of ultrasmall superparamagnetic iron oxides (USPIOs)

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    <p>Abstract</p> <p>Background</p> <p>Drug and contrast agent delivery systems that achieve controlled release in the presence of enzymatic activity are becoming increasingly important, as enzymatic activity is a hallmark of a wide array of diseases, including cancer and atherosclerosis. Here, we have synthesized clusters of ultrasmall superparamagnetic iron oxides (USPIOs) that sense enzymatic activity for applications in magnetic resonance imaging (MRI). To achieve this goal, we utilize amphiphilic poly(propylene sulfide)-<it>bl</it>-poly(ethylene glycol) (PPS-b-PEG) copolymers, which are known to have excellent properties for smart delivery of drug and siRNA.</p> <p>Results</p> <p>Monodisperse PPS polymers were synthesized by anionic ring opening polymerization of propylene sulfide, and were sequentially reacted with commercially available heterobifunctional PEG reagents and then ssDNA sequences to fashion biofunctional PPS-bl-PEG copolymers. They were then combined with hydrophobic 12 nm USPIO cores in the thin-film hydration method to produce ssDNA-displaying USPIO micelles. Micelle populations displaying complementary ssDNA sequences were mixed to induce crosslinking of the USPIO micelles. By design, these crosslinking sequences contained an EcoRV cleavage site. Treatment of the clusters with EcoRV results in a loss of R<sub>2 </sub>negative contrast in the system. Further, the USPIO clusters demonstrate temperature sensitivity as evidenced by their reversible dispersion at ~75°C and re-clustering following return to room temperature.</p> <p>Conclusions</p> <p>This work demonstrates proof of concept of an enzymatically-actuatable and thermoresponsive system for dynamic biosensing applications. The platform exhibits controlled release of nanoparticles leading to changes in magnetic relaxation, enabling detection of enzymatic activity. Further, the presented functionalization scheme extends the scope of potential applications for PPS-b-PEG. Combined with previous findings using this polymer platform that demonstrate controlled drug release in oxidative environments, smart theranostic applications combining drug delivery with imaging of platform localization are within reach. The modular design of these USPIO nanoclusters enables future development of platforms for imaging and drug delivery targeted towards proteolytic activity in tumors and in advanced atherosclerotic plaques.</p

    Emerging roles of lymphatic endothelium in regulating adaptive immunity

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    Emerging research on the roles of stromal cells in modulating adaptive immune responses has included a new focus on lymphatic endothelial cells (LECs). LECs are presumably the first cells that come into direct contact with peripheral antigens, cytokines, danger signals, and immune cells travelling from peripheral tissues to lymph nodes. LECs can modulate dendritic cell function, present antigens to T cells on MHC class I and MHC class II molecules, and express immunomodulatory cytokines and receptors, which suggests that their roles in adaptive immunity are far more extensive than previously realized.. This Review summarizes the emergent evidence that LECs are important in maintaining peripheral tolerance, limiting and resolving effector T cell responses, and modulating leukocyte function

    Describing interruptions, multi-tasking and task-switching in the community pharmacy: A qualitative study in England

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    Background: There is growing evidence base around interruptions and distractions in the community pharmacy setting. There is also evidence to suggest these practices may be associated with dispensing errors. Up to date, qualitative research on this subject is limited. Objective: To explore interruptions and distractions in the community setting; utilising an ethnographic approach to be able to provide a detailed description of the circumstances surrounding such practices. Setting: Community pharmacies in England, July to October 2011. Method: An ethnographic approach was taken. Non participant, unstructured observations were utilised to make records of pharmacists’ every activities. Case studies were formed by combining field notes with detailed information on pharmacists and their respective pharmacy businesses. Content analysis was undertaken both manually and electronically, utilising NVivo 10. Results: Response rate was 12% (n=11). Over fifteen days, a total of 123 hours and 58 minutes of observations were recorded in 11 separate pharmacies of 11 individual pharmacists. The sample was evenly split by gender (female n=6; male n=5) and pharmacy ownership (independent n=5; multiple n=6). Employment statuses included employee pharmacists (n=6), owners (n=4) and a locum (n=1). Average period of registration as a pharmacist was 19 years (range 5-39 years). Average prescriptions busyness of pharmacies ranged from 2,600 – 24,000 items dispensed per month. Two key themes were: “Interruptions and task-switching” and “distractions and multi-tasking.” All observed pharmacists’ work was dominated by interruptions, task-switches, distractions and multi-tasking, often to manage a barrage of conflicting demands. These practices were observed to be part of a deep-rooted culture in the community setting. Directional work maps illustrated the extent and direction of task switching employed by pharmacists. Conclusions: In this study pharmacists’ working practices were permeated by interruptions and multi-tasking. These practices are inefficient and potentially reduce patient safety in terms of dispensing accuracy

    Size- and charge-dependent non-specific uptake of PEGylated nanoparticles by macrophages

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    The assessment of macrophage response to nanoparticles is a central component in the evaluation of new nanoparticle designs for future in vivo application. This work investigates which feature, nanoparticle size or charge, is more predictive of non-specific uptake of nanoparticles by macrophages. This was investigated by synthesizing a library of polymer-coated iron oxide micelles, spanning a range of 30–100 nm in diameter and −23 mV to +9 mV, and measuring internalization into macrophages in vitro. Nanoparticle size and charge both contributed towards non-specific uptake, but within the ranges investigated, size appears to be a more dominant predictor of uptake. Based on these results, a protease-responsive nanoparticle was synthesized, displaying a matrix metalloproteinase-9 (MMP-9)-cleavable polymeric corona. These nanoparticles are able to respond to MMP-9 activity through the shedding of 10–20 nm of hydrodynamic diameter. This MMP-9-triggered decrease in nanoparticle size also led to up to a six-fold decrease in nanoparticle internalization by macrophages and is observable by T2-weighted magnetic resonance imaging. These findings guide the design of imaging or therapeutic nanoparticles for in vivo targeting of macrophage activity in pathologic states

    The Pneumonia Etiology Research for Child Health Project: A 21st Century Childhood Pneumonia Etiology Study

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    The Pneumonia Etiology Research for Child Health (PERCH) project is a 7-country, standardized, comprehensive evaluation of the etiologic agents causing severe pneumonia in children from developing countries. During previous etiology studies, between one-quarter and one-third of patients failed to yield an obvious etiology; PERCH will employ and evaluate previously unavailable innovative, more sensitive diagnostic techniques. Innovative and rigorous epidemiologic and analytic methods will be used to establish the causal association between presence of potential pathogens and pneumonia. By strategic selection of study sites that are broadly representative of regions with the greatest burden of childhood pneumonia, PERCH aims to provide data that reflect the epidemiologic situation in developing countries in 2015, using pneumococcal and Haemophilus influenzae type b vaccines. PERCH will also address differences in host, environmental, and/or geographic factors that might determine pneumonia etiology and, by preserving specimens, will generate a resource for future research and pathogen discovery

    Is the Unitarity of the quark-mixing-CKM-matrix violated in neutron β\beta-decay?

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    We report on a new measurement of neutron β\beta-decay asymmetry. From the result \linebreak A0A_0 = -0.1189(7), we derive the ratio of the axial vector to the vector coupling constant λ\lambda = gA/gV{\it g_A/g_V} = -1.2739(19). When included in the world average for the neutron lifetime τ\tau = 885.7(7)s, this gives the first element of the Cabibbo-Kobayashi-Maskawa (CKM) matrix VudV_{ud} . With this value and the Particle Data Group values for VusV_{us} and VubV_{ub}, we find a deviation from the unitarity condition for the first row of the CKM matrix of Δ\Delta = 0.0083(28), which is 3.0 times the stated error

    The impact of childhood vaccines on bacterial carriage in the nasopharynx: a longitudinal study.

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    BACKGROUND: There is increasing evidence that childhood vaccines have effects that extend beyond their target disease. The objective of this study was to assess the effects of routine childhood vaccines on bacterial carriage in the nasopharynx. METHODS: A cohort of children from rural Gambia was recruited at birth and followed up for one year. Nasopharyngeal swabs were taken immediately after birth, every two weeks for the first six months and then every other month. The presence of bacteria in the nasopharynx (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) was compared before and after the administration of DTP-Hib-HepB and measles-yellow fever vaccines. RESULTS: A total of 1,779 nasopharyngeal swabs were collected from 136 children for whom vaccination data were available. The prevalence of bacterial carriage was high: 82.2% S. pneumoniae, 30.6%, S.aureus, 27.8% H. influenzae. Carriage of H. influenzae (OR = 0.36; 95% CI: 0.13, 0.99) and S. pneumoniae (OR = 0.25; 95% CI: 0.07, 0.90) were significantly reduced after measles-yellow fever vaccination; while DTP-Hib-HepB had no effect on bacterial carriage. CONCLUSIONS: Nasopharyngeal bacterial carriage is unaffected by DTP-Hib-HepB vaccination and reduced after measles-yellow fever vaccination

    Population pharmacokinetic and pharmacodynamic properties of intramuscular quinine in Tanzanian children with severe Falciparum malaria.

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    Although artesunate is clearly superior, parenteral quinine is still used widely for the treatment of severe malaria. A loading-dose regimen has been recommended for 30 years but is still often not used. A population pharmacokinetic study was conducted with 75 Tanzanian children aged 4 months to 8 years with severe malaria who received quinine intramuscularly; 69 patients received a loading dose of 20 mg quinine dihydrochloride (salt)/kg of body weight. Twenty-one patients had plasma quinine concentrations detectable at baseline. A zero-order absorption model with one-compartment disposition pharmacokinetics described the data adequately. Body weight was the only significant covariate and was implemented as an allometric function on clearance and volume parameters. Population pharmacokinetic parameter estimates (and percent relative standard errors [%RSE]) of elimination clearance, central volume of distribution, and duration of zero-order absorption were 0.977 liters/h (6.50%), 16.7 liters (6.39%), and 1.42 h (21.5%), respectively, for a typical patient weighing 11 kg. Quinine exposure was reduced at lower body weights after standard weight-based dosing; there was 18% less exposure over 24 h in patients weighing 5 kg than in those weighing 25 kg. Maximum plasma concentrations after the loading dose were unaffected by body weight. There was no evidence of dose-related drug toxicity with the loading dosing regimen. Intramuscular quinine is rapidly and reliably absorbed in children with severe falciparum malaria. Based on these pharmacokinetic data, a loading dose of 20 mg salt/kg is recommended, provided that no loading dose was administered within 24 h and no routine dose was administered within 12 h of admission. (This study has been registered with Current Controlled Trials under registration number ISRCTN 50258054.)
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