523 resultados para Middleton
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The development of appropriate Electric Vehicle (EV) charging strategies has been identified as an effective way to accommodate an increasing number of EVs on Low Voltage (LV) distribution networks. Most research studies to date assume that future charging facilities will be capable of regulating charge rates continuously, while very few papers consider the more realistic situation of EV chargers that support only on-off charging functionality. In this work, a distributed charging algorithm applicable to on-off based charging systems is presented. Then, a modified version of the algorithm is proposed to incorporate real power system constraints. Both algorithms are compared with uncontrolled and centralized charging strategies from the perspective of both utilities and customers. © 2013 IEEE.
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Burkholderia cepacia infection in cystic fibrosis (CF) patients is associated with significant morbidity and mortality, yet no definitive treatment is currently available. This report describes a new approach to treat B. cepacia infection in CF patients, using a combination of amiloride and tobramycin aerosols. Four adults with the typical clinical syndrome of CF were recruited after repeated positive sputum cultures for B. cepacia. Aerosols of amiloride and tobramycin were given three times daily for 1-6 months, and repeated sputum cultures were collected to assess efficacy. Three of the four patients treated with the combined therapy eradicated B. cepacia from their sputum cultures for at least 2 yrs, and there were no adverse events. This novel combination may provide a new therapeutic option for Burkholderia cepacia infections. Furthermore, the strategy of combining antibiotics with ion transport agents may have ramifications for the treatment of other multi-resistant organisms.
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Aims: Preterm infants are deprived of the normal intra-uterine exposure to maternal melatonin and may benefit from replacement therapy. We conducted a pharmacokinetic study to guide potential therapeutic trials. Methods: Melatonin was administered to 18 preterm infants in doses ranging from 0.04-0.6μgkg-1 over 0.5-6h. Pharmacokinetic profiles were analyzed individually and by population methods. Results: Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1μgkg-1h-1 for 2h showed a median half-life of 15.82h and median maximum plasma concentration of 203.3pgml-1. On population pharmacokinetics, clearance was 0.045lh-1, volume of distribution 1.098l and elimination half-life 16.91h with gender (P = 0.047) and race (P < 0.0001) as significant covariates. Conclusions: A 2h infusion of 0.1μgkg-1h-1 increased blood melatonin from undetectable to approximately peak adult concentrations. Slow clearance makes replacement of a typical maternal circadian rhythm problematic. The pharmacokinetic profile of melatonin in preterm infants differs from that of adults so dosage of melatonin for preterm infants cannot be extrapolated from adult studies. Data from this study can be used to guide therapeutic clinical trials of melatonin in preterm infants. © 2013 The British Pharmacological Society.
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Background: RAS is mutated (RASMT) in ~55% of mCRC, and phase III studies have shown that patients harbouring RAS mutations do not benefit from anti-EGFR MoAbs. In addition, ~50% of RAS Wild Type (RASWT) will not benefit from the addition of an EGFR MoAb to standard chemotherapy. Hence, novel treatment strategies are urgently needed for RASMT and > 50% of RASWT mCRC patients. c-MET is overexpressed in ~50-60%, amplified in ~2-3% and mutated in ~3-5% of mCRC. Recent preclinical studies have shown that c-MET is an important mediator of resistance to MEK inhibitors (i) in RASMT mCRC, and that combined MEKi/METi resulted in synergistic reduction in tumour growth in RASMT xenograft models (1). A number of recent studies have highlighted the role of c-MET in mediating primary/secondary resistance to anti-EGFR MoAbs in mCRC, suggesting that patient with RASWT tumours with aberrant c-MET (RASWT/c-MET+) may benefit from anti-c-MET targeted therapies (2). These preclinical data supported the further clinical evaluation of combined MEKi/METi treatment in RASMT and RASWT CRC patients with aberrant c-MET signalling (overexpression, amplification or mutation; RASWT/c-MET+). Methods: MErCuRIC1 is a phase I combination study of METi crizotinib with MEKi PD-0325901. The dose escalation phase, utilizing a rolling six design, recruits 12-24 patients with advanced solid tumours and aims to assess safety/toxicity of combination, recommended phase II (RPII) dose, pharmacokinetics (PK) and pharmacodynamics (PD) (pERK1/2 in PBMC and tumour; soluble c-MET). In the dose expansion phase an additional 30-42 RASMT and RASWT/c-MET mCRC patients with biopsiable disease will be treated at the RPII dose to further evaluate safety, PK, PD and treatment response. In the dose expansion phase additional biopsy and blood samples will be obtained to define mechanisms of response/resistance to crizotinib/PD-0325901 therapy. Enrolment into the dose escalation phase began in December 2014 with cohort 1 still ongoing. EudraCT registry number: 2014-000463-40. (1) Van Schaeybroeck S et al. Cell Reports 2014;7(6):1940-55; (2) Bardelli A et al. Cancer Discov 2013;3(6):658-73. Clinical trial information: 2014-000463-40.
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The effects of repeated survey and fieldwork timing on data derived from a recently proposed standard field methodology for empirical estimation of Relative Pollen Productivity have been tested. Seasonal variations in vegetation and associated pollen assemblages were studied in three contrasting cultural habitat types; semi-natural ancient woodlands, lowland heaths, and unimproved, traditionally managed hay meadows. Results show that in woodlands and heathlands the standard method generates vegetation data with a reasonable degree of similarity throughout the field season, though in some instances additional recording of woodland canopy cover should be undertaken, and differences were greater for woodland understorey taxa than for arboreal taxa. Large differences in vegetation cover were observed over the field season in the grassland community, and matching the phenological timing of surveys within and between studies is clearly important if RPP estimates from these sites are to be comparable. Pollen assemblages from closely co-located moss polsters collected on different visits are shown to be variable in all communities, to a greater degree than can be explained by the sampling error associated with pollen counting, and further study of moss polsters as pollen traps is recommended.
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Pour montrer comment s'articulent les mécanismes de l'interprétation dans la chanson populaire, nous nous sommes inspirée [inspirés] de travaux de sociologues qui se sont penchés sur la chanson depuis une vingtaine d'années (Authelain, Buxton, Calvet, Giroux, Hennion, Frith, Middleton) ou sur le marché des biens symboliques (Bourdieu), ainsi que de la sémiologie musicale de Jean-Jacques Nattiez. Comme lui, nous avons identifié un processus poïétique, un niveau neutre et un processus esthésique dans la pratique de la chanson, processus qui se dédoublent dans la chanson populaire selon le point d'ancrage de l'analyse: la partition (la trace, constituant un premier"niveau neutre") puis la chanson interprétée (ou résultat musical, qui constitue un second"niveau neutre"). Nous avons par la suite identifié les différents lieux où entre en jeu l'interprétation: chez les exécutants (musiciens et interprètes) qui actualisent la partition, produisant ainsi la chanson interprétée; dans le processus de production/promotion, où s'élaborent l'image de marque de l'artiste et les discours promotionnels; chez le public où l'interprétation apparaît aussi sous ses deux facettes, c'est-à-dire l'exécution possible par les auditeurs/spectateurs, mais surtout la lecture que propose le discours critique. Un exemple précis, l'album D'instinct (1995) de l'auteur/compositeur/interprète Richard Séguin, nous a permis de mettre à l'épreuve ce modèle ainsi qu'une méthode d'analyse qui permet à la fois de se pencher sur une chanson et sur la chanson. Dans un premier temps, nous avons analysé une chanson à partir de la partition puis de la chanson interprétée (sous forme de chanson, d'album, de vidéoclip et de spectacle), sans tenir compte des discours que l'on tient sur cette chanson. Dans un deuxième temps, notre attention s'est portée sur la chanson, analysant l'objet"chanson" transformé par les discours, puis les discours eux-mêmes. Ces analyses nous ont permis de nous pencher sur l'interprétation, d'abord comme exécution (de la partition), et surtout comme lecture, puis de schématiser le réseau des discours, promotionnels et critiques, qui circulent entre l'artiste (et sa musique) et l'auditeur/spectateur. Notre recherche s'intéresse ainsi de façon nouvelle à la chanson populaire et la méthode d'analyse que nous proposons permet de tenir compte de la spécificité de son objet: une approche multidisciplinaire s'imposait pour étudier un phénomène pluridimensionnel comme la chanson. Aussi, les résultats de nos analyses confirment que le modèle et la méthode sont opératoires, mais surtout, ils laissent entrevoir de nombreuses possibilités d'analyses nouvelles d'une/de la chanson, analyses qui permettraient d'en saisir le caractère stylistique, les qualités esthétiques, etc. et même, il nous semble qu'ils pourraient s'avérer tout aussi opératoires appliqués à d'autres corpus."--Résumé abrégé par UMI
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Concert program for Summer Quarter Music, July 11, 1940
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Dissertação apresentada à Escola Superior de Comunicação Social como parte dos requisitos para obtenção de grau de mestre em Jornalismo.
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AIMS/HYPOTHESIS: Several susceptibility genes for type 2 diabetes have been discovered recently. Individually, these genes increase the disease risk only minimally. The goals of the present study were to determine, at the population level, the risk of diabetes in individuals who carry risk alleles within several susceptibility genes for the disease and the added value of this genetic information over the clinical predictors. METHODS: We constructed an additive genetic score using the most replicated single-nucleotide polymorphisms (SNPs) within 15 type 2 diabetes-susceptibility genes, weighting each SNP with its reported effect. We tested this score in the extensively phenotyped population-based cross-sectional CoLaus Study in Lausanne, Switzerland (n = 5,360), involving 356 diabetic individuals. RESULTS: The clinical predictors of prevalent diabetes were age, BMI, family history of diabetes, WHR, and triacylglycerol/HDL-cholesterol ratio. After adjustment for these variables, the risk of diabetes was 2.7 (95% CI 1.8-4.0, p = 0.000006) for individuals with a genetic score within the top quintile, compared with the bottom quintile. Adding the genetic score to the clinical covariates improved the area under the receiver operating characteristic curve slightly (from 0.86 to 0.87), yet significantly (p = 0.002). BMI was similar in these two extreme quintiles. CONCLUSIONS/INTERPRETATION: In this population, a simple weighted 15 SNP-based genetic score provides additional information over clinical predictors of prevalent diabetes. At this stage, however, the clinical benefit of this genetic information is limited.
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Smoking is a leading global cause of disease and mortality. We established the Oxford-GlaxoSmithKline study (Ox-GSK) to perform a genome-wide meta-analysis of SNP association with smoking-related behavioral traits. Our final data set included 41,150 individuals drawn from 20 disease, population and control cohorts. Our analysis confirmed an effect on smoking quantity at a locus on 15q25 (P = 9.45 x 10(-19)) that includes CHRNA5, CHRNA3 and CHRNB4, three genes encoding neuronal nicotinic acetylcholine receptor subunits. We used data from the 1000 Genomes project to investigate the region using imputation, which allowed for analysis of virtually all common SNPs in the region and offered a fivefold increase in marker density over HapMap2 (ref. 2) as an imputation reference panel. Our fine-mapping approach identified a SNP showing the highest significance, rs55853698, located within the promoter region of CHRNA5. Conditional analysis also identified a secondary locus (rs6495308) in CHRNA3.
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Référence bibliographique : Rol, 59979
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Handwritten note (1 page, single sided) stating that Ezekiel Woodruff was born in Littlefield Ct. July 29, 1763. He married Sally Hall who was born in Middleton, Ct on May 21 [the date is listed as the 23 in the Woodruff Genealogy book], 1765. She was the daughter of Capt. Giles and A. Hall. Ezekiel Woodruff died in Niagara Falls, New York on January 7, 1836 [the 6 is crossed out and a 7 penciled in]. Sally Woodruff died in Niagara Falls, New York on Nov. 26, 1835, n.d.
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UANL