This article proposes to study the rebirth of a nation, Wales, during the Edwardian years, by first considering the deep changes affecting the country, be they economic, social and cultural, giving ...it a new lease of life. Such changes led to a new prominence of the symbols and institutions of Welsh nationhood, and successes, especially in sport. All these areas of dominance owed their essence to politics, notably the Liberal domination, that came to be questioned.
Metamaterials are being applied to the development and construction of many new devices throughout the electromagnetic spectrum. Limitations posed by the metamaterial operational bandwidth and losses ...can be effectively mitigated through the incorporation of tunable elements into the metamaterial devices. There are a wide range of approaches that have been advanced in the literature for adding reconfiguration to metamaterial devices all the way from the RF through the optical regimes, but some techniques are useful only for certain wavelength bands. A range of tuning techniques span from active circuit elements introduced into the resonant conductive metamaterial geometries to constituent materials that change electromagnetic properties under specific environmental stimuli. This paper presents a survey of the development of reconfigurable and tunable metamaterial technology as well as of the applications where such capabilities are valuable.
BACKGROUND:Ticagrelor has superior efficacy to clopidogrel in the management of acute coronary syndromes but has not been assessed in patients undergoing percutaneous coronary intervention for stable ...coronary artery disease. We compared the pharmacodynamic effects of ticagrelor and clopidogrel in this stable population.
METHODS:One hundred eighty aspirin-treated stable coronary artery disease patients, who were planned to undergo elective percutaneous coronary intervention in a single center, were randomized 1:1:1 to either a standard clopidogrel regimen or 1 of 2 regimens of ticagrelor, either 90 mg (T90) or 60 mg twice daily (T60), both with a 180 mg loading dose. Cellular adenosine uptake was assessed, at the time of the procedure and pre- and postdose at 1 month, by adding adenosine 1 µmol/L to aliquots of anticoagulated whole blood and mixing with a stop solution at 0, 15, 30, and 60 seconds, then measuring residual plasma adenosine concentration by high-performance liquid chromatography. Systemic plasma adenosine concentration and platelet reactivity were assessed at the same timepoints. High-sensitivity troponin T was measured pre- and 18 to 24 hours postpercutaneous coronary intervention.
RESULTS:One hundred seventy-four patients underwent an invasive procedure, of whom 162 received percutaneous coronary intervention (mean age 65 years, 18% female, 21% with diabetes mellitus). No effect on in vitro adenosine uptake was seen postdose at 1 month for either ticagrelor dose compared with clopidogrel (residual adenosine at 15 seconds, mean±SDclopidogrel 0.274±0.101 µmol/L; T90 0.278±0.134 µmol/L; T60 0.288±0.149 µmol/L; P=0.37). Similarly, no effect of ticagrelor on in vitro adenosine uptake was seen at other timepoints, nor was plasma adenosine concentration affected (all P>0.1). Both maintenance doses of ticagrelor achieved more potent and consistent platelet inhibition than clopidogrel (VerifyNow P2Y12 reaction units, 1 month, mean±SDpredose, T6062±47, T9040±38, clopidogrel 181±44; postdose, T6034±30, T9024±21, clopidogrel 159±57; all P<0.0001 for ticagrelor versus clopidogrel). High platelet reactivity was markedly less with both T60 and T90 compared with clopidogrel (VerifyNow P2Y12 reaction units>208, 1 month postdose0%, 0%, and 21%, respectively). Median (interquartile range) high-sensitivity troponin T increased 16.9 (6.5–46.9) ng/L for clopidogrel, 22.4 (5.5–53.8) ng/L for T60, and 17.7 (8.1–43.5) ng/L for T90 (P=0.95). There was a trend toward less dyspnea with T60 versus T90 (7.1% versus 19.0%; P=0.09).
CONCLUSIONS:Maintenance therapy with T60 or T90 had no detectable effect on cellular adenosine uptake at 1 month, nor was there any effect on systemic plasma adenosine levels. Both regimens of ticagrelor achieved greater and more consistent platelet inhibition than clopidogrel but did not appear to affect troponin release after percutaneous coronary intervention.
CLINICAL TRIAL REGISTRATION:URLhttps://www.clinicaltrials.gov. Unique identifierNCT02327624.
Abstract
Delayed onset of action of oral P2Y
12
inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic ...strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2–3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y
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inhibition was determined by VerifyNow P2Y12 assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y
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inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y
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inhibition.
This book provides a thoroughly researched biography of the naval career of Matthew Flinders, with particular emphasis on his importance for the maritime discovery of Australia. Sailing in the wake ...of the 18th-century voyages of exploration by Captain Cook and others, Flinders was the first naval commander to circumnavigate Australia's coastline. He contributed more to the mapping and naming of places in Australia than virtually any other single person. His voyage to Australia on H.M.S. Investigator expanded the scope of imperial, geographical and scientific knowledge. This biography places Flinders's career within the context of Pacific exploration and the early white settlement of Australia. Flinders's connections with other explorers, his use of patronage, the dissemination of his findings, and his posthumous reputation are also discussed in what is an important new scholarly work in the field.
Kenneth O. Morgan Morgan, Kenneth. O
2015., 20160309, 2015, 2015-09-15, 2015-08-11, Letnik:
56217
eBook
The eventful life, scholarly work and political and personal experience of Wales's leading historian, reflecting on the challenges and achievements which have peppered his long and successful career.
Background IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated ...with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy. Objective To investigate the association between filaggrin loss-of-function mutations and peanut allergy. Methods Case-control study of 71 English, Dutch, and Irish oral food challenge–positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥8 mm and/or peanut-specific IgE ≥15 kUL−1 ) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis. Results Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge–positive patients ( P = 3.0 × 10−6 ; odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study ( P = 5.4 × 10−5 ; odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant ( P = .0008) after controlling for coexistent atopic dermatitis. Conclusion Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.
Modern drug-eluting stents are constructed with thin struts and are easy to deliver and highly conformable. However, although innovative designs have enabled maintenance of radial strength, ...longitudinal strength may be lower with these stents and there have been recent reports of longitudinal stent compression of ostially deployed stents. We report the experience in our centre on longitudinal stent deformation and explore mechanisms of this complication and its frequency with various drug-eluting stent platforms.
Nine cases of longitudinal stent deformation were identified over a four year period representing 0.2% of cases and affected 0.097% of stents deployed. There were several mechanisms for this complication including compression by post-dilatation balloons, guide catheter extensions and proximal embolic protection devices. The rate of stent deformation varied from 0% in several stent types to 0.86% in the case of the Promus Element stent. There was one case of late stent thrombosis attributable to longitudinal stent deformation.
Longitudinal stent deformation can occur secondary to a variety of mechanisms and identification is important as, left untreated, it may be associated with a risk of stent thrombosis. Although seen with several different stents, in our series it was more commonly observed with the Promus Element stent.
Attempts at a Labour–Liberal Democrat Progressive Alliance came to nothing prior to the 1997 general election. The original idea of progressivism, first mooted in Britain in 1896, was an American ...one. Suggestions for a progressive alliance in the UK came from Lloyd George in 1914, and then again in 1931, each time with little effect. Nothing emerged after 1945 until the Lib–Lab pact negotiated by Callaghan and Steel in 1977, which led to electoral misfortune for both and the rise and fall of the SDP. In 2010 a coalition between the Lib Dems (under Clegg) and the Conservatives was always much the more likely option. Most Labour people no longer saw the Lib Dems as a party of the left. The Coalition Agreement in 2010 showed the idea of an alliance to be a centrist, elitist one with little grass‐roots support. Such an alliance would flourish through pressure groups rather than popular democracy, especially with a Labour party led by Corbyn. In the US and the UK, progressivism went badly wrong in its politics: Theodore Roosevelt's New Nationalist campaign of 1912 divided American reformers fatally, as did Lloyd George's postwar Coalition in Britain after 1918. Now, even after Brexit, a progressive alliance seems further away than ever. The story of the ‘Progressive Dilemma’ remains one of unrealistic projects, invariably disappointed.
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