84 research outputs found

    House of Commons Library: Briefing paper: Number 07147, 13 April 2018: School places in England: applications, allocations and appeals

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    Background: We previously reported that ginsenoside Re (GRe) attenuated against methamphetamine (MA)-induced neurotoxicity via anti-inflammatory and antioxidant potentials. We also demonstrated that dynorphin possesses anti-inflammatory and antioxidant potentials against dopaminergic loss, and that balance between dynorphin and substance P is important for dopaminergic neuroprotection. Thus, we examined whether GRe positively affects interactive modulation between dynorphin and substance P against MA neurotoxicity in mice. Methods: We examined changes in dynorphin peptide level, prodynorphin mRNA, and substance P mRNA, substance P-immunoreactivity, homeostasis in enzymatic antioxidant system, oxidative parameter, microglial activation, and pro-apoptotic parameter after a neurotoxic dose of MA to clarify the effects of GRe, prodynorphin knockout, pharmacological inhibition of κ-opioid receptor (i.e., nor-binaltorphimine), or neurokinin 1 (NK1) receptor (i.e., L-733,060) against MA insult in mice. Results: GRe attenuated MA-induced decreases in dynorphin level, prodynorphin mRNA expression in the striatum of wild-type (WT) mice. Prodynorphin knockout potentiated MA-induced dopaminergic toxicity in mice. The imbalance of enzymatic antioxidant system, oxidative burdens, microgliosis, and pro-apoptotic changes led to the dopaminergic neurotoxicity. Neuroprotective effects of GRe were more pronounced in prodynorphin knockout than in WT mice. Nor-binaltorphimine, a κ-opioid receptor antagonist, counteracted against protective effects of GRe. In addition, we found that GRe significantly attenuated MA-induced increases in substance P-immunoreactivity and substance P mRNA expression in the substantia nigra. These increases were more evident in prodynorphin knockout than in WT mice. Although, we observed that substance P-immunoreactivity was co-localized in NeuN-immunreactive neurons, GFAP-immunoreactive astrocytes, and Iba-1-immunoreactive microglia. NK1 receptor antagonist L-733,060 or GRe selectively inhibited microgliosis induced by MA. Furthermore, L-733,060 did not show any additive effects against GRe-mediated protective activity (i.e., antioxidant, antimicroglial, and antiapoptotic effects), indicating that NK1 receptor is one of the molecular targets of GRe. Conclusions: Our results suggest that GRe protects MA-induced dopaminergic neurotoxicity via upregulatgion of dynorphin-mediated κ-opioid receptor and downregulation of substance P-mediated NK1 R

    Randomized Trial of Stents Versus Bypass Surgery for Left Main Coronary Artery Disease 5-Year Outcomes of the PRECOMBAT Study

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    AbstractBackgroundIn a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery stenosis at 1 year.ObjectivesThis study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of unprotected left main coronary artery stenosis.MethodsWe randomly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI with a sirolimus-eluting stent (n = 300) or CABG (n = 300). The primary endpoint was a major adverse cardiac or cerebrovascular event (MACCE: a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven target vessel revascularization) and compared on an intention-to-treat basis.ResultsAt 5 years, MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group (cumulative event rates of 17.5% and 14.3%, respectively; hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 0.84 to 1.90; p = 0.26). The 2 groups did not differ significantly in terms of death from any cause, myocardial infarction, or stroke as well as their composite (8.4% and 9.6%; HR, 0.89; 95% CI, 0.52 to 1.52; p = 0.66). Ischemia-driven target vessel revascularization occurred more frequently in the PCI group than in the CABG group (11.4% and 5.5%, respectively; HR: 2.11; 95% CI: 1.16 to 3.84; p = 0.012).ConclusionsDuring 5 years of follow-up, our study did not show significant difference regarding the rate of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG. However, considering the limited power of our study, our results should be interpreted with caution. (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [PRECOMBAT]; NCT00422968

    Efficacies of the new Paclitaxel-eluting Coroflex Please™ Stent in percutaneous coronary intervention; comparison of efficacy between Coroflex Please™ and Taxus™ (ECO-PLEASANT) trial: study rationale and design

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    <p>Abstract</p> <p>Background</p> <p>Previous randomized trials have showed the superiority of Paclitaxel-eluting stent over bare metal stent in angiographic and clinical outcomes. Coroflex Please™ stent is a newly developed drug eluting stent using the Coroflex™ stent platform combined with the drug paclitaxel contained in a polymer coating. PECOPS I trial, one-arm observational study, showed that the clinical and angiographic outcomes of Coroflex Please™ stent were within the range of those of Taxus, the 1<sup>st </sup>generation paclitaxel-eluting stent (PES). However, there have been no studies directly comparing the Coroflex Please™ stent with the Taxus Liberte™ stent that is the newest version of Taxus. Therefore, prospective, randomized trial is required to demonstrate the non-inferiority of Coroflex Please™ stent compared with Taxus Liberte™ stent in a head-to-head manner.</p> <p>Methods</p> <p>In the comparison of Efficacy between COroflex PLEASe™ ANd Taxus™ stent(ECO-PLEASANT) trial, approximately 900 patients are being prospectively and randomly assigned to the either type of Coroflex Please™ stent and Taxus Liberte™ stent via web-based randomization. The primary endpoint is clinically driven target vessel revascularization at 9 months. The secondary endpoints include major cardiac adverse events, target vessel failure, stent thrombosis and angiographic efficacy endpoints.</p> <p>Discussion</p> <p>The ECO-PLEASANT trial is the study not yet performed to directly compare the efficacy and safety of the Coroflex Please™ versus Taxus Liberte™ stent. On the basis of this trial, we will be able to find out whether the Coroflex Please™ stent is non-inferior to Taxus Liberte™ stent or not.</p> <p>Trial registration</p> <p>ClinicalTrials.gov number, NCT00699543.</p

    Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

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    Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

    Flexible electronics based on one-dimensional and two-dimensional hybrid nanomaterials

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    Research on flexible or wearable electronics has been grown remarkably due to theadvent of nanomaterials, such as metal nanowires, graphene, or transition metaldichalcogenides. Although each nanomaterial has mechanical and electrical charac-teristics that can be applied into flexible electronics, the limitations of each nano-material are also clear. In order to overcome the limitations of these nanomaterials,research on the hybrid structures of nanomaterials has been extensively conducted.In this study, we introduce the properties of one-dimensional nanomaterials, two-dimensional nanomaterials, and their hybrid nanomaterials. And then, we provideinformation concerning various flexible electronics based on these nanomaterials.11Nsciescopu

    ENVIRONMENTAL FATIGUE OF METALLIC MATERIALS IN NUCLEAR POWER PLANTS – A REVIEW OF KOREAN TEST PROGRAMS

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    Environmental fatigue of the metallic components in light water reactors has been the subject of extensive research and regulatory interest in Korea and abroad. Especially, it was one of the key domestic issues for the license renewal of operating reactors and licensing of advanced reactors during the early 2000s. To deal with the environmental fatigue issue domestically, a systematic test program has been initiated and is still underway. The materials tested were SA508 Gr.1a low alloy steels, 316LN stainless steels, cast stainless steels, and an Alloy 690 and 52M weld. Through tests and subsequent analysis, the mechanisms of reduced low cycle fatigue life have been investigated for those alloys. In addition, the effects of temperature, dissolved oxygen level, and dissolved hydrogen level on low cycle fatigue behaviors have been investigated. In this paper, the test results and key analysis results are briefly summarized. Finally, an on-going test program for hot-bending of 347 stainless steel is introduced

    Multicolor Cholesteric Liquid Crystal Display in a Single-Layered Configuration using a Multi-Pitch Stabilizations

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    We report a cholesteric liquid crystal (ChLC) display with multicolor in a single-layered configuration using a multi-pitch stabilization by reactive mesogen (RM). The cholesteric pitches were modulated by temperature and stabilized at room temperature by polymerization of the RMs through ultraviolet (UV) exposure. In a single-layered ChLC display without any additional layer such as a color filter, multicolor was obtained by a multipitch stabilization through spartially selective UV expose at several temperatures.

    Influence of Hold Time and Stress Ratio on Cyclic Creep Properties Under Controlled Tension Loading Cycles of Grade 91 Steel

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    Influences of hold time and stress ratio on cyclic creep properties of Grade 91 steel were systemically investigated using a wide range of cyclic creep tests, which were performed with hold times (HTs) of 1 minute, 3 minutes, 5 minutes, 10 minutes, 20 minutes, and 30 minutes and stress ratios (R) of 0.5, 0.8, 0.85, 0.90, and 0.95 under tension loading cycles at 600°C. Under the influence of HT, the rupture time increased to HT = 5 minutes at R = 0.90 and R = 0.95, but there was no influence at R = 0.50, 0.80, and 0.85. The creep rate was constant regardless of an increase in the HT, except for the case of HT = 5 minutes at R = 0.90 and R = 0.95. Under the influence of stress ratio, the rupture time increased with an increase in the stress ratio, but the creep rate decreased. The cyclic creep led to a reduction in the rupture time and an acceleration in the creep rate compared with the case of monotonic creep. Cyclic creep was found to depend dominantly on the stress ratio rather than on the HT. Fracture surfaces displayed transgranular fractures resulting from microvoid coalescence, and the amount of microvoids increased with an increase in the stress ratio. Enhanced coarsening of the precipitates in the cyclic creep test specimens was found under all conditions

    Subjectivity Analysis of Underground Incinerators: Focus on Academic and Industry Experts

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    Recently, incinerators have been shifted to underground complexes because of concerns regarding environmental pollution and declining land prices. In Korea, an underground waste incinerator has been built for the first time, with additional construction being expected in the near future. Therefore, a perception survey was conducted to acquire responses from South Korean experts regarding the impact of underground complex incinerators. The Q-methodology was used in the survey to examine various viewpoints. Academicians showed concerns regarding environmental effects of ground incinerators, and environmental and economic effects of underground complex incinerators; conversely, industrialists were concerned about civil complaints and administrative processing, indicating that the academicians were more concerned about scientific issues, whereas the industrialists were more concerned about democratic issues. Furthermore, both groups expressed concerns regarding land value and civil complaints of ground incinerators, safety issues and resultant social distrust of underground incinerators. The findings suggest that, to address the safety issues involving underground incinerator construction, governance by local experts is required for a holistic evaluation of environmental issues and economic feasibility of underground incinerators. To establish a link between science and democracy, measures for transparently sharing information are necessary
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