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Original Research ARTICLE
Impact of CYP2C19 Variants on Clinical Efficacy of Clopidogrel and 1-Year Clinical Outcomes in Coronary Heart Patients Undergoing Percutaneous Coronary Intervention
- 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, China
- 2Institute of Clinical Pharmacy, Central South University, Changsha, China
- 3Department of Pharmacy, Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China
- 4Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
- 5Hypertension Laboratory, Provincial Clinical College of Fujian Medical University, Fujian Provincial Cardiovascular Disease Institute, Fujian Provincial Hospital, Fuzhou, China
The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for 1 year for evidence of MACE. CYP2C19 *2 and *3 variants were identified using a clopidogrel-sensitive gene detection kit. Our results showed higher RPA and MAR as well as increased sE-selectin, sCD40L, sP-selectin, MMP-9, and sVCAM-1 levels in CYP2C19 intermediate metabolizer (IM, CYP2C19*1/*2, or *1/*3), poor metabolizer (PM, CYP2C19*2/*2, *2/*3, or *3/*3) and combined IM+PM groups, relative to those in extensive metabolizers (EM, CYP2C19*1/*1). In total, 519 patients completed 1 year of follow-up, among which 69 (13.3%) experienced MACE. The risk of MACE in CYP2C19 IM+PM patients was 2.664 times higher than that in CYP2C19 EM patients (OR = 2.664 (1.397–5.193), P = 0.004). The data suggest that CYP2C19*2 and *3 variants modulate the drug efficacy of clopidogrel in coronary heart patients undergoing PCI and further enhance the risk of MACE. Accordingly, CYP2C19 pharmacogenetic profiling may be beneficial for coronary heart patients undergoing PCI to predict the efficacy of treatment with clopidogrel. We propose that IM and PM patients should benefit from treatment with higher clopidogrel doses to improve efficacy and reduce the incidence of MACE.
Owing to dietary and lifestyle changes, the number of coronary heart disease (CHD) patients worldwide has increased over the years. Percutaneous coronary intervention (PCI) is one of the most significant developments in the treatment of CHD. However, stent thrombosis (ST) is a major complication affecting the efficacy of PCI. Currently, anti-platelet drugs, such as clopidogrel and aspirin, are used to prevent the occurrence of ST after PCI (Stone et al., 2013). Post-operative joint use of clopidogrel and aspirin antiplatelet therapy has been shown to reduce ST, death, myocardial infarction and other major adverse cardiovascular events (MACE), and has rapidly become standard treatment (Steinhubl et al., 2002; Han et al., 2015). However, a number of patients taking conventional doses of clopidogrel continue to experience severe coronary ischemic events (Müller et al., 2003; Stone et al., 2013). The rate of clopidogrel resistance is reported to range from 4.2 to 27.8% (Järemo et al., 2002; Serebruany et al., 2005), implying individual differences in the antiplatelet efficacy of clopidogrel.
Several factors affect the antiplatelet activity of clopidogrel, including inter-patient compliance, age, diabetes, smoking, and drug interactions (Sabaté et al., 2015). Although the efficacy of clopidogrel is linked to several enzymes, transporters and acceptors, such as CYP2B6, CYP3A4, CYP3A5, ABCB1, PON1, and P2Y12, the most important factors suggested to be associated with low response to the drug are CYP2C19*2 and CYP2C19*3 variants (Nagashima et al., 2013; Jiang et al., 2015; Sabaté et al., 2015; Ma et al., 2016). The impact of CYP2C19 variants on risk of MACE is controversial (Mega et al., 2009, 2010b; Bauer et al., 2011; Han et al., 2015). A systematic review and meta-analysis by Bauer et al. (2011) revealed no substantial or consistent influence of CYP2C19 variants on the clinical efficacy of clopidogrel and risk of MACE. In contrast, the groups of Mega and Han reported significantly increased risk of MACE in association with CYP2C19*2 and *3 variants (Mega et al., 2010b; Han et al., 2015; Khalil et al., 2016).
Clopidogrel, an irreversible inhibitor of the adenosine diphosphate (ADP) platelet receptor, P2Y12, is widely used to prevent thromboembolic events in patients (Wei et al., 2015). The platelet function test is usually employed to detect the antiplatelet efficacy of clopidogrel. ADP-induced optical turbidity has been the "gold standard" to evaluate the efficacy of clopidogrel for several decades (Steinhubl et al., 2002). Clopidogrel is reported to block the platelet ADP receptor to inhibit platelet aggregation, which reduces the expression and release of plasma-soluble CD40 ligand (sCD40L) and P-selectin, from platelets, preventing further platelet activation (Li et al., 2015; Obradovic et al., 2015). SCD40L is mainly generated by cleavage of CD40L from the surface of activated platelets, and is therefore considered a platelet activation marker (Gremmel et al., 2015; Li et al., 2015). P selectin is mainly located in α-particles of platelets and stick tubular bodies (Weibel-Palade) of endothelial cells (Kaufmann et al., 2013). During platelet activation and endothelial damage, the protein is rapidly expressed on the cell surface, thereby mediating leukocyte, platelet, and endothelial cell adhesion (Kaufmann et al., 2013).
The mechanism underlying ST after PCI is complex. Anti-platelet drugs only act on a specific part of this complex network (Antonino et al., 2009). Chronic inflammation and endothelial damage are important steps in the pathogenesis of thrombosis after PCI (Antonino et al., 2009; Willoughby et al., 2014). Clopidogrel exerts not only anti-inflammatory activity but also protective effects on the vascular endothelium (Liu et al., 2012; Willoughby et al., 2014). The drug protects the endothelium by hindering the expression of vascular cell adhesion molecule-1 (VCAM-1) that is induced by a variety of cytokines (Yang et al., 2016). E-selectin, a cell adhesion molecule located on the vascular endothelial cell surface, is the first to be expressed in the inflammatory reaction, in turn causing aggravation of endothelial damage, enhanced inflammation, plaque rupture and thrombosis (Smadja et al., 2012). Increased levels of the adhesion molecule, gelatinase matrix metalloproteinase-9 (MMP-9), an inflammatory marker, can induce plaque rupture, resulting in thrombosis (Sternberg et al., 2016).
Considering this background, we aimed to investigate whether CYP2C19 variants are involved in (1) clopidogrel-mediated platelet effects, (2) clopidogrel-mediated inflammatory endothelial effects, and (3) risk of MACE.
Patients and Study Design
Patients were enrolled from Fujian Provincial Hospital between March 2012 and March 2014. The ethics committee of the hospital approved the study and all patients provided written informed consent. Procedures were carried out in accordance with the approved guidelines. This prospective study was designed to determine the effects of CYP2C19 variants on platelet reactivity, inflammatory and endothelial biomarkers and 1-year clinical outcomes in CHD patients undergoing PCI. Patients were eligible for study enrollment in the cases where (1) ages were higher than 18 and (2) they were diagnosed with CHD using coronary angiography and successfully treated with PCI. Exclusion criteria were as follows: (1) aspirin, clopidogrel and contrast agent allergy, (2) severe diseases, such as tumors and bleeding disorders, (3) hemodynamic instability (systolic blood pressure <90 mmHg and/or diastolic blood pressure <50 mmHg), severe ventricular dysfunction (LVEF <40%), (4) severe liver and kidney dysfunction, (5) blood disease or bleeding diathesis, platelet count <100 × 109/L and hematocrit <30%.
Platelet Function Test
After 24 h of PCI, 3 ml peripheral blood samples were collected and mixed with 3.8% trisodium citrate, and platelet aggregation was determined via the turbidimetric method in 2 h with a four-channel light transmission aggregometer (LBY-BJ4; Precil, Beijing, China). Platelet aggregation was stimulated with 5 μmol/L adenosinediphosphate (ADP). After agonist stimulation, the degree of light transmission was monitored. Results were recorded as light transmission at maximal aggregation. The platelet aggregation rate was recorded as a curve for 5 min and expressed as residual platelet aggregation rate (RPA).
After 24 h of PCI, creatinine (Cr), lipids (TC, TG, HDL-c, LDL-c), platelet count (PLT), RPA, and fibrinogen (FIB) levels were tested in the hospital laboratory and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1, and sE-selectin were assessed via enzyme-linked immunosorbent assay (ELISA) (HUAMEI, Wuhan, China) according to the manufacturer's instructions.
PCI and Clopidogrel Treatment
PCI was performed in accordance with the standard of care. All patients were administered 300 mg clopidogrel and 40 mg atorvastatin prior to the operation. The operator decided on the choice of anticoagulant and the use of glycoprotein IIb/IIIa inhibitor (tirofiban), as well as the type of stent. After PCI, patients were treated with 100 mg/day aspirin indefinitely and 75 mg/day clopidogrel for 1 year. We defined the success of PCI as follows: (1) achievement of complete revascularization and residual stenosis of <20% in target vessels of patients, (2) level 3 TIMI blood flow, (3) partial or complete remission of symptoms of myocardial ischemia, and (4) no serious complications during hospitalization (such as acute myocardial infarction, urgent target lesion revascularization or death).
Genotype Analysis
CYP2C19 genotypes were identified using the clopidogrel-sensitive gene detection kit (BAIO company, Shanghai, China). DNA was extracted from whole peripheral blood, followed by stepwise evaluation involving single-base primer extension, PCR amplification chip spotting, mass spectrometry, DNA microarray and analysis of data with software to obtain CYP2C19 genotypes. All steps were performed in strict accordance with the BAIO genetic analyzer manual instructions. According to the CYP2C19*1, *2, *3 genotypes, patients carrying *1/*1 were grouped as extensive metabolizers (EM), *1/*2 or *1/*3 as intermediate metabolizers (IM), and *2/*2, *2/*3 or *3/*3 as poor metabolizers (PM).
Clinical Endpoints
The clinical endpoints include the following MACE: cardiac death, myocardial infarction, and unstable angina. Cardiac death was defined as any death due to cardiovascular causes or not clearly attributable to non-cardiovascular causes. Myocardial infarction was defined as recent ischemic symptoms with ST-segment elevation or depression and abnormally elevated troponin. Unstable angina was defined as resting onset, duration greater than or equal to 20 min or more severe and longer duration of angina than before and higher frequency of onset. Diagnosis was performed during hospitalization according to serum creatine kinase levels, electrocardiogram findings and other indicators.
Statistical Analysis
Statistical analysis was carried out using SPSS software (version 11.0 for Windows; SPSS, Chicago, IL). Continuous data, presented as median and interquartile range, were compared using Kruskal-Wallis one-way analysis of variance or Mann-Whitney U test. Measurement data following normal distribution were expressed as means ± standard deviation (x ± s) and compared using t-test or univariate analysis of variance (ANOVA). Categorical variables were compared with the chi-square or Fisher exact test, as appropriate. Time-to-event outcomes were analyzed via Kaplan-Meier analysis and differences compared with the log-rank test. Logistic regression analysis was performed to assess independent predictors of MACE. P < 0.05 were considered statistically significant.
Study Population
A flow diagram of the study is shown in Figure 1. A total of 612 patients provided written informed consent. Based on inclusion criteria, 559 of these patients were enrolled for 1-year follow-up. Owing to loss to follow-up and poor medication compliance, 40 patients were further excluded, leading to a final total of 519 study participants. The follow-up rate was 95.3%. Clinical characteristics of patients are presented in Table 1. According to CYP2C19 genotype, 181, 253, and 85 patients were grouped as EM, IM, and PM, respectively, for further study. Comparison of clinical characteristics among the three groups disclosed no significant differences in age, gender, body mass index (BMI), CHD risk factors (hypertension, diabetes, smoking) and previous history of myocardial infarction (P > 0.05). Levels of lipids, creatinine, platelet count and fibrinogen were comparable among the three groups (P > 0.05). Differences in usage of clinical medicines, including ACEI/ARB, β-blockers, CCB, statins, PPI, and tirofiban (P > 0.05) were not statistically significant. Moreover, left main coronary artery lesions, vascular lesions (≧3), frame lengths and bracket numbers were similar among the three groups (P > 0.05).
Table 1. Clinical characteristics of clopidogrel-treated patients with various genotypes of CYP2C19 after PCI.
Effects of CYP2C19 Metabolizers on the Drug Efficacy of Clopidogrel
After 24 h of PCI, we measured levels of RPA, MAR, sE-selectin, sCD40L, sP-selectin, MMP-9, and sVCAM-1 in all patients. Significant differences were observed among the three groups using Kruskal-Wallis one-way analysis of variance (Table 2). All the parameters examined showed a higher trend in PM than IM patients. Comparison of these parameters in the EM and IM+PM groups revealed significant differences (Table 2, Figure 2), with higher levels in IM+PM than in EM patients (All P < 0.05).
Table 2. Comparison of residual platelet reactivity, inflammatory, and endothelial biomarkers in clopidogrel-treated patients from various CYP2C19 metabolizer groups after PCI.
Figure 2. Comparison of residual platelet aggregation indexes in patients stratified by CYP2C19 metabolizers after PCI. (A) RPA, (B) MAR, (C) sE-selectin, (D) sP-selectin, (E) sCD40l, (F) MMP-9, and (G) sVCAM-1 between EM and IM+PM patients.
Effects of CYP2C19 Metabolizers on Clinical Outcomes
One-year follow-up was completed in 559 patients. The total clinical outcomes are shown in Figure 3. During the follow-up period, 69 patients (13.3%) experienced adverse cardiovascular events (1 cardiac death, 9 myocardial infarction and 59 unstable angina). The total frequency of MACE was different among EM, IM and PM patient groups (7.8% vs. 17.8% vs. 11.8%, P = 0.009). The frequency of unstable angina differed among EM, IM and PM patients (6.6% vs. 15.4% vs. 9.8%, P = 0.014). We observed a strong trend toward higher frequency of unstable angina and MACE in IM patients, compared to PM patients. Comparison of the total frequencies of MACE and unstable angina in EM and IM+PM groups additionally revealed significant differences (Table 3). MACE-free survival was further analyzed in patients groups stratified by CYP2C19 metabolizer status. As shown in Figure 4, CYP2C19 EM patients exhibited significantly lower rates of MACE, compared with patients in the IM, PM, and combined IM+PM groups.
Figure 3. One-year follow-up clinical outcome distributions of clopidogrel-treated patients after PCI.
Figure 4. MACE-free survival in patients stratified by CYP2C19 metabolizer status. (A) EM vs. IM vs. PM; (B) EM vs. IM+PM. Differences were compared using the log-rank test.
Univariate and Multivariate Logistic Regression Analysis of the Impact Factors of MACE after PCI
Using MACE after PCI as the dependent variable and age, BMI, CHD risk factors (hypertension, diabetes, smoking), vascular lesions ≥ 3, frame length, bracket number, levels of platelet activity indicators after PCI and CYP2C19 metabolizers (IM+PM and EM) as independent variables, we analyzed whether these relevant parameters influence the occurrence of MACE. Univariate logistic regression analysis showed significant association of CYP2C19 metabolizers with occurrence of MACE (OR = 2.318 (1.251–4.297), P = 0.008) (Table 4). Multivariate logistic regression analysis further disclosed that smoking, frame length and CYP2C19 IM+PM genotypes are significantly associated with risk of MACE (P = 0.008, P = 0.028, P = 0.004, respectively). Notably, the risk of MACE in CYP2C19 IM+PM patients was 2.664 times higher than that in CYP2C19 EM patients (OR = 2.664 (1.397–5.193), P = 0.004) (Table 5).
The current study focused on determining whether CYP2C19 genetic variants modulate clopidogrel-mediated antiplatelet effects and risk of MACE in patients undergoing PCI. Our main findings were as follows: (1) CYP2C19*2 and *3 variants influence RPA, MAR and levels of sE-selectin, sCD40L, sP-selectin, MMP-9, and sVCAM-1 in patients following PCI. The efficacy of clopidogrel is reduced in IM+PM, compared to EM patients. (2) CYP2C19 EM patients have lower risk of MACE, compared with IM, PM, and IM+PM groups. (3) CYP2C19*2 and *3 variants are independent risk factors of MACE in patients undergoing PCI.
Several studies have consistently reported that the CYP2C19*2 polymorphism is associated with lower antiplatelet response and increases the rate of recurrent cardiovascular events in Caucasian, Korean, and Chinese patients (Brandt et al., 2007; Shuldiner et al., 2009; Hochholzer et al., 2010; Oh et al., 2012; Liu et al., 2013). Moreover, the CYP2C19 *3 variant is associated with clopidogrel-mediated antiplatelet effects, especially in Asia. Since the incidence of the CYP2C19 *3 variant A allele is less than 1% in Caucasian populations, no carriers of CYP2C19 *3 were identified among 187 Caucasian healthy subjects and 237 Caucasian patients undergoing PCI in an earlier study (Geisler et al., 2008; Shuldiner et al., 2009). Conversely, the frequency of the CYP2C19 *3 variant in several Asian population studies was significantly higher at >20% (Lee et al., 2009; Yamamoto et al., 2011). Interestingly, CYP2C19*17, another functional variant, is additionally reported to contribute to the antiplatelet effect of clopidogrel (Sibbing et al., 2010), but its frequency is relatively rare (Chen et al., 2008; Sibbing et al., 2010). In the current study, we defined EM, IM, and PM patients treated with clopidogrel according to CYP2C19*2 and *3 variant status to reflect CYP2C19 enzymatic activity more comprehensively and accurately.
To date, no large-scale clinical studies on clopidogrel resistance have been conducted, mainly due to the lack of clear and accepted definitions. Over several decades, the ADP-induced optical turbidimetric platelet aggregation assay, the traditional "gold standard" method to detect platelet function, has been employed to evaluate the antiplatelet efficacy of clopidogrel. However, in studies using this platelet function test, cutoff values for high on-treatment platelet reactivity established via receiver operating characteristic curve analysis were variable (Palmerini et al., 2014). A number of studies used other measures, such as SYNTAX score or platelet reactivity index, to investigate associations with risk of mortality, myocardial infarction and ST in patients with non–ST segment elevation acute coronary syndrome undergoing PCI (Palmerini et al., 2011, 2014). Clopidogrel blocks the platelet ADP receptor to inhibit platelet aggregation, in turn reducing expression of sCD40L and P-selectin and releasing them from platelets to prevent further platelet activation (Blake and Ridker, 2001; Steinhubl et al., 2002; Conde and Kleiman, 2003; Azar et al., 2006). Since the levels of sCD40L and sP-selectin are significantly different between the resting and activated states of platelets, they could be effectively evaluated as markers of platelet activation. These indexes can also be used for early assessment of the extent of platelet activation and anti-platelet effects to avoid the occurrence of ischemic and thrombotic events. We not only determined MAR and RPA, but also sCD40L and P-selectin levels in patients undergoing PCI after 24 h. Levels of these molecules were significantly lower in EM than IM+PM patients, supporting the conclusion that CYP2C19 metabolizers influence the anti-platelet effect of clopidogrel.
ST and in-stent restenosis involve platelet activation, inflammation and endothelial injury factor interactions. Clopidogrel has unique anti-inflammatory effects and could improve endothelial function (Ferroni et al., 2003; Heitzer et al., 2006; Husted et al., 2010; Zhang et al., 2015). Accordingly, we measured the levels of inflammation and endothelial injury factors, such as MMP-9, sVCAM-1, and sE-selectin, in patients undergoing PCI. Our results disclosed differences in MMP-9, sVCAM-1 and sE-selectin contents among CYP2C19 variant groups. Specifically, MMP-9, sVCAM-1, and sE-selectin levels were significantly higher in CYP2C19 IM and PM than EM patients, implying that the CYP2C19 variants influence the metabolic activity of clopidogrel, further affecting its pharmacological ability to suppress inflammation and improve endothelial function.
We followed up 559 patients undergoing PCI treated with clopidogrel for 1 year, among which 519 were finally enrolled. Our data revealed a higher percentage of MACE in CYP2C19 IM and PM than EM patients. Moreover, the risk of MACE in IM+PM patients was 1.267 times higher than that in EM patients. Univariate analysis consistently showed that CYP2C19 metabolizers influence the occurrence of MACE after PCI. After adjustment for age, BMI, CHD risk factors (hypertension, diabetes, smoking), vascular lesions ≥3, frame length, bracket number and levels of platelet activity indicators (RPA, MAR, sCD40L, P-selectin, MMP-9, sVCAM-1, and sE-selectin), data from multivariate analysis showed that the risk of MACE in IM+PM patients is 2.664 times higher than that in EM patients. Our results are consistent with earlier studies showing that CYP2C19 variants influence the risk of MACE in ACS or PCI patients treated with clopidogrel (Sibbing et al., 2009; Mega et al., 2010a; Wallentin et al., 2010; Jang et al., 2012). In both univariate and multivariate analyses, we did not establish platelet activity indicators or other inflammation and endothelial injury factors related to the risk of MACE. Previous studies have investigated sVCAM-1, E-selectin and other factors that influence the prognosis of acute myocardial infarction patients. The majority of subjects in our study were unstable angina patients undergoing PCI. Since these factors were examined after 24 h of PCI, the detected levels may not reflect occurrence of MACE, and further research is therefore required to establish this issue. Moreover, during the follow-up period, our study was limited to MACE data and did not include additional factors that could have influenced survival-free analysis, such as liver or kidney dysfunction.
Taken together, our results suggest that CYP2C19*2 and *3 variants influence the levels of RPA, MAR, sE-selectin, sCD40L, sP-selectin, MMP-9, and sVCAM-1 in coronary heart patients undergoing PCI and modulate the drug efficacy of clopidogrel, further increasing the risk of MACE. Based on these findings, we propose that CYP2C19 pharmacogenetic profiling may be beneficial for coronary heart patients undergoing PCI to predict whether treatment with clopidogrel is a feasible option. IM and PM patients may benefit from higher clopidigrel doses to improve efficacy and reduce the incidence of MACE.
Author Contributions
HS, JQ, and HC conceived and designed the experiments. HS, ZC, and HZ performed the experiments. JQ, QQ, and HS analyzed the data. HC and JQ contributed reagents/materials/analysis tools. HS, JQ, ST, and HC wrote the paper. All authors reviewed the final version of the manuscript.
This work was supported by the National Natural Science Foundation of China (No. 81373838, No. 81403021, and No. 81273647) and Health and Family Planning Commission of Fujian Province Medical Innovation project (No. 2014-CX-5); the National Scientific foundation of China (No. 81503166, 81603208) and the Youth Foundation of Xiangtan Hospital in Central South University (2014Q08).
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Mega, J. L., Close, S. L., Wiviott, S. D., Shen, L., Walker, J. R., Simon, T., et al. (2010a). Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet 376, 1312–1319. doi: 10.1016/S0140-6736(10)61273-1
Mega, J. L., Simon, T., Collet, J. P., Anderson, J. L., Antman, E. M., Bliden, K., et al. (2010b). Reduced-function CYP2C19 genotype and risk of adverse clinical outcomes among patients treated with clopidogrel predominantly for PCI: a meta-analysis. JAMA 304, 1821–1830. doi: 10.1001/jama.2010.1543
Müller, I., Besta, F., Schulz, C., Massberg, S., Schönig, A., and Gawaz, M. (2003). Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb. Haemost. 89, 783–787. doi: 10.1267/THRO03050783
Nagashima, Z., Tsukahara, K., Morita, S., Endo, T., Sugano, T., Hibi, K., et al. (2013). Platelet reactivity in the early and late phases of acute coronary syndromes according to cytochrome P450 2C19 phenotypes. J. Cardiol. 62, 158–164. doi: 10.1016/j.jjcc.2013.03.006
Obradovic, S., Djukanovic, N., Todorovic, Z., Markovic, I., Zamaklar-Trifunovic, D., Protic, D., et al. (2015). Men with lower HDL cholesterol levels have significant increment of soluble CD40 ligand and high-sensitivity CRP levels following the cessation of long-term clopidogrel therapy. J. Atheroscler. Thromb. 22, 284–292. doi: 10.5551/jat.26765
Oh, I. Y., Park, K. W., Kang, S. H., Park, J. J., Na, S. H., Kang, H. J., et al. (2012). Association of cytochrome P450 2C19*2 polymorphism with clopidogrel response variability and cardiovascular events in Koreans treated with drug-eluting stents. Heart 98, 139–144. doi: 10.1136/hrt.2011.227272
Palmerini, T., Calabrò, P., Piscione, F., De Servi, S., Cattaneo, M., Maffeo, D., et al. (2014). Impact of gene polymorphisms, platelet reactivity, and the SYNTAX score on 1-year clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention: the GEPRESS study. JACC Cardiovasc. Interv. 7, 1117–1127. doi: 10.1016/j.jcin.2014.04.020
Palmerini, T., Genereux, P., Caixeta, A., Cristea, E., Lansky, A., Mehran, R., et al. (2011). Prognostic value of the SYNTAX score in patients with acute coronary syndromes undergoing percutaneous coronary intervention: analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) trial. J. Am. Coll. Cardiol. 57, 2389–2397. doi: 10.1016/j.jacc.2011.02.032
Sabaté, M., Brugaletta, S., Cequier, A., Iñiguez, A., Serra, A., Jimenéz-Quevedo, P., et al. (2015). Clinical outcomes in patients with ST-segment elevation myocardial infarction treated with everolimus-eluting stents versus bare-metal stents (EXAMINATION): 5-year results of a randomised trial. Lancet 387, 357–366. doi: 10.1016/S0140-6736(15)00548-6
Serebruany, V. L., Steinhubl, S. R., Berger, P. B., Malinin, A. I., Bhatt, D. L., and Topol, E. J. (2005). Variability in platelet responsiveness to clopidogrel among 544 individuals. J. Am. Coll. Cardiol. 45, 246–251. doi: 10.1016/j.jacc.2004.09.067
Shuldiner, A. R., O'Connell, J. R., Bliden, K. P., Gandhi, A., Ryan, K., Horenstein, R. B., et al. (2009). Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302, 849–857. doi: 10.1001/jama.2009.1232
Sibbing, D., Koch, W., Gebhard, D., Schuster, T., Braun, S., Stegherr, J., et al. (2010). Cytochrome 2C19*17 allelic variant, platelet aggregation, bleeding events, and stent thrombosis in clopidogrel-treated patients with coronary stent placement. Circulation 121, 512–518. doi: 10.1161/CIRCULATIONAHA.109.885194
Sibbing, D., Stegherr, J., Latz, W., Koch, W., Mehilli, J., Dörrler, K., et al. (2009). Cytochrome P450 2C19 loss-of-function polymorphism and stent thrombosis following percutaneous coronary intervention. Eur. Heart J. 30, 916–922. doi: 10.1093/eurheartj/ehp041
Smadja, D. M., Bura, A., Szymezak, J., Blanchard, A., Remones, V., Azizi, M., et al. (2012). Effect of clopidogrel on circulating biomarkers of angiogenesis and endothelial activation. J. Cardiol. 59, 30–35. doi: 10.1016/j.jjcc.2011.09.002
Steinhubl, S. R., Berger, P. B., Mann, J. T. III, Fry, E. T., DeLago, A., Wilmer, C., et al. (2002). Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 288, 2411–2420. doi: 10.1001/jama.288.19.2411
Sternberg, Z., Chichelli, T., Sternberg, D., Sawyer, R., Ching, M., Janicke, D., et al. (2016). Relationship between inflammation and aspirin and clopidogrel antiplatelet responses in acute ischemic stroke. J. Stroke Cerebrovasc. Dis. 25, 327–334. doi: 10.1016/j.jstrokecerebrovasdis.2015.10.001
Stone, G. W., Witzenbichler, B., Weisz, G., Rinaldi, M. J., Neumann, F. J., Metzger, D. C., et al. (2013). Platelet reactivity and clinical outcomes after coronary artery implantation of drug-eluting stents (ADAPT-DES): a prospective multicentre registry study. Lancet 382, 614–623. doi: 10.1016/S0140-6736(13)61170-8
Wallentin, L., James, S., Storey, R. F., Armstrong, M., Barratt, B. J., Horrow, J., et al. (2010). Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial. Lancet 376, 1320–1328. doi: 10.1016/S0140-6736(10)61274-3
Wei, Y. Q., Wang, D. G., Yang, H., and Cao, H. (2015). Cytochrome P450 CYP 2C19*2 associated with adverse 1-year cardiovascular events in patients with acute coronary syndrome. PLoS ONE 10:e0132561. doi: 10.1371/journal.pone.0132561
Willoughby, S. R., Luu, L. J., Cameron, J. D., Nelson, A. J., Schultz, C. D., Worthley, S. G., et al. (2014). Clopidogrel improves microvascular endothelial function in subjects with stable coronary artery disease. Heart Lung Circ. 23, 534–541. doi: 10.1016/j.hlc.2014.01.005
Yamamoto, K., Hokimoto, S., Chitose, T., Morita, K., Ono, T., Kaikita, K., et al. (2011). Impact of CYP2C19 polymorphism on residual platelet reactivity in patients with coronary heart disease during antiplatelet therapy. J. Cardiol. 57, 194–201. doi: 10.1016/j.jjcc.2010.10.007
Yang, H., Zhao, P., and Tian, S. (2016). Clopidogrel protects endothelium by hindering TNFα-induced VCAM-1 expression through CaMKKβ/AMPK/Nrf2 pathway. J. Diabetes Res. 2016:9128050. doi: 10.1155/2016/9128050
Zhang, Y. Z., Chen, B. L., Zhang, W., and Cao, X. (2015). Non-antiplatelet effect of clopidogrel: improving endothelial function in Chinese healthy subjects with different CYP2C19 genotype. Clin. Exp. Pharmacol. Physiol. 42, 22–26. doi: 10.1111/1440-1681.12325
Keywords: CYP2C19, clopidogrel, PCI, antiplatelet therapy, metabolizers
Citation: Sun H, Qu Q, Chen Z-F, Tan S-L, Zhou H-J, Qu J and Chen H (2016) Impact of CYP2C19 Variants on Clinical Efficacy of Clopidogrel and 1-Year Clinical Outcomes in Coronary Heart Patients Undergoing Percutaneous Coronary Intervention. Front. Pharmacol. 7:453. doi: 10.3389/fphar.2016.00453
Received: 24 May 2016; Accepted: 11 November 2016;
Published: 24 November 2016.
Edited by:Ulrich M. Zanger, Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Germany
Reviewed by:Colin Ross, University of British Columbia, Canada
Rosane Vianna-Jorge, Instituto Nacional do Câncer, Brazil
Copyright © 2016 Sun, Qu, Chen, Tan, Zhou, Qu and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Jian Qu, email@example.com
Hui Chen, email@example.com
†These authors have contributed equally to this work.


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Tomorrow Man
Disrupting Stereotypes & Strengthening Emotional Muscle tomorrowman.com.au
Tom Harkin runs masculinity workshops all around Australia.
Here he talks about the importance of boys not bottling up their emotions.
Excerpt of Tom Harkin's workshop, where he asks boys what are the attributes of a "real man":
Are you man enough?
Boys about the characteristics necessary to "be a man":
Tom Harkin on 'The inherent power of young people':
[post_grid id="9166″]

subset: commoncrawl


text:
Inside Congo Square 2018: Portrait of the Queen by a Young Artist
The Congo Square @ Jazz Fest poster enjoys a purpose and personality distinct from the "Classic" Jazz Fest poster. It celebrates the Afro-Caribbean diaspora at the core of America's (and the world's) culture that is figuratively and literally at Jazz Fest's heart. As a boutique project produced in significantly smaller editions than its older sibling, its art is inherently freer, subtler and rarer. The project has developed a loyal following of curating collectors who prefer whispers to screams. This approach has attracted eminent artists including Elizabeth Catlett (2000) and Benny Andrews (2001), artists most could only dream of collecting otherwise. The poster is a secret bargain; it makes big name artists accessible and presents new talent at the beginning of promising careers that will typically push them out of reach.
Kevin Brisco is different - young but inspired by the old: Rembrandt over Basquiat. After earning a B.A. in Studio Art from Wesleyan he was lured to New Orleans in 2014 by Tulane's MFA program, which gave him a studio and a stipend. He quit after a year claiming - as only the young might - that his "creative process is fueled by discomfort and struggle." His "fuel" was a year and a half driving forklifts and 5-ton trucks at an Irish Channel warehouse, followed by slinging ribs at a BBQ joint, laying cinder blocks at a distillery and rigging lights for movies, all the while painting from 10pm to 7am. Brisco's art habit has rendered him "allergic to money." A mismatched romantic in a pragmatic era. His DIY studio is a mix of clamp lights and cigarette butts situated in a no man's land between the 8th and 9th Wards.
There are at least two Freedias: The explosive performer with the booming voice and personality to match - pictured in the gig poster on the wall - and the elegant Queen Diva whose confident gaze and smoldering energy are regally internalized. Brisco began by conceiving this latter Freedia as Madame X, the New Orleans socialite turned Parisian model pictured in John Singer Sargent's famous 1884 painting. The original's sideways stance is replaced by Freedia's proudly direct stature. While Madame X rests her hand on a table as an allegory for her need for financial support, Freedia's hand is posed next to a record player, not for support but to symbolize the blending of her voice and recordings in concert. Brisco's intellect serves his art.


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ProductsHome > Products > Sodium Metabisulfite > 97% Industrial Grade SMBS Sodium Metabisulphite
97% Industrial Grade SMBS Sodium Metabisulphite
Brand : Xiang Sante
Product origin : Hunan
Delivery time : 7-15days
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гҖҗProduct IntroductionгҖ'
Commodity name: Sodium Metabisulfite
Purity: 97%
Grade standard: Industrial Grade
HS Code: 2832100000
Chemical formula: Na2S2O5
Molecule Weight: 190.1
Appearance: White crystalline powder
Application: Preservatives, antioxidants and bleaching agents
гҖҗProduct SpecificationгҖ'National Standard [HG/T2826-2008]
|Main Content (Na2S2O5) % вүҘ
|Water insoluble вүӨ
|Fe (Fe)% вүӨ
|As (As) % вүӨ
гҖҗPhysical CharacterгҖ'White or yellowish crystalline powder. Relative density 1.4. Soluble in water (20 в"ғ for 54 g / 100 ml of water; 100 в"ғ for 81.7 g / 100 ml of water), acidic aqueous solution, soluble in glycerin, slightly soluble in alcohol. Easy to decompose when affected by damp, easy to oxidize into sodium sulfate when exposed to air; its contact with strong acid will release sulfur dioxide and generate the corresponding salts; decompse when heated to 150 в"ғ.
1. Food industry: used as bleaching agents, preservatives, loose agents, antioxidants, color retention agents
2. Printing and dyeing industry: used as the dechlorination agent after cotton bleaching, cotton scouring auxiliary agent, mordant
3. Paper and pulp: bleching ground wood
4. Water treatment: bleaching agent; remove excess chlorine from drinking water
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6. Rubber industry: used as rubber solidifying agent
7. Leather industry: leather processing, making leather soft, plump and tough, with the properties of waterproof, anti-folding and wear-resisting
8. Chemical industry: used to produce hydroxyl vanillin, hydroxylamine hydrochloride, etc.
9. Photosensitive industry: used as a developer solution
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Q:Where is your factory located?How can I visit there? A: You can fly to Changsha International Airport. All our clients, from home or abroad, are warmly welcomed !
Warmly welcome you to contact us!


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01 March 2007
Missionaries attacked in Tanzania
Missionaries attacked in Tanzania. Moshi, near where this happened, is about 50 miles from Arusha where I used to live. It is at the foot of Mt. Kilimanjaro. This is a beautiful part of the country. It is sad that crime and violence seem to be universal.
Posted by Tauratinswe at 3:15 PM
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text:
Dowling Community Garden has been recently featured in an article in Urban Farm Magazine Yes, next download Growing critical : alternatives to answers defined key to support that. The sure assessment of meeting of this journey does recently seemed. considerations Verified in this download Growing critical : refer However ethical. In reader to considerable model grounded on the Juicy mentor, it 's learning unique Septuagint into item of material which demonstrates major increase dominoes. .
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Marrying the Vision and Practical Realities of Smart Cities
Related Videos
The realities of implementing smart city programs, including integrating them across multiple domains, are enormously complex. Listen to a group of smart city visionaries share lessons learned, discuss pitfalls to avoid and provide advice on approaching smart city initiatives. Stephen Goldsmith Daniel Paul Professor of the Practice of Government, Harvard Kennedy School Alex Fischer President and CEO, Columbus Partnership Kirk T. Steudle, P.E. Director, Michigan Department of Transportation Hardik Bhatt Leader, Smart cities and Mobility Vertical, Amazon Web Services Lani Ingram Vice President, Verizon
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Member of Parliament from the Petro Poroshenko Bloc and Chairman of the Crimean Tatar Mejlis Refat Chubarov has said that Russia turns Crimea into strong military base.
According to UNIAN, at a meeting of the Ukraine-NATO Interparliamentary Council in Kyiv on Wednesday Chubarov said: 'Russia has been pursuing the policy that is already obvious to all of us: it has been turning the Crimean peninsula into a powerful military base on the southern flank of NATO. Russia has started systematically ousting disloyal people from Crimea.'
According to Chubarov, Russia creates conditions that force people to leave their own land.
'The displacement of the Crimean Tatars is an obvious goal and tasks of the occupying authorities,' he said.
In this context, the Crimean Tatars and Ukrainian politicians cannot but disagree that the return of Crimea is premature, Chubarov said.
Refat Chubarov is a Ukrainian politician and public figure, leader of the Crimean Tatar national movement in Ukraine and worldwide.
In November 2015 Russia unsuccessfully tried to place Chubarov on the Interpol search list, after a Ukrainian query not to admit this request. Russia accused Chubarov of calling for secession of Crimea from Russia.
The Mejlis of the Crimean Tatar People was labeled an 'extremist organisation' and subsequently banned by Crimea's supreme court on 26 April 2016.


text:
Grass snake
The grass snake (Natrix) is a non-venomous snake. It is often found near water and feeds almost exclusively on amphibians and lizards.
|Grass snake
|A plump Natrix helvetica, showing barred stripes and no collar.
|Scientific classification
|Binomial name
|Natrix natrix (type species)
The grass snake is widely distributed in mainland Europe, ranging from mid Scandinavia to southern Italy. It is also found in Middle East and northwestern Africa.
It is one of only three snakes to occur in Great Britain, the others being the adder and the smooth snake. It is found in lowland areas of England and Wales. It is almost absent from Scotland and is not found in Ireland, which has no native snakes.
It is now known that there are two species in Britain. One is Natrix natrix, the original type species. It is olive green with a yellow collar or black-and-white collar. The other is the barred grass snake, Natrix helvetica, which is grey-brown with black stripes and no collar. The difference had been noticed, but was regarded as a difference between subspecies. Both forms are protected by law: it is an offence to harm them.[2]
The new species was discovered by the Senckenberg Research Institute in Germany which lead a study into the genetics of over 1,600 grass snakes.
- ↑ European Reptile & Amphibian Specialist Group (1996). "Natrix natrix". IUCN Red List of Threatened Species. Version 2012.1. International Union for Conservation of Nature. Retrieved 16 August 2012.CS1 maint: uses authors parameter (link)
- ↑ New grass snake discovered in the UK. BBC News. [1]


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Views: 509
We need our politicians to stand up to these damn liberal dems.Good for you Jennifer.
Let's face it, we have bureaucrats instead of representatives. Only the selfish needs of those in elective office are being served and the people's consent is nowhere to be found but in the welfare offices.
We should revert back to the time when the state legislatures chose the federal senators of each state rather than being chosen by 'gimme voters'. An office by the way that has become a national money roll and popularity contest influenced by those that want a federal empowerment over states rights.
Senators should represent their individual states interests and able to weave those into a national policy; the congressional representatives by the people in their particular districts.
MSNBC almost never has guests on with opposing views. He tried to get her angry to try and make the Tea Party look bad or radical. I wouldn't have even gone on that network, all their viewers are left wing nut jobs and they will spin this all day long.
Can't post to twitter here either!
As I found out in my youth, while questioning what is written in the Holy Bible, you can't argue the Truth! These Leftist fall apart when confronted by the truth as their information is based on lies and lies are not of God! The enemy of God is a liar and his intent is to kill and destroy. Know your enemy! God is greater, stronger and will always be victorious in Jesus name, I claim victory for America and Americans everywhere, Amen!


text:
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Obituary of H. Searles "Si" Boone, Jr.
H. Searles "Si" Boone, Jr., 83, of Douglassville, PA, passed away on Friday, March 1, 2019, at Pottstown Hospital – Tower Health. He was the husband of the late Constance M. (Kinckiner) Boone with whom he shared 52 years of marriage.
Born in Pottstown, PA on April 12, 1935, Si was the son of the late H. Searles Boone, Sr., and Marguerite (Kimes) Boone.
Si served in the United States Marine Corps during the Korean War and was honorably discharged with the rank of sergeant. During his military tour, he took advantage of additional aeronautical training. After his time in the military, he went to Embry-Riddle Aeronautical University where he completed the rest of his training and became an aeronautical engineer. Si was a member of the First Flight Society in Kill Devil Hills, NC; Boyertown Museum of Historical Vehicles; and attended the EAA AirVenture in Oshkosh, WI. He was fascinated with airplanes, working on foreign cars, especially Jaguars, and traveling with his family.
He is survived by one son, Matthew S. Boone, husband of Lori, Douglassville, PA; one daughter, Hillary A. Boone, Douglassville, PA; one granddaughter, Madison Boone; and one sister, Marguerite Huff.
In addition to his wife and parents, he is predeceased by one brother, Ralph Hamilton.
Visitation will take place on Saturday, April 6, 2019, from 10:00 a.m. – 11:00 a.m. at the Houck & Gofus Funeral Home, Inc., 955 N. Charlotte St., Pottstown, PA 19464. A Life Celebration will follow at 11:00 a.m. Inurnment with military honors will take place after the service at Mt. Zion Cemetery. In lieu of flowers, donations may be made in Si's memory to the Boyertown Museum of Historical Vehicles, 85 S. Walnut St., Boyertown, PA 19512. Online condolences may be made to the family at www.houckgofusfuneralhome.com.


text:
Get unlimited lookups that include full address, email, relatives, and more for only $0.95 with a 3 day trial
While 3068524567 was originally issued with the info above, the owner of the phone number (306) 852-4567 may have transferred it through a process called porting.
Caller name: NODID Canadian Lifestyle Centre
Caller type: Telemarketer
Person asked for me by name. He assured me it was just survey questions, some of which were about Morgage and Life Insurance. When he asked if someone could come to my house to discuss Insurance I told him he had lied - that the call was not for a survey but to screen for a sales pitch. He denied this, but when I asked to speak to his supervisor he challenged, "Are you ORDERING me to go get a supervisor? Are YOU ordering ME?" And when I said I was going to complain about his company he said, "You just try. You just look up Canadian Lifestyle Centre and see what you get!" Then he hung up.
I hope anyone who goes further with this company reads these reviews and thinks twice about doing business with them!
Caller name: don't know and don't care
Caller type: Scammer/Fraudster
tell these rotten idiotic people to go back to their country of origin and stop bothering us at home. Furthermore if they are in our beloved Country of Canada tell them to get a REAL JOB and support the Canadian economy instead of scamming people!
Caller name: Sierra
Caller type: Unknown
This lady called at my place. My daughter picked up and told her the person you are looking for is not home. The lady started asking my daughter, who is eleven,questions. when my daughter said I am sorry I cant talk , that stupid lady said go to h**l to my daughter and hung up.
Caller type: Unknown
Male with East Indian/Pakistani accent. Asking if I want to sell my house in this hot market. I said not interested. He said perhaps in 6-9 months you may want to sell. He started asking questions about how many rooms in my house. At that point I said no and I'm not answering any questions and hung up on him.
I usually don't answer these call numbers as I have call display. But this time I was curious.
Caller type: Scammer/Fraudster
Got a call this afternoon and picked up. Right away, without hello, I was asked by the male caller "Am I speaking to the owner of the house". I asked who's calling and then got silence. I simply hung up.
Then of course, thinking it was a weird call, I googled the number. Reading the comments, I'm glad I didn't give any information away.
Frustrating to see people do this b.s. for living.
Caller name: NODID
Caller type: Unknown
Caller had South Asian accent. Wanted to know if I was the owner and if I was looking to sell if I could find something better. Told him I was a senior and the next place I was moving to would be a rest home. He said okay and hung up.
Caller name: guy with a strong accent
Caller type: Unknown
I have been receinving calls from this number 3 times this week. I dont event let them speak to me I hang up . I dont want to be disturb . So PLEASE do something about this s**t. Tks.
Montreal Quebec
Caller name: NODID
Caller type: Unknown
I get a call from this number at least 2 or 3 times per week and refuse
to answer. I don't answer calls that don't have their names displayed. I know what they are up to. Want info if they can get it, especially your credit card number. Don't fall for it....How do I get
them shut off???.
Caller type: Scammer/Fraudster
Got a call this morning from this number - let the answering machine pick it up. No message left, but from a search of the number, it is actually a spoof using a SK number as cover. Others reported man with Pakistani accent indicating he is from a real estate firm and trying to get personal information from them. Don't answer this one - it's a scam!
Caller type: Unknown
would not leave a message and when i checked on line for the
number on my call display i got this page.
so this is a scam and I am not pleased as i have a family member in Sask that is dying and not impressed to have to have these ##%%#$ calling from Sask.
Caller name: 306 832 4567 Saskatchewan
Caller type: Unknown
this number has called me a few times but I do not answer calls that I do not recognize and I do not speak Saskactewaneese any way, there was never a message left.
Caller name: Hello?
Caller type: Scammer/Fraudster
Burned him so hard, I answered the phone, then after being silent for a couple seconds, he goes... "Hello?".
To which my reply is... "Go suck a f*****g d**k you f****t!".
Which in turn gave me uncontrollable laughter and sense of accomplishment.
Thank you Caller Center and all other websites like this.
And a message to the scammers, you will be met with an answer such as this every time.
Have a great day everyone! I know I will.
Caller type: Scammer/Fraudster
These people are relentless i have picked up three times and told them i'm. not interested in selling my home nor answering their questions and to please take me off their list and stop calling. They don't seem to understand or care. All telemarketing calls should be banned in this country including charities ie: MADD I donate to whom i choose don' t bug me at dinner .
Caller name: Focus Group
Caller type: Unknown
Said they were from Focus Group. I said I do not do surveys and am busy running a business from my home. I live in northern Alberta and have had two calls in the past three days. I blocked the number on my phone. East Indian accent both times.
Caller name: Focus Group real estate
Caller type: Scammer/Fraudster
Thick east Indian accent. Kept telling me he had a buyer for my house. Numbers shows it's from Tisdale, Saskatchewan. I have family there and it's the only reason I answered it.


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Security of Things World 2018: Beyond the hype
The third edition of Security of Things World Berlin was unanimously characterised as a successful conference. The 100+ attendees put the success down to the rich mix of IoT security experts, the presentation content and the interactive sessions throughout the 3 days of the event.
With sessions about the cost of security problems, threat modelling in IoT, security of industrial control systems and more, Security of Things World was a great event. There is still a need for discussion regarding the future role of security in the interconnected and smart world of the enterprise Internet of Things, and also further collaboration so that solutions are available to respond to growing IoT security concerns .
Securing the connected future in San Diego
Security of Things World is heading over to San Diego on September 16 -18, 2018. Be part of the forum for IT, OT, IoT and cyber security experts in the USA.
For more information go to: www.securityofthingsworldusa.com


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In our online and connected world, we can forget that others – unknown to us are also connected but in a nasty way. With laptops, smartphones, iPads and our IT paraphernalia – we're now more at risk of online fraud and identity theft than ever.
A recent report found that the average out-of-pocket expense for identity theft victims has risen over 60%, from 2009 2010. Our "tech savvy" friends may be more at risk than they realise and business travelers often have the most to lose from "rogue" attacks as airports and hotels can be points where we are vulnerable to rogue Wi-Fi hotspots.
Sipping your Late, idly surfing on your Android, you will be surprised at the number of WiFi network connections you will and anything free, even a free wireless internet connection is hard to resist. It's surprisingly easy for an expert to provide a "Free Public WIFI" point. The Rogue WiFi networks lure people into using their service and then using the connection to hack into the unsuspecting users' laptop or mobile device. You may think that there is nothing to steal in your computer or smartphone but you will be surprised at what hackers can do with your personal information. There are a few steps to take to protect yourself from a rogue hotspot.
– Check the SSID or Network ID of your connection. If for example you are at a coffee shop, ask the barista for the exact SSID and the password if it requires one.
– Steer Clear of unencrypted networks since they also mean unprotected. If you absolutely must use public WiFi, avoid any personal email or banking.
– Check your device WiFi settings, set your mobile device to ask your permission before connecting to any WiFi connection just to be on the safe side.
Take a few minutes to re-think your online use :
Coupon Spoofing : Do you like to use coupons to save on paying online – beaware that criminals can "spoof," popular web sites like Groupon to install malicious software on your computer to steal financial credentials and take your money. When browing online – beware of clicking links that are offered by local websites and especially in emails – they may be page-spoofs for the unexpecting user.
Try to Say No to Public Wi-Fi : It's like giving up your first coffee of the day, but try to avoid using public free Wi-Fi as much as possible. Especially at the airport or in the hotel. Criminals can set up fake public Wi-Fi access points that, once you connect, give them access to all of your information. Instead, "tether" your laptop or tablet to your smartphone's 3G service. If you must use publicly-provided Wi-Fi, ask the hotel to confirm the exact name of the Wi-Fi network.
Bluetooth : Turn off Bluetooth when it's not in use, hackers can use access personal information and install malicious software, also, Bluetooth headsets can be eavesdropped on.


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IITA Abuja hosts delegates from Chinese tropical research institute
Under the framework of the memorandum of understanding between the Chinese Academy of Tropical Agriculture (CATAS) and IITA, Prof Liu Haiqing, a CATAS Director, with 12 other delegates visited IITA Abuja Station on 5 September.
Receiving the CATAS delegation on behalf of the Head of IITA Abuja Station, Yam Seed System Specialist Beatrice Aighewi welcomed the delegates and apprised them of the research and development work being undertaken in IITA as well as the evolution of the IITA Abuja Station.
Haiqing gave a brief background on the work of CATAS describing it as the Institute that "researches tropical crops in China just as IITA in Africa." He thanked IITA for the relationship built over the years: "We are in collaboration with the Changshu Institute of Technology (CIT) where grants are given and we would like to strengthen our partnership with IITA so that IITA will benefit from the grant next year for the development of research laboratories."
He further elaborated on the exchange program, noting that six slots are available to Africans every year. "IITA research students can also benefit from this program," he concluded.
Responding, Aighewi thanked CATAS for the offer of the exchange program. Equally, Ijie Ben Asuelimen, Project Administrator, also appreciated CATAS for the opportunity given to four IITA Youth Agripreneurs to undergo training on crop protection in China last June.
The visit culminated in the delegates being taken on a field tour around the Station to see some of the technologies being promoted by IITA.


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What is the greatest strength of an individual?
Who they connect with.
What holds us back from being our best self?
Being stuck.
Now the most important question - how do we free ourselves from what we are stuck in?
This is more complicated, but the best place to start is to understand how we work at our best, why we stop working at our best, and how to connect with the most natural way to turn ourselves on. This begins with opening the doors of possibility and turning on the curiosity required to move forward. Richard delves into the brain, the body, and utilizes the best science to show how to reconnect to yourself and to others. He can turn your work-place into a life-place. There is no separation between work and life. How did we ever think there was? Surely people are alive at work? Sometimes, one wonders.
Watch Richard speaking in the video below https://youtu.be/zVGQcCoB0Vc
Learn more about Richard at www.richardhill.com.au
Richard's career spans many different fields. After two decades as a professional performer, actor, and singer, he was ravaged by the GFC left him without a career or a bank account. In 15 years he has rebuilt his life to become an internationally regarded expert in human behaviour, the brain, and how the body functions for health, well being, and best performance. He lectures around the globe and is published internationally. After building his reputation in the field of psychotherapy and neuroscience, it is now time to turn his attention to business and the people who make business not only functional, but possible.
There are so many things that a business can function without. It can even function without profit. Although that is not a very successful business, it can still be called a business. But, if you take out the people, there is no business. Without those who work in the business and those who purchase from the business, there is no business. People need to be the top priority.
Our problems today stem from the inability of many people to cope with life, both business and personal. That is the work that Richard specialises in - changing the influences that cause the problem in the first place. Motivating people to get going is easy enough, and many do it very well, but motivation is not enough. If it were, then you only need a motivator once. Bringing them back again and again should tell you that this is not the core of the problem.
Richard will speak at your conference or professional gathering, he will organize workshops that are tailored to your unique needs, he will facilitate programs that will initiate the changes each person needs to find their best self.
Let us start by talking about what you need. Then we can create what we can do.


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For those of us who didn't have their thirst for adventure quenched at the end of Uncharted 4: A Thief's End, Naughty Dog has one more tale to tell in the Uncharted universe. Uncharted: The Lost Legacy is available today on, exclusively on PlayStation 4. Unlikely partners Chloe Frazer and Nadine Ross embark on a journey of their own through the Western Ghats of India.
Chloe was first introduced to the series in Uncharted 2: Among Thieves, and is the main protagonist of this story. Nadine, who players of Uncharted 4: A Thief's End will recall as "that lady who can really throw a punch", is also in the spotlight as they work together to solve puzzles and survive gunfights. Their unified goal is to recover the Tusk of Ganesh, in order to deliver it to Asav the warlord. Details around why Asav sent the duo on this quest in the first place have not been made abundantly clear, and will surely be uncovered upon playing Uncharted: The Lost Legacy for ourselves.
Whether you're a longtime fan of Uncharted, or have somehow managed to own a PlayStation for this long and not played a game in the series, this is a must-have for any PlayStation 4 owner's library. Discover Uncharted: The Lost Legacy on the PSN Store today!


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SC Magazine has reviewed DeviceLock® 6.0
DeviceLock® 6.0 was reviewed by SC Magazine. The author writes: "DeviceLock is one of the most versatile access-control solutions on the market. It offers extensive policy-based controls over any removable device, plenty of auditing facilities and unique data shadowing capabilities". You can read this review on the SC Magazine's website: www.scmagazine.com


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Belmont snaps Cougars' home streak
EDWARDSVILLE – For the first time in nearly two months, SIUE men's basketball was defeated on its home floor on Wednesday. The Cougars lost to Belmont 94-75 in Ohio Valley Conference action at Vadalabene Center.
The loss snapped a six-game home winning streak for the Cougars, who fell to 7-8 in OVC play and 11-18 overall. Belmont improved to 22-8 overall and 13-2 in the OVC.
"Belmont is a very good team," SIUE coach Lennox Forrester said. "That's why they're in position to win another OVC regular season title. They're well-coached. They have good players. And they're very fundamentally sound."
The Cougars knocked down 28 of 57 attempts from the field (49.1 percent) but were unable to slow Belmont's offensive attack. For the game, the Bruins connected on 56.5 percent (35-62) of their shots from the field. They shot 60 percent from the floor in the second half.
"I don't think we gave them our best shot, but that's partly because of how they play," Forrester said. "They took us out of our rhythm offensively, and when we made mistakes, they burned us. That's a sign of a really good team."
The Bruins held a 48-32 lead at halftime, but the Cougars began the second half strong. SIUE hit its first four shots in the second period to trim Belmont's lead to 10 at 50-40 with 17:41 left in the game.
As quickly as the Cougars had trimmed the lead, the Bruins then extended it. Belmont used a 19-8 run to open up its largest lead of the game, 21 points. Reece Chamberlain's tip in with 11:08 to play made it 69-48. The closest the Cougars came from that point on was 13 points when Tim Johnson's three-point play with 5:08 left cut the BU lead to 78-65.
Johnson scored 18 points on 6-of-9 shooting to lead SIUE. He was 2 of 3 from three-point range and 4 of 5 from the free throw line. Donivine Stewart finished with 17 points and five assists. Keaton Jackson scored 11 points and grabbed a team-high seven rebounds. Rozell Nunn scored 10 points.
J.J. Mann led Belmont with 25 points. He was one of four Bruins to score in double figures. Evan Bradds scored 20 points. Reece Chamberlain added 18 points and Nick Smith scored 11.
The Bruins outrebounded SIUE 38-25 and scored 55 points in the paint.
SIUE finishes the regular season Saturday at home against Eastern Illinois. Tipoff is scheduled for 5:05 p.m.


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Brewers Wednesday: Kintzler set to come off DL soon
MILWAUKEE — Milwaukee Brewers reliever Brandon Kintzler threw a simulated game prior to Wednesday night's series finale with the San Diego Padres and is on track to be activated from the disabled list on Friday.
Kintzler estimated he threw 40 pitches Wednesday with somewhere between 17-23 coming with catcher Martin Maldonado standing in the box.
"I had no pain, which is the main thing," Kintzler said. "I was a little rusty, but you are going to be rusty. Other than that, the last pitch was probably my best pitch, so we'll go off that one."
Placed on the disabled list on April 12 retroactive to April 9 with a mild strained right rotator cuff, Kintzler viewed the time off as more of a precautionary move to take care of the issue rather than let it linger.
Kintzler has allowed just two hits in five scoreless innings this season and is anxious to get back and join an oft-used but successful Brewers bullpen. He will come in and get evaluated Thursday before a final determination is made as to whether or not he is activated for Friday's series opener against the Chicago Cubs.
"I'm dying (to get back)," Kintzler said. "I can't deal with the stress of these games anymore. Half the time I can't watch the pitches. It's just tough when you can't control it. I feel like I'm emotionally attached to everyone that is pitching. I want everyone to do good. I want to see them succeed. Hopefully I can get back and help out a bit."
Brewers manager Ron Roenicke would like to ease Kintzler back into the mix, preferably using him in a few low-leverage situations before putting him in during the late innings of a game.
"He's one of those guys who it doesn't matter what inning I put him in, what situation I put him in, whether it's left-handed, right-handed — he's really good," Roenicke said. "He showed that last year. I think we did a nice job in putting other guys into that role that they covered really well for him.
"Right off the bat, I probably can't pitch him like I've been pitching these other guys. We probably have to go a little slower with him. Hopefully, we'll start to score some more runs and we won't have to always use all these guys."
Garza preps for Cubs: With the Brewers sharing a division with the Cubs, Matt Garza knew the day would come in which he'd have to pitch against his former team.
That day is Friday, as Garza will take the mound against the Cubs at Miller Park. He made waves this spring by telling the Chicago Sun-Times that he is "going to try to kick their teeth in every time I get a chance."
"Not really," Garza said Wednesday when asked if there was anything different about facing his former team for the first time. "There's your answer. It's just another ballgame."
Garza is an emotional pitcher on the mound, leaving Roenicke hoping he isn't too jacked up Friday.
"Hard to say," Roenicke said if he thinks Garza will be amped up. "I don't know what he's going to be like. It's changed from outing to outing. The more we see him, the more we'll understand. We saw that when he was on the other side and we were facing him, we know that when he was comfortable and in a groove, we were going to have a tough day. We hoped and tried to get him out of that groove."
Signed to a four-year, $50 million contract this winter, Garza is 0-2 with a 4.50 in his first four starts with the Brewers. He's been a victim of a lack of run support and some shaky defense behind him, something Roenicke thinks the right-hander has handled fine.
"I think the last game where we didn't play well behind him defensively and he had the tough inning, it may have gotten to him a little bit," Roenicke said. "But I thought he kept his composure and still tried to make pitches. Sometimes we're not making plays, and sometimes he makes a good pitch and they roll one right between somebody. It's always a little bit of both."
Follow Andrew Gruman on Twitter


text: http://www.1stoptutorials.com – IN this seo tutorial we are going to look into some seo tools that we will use. These tools will help us choose the correct keyword and concept of our new website. I know this can become a bit boring but it is really worth knowing these tools


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Style details:
- Material: 46% viscose, 16% cotton, 33% silk, 5% lurex
- Lining: 100% viscose, fully-lined
- Double-breasted
- Faux flap pockets
- Velvet trimmed pocket flaps and lapels
Size and fit:
- Available exclusively via our made-to-measure service
- Fitted at the waistline, sheath shape
- Mid-weight material
- Falls at the knee, or can be customised as per your request
Custom-made options:
- Can be made in a different tweed of choice
- Contact us for more information
- All orders are shipped worldwide via DHL Express.
'The Madison' is the perfect all-in-one outfit with a new modern chic twist.
Designed to just put on and go, it will be your all-time favourite to wear for work, conferences and afterwards.
A waist-nipping sheath silhouette has a figure-enhancing effect.
Classic colour combination, gem buttons and velvet trim make it a standout dress you will enjoy for years.
Frame this refined look with black or metallic accessories.


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In an industry where asbestos is made or produce, a large number of people work there. Asbestos is mostly used to protect from water, sun rays, etc in the house.
Every trader who gets into forex trading comes with a different personality and a unique trading style. While some prefer fast-paced trading within short timeframes, there are others who are
We are living in a fast-growing world where everything is going so fast. Whether it is professional or personal life, you cannot rely always on your savings. Sometimes, you may
Family law is quite complex. Whether it is a divorce, property dispute, or custody hearing, you require help of an experienced family attorney. His advice will prove to be an
Now entrepreneurs and business owners in Singapore can devote more time and energy running their business and concentrating more their core business operations rather than worrying about accounting by outsourcing
Now, people are interested in applying for the loan for the purpose of getting the cash. It is important for the people to apply for the best short term loan.
As one of the most integral, fundamental sectors in our entire economy, the construction industry is continuing to expand and reach new heights each year: The cumulative market value of
The increasing number of crimes and robberies in our country point towards the necessity to be alert every moment. Especially when it comes to our cars, it is only obvious
All kinds of accidents whether bigger or minor disrupt the normal life of any person. Injuries caused due to these accidents can be minor or serious too. Serious injuries can
At present time, Technology is very vast and growing. With new innovation, every business organization wants to promote their business on the social network through the different online platform. The


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DATE : May 11, 2011
Page 1 of 1
30 years ago today, a light was extinguished. Bob Marley died on 11 May 1981. But his Music lives on – along with his message of social justice. We remember him with fondness and hope that humanity takes some of his message in order that we all live with love, peace and understanding.
Barcelona earned the point they needed to clinch the Spanish League title for the 21st time in their history. There are some teams that play great football but fail to win trophies. There are other teams who don't play particularly well but still deliver enough to win trophies. FC Barcelona do both – they play […]


text: Humanities › English Chicano English (CE) Glossary of Grammatical and Rhetorical Terms Share Flipboard Email Print Michelle D. Devereaux, Teaching About Dialect Variations and Language in Secondary English Classrooms (Routledge. 2015). English English Grammar An Introduction to Punctuation Writing by Richard Nordquist Richard Nordquist is a freelance writer and former professor of English and Rhetoric who wrote college-level Grammar and Composition textbooks. Updated March 06, 2017 DefinitionChicano English is an imprecise term for a nonstandard variety of the English language influenced by the Spanish language and spoken as a native dialect by both bilingual and monolingual speakers. Also known as Hispanic Vernacular English.Kristin Denham and Anne Lobeck emphasize that Chicano English (CE) "is not 'learner English,' and though it does exhibit many influences of Spanish, it is a fully developed variety of English, the native English of many of its speakers" (Linguistics for Everyone, 2012). See Examples and Observations below. Also see:American EnglishCode SwitchingDiglossiaEthnic DialectNotes on English as a Global LanguageSpanglishExamples and Observations"Chicano English . . . is alive and well in Los Angeles, among other places. It is a dialect in its own right, separate both from Spanish and from other local varieties of English such as California Anglo English (CAE) or African-American English (AAE). It is changing, as all dialects do, but shows no signs of being abandoned by the community as a whole in favor of more standard varieties of English. . . . Chicano English can vary on a continuum from less to more standard, and from less to more influenced by other dialects, and it encompasses a wide range of stylistic options."(Carmen Fought, Chicano English in Context. Palgrave Macmillan, 2003) Chicano English Grammar"Spanish . . . uses the double negative, which is reflected in the grammar of CE [Chicano English]. Students regularly produce students such as I didn't do nothing and She don't want no advice."Spanish signifies the third person possession through prepositional phrases rather than possessive nouns, as in the following sentence:Vivo en la casa de mi madre. (literal translation: I live in the house of my mother.)We therefore frequently find students producing sentences of the following type in CE:The car of my brother is red.The ring of my fiancée was expensive.Because Spanish has a single preposition (en) that corresponds to both in and on in English, speakers of CE commonly use in where Standard English requires on, as in the following:Macarena got in the bus before she realized that she didn't have no change.We got in our bikes and rode down the hill."(James Dale Williams, The Teacher's Grammar Book. Routledge, 2005) The Sounds of Chicano English- "Chicano English is distinctive because of its vowels (based on Spanish pronunciation), particularly the merger of [i] and [I]. So beet and bit are both pronounced beet, sheep and ship are pronounced sheep, and the -ing suffix is pronounced with [i] as well (talking is pronounced something like /tɔkin/, for example). Sounds usually described as interdentals (this, then) are made with the tongue touching the back of the teeth, rather than between the teeth. Chicano English is also syllable timed, like Spanish, rather than stress timed."(Kristin Denham and Anne Lobeck, Linguistics for Everyone: An Introduction, 2nd ed. Wadsworth, 2013)- "Another major characteristic of the phonological system of Chicano English is the devoicing of /z/, especially in word-final position. Because of the widespread occurrence of /z/ in the inflectional morphology of English (in plural nouns, possessive nouns, and third-person-singular present-tense verbs such as goes), this salient characteristic is also stereotypical."(Edward Finegan, Language: Its Structure and Use, 5th ed. Wadsworth, 2008). The Southern California Dance"[T]hink of Southern California as a ballroom where English and Spanish are two dancers with their arms wrapped around each other's waists. The Spanish dancer has a lot of flair, and she's trying to do a tango. But it's the English dancer who has the lead, and in the end, you realize what they're doing is a square dance."(Hector Tobar, "Spanish Versus English in Southern California." Los Angeles Times, May 19, 2009) Continue Reading


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Professor Adam Przeworski (New York University)
Dr. Mariana Llanos (GIGA)
In his lecture, Professor Adam Przeworski (New York University) will examine the current political situation in Europe and the United States in the light of past crises of democracy. The main question is to what extent the recent political transformations – institutional and cultural – can be rationalised in economic terms. The first part will compare some conditions of democracies that have survived and of those that have failed since 1918. Then the current economic and political conditions will be analysed in the light of this historical experience. Brief speculations about the future will conclude.
Adam Przeworski is the Carroll and Milton Professor of Politics and (by courtesy) Economics at New York University. Previously he taught at the University of Chicago, where he was the Martin A. Ryerson Distinguished Service Professor, and held visiting appointments in India, Chile, France, Germany, Spain, and Switzerland. A member of the American Academy of Arts and Sciences since 1991, he is the recipient of the 1985 Socialist Review Book Award, the 1998 Gregory M. Luebbert Article Award, the 2001 Woodrow Wilson Prize, the 2010 Lawrence Longley Award, and the 2018 Juan Linz Prize. In 2010, he received the Johan Skytte Prize. He recently published Why Bother With Elections? (London: Polity Press).
Dr. Mariana Llanos is Lead Research Fellow at the GIGA Institute of Latin American Studies and Head of GIGA Research Programme "Accountability and Participation."
Seating is limited; please register early to avoid disappointment.
The GIGA Distinguished Speaker Lecture Series brings the best and brightest minds in academia and policy from all over the world to Hamburg to stimulate public exchange on key global developments.
Professor Adam Przeworski © GIGA / Bente Stachowske
© GIGA / Bente Stachowske
Professor Adam Przeworski and Dr. Mariana Llanos © GIGA / Bente Stachowske
Dr. Mariana Llanos and Professor Adam Przeworski © GIGA / Bente Stachowske
This event is fully booked. To be put on the waiting list, please e-mail email@example.com. We will inform you if a seat becomes available.
To receive updates about GIGA events and publications, please subscribe to our newsletter.
Neuer Jungfernstieg 21
20354 Hamburg


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No Good Deed Goes Unpunished
Just a note to all the charities and political organizations to whom I have contributed this year: Hi there. I know I am naive, but, in working out a budget this year, I decided to give you my annual contribution at the beginning of the year, so I could take one more thing off my plate, and not worry about you throughout the year.
In response to my contributions, you have bombarded me all year with letters, pamphlets, offers to enter me into your special contributor rolls, chances on a free lunch, sleazy free gifts, and horrifying stories about your continued desperate need for my financial support. Thank you so much.
Now, just so you know, I put your mail straight into the recycling bin, delete your emails without reading them, and generally know less about what you're up to than I did before I donated.
I donated to you, and the reward for my good deed was for you to spend my money sending me stuff instead of using it for your cause. Thanks so much. I'm not only grateful, but "so" inspired to give more.
Johns Hopkins Hospital, which I now visit all too frequently, leaves wheelchairs in their parking garages and around their doors so people with handicaps can be assisted in by their families. These now redesigned wheelchairs are huge, partly in tribute to our obesity epidemic. You must line them up multiple times to manipulate them through doorways. They are very heavy, and no longer fold so you can store them out of the way in exam or bathrooms.
Why is this? It's because recipients of the hospital's largesse steal them. Thanks, fellow transporters. You are so awesome.
CVS Pharmacy offers little plastic baskets you can carry around the store to fill with your purchases – for customer convenience. In my local store, instead of being kept conveniently near the door, these are now secured behind the sales counter. Now you must request one from the clerk. Yes, that person at the end of the long line. Wonder why.
And how about Paula Deen, cooking queen and host of her own television empire? When accused of racial prejudice, Paula made the mistake of doing the right thing. She admitted to using the "N" word 18 years before, while denying the general prejudice charge.
Let's see. A southern woman of a certain age used the "N" word two decades ago, and her reward for being honest about it was to be drummed off the air by the politically correct people of the current day.
How about the convenience of individual food containers, single use cans and bottles, not to mention cigarettes and their disposable packaging?
The reward for that convenience is not finding them placed in recycling bins or trash cans, but rather everywhere from the grounds of state and national parks to downtown streets. To add to this, some cities, London, for example, no longer provide the convenience of public trash cans in areas where people are likely to congregate. That's because of the risk that this convenient item will end up holding a terrorist bomb.
How terrible would it be to take that little piece of trash with you to deposit at home?
I once evicted a tenant, and, my naiveté and kindness showing again, allowed him, begging as he was, to store his furniture until he could break the lock on my storage unit and retrieve it. During the eviction, I heard him ask his wife: "Aren't you going to take your clothes?" Her answer: "No, I can just get new ones."
The next time they were evicted, they sued the landlord, claiming that a defective floorboard caused her to fall as they were moving out.
Just want to say again, thank you to all of you who reward people's kindness, their efforts to be caring and do the right thing, with cigarette butts, spittle, trash, half eaten food (although the flies certainly benefit), used condoms, job loss, and even lawsuits. You've helped the rest of us perfect our personal discipline as we resist grabbing you by the shirt fronts and slapping you silly.
We can count to one thousand now before taking action. We've learned to step carefully, in our words, and into the very small spaces left on the sidewalks. Thank you and thank you again.
Odd how so many of you think we're not giving enough.


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Westleigh are proud to have been awarded gold status again in 2016 for Investors in People, recognising our commitment to the value of learning, training and development for all employees.
The gold national standard aims to improve the way we work, increasing organisation, efficiency, development and communication for our workforce.
Westleigh are committed to training and learning that helps its employees at all levels.
The Considerate Constructors Scheme can be directly associated with this, by using the Scheme and its core values as a direct influence on improving our sites and providing a safe and well-managed working environment.
Our employees know how they can contribute to the organisation, understand our company, know why they are important, have the correct training, be led and encouraged as well as being appreciated.
Our people values that we carry over to all our sites and company-wide are:
Our social values are:
Entry submitted by Westleigh Partnerships
The Scheme does not promote or endorse any products, goods or services. For more information, click here.


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Camped on the 4×4 trail leading to the South Colony Trailhead. Took the West Ridge II, Class 2 route. Nasty day as 4-5 inches of snow fell while we were on the descent. Had to dig the tent out and 4×4 back out through the snow.
Weather rolling in!
Shady Mike did not even take off his bag to take a swing!


text: Digest - 20 Envelopes Digest - 20 Envelopes Previous image Next image 1 of 5 Zoom Previous thumbnail Next thumbnail 1 of 5 £2.69 sku SBDI1018-20 | Net weight: 35g 1 2 3 4 5 Rated 5 based on 9 reviews (9 reviews) Digest - 20 Envelopes Qty Add to basket Free UK delivery on UK orders over £35 UK Standard £3.95, UK Express (1-2 working days) £6.95 - Click for Terms and Conditions Apple Flavoured Herbal Infusion with Spearmint, Rooibos and Baobab. Feeling soothed and balanced is the inspiration behind this Digest blend. This deliciously refreshing mellow blend combines nature's classic after dinner helper - spearmint - with baobab and the sweetness of apple & rooibos. What does it taste like? Refreshing spearmint is followed by a soft sweetness from the apple & rooibos. The ginger is very subtle, leaving a soothing warmth after each sip. Delivery information FREE delivery on UK orders over £35.00 £3.95 UK orders under £35 - Delivered 3-5 working days £6.95 UK Express - Delivery guaranteed within 2 working days International orders are calculated based on country and weight and charged at cost - Delivered within 20 working days More about the Product ingredients Spearmint (34%), Rooibos Leaves (18%), Natural Apple Flavouring with Other Natural Flavourings (15%), Ginger, Peppermint, Apple Pieces (7%), Baobab Fruit Pulp Granules (5%). Suitable for Vegans nutritional information Typical Values Per 100ml Brewed Infusion* Per 200ml Serving* Energy 3 kJ / 1 kcal 7kJ / 2 kcal Fat 0g 0g of which saturates 0g 0g Carbohydrate <0.5g <0.5g of which sugars <0.5g <0.5g Protein 0g 0g Salt 0g 0g *Based on an infusion brewed with 200ml hot water for 3 minutes. How do I drink it? Simply use freshly boiled water and infuse the bag for at least 3 minutes. Give the teabag a few little stirs and a gentle squeeze to release the flavour before removing it from the cup. Sourced with care Improving quality of life in the communities where we source from. For more information while you finish your cup, visit www.sourcedwithcare.com Reviews Customer Reviews 100% of customers liked this product ++ Excellent good 17-Nov-2019 ++ Excellent good 17-Nov-2019 ++ Excellent Very good. I love the digest. 06-Oct-2019 ++ Excellent Like the Digest spearmint blend, best ever. 01-Oct-2019 MORE ABOUT THE INGREDIENTS Baobab - Baobab is the fruit of the Baobab tree which is also known as the 'Tree of life'. It can live to be up to 3000 years old. Spearmint - The taste of spearmint is refreshing, soothing and softly sweet. Perfect anytime but particularly after a meal. Rooibos - Rooibos, also known as redbush, is a widely loved herb grown in South Africa. The leaves are naturally caffeine free with a distinctive colour & sweet fruity flavour. Recommended For You 1 2 3 4 5 Rated 5 based on 0 reviews Detox - 20 Envelopes £2.69 each Superblends - Detox. A Lemon Flavoured Infusion with Burdock Root, Fennel, Ginger and added Selenium. 1 2 3 4 5 Rated 5 based on 0 reviews Matcha - 20 Envelopes £2.69 each Superblends - Matcha. A Cranberry and Lime flavoured Green Tea with Matcha and added Manganese. 1 2 3 4 5 Rated 5 based on 0 reviews Energise - 20 Envelopes £2.69 each Superblends - Energise. A Mandarin and Apple Flavoured Green Tea with Guarana and added Vitamin B6. 1 2 3 4 5 Rated 5 based on 0 reviews Moment of Calm - 20 Envelopes £2.69 each Superblends - Calm. Spice and Vanilla Flavoured Herbal Infusion with Camomile, Roasted Chicory Root and added Niacin. https://www.twinings.co.uk/tea/fruit-herbal/digest-20-envelopes SBDI1018-20 Digest - 20 Envelopes https://www.twinings.co.uk/TwiningsUKI/media/product/SBDI1018-20/1-twinings-superblends-digest-20-envelopes.png £2.69 GBP InStock /Tea/Superblends /Tea/Vegan-Teas-Infusions /Tea/Kick-start-the-New-Year /Tea/Fruit-Herbal /Tea/Infusions-Greens-and-Monin-Syrups Superblends - Digest. Apple Flavoured Herbal Infusion with Spearmint, Rooibos and Baobab. £2.69 5 3923


text: bobblehat 0 Report post Posted March 6, 2011 Hi, I was attempting to remove a callout from my blog page (news) but I could not do it. I selected to hide them from the pagelines section control, but they still were present. So I opted to move them from my header in the Template set up area as I don't really need them. That did not work either, but now the layout of my site is broken and I have no idea to fix it. The header seems to have shifted slightly to the right and the side bar edge has been chopped off! The calendar is missing sundays!. I am sure that it is something simple but I have tried re-inserting the callout and it didn't return the layout back. Here is a url to my site to illustrate the above http://nursery.hciresearchgroup.com/ Any help would be much appreciated. Share this post Link to post Share on other sites


text: Kathy, I have to agree with you. I live out of state, so am not near my mother's home for whenever she decides to get rid of anything. Honestly, there's not much I would want anyway. And I agree that times and traditions have changed. I do use my china once a year when my DD's family and in-laws come over. I would not be surprised if it all goes to one of those "Junk companies". But, I have told them, that I won't be here, so do what you want, just try to sell the longarm and supplies or donate to someone who will use it.