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An investigation of the effects of lipid-lowering medications: genome-wide linkage analysis of lipids in the HyperGEN study.
ABSTRACT: Use of anti-hyperlipidemic medications compromises genetic analysis because of altered lipid profiles. We propose an empirical method to adjust lipid levels for medication effects so that the adjusted lipid values substitute the unmedicated lipid values in the genetic analysis.Published clinical trials were reviewed for HMG-CoA reductase inhibitors and fibric acid derivatives as mono-drug therapy. HMG-CoA reductase inhibitors showed similar effects in African Americans (AA) and non-African Americans (non-AA) for lowering total cholesterol (TC, -50.7 mg/dl), LDL cholesterol (LDL-C, -48.1 mg/dl), and triglycerides (TG, -19.7 mg/dl). Their effect on increasing HDL cholesterol (HDL-C) in AA (+0.4 mg/dl) was lower than in Non-AA (+2.3 mg/dl). The effects of fibric acid derivatives were estimated as -46.1 mg/dl for TC, -40.1 mg/dl for LDL-C, and +5.9 mg/dl for HDL-C in non-AA. The corresponding effects in AA were less extreme (-20.1 mg/dl, -11.4 mg/dl, and +3.1 mg/dl). Similar effect for TG (59.0 mg/dl) was shown in AA and non-AA. The above estimated effects were applied to a multipoint variance components linkage analysis on the lipid levels in 2,403 Whites and 2,214 AA in the HyperGEN study. The familial effects did vary depending on whether the lipids were adjusted for medication use. For example, the heritabilities increased after medication adjustment for TC and LDL-C, but did not change significantly for HDL-C and TG.Ethnicity-specific medication adjustments using our empirical method can be employed in epidemiological and genetic analysis of lipids.
Project description:Background Elevated total cholesterol ( TC ), low-density lipoprotein cholesterol ( LDL -C), triglycerides, and non-high-density lipoprotein cholesterol (non- HDL -C) and low high-density lipoprotein cholesterol ( HDL -C) concentrations correlate with atherosclerotic cardiovascular disease ( ASCVD ) and mortality. Therefore, understanding how lipid trajectories throughout adulthood impact ASCVD and mortality risk is essential. Methods and Results We investigated 3875 Framingham Offspring participants (54% women, mean age 48 years) attending ≥1 examination between 1979 and 2014. We evaluated longitudinal correlates of each lipid subtype using mixed-effects models. Next, we clustered individuals into trajectories through group-based modeling. Thereafter, we assessed the prospective association of lipid trajectories with ASCVD and mortality. Male sex, greater body mass index, and smoking correlated with higher TC , LDL -C, triglycerides, non- HDL -C, and lower HDL -C concentrations. We identified 5 TC , HDL -C, and LDL -C trajectories, and 4 triglycerides and non- HDL -C trajectories. Upon follow-up (median 8.2 years; 199 ASCVD events; 256 deaths), elevated TC (>240 mg/ dL ), LDL -C (>155 mg/ dL ), or non- HDL -C (>180 mg/ dL ) concentrations conferred >2.25-fold ASCVD and mortality risk compared with concentrations <165 mg/ dL , <90 mg/ dL , and <115 mg/ dL , respectively ([ TC hazard ratio ( HR )ASCVD=4.17, 95% CI 1.94-8.99; TC HR death=2.47, 95% CI 1.28-4.76] [ LDL -C HRASCVD=5.09, 95% CI 1.54-16.85; LDL -C HR death=4.04, 95% CI 1.84-8.89] [non- HDL -C HRASCVD=4.60, 95% CI 1.98-10.70; LDL -C HR death=3.74, 95% CI 2.03-6.88]). Consistent HDL -C concentrations <40 mg/ dL were associated with greater ASCVD and mortality risk than concentrations >70 mg/ dL (HRASCVD=3.81, 95% CI 2.04-7.15; HR death=2.88, 95% CI 1.70-4.89). Triglycerides trajectories were unassociated with outcomes. Conclusions Using a longitudinal modeling technique, we demonstrated that unfavorable lipid trajectories over 35 years confer higher ASCVD and mortality risk later in life.
Project description:The total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio, estimated low-density lipoprotein cholesterol (LDL-C), and non-HDL-C are routinely available from the standard lipid profile. We aimed to assess the extent of patient-level discordance of TC/HDL-C with LDL-C and non-HDL-C, because discordance suggests the possibility of additional information.We compared population percentiles of TC/HDL-C, Friedewald-estimated LDL-C, and non-HDL-C in 1?310?432 US adults from the Very Large Database of Lipids. Lipid testing was performed by ultracentrifugation (Vertical Auto Profile, Atherotech, AL). One in 3 patients had ?25 percentile units discordance between TC/HDL-C and LDL-C, whereas 1 in 4 had ?25 percentile units discordance between TC/HDL-C and non-HDL-C. The proportion of patients with TC/HDL-C > LDL-C by ?25 percentile units increased from 3% at triglycerides <100 mg/dL to 51% at triglycerides 200 to 399 mg/dL. On a smaller scale, TC/HDL-C > non-HDL-C discordance by ?25 percentile units increased from 6% to 21%. In those with <15th percentile levels of LDL-C (<70 mg/dL) or non-HDL-C (<93 mg/dL), a respective 58% and 46% were above the percentile-equivalent TC/HDL-C of 2.6. Age, sex, and directly measured components of the standard lipid profile explained >86% of the variance in percentile discordance between TC/HDL-C versus LDL-C and non-HDL-C.In this contemporary, cross-sectional, big data analysis of US adults who underwent advanced lipid testing, the extent of patient-level discordance suggests that TC/HDL-C may offer potential additional information to LDL-C and non-HDL-C. Future studies are required to determine the clinical implications of this observation.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01698489.
Project description:Studies addressing the effects of aerobic exercise and a prudent diet on lipid and lipoprotein concentrations in adults have reached conflicting conclusions. The purpose of this study was to determine the effects of aerobic exercise combined with a prudent diet on lipid and lipoprotein concentrations in adults.Studies were located by searching nine electronic databases, cross-referencing, and expert review. Two independent reviewers selected studies that met the following criteria: (1) randomized controlled trials, (2) aerobic exercise combined with diet recommendations (saturated/trans fat intake less than 10% of total calories and cholesterol less than 300 mg/day and/or fiber intake ? 25 g/day in women and ? 35 grams per day in men), (3) intervention ? 4 weeks, (4) humans ? 18 years of age, (5) published studies, including dissertations and Master's theses, (6) studies published in any language, (7) studies published between January 1, 1955 and May 1, 2009, (8) assessment of one or more of the following lipid and lipoprotein concentrations: total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), ratio of TC to HDL-C, non-HDL-C, low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Two reviewers independently extracted all data. Random-effects models that account for heterogeneity and 95% confidence intervals were used to pool findings.Of the 1,401 citations reviewed, six studies representing 16 groups (8 intervention, 8 control) and up to 559 men and women (282 intervention, 277 control) met the criteria for analysis. Statistically significant intervention minus control reductions were found for TC (-15.5 mg/dl, 95% CI, -20.3 to -10.7), TC:HDL-C (-0.4 mg/dl, 95% CI, -0.7 to -0.2), LDL-C (-9.2 mg/dl, 95% CI, -12.7 to -5.8) and TG (-10.6 mg/dl, 95% CI, -17.2 to -4.0) but not HDL-C (-0.5 mg/dl, 95% CI, -4.0 to 3.1). Changes were equivalent to reductions of 7.5%, 6.6%, 7.2% and 18.2% respectively, for TC, TC:HDL-C, LDL-C and TG. Because of missing variance statistics, non-HDL-C was excluded.Aerobic exercise combined with a prudent diet is highly efficacious for improving TC, TC:HDL-C, LDL-C and TG, but not HDL-C concentrations, in adults. However, additional studies are needed, including effectiveness studies using intention-to-treat analysis.
Project description:Early highly active antiretroviral therapy (HAART) is recommended for HIV-1-infected infants. There are limited data on lipid changes during infant HAART.Nonfasting total (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol and triglycerides (TG) were measured at 0, 6 and 12 months. Correlates of lipid levels and changes post-HAART were assessed using linear regression.Among 115 infants, pre-HAART median age was 3.8 months, CD4% was 19% and weight-for-age Z score was -2.42. Pre-HAART median lipid levels were: TC, 108.7 mg/dL; LDL, 42.5 mg/dL; HDL, 29.4 mg/dL and TG, 186.9 mg/dL. Few infants had abnormally high TC (6.2%) or LDL (5.6%), but many had low HDL (76.5%) or high TG (69.6%). Higher pre-HAART weight-for-age and height-for-age Z scores were each associated with higher pre-HAART TC (P = 0.04 and P = 0.01) and LDL (P = 0.02 and P = 0.008). From 0 to 6 months post-HAART, TC (P < 0.0001), LDL (P < 0.0001) and HDL (P < 0.0001) increased significantly, and 23.1% (P = 0.002), 14.0% (P = 0.2), 31.3% (P < 0.0001) and 50.8% (P = 0.2) of infants had abnormally high TC, high LDL, low HDL and high TG, respectively. Changes in TC and HDL were each associated with higher gain in weight-for-age Z score (P = 0.03 and P = 0.01) and height-for-age Z score (P = 0.01 and P = 0.007). Increased change in LDL was associated with higher gain in height-for-age Z score (P = 0.03). Infants on protease inhibitor-HAART had smaller HDL increase (P = 0.004).Infants had substantive increases in lipids, which correlated with growth. Increases in HDL were attenuated by protease inhibitor-HAART. It is important to determine clinical implications of these changes.
Project description:Docosahexaenoic acid (DHA) has regulatory effects on lipid and glucose metabolism. Differences in DHA availability during specific developmental windows may program metabolic changes.We investigated the effects of maternal DHA supplementation during pregnancy on the nonfasting serum lipid and glucose concentrations of offspring at 4 y of age.We used data from the Prenatal Omega-3 Fatty Acid Supplementation, Growth, and Development trial, a double-blind randomized controlled trial conducted in Mexico. Pregnant women were supplemented daily with 400 mg DHA or placebo from 18-22 wk of gestation to delivery. The primary outcomes of the trial were offspring growth and neurological development. Nonfasting blood samples were obtained from the offspring at 4 y of age. We analyzed serum total, HDL, non-HDL, and LDL cholesterol; the total-to-HDL cholesterol ratio; apolipoprotein B (apoB); triglycerides; glucose; and insulin as secondary outcomes and compared their concentrations between treatment groups.Data from 524 offspring were available. The women were compliant with the intervention based on pill counts and changes in cord blood and breast milk DHA concentrations. None of the between-group differences (DHA compared with placebo), adjusted for maternal height and time since last food intake, were significant (P range 0.27-0.83). Means (95% CIs) were as follows: total cholesterol (TC), 1.73 mg/dL (-2.63, 6.09 mg/dL); HDL cholesterol, 0.66 mg/dL (-1.07, 2.39 mg/dL); non-HDL cholesterol, 1.77 mg/dL (-1.83, 5.37 mg/dL); LDL cholesterol, 1.62 mg/dL (-2.21, 5.45 mg/dL); TC:HDL ratio, 0.01 (-0.09, 0.11); apoB, -0.15 mg/dL (-2.78, 2.48 mg/dL); triglycerides, 0.21 mg/dL (-10.93, 10.52 mg/dL); glucose, -0.67 mg/dL (-2.46, 1.11 mg/dL); and insulin, 0.62 ?U/mL (-0.88, 2.11 ?U/mL).Prenatal DHA supplementation does not affect nonfasting serum lipid and glucose concentrations of offspring at 4 y of age. This trial was registered at clinicaltrials.gov as NCT00646360.
Project description:Transcription factor 7 like 2 (TCF7L2) rs7903146 polymorphism has been associated with metabolic disturbance and cardiovascular disease. The aim of this study was to analyze the association between TCF7L2 rs7903146 polymorphism and potential disturbances on the lipid profile in human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. We performed a cross-sectional study on 263 HIV/HVC-coinfected patients. TCF7L2 polymorphism was genotyped by GoldenGate assay. The analysis was performed by linear and logistic regression under a dominant model of inheritance. The variables analyzed were total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), non-HDL-C, and triglycerides. Patients harboring the rs7903146 TT/TC genotype showed a diminished concentration of TC (p=0.003), LDL-C (p=0.004), HDL-C (p=0.012), and non-HDL-C (p=0.013), a lower percentage of TC?200?mg/dl (p=0.038), and a higher percentage of HDL?40?mg/dl (p=0.023). In addition, we observed that rs7903146 was differently related to fasting serum lipid levels according to the HCV-genotype (HCV-GT). With regard to HCV-GT1 patients, the rs7903146 TT/TC genotype was associated with lower levels of HDL-C [adjusted arithmetic mean ratio (aAMR)=0.91; p=0.049] and an elevated percentage of patients with HDL-C?40?mg/dl [adjusted odds ratio (aOR)=3.26; p=0.003]. For HCV-GT3 patients, the rs7903146 TT/TC genotype was associated with lower serum values of TC (aAMR=0.81; p=0.037), LDL-C (aAMR=0.67; p=0.001), and non-HDL-C (aAMR=0.75; p=0.002) and a reduced percentage of TC?200?mg/dl (aOR=0.089; p=0.037). In conclusion, the TCF7L2 rs7903146 TT/TC genotype was associated with lower levels of TC, LDL, and HDL in HCV-GT3 patients, and lower levels of HDL-C in HCV-GT1 patients, suggesting a role in cardiovascular disease and a potential use as a biomarker in HIV/HCV-coinfected patients.
Project description:Phytosterols and red yeast rice are largely studied cholesterol-lowering nutraceuticals, respectively inhibiting the bowel absorption and liver synthesis of cholesterol. Our aim was to test the effect of combined nutraceutical-containing phytosterols and red yeast rice vs. a placebo on the lipid profile. We performed a parallel arms, double-blind, placebo-controlled clinical trial, randomizing 88 moderately hypercholesterolemic subjects to treatment with a combined nutraceutical containing phytosterols (800 mg) and red yeast rice, standardized to contain 5 mg of monacolins from Monascus purpureus, with added niacin (27 mg) and policosanols (10 mg) (LEVELIP DUO®), or placebo. The mean LDL-Cholesterol (LDL-C) change at Week 8 was -32.5 ± 30.2 mg/dL (-19.8%) in the combined nutraceutical group and 2.5 ± 19.4 mg/dL (2.3%) in the placebo group. The estimated between-group difference of -39.2 mg/dL (95% CI: -48.6; -29.8) indicates a statistically significant difference between treatments in favor of the combined nutraceutical (p < 0.0001). Total Cholesterol (TC), non-HDL cholesterol (non-HDL-C), Apolipoprotein B, TC/HDL-C and LDL-C/HDL-C improved in a similar way in the combined nutraceutical group only. No significant changes in other clinical and laboratory parameters were observed. In conclusion, the tested combined nutraceutical was well tolerated, while significantly reducing the plasma levels of LDL-C, TC, non-HDL-C, ApoB, TC/HDL-C and LDL-C/HDL-C ratios in mildly hypercholesterolemic patients. Trial registration (ClinicalTrials.gov): NCT03739242.
Project description:OBJECTIVE:We sought to determine whether APOE genotype influences a previously observed decline in serum total cholesterol (TC) and low-density lipoprotein (LDL) levels preceding primary intracerebral hemorrhage (ICH), as a potential demonstration of nonamyloid mechanisms of APOE in ICH risk. METHODS:We performed a single-center retrospective longitudinal analysis using patients with known APOE genotype drawn from an ongoing cohort study of ICH. Serum lipid measurements for TC, triglycerides (TGs), LDL, and high-density lipoprotein (HDL) collected within 2 years before and after index ICH were extracted from electronic medical records. Piecewise linear mixed-effects models were used to compare APOE allele-specific effects on temporal serum lipid trends in ICH. Demographics, medical history, medications, and health maintenance data were included as fixed effects. Inter- and intraindividual variations in lipid levels were modeled as random effects. RESULTS:A total of 124 ICH cases were analyzed. APOE ?4 carriers had greater rates of decline in serum TC and LDL within 6 months preceding ICH (TC: -7.30 mg/dL/mo, p = 0.0035; LDL: -8.44 mg/dL/mo, p = 0.0001). Conversely, serum TC and LDL levels in APOE ?2 carriers were unchanged within the same time period. APOE genotype had no associations with serum HDL or TG trends. CONCLUSIONS:APOE allele status predicts serum TC and LDL changes preceding acute ICH. Our results have implications for ongoing efforts in dissecting the role of dyslipidemia in cerebrovascular disease risk. APOE genotype-specific influence on lipid trends provides a clue for one mechanism by which APOE may influence risk of ICH. Further characterization of the metabolic roles of APOE is needed to improve the understanding of APOE biology in cerebrovascular disease risk.
Project description:Dyslipidaemia is a common complication among HIV-infected children after antiretroviral therapy (ART); however, HIV itself can cause abnormal lipid metabolism. There is limited information of lipid profiles among Asian HIV-infected children naive to ART.A total of 274 HIV-infected ART-naive Thai and Cambodian children aged 1-12 years with CD4% between 15% and 24% were included. Patients were fasted for ?4 h before blood was drawn. Abnormal lipid levels were defined as triglyceride (TG)>130 mg/dl, total cholesterol (TC)>200 mg/dl, low-density lipoprotein (LDL)>130 mg/dl and high-density lipoprotein (HDL)?40 mg/dl.The mean (±SD) was 76.6 (33.8) months for age and -1.3 (1.0) for weight Z-score. Mean (±SD) CD4% was 19.9 (4.8) % and HIV RNA was 4.6 (0.6) log(10) copies/ml. The median (±SD) fasting time was 13.0 (2.7) h. Mean (±SD) for lipids were 116 (62) mg/dl for TG, 139 (29) mg/dl for TC, 73 (29) mg/dl for LDL and 45 (19) mg/dl for HDL. Overall 63.9% had dyslipidaemia with hypertriglyceridaemia and hypo-HDL being the most common (28% and 45%, respectively), while 2% had hypercholesterolaemia or hyper-LDL. After adjusting for age, having HIV RNA>5 log(10) copies/ml was associated with hypo-HDL with ORs of 8.1 (95% CI 2.7-24.3).Up to two-thirds of ART-naive, HIV-infected Asian children with mild-to-moderate immune suppression had dyslipidaemia. Low HDL was the most common and was associated with high HIV viraemia. The long-term consequence of low HDL deserves further investigation in children.
Project description:Dyslipidemia is a global health problem and a high risk factor for atherosclerosis, which can lead to serious cardiovascular disease (CVD). Existing studies have shown inconsistent effects of turmeric and curcuminoids on blood lipids in adults. We performed this systematic review and meta-analysis to evaluate the effects of turmeric and curcuminoids on blood triglycerides (TG), total cholesterol (TC), LDL cholesterol, and HDL cholesterol. We searched the English databases of the Web of Science, PubMed, Ovid (including EMBASE and MEDLINE), Scopus, and the Cochrane Library and 2 Chinese databases, Wanfang Data and China National Knowledge Infrastructure, for randomized controlled trials (RCTs) that studied the effects of turmeric and curcuminoids on blood TG, TC, LDL cholesterol, and HDL cholesterol in subjects with metabolic diseases. With random-effects models, separate meta-analyses were conducted by using inverse-variance. The results are presented as the mean difference with 95% CIs. Evidence from 12 RCTs for TG, 14 RCTs for TC, 13 RCTs for LDL cholesterol, and 16 RCTs for HDL cholesterol showed that turmeric and curcuminoids could lower blood TG by -19.1 mg/dL (95% CI: -31.7, -6.46 mg/dL; P = 0.003), TC by -11.4 mg/dL (95% CI: -17.1, -5.74 mg/dL; P < 0.0001), and LDL cholesterol by -9.83 mg/dL (95% CI: -15.9, -3.74 mg/dL; P = 0.002), and increase HDL cholesterol by 1.9 mg/dL (95% CI: 0.31, 3.49 mg/dL; P = 0.02). In conclusion, turmeric and curcuminoids can significantly modulate blood lipids in adults with metabolic diseases. However, these findings should be interpreted cautiously because of the significant heterogeneity between included studies (I2 > 50%). There is a need for further RCTs in future.

domain: medical


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This recipe for watermelon, vodka and mint popsicles (“poptails”) also works as a granita (adult snowcones!!). Super easy, delicious and perfect for a hot July afternoon or balmy summer evening. As you can see, they’re also beautiful.
makes 36 popcicles
8 cups cubed watermelon
4 peeled limes
1 cup fresh mint
3/4 cup vodka
1/3 cup sugar
1/3 cup water
- Put sugar and water in a small pot. Heat over medium high heat to a boil. Turn heat down and simmer for 3-4 minutes or until syrup consistency is reached. Remove from heat and set aside.
- Puree watermelon, lime and mint in a blender. Strain using a fine mesh sieve.
- Add 1/2 cup of cooled syrup and vodka to strained watermelon and lime. Whisk thoroughly.
- For popsicles: pour into popsicle molds, place in freezer for 18 hours or until set.
- For snowcones (granita): pour into a 9″x 11″ dish. Cover tightly with plastic wrap and place in the freezer. Every 4 hours or so, use a fork to scrape the mixture. Or, if you’re like me and can’t remember to check on it every 4 hours, freeze for about 12-18 hours. Just before ready to serve, use a fork the roughly mash up any frozen chunks, making a granita texture.
- To make these kid friendly, use 1/2 cup water instead of vodka. They will freeze much quicker!
- Enjoy responsibly!

domain: food


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Artemis Fowl and the Opal Deception facts for kids
First edition cover
|Series||Artemis Fowl series|
|30 April 2005|
|Media type||Print (hardback and paperback), Audiobook CD|
|Pages||352 (first edition, hardback)|
|ISBN||0-14-138164-7 (first edition, hardback)|
|Preceded by||The Eternity Code (2003)|
|Followed by||The Lost Colony (2006)|
Artemis Fowl and the Opal Deception, known in America as Artemis Fowl: The Opal Deception, is a teen fantasy novel published in 2005, the 4th book in the Artemis Fowl series by the Irish author Eoin Colfer. Preceded by Artemis Fowl: The Eternity Code and followed by Artemis Fowl: The Lost Colony, it is centred on the brilliant pixie Opal Koboi's second try at rebellion (after her first attempt was a failure) and Artemis Fowl II and his fairy comrades' efforts to stop her. Critical reception was mixed, with some reviews praising the book and others deeming its writing poor and confusing.
The book begins with the pixie Opal Koboi faking a coma inside a hospital to avoid incarceration by the Lower Elements Police (LEP) after her failed rebellion and attempt of world domination (which took place in Artemis Fowl and the Arctic Incident).
Opal Koboi, who had been under 24-hour surveillance, had DNA tests done every 4 hours, a seeker-sleeper planted in her arm (a device that can make the criminal faint, it also giving their position away) and had her in a net trapped with monitoring pads by the LEP to ensure that Opal was actually in the asylum cell, with help from the Brill Brothers manages to replace herself with a clone, which is identical to herself (the only difference being that the clone is brain dead).
Opal lures Commander Julius Root and Captain Holly Short of the LEP into a lava chute alone by putting General Scalene under the mesmer there. Koboi then kills Commander Root by using a 30 centimeter metal box packed with explosive gel and covered in stealth ore (framing Captain Holly Short as the murderer by blocking the LEP camera and changing the video to Holly shooting her commander), and launches a bio-bomb at Artemis Fowl, which fails to kill him and his bodyguard Domovoi Butler because Butler jumps from the three-story hotel with Artemis.
Artemis Fowl was mindwiped in the third book of the series, Artemis Fowl and the Eternity Code and has no memory of meeting the fairies. This has also caused him to revert to his former self - the one cruel enough to kidnap a fairy. But he has a conscience that he chooses not to listen to.
Artemis is rescued from the scene of the bio-bomb attack by Holly. She tells him who she is, in hopes to ignite his memory. He does not regain his memories of the past adventures but agrees to help her for a fee. They are then recaptured by Koboi and thrown into a troll-infested abandoned fairy theme park known as the "Eleven Wonders of the Human World" (containing scale-models not only of the Seven Wonders of the Ancient World but also the additions of Abu Simbel, Borobodur, Rapa Nui and the Throne Hall at Persepolis). After a desperate battle against the troll hordes on a model of the Temple of Artemis at Ephesus, they are rescued by former criminal Mulch Diggums and Butler. Holly and Artemis become friends "bonded by trauma" and Artemis says he feels that he doesn't need money to help a friend.
Opal then proceeds with her plan to help renowned Italian billionaire environmentalist Giovanni Zito send a probe downward by mesmerising him that she is his pampered adopted daughter Belinda Zito, which, according to Koboi's plan, will cause the humans to find the fairies and start an inter-species war, leading to fairy genocide. The plan is to blow his fields with several megatons of TNT and then wait for the 118 million tons of iron, with a probe in it, to sink to the core at a rate of 5 metres (16 ft) per second.
After being rescued, Mulch gives Artemis the disk that had been passed off as a gold medallion, which Butler was given earlier in the book. Artemis views the disk and regains his memories. He is overcome with the guilt of what he had done to the fairies but to Holly the most and for the first time, he apologizes for kidnapping her. He realises that Holly, Butler, and Mulch were the only friends he had. Together, the four friends take on Opal Koboi, knowing that they are the only ones that know she's escaped. It becomes a more difficult task with the LEP on their tail, who still thinks Holly is the one who killed the Commander. The new Commander refuses to believe anything, despite the fact that everyone knows Root was like a father to Holly.
Afterwards, the story follows the struggle over the probe, which is closing in on the E7 chute. The probe eventually misses the chute, and Koboi crashes into a woman's vine field. She uses her last bits of magic to mesmerize the woman that she is Belinda, her child. However, a week later, Koboi is detained by the LEP, and Holly is cleared of all charges over Commander Root's murder. However, she is frustrated by Commander Root's replacement, Ark Sool, so she resigns and starts a private investigation firm with Mulch Diggums.
It is also apparent that Artemis has had a change of heart, as he anonymously donates the famed painting The Fairy Thief, which he had stolen directly before Koboi's bio-bomb attack, to the Louvre museum.
There is a secret code at the bottom of the book, containing a message from Foaly. This is translatable if one has the Gnommish alphabet, available in The Artemis Fowl Files by Eoin Colfer, or the Artemis Fowl website.
The message on the cover of the US publication, barely decipherable, reads "Opal wants revenge", it is faintly repeated several times on the sides of the tube.
The Gnommish symbols around the molecules on the front cover read "DNA never lies".
Artemis Fowl and the Opal Deception Facts for Kids. Kiddle Encyclopedia.

domain: library


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Copies of Vietnamese Birth Certificates
According to Vietnamese law, one can obtain copies of Birth Certificate by filing an application with the provincial Justice Department, providing all information related to the birth (date of birth, place of birth, parents’ names…). If the child’s parents registered the birth with local authorities, the Justice Department staff will check their birth registration book and issue copies of the birth certificate.
If the parents did not register the birth with local authorities, the parents can ask for a late registration of birth or re-registration of birth. The procedure for this process differs depending upon the province. Applicants should check with the Justice Department of the birth province for specific information. For example, in Hanoi, applicants must submit a confirmation from the local (ward) People’s Committee stating that they have never been issued a Birth Certificate and provide all available forms of identification to prove their date of birth. In some provinces, applicants may be asked to submit statements from two witnesses in the same village who knew about the birth.
If the applicant is not in Vietnam, he/she may ask relatives or friends in Vietnam to submit application on his/her behalf. Each provincial Justice Department has its own requirements. Some provinces ask for a notarized Power of Attorney from an applicant to assign a person in Vietnam to obtain the Birth Certificate. Again, check with the provincial Justice Department for specific information.
The IRS has created a new comprehensive tax page on its website which is directed to U.S. citizens and Resident Aliens abroad. This page contains basic tax information and also includes links to more detailed topics such as the foreign earned income exclusion, foreign tax credit, reporting foreign bank accounts, Fulbright grants, state taxes, and a myriad of others.
The Form 8938 (Statement of Specified Foreign Financial Assets) should be filed by taxpayers with specific types and amounts of foreign financial assets or foreign accounts. It is important for taxpayers to determine whether they are subject to this new requirement because the law imposes significant penalties for failing to comply.
Find here the Form 8938 instructions, regulations implementing this new foreign asset report, and other information to help taxpayers determine if they are required to file Form 8938.
U.S. citizens may be asked to present a “certificate of good conduct” or “lack of a criminal record” for a variety of reasons for use abroad including adoption, school attendance, employment, etc.
U.S. citizens can request a criminal background check in the U.S. or in Vietnam.
To obtain a criminal background check in Vietnam:
- Persons who have been living in Vietnam for 6 months or more can request this document from their local provincial justice office.
- If you no longer live in Vietnam, but need a criminal background check for the period of time you stayed in Vietnam, you can request it from:
The National Center for Criminal Checks
58-60 Tran Phu Street, Ba Dinh District, Hanoi
Note: Foreigners who cannot appear in person when requesting a criminal background check may provide a Power of Attorney authorizing another person along with photocopies of the requestor’s current passport and the requestor’s passport previously used in Vietnam (if different from current passport) to obtain the criminal background check. The Power of Attorney and copy of the U.S. passport must be authenticated by a Vietnamese Embassy overseas or by the Vietnamese Ministry of Foreign Affair’s Consular Department. The Power of Attorney must be translated into Vietnamese by a Vietnamese notary public.
Getting your fingerprints taken:
A U.S. citizen can have his/her fingerprints taken at the Consular Section, U.S. Embassy, 170 Ngoc Khanh Street, Hanoi, every Thursday afternoon (except Vietnamese and U.S. holidays) between 1:00 p.m. and 3:00 p.m. Please make an appointment for this service. Select "Notarial services and other services".
You do not have to pay for this service but you are responsible for sending the cards to your local police department or FBI.
Emergency Contact Information
If you are a citizen of the United States with an after-hours emergency, please call our hotline at: (04) 3850-5000/3850-5105 within Vietnam, or +84-4-3850-5000 internationally.
For non-emergency issues contact us here.
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All About Jazz needs your help and we have a deal. Pay $20 and we'll hide those six pesky Google ads that appear on every page, plus this box and the slideout box on the right for a full year! You'll also fund website expansion.
I must admit, I didn't consider Kevin Norton's latest entitled Time-Space Modulator to be a reference to L'szl' Moholy-Nagy's sculpture "Light-Space Modulator." Nope. I referenced the drummer's work with, and admiration for Anthony Braxton, and immediately connected this disc with Bugs Bunny's encounters with Marvin the Martian. I can even picture Braxton speaking with Marvin's voice and calling for "the P-53 time-space modulator."
But then I digress.
Norton, like Braxton (and Marvin) are partial to a highly intellectual approach to their craft. He has previously written about Situationalist founder Guy DeBord and activist Cathleen Chang. As a sideman he can be heard on numerous Braxton discs, playing Ghost Trance Music and with Paul Dunmall, Paul Rogers, and on some favorite recordings of Phillip Johnston's Big Trouble.
The nice surprise here is the balance between complex constructions and free blowing. This live disc opens with the lengthy "Mother Tongue," a turbulent sea of a song with John Lindberg's bass riding above the maelstrom. Norton switches to mallets and his vibraphone, cymbals and bells for the group improvisation on "Seoul Soul." With Lindberg tapping his bow, the band maintains an interesting mix with just a minimal sound.
The tracks "Milt's Forward Looking Tradition" (for Milt Hinton), "Atie Aife," and "Difficulty" all flow together as if they are parts of one composition. "Milt's" plays off the heavy bass groove laid down as Norton's brush backs the horn lines. Both trumpeter Dave Ballou and saxophonist Tony Malaby are sympathetic partners in this undertaking, working their warmest of tones through their parts on these peaceful compositions. Norton chooses the vibraphone as his token of peace. They are reflective, beautiful tracks.
These tracks act as the meat between the sandwiched energy opener and closing tracks. With "Moonstruck" band goes out as it came in, on a wave of pulsing energy.
I can almost hear the curtain call... "Goodnight little rabbit."
I love jazz because with it I found my true voice. I have always sung since I was a very small child in school and church. And there have been many genre that I have enjoyed including spiritual, folk, country, latin, soca and pop
I love jazz because with it I found my true voice. I have always sung since I was a very small child in school and church. And there have been many genre that I have enjoyed including spiritual, folk, country, latin, soca and pop. But nothing has touched my artistic sensiblities like JAZZ! Two years ago I moved to Sarasota, FL where I renewed my focus on my singing career and I was so impressed with the quality, quantity and generousity of talented jazz musicains in the Suncoast area. I soon partnered with piano legend Billy Marcus and his trio with Don Mopsick and Stephen Bucholtz. What a blast working with these guys and having them back me up on my first jaz album, Here's To You... which was just released on October 1st. I can't wait to see where the coming year brings me! Check out syniacarrolljazz.com


SUN Mobility announced its plan to roll out 100 battery swapping stations, called Swap Points, in Bengaluru by the end of 2021. In a virtual event, the Chief Minister of Karnataka, BS Yediyurappa, formally commenced the commercial launch of SUN Mobility’s swapping network in Bengaluru. At present, four swap points are available at IOCL outlets in the areas of Indiranagar, Jayanagar, Koramangala, and HSR Layout.
“We want to create a similar supporting ecosystem by deploying 100 Swap Points that can power and support all forms of shared mobility in the city, including 2-wheelers, 3-wheelers, and last-mile delivery trucks,” said Chetan Maini, Co-Founder, and Vice-Chairman, SUN Mobility.
SUN Mobility also announced its partnership with the City’s MetroRide, a sustainable and environmentally friendly shared mobility solution to solve first and last-mile connectivity for Metro rails. MetroRide’s fleet of Piaggio Ape E-City electric three-wheelers will make use of SUN Mobility’s Swap Points deployed at prime IOCL outlets.
With the roll-out of the 100 Swap Points, SUN Mobility looks forward to working with infrastructure enablers, BESCOM and BMRC, to enable a robust network of battery swapping infrastructure in the city. This will provide the right impetus to meet the Government of Karnataka’s goal of providing one charging station in a 3km radius grid in Bengaluru, as part of its EV Policy released in 2017.


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First the doctor pulls the living fetus feet-first out of the birth canal, except for the head. The skull of the fetus is then punctured with scissors and a tube is inserted into the back of the head. The brains are then swiftly sucked out causing the head to collapse. The now-dead baby is delivered and disposed of. This brutal, vicious procedure goes on daily in the United States, but not for much longer.
The Partial-Birth Abortion Ban Act has finally passed the House of Representatives and Senate to be signed into law by President Bush. The federal law will effectively put an end to abortions that occur in the seventh, eighth or ninth month of pregnancy.
Hopefully this means the tide is turning against the vile and far-reaching precedent set by the 1973 Supreme Court decision Roe v. Wade. This gross breach of power by the influential court deemed that a woman has a “right to privacy” that allows her to abort her child without any government intervention. May this act be the first of many to formally end abortion in all forms in the United States.
The decision has snowballed from restricted, heavily-regulated abortions in the ’70s, to the point now where the majority of partial-birth abortions occur with a healthy child and mother.
Annually, there are an average of 1.5 million abortions performed and 3,000 to 5,000 are partial-birth, according to Planned Parenthood.
Since 1973 over 40 million lives have been snuffed out due to what proponents have so deceivingly dubbed a “woman’s right to choose.” Where was this right spelled out and on what authority is the right founded on?
The U.S. Constitution surely does not define this right. Most abortion supporters consistently contend that the Constitution, through Supreme Court interpretation, guarantees a “right to privacy.”
Rarely do they take into account the Declaration of Independence’s statement that all people have “certain unalienable rights” including a right to “life…”
The entire American tradition is based on the belief that each human being has a right to live.
The fact that daily infanticide occurs is simply a sign of the times. Our society seems quicker to defend the rights of whales than the rights of supremely innocent babies.
We encourage people not take to responsibility for actions they willingly took part in. Got pregnant and did not plan on it? Abort your child.
The fact is that children are not planted in women during the night by some mysterious stork. Pregnancy is not a random occurrence. There is a very specific action that must occur for pregnancy to ensue. Consequences are a part of life.
The federal abortion ban contains amendments allowing abortions for rape and cases where the mother’s life would be in jeopardy if the child was not aborted, as it should.
If the mother’s life is in jeopardy there is no reason that two lives be needlessly lost. In the case of rape, the issue is a bit less black and white. No male can ever understand the powerful emotions felt by a female rape victim, but here is just a thought. Would not giving the child up for adoption be a less difficult experience than adding the trauma of abortion to the pain of being a rape victim?
For mothers who are faced with a non-rape pregnancy they were not planning on, aborting the child should not be an option. The options for unwanted pregnancies are endless. A mom can even leave her child on a government building’s doorstep with no questions asked. Hundreds of thousands of couples across America are just waiting for an opportunity to adopt. Adoption is most certainly a better option than abortion.
Most of the “unwanted” children will grow up in terrible environments, some moving from foster home to foster home and others living with parents who don’t want them.
Some abortion proponents claim that abortion saves children from experiencing this, in essence, saving them from life itself. How can you determine whether a life is worth living? How many people have overcome a difficult childhood to make a powerful mark on our world?
Pro-choice groups, such as Planned Parenthood, often take newly pregnant women that are in a financial strain and try to persuade them to have an abortion, according to a disturbingly large number of female testimonies.
A woman faced with an unexpected pregnancy and the thought of her world turned upside down does not need the pain of an abortion branded on her forever. The predicament young women across this nation face with unexpected pregnancies is profound. The psychological pain associated with an abortion is the last burden that should be laid on the weary shoulders of a new mother.
The feelings after an abortion, now called Post Abortion Syndrome, can leave a woman racked with pain and guilt for years to come.
“You see, abortion doesn’t make your baby ‘just go away'”, said Lisa Musil, 39, who had an abortion at the age of 19. “That baby lives in your heart for the rest of your life.” This was the start of a letter Musil sent into an online column, “Dear Becky.” The column is crowded with stories very similar to her own.
The cycle of pain that un-expectant mothers experience should never end in abortion. There are volunteer groups across the country that will come to the aid of mothers and help ease the often unspeakably brutal period of unexpected pregnancy.
May the stone that has begun to roll with the Partial Birth Abortion Ban Act continue to roll until it crushes the procedure that has shattered and destroyed millions of lives.
One of the legislation’s chief proponents, Rep. F. James Sensebrenner, R-WI, said this to his fellow Representatives regarding late-term abortions: “Implicitly approving such a brutal and inhumane procedure by choosing not to prohibit it will further coarsen society to the humanity of not only newborns, but vulnerable and innocent human life.”

domain: politics


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I may not be a qualified medical practitioner, but one thing I can tell you is, sticking an eel up your anus would be a terrible idea.
New Zealand becomes the 13th nation to support Marriage Equality.
Mark Hamill recently said that he had previously been approached to reprise his role as Luke Skywalker and […]
Having quite a few trans-friends, I understand some of the struggles that they have to deal with. Something that many of us who are comfortable in our own genders seem to sometimes overlook. I guess that’s why this story really touched my heart.
Now I won’t lie, this news has me all kinds of happy. Nothing beats a homophobic bigot leaving […]
“Pucker up girls, it’s time to find Nemo!” Well this just goes to show if you can’t look […]
These days when you see a headline with the Westboro Babtist Church, you kind of just overlook it and […]
Honestly, David Beckham’s butt totally deserves its own show, with or without underwear! Guy Ritchie directed David Beckham in […]
The stunning and extremely handsome Italian ballet dancer Roberto Bolle was recently photographed by Marc Hom for the January 2013 issue […]
The Liberal Party releases ‘Our Plan – Real Solutions for all Australians’ that doesn’t include the LGBTI community.
Now why does this not come as a surprise? Oh that’s right, with a leader like Tony Abbott, […]
Sorry if I offend certain people here, but I’m just gonna go ahead and say it, just because […]
Get excited peeps! Australia’s own openly gay ukulele playing Olympian, Matthew Mitcham is now adding writing to his long list of […]
Wow it’s about time this woman showed a bit of integrity. A little while back I wrote about […]
Exciting times on this side of the globe! Tasmania is taking positive steps forward for marriage equality. Last […]
While people all over the world continue to voice their outrage against the unfair judgement and jailing of […]

domain: news


In this talk produced by Bahaiteachings.org, Baha’i actress Eva LaRue describes heartbreak—“an aching, crippling grief”—following a career low and the end of her marriage. “It left me feeling like a gutted shell of myself,” she says, “someone I didn’t even recognize any more.” To find authentic joy, Eva shares a spiritual process of stripping away her preconceptions and her self-limiting ideas and finding a way to forgive the past.
For more videos like this, check out Baha’i Teachings’ YouTube channel or visit Bahaiteachings.org. You can also follow them on Facebook, Twitter and Instagram.
You can also listen to our blogcast with Rainn Wilson where he interviews Payam Zamani, co-founder of Bahaiteachings.org.
For more Baha’i-inspired talks, visit Baha’i Blog’s Soundcloud page: soundcloud.com/bahai-blog/sets/bahai-talks. You can also listen to talks on Baha’i Blog’s YouTube channel: http://bit.ly/2ia1Yxp.
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Jerusalem Is Prize in Game of Cat-and-Mouse : Mideast: Israelis are incensed that Palestinian minister ‘secretly’ visited the holy city, which each side claims as its capital.
This holy city--always the emotional heart of the Arab-Israeli conflict--has become the setting for a recent, elaborate, high-stakes cat-and-mouse game between Israelis and Palestinians.
Palestinian officials are playing the mice, scurrying in and out of Jerusalem, trying to force the Israelis to put discussions of sovereignty on the table. The Israelis are the increasingly frustrated, angry cats.
Both sides believe their every move may determine the ultimate status of a city each claims as its capital.
The game is played in rhetoric and deed. It came close to theater of the absurd this week, with the revelation by outraged Israeli officials that a senior Palestinian official had “secretly” visited Al Aqsa mosque on Wednesday.
Neither side is laughing.
Even as Yasser Abed-Rabbo, minister of information in the Palestinian Authority, made his unauthorized visit that so incensed the Israeli government, Jordan’s King Hussein flew over the city for the first time since the Jordanian loss of Jerusalem in the 1967 Middle East War.
The king’s move was welcomed here as further evidence of Jordan’s willingness to make peace. Abed-Rabbo’s gesture was denounced in a formal statement by Moshe Shahal, the Israeli police minister, as not in keeping with conduct appropriate to a Palestinian minister.
Israel insists it has the right to say when and where Palestinian ministers may travel inside Israel; it considers all of Jerusalem part of Israel. “There is no question of whether or not they are allowed to visit,” Shahal said. “The question is of prior coordination and acting according to agreements.”
Jerusalem Mayor Ehud Olmert was more blunt, saying of Abed-Rabbo’s visit: “This was done clearly and with prior planning as a provocation, which is aimed to serve specific public relations purposes and to give some sort of political expression and to get reactions both among us and the Palestinian public. In a situation like this, to create provocations around the Temple Mount, this is playing with fire.”
For the Israelis, the difference between Hussein’s interest and that of the Palestinians is clear and crucial.
The king, who claims the Prophet Mohammed as a direct ancestor, has taken to saying recently that only God should be sovereign over Jerusalem’s holy sites. Israel took that to mean that he was willing to allow Israel to exercise political sovereignty over the city, so long as Muslims were granted “sovereignty” over Temple Mount in the walled Old City.
PLO Chairman Yasser Arafat, in contrast, insists that someday Jerusalem will be the capital of a future Palestinian state. Israel has not yet agreed to a Palestinian state, let alone to sharing political sovereignty over Jerusalem. And it has not agreed to an Arafat visit to Jerusalem. By tacit agreement, he has not yet asked to come; Israel has not invited him.
“It is a gentlemen’s agreement,” said Uri Dromi, an Israeli government spokesman. “It reflects the sober understanding of both sides that a visit by Arafat would be something more than a religious pilgrimage to the mosque and that it could trigger a lot of public unrest on both sides.”
But Arafat, who heads the Palestinian Authority, feels that Israel violated its accord with him over Jerusalem by acknowledging a role here for Hussein.
Prime Minister Yitzhak Rabin included a clause on Jerusalem in the declaration he signed July 25 in Washington with the king, ending the state of war between Israel and Jordan. The language recognizes Jordan’s role in maintaining Muslim holy sites in the city, stating: “Israel respects the present special role of the Hashemite Kingdom of Jordan in Muslim holy shrines in Jerusalem. When negotiations on the permanent status will take place, Israel will give high priority to the Jordanian historic role in these shrines.”
But this statement also raised hackles among Israeli rightists, who said it opened the door to Israel negotiating away sovereignty over all of Jerusalem. It infuriated the Palestinians, who said Jordan has no role to play in Jerusalem’s future status.
Arafat last week demanded immediate talks with Israel on the future of Jerusalem--a demand instantly rejected by Israel. Israeli officials noted that the agreement Israel and the Palestine Liberation Organization signed in September calls for talks on Jerusalem to begin in the final stages of Israeli-Palestinian negotiations--no later than 1996.
And so the tug of war continues.
Ahmed Suleiman Khoury, the Palestinian who secretly negotiated the agreement with Israel that set the framework for Palestinian autonomy, was not allowed to attend an economics conference in Jerusalem.
Nabil Shaath, the Palestinian minister for planning and foreign relations, who this week traveled to Tel Aviv for talks with Shahal, was granted permission to go to Jerusalem. But it was revoked at the last minute.
The Palestinians announced that Intisar Wazir, minister of social affairs, prayed at Al Aqsa mosque before Abed-Rabbo. Israeli officials said her visit also was unauthorized.
And the Israelis continue to deny the Palestinians the chance to conduct any official business of the self-governing areas from Jerusalem.
Although Israeli officials met this week in Jerusalem with Palestinian officials to discuss economic cooperation, Israel will not allow the Palestinian Economic Council for Development and Reconstruction to have telephones.
Instead, officials of that agency, which is supposed to distribute money to the self-governing authority from the World Bank and donor countries, must use cellular telephones. Why? Their office is within Jerusalem’s municipal boundaries.


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The magnitude of benefit with LCZ696 against enalapril in HF-REF patients was highly statistically significant and clinically important. In the study, the benefit of LCZ696 was seen early, was sustained and was consistent across subgroups. LCZ696:
- reduced the risk of death from cardiovascular causes by 20% (p=0.00004)
- reduced heart failure hospitalizations by 21% (p=0.00004)
- reduced the risk of all-cause mortality by 16% (p=0.0005)
Overall there was a 20% risk reduction on the primary endpoint, a composite measure of CV death or heart failure hospitalization (p=0.0000002).
"By demonstrating a very significant reduction in cardiovascular deaths while improving Quality of Life, Novartis' new heart failure medicine, LCZ696, represents one of the most important cardiology advances of the last decade," said David Epstein, Division Head, Novartis Pharmaceuticals. "We want to thank leading cardiologists from around the world for their collaboration with us and their determination in advancing this important new life saving therapy for heart failure patients."
LCZ696, a twice a day tablet being investigated for heart failure, has a unique mode of action which is thought to reduce the strain on the failing heart,,. It acts to enhance the protective neurohormonal systems of the heart (NP system) while simultaneously suppressing the harmful system (the RAAS),. Currently available medicines for HF-REF work only to block the detrimental effects,. Despite existing therapies, the mortality rate remains very high with up to 50% of patients dying within 5 years of a diagnosis of heart failure,,. Approximately half of patients with heart failure have HF-REF.
Analysis of the safety data from PARADIGM-HF showed side effects were manageable in the study. Fewer patients on LCZ696 discontinued study medication for any adverse event compared to those on enalapril (10.7% vs 12.3%, respectively, p=0.03). The LCZ696 group had more hypotension and non-serious angioedema but less renal impairment, hyperkalemia and cough than the enalapril group.
Novartis plans to file the application for marketing authorization with the US FDA by the end of 2014 and in the EU in early 2015.
About the PARADIGM-HF study
PARADIGM-HF is a randomized, double-blind, phase III study evaluating the efficacy and safety profile of LCZ696 versus enalapril (a widely studied ACE inhibitor) in 8,442 patients with HF-REF,. The baseline characteristics showed the patients enrolled were typical HF-REF patients with NYHA Class II-IV heart failure. PARADIGM-HF was specifically designed to see if LCZ696 could decrease CV mortality by at least 15% vs. enalapril. Patients received LCZ696 or enalapril in addition to current best treatment regimen. The primary endpoint is a composite of time to first occurrence of either cardiovascular death or heart failure hospitalization, and is the largest heart failure study ever done.
Secondary endpoints are change in the clinical summary score for heart failure symptoms and physical limitations (as assessed by Kansas City Cardiomyopathy Questionnaire) at 8 months; time to all-cause mortality; time to new onset atrial fibrillation; and time to occurrence of renal dysfunction. It was initiated in December 2009 and in March 2014 the Data Monitoring Committee confirmed that patients given LCZ696 were significantly less likely to die from CV causes, leading to the trial being stopped early. The DMC also confirmed the primary endpoint had been met.
About LCZ696 in heart failure
LCZ696 is an ARNI (Angiotensin Receptor Neprilysin Inhibitor) and has a unique mode of action which is thought to reduce the strain on the failing heart,. It harnesses the body's natural defences against heart failure, simultaneously acting to enhance the levels of natriuretic and other endogenous vasoactive peptides, while also inhibiting the renin-angiotensin-aldosterone system (RAAS).
Heart failure is a debilitating and potentially life-threatening disease in which the heart cannot pump enough blood around the body. Symptoms such as breathlessness, fatigue and fluid retention can appear slowly and worsen over time, significantly impacting quality of life,.
It is a significant and growing public health concern with a high unmet need for new treatments. Every year, HF costs the world economy $108 billion, and hospitalizations comprise 60-70% of treatment costs,.
Novartis provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2013, the Group achieved net sales of USD 57.9 billion, while R&D throughout the Group amounted to approximately USD 9.9 billion (USD 9.6 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 135,000 full-time-equivalent associates and sell products in more than 150 countries around the world.
1. McMurray JJV et al. Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure, N Engl J Med 2014; DOI: 10.1056/NEJMoa1409077
2. Effect of ACE inhibitor vs placebo derived from SOLVD-Treatment trial, that showed enalapril reduced risk of death by 16% vs placebo; Effect of LCZ696 vs ACE inhibitor derived from PARADIGM-HF trial.
3. Ambrosy AP et al. J Am Coll Cardiol 2014;63:1123-33. doi: 10.1016/j.jacc.2013.11.053
4. Gheorghiade M, Pang P, Acute heart failure syndromes, Journal of the American College of Cardiology 2009; 53 (7):557-73
5. Harrison's 'Principles of Internal Medicine', Seventeenth Edition pages 1442 - 1455
6. McMurray JJ, Packer M, Desai AS, et al. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF). Eur J Heart Fail 2013;15,1062-1073 (doi:10.1093/eurjhf/hft052)
7. Langenickel TH et al. Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Discovery Today: Therapeutic Strategies.2012, Vol 9. No.4
8. Solomon SD et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012;380:1387-95
9. Lloyd-Jones et al. Heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010;121:e46-215
10. Zannad F. et al, Heart failure burden and therapy, Europace 2009, 11; v1-v9.
11. Loehr LR, Rosamond WD, Chang PP, Folsom AR, Chambless LE. Heart failure incidence and survival (from the Atherosclerosis Risk in Communities study). Am J Cardiol. 2008;101(7):1016
12. Doughty R.N., The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis, European Heart Journal (2012);33(14):1750-1757
13. Clincaltrials.gov, NCT01035255 last accessed online 19 March 2014
14. Novartis press release 'PARADIGM-HF trial of Novartis' LCZ696 for chronic heart failure stopped early based on strength of interim results' issued on March 31, 2014
15. Mosterd A, Hoes, A, Clinical epidemiology of heart failure, Heart 2007;93:1137
16. Cook C, Cole G, Asaria P, Jabbour R, Francis DP. The annual global economic burden of heart failure. Int J Cardiol. 2014.;171(3):368-76
17. Neumann T, Biermann J, Erbel R, Neumann A, Wasem J, Ertl G, et al.,. Heart failure: the commonest reason for hospital admission in Germany: medical and economic perspectives. Dtsch Arztebl Int. 2009;106:269-75.
18. Stewart S, Jenkins A, Buchan S, McGuire A, Capewell S, McMurray JJ. The current cost of heart failure to the National Health Service in the UK. Eur J Heart Fail. 2002 Jun;4(3):36-71.


On October 11, Alexander McQueen will showcase once more in London, choosing once more to disregard the traditional fashion week calendars. Paolo Roversi’s mission has been the brand’s choice for the new campaign for the FW22 collection. The clothing of Sarah Burton was propelled into a surreal setting with a clear emphasis on shades.
The photographs by Paolo Roversi, which feature the models Awar Odhiang, Lucia Fairfull, Florence Nicholls, Celina Ralph, Wang Han, and Achenrin Madit, range from ultra-tight tubes to leather suits without sacrificing the iconic studded accessories or bright tints. The models are all living sculptures.


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Urban Outfitters, a trendy, sometimes quirky clothing store that also carries furniture and accessories, will open the doors to its new store, located in the old Hudson Trail Outfitters location on York Road in downtown Towson, on Thursday, Oct. 6.
The opening of the new store, which spans two floors and 8,746 square feet, is seen by some as a positive step for a downtown Towson area that has been having trouble keeping its old businesses and drawing in new ones in recent years.
While an Urban Outfitters spokesman said it is the company's policy to not give interviews, county officials and residents are optimistic about the possibilities the store brings.
Fifth District County Councilman David Marks, who represents Towson, called the new store a "fantastic addition to downtown Towson."
"It's another sign that revitalization is happening, from the renovation of the old Investment Building to new movement on the Towson Circle III project," said Marks. "Even in a rough economy, these good things are happening."
County Department of Planning Director Andrea Van Arsdale said Urban Outfitters' choice of Towson for a location represents a "major win" for the area.
"It's bringing a national retailer with a huge following into downtown Towson," Van Arsdale said. "It should have huge synergistic affects for the area. Every young kid is going to be there."
Nancy Hafford, director of the Towson Chamber of Commerce, said that the addition of a clothing store to the Towson core was necessary.
"We have great restaurants and jewelry shops, but no clothing stores," Hafford said.
Hafford believes that the store, which targets young people, will be a hit with the college students.
"I think this is going to bring a lot of students from Towson University and Goucher into town," she said. "We love that they support the mall, but would also love for them to spend money in the Towson core."
Matthew Sikorski, president of the Towson University Student Government Association, said the store has already been featured in The Towerlight, Towson's student newspaper, and that students and community members are excited for the store's opening.
"A lot of the students that I talked to love the store, so they were happy to see it come so close to campus," Sikorski said.
He added that the store will be a "welcome addition" to an uptown Towson area that is a "very integral part of the Towson student experience."
"With the mall, various restaurants and music venues, a majority of students will take a trip up to that part of town at the very least once a year, if not multiple times a month," Sikorski said.
"I don't necessarily think that this clothing store will change the perception of the area," he said, "because students use it so much already."

domain: economics


14.01.2012 19.Tewet. 5772 Schmot
Renana Raz presents her Youtube innovation YouMake ReMake.
If YouTube were a nightclub, it would be packed every single night. Whereas 15 years ago “the place to be” was a physical location, today it has shifted into cyberspace. YouTube has become a black hole into which hours are sucked, a forum in which to share wacky recipes and exercise routines and a hodgepodge of just about anything anyone can, will or has ever thought of. It is also the basis for Renana Raz’s evening YouMake ReMake, which will premiere its second edition later this month.
Last year, Raz received rave reviews for the first edition of this work. Propelled by the success, Raz presented the final showing of Edition #1 in late 2011 and got to work on the next montage….


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Angry mob stormed Kairaba Police Station demanding “Yankuba Touray must testify”.
Hundreds of angry Gambians have stormed the police station at Kairaba Avenue demanding the state to ensure the prosecution of former junta member Yankuba Touray after the ex-soldier refused to testify before the Truth Commission.
Touray appeared before the Truth Commission on Wednesday but refused to talk on claims that he has immunity granted to him by the 1997 constitution from any crimes he may have committed.
Touray is wanted for several killings from 1994 when the military took over to 1997. He told the Commission that the 1997 constitution gave him immunity.
This is the first time someone adversely mentioned in relations to crimes such as murder and torture has refused to appear before the Commission for public hearing.
“I therefore have no choice but to order the immediate arrest of Yankuba Touray and to hand him over forthwith to the police station with jurisdiction over this area,” said Commission’s Chairman Dr Lamin Sise.
Touray is currently charged with contempt of court. He may also face prosecution on murder charges in connection to the death of Ousman Koro Ceesay and November 11, 1994 killed soldiers.
Yankuba was taken away in an armored police truck which was heavily stoned by angry mob, leading the police to fire a single teargas canister. This caused a huge tension between the people and the police.


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So we’re talking to them the most but at the same time we’re talking to a couple of other teams as well case things go sideways, then we have a back-up option. It starts with a slide to the left, then a shimmy to the right and a wiggle of the legs. Here is Around The NFL ‘s latest Rookie of the Year watch for Cheap NFL Jerseys China Cheap NFL Jerseys Usa Week 11: From Rams general manager Les Snead: He reminds you of three Cheap NFL Jerseys Usa or four different people, and those people, they’re usually the best at one style or skill. You have guys you have to plug into different areas and do the job, and we feel pretty confident that Pouliot can do that. Backup goalie has been superb and Cheap Jerseys From China he’ll be much cheaper than Jones. 8-93 Cowboys >From a pure talent standpoint, they are one of the best two or three teams ever. He went through his positional workout extremely well. Added Big Ten Rimington-Pace Cheap Milwaukee Brewers Jerseys Offensive Lineman of the Year, first-team All-Big Ten , second-team All-American, second-team Steele Postseason All-American, first-team Steele Postseason All-Big Ten, R. The Rockies scored their biggest upsets LA, though.
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domain: sports


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The travel and lifestyle blog of In My Footsteps Podcast host and author Christopher Setterlund. Discovering and sharing the best of today and yesterday. Beautiful and inspiring places to visit now, along with incredible stories of times gone by. From Cape Cod to New England and beyond, from present-day, to some classic 1980's nostalgia, to days long gone by. There is something for everyone here much like with the podcast.
Friday, September 16, 2022
In My Footsteps Podcast: Episode 85 - Cape Cod's Marconi Wireless Station, Rutland Vermont, Video Arcade Heyday, Worst As-Seen On TV Products, Phineas Gage
Posted by Christopher Setterlund at 9:38 AM
Labels: as seen on tv, cape cod, history, in my footsteps, lifestyle, marconi, new england, nostalgia, phineas gage, podcast, road trip, rutland, setterlund, travel, vermont, video arcade, wireless
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domain: geography


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Date posted: May 29, 2014
The Adana branch of the Association of Health Employees (SAMEDER) held a farewell ceremony in honor of the volunteer doctors on Wednesday. Dentist Yasin Türkoğlu, who addressed the attendees of the event, said that that Dr. Necdet Kızılkaya from Adana was the first to decide to volunteer in Uganda.
The Nile Hospital will be opened very soon, Türkoğlu said, adding that the second doctor to commit to serving Ugandan patients was Sami Kiper.
“I am congratulating our colleagues, who are giving their profession its due. The prayers of our nation are with you,” Türkoğlu said, adding that Kiper will be helping the people of Uganda.
SAMEDER chairman Önder Önem said each doctor would pursue their vocation with a sense of honor. “It is good to see that our doctors under the auspices of SAMEDER and Kimse Yok Mu are continuing to take on the tasks that befit the profession of medicine. We are happy and honored to see these people,” Önem said.
Scores of doctors attended the farewell ceremony to give Kiper and Kızılkaya a proper sendoff. In a speech at the event, Kiper talked about the serious health problems Ugandans are facing, saying, “We will be trying together with my Turkish and Ugandan colleagues to help the people by providing remedies for them. During this term, our families will also be supporting us. We are also grateful to them.”
The doctors have taken their families to the Ugandan town of Jinja, which the Nile Hospital will serve.
Source: Todays Zaman , May 29, 2014
Tags: Africa | Hizmet (Gulen) movement | Humanitarian aid | Uganda |


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President Joe Biden has maintained "there's no 'there' there" in his handling of classified documents, but one conservative columnist argued that only makes his case look the same as Donald Trump's.
The former president stashed top-secret government materials at his private Mar-a-Lago resort after leaving office and refused to return them to the National Archives when asked, but The Bulwark's Will Saletan said the Biden administration was sending a confusing message by insisting the current president had done nothing wrong.
"Biden is completely wrong," Saletan wrote. "The 'no "there" there' defense doesn’t distinguish him from Trump. It makes the two cases look alike. It positions Biden, like Trump, as a denier of obvious reality. Biden shouldn’t have had classified records in his home, his garage, or other unauthorized locations. But he did."
The president read a scripted statement last week saying he had no regrets about taking classified materials to one of his old private offices, his home library and a garage at his residence, but two days later FBI agents again found classified documents at his Wilmington home in the presence of Biden's personal legal team and the White House counsel's office.
IN OTHER NEWS: Top NY paper dunks on Trump after they prove he lied
"Stop pretending there isn’t anything to see here," Saletan wrote. "We already know there is. The only remaining question is how bad it is. So far, there’s no evidence that Biden, his lawyers, or the White House resisted attempts by DOJ or the National Archives to recover documents, as Trump did. But as to how many classified files Biden improperly retained, or what they were: We don’t yet know."


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domain: artistic


NYTimes The Collection: The Times launches its second iPad app in support of its fashion editorial
If I have had one serious criticism of the New York Times digital strategy of late, it has been that the company has been lagging far behind others in experimenting with both the mobile and tablet publishing platforms.
But the release of NYTimes The Collection is a move in the right direction. The app is free to download, but the app description states that after the New Year only some content will remain free but to gain unlimited access the reader will have to be a NYT subscriber to the tablet plan or the all-access plan. To me, this shows that readers have reject the NYT tablet edition in favor of web and smartphone access. Customers are certainly telling the Times that their tablet efforts have been weak – this doesn’t solve the NYT tablet app issue, it covers it up.
The app is another of those Flipboard box design apps, but I will admit that the concept definitely works here. The reason is that box design fails to convey editorial curation, the prioritizing of stories – that is unnecessary here. Instead the reader can browse the stories at their leisure in an unhurried manner.
There is a fair amount of content here that the reader can access, which is important in an app that a reader will linger over. From the app description:
Readers of this app also get:
- Updates from across the fashion industry and behind-the-scenes interviews.
- Photos of all the latest looks fresh from the runways in New York, Paris, London and Milan.
- New products that are hot in stores and the latest in beauty and cosmetic trends.
- Street fashion from Bill Cunningham’s On the Street, T’s Look of the Moment and reader-submitted slide shows.
- Shopping videos.
- The ability to seamlessly share their favorite articles, videos and slide shows via Facebook, Twitter and e-mail.
- Fashion reviews from Cathy Horyn and Suzy Menkes.
“It’s one of our first forays into what we think of as vertical app strategy,” Times product management executive director M.Z. Goodman told Women’s Wear Daily’s John Koblin. “What can we do with all the content we produce that might stand alone well? It’s sort of an experiment.”
Yes, it is. But this is what the NYT should be doing. It is what will continue to separate the NYT brand from other newspapers.
While many newspaper publishers see the new digital platforms as simply a way of extending the print product, others realize that tablets are a unique platform requiring their own unique, specially designed products. NYT The Collection is an “experiment” worth conducting.


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Stanford”s junior star Jordan Morris scored two goals, caused a penalty for another goal and the No. 8 Cardinal stunned second-seeded Clemson 4-0 to win its first ever NCAA men”s soccer title.
Seniors Brandon Vincent and Eric Verso added goals for Stanford (18-2-3), which gave the school its 108th NCAA title and at least one national championship for 40 consecutive years.
The two-time Pac-12 champions did not allow a goal during the College Cup, advancing over Akron in a penalty shootout in Sporting Park in Kansas City.
Stanford was competing in its first College Cup in 13 years, and the first for coach Jeremy Gunn, who took over the program four years ago.
Morris, a MAC Hermann Trophy finalist, scored 1:27 into the game as Stanford matched the largest margin of victory in a national final. In 1969, Saint Louis defeated USF 4-0.
Morris, a U.S. national team striker, might leave after the season to join Seattle Sounders FC, which owns his rights as a homegrown player.


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Democrats First – Catholics Last (George Neumayr)September 22, 2020
Saint of the Day for September 22: St. Lorenzo Ruiz and CompanionsSeptember 22, 2020
By Beth Baumann, Townhall, Sept. 21, 2020
SAGINAW, Mich. – For months we have heard about the “Silent Majority,” the idea that the majority of our nation are conservative, law-abiding citizens who support President Trump. These Americans care about issues like jobs and the economy. They support law enforcement, disagree with Black Lives Matter rioters and, by and large, want government to stay out of their lives.
In Central Michigan, the “Silent Majority” is alive and well. The problem, however, is they’re silent because they’re afraid of being retaliated against.
“They know they can be humiliated and, probably, a little bit afraid of these activists coming in and doing some damage to their house and they don’t want to make that statement,” a 60-year-old Bay City woman said, referencing Black Lives Matter rioters. …


As a boater, you naturally love water. But you definitely don’t want it in your boat’s fuel.
If water gets into your fuel, it can cause lots of problems for your engine. And, when it mixes with ethanol-blended gas, it undergoes a process called “phase separation,” which creates sludge in your tank and can cause engine damage.
Check for water in your fuel by using a clear glass jar. Dump the contents of your fuel filter into the jar and let is settle for a few minutes.
If there’s no water in your fuel, the contents in the jar will all be the same yellowish color. If you do have water, gas floats on water, so you’ll see a bubble at the bottom of the jar. You can siphon the water from the bottom of your tank, or take it to a professional.
If phase separation is occurring from mixing water and ethanol, the bubble at the bottom will be gelatinous. If that’s the case, contact an environmental services company to properly dispose of this fuel.
Should you find water in your fuel, look for how it is getting into your fuel tank. Among the possible reasons could be a bad fuel cap seal or a broken vent.