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Percentages were calculated per 100 000 treated patients using 100 000 Monte Carlo simulations. For every 100 000 patients treated (treatment naive, prevalent cohort aged 60 years), the percentage of the advanced liver disease cases that could be averted by treating all stages with combined sofosbuvir and ledipasvir for 8 or 12 weeks compared with treating stages F3 and F4 only are shown. By treating all stages of fibrosis vs waiting to treat at stages F3 and F4, the percentage of averted cases of liver transplant, decompensated cirrhosis, hepatocellular carcinoma, and liver death are 26%, 17%, 27%, and 25%, respectively. Fibrosis is measured using the METAVIR stages (described in the Model Overview subsection of the Methods section).
The tornado diagram depicts 1-way sensitivity analyses for the inputs with the greatest effect on the ICER. Bars to the right of the base-case ICER ($39 475 per quality-adjusted life-year [QALY] gained, represented by the vertical line) indicate an increase in the ICER relative to the base case to the upper limit of the input variable; bars to the left indicate the inverse. For example, as age increases from 20 years through the base-case age of 60 years to 70 years, the ICER increases. A high-to-low order of the range, as for the annual cost of treating stage F0 disease and no sustained virologic response (SVR), indicates an inverse relationship between the input value and the ICER. Fibrosis is measured using the METAVIR stages (described in the Model Overview subsection of the Methods section). Drug therapy indicates sofosbuvir-ledipasvir.
Results of 10 000 Monte Carlo simulations (probabilistic sensitivity analysis) in which all input variables are varied simultaneously based on the listed ranges. The graph shows the percentage of simulations in which treating all patients (regardless of fibrosis stage) with sofosbuvir-ledipasvir for 8 or 12 weeks was considered cost-effective compared with treating only patients who reached fibrosis stages F3 and F4, depending on the willingness-to-pay (WTP) threshold. As the WTP increases (from left to right on the x-axis), the percentage of simulations resulting in treatment of all patients being cost-effective also increases. For example, for treatment at a WTP of $50 000 per quality-adjusted life-year (QALY), treating all patients is cost-effective in 74%; at a WTP of $150 000 per QALY, treating all patients is cost-effective in 96%. Fibrosis is measured using the METAVIR stages (described in the Model Overview subsection of the Methods section).
The figure shows total drug costs for treating 25%, 50%, 75%, and 100% of the 1.37 million treatment-naive patients (identified during the next 5 years) with combined sofosbuvir and ledipasvir for 8 or 12 weeks. The analyses are subcategorized by treating all patients (treatment regardless of fibrosis stage) and treating only patients who reached stages F3 and F4. Offsets in savings in lifetime health care costs (exclusive of drug costs) achieved by treating all patients vs treating those with stages F3 and F4 are also shown. Fibrosis is measured using the METAVIR stages (described in the Model Overview subsection of the Methods section).
eTable 1. METAVIR Fibrosis Score, Treatment Policies for Evaluation and Modeled Treatment Options
eTable 2. Model Comparison Using Sim/Sof and Sof/R Treatment Regimens
eTable 3. Distribution of Fibrosis Stages in Chronic Hepatitis C Population
eTable 4. Chronic Hepatitis C Natural History Disease Progression, Post-SVR Progression, and Regression and Mortality
eTable 5. Weekly Cost of Drugs for the Modeled Therapies
eTable 6. Chronic Hepatitis C Health Care Costs by Disease State
eTable 7. Other Health Care–Related Costs: Follow-up, Testing, and Management of Treatment
eTable 8. Frequency, by Week, of Follow-up/Testing/Management of Each Treatment Modality
eTable 9. Total Cost of Treatment-Associated Adverse Events
eTable 10. Health State Utilities in Chronic Hepatitis C
eTable 11. Utility Loss With Chronic Hepatitis C Treatment
eTable 12. SVR and Treatment Discontinuation Rates of All Modeled Therapies, Based on Meta-analyses of Clinical Trials
eTable 13. Base-Case Results: Treatment by Fibrosis Stage and Treat All vs Treat at F3/F4 Strategies, for All Treatment Options
eTable 14. Long-term Health Outcomes With Treatment at an Earlier Fibrosis Stage (or Treat All) vs Treating at a Later Fibrosis Stage (or Treating at F3/F4): Number of Advanced Liver Disease Cases per 100 000 Treated Patients
eTable 15. Budget Impact, in Total Drug and Health Care Costs, of Therapies: Treating All vs Treating at F3/F4
eTable 16. Sensitivity Analyses Results: 46% Reduction in Cost of Sofosbuvir/Ledipasvir
eTable 17. Scenario Analysis–Age 50: By Treat All vs Treat at F3/F4
eTable 18. Scenario Analysis–Age 50: By Fibrosis Stage
eTable 19. Sensitivity Analyses Results: 46% Reduction in Cost of Sim/Sof
eFigure 1. Natural History Markov Model Describing HCV Progression Following No Treatment, Treatment Failure, or Discontinuation
eFigure 2. Markov Model Showing Progression and Regression of CHC Following Successful Treatment (Post-SVR)
eFigure 3. Selected Nodes of the Tree Structure Associated With Each Policy
eFigure 4. Model Calibration and Validation: Cumulative Probability of Developing Cirrhosis
eFigure 5. Two-way Sensitivity Analysis on Cost of Sofosbuvir and Simeprevir
eFigure 6. Tornado Diagram: ICER of 3D, Treat All vs Treat at F3/F4
eFigure 7. Tornado Diagram: ICER of SOF/LDV (12 weeks), Treat All vs Treat at F3/F4
eFigure 8. Tornado Diagram: ICER of Sim/Sof, Treat All vs Treat at F3/F4
eFigure 9. Cost-effectiveness Acceptability Curve: All Treatment Options, Treating All vs Treating at F3/F4
eFigure 10. Cost-effectiveness Acceptability Curve: SOF/LDV (8/12 Weeks), Treatment by Fibrosis Stage
eFigure 11. Cost-effectiveness Acceptability Curve: SOF/LDV (12 Weeks), Treatment by Fibrosis Stage
eFigure 12. Cost-effectiveness Acceptability Curve: 3D, Treatment by Fibrosis Stage
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Chahal HS, Marseille EA, Tice JA, et al. Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population. JAMA Intern Med. 2016;176(1):65–73. doi:10.1001/jamainternmed.2015.6011
Novel treatments for hepatitis C virus (HCV) infection are highly efficacious but costly. Thus, many insurers cover therapy only in advanced fibrosis stages. The added health benefits and costs of early treatment are unknown.
To assess the cost-effectiveness of (1) treating all patients with HCV vs only those with advanced fibrosis and (2) treating each stage of fibrosis.
Design, Setting, and Participants
This study used a decision-analytic model for the treatment of HCV genotype 1. The model used a lifetime horizon and societal perspective and was representative of all US patients with HCV genotype 1 who had not received previous treatment. Comparisons in the model included antiviral treatment of all fibrosis stages (METAVIR [Meta-analysis of Histological Data in Virial Hepatitis] stages F0 [no fibrosis] to F4 [cirrhosis]) vs treatment of stages F3 (numerous septa without cirrhosis) and F4 only and by specific fibrosis stage. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015.
Six HCV therapy options (particularly combined sofosbuvir and ledipasvir therapy) or no treatment.
Main Outcomes and Measures
Cost and health outcomes were measured using total medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), calculated as the difference in costs between strategies divided by the difference in QALYs.
We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In the base-case analysis, among patients receiving 8 or 12 weeks of sofosbuvir-ledipasvir treatment, treating all fibrosis stages compared with treating stages F3 and F4 adds 0.73 QALYs and $28 899, for an ICER of $39 475 per QALY gained. Treating at stage F2 (portal fibrosis with rare septa) costs $19 833 per QALY gained vs waiting until stage F3; treating at stage F1 (portal fibrosis without septa), $81 165 per QALY gained compared with waiting until stage F2; and treating at stage F0, $187 065 per QALY gained compared with waiting until stage F1. Results for other regimens show a similar pattern. At base-case drug prices, treating 50% of all eligible US patients with HCV genotype 1 would cost $53 billion. In sensitivity analyses, the ICER for treating all stages vs treating stages F3 and F4 was most sensitive to cohort age, drug costs, utility values in stages F1 and F2, and percentage of patients eligible for 8-week therapy. Except for patients aged 70 years, the ICER remains less than $100 000 per QALY gained. A 46% reduction in cost of sofosbuvir-ledipasvir therapy decreases the ICER for treating at all fibrosis stages by 48%.
Conclusions and Relevance
In this simulated model, treating HCV infection at early stages of fibrosis appeared to improve health outcomes and to be cost-effective but incurred substantial aggregate costs. The findings may have implications for health care coverage policies and clinical decision making.
In the United States, prevalence of chronic hepatitis C virus (HCV) infection is estimated to be 3.2 million and is the leading cause of liver-related deaths, hepatocellular carcinoma, and liver transplant.1 The primary mode of acquisition is percutaneous exposure to blood, including sharing of injection paraphernalia and a historically contaminated blood supply, which led to a maximum prevalence in the cohort of individuals born from 1945 to 1965.2,3
Previously, treatment of HCV genotype 1 required as long as 48 weeks, with cure rates of 40% to 70% in patients with HCV monoinfection.1 With the introduction of HCV nucleotide analogue nonstructural protein 5A and B inhibitors, such as ledipasvir, ombitasvir, dasabuvir, and sofosbuvir, treatment duration has decreased for most patients to 12 weeks or less, with reduced toxic effects by the exclusion of interferon and often with the exclusion of ribavirin.4 The cure rate with the new therapies generally exceeds 90% and reaches 100% in some subgroups in clinical trials.4-7 The new drugs cost $1000 per day or more based on the wholesale acquisition price.8 Such costs are prohibitive for many patients and health care systems. Health care professionals may therefore resort to less effective drugs or wait for disease progression before initiating treatment.
Recent cost-effectiveness studies show that treatment with new therapies compared with older drugs is cost-effective for patients with HCV genotype 1, with a net cost per quality-adjusted life-year (QALY) ranging from $10 000 to $30 000.9,10 These studies, however, do not analyze the implications of treatment at various stages of liver fibrosis. Thus, the optimal timing of treatment is unknown.
Despite clinical practice guidelines recommending the new antiviral drugs, some payers require a higher level of fibrosis before authorizing treatment.11-15 Untreated chronic HCV infection can progress with increasing fibrosis, reaching cirrhosis in 20% to 30% of patients, and related liver complications, including premature death, in a smaller subset.16-18 Even with viral elimination, some patients may experience disease progression. Earlier treatment might provide important clinical and cost benefits. The objective of this study was to determine the most cost-effective liver fibrosis stage at which to initiate treatment with direct-acting antiviral agents in US treatment-naive patients with HCV genotype 1 infection and was based on commonly accepted thresholds. We present an analysis of a fixed-dose combination of sofosbuvir and ledipasvir (hereinafter, sofosbuvir-ledipasvir). Other regimens are analyzed in eTable 1 in the Supplement.
We constructed a decision-analytic model of HCV to examine the clinical outcomes and costs of treatment initiated at different disease stages. The disease states reflect progression through the 5 METAVIR (Meta-analysis of Histological Data in Viral Hepatitis) liver fibrosis stages (F0, no fibrosis; F1, portal fibrosis without septa; F2, portal fibrosis with rare septa; F3, numerous septa without cirrhosis; and F4, cirrhosis; eTable 1 in the Supplement) to advanced liver disease and regression of liver damage after successful treatment. We simulated a prevalent closed cohort (normalized to a single HCV-infected person) of US treatment-naive patients with HCV genotype 1 until death, tracking costs and QALYs discounted to the present. We validated the model by comparing predictions with the results of empirical natural history studies and prior models. The cost-effectiveness of initiating treatment earlier was calculated by running the model twice, with different start times for antiviral therapy. Additional details are provided below and in the eMethods and eTable 2 in the Supplement, and input variables are available in eTables 3 through 12 in the Supplement. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015. This project does not meet the criteria for human research and was not required to undergo evaluation by the University of California, San Francisco, Committee on Human Research.
The model considered therapies for HCV genotype 1 infection by regimens and doses approved by the US Food and Drug Administration.19 The goal of treatment is an undetectable serum level of HCV RNA 12 weeks after completion of therapy, also termed a sustained virologic response (SVR).20 The likelihood of an SVR and treatment discontinuation were determined by meta-analyses of phases 2 and 3 clinical trials stratified by the presence or absence of cirrhosis.15 Discontinuation of therapy was calculated as patient withdrawal from clinical trials for any reason, with an intent-to-treat approach. The discontinuation and SVR rates were subjected to sensitivity analyses.
We present results for sofosbuvir-ledipasvir treatment for 8 or 12 weeks. Duration of sofosbuvir-ledipasvir treatment can be 8 weeks if the baseline viral load is less than 6 million IU/mL with no cirrhosis. Thus 67% of the patients with fibrosis stages F0 to F3 received 8 weeks of treatment and 33% received 12 weeks; all patients with stage F4 received 12 weeks of treatment.15 These proportions were varied in sensitivity analyses. We modeled 6 other HCV treatment regimens (eTable 1 in the Supplement).
Chronic HCV progression through increasingly severe liver fibrosis is classified with fibrosis scores F0 to F4 (eTable 1 and eFigure 1 in the Supplement). We used these scores and major liver complications to define Markov model disease states (eFigures 1-3 in the Supplement). Transition probabilities between states are based on our review of the published literature. We validated this natural history model by demonstrating correspondence with empirical data on cirrhosis incidence and prior modeling (eTable 2 and eFigure 4 in the Supplement).21,22 The model starts with a prevalent cohort in which the patients are distributed across the 5 stages of fibrosis according to proportions observed in the US population with HCV infection.23
First, we compared treating all patients with treating patients who have disease progression to stage F3 or stage F4, the historical standard at which to consider treatment.11-15 Second, we compared treatment by fibrosis stage to assess finer distinctions. We considered 6 timing options. The first option treats all patients with HCV. The second option omits treatment of patients at stage F0 but includes those with stages F1 to F4. In this option, the patients with stage F0 disease must progress to stage F1 to be treated. Each successive option (third through fifth) adds 1 fibrosis stage. In the sixth option, for comparison, no treatment is provided.
Achieving SVR slows progression and liver complications by more than 90%.24,25 In addition, some patients experience regression of liver fibrosis after therapy.25-30 Our model portrays slowed progression via lowered transition probabilities and regression via new transition paths and values.
We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In our base-case scenario, we portray a cohort of 60-year-old patients (birth year, 1955) weighing 75 kg who are already aware of their HCV infection. The characteristics of patients in the analytic cohort were specified based on data from the 2010 National Health and Nutrition Examination Survey, indicating that 70% of HCV-infected persons were born from 1945 to 1965.31 As this cohort ages, the incidence of complicated liver conditions will increase.32-34 Other age cohorts ranging from 20 to 70 years are used for scenario analyses. The model does not distinguish patients on the basis of viral concentration, sex, or race, although these factors may affect treatment outcomes.35
Mortality for patients with stages F3 and F4 and no SVR is 2.37 times the age-specific background rates from the 2009 US life tables and based on evidence from a prospective cohort study.36,37 Individuals with decompensated cirrhosis and hepatocellular carcinoma have high rates of mortality.25,38 Patients who receive a liver transplant can die of transplant-related complications..25,38 Patients with stages F3 and F4 who achieve SVR have mortality 1.4 times the background population rate based on a meta-analysis of 8 HCV follow-up studies and input from HCV experts.39 Mortality for patients with stages F0 to F2 was assumed to be equal to the rate for the background population.
We adopted a societal perspective, including all direct medical costs for HCV management and therapy. Our intent is to portray societal costs, as approximated by the cost of care sources on which we rely. For unit costs based on reimbursement, the omission of small patient contributions slightly underestimates total costs (a synopsis of each study is provided in the eMethods in the Supplement). Owing to the imprecision of unit cost inputs and the greater uncertainty introduced by estimated rates of patients under current care and use of health care resources, we examined wide ranges of costs in our sensitivity analyses. Costs are in US dollars adjusted to 2014 using the medical component of the US Consumer Price Index.40
Costs of drugs were determined using the wholesale acquisition price from Red Book Online8 in February 2015 and varied widely in sensitivity analyses. In a scenario analysis, drug costs were reduced by 46%, reflecting recent price reductions announced by Gilead Sciences, Inc.41
Annual health care costs associated with a diagnosis of chronic HCV were determined by adapting published empirical data to our cohort of individuals with known chronic HCV.42-44 Pre-SVR costs ($810 for stages F0-F2, $2150 for stage F3, and $2575 for stage F4) were based on costs from a managed care database that were adjusted for the proportion of known chronic HCV cases estimated to receive health care.44,45 Post-SVR costs for stages F0 to F4 were estimated at 50% lower by taking the midpoint of 2 pre-SVR vs post-SVR cost ratios derived from medical care payment databases in the United States and the United Kingdom.42,46 The model accounted for costs of HCV genotyping, fibrosis staging, and therapy monitoring, including clinic visits, blood and hepatic tests, and HCV RNA quantification. These costs were determined using the Medicare reimbursement schedule and published literature.47-49 The frequency of monitoring visits and tests was based on HCV treatment guidelines and clinical judgment.11,50
The costs of management of adverse effects were estimated using the frequency of common and serious adverse effects (determined using regimen-specific meta-analysis of clinical trials). We applied the published costs of similar adverse events.15,51
The model incorporates health state utility values by fibrosis stage with and without SVR and transient loss of utility during treatment. Utility values determined from a literature review indicate a utility score of 0.76 in stage F4, 0.79 in stage F3, 0.92 in stage F2, and 0.98 in stages F1 and F0. The SVR raises utility scores to 0.83 in stage F4, 0.86 in stage F3, 0.93 in stage F2, and 1.00 in stages F1 and F0. The utility penalty of treatment was modeled using utility weights of common and serious adverse events, weighted by the frequency of similar events observed in clinical trials.11,50
The model produces discounted lifetime QALYs and direct medical costs for each strategy. It then calculates incremental cost-effectiveness ratios (ICERs) as the ratio of the difference in costs between treatment strategies divided by the difference in QALYs. A policy producing an ICER of $150 000 per QALY or less was considered cost-effective; a policy producing an ICER of $50 000 per QALY was considered highly cost-effective. The model was constructed using TreeAge Pro 2014,52 and Excel software53 was used to analyze the data.
We conducted 1-way sensitivity analysis on each variable to determine effects on the ICER and 2-way sensitivity analysis on selected variables. The aggregate uncertainty from multiple inputs was quantified via probabilistic sensitivity analysis using uniform distributions. The range in input values was determined by 95% CIs from primary literature sources or meta-analyses. When such data were unavailable, we varied the base-case value from 50% to 150%.
We present results only for 8 and 12 weeks of sofosbuvir-ledipasvir treatment. Results for other regimens are similar and are presented in eTable 13 in the Supplement.
For sofosbuvir-ledipasvir treatment for 8 and 12 weeks, treating all stages of fibrosis compared with treating stages F3 and F4 produced a QALY gain of 0.73 (Table) owing to a higher health state utility value after SVR in early fibrosis (69% of the QALY benefit) and to averted liver complications and death (Figure 1 and eTable 14 in the Supplement; 31% of the QALY benefit). Treating all stages of fibrosis compared with treating stages F3 and F4 increases drug costs by $33 721. An SVR lowers lifetime health care costs by about $5000, resulting in net increased costs of $28 899 for sofosbuvir-ledipasvir treatment (Table and eTable 15 in the Supplement). Treating all stages of fibrosis with sofosbuvir-ledipasvir compared with treating stages F3 and F4 only has net costs per QALY gained of $39 475 (Table).
Sofosbuvir-ledipasvir treatment at earlier stages of fibrosis results in a gain in QALYs (Table). Treating stage F3 increases QALYs by 2.27 compared with treating stage F4; treating stage F2 compared with stage F3 has a QALY gain of 0.55; treating stage F1 compared with stage F2 has a QALY gain of 0.14; and treating stage F0 compared with stage F1 has a QALY gain of 0.03. These QALY gains reflect higher health state utility values in early fibrosis and prevention of advanced liver complications, including premature death.
Treating stage F3 has a $14 798 higher cost compared with waiting until stage F4 (Table). Incremental costs decrease with earlier fibrosis stage comparisons. The cost for treating stage F2 compared with stage F3 is $11 007; for stage F1 compared with stage F2, $11 682; and for stage F0 compared with stage F1, $6210. The higher net costs for initiating treatment in earlier fibrosis stages are driven by the cost of drugs for individuals treated only under broader treatment criteria, which are partially offset by averted costs of care for chronic HCV and advanced liver disease. As shown in the Table, the net cost per QALY gained by sofosbuvir-ledipasvir treatment is $11 252 for treating stage F4 compared with no treatment, $6522 for treating stage F3 compared with stage F4, $19 833 for treating stage F2 compared with stage F3, $81 165 for treating stage F1 compared with stage F2, and $187 065 for treating stage F0 compared with stage F1.
The inputs to which the ICER for treating all fibrosis stages compared with treating stages F3 and F4 are most sensitive are cohort age and drug cost, with much lower sensitivity to discount rate, utility values in stages F1 and F2 (without SVR), and proportion of patients with disease regression to healthier fibrosis stages (Figure 2). For age, use of a cohort age of 50 years (vs 60 in the base-case analysis) produced the more favorable ICER or $25 443 per QALY gained. At 20 years of age, the ICER is $999 per QALY gained owing to a high likelihood of progression without SVR. At 70 years of age, the ICER is $118 889 per QALY gained owing to the reduced likelihood of untreated chronic HCV causing death. For age analyses, age-dependent fibrosis progression probabilities were used with base-case fibrosis prevalence (eTable 4 in the Supplement). For drug prices, we referenced a recent announcement by Gilead Sciences, Inc (the manufacturer of sofosbuvir-ledipasvir), of a mean price discount to 46%.41 This reduction lowers the cost per QALY gained to $18 807 for treating all stages vs treating stages F3 and F4; similar trends are seen for analysis by fibrosis stage (eTable 16 in the Supplement). Sensitivity analyses on other regimens are available in eTables 17 to 19 and eFigures 5 to 8 in the Supplement.
Monte Carlo simulations are shown in Figure 3 as the likelihood of a timing option to be considered cost-effective at different willingness-to-pay thresholds. At a willingness-to-pay threshold of $50 000 per QALY, treating all stages is cost-effective in 74% of simulations. This proportion rises to 96% at a willingness-to-pay threshold of $150 000 per QALY. Probabilistic sensitivity analyses for other regimens are available in eTable 13 and eFigures 9 to 12 in the Supplement.
A prior analysis determined 1.32 million treatment-naive persons in the United States would be aware of their HCV infection status by 2014, with an additional 510 000 identified by 2019, for a total of 1.83 million patients.9,54 Assuming that 75% of these patients have HCV genotype 1 (1.37 million), we determined the total cost of drugs required to treat 25%, 50%, 75%, and 100% of these patients during the next 5 years in our budget impact analysis (full details are available in eTable 15 in the Supplement). Figure 4 shows the drug costs of sofosbuvir-ledipasvir treatment. If 50% of eligible patients with HCV genotype 1 (ie, 686 000 patients) are treated regardless of fibrosis stage during the next 5 years, the estimated unadjusted treatment costs are $53 billion. With the 46% reduction in drug prices discussed above, the cost decreases to $29 billion. Alternatively, if 50% of these patients are treated at stages F3 and F4 during the next 5 years, the costs are $30 billion with sofosbuvir-ledipasvir treatment and $16 billion with a 46% decrease in drug prices. Figure 4 depicts the savings in lifetime health care costs exclusive of drug costs gained by treating all stages compared with treating stages F3 and F4, which is $3.3 billion with sofosbuvir-ledipasvir treatment.
The new HCV interferon-free therapies offer potentially huge individual and societal benefits but at a large cost. Health plans and health systems concerned about costs frequently require evidence of advanced liver fibrosis before authorizing the new therapies.11-14 We herein examined the health impact, cost, and cost-effectiveness of earlier treatment.
Although early treatment with sofosbuvir-ledipasvir is expensive, the net cost is substantially lower owing to savings in medical care and the likelihood of later treatment with a delayed treatment policy. Furthermore, we found substantial short- and long-term health gains. Thus, for sofosbuvir-ledipasvir treatment, treating patients at all fibrosis stages compared with waiting for advanced fibrosis is cost-effective (<$50 000 per QALY gained). A detailed analysis of timing of therapy by fibrosis stage shows that treating the disease at as early as stage F1 is cost-effective (ICERs of $50 000-$150 000 per QALY gained) and less than $50 000 per QALY gained when treatment is initiated at stage F2 vs stage F3. The ICER is lower when treatment is initiated at stage F3 compared with waiting for cirrhosis (stage F4). Results are similar for treatment with other new antiviral regimens.
Although the new therapies promise a high SVR, their long-term effects on clinical outcomes are not yet known. Sustained virologic response, a surrogate marker, may not lead to better long-term health outcomes with new treatments. Past studies with older regimens, however, have shown that achieving SVR can result in positive, long-term clinical benefits for patients.55-60 A 2011 systematic review61 found that achieving SVR can reduce liver-related mortality, incidence of hepatocellular carcinoma, and decompensation and foster regression of fibrosis and cirrhosis.
For budgetary considerations, if only 50% of eligible patients with HCV genotype 1 were to be treated with sofosbuvir-ledipasvir during the next 5 years, the cost of drugs in the United States would be $53 billion at current prices. Many payers negotiate prices, as has been seen with exclusivity deals with drug manufacturers.62-65 If a mean 46% reduction in drug prices occurred, the cost of treating 50% of patients with HCV genotype 1 during the next 5 years could be as high as $29 billion, partly offset by $3 billion in savings in the management of chronic HCV and advanced liver disease.
Our model has several assumptions and limitations. First, we assumed that patients who achieve SVR have no risk for reinfection with HCV, thus tending to overestimate cost-effectiveness. Second, the model does not consider benefits for patients who receive therapy but do not achieve SVR. Third, the model does not consider the reduction in HCV transmission to seronegative individuals as a consequence of successful therapy. These latter 2 assumptions would underestimate the societal and economic benefits of treatment.
Fourth, the model did not consider extended treatment for patients with slow responses or the repeated treatment of patients who do not achieve SVR. Additional therapy would add to the costs of treatment and possibly improve efficacy. Fifth, the model uses aggregated annualized transition probabilities to simulate progression from one clinical state to the next, adjusted for age but not for other individual traits. This approach focuses the overall simulation on population-level natural history. Individual heterogeneity in chronic hepatitis C virus progression is represented by varying progression rates in sensitivity analyses. Sixth, the analysis took into account only direct medical costs, omitting potential gains in productivity. Seventh, the model considered only patients monoinfected with HCV, excluding coinfections with hepatitis B virus and human immunodeficiency virus.
Eighth, we used meta-analyses of clinical trials to determine SVR and discontinuation rates. The point estimates may differ from those of published phases 2 and 3 trials. We used an intent-to-treat analysis to determine discontinuation rates, and our values may therefore be higher than other estimates. Point estimates from clinical trials may not represent real-world results, which can be lower for SVR and higher for discontinuation rates.66,67 However, our meta-analysis 95% CIs are wide, which allowed us to test SVRs across a wide range in sensitivity analyses.
Ninth, we had imperfect cost data. Costs for HCV care, treatment, and adverse effects are sparsely reported. We attempted to portray societal costs, as measured by the source studies. Our priority in selecting cost sources was addressing a scope of care closely aligned with our model categories. Owing to limited data, we never had to choose between multiple sources for the same data point; therefore, we had to rely on the relevant source’s costing methods (eMethods in the Supplement). However, the most challenging aspect of costing was extrapolating from very good costing data for the identified population receiving care (defined by ≥2 HCV codes in a year, thus likely omitting clinically healthy individuals with HCV) to the broader population receiving care and the even larger infected population. The future cost of new HCV therapy is also a major unknown. Because of these various uncertainties, we carefully explored the implications of different cost estimates for the cost-effectiveness outcomes via sensitivity analyses of the cost inputs and of the discount rate that affects the evaluation of future expected costs.
Finally, this model did not simulate changing drug costs over time and how that would affect the cost-effectiveness of early treatment. Market or political forces may result in significantly decreased drug costs in the next several years, and a subset of patients, given the slow progression of HCV, may be treated at a lower cost without a risk for serious clinical progression. These possibilities would make early treatment less cost-effective. However, as in the case of therapies for multiple sclerosis and insulin, the cost of drugs may increase despite being on the market for a number of years and despite new entrants.68,69
This analysis suggests that treatment with new HCV drugs is cost-effective when started with any evidence of fibrosis (stage F1). Because of the investment required for these drugs, budgetary constraints on health systems typically restrict access to insured patients until they experience higher levels of liver damage or failure of older treatments, and uninsured patients would be unable to receive treatment without patient assistance programs. A reduction in the price will improve cost-effectiveness and increase affordability and access.
Corresponding Author: James G. Kahn, MD, MPH, Institute for Health Policy Studies, Global Health Economics Consortium, University of California, San Francisco, 3333 California St, Ste 265, PO Box 0936, San Francisco, CA 94118 (firstname.lastname@example.org).
Accepted for Publication: September 7, 2015.
Published Online: November 23, 2015. doi:10.1001/jamainternmed.2015.6011.
Author Contributions: Drs Chahal and Marseille had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: All authors.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Chahal, Kahn.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Chahal, Kahn.
Obtained funding: Pearson, Kahn.
Administrative, technical, or material support: Chahal, Marseille, Tice, Ollendorf, Kahn.
Study supervision: Pearson, Ollendorf, Kahn.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by the Blue Shield of California Foundation and the California Health Care Foundation (through the Institute for Clinical and Economic Review); by the Clinical and Translational Sciences Institute, University of California, San Francisco; and by grant DA15612 from the National Institute on Drug Abuse, National Institutes of Health.
Role of the Funder/Sponsor: The Institute for Clinical and Economic Review collaborated on the design, conduct, and reporting of this study. The other funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Additional Contributions: Karen Shore, PhD, Institute for Clinical and Economic Review, coordinated this effort. Jed Weissberg, MD, Institute for Clinical and Economic Review, and Marion Peters, MD, University of California, San Francisco, provided guidance on clinical issues. They received no compensation for these roles.

domain: literature


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Between the more than 35,000 victims that are already accounted for the earthquake that shook Turkey and Syria it’s found a female basketball player, whose death was confirmed by the Turkish Basketball Federation in social networks.
Nilay Aydogannational player ofe Cankaya University, one of the teams in the Women’s Basketball Super League, was found lifeless among the ruins left by the 7.8 magnitude earthquake that occurred last week.
“It is with deep sadness that we learn that Nilay Aydoğanthe national player of Çankaya University, one of the teams in the ING Women’s Basketball Super League, lost his life in the earthquake disaster. May God have mercy on the deceased, we express our condolences to his family, relatives and basketball community,” the federation published on its official Twitter account.
“Unfortunately, we have received the news of the death of our national basketball player Nilay Aydogan, who was under the rubble in Malatya after the earthquake disaster. May God have mercy on our athlete. My condolences to his family and our community, ”added former player Hidayet Türkoğlu, current adviser to the president of Turkey, and who played 15 NBA seasons, with teams like the Orlando Magic and the LA Clippers.
You may also be interested in:
Messi pronounces on the earthquake in Turkey and Syria asking for help through donations
Many athletes are missing and others have lost their lives due to the earthquake in Turkey and Syria
Turkish footballer will auction shirt signed by Cristiano Ronaldo to raise funds and support the victims of the earthquake

domain: news


text:
Daily cleaning, installation of cabin HEPA filters on flights from New Hampshire to Fairbanks
KAYAK is a travel search engine. That means we look across the web to find the best prices we can find for our users. With over 2 billion flight queries processed yearly, we are able to display a variety of prices and options on flights from New Hampshire to Fairbanks.
KAYAK’s flight Price Forecast tool uses historical data to determine whether the price for a flight to Fairbanks from New Hampshire is likely to change within 7 days, so travelers know whether to wait or book now.
Hacker Fares allow you to combine one-way tickets in order to save you money over a traditional round-trip ticket. You could then fly to Fairbanks with an airline and back to New Hampshire with another airline.
Sometimes travel dates aren't set in stone. If your preferred travel dates have some wiggle room, flexible dates will show you all the options when flying to Fairbanks from New Hampshire up to 3 days before/after your preferred dates. You can then pick the flights that suit you best.
Scores according to KAYAK customer reviews
Pros: "Crew excellent!"
Cons: "The flight was crowded!"
Pros: "the seats are ok, but service was awful"
Cons: "the fight attendants attitude"
Pros: "Wonderful crew, Shefan provided excellent service. This was my first time flying first class and my expectations were exceeded."
Pros: "The crew was great!"
Cons: "The American Airlines staff seemed like they were in a bad mood, not very friendly. Nothing outrageous though."
Pros: "Plane was new"
Cons: "Extremely cramped, surly flight attendants, and terrible food."
Cons: "ages they don’t came"
Pros: "On time despite ground hold"
Cons: "Having flight attendants board with 4 bags and taking most storage"
Pros: "Everyone was nice and it went smoothly!"
Pros: "great trip and crew"
Pros: "Robbie and Carlos were exceptional. The gate agents were exceedingly rude and I will be filing a formal complaint."
Cons: "Gate agents"
Cons: "A delay in take off"
Pros: "Included drink and pretzels. Free carry on and seat."
Cons: "First of all, the line to check in was extremely long and the employees were rude. When I put my bags through the check out they stopped me and said I had to throw away my cologne because it was too large. However, on the Spirit Airlines I had no problem whatsoever. Will never fly with American Airlines again!"
Pros: "Crew was very friendly."
Cons: "Seatbelt was far too short for someone plus sized."
Pros: "nothing good nothing bad, just ok."
Cons: "737 might as well be a cattle cart..."
Cons: "Pésimo perdí mi vuelo de conexión porque el vuelo estaba retrasado 1hora y media"
Pros: "I appreciated that they were interested in the general welfare of the whole craft in the midst of storms."
Cons: "The long delays, the cancellation near midnight, the long lines to what I thought was going to be some type of reimbursement for all the inconvenience at now having to find lodging for the evening, spend an entire day back at the airport, and transport myself from the NEW airport they made available for me from the original airport I had chosen. Absolutely NO compensation or reimbursement due to "weather." While I understand they can't control the weather, this is literally one of the greatest elements in their company. They should have provisions FOR it. Running out of airlines I could trust and rely on, and thought American would deliver. But No, not even this one. Extremely disappointed and staying away from AA."
Pros: "Hostesses were great. And pilot landed safely"
Cons: "Stayed too long on the jet way. No available gate"
Cons: "Plane was delayed all day and when we finally boarded we were told it was due to an engine problem!! Not good!!"
Pros: "The crew was ok"
Cons: "It was 1:45 late . It was American Airline, we had extra passenger on board. It took them long time to figure it out. I was so rush, I barely made the connectiog flight and I only had carry on luggage."
Cons: "No charging outlets on seat ( this something pretty standard on most planes now). The flight was delayed because of the plane had a problem with the tire. The passenger next to me had a broken tray with tape around it. The bathroom had a broken sink."
Pros: "The crew was very nice and helpful"
Cons: "The new AA rule about not being able to bring any carry on. Next we won’t be able to get a coat or a purse on. They making it harder and harder to fly with them."
Cons: "The plane had a problem. No mechanic in Huntington. Poor communication from American to the crew in Huntington. Connecting flight missed. Had to wait for standby. Luggage ruined by broken wheel and chunk missing where the wheel had been."
Pros: "On time. Comfortable seat. Courteous crew. Easy transfer."
Pros: "The process of boarding, baggage check, etc"
Pros: "that i finally came home"
Pros: "The food was fabulous!"
Pros: "Comfortable and food was great So was the service"
Cons: "No complaints"
Pros: "Plane was newer, had TV/interactive entertainment centers in the back of all the headrests. Crew on board was polite, cheerful, & friendly. Excellent service from the on board staff. Plane had WiFi & plug ins to charge/use items"
Cons: "Almost missed our flight home because American Airlines lost/screwed up our round trip tickets. We were not able to check in quickly or efficiently, & service was appalling, staff was either poorly trained or uneducated. We tried using the kiosk to check in, to avoid the long line. That didn’t work, so we found help. They told us to retry, wasting time, finding out what we had already informed them of. They passed us off to another gate/service counter, who’s line was closed off. So we had to duck the divider. They then redirected us to the kiosks after we informed them it couldn’t find our reservations, so they tried (wasted more time) failed & sent us back to the line we were already in. After that wait we talked to the person at the desk, who also couldn’t find our reservation. They said “I don’t know it’s not in here, what do you want me to do?” I had to tell them to call a manager to get it fixed, we were going to miss our flight. They called & found the problem, then at 3:15ish reissued us tickets for our 3:30 return flight. Still had to get through TSA! There was also NO phone call to hold the plane or to arrange an airport people mover cart. They talked with the TSA agent who told us to go 2 checkpoints down where the line was shorter. So the American Airlines attendant told us to run. Turns out in Miami Airport there is almost a quarter mile of poorly labeled counter space. Went through TSA having 12 min before our reassigned flight left. TSA was helpful, & did their best to get us through quickly. We were then informed we were near gate 22 & our gate was 3, so rushing down another concourse we barely made our return flight home. Where we were forced to check our carry-on. My girlfriend was crying, we were sweaty (from hustling when we never should of had too), hungry, embarrassed, enraged, & not sitting together for our 3+ hr flight! Unacceptable after a 4hr drive to the airport in traffic & returning the rental car at 1:40!"
Cons: "Just never enough leg room❗"
Cons: "The entire flight. Bumbing, disabled seating was not provided as promised, neither was off boarding to baggage area."
Pros: "Can't think of anything good"
Cons: "SEE: Customer Relations request #1-249830721"
Pros: "Smooth flight and on time."
Cons: "Small plane. Even small carry-ons had to be gate checked"
Pros: "good price."
Cons: "La Guardia Airport is a kind of messy. Some people in AA are rude, specially ground personnel."
Pros: "The meals were pretty decent and I loved that I was given chocolates during the flight."
Cons: "Food was the worst of any plane I've ever taken"
Pros: "Great service and Manchester is way better than flying to Boston"
Cons: "Your rating app doesn't have a N/A option"
Cons: "Carry on luggage does not fit for the whole plane. We had to check and wait for it to be unloaded in the jetway."
Cons: "2 days late"
Cons: "No entertainment"
Pros: "I like it! Thank you, kayak"
Pros: "The boarding process was efficient and the staff was friendly."
Cons: "The plane was antiquated and the seat space and leg room were minimal."
Pros: "It was last minute booking, I was balky for the price and the overall experience was comfortable."
Cons: "They forgot to get my coffee but it's nothing major plus we were about to land in 30 mins or so"
Pros: "Once in flight, it was a standard smooth ride to Tokyo."
Cons: "Late announcement of flight delay. Cost me 4 extra hours at LAX, doing nothing. Then, flight delayed again for 30 minutes prior to boarding...and yet AGAIN while on the plane...because of a water shortage. What had the crew been doing in between flights?? Lastly, these delays caused the plane to arrive in Tokyo at 12:30AM (originally it was 10:30PM). All transportations options were closed. I had to take a $90 USD taxi fare into the city. JAL or AA should have given travel vouchers to everyone who needed them. BAD SERVICE, BAD COMMUNICATIONS, BAD RATING."
Pros: "Boarding was good"
Cons: "No drinks or snacks. We were told the hour and a half flight was too short for service. Really??? First class got their drinks."
Airlines flying from New Hampshire to Fairbanks have enacted additional safety measures and adjusted policies to better accommodate travelers. Policies vary by airline.
Daily cleaning, installation of cabin HEPA filters on flights from New Hampshire to Fairbanks
Masks required on board, masks provided on flights from New Hampshire to Fairbanks
Social distancing seating
Middle seats unavailable to book on flights from New Hampshire to Fairbanks
Testing for antibodies, testing for symptoms for flights from New Hampshire to Fairbanks
Waiving of change fees. Search flexible flights from New Hampshire to Fairbanks

domain: travel


text:
We've spoken with lots of pet parents who have actually found out about animal insurance however who have actually stayed clear of looking at it in any information. More often than not this is because they just weren't given the completely tale about exactly how it worked or why. We're going to take a look at six misconceptions that we hear regularly.
Misconception # 1: You cannot get pet insurance coverage for an older pet.
Reality: Just due to the fact that your animal isn't really a puppy or kitten any longer does not suggest you cannot insure him! Pet insurance coverage business will generally issue a new policy to pets as much as 8 or 10 years old, often older if you get your veterinarian to do a wellness appointment. Your premium might be higher than on a more youthful animal and some pre-existing conditions might be left out. Naturally the best thing is to enlist your pet when he's young and healthy so you can stay clear of pre-existing conditions.
Myth # 2: Since my animal is well now there's no point buying pet insurance coverage. Truth: Precisely because your animal has actually been well indicates that now is in fact the best time to purchase animal insurance coverage because your animal probably has no pre-existing conditions. Keep in mind, pet insurance coverage is the one thing you cannot get when you require it the most! Why wait till after your animal becomes sick and you wish you had pet insurance coverage? Why wait until your animal gets a pre-existing condition that animal insurance will not cover? No matter how well your pet is today, there is always an opportunity that your pet can fall unwell or get hurt. Pet insurance is designed to safeguard you against the unknown however you need to plan ahead of time.
Myth # 3: I need to wait until my pet's present clinical condition has actually resolved itself before getting pet insurance coverage.
Truth: Your pet's current condition could be considered a short-term pre-existing condition however that doesn't indicate you can not get pet insurance coverage to cover everything else. For example, if your pet recently cut its leg terribly and is still undergoing treatment, conditions associating with this cut could be omitted for your first year of insurance coverage however if everything resolves and clears up you will generally be qualified for complete coverage once again in the 2nd and succeeding years. The best thing to do is to talk with the pet insurance coverage company and learn for sure.
Myth # 4: Pet insurance coverage is just worthwhile if you have an extremely active pet or an older pet that is most likely to develop issues.
Truth: While it holds true that an older animal is most likely to require a greater level of medical attention than a younger animal that doesn't mean that more youthful pets can not get sick or hurt. And just due to the fact that an animal isn't really highly active doesn't suggest it can't get sick. The truth is that, just as in humans, ailment can strike even the healthiest pet and having pet insurance indicates you'll constantly have the ability to get the very best look after your animal, not exactly what you can afford.
For example, our company recently handled a claim for $3,565 for a 3-month old Akita that was attacked with the fence by a neighbor's pet. And the current pet food remember reminds us all that sometimes things come completely out of the blue.
Myth # 5: Pet insurance simply doesn't pay. Fact: Sadly, there is (or was) more fact to this than not. For the lengthiest time most pet owners only had the option of picking from from a couple of pet insurance coverage plans. These strategies frequently capped claim payouts at ridiculously reduced levels that left pet parents significantly out of pocket. But today pet moms and dads have more selections and numerous strategies now pay based upon the actual veterinarian bill which means you get much more back at claim time. Just ensure you ask exactly how claims are reimbursed.
Misconception # 6: I do not need animal insurance coverage because I can conserve a small amount each month to pay for anything that could occur.
Truth: Setting aside a small amount each month can definitely help. However there are 2 downsides to consider: one is that many of us find it tough to save something every month, the other is that you may need to wait a very long time before you've built up enough cost savings to spend for a major ailment or accident. For instance, if you save $25 each month at 4 % interest (paid monthly) after 5 years you will have saved $1,657. Your cat or dog is not going to wait till you've got adequate money saved around get sick! That very same $25 could get you instead.
We hope that these answers will help you make smarter decision about whether pet insurance coverage is right for you and your pet.

domain: pet


- Ostrow Off The Record - http://blogs.denverpost.com/ostrow -
Tim Gill Center for Public Media, result of $1.3 million gift to Rocky Mountain PBS
Posted By Joanne Ostrow On July 17, 2012 @ 11:58 am In Celebrities,Local Media,Social Media,Technology,Television & Media News,TV News | No Comments
The idea is to create the Tim Gill Center for Public Media , which will produce “cross-platform content for public media.”
Some 21 media entities will participate, increasing the profile of public media in Colorado and giving area college students access to equipment and training. University of Colorado-Colorado Springs, Colorado College, KRCC 91.5 FM, Pikes Peak Community College and RMCommunity
Radio are among those involved.
Doug Price, head of RMPBS Doug Price, head of RMPBS , said the investment is the largest private gift in the station’s 56-year history. The Gill Foundation previously consolidated its physical location to Denver offices.
Article printed from Ostrow Off The Record: http://blogs.denverpost.com/ostrow
URL to article: http://blogs.denverpost.com/ostrow/2012/07/17/tim-gill-center-for-public-media-gift-to-rmpbs/9544/
URLs in this post:
 Image: http://blogs.denverpost.com/ostrow/2012/07/17/tim-gill-center-for-public-media-gift-to-rmpbs/9544/gill-foundation-building-3/
 Tim Gill’s Gill Foundation: http://www.gillfoundation.org/
 Rocky Mountain PBS: http://www.rmpbs.org/
 Tim Gill Center for Public Media: http://www.rmpbs.org/TimGillCenter/


This powerful stock music track unites all the bikers of the world to explore and enjoy natural beauties and wonders! This one is a punchy hip hop, rock, composition featuring overdrive alternative guitar riff, acoustic guitars, vocal chops, 808 bass, hip-hop beat and urban style elements. It is perfect for advertising, action, military, martial arts, urban, sport videos, modern commercials and promos, youtube contents, explainer videos, vlogs and more projects. Thank you.
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text:
How do you feel if I say that "CAKE MATTERS"? There are different ways of going around dull and dark days and one of them is to indulge and sweeten yourself up by buying one of the cakes you most fancy or.. as a proper therapy to make them yourself too.
Let me introduce you to a treat made of a generous layer of silky lemony creme patisserie in between two crunchy biscuits with the nutty bite of hazelnuts for a touch of luxury.
It is half term holiday and I need to keep my children busy: baking biscuits, making pasta, helping make risotto, laying the table, loading the dishwasher.. soon they will be doing the hoovering too! All good manual skills which seem to have no importance these days; I think they are highly educational.
Today we baked. Please do try these biscuits, they are simple to make and they resemble in taste the patisserie you would buy in a proper bakery.
For the pastry:
130 g self raising flour
3 tbsp oil
1 tbsp vanilla extract
3 tbsp icing sugar
For the custard:
300 ml full fat milk
2 tbsp flour
1 lemon organic or unwaxed
3 egg yolks
80 g sugar
a dash of brandy or rum
to finish off:
- Prep Time : 45 minutes
- Cook Time : 20 minutes
On your worktop put the flour, egg, vanilla extract, sugar and oil. Combine the ingredients well with a fork
Now with your hands shape it into a smooth ball. If it feels sticky wrap it in cling film and put it in the fridge for 30 minutes
With a rolling pin flatten the pastry about 5 mm thick and with a pastry cutter make about 30 small circles
Line them up well on a baking tray over a piece of baking paper or over a silicone baking sheet (I recommend it! It is so handy to have in the kitchen!)
Cook at 170C for about 10 minutes or until slightly golden.
In the meantime make the custard by whipping the yolks with the sugar. They should look pale and creamy. Now add the flour and stir it well in.
Wash and dry the lemon and peel the zest with a knife. Bring the milk to the boil with the lemon zest. Take the zest out and slowly pour the milk over the egg mixture whilst stirring all the time
Put it over a source of heat and cook gently whilst stirring all the time until the sauce has thickened (this will take about 10 minutes). Add the liquor during the last couple of minutes of cooking.
Toast the chopped nuts in a pan for a few minutes. Now let's assemble the biscuits: with a syringe or with a teaspoon put some cooled down custard over one biscuit
Cover with another biscuit just like a sandwich and roll it into the nuts
Finish off with a sprinkle of icing sugar

domain: hobby


Ramadan events are in full swing
Traditional Ramadan events organized every year by Denizli Metropolitan Municipality continue with beautiful program shows. Turkish Folk Music and Sufi music concerts together with Semazen shows took great acclaim from the citizens in İmcilipınar and Adalet Park.
Denizli Metropolitan Municipality organizes different shows every evening during Ramadan activities in order to meet the citizens with the old month of Ramadan. Various programs organized in İncilipınar and Adalet Park have a great interest of people. Artists of Denizli Metropolitan Municipality Conservatory took a great acclaim with the Turkish folk music and Sufi music concerts and the Semazen shows. At the concert held in Adalet Park, the artist Hakan Eyiden of Denizli Metropolitan Municipality Conservatory gave about 2 hours of tasaavvuf music concert. The whirling dervishes team of Denizli Metropolitan Municipality Conservatory also took the stage. In order to keep alive the spirit of Ramadan Denizli Metropolitan Municipality organizes different activities every day for thousands of people enjoyment. Deputy Secretary General of Denizli Metropolitan Municipality Mustafa Gökoğlan and Director of the Department of Cultural and Social Affairs of Denizli Metropolitan Municipality Hüdaverdi Otaklı presented a plaque to artists to commemorate the night.
The future program
Within the program prepared for Thursday, July 3 Denizli Metropolitan Municipality is organizing the Sufism concert of the artist Yunus Çoban and poetry recital in the Adalet Park and Turkish Folk Music concert of the artist Hakan Eyiden of the Metropolitan Municipality Conservatory in İncilipınar Park. On Friday evening, July 4 two famous names in Turkey take the stage for Denizli's people. On Friday evening the Turkish Art Music and Sufi Music Artist Ahmet Özhan will give a concert in the Adalet Park. On the same day, the famous comedian Yavuz Seçkin will entertain the citizens with a stand-up show in İncilipınar Park. The famous comedian Yavuz Seçkin will also meet with his fans on Saturday evening, July 5 in Adalet Park.
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Does it mean you have erectile dysfunction if you can’t get hard? Find out in this article as there can be some harmless reasons why you are not getting hard in bed.
Erectile dysfunction includes trouble getting or keeping an erection and may also lead to a loss of sexual libido. It is a common clinical issue that affects mainly men older than 40 years of age. Inadequate erections, otherwise known as erectile dysfunction (ED) or impotence, is defined as the inability to achieve or maintain an erection sufficient for sexual intercourse.
Temporary periods of erection problems are common in all men. They can resolve on their own and this does not necessarily mean erectile dysfunction unless the problem persists. More ED information is available here.
Can’t get hard – Reason 1
You have had one too many drinks, one of the most unfortunate reasons why men do not achieve hard erections.
Alcohol is a depressant and this can have a negative effect on your central nervous system. It decreases blood flow to your manhood, which can prevent you from getting hard erections.
It is important to be conscious of your limits, men should have just a couple of drinks especially if planning on sexual activity.
Can’t get hard – Reason 2
You are nervous.
Your confidence is at a low level because you are with someone new. This is a Psychological reason. Feelings of insecurity of penis size or difficult sexual experiences in the past can contribute to this anxiety. Sexual performance anxiety always stems from your thoughts and expectations and this is what makes you nervous.
Generally any form of anxiety or stress can exhaust you and affect your erections. Talking with your partner about your anxiety can help some of your concerns and make you feel more calm.
Can’t get hard – Reason 3
You are taking certain medications
There are many medications that can interfere with your ability to get hard and this includes certain high blood pressure medications, like beta-blockers. Many medications can affect your nervous system and blood vessel walls which in turn can restrict the blood flow to your manhood.
Talk to your doctor about any other options. In many cases, they will work with you to find an alternative solution. You can’t just stop taking those medications.
Erectile dysfunction is a symptom caused by more complex factors. ED can occur when there is a restriction in any of the processes linked to getting an erection, This is including a man’s emotional and physical state. Erectile dysfunction can often be related to the nerves in the body, hormone levels and circulation. Check out the official Beating Erectile Dysfunction site if you would like more information on the causes.
These are some things that may contribute to ED include:
• low testosterone levels
• poor diet
• kidney disorders
• other illnesses
Regular exercise & improved diet may help with ED
Findings research have shown that certain lifestyle factors, such as smoking, obesity and limited physical exercise may be making matters worse. In several studies, a simple modification in lifestyle habits, through exercise and diet can lead to improvement of erectile dysfunction.
Getting little or no physical exercise can have an effect on erection quality. 20 to 30 minutes of exercise a few times a week may be all that is required and can reduce stress and anxiety levels.
Improving diet can now be regarded as a first-line treatment for erectile dysfunction if you can’t get hard. Flavonoids and other antioxidants in the diet have positive effects on people. The main advantage lies in improvement of blood pressure levels and decreased cholesterol, both of which are factors that contribute to erection issues. Onions and garlic contain allicin, which help with increased blood flow and this is essential in any ED reversal plan.
If you can’t get hard and are looking to stop your erectile dysfunction permanently and start having hard erections, these foods can Help Erectile Dysfunction Read here our featured story of how men are using 1 natural remedy at home to cure erectile dysfunction.
Visit http://www.BeatingErectileDysfunction.com to find out how to stop erectile dysfunction. You will never worry about your sexual performance again.

domain: medical


text:
This archived news story is available only for your personal, non-commercial use. Information in the story may be outdated or superseded by additional information. Reading or replaying the story in its archived form does not constitute a republication of the story.
PROVO — What felt like over a decade ago — it was actually just seven years ago in 2011 — running back Matt Hadley was setting state records and leading small-school Connell to a Washington state title.
On Saturday night, he was back in the end zone — this time at BYU, at a position he wasn’t supposed to be playing, in a season he wasn’t supposed to still be in school.
The medical-redshirt senior ran for a team-high 91 yards and a touchdown late Saturday night in the Cougars’ 49-23 win over a Hawaii team that carried a 6-1 record and lofty expectations into LaVell Edwards Stadium.
And while most of the headlines revolve around the emergence of true freshman quarterback Zach Wilson — deservedly so, after he threw for 194 yards and three touchdowns, and ran for a 23-yard score — don’t overlook the raised contributions of a number of BYU offensive players as they helped snap a two-game losing skid to improve to 4-3 on the year.
"It actually felt really good," Hadley said as he tiredly pulled himself into the postgame press area beneath the stadium with other offensive players like lineman James Empey. "It's my first time (running for a touchdown) since high school, which has probably been over a decade for me. At least, it felt that way.
"I loved the atmosphere and I loved the experience."
Wilson's highlights shouldn’t be underserved, and they won’t be. Plenty of tape, highlights and film review will dissect the every move of a 19-year-old freshman just a few months removed from his senior prom. Those takes will see his brilliant throws — like a 26-yard touchdown to Gunner Romney on fourth down after the Rainbow Warriors called timeout trailing 42-23 with just under four minutes remaining.
They'll also see the poor throws, like Wilson hedging back-to-back ill-advised tosses into cornerback Rojesterman Farris II, one of which went for a brief 4-yard interception return.
But Wilson was the only BYU player who was challenged — and rose to the occasion — Saturday night.
"Everyone knows a quarterback can’t be successful without a good line, or good receivers — or, shoot, even a good scheme," Wilson said. "Everything was in place tonight."
And Wilson — well, we'll just wrap up his section by saying, not bad for a rookie. A 19-year-old "baby quarterback," even.
There was redshirt freshman Lopini Katoa, the former American Fork standout who burst onto the scene in a big way with 83 yards on 16 carries, including a 12-yard touchdown to open the scoring.
Riley Burt, a former Box Elder High star, came back from an injury-plagued career to added 59 yards and a touchdown on nine carries. Romney had 39 yards and a touchdown in back-to-back games, Aleva Hifo rebounded from his role as jet-sweep initiator to catch three passes for 45 yards and a score, and former Lehi standout Dallin Holker caught his first career TD, a 13-yard strike from Wilson that gave the Cougars a 28-3 lead at halftime.
The high-powered offense was the opposite of what head coach Kalani Sitake described a week ago after a blowout loss to Utah State.
"That's more like BYU football," BYU center James Empey said. "We have a long ways to go, and tonight was far from perfect. But we’ll see it on film, and where we can get better."
Then there were the "big uglies" up front, an offensive line of Empey, Tristen Hoge, Keanu Saleapaga, Brady Christensen and Austin Hoyt that plowed the way to 474 yards of offense, including 28 yards on the ground, against a soft underbelly of Hawaii’s defense.
"Those guys are unbelievable," Hadley said. "Not only are they strong and execute like they are supposed to, but they are smart. For us, as ball carriers and quarterbacks, you love that."
Empey likewise deflected the credit Hadley try to throw on him.
"We had a goal tonight to run the ball, and we attacked it this week with technique and just to be a little bit nastier," Empey said. "We were able to do that, to get up on them.
"But it's nice to have backs who hit holes, who run hard, and who break some tackles, too."
BYU enters its bye week above .500 and with as many wins as the entire 2018 season combined. They’ll come out the other side of the bye with a home game against Northern Illinois before traveling to the blue turf at Boise State.
The rest of the season includes dates with UMass, New Mexico State and the season finale at rival Utah.
There’s still a lot of football left to be played — but after Saturday night, the Cougars look forward to facing the schedule. Sitake wouldn’t even commit to playing Wilson at quarterback against the Huskies; the quarterback competition will resume Monday in practice with senior signal caller Tanner Mangum and freshman Jaren Hall, he said.
But even if for one night, the Cougars got a little bit of swagger back.
"I think each team has to find their identity and find their rhythm," Hadley said. "It's different for every team, but I think we are on our way.
"I think that today gave us a bit of a spark, and I feel good and confident that we can turn that into a flame and keep it burning."


text:
Pa. woman's shopping list included chicken breast, muscle relaxers
Police said they found a list in Carolyn Murray's car that read, "Chicken Breast, German Potato salad, Pepsi, Xanex, Cocaine, get high and muscle relaxers."
Whitemarsh Township Police arrested 21-year-old Carolyn Murray of Collegeville on April 28 following a fender-bender, during which she allegedly rear-ended a car being driven by a 76-year-old man as it was stopped at a stop sign.
But it was the shopping list investigators allegedly found in the young woman's car that really got their attention.
According to a police report posted on The Smoking Gun, the list spelled out the following items:"Chicken breast, German potato salad, Pepsi, Xanex [sic], Cocaine, get high and muscle relaxers."
After the accident – during which the elderly driver was reportedly at a full stop and officers found no indication Murray attempted to bring her vehicle to a halt – "Murray was very out of it, her speech was slurred and she had no idea where she was," according to the police report.
"Murray could also not locate her insurance information and registration for her vehicle."
As an officer attempted to help Murray find the documents, he allegedly found the debauched to-do list, written on a yellow index card and stashed in the car's center console.
Murray was taken to Chestnut Hill Hospital and her blood was drawn "due to Murray showing signs of impairment and the index card that was located," the police report reads.


text:
Washington County Quorum Court passes 2018 budget with $4M gap
Washington County Judge Joseph Wood called a special meeting for Monday night for quorum court members to review the 2018 budget.
The quorum court failed to pass the budget, which included a $5 million shortfall, on Thursday after some members expressed concerns that revisions needed to be made.
Bill Ussery, the new chairman of the budget committee, said it was discovered that there was a clerical mistake showing a request for nearly $800,000. Once that was corrected, other county departments were asked to review their budgets and make some cuts - ultimately shaving off $1 million.
The approved budget now shows a $4 million difference in expenditures versus revenue.
"We still saw very few cuts coming through, and we saw no increase in revenue. You heard some talk about a million dollars tonight. Well,there was an $800,000 mistake that was found. That’s the majority of where it came from," said Justice of the Peace Daniel Balls.
Balls said since the millage did not pass, there will be no new money coming in. He said the lack of new revenue will need to be addressed by quorum court members in the near future.
"We do need to make some cuts, but we need to make them where they can be made. And, we are going to have to bring in new sources of revenue. Nobody wants to have to cut a department's budget, but these are hard questions that need to be asked. We need to look at what we can do. And, I think the people of Washington County need to talk to us about what they want to see done."
The Washington County Sheriff, Tim Helder, said he's grateful his budget requests were approved. The sheriff requested a $1.4 million dollar increase for 2018 to add positions.
Helder said with the rapid growth in the county, he needs more deputies and his increase in staff was justified.
“The good news is, we are going to be able to increase our patrol staff by two deputies per shift. The bad news is, for the people, it will take us six to eight months to get new deputies hired and trained. But ultimately, this is going to help us, in the type of response we can give our citizens, and the safety of our deputies" Helder said.
Ussery told court members that there will be leftover money from the 2017 budget that wasn't spent. Ussery said that money will roll over, which will help the deficit.
Justice of the Peace Eva Madison, who opposed the revised budget during the review meeting, addressed the quorum court during public discussion. She said that she ultimately voted "yes" because she wanted to see all the members come together.
However, she voiced her concerns to the court that she fears the deficit will make things more difficult in 2018.

domain: economics


text:
Business, Restaurant, Remax
20 Question Technique
to use when assessing a property investment.
Key questions to use when assessing a property investment. Key questions for buyers include:
� What is the cash flow of the property?
� What is the vacancy rate in the area?
� What is the competition?
� What improvements are being panned for in the area?
� What are council/government plans for the area?
� What's the population growth like?
� Why do people live in this area?
� What's the economy like in this area?
� What services are available (shops, schools, etc.)
� Is there transport nearby?
� Is the property tenant friendly?
� What condition is it in?
Choosing the Right Property
Where would you Buy? Focusing on an area:
1. Is the area's average income increasing faster than the
2. Is the area's population growing faster than the provincial average?
3. Is the area creating jobs faster than the provincial average?
4. Does the area have more than one major employer?
5. Is real estate in the surrounding regions booming?
6. Will the property value benefit from a major new development nearby?
7. Has the local and provincial political leadership created a growth atmosphere in the area?
8. Is the region's economic development office helpful and proactive?
9. Is the area located in an area of renewal or gentrification?
10. Is the major transportation improvement occurring nearby?
11. Is the area attractive to Baby Boomers?
What would You BUY?
Buy- but not just anything
The more property we had, of course, the greater chance of
cashing in on capital growth. But you need to be in a position
to see out the wait for capital growth to kick in and that's
why you should only move for the right sort of property.
I think the current property market is exciting for investors
but you need to proceed with some caution. Whatever you
decide to buy, you have to feel confident that you can afford
to keep it. Nothing is ever guaranteed and capital values
certainly aren't guaranteed. So if you're banking on making a
capital gain but are in a negative cash flow position with the
property, you could be in strife.
If you lost your job or your business went bad the property
doesn't support itself, you could be in trouble. Whatever
property you go into, you've got to make sure that it can be
renovated to improve its value and equity also to improve its
potential for rent.
You really need to achieve as high a yield as possible so you can hold it as possible and achieve the passive gains. For small investors at this time, yield needs to be a major factor in the decision to buy again.
We don't know if prices are going to get much lower but personally think now is an incredibly good time to buy and I'd recommend that people go out and get their first property if they don't have one already.
I have no doubt the market and it is definitely "buy" time.
Stick to the basics. They are reliable and a lot safer for the small or medium investor looking to expand the portfolio. Now is the time to buy property that you can get for low dollars and that has a constant demand. If people are forced out of the home ownership market, which some unfortunately will be, they have to live somewhere. So property at the lower end of the market is always in rental demand.
Focus on Opportunities not
Proper use of upcoming
opportunities is the key to success
when we talk about investment.
The dictionary definition of an
opportunity is " a favorable time
or occasion". In a business and
investing context it's a new
opening for profits.
I have seen many prospect investors who focus on the property itself instead of paying attention to the possible opportunity in purchasing process. Another words, there are buyers who concentrate on condition of plumbing, bathrooms or the roof while they may miss the opportunities which exist around the property.
Any problems you solve with your properties (replacing a furnace, upgrading bathrooms and renting a vacant unit) are important to keep them ticking over. But solving problems is different from seizing opportunities and it's the latter that produces big gains.
Opportunities might include not limited to such things as:
� You get a new appraisal of your property higher than expected-this means more equity for new investment.
� You observe a temporary economic setback in specific area- a desirable area to purchase new investments in it.
� A rise in interest rates leads to more motivated sellers and property bargains.
� Distress sales, Fixer uppers and bargain properties are all true opportunities for investors.
� Government Grant Projects are other example of available opportunity in property investment.
IF BUYING A CONDO AS AN INVESTMENT:
Know the costs:
Make sure to calculate all your expenses, including down payment, legal fees, strata(condo) fees, property taxes, property transfer tax, home inspection fees, appraisal fees, painting, appliances and assessments to fix leaks or defects.
Know your ROI:
For a property that costs $ 250,000 and generates $ 1,300 per month in rent the cap rate is 6.24%(15,600 divided by $250,000). The rule tends to be that if you get less than an 8% cap rate, the property may not produce positive cash flow each month. That' because if you have a $ 200,000 mortgage, at a rate of 6% amortized over 25 years, for example, your monthly payment will be $1,292.Then added condo fee, insurance and upkeep.
Know the laws:
get a copy of provincial condo legislation and by laws. Make sure rentals are allowed. Scrutinize strata council meeting minutes to see if there are recurring problems that could become your nightmare.
Know the deductions:
There are tax implications and deductions. Keep records such as receipts for extensions. Get professional advice from accountant and a lawyer.
Know the market:
there will be dips and downturns in any area, but overall the trend line is usually up. Typically, the best location to get maximum price appreciation is in an area with good transportation and shopping close to downtown.
Know your limits:
Do you want to get up in the middle of the night to unclog a toilet? If not higher a manager.


text:
Forlime is a service company with worldwide activities and specialised
in lime technology.
Forlime was created in 1997 with the objective of providing manufacturers
and users of lime with technical, scientific and commercial assistance
in order to improve the production and quality of lime and to develop
Forlime is an independent company formed by three specialists
with worldwide experience in the field of lime.
Philippe Dumont has worked for 33 years in the lime industry as
manager of research and development and quality control. He has
taken out several patents for the production and use of lime.
Jan Baeyens Professor at Faculty of Engineering of the University
of Leuven and Antwerp. He has acquired vast experience in the field
of lime and gas treatment and has published numerous articles on
Albert Bolle Professor at the University
of Liège in the
Sector of Infrastructure and Geomecanics, specialised in the use
of lime for construction (mortars, soil stabilisation, solid waste
and sludge treatment…).

domain: chemistry


text:
I was going through some old New Warriors comics and I came across this cool ninja looking character but everybody called her Jube or Jubilee... is this the mutant Jubilee or is there another character with the same name?
Jubilee a part of SHIELD?
This edit will also create new pages on Comic Vine for:Beware, you are proposing to add brand new pages to the wiki along with your edits. Make sure this is what you intended. This will likely increase the time it takes for your changes to go live.

domain: entertainment


text:
Mississippi state senator speaks about his decision to get vaccinated
BILOXI, Miss. (WLOX) - Mississippi remains last in the nation in terms of COVID-19 vaccination rate. The state’s population is 35% fully vaccinated against the virus, even after a surge in people taking the shot from late July and into August.
One of those Mississippians is State Sen. Joel Carter of the 49th District, who made a snap decision to get the shot at Walmart Thursday morning.
“I’ve been pretty anti-vaccine, to be honest with you, for a long time,” Carter said. “I’ve had serious reservations about it, something that has been pushed out so quickly.”
The state senator kept up that mentality for most of the pandemic, even after he caught the virus last year. However, a busy travel schedule in the middle of the delta variant spike made him rethink his position.
“I didn’t want to come back from a conference, be infected, bring it home or bring it to the office,” he said. “I didn’t feel like that was fair.”
Carter did what a lot more people are doing nowadays, relying on the experts with COVID-19 information.
“I just felt like it was the right decision for me after talking to my doctors,” he said.
After opinions from two physicians, the state senator decided to get his first shot of the Moderna vaccine last week and announced it on social media after he had mild but expected symptoms.
“On Friday I had some muscle aches, but it wasn’t anything Tylenol couldn’t take care of,” he said.
Carter said his initial struggle with the vaccine was the limited information about long-term side effects.
Nevertheless, with ICU beds filling up and COVID-19 deaths on the rise throughout Mississippi, he said the data showed the outcome for vaccinated people who get the virus is much better.
“It’s got to make you worry. It’s got to make you think about your decision if you haven’t been vaccinated,” he said.
Now, he’s encouraging others to do what he did.
“Talk to your physician. Ask them about the vaccine. Make a good, informed decision,” he said.
Carter hopes to document his experience with the vaccine more in-depth on his social media after he gets his second dose of Moderna.
Copyright 2021 WLOX. All rights reserved.

domain: politics


text:
The way I choose to teach is to give you the information and allow you to do what you will with it. I will show you how to program and will give you structure and how to arrange your code, naming conventions etc. I can give you ideas of what to code and we can then walk through those programs together. I will not be strict due to the fact that you are choosing to learn this yourself for the enjoyment rather than anything pressingly academic.
I am a computer science student studying at the University of Southampton. I have previously done A Level and GCSE computer science (so I know what I am on about) and have a love of programming and teaching. I will attempt to teach you how to program, rather than a specific programming language.
computer programming lessons closeby? Here's a selection of tutor listings that you can check out.
Superprof can also suggest visual basic lessons to help you.
Learning isn't a problem, java lessons for all!
|at her home||at your home||By webcam|
|1 hour||Not available||£9||£7|
|5 hours||Not available||£40||£35|


text:
Lawsuit Filed Against Famous Author
Friday, September 28th 2007, 9:37 am
By: News On 6
A famous author is being sued by some Oklahomans. John Grisham and several other co-defendants are named in a federal defamation lawsuit filed in Muskogee Friday morning. News On 6 anchor Craig Day reports theyâ€™re accused of conspiracy and libel in connection with books written about a wrongful conviction in Oklahoma.
A year ago, John Grisham came out with a non-fiction book called "The Innocent Man." The book was about a murder conviction in Oklahoma that was later overturned. Now, two of the main players in the investigation are suing Grisham, publishers and authors of two other books on the case.
The lawsuit, filed in U.S. District Court, claims John Grisham, two other authors, their publishers and a death penalty opponent engaged in a deliberate defamatory attack. The federal lawsuit stems from books, including one by Grisham, written about the 1982 murder of Debbie Sue Carter in Ada. Attorney Gary Richardson believes it was unfairly critical of those investigating the case.
"In doing so, unbelievable maligned Bill Peterson, the D.A. of three counties in Oklahoma as well as Gary Rogers, very well known, former OSBI investigator for years, real men of integrity," attorney Gary Richardson said.
The two men originally convicted of Carter's murder, Ron Williamson and Dennis Fritz, were later exonerated by DNA evidence and freed after 12 years in prison. Their experiences are chronicled in two books, Fritz's "Journey Toward Justice" and John Grisham's first non-fiction book, "The Innocent Man."
"We think that somewhere along the line he must have forgotten that he was writing a non-fiction book and kind of slipped back into the mold of a non-fiction book. It's that bad," said Richardson.
The lawsuit claims the defendants launched a massive defamatory attack on the plaintiffs, through libel and slander, exposing them to public hatred, contempt and ridicule.
"It's the situation of two men, and their careers being severely impacted for the balance of their life," said Gary Richardson.
So what about the conspiracy allegations in the lawsuit filed in federal court in Muskogee? Richardson claims there was a conspiracy involving the defendants motivated in part by a desire to abolish the death penalty.
The lawsuit, seeks damages of more than $75,000.
"We think it is time for some justice to prevail for some good Oklahoma citizens," attorney Gary Richardson said.
It's expected to be a few months before John Grisham and the other co-defendants must answer to the lawsuit.
Death penalty opponent Barry Scheck is also named in the case. He's the head of the Innocence Project which helps clear death row inmates through DNA testing.
Watch the video: Oklahomans Sue Famous Author
10/12/2006 Books Chronicle Oklahomans' Wrongful Arrest, Conviction

domain: law


text:
Register for an ESL account
ESL is world's largest, independent eSports brand, leading the industry across various games with numerous online and offline competitions. This includes high profile international and national leagues and tournaments such as the Intel® Extreme Masters, ESL One, ESL Pro Series, Starcraft® II World Championship Series, as well as grassroots amateur cups, leagues and matchmaking systems. Registration and Participation in these grassroots Ladders and Leagues are for free. This is how you register:
- 1. Click on Login/Register
- 2. Click on Create Account
- 3. Fill in the form
- 4. Confirm your registration
Hint: It is possible that your e-Mail provider will sort out our automatic generated Mails as Spam. Please take a look in your Spam folder.
Rocket League Getting Started
Please read carefully and follow all the steps below
1. Please make sure the players on your team have clicked on the team join link that was provided to you.
2. Click this for your Rocket League Tournament Cup
3. On the right side of the cup ROCKET LEAGUE NICKNAME (AMERICA) click on Register to enter in your Summoner's name (Case Sensitive).
4. Enter in your Rocket League nickname and click Confirm
This only applies to Rocket League and does not apply to League of Legends
How to find and report your match results
1. Your matches are found under the Results Tab
2. Click on Info next to your match
3. Click on Match setup (enter result, reschedule)
4. Enter in the score of the matches, then click Send.
5. Confirm the score
6. Confirm your line up and click save data
If you're opponant already entered their score you will have to confirm the score as well
If you need help feel free to Click here to open a ticket or contact one of our admins on Discord
Info: Main Tournament information such as quick rules, game format, and game settings!
Rankings: Your current rankings/standings in the tournamment
Results: Your match schedule and matches
Teams: Current teams in the competition
Rules: Rules of the tournament
Support: Need help? open a support ticket or contact an Admin on Discord

domain: game


text:
Lea Michele ink tribute to Cory Monteith
Tattoos can be a way to honor or remember those we have lost. That’s just what Lea Michele did in a heartfelt tribute to her late boyfriend and ‘Glee’ co-star Cory Monteith.
The 29-year-old actress had the number “5” etched onto her side in reference to Cory’s ‘Glee’ character Finn Hudson, a quarterback in the high school football team who he played in the musical Fox television series from 2009 until his death.
The piece was designed by New York City’s Prospect Tattoos and Lea shared a picture of it on her Instagram account, alongside the caption: “And one more … for my Quarterback… #5 (sic)”
The couple – who met on the show – dated for two years until Cory’s tragic death from a drug overdose in July 2013.
It’s the second permanent tribute the ‘Scream Queens’ actress has had done after she shared a picture of her coffee cup finger art, which she had done in memory of her late grandmother who passed away last week.
Alongside the photo of the small tattoo, she wrote yesterday (04.11.16): “I lost my beautiful grandma this week … She wasn’t your typical grandma. She gave me my first cup of coffee when I was 8 years old. She said something inappropriate to every boyfriend I’ve ever had. She never made pie or knit me a sweater. But she was my grandma and I loved her … More than anything … I love you Grandma @prospect_tattoos Bronx NY (sic)”

domain: artistic


WEAR ABC 3 - Search Results
Highest paid women
Fortune magazine has come out with its list of the 25 highest paid women.
Topping the list of executives is Safra Catz, President and CFO of Oracle, earning 43-million dollars.
Next is Yahoo's CEO, Marissa Mayer, at 36 million.
And rounding out the top three is Facebook COO, Sheryl Sandberg, with 26 million.


text:
As you know, at the Conversation of Our Generation, we are trying to build a dialogue and discuss the ideas that affect our society, culture, politics and philosophy. As we discuss the ideas that will define our generation, it is important to look back at the foundations of thought. This book is great for understanding how the dialogue developed and how these ideas are still relevant today.
Also, there’s a little idea on walking through the evolution of thought that I am trying, and I hope some of you will try as well!
Join the Conversation of Our Generation!!!Subscribe to our email list
for our Recommended Reading, reviews on books and other content that can grow your store of knowledge. New products will be coming soon, exclusively for subscribers.
If would like to join me in the Conversation of Our Generation, follow me on Twitter @ConOfOurGen
, Facebook Conversation of Our Generation Facebook Page
and SteemIt @jamell
Also, you can find me on YouTube Conversation of Our Generation YouTube Channel
I am just trying to join the Conversation of Our Generation. Let’s get the dialogue going with comments, shares, questions, just say something!


text:
JACKSONVILLE -- Beating a cap-related deadline by several hours, ESPN.com has confirmed on Monday that the Jacksonville Jaguars signed fourth-year veteran Brad Meester to a five-year extension, making him one of the 10 highest-paid centers in the league.
The contract extension is believed to be worth $13 million, with a signing bonus of about $3.5 million -- dramatically increasing Meester's compensation for '03 and providing him with security for the future. Monday was the deadline for teams to sign players to new contracts or extensions and have the signing bonus count as 2003 base salary.
The bookkeeping maneuver permits teams to significantly soften the blow of future cap charges on extended deals. The Arizona Cardinals, for instance, signed five veterans to contract extensions on Saturday to beat the deadline. Most notable was standout offensive left tackle L.J. Shelton.
Without the extension, Meester would have been eligible for unrestricted free agency at the end of this season. The fourth-year veteran, a second-round pick in the 2000 draft, was in the final season of his initial NFL contract with a base salary of just $450,000.
His cap number for 2003 will rise from its current $668,000 but, for one of the few times in recent years, Jacksonville, which has struggled with the spending limit in the past, had sufficient wiggle room to cover it.
Meester, 26, is one of the young "nucleus" players around whom the organization plans to rebuild the franchise. Retaining him was a priority and contract discussions took place over the past month.
The former Northern Iowa standout has started all 56 games with Jacksonville during his NFL career. In his first three years, Meester started all 48 contests at left guard. He moved to center for the 2003 season.
Although a bit undersized, Meester is a solid technician and an excellent athlete.
Len Pasquarelli is a senior NFL writer for ESPN.com


text:
Professional acting is both an art and a business, and this book advises beginning actors on how to cope successfully on both fronts. Opening chapters describe the difficulties every budding actor encounters and explains basic acting techniques, which include memory exercises and methods for developing stage presence. Chapters that follow instruct in--
|Book:||The Acting Bible: The Complete Resource For Aspiring Actors|
|Publisher:||Barron's Educational Series|
|Number of Pages:||256|
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text:
Big Fish Audio has introduced London Solo Strings, a string sample library.
The most playable string library available. Violin, Viola, Cello & the oft-omitted Double-Bass like you’ve never heard them before. 24 bit, multiple microphone positions, played by world class performers. Articulations include: arco, marcato, spiccato, sul tasto, ponticelli, pizzicato, harmonics, snap pizzicato, FX & more. This library delivers realism & flexibility packaged with the most creative programming to date.
Kontakt Player (PC/Mac/AU/DXi2/RTAS/VSTi) – $399.95
GigaSampler – $399.95


The first two words of DACA are “Deferred Action.” This implies (requires) at some future time action needs (must) be taken.
This country, a representative republic (not a democracy) is governed under the Constitution of the U.S.A.
Congress, not the president, is charged with establishing the laws. The president is charged with enforcing the laws.
Understanding President Obama’s frustration with the Senate’s (Democratically controlled) failure to address meaningful immigration reform, his DACA proclamation is just that — a proclamation, not law.
What President Trump has done, as unpopular as it is, has put it back on track to become law!
What all who support DACA should be spending their energy on (as opposed to their Trump-bashing) is to be lobbying their federal representatives — Sens. Dianne Feinstein and Kamala Harris and House Rep. Jared Huffman — for their desired outcomes.
Charlie Giannini, Fortuna


text:
Four young adults aged 19 to 23 were travelling in a Honda Civic when the driver lost control of the vehicle and the vehicle left the road. The crash occurred at approximately 1:50 a.m. on October 20, 2010. The driver, a 20-year-old female from Saint-Léolin, died as a result of her injuries on October 21, 2010 at the Tracadie-Sheila hospital.
Alcohol and speed may have been contributing factors in the crash.
The other three occupants of the vehicle have been released from hospital. The name of the victim is not being disclosed at this time.
A collision reconstructionist was called to the scene.
The investigation is ongoing.


text:
Well, it's finished at last but I can't quite believe how long this has taken to knit. Almost unbelievably, I started it back in February ! I know I dithered a lot over shaping and amount of yarn as I wasn't working from a pattern but even so - that's a long while for one cardie!
I'm really pleased with it - it's a good length, it's shaped in at the waist so not too bulky, the neck is not so high that I feel throttled and the only thing I'd change is the length of the sleeves which could have been shorter.
On now to the next project - probably a rather similar garment, just a different colour.


Nothing sets off a house better compared to a very much kept grass – Automower 315 uniformly green, overall a similar length and variety and seeming to be velvet.
A mechanical lawnmower does precisely that with no contribution from any human aside from the underlying setting up – it is totally programmed.
This robot, in contrast to petroleum trimmers, emits no destructive discharges. (Did you had at least some idea that a petroleum trimmer laboring for an hour emits as much CO2 as 35 vehicles traveling for 100 miles?)
A programmed lawnmower might be modified to cut the grass whenever of day or night. The robot naturally cuts such a modest quantity of grass during a period that there is no buildup and the clippings mulch into a compost for the yard. So… there are no disgusting stores of decaying grass to manage.
When the long life lithium battery is getting low, the trimmer returns itself to a charging house and once stimulated, comes out again to cut the grass.
Standard trimmers are excessively wide for uneven yards and scalp the hillocks and leave long grass in the plunges – the grass looks sketchy. All programmed lawnmowers are adequately little to cut into the plunges leaving the yard looking level regardless of whether it isn’t. Assuming your yard is now level it will wind up seeming to be the bowling green at the savviest club.
There are many models of programmed lawnmowers for each size grass from the littlest to 4 sections of land – all are portrayed on the web so investigate see which cutter would suit your yard.
YOU DON’T Need TO BE A ROBOT TO GET YOUR Yard LOOKING AND BEING GREEN!