text:
P T. 2016;41(6): 357-360
Drug Forecast
Dulaglutide (Trulicity): The Third Once-Weekly GLP-1 Agonist
Lillian L. Smith PharmD, CPh, MBA
Juan F. Mosley PharmD, CPh, AAHIVP
Crystal Parke PharmD
Jamal Brown PharmD
Lillian S. Barris PharmD
Linh D. Phan PharmD
Diabetes is a rapidly growing, nondiscriminatory disease that affects people of all ages and ethnicities. It is estimated that 9.3% of the United States population has diabetes.1 This equates to 29.1 million Americans who have the condition, of which 8.1 million are undiagnosed.1
Pharmacological treatment of type-2 diabetes has changed dramatically over the past five years, with new classes and drugs becoming available. Many of the medications used in the treatment of type-2 diabetes can be used in combination with various other oral therapies to achieve better glycemic control. Some can be given once weekly, an option that provides an avenue to limit polypharmacy and noncompliance, which otherwise may not have been achieved with daily monotherapy. Agents used in diabetic therapy include the following classes: selective sodium-glucose cotransporter-2 inhibitors, biguanides, meglitinide derivatives, sulfonylureas, alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones, insulins, amylinomimetics, bile acid sequestrants, and dopamine agonists.2
Nonpharmacological interventions, including lifestyle changes such as diet modifications, are still considered the mainstay of adjunctive treatment for diabetes. Patients newly diagnosed with diabetes who actively incorporate diet and exercise into their disease-state management usually have more control of their glycemic levels than those who are insulinopenic.
Type-2 diabetes is the most common type of diabetes, and patients commonly rely on both oral and injectable agents to control it.2 With respect to the injectable agents, glucagon-like peptide-1 (GLP-1) agonists are growing in popularity. GLP-1 agonists, also known as "incretin mimetics," increase insulin secretion, decrease glucagon secretion, slow gastric emptying, improve satiety, and may result in weight loss.3
Type-2 diabetics often lack or have reduced incretin effect. Therefore, utilization of the incretin system is an ideal approach to the treatment of type-2 diabetes. Recent research endeavors show that targeting the incretin system not only improves glycemic control, but also has the ability to decrease systolic blood pressure and body weight.4 The GLP-1 class currently consists of exenatide (Byetta, AstraZeneca; Food and Drug Administration [FDA]-approved in April 2005); liraglutide (Victoza, Novo Nordisk; FDA-approved in January 2010); exenatide extended-release (Bydureon, Astra-Zeneca; FDA-approved in January 2012); albiglutide (Tanzeum, GlaxoSmithKline; FDA-approved in April 2014); and the newest addition, dulaglutide (Trulicity, Eli Lilly and Company; FDA-approved in September 2014). Exenatide extended-release, albiglutide, and dulaglutide are administered via once-weekly injections.2 This review will discuss the background and efficacy of dulaglutide while distinguishing key differences in the various alternative treatment options.
INDICATION AND USAGE
Dulaglutide is indicated to improve glycemic control in adults with type-2 diabetes mellitus as an adjunct to diet and exercise.5
The primary mechanism of action of dulaglutide, as an incretin mimetic hormone or an analogue of human glucagon-like peptide-1, is to increase insulin secretion when glucose levels are elevated, decrease glucagon secretion, and delay gastric emptying in an effort to lower postprandial glucose level.6 Dulaglutide also activates the membrane-bound cell-surface receptor in pancreatic beta cells known as the GLP-1 receptor.5
PHARMACODYNAMICS
After a single dose, dulaglutide has the ability to decrease fasting glucose levels and reduce postprandial glucose concentrations in type-2 diabetes patients. 5
Fasting and Postprandial Glucose
In a study of adults with type-2 diabetes mellitus, treatment with once-weekly dulaglutide resulted in a reduction of fasting and two-hour postprandial glucose concentrations, and postprandial serum glucose incremental area under the curve (AUC), when compared to placebo (−25.6 mg/dL, −59.5 mg/dL, and −197 mg/h/dL, respectively); these effects were sustained after six weeks of the 1.5-mg dose.5
First- and Second-Phase Insulin Secretion
In type-2 diabetic patients who were treated with dulaglutide, both first- and second-phase insulin secretions increased when compared with placebo.5
Insulin and Glucagon Secretion
Dulaglutide reduces glucagon secretion and prompts glucose-dependent insulin secretion. When patients were treated with dulaglutide 0.75 mg and 1.5 mg once weekly, their fasting insulin increased from baseline at week 26 by 35.38 and 17.50 pmol/L, respectively, and C-peptide concentration by 0.09 and 0.07 nmol/L, respectively, in a phase 3 monotherapy study.7 In the aforementioned study, fasting glucagon concentrations were also reduced by 1.71 and 2.05 pmol/L from baseline.5
Gastric Motility
Dulaglutide delays gastric emptying, with the largest delay occurring after the first dose and then lessening with succeeding doses.5
Cardiac Electrophysiology (QTc)
In a QTc study utilized to determine the effect of dulaglutide on cardiac repolarization, dulaglutide did not produce QTc prolongation.5
The pharmacokinetics of dulaglutide can be seen following subcutaneous administration. The time to maximum concentration at steady state ranges from 24 to 72 hours, with a median of 48 hours. Steady-state concentrations were achieved between two and four weeks after once-weekly administration. After multiple-dose administration of 1.5 mg to steady state, the mean peak plasma concentration and total systemic exposure (AUC) of dulaglutide were 114 ng/mL and 14,000 ng•h/mL. The accumulation ratio was approximately 1.56.5 There was no statistically significant effect based on exposure sites.5
Absorption and Distribution
The mean absolute bioavailability of single 0.75-mg and 1.5-mg doses of dulaglutide was 65% and 47%, respectively.5 The mean volumes of distribution were approximately 19.2 L and 17.4 L, respectively.5
Metabolism and Elimination
It is assumed that dulaglutide is degraded into its component amino acids upon administration.5 However, at steady state, the mean apparent clearance is approximately 0.111 L per hour for the 0.75-mg dose and 0.107 L per hour for the 1.5-mg dose. The elimination half-life of dulaglutide for both doses is approximately five days.5 As with most medications in the class, dulaglutide should be used with caution, and both renal and hepatic function should be monitored. Nevertheless, dulaglutide does not require dose adjustments.
PIVOTAL CLINICAL TRIALS
The FDA's approval of dulaglutide was based on a combination of studies. The trials evaluated the use of dulaglutide 0.75 mg and 1.5 mg.7 Uptitration of dulaglutide was not performed in any of the trials; patients were initiated and maintained on either 0.75 mg or 1.5 mg for their duration.5 In patients with type-2 diabetes mellitus, dulaglutide produced reductions from baseline in hemoglobin A1c (HbA1c) compared to placebo. No overall differences in glycemic effectiveness were observed across demographic subgroups (age, gender, race/ethnicity, or duration of diabetes).5
Monotherapy Trials
Wysham et al
Wysham and colleagues conducted a 52-week, multicenter, parallel-arm study that randomized patients to dulaglutide 0.75 mg, dulaglutide 1.5 mg, exenatide 10 mcg, or placebo. This study included both men and women who were at least 18 years of age with a body mass index between 23 and 45 kg/m2 and an HbA1c between 7% and 11%. Patients also had to be on an oral antihyperglycemic medication (OAM) as monotherapy.8
Eligible patients were treated with metformin (1,500–3,000 mg) and pioglitazone (30–45 mg).8 Over a period of 12 weeks prior to the study, previous OAMs other than metformin and pioglitazone were discontinued. Patients were then titrated on a dual-OAM regimen of maximum tolerated metformin and pioglitazone.8 After patients were stabilized prior to randomization, their HbA1c had to be greater than 6.5% to maintain eligibility. All eligible patients were then randomized to one of four arms.8
The mean age of patients was 56 years with a mean duration of type-2 diabetes of three years. Forty-four percent were male. Patients were 74% white, 7% black, and 8% Asian, and 29% of the study population was in the U.S.5
Exenatide patients received 5 mcg twice a day for the first four weeks and 10 mcg twice a day for the remainder of the study. At 26 weeks, placebo-treated patients were then switched in a blinded fashion to either dulaglutide 1.5 mg or dulaglutide 0.75 mg.5
Treatment with dulaglutide 0.75 mg and 1.5 mg once weekly resulted in a reduction in HbA1c (1.3% and 1.5%) compared to placebo (0.5%) and compared to exenatide (1.0%) at 26 weeks. During the 52-week study, 8.9% of patients required glycemic rescue in the dulaglutide 0.75 mg plus metformin and pioglitazone treatment group, 3.2% in the dulaglutide 1.5 mg once weekly plus metformin and pioglitazone treatment group, and 8.7% in the exenatide twice a day plus metformin and pioglitazone treatment group.5
Umpierrez et al
Umpierrez and colleagues conducted a 52-week double-blind study to compare the efficacy and safety of monotherapy with dulaglutide to metformin-treated patients with type-2 diabetes mellitus. Patients were randomized to receive dulaglutide 0.75 mg, dulaglutide 1.5 mg, or metformin 1,500–2,000 mg per day.9 Patients were included in the study if their HbA1c was lower than 9.1% but higher than 6.5% with lifestyle modification or low-dose OAM monotherapy.9
Reductions in HbA1c were noted at 26 weeks. Dulaglutide 0.75 mg showed a reduction of 0.71% ± 0.06%, dulaglutide 1.5 mg showed a reduction of 0.78% ± 0.06%, and metformin showed a reduction of 0.56% ± 0.06%, demonstrating that both dulaglutide 0.75 mg and dulaglutide 1.5 mg were superior to metformin.9 No severe hyperglycemia was reported during the study, and weight loss was similar to that of metformin in both dulaglutide groups. The most common adverse effects seen over the 52-week period were nausea, diarrhea, and vomiting.9 Overall, dulaglutide improved the glycemic control of patients and demonstrated the ability to be well tolerated as monotherapy in patients with early-stage type-2 diabetes.
Combination Therapy Trial
Nauck et al.
In this 104-week, multicenter, double-blind, parallel-arm study, Nauck and colleagues compared the efficacy and safety of two doses of once-weekly dulaglutide to sitagliptin in uncontrolled, metformin-treated patients with type-2 diabetes. This study included 1,098 randomized patients with an average age of 54 years; an average HbA1c of 8.1%; an average weight of 86.4 kg; and diabetes for an average of seven years.9 Patients received either dulaglutide 0.75 mg once weekly, dulaglutide 1.5 mg once weekly, sitagliptin 100 mg per day, or placebo.10
The average HbA1c reductions were −1.10 ± 0.06%, −0.87 ± 0.06%, and −0.39 ± 0.06% for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and sitagliptin.10 Both dulaglutide doses were superior to sitagliptin. During the study, the most common adverse events were nausea, diarrhea, and vomiting with both doses of dulaglutide.10
In conclusion, treatment with dulaglutide 0.75 mg and 1.5 mg once weekly resulted in a statistically significant reduction in HbA1c compared to placebo at 26 weeks and compared to sitagliptin at both 26 and 52 weeks, all of which were in combination with metformin.
At baseline, 2.5% of the population reported retinopathy, and baseline estimated renal function was normal or mildly impaired (estimated glomerular filtration rate 60 mL/min/1.73 m2 or higher) in 96% of the pooled study populations.5 Adverse reactions were not present at baseline, occurred more commonly on dulaglutide than on placebo, and occurred in at least 5% of patients treated with dulaglutide.5 The most common adverse reactions to dulaglutide reported in 5% or more of patients included nausea, diarrhea, vomiting, abdominal pain, decreased appetite, dyspepsia, and fatigue. Other adverse reactions include hypoglycemia, tachycardia, immunogenicity, hypersensitivity, injection-site reactions, PR interval prolongation and first-degree atrioventricular block, and amylase and lipase increase.5
Monitoring and caution should be employed when oral medications are concomitantly administered with dulaglutide because it slows gastric emptying and thus has the potential to reduce the rate of absorption of concomitantly administered oral medications.5 Drug levels of oral medications with a narrow therapeutic index should be adequately monitored when concomitantly administered.5
Dulaglutide has an absolute contraindication in patients with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2.5 Dulaglutide should also not be used if there is a history of serious hypersensitivity to dulaglutide or any product components.5
Dulaglutide carries a boxed warning of thyroid C-cell tumors and may result in an increased risk for medullary thyroid carcinoma and pancreatitis. If a patient suspects the development of pancreatitis, dulaglutide should be discontinued.5 Dulaglutide is not recommended in patients with severe gastrointestinal (GI) disease (i.e., colitis, Crohn's disease, GI obstruction, GI perforation, gastroparesis, ileus, inflammatory bowel syndrome, pseudomembranous colitis, ulcerative colitis, and/or undiagnosed GI bleeding).5
As with any antidiabetic treatment, hypoglycemia may occur. If dulaglutide is used with an insulin secretagogue (i.e., sulfonylurea, meglitinide) or insulin, consider lowering the dose of the secretagogue or the insulin to reduce the risk of hypoglycemia.5 Renal function should be monitored in patients with renal impairment reporting severe adverse gastrointestinal reactions.
Dulaglutide should be administered once weekly at any time of the day. It is to be injected subcutaneously in the abdomen, thigh, or upper arm. The starting dose is 0.75 mg subcutaneously once weekly.5 The dose can be increased to 1.5 mg once weekly for additional glycemic control. If a dose is missed, administer it within three days (72 hours) of the missed dose.5
The average wholesale price for a 28-day pack with four injection pens (0.75 mg or 1.5 mg) is approximately $690.11
P&T COMMITTEE CONSIDERATIONS
For the type-2 diabetes patient, 11 drug classes are currently available; however, in the hospital setting it can sometimes be unclear which of these agents should be added to the hospital's formulary. Among the 11 classes of drugs, incretin-based therapies (GLP-1 receptor agonists and DPP-4 inhibitors) have become fundamental treatment options in treatment guidelines. They both target the therapeutic usefulness of the incretin system in distinct ways, but their ultimate goal is to increase insulin release from the pancreatic beta cells and decrease glucagon secretion from the pancreatic alpha cells, which results in decreased hepatic glucose production, slow gastric emptying, improved satiety, and weight loss. However, this mechanism is more often seen in the GLP-1 receptor agonists. GLP-1 receptor agonists mimic the action of incretin, while DPP-4 inhibitors inhibit the DPP-4 enzyme that inactivates incretin, promoting higher levels of incretin during the postprandial phase.
Since the approval of exenatide and sitagliptin, the use of GLP-1 receptor agonists and DPP-4 inhibitors has been widely incorporated into outpatient settings through treatment guidelines and clinical practice. However, it is important to understand that while these new classes of medications could be safe to use in the inpatient population, the long-term safety profile of their use has yet to be determined.12
Many diabetes associations support the use of insulin as the preferred agent in the hospital setting regardless of a history of diabetes because of the short half-life of circulating insulin and the luxury of intravenous administration. This route allows for rapid dosing adjustments upon assessing a patient's status.13
When examining the classes side by side, there are currently only a handful of studies investigating the use of GLP-1 agonists in the inpatient setting, while there are many studies that support the use of insulin in hospitalized patients. To date, no major benefits have been demonstrated with the use of GLP-1s in the inpatient setting; and in many GLP-1–treated patients, rescue therapy with insulin was required to achieve and maintain the desired glycemic targets. GLP-1s also have an added risk for gastrointestinal side effects such as nausea, vomiting, and constipation.
When compared to other therapies, insulin has also proven to be safe and effective for glycemic management and to reduce hospital complications.8 While there are indeed many advances in diabetes pharmacotherapy, insulin may remain the preferred blood glucose-lowering agent of choice for inpatient hyperglycemia management simply because of its tolerability, cost, and proven long-term results. It is also important to note that patients typically seen in the hospital setting are often in distress, which requires an immediate action or dose of medication. Noninsulin therapies often take more time to reach their full effectiveness, and OAMs are not able to adjust to the infrequent changes in glucose levels sufficiently. Therefore, any recommendation against the use of noninsulin therapies due to efficacy concerns is warranted.
The GLP-1 class of medications has shown its ability to improve glycemic control while reducing body weight and systolic blood pressure in patients with type-2 diabetes. Dulaglutide is the newest edition to the GLP-1 receptor agonist family for the treatment of type-2 diabetes mellitus in conjunction with adequate diet and exercise. Recent studies have demonstrated that dulaglutide is more effective than other antidiabetic agents by reducing the HbA1c by close to or greater than 1%.8 It is also the only GLP-1 agonist that has had a successful head-to-head trial showing noninferiority to liraglutide.13
Similar to other agents in the class, dulaglutide has demonstrated weight loss of approximately 6 pounds, which has been sustained over at least 26 weeks. However, one of the substantial benefits dulaglutide provides, and one that patients may place quite a bit of value on, is the convenience of once-weekly dosing compared with other agents' once-daily dosing.14 While dulaglutide use is not without risks and the adverse effects and contraindications must be considered, it is important to take into careful consideration its long-term safety profile by staying abreast of the current research taking place in regard to major cardiovascular events and the risk of pancreatitis or pancreatic cancer.15 Therefore, while dulaglutide has both risks and advantages, it is currently proven to be an adequate choice of treatment for patients with type-2 diabetes in the outpatient setting.
Drs. Smith, Mosley, Parke, and Brown are Assistant Professors of Pharmacy Practice at the Florida Agricultural and Mechanical University, College of Pharmacy and Pharmaceutical Sciences, in Tallahassee, Florida. At the time of writing, both Lillian Barris and Linh Phan were PharmD candidates at this institution.
Centers for Disease Control and Prevention. National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014 Atlanta, Georgia: U.S. Department of Health and Human Services. 2014;
Khardori R. Type 2 diabetes mellitus medication. Medscape October 82015;Available at: https://emedicine.medscape.com/article/117853-medication. Accessed May 18, 2016.
Dungan K, Buse J. Glucagon-like peptide 1-based therapies for type 2 diabetes: a focus on exenatide. Clin Diabetes 2005;23;(2):56–62.Available at: http://clinical.diabetesjournals.org/content/23/2/56.full. Accessed February 10, 2015.
Garber A. Long-acting glucagon-like peptide 1 receptor agonists: a review of their efficacy and tolerability. 2011;34;(suppl 2):S279–S284.10.2337/dc11-s231
Trulicity (dulaglutide) prescribing information Indianapolis, Indiana: Eli Lilly and Company. 2014;
Grunberger G, Chang A, Soria GG, et al. Monotherapy with the once-weekly GLP-1 analogue dulaglutide for 12 weeks in patients with type 2 diabetes: dose-dependent effects on glycaemic control in a randomized, double-blind, placebo-controlled study. Diabet Med 2012;29;(10):1260–1267.10.1111/j.1464-5491.2012.03745.x
RxList. Trulicity clinical pharmacology. November 102014;Available at: www.rxlist.com/trulicity-drug/clinical-pharmacology.htm. Accessed February 9, 2015.
Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (AWARD-1). Diabetes Care 2014;37;(8):2159–2167.10.2337/dc13-2760
Umpierrez G, Tofé Povedano S, Pérez Manghi F, et al. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care 2014;37;(8):2168–2176.10.2337/dc13-2759
Nauck M, Weinstock RS, Umpierrez GE, et al. Efficacy and safety of dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a randomized controlled trial (AWARD-5). Diabetes Care 2014;37;(8):2149–2158.10.2337/dc13-2761
Red Book Online Ann Arbor, Michigan: Truven Health Analytics. Accessed May 17, 2016.
Schwartz S, DeFronzo R. Is incretin-based therapy ready for the care of hospitalized patients with type 2 diabetes? The time has come for GLP-1 receptor agonists!. Diabetes Care 2013;36;(7):2107–2111.10.2337/dc12-2060
Farrokhi F, Smiley D, Umpierrez G. Glycemic control in non-diabetic critically ill patients. Best Pract Res Clin Endocrinol Metab 2011;25;(5):813–824.
DiaTribe. Lilly's GLP-1 agonist Trulicity shows promising results in trials. July 202014;Available at: https://diatribe.org/drugdevice-name/dulaglutide. Accessed February 9, 2015.
Edwards KL, Minze MG. Dulaglutide: an evidence-based review of its potential in the treatment of type 2 diabetes. Core Evid 2015;10:11–21.10.2147/CE.S55944


text:
Media Spin Louisiana Flooding as 'Climate Change' After Obama Report
Facebook/Ben Husser
John Binder
7 Sep 2016 Baton Rouge, LA
BATON ROUGE, Louisiana – Following unprecedented flooding that took the lives of 13 people and displaced more than 100,000 residents, the mainstream media were late to the scene for all the wrong reasons.
Weeks after the storms, even The New York Times editors admitted they had failed to cover the natural disaster, saying it took them two days before a story was ever posted on their website.
The Obama Administration's recent labeling of the event as proof of "climate change" has piqued the mainstream media's attention, however.
In a new report by the National Oceanic and Atmospheric Administration (NOAA), scientist Karin van der Wiel claims that climate change was the cause of much of the flooding that swept southeast Louisiana.
"Human-caused, heat-trapping greenhouses played a 'measurable' role in the colossal rainfall totals, which were fueled by high humidity and a stalled storm system above the Gulf Coast," van der Wiel said in the report, according to USA Today.
"The burning of fossil fuels such as oil, gas and coal releases greenhouse gases such as carbon dioxide into the Earth's atmosphere, which has warmed to levels that cannot be explained by natural variability, scientists say," USA Today reports. "Rainfall patterns and humidity levels are also affected by this process, as warmer air can hold additional amounts of water vapor."
Van der Wiel argues that rainfall in the state "is now expected to occur at least 40% more often" than in the past, citing computer models from NOAA which measured the amount of rain that impacted the region.
Likewise, The New York Times reported on the finding as well, though the liberal-leaning newspaper actually released a story in August immediately after the storm titled "Flooding in the South Looks a Lot Like Climate Change."
The Washington Post reported the study as almost being settled fact, writing "The disaster was caused by two weather-related features, extreme humidity and near-stationary low pressure that hovered over the Gulf Coast for days. The moisture component is where climate change comes in — warmer air can hold more water vapor."
And in lockstep with The New York Times, The Washington Post's editorial board published a piece after the flooding, claiming the disaster should serve as a "warning" of climate change, complete with social Marxist language.
"The future is being rigged against vulnerable people by a system in which government and industry are complicit," the Post wrote at the time. "No, we are not talking about the electoral system — we are talking about the climate."
During the Louisiana flooding, famed New Orleans Meteorologist Bob Breck cautioned that the mainstream media and federal agencies would begin pushing the climate change narrative.
Breck wrote on his blog at the time that "Before the Global Warming folks jump on our recent extreme rain event" they needed to look at the issue of urbanization, writing "Man building and paving over previous fields that soaked up the rains. Now that additional runoff is causing water in areas that had never seen water before."
John Binder is a contributor for Breitbart Texas. Follow him on Twitter at @JxhnBinder.
Border / Cartel ChroniclesMediaBarack ObamaBaton RougeClimate ChangeGlobal WarmingLouisianaLouisiana FloodingNational Oceanic and Atmospheric AdministrationNew OrleansNew York TimesNOAAObama administrationusa todayWashington PostWeather
Joe Biden's Brother Frank Linked to Taxpayer-Funded Projects
Report: Trump Readies Plan to Crack Down on 'Birth Tourism' in U.S.
Poll: Trump Approval Among Farmers Hits Record High

redpajama_set_name: RedPajamaCommonCrawl


text:
I thought you might be interested in this item at http://www.worldcat.org/oclc/912534 Title: The World almanac and book of facts. Publisher: New York : The New York World, New York : The New York World-Telegram New York : World Almanac Books Pleasantville, NY : World Almanac Books Westminster, MD : Random House. [1868-1876], [1886-] ISBN/ISSN: 0084-1382 OCLC:912534
The World almanac and book of facts.
New York : The New York World, New York : The New York World-Telegram New York : World Almanac Books Pleasantville, NY : World Almanac Books Westminster, MD : Random House. [1868-1876], [1886-]
Journal, magazine : Periodical : EnglishView all editions and formats
Lists news events, population figures, and miscellaneous data of an historic, economic, scientific and social nature.
The World Almanac and Book of Facts is a US published reference work and conveys information about such subjects as world changes, tragedies, sports feats, etc. It has been published yearly from 1868 to 1875, and again every year since 1886. The first edition of The World Almanac was published by The New York World newspaper in 1868 (the name of the publication comes from the newspaper itself, which was known as The World). Published just three years after the end of the US Civil War and the assassination of President Abraham Lincoln, its 120 pages of information touched on such events as the process of Reconstruction and the impeachment of President Andrew Johnson. Publication was suspended in 1876, but in 1886 newspaper publisher Joseph Pulitzer, who had purchased The New York World and quickly transformed it into one of the most influential newspapers in the country, revived The World Almanac with the intention of making it a compendium of universal knowledge. The World Almanac has been published annually since. Read more...
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Title varies: 18 -93, The World almanac. 1894-1922, The World almanac and encyclopedia. 1923 The World almanac and book of facts.
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The World Almanac and Book of Facts is a US published reference work and conveys information about such subjects as world changes, tragedies, sports feats, etc. It has been published yearly from 1868 to 1875, and again every year since 1886. The first edition of The World Almanac was published by The New York World newspaper in 1868 (the name of the publication comes from the newspaper itself, which was known as The World). Published just three years after the end of the US Civil War and the assassination of President Abraham Lincoln, its 120 pages of information touched on such events as the process of Reconstruction and the impeachment of President Andrew Johnson. Publication was suspended in 1876, but in 1886 newspaper publisher Joseph Pulitzer, who had purchased The New York World and quickly transformed it into one of the most influential newspapers in the country, revived The World Almanac with the intention of making it a compendium of universal knowledge. The World Almanac has been published annually since.
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According to our database1, Patrick Hild authored at least 13 papers between 2001 and 2017.
An accurate local average contact method for nonmatching meshes.
Optimal Convergence for Discrete Variational Inequalities Modelling Signorini Contact in 2D and 3D without Additional Assumptions on the Unknown Contact Set.
Symmetric and non-symmetric variants of Nitsche's method for contact problems in elasticity: theory and numerical experiments.
A Nitsche-Based Method for Unilateral Contact Problems: Numerical Analysis.
An Improved a Priori Error Analysis for Finite Element Approximations of Signorini's Problem.
A Sign Preserving Mixed Finite Element Approximation for Contact Problems.
A stabilized Lagrange multiplier method for the finite element approximation of contact problems in elastostatics.
Residual Error Estimators for Coulomb Friction.
An Error Estimate for the Signorini Problem with Coulomb Friction Approximated by Finite Elements.
A posteriori error estimations of residual type for Signorini's problem.
Numerical Approximation of the Elastic-Viscoplastic Contact Problem with Non-matching Meshes.
Mixed finite element methods for unilateral problems: convergence analysis and numerical studies.
A Posteriori Error Control of Finite Element Approximations for Coulomb's Frictional Contact.


This does not really outline any information, however it does outline what the category title means, that's, what an object of the category will include and what operations may be performed on such an object. Along with that, the second side of Java, and lots of world argue a very powerful, Java is platform independent. Exterior code can use an object by calling a specific occasion technique with a certain set of input parameters, read an instance variable, or write to an instance variable. Another advantage is that if you happen to can seek advice from a instructor or scholar object as a SchoolMember object which may very well be useful in some conditions corresponding to counting of the variety of faculty members. Python is highly object-oriented and understanding these concepts rigorously will help you a large number in the long term.
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The point is to present some indication of the flavour of the languages and some perception into the true-world application of OO ideas. Encapsulation is an Object Oriented Programming concept that binds collectively the data and capabilities that manipulate the data, and that keeps each safe from outdoors interference and misuse.


Experience Yoga at the North Sea!
Our inviting retreat house is a renovated farmhouse offering a family friendly, spiritual and natural atmosphere. The property includes beautiful lawns, children's playground, orchard and magnificent old trees.
Guided walks across the mudflats.


Kuku sabzine does not have a single recipe like many recipes, everybody cooks it differently.
Its basic features are having plenty of green spices, the amount of eggs is less than herbs and the egg is used only as a binder, the taste is supported with powder spices.
Walnut and dried fruit can be added just like I do, or just to decorate. The baking powder is again optional. The greenery and the spices are completely based on your taste. But keep it in mind that generally the fresh herbs such as fresh onion or garlic is used. Unfortunately I could not use onions and garlic because of stomach problems. I also could not dare to put very dense tastes together, so I used purslane. In addition I used plenty of parsley, dill, fresh mint, fresh thyme in my herb mixture.
Then turn it upside down and cook for five mins. more.
Hi. I love your recipes. Can you tell me what kind of dried berries I need for this recipe ? Thank you. Çok teşekkürler.
Originally barberries are used but it's not easy to find them everywhere, so feel free to use any you can find. Cranberries or blueberries will work out for example.


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Robo Dialer saying I have a warrant for my arrest.....if this were true they would have mailed me something months ago as I have been harrassed by these dialers for over 6 months now.
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1916, portions of NC 133, particularly between its northern terminus and Wilmington were added to the state's highway system as NC 40 and NC 60. The segment. Route 133 is a 40. 87-mile-long east–west Massachusetts state route that runs from Route 38 and Route 110 in Lowell to Route 127 in Gloucester. Illinois Route 133 is an east–west state road in east-central Illinois. It runs from Illinois Route 32 in Lovington to U.S. Route 150 and Illinois Route. State Route 133 southeast-to-northwest state highway in the southwestern part of the U.S. state of Georgia. It. The Bücker Bü 133 Jungmeister was an advanced trainer of the Luftwaffe in the 1930s. It was a single-engine, single-seat biplane of wood and tubular steel. Route 133 is a historic and heritage road of the Estrie and Montérégie regions in the province of Quebec, with north/south orientation and located on. STS-133 was the 133rd mission in NASA's Space Shuttle program; during the mission, Space Shuttle Discovery docked with the International. Consists of a single pad, originally designated 133/1, and later 133/3. The first launch from Site 133 was of a Kosmos-2I, on 16 March 1967, carrying the.
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36, no. 4, pp. 133–136, Bibcode:2009MPBu. 36. 133P. Asteroid Data. 133rd Armored Division Littorio was an armored division of the Royal Italian Army during World War II. 133° The meridian 133° east of Greenwich is a line of longitude extending from the North Pole across the Arctic Ocean, Asia, Australia, the Indian Ocean. 133° The meridian 133° west of Greenwich is a line of longitude that extends from the North Pole across the Arctic Ocean, North America, the Pacific Ocean. Probable G-protein coupled receptor 133 is a protein that in humans is encoded by the GPR133 gene. This gene encodes a member of the adhesion-GPCR family. Conducted by Statistics Canada, the RM of Bengough No. 40 had a population of 305 living in 116 of its 133 total private dwellings, a change of 8. 5% from its. Diesel engine KamAZ-7403. Serially not produced ZIL-133G40 – further development of the ZIL-133GYa with the cab of ZIL-4331 and diesel engines. USS Pillsbury was an Edsall-class destroyer escort in service with the United States Navy from 1943 to 1947. She served again as a radar picket. 112 BC was a Roman politician and historian of plebeian origin, consul in 133 BC and censor in 120 BC.
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Piso belonged to the plebeian gens Calpurnia, which. Service June 1917. The first Mark 4, gun No. 133, was completed July 1896. Production numbers were Nos. 133–196, 260–263, and 423–426. It was the first. GRO J1655-40 is a binary star consisting of an evolved F-type primary star and a massive, unseen companion, which orbit each other once every 2. 6 days. Municipal Boundaries v t e v t e. O'Reilly 52 Wynne-Thomas, Peter. Coordinates: 40°08′N 44°26′E / 40. 133°N 44. 433°E / 40. 133; 44. 433 Agdzhakishlag or Aghjaghshlagh is a town in the Yerevan Province of Armenia. Agdzhakishlag. Coordinates: 40°58′N 49°08′E / 40. 967°N 49. 133°E / 40. 967; 49. 133 Kyucheyri is a village in the Khizi Rayon of Azerbaijan. Kyucheyri. Coordinates: 40°08′N 43°40′E / 40. 133°N 43. 667°E / 40. 133; 43. 667 Bakhchalar is a town in the Armavir Province of Armenia. Armavir. The 133rd Tank Regiment is an inactive tank regiment of the Italian Army based in Altamura in Apulia. Originally the. The 12. 8 cm FlaK 40 was a German World War II anti-aircraft gun.
Although it was not produced in great numbers, it was reportedly one of the most effective. Coordinates: 40°08′N 46°06′E / 40. 133°N 46. 100°E / 40. 133; 46. 100 Qasımlar is a village in. Coordinates: 40°08′N 45°51′E / 40. 133°N 45. 850°E / 40. 133; 45. 850 Karakoyun is an abandoned village in the Gegharkunik Province. Coordinates: 40°56′N 45°08′E / 40. 933°N 45. 133°E / 40. 933; 45. 133 Lusadzor is a village in the Tavush Province of Armenia. The. Coordinates: 40°48′50″N 73°56′41″W / 40. 81389°N 73. 94472°W / 40. 81389; -73. 94472 133rd Street is a street in Manhattan and the Bronx, New York City. Route 133 is a Transport for London contracted bus route in London, England, running between Streatham and Liverpool Street stations. Route 133 commenced. Coordinates: 40°24′N 46°08′E / 40. 400°N 46. 133°E / 40. 400; 46. 133 Şahkərəm is a village in the Dashkasan Rayon of Azerbaijan. The. Coordinates: 40°08′N 44°01′E / 40. 133°N 44. 017°E / 40. 133; 44. 017 Norapat is a former town in the Armavir Province of Armenia.
King's Highway 40, commonly referred to as Highway 40, is a provincially maintained highway in the southwestern portion of the Canadian province of Ontario. USS SC-40, until July 1920 known as USS Submarine Chaser No. 40 or USS S. C. 40, was an SC-1-class submarine chaser built for the United States Navy during. This Is 40 is a 2012 American comedy film written and directed by Judd Apatow and starring Paul Rudd and Leslie Mann. A sort-of sequel to Apatow's 2007. The 133rd Pennsylvania Volunteer Infantry was an infantry regiment that served in the Union Army during the American Civil War. The 133rd Pennsylvania. The 133d Air Refueling Squadron is a unit of the New Hampshire Air National Guard 157th Air Refueling Wing located at Pease Air National Guard. Coordinates: 40°08′N 47°03′E / 40. 133°N 47. 050°E / 40. 133; 47. 050 Ayaq Qərvənd. Coordinates: 40°16′N 46°08′E / 40. 267°N 46. 133°E / 40. 267; 46. 133 Qaradağlı is a village in the Kalbajar District of Azerbaijan. It is. Coordinates: 40°07′N 47°08′E / 40. 117°N 47. 133°E / 40. 117; 47. 133 İkinci Yüzbaşılı.
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Don't get stuck in a post-holiday slump! We know Boston winters can be long, but there is a bright side: Crush's Winter Sale! We've got incredible deals from all of our favorite designers to keep you looking stylish whether it's sunny or snowy. We're excited to share some of our staff's picks from this year's sale, but we can't show it all so make sure to swing by both Crush Boutique locations or check out our Instagram stories for the inside scoop!
Leaving on a jet plane for a warm vacation? We've been carrying cult favorite MISA Los Angeles for a few seasons now and their breezy, boho vibe is perfect for beach vacations.
We've loved Rails since the beginning of their button down journey and so have you! There's nothing better on a cold day than the buttery softness of this Crush classic!
Of course, cashmere is a must-have to survive any New England winter, and, let's face it, spring!
Speaking of spring, this sunny dress from Milly is sure to warm you right up!
Our annual winter sale never lasts long so plan a trip to one of our stores in Boston soon! Don't forget to follow us on Instagram for all the details on new arrivals, events, and special surprises! Not in Boston? Just send us a DM or call 617-720-0010 to order!


Big box retailer, Meijer, and the U.S. Consumer Product Safety Commission today announced the recall of some 68,000 bicycles sold between March and August throughout the midwest. The recall arises from what seems to be poor assembly of the bicycles' pedals on-site at Meijer stores by an outside company, Serv-U-Success. Meijer has received "29 reports of pedals detaching or coming loose during use," with 16 reports of injuries, according to the Commission. The recall applies to various models of Huffy, Iron Horse, Mongoose, Northwoods, Pacific, Razor and Schwinn bicycles. Click here to view all of the models affected.
Owners of the bikes should stop using them immediately and return them to a Meijer store for a replacement bike or full refund.


The 50th International October Conference on Mining and Metallurgy is organized annually, aims at providing a forum for presentation and discussion of scientific research, technological development and practice on the subjects of geology, mining, metallurgy, material science, technology, environmental protection, energy efficiency, recycling, industrial informatics, industrial management and related engineering topics. The Conference has been organized jointly by the Mining and Metallurgy Institute Bor and Technical Faculty in Bor, University of Belgrade. Firstly, it was a national conference, then a conference with international participation, and since 2002 – international conference.
The Conference has been organized jointly by the Mining and Metallurgy Institute Bor and Technical Faculty in Bor, University of Belgrade.


Rachel jumped in and described Tom as a hippie with an affinity for dad jokes.3.
They Had Thoughts on Online Dating: Speaking of online, they are all spoken for romantically, but we asked them their thoughts about online dating—specifically Tinder.
They Dished on Their Celebrity Crushes: Rachel admitted to crushing on Dave Grohl, Tom applauded Tatiana Maslany from .
Last night we met up with country music superstars Gloriana in between their soundcheck and their live concert in Los Angeles.
The band was in town to perform as a part of The Grove's 2015 Summer Concert Series in partnership with Glade.
The conference will have two keynote talks by world-renowned scholars of the Elizabethan-era.
John Cooper, Senior Lecturer at the University of York and Principal Investigator for the St. The conference will take place at the Tower of London, a world-famous historic site and royal palace linked to Queen Elizabeth, and centrally located for travel by both UK and international scholars.
The Gloriana Society invites advanced graduate students and faculty to attend the inaugural meeting of our biannual conference In the Light of Gloriana, Nov 18-21, 2016 at the Tower of London. Levin is the Willa Cather Professor of History and Director of the Medieval and Renaissance Studies Program at the University of Nebraska-Lincoln. We seek to bring together scholars and presentations that look at all aspects of the Elizabethan era, from religion, politics, diplomacy, education, music, and trade; to medicine, literature, theater, gender, art, law, war, and daily life.


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Trae tha Truth Is Rescuing Victims of Hurricane Harvey, Houston Rappers Assisting on Social Media [VIDEO]
Trent Fitzgerald Published: August 29, 2017
The city of Houston is currently under water and the ongoing rain from Hurricane Harvey is causing catastrophic flooding all over the city and in surrounding areas.
Several rappers from the Houston area have been using their social media platforms to deliver disaster information and mobilize relief efforts for the citizens of H-Town.
Houston legend Trae tha Truth has been on the front lines of the relief efforts in the flooded city. The Rap-A-Lot artist was in a boat rescuing people who were trapped in their flooded homes. While being interviewed on Fox26, he urged people who have boats and trucks to come and help in anyway they can. He said folks need supplies, clothes and food as well.
Other Houstonians like Baby Bash is stuck inside his home and is trying to figure out how he's going to help his city. The rapper is fine and well but told TMZ that the chaos and looting is already starting in Houston.
"It's chaos, tragedy," he said. "It's almost like a biblical, historical flood. We just want people to understand this is real, this is not no joke. This is devastating.The flood is one thing. And then, the chaos and the anarchy and the craziness and the people just desperate to steal to survive is gonna be a whole other issue."
Meanwhile, fellow H-Town rappers Slim Thug, Paul Wall and Devin the Dude have been posting disaster information on their Instagram accounts.
As we reported earlier, Houston native Beyoncé vowed to do everything she can to help the victims in her beloved city. In a statement given to the Chronicle, the pop superstar said, "My heart goes out to my hometown, Houston, and I remain in constant prayer for those affected and for the rescuers who have been so brave and determined to do so much to help. I am working closely with my team at BeyGOOD as well as my pastor (Rudy Rasmus) to implement a plan to help as many as we can."
If you want to help Houston and other affected areas in Texas, the Chronicle posted a list of how you can donate and assist.
Prayers up for Houston.
Baby Bash Describe Chaos in Houston After Hurricane Harvey
50 Inspirational Quotes From Your Favorite Rappers
Source: Trae tha Truth Is Rescuing Victims of Hurricane Harvey, Houston Rappers Assisting on Social Media [VIDEO]
Filed Under: Beyonce, Slim Thug, The AllThatYaz Show, TRAE THE TRUTH, Yasmin Young
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Six Stories was a new piece of work created for the Brighton Digital Festival in 2014.
It was one of a small number of successful Grassroots Awards.
We interviewed Six older people, and turned their stories into a video-mapped installation.


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Daveed Diggs Raps Fast Jimmy Fallon – You Didn't Know This
The Plot of Daveed Diggs Raps Fast Jimmy FallonDaveed Diggs Raps Fast Jimmy Fallon
The train is divided into classes, where the lower class lives in squalor while the upper class takes pleasure in the best life has to use. When Curtis, a member of the lower class, discovers of a plot to take and overthrow the elite control of the train for themselves, he needs to decide whether or not to sign up with in.
Jennifer Connelly and Daveed Diggs star alongside Mickey Sumner, Alison Wright, Iddo Goldberg, Susan Park, Katie McGuinness, Sam Otto, Sheila Vand, Mike O'Malley, Annalise Basso, Jaylin Fletcher, Lena Hall and Roberto Urbina. Steven Ogg, Rowan Blanchard, and Sean Bean signed up with the main cast in the second season and both Chelsea Harris and Archie Panjabi signed up with the primary cast in the third season.
Rowan Blanchard is a young starlet who is quickly rising to popularity. She is best understood for her role as Riley Matthews on the Disney Channel program Girl Fulfills World. It was produced by ABC Studios and stars Rowan Blanchard, Ben Savage, Sabrina Carpenter, Vincent Martella, Peyton Meyer and Mitchell Hope.
She made her film debut in 1984's "Maze" and continued to work steadily in films throughout the '80s and '90s. In recent years, she has starred in such movies as "He's Just Not That Into You" (2009) and "Rage of the Titans" (2012 ).
In Daveed Diggs, we see an artist who defies classification. He is a rap artist, a singer, an actor, and a writer, and he has actually managed to excel in all of these fields. His work is both innovative and powerful, and it has won him crucial honor and a big following.
Sean Bean is an English actor best understood for his functions in the television series "Sharpe" and the films "Goldeneye," "The Lord of the Rings," and "Game of Thrones." Born in Sheffield, England, Bean began his acting profession in 1987 with a function in the Royal Shakespeare Company's production of "Antony and Cleopatra." He has given that starred in many movies and tv series, earning a reputation as one of Hollywood's the majority of versatile actors.
Snowpiercer is a 2013 American science fiction action film based on the French graphic unique Le Transperceneige by Jacques Lob, Benjamin Legrand and Jean-Marc Rochette. Set in a future where a failed climate-change experiment has eliminated all life on the world except for those aboard the Snowpiercer, a train that takes a trip around the globe, the film follows its guests as they fight for their survival. Daveed Diggs Raps Fast Jimmy Fallon
The team includes showrunner Graeme Manson and director Scott Derrickson.
The world is about to alter. A new post-apocalyptic society has actually been created, where the only method to endure is by riding the tracks of a huge train that circles around the world. The travelers of this train are divided into classes: the rich elites, who live in high-end on the upper levels; and the rest of the guests, who live on floors below in squalor. On board this train are a diverse group of characters, all having a hard time to find a location they can call home.
On a train that never stops, the last people alive live in a world of their own. The train is divided into classes, where the lower class lives in squalor while the upper class delights in the finest life has to offer. When Curtis, a member of the lower class, finds out of a plot to topple the elite and take control of the train for themselves, he needs to decide whether or not to join in. Set in a future where a failed climate-change experiment has actually killed all life on the planet except for those aboard the Snowpiercer, a train that travels around the globe, the film follows its guests as they battle for their survival.
The guests of this train are divided into classes: the wealthy elites, who live in luxury on the upper levels; and the rest of the passengers, who live on floorings listed below in squalor.


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LEONARD, CHRISTOPHE
Cholet Basket 12 Forward
Height: 1.99 Born: 3 January, 1990 Nationality: France
EuroCup 2009-10 STATISTICS
Totals 3 1 22:43 2 1/4 0/1 0/0 0 2 2 0 0 2 0 0 3 1 -4
Averages 3 1 7:34 0.7 25% 0% 0% 0 0.7 0.7 0 0 0.7 0 0 1 0.3 -1.3
1 vs Benetton Basket 9:43 0/2 0/1 2 -5
2 * at Dynamo Moscow 5:32 0/1 1 1 2 -2
6 vs Dynamo Moscow 7:28 2 1/1 1 1 1 1 3
3 Totals 22:43 2 1/4 0/1 0/0 0 2 2 0 0 2 0 0 3 1 -4
Average 7:34 0.7 25% 0% 0% 0 0.7 0.7 0 0 0.7 0 0 1 0.3 -1.3
EuroCup 2009-10 individual rankings
Index rating 3 Cholet Basket vs. DYNAMO MOSCOW 1/12/2010
Points 2 Cholet Basket vs. DYNAMO MOSCOW 1/12/2010
Offensive rebounds 0 Cholet Basket vs. DYNAMO MOSCOW 1/12/2010
Defensive rebounds 1 Cholet Basket vs. DYNAMO MOSCOW 1/12/2010
Total rebounds 1 Cholet Basket vs. DYNAMO MOSCOW 1/12/2010
Assists 0 Cholet Basket vs. DYNAMO MOSCOW 1/12/2010
Steals 0 Cholet Basket vs. DYNAMO MOSCOW 1/12/2010
Blocks 0 Cholet Basket vs. DYNAMO MOSCOW 1/12/2010
Minutes 9 Cholet Basket vs. Benetton Treviso 11/24/2009
Played with Centre Federal du Basket (2005-08).
Signed for the 2008-09 season by Cholet Basket.
He's still playing there.
Won the 2009-2010 French National Championship with Cholet Basket.
Won the 2010 French Super Cup with Cholet Basket.
Has been member of the French U-16, U-18, U-19 and U-20 National Team.
Won the gold medal at the 2010 European U-20 Championship.
Played at the 2009 World U-19 Championship.
2010-11 Cholet Basket 8 36 4.5 13/22 59.1 2/3 66.7 4/4 100 21 2 3 1
Totals 8 36 4.5 13/22 59.1 2/3 66.7 4/4 100 21 2 3 1
Averages 8 36 4.5 13/22 59.1 2/3 66.7 4/4 100 2.6 0.3 0.4 0.1
2009-10 Cholet Basket 3 2 0.7 1/4 25 0/1 0 0/0 0 2 0 0 0
Totals 3 2 0.7 1/4 25 0/1 0 0/0 0 2 0 0 0
Averages 3 2 0.7 1/4 25 0/1 0 0/0 0 0.7 0 0 0
2006/07 Centre Fed. 14 100 7.1 24/43 55.8 8/19 42.1 28/42 66.7 28 13 12 4
2007/08 Centre Fed. 29 439 15.1 145/281 51.6 17/95 17.9 98/156 62.8 174 32 55 6
2008/09 Cholet 6 8 1.3 4/5 80 0/2 0 0/0 0/0 3 2 0 0
2009/10 Cholet 8 14 1.8 4/8 50 1/3 33.3 3/6 50 6 1 1 0


Surprisingly, the sport is not only interesting to the active sportsmen but also attracts a lot of attention of the audience. More often, sports are not venturous, but there are some areas where you can quench your thirst for thrills by betting. Professionals make the best today's sports predictions and publish them on various resources where the information is available to the public. There are both free general predictions and paid on an individual request. Users of such portals are interested in predictions for profitable bets; so many gamblers are willing to pay for valuable information. Experienced gamers also make today's sports betting predictions, but, as a rule, in personal interests, and with free access.
Simple single bets are the most common type that is used by gamblers in real and virtual bookmakers. More often, users choose a particular outcome of the event for the team: victory, defeat or draw. In each case, there is a payout ratio, which directly depends on the probability of this event. Today's prediction for the football events is often used by gamers to determine the favorite of the upcoming match.
There is an option of betting for two outcomes at the same time. For example, you can bet on a win or draw of your favorite team. In this case, the payout ratio will be smaller than in the first variant. However, it is easier to guess the outcome of the event. Such a stake is used if you are sure that the team will not lose.
The handicap is an unusual and exciting type of betting. Its point is to equalize the chances for gamblers of two teams with different strengths. As a rule, the favorite team needs to make much more efforts to play the bet. But the outsider team needs to lose by a minimum margin. Thus, the probability of winning of the first or second team is more or less equalized. We should not reject the option when the stake is a draw. In this case, the gambler returns his bet. Top today's sports predictions will surely come in handy for a winning bet.
The total is a stake that does not depend on the victory of a particular team. In this case, you have to predict the total number of points scored, goals, etc. A gambler bets either on the fact that more goals will be scored than the bookmaker said, or less. The payout ratios are minimal.
More complex bets can bring a solid win to users. So, for example, having studied a today's football prediction and guessed the outcome of the game in the first, as well as in the second half, a bettor gets a win. However, if at least in one half the prediction was incorrect, the bet is automatically lost. We can find this bet under the name Time / Match.
«burns out». In case of victory, the bettor gets a win made on the multiplied coefficients, which means that even with a minimum bet, you can hit a huge jackpot.
What Kind Of Sport Can I Bet On?
Today's sports predictions from professionals will help both beginners and experienced bettors.