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Megabucks are slots with progressive jackpots, combined into a single network that covers casinos in several American states. The owner and operator of this network is International Game Technology, better known by its abbreviated name IGT.
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Megabucks slot is considered as an alternative to state lotteries and enjoys incredible popularity among Americans. Actually, there is an opinion that IGT specifically released it to create a lottery competition. Since the beginning of the eighties in the twentieth century, when the slot was launched for the first time, this slot made dozens of players millionaires.
The Airport: There are plenty of slot machines at McCarran International Airport in Las Vegas as well as in the Reno-Tahoe International Airport serving Northern Nevada. These should be avoided like the plague. They’re clean, well run and offer many up-to-date models. Awaiting an airport for your fight isn’t so bad after all this California woman with playing a slot machine at the Las Vegas airport before returning home. She says she visits face several times a. This is my Biggest slot machine jackpot handpay at Las Vegas Airport!! Often times during our Las Vegas trips, we play the Dragon Link Slot Machines while wa.
Thanks to the skillfully organized advertising company, every Megabucks jackpot, when it reaches a considerable size, causes a real excitement among the gambling public. And every hit of the progressive jackpot is widely covered in the media, attracting even more casino visitors to the slot. No other slot in the world is overgrown with so many incredible myths, rumors, and legends. But with all this, there are a lot of gambling experts and just experienced players who consider Megabucks a hideous slot that absolutely does not deserve so much attention. So, who is right: fans or opponents of this slot?Where to Play the Megabucks Slot
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The classic version of the Megabucks slot from IGT is a 3-reel slot machine with the only one payline. In order to qualify for a progressive jackpot, the player must definitely bet three dollars. There are a lot of stories (both true and fictitious) about casino customers, who had the jackpot combination, but they did not receive any jackpot because of a bet less than three dollars.
The progressive jackpot is not completely nullified when a lucky winner gets it but starts to grow from a certain amount. In recent years, this fixed amount is $10,000,000. There are persistent rumors that soon this initial sum of the jackpot should increase by one million.Megabucks Slot Odds
Strange as it may seem, there is no official information about the probability of winning the Megabucks jackpot. Some casinos say that the player has one chance out of 50 million, while others claim that this is one chance of 17 million. Whatever it was, when the sum of the jackpot is large enough, fans of this slot are ready to fly thousands of kilometers to try their luck.
What do Lady Luck’s favorites have from this slot? Do they get all that huge amount of money that is advertised? When you win a jackpot, events can unfold as follows. First of all, the lucky guy will receive a check for $1,400,000. Then the winner is given two or three months to decide how he wants to get his winnings. There are two options: the amount is divided into annual payments, which will be transferred to the player within twenty-five years, or he can get the winnings immediately at a time, but at a rate of 60% of the jackpot.
That is, having won ten million, the winner can receive in the second variant only six million, but at once and with one payment. After receiving the win, he still has to pay taxes. Unsurprisingly, almost all holders of Megabucks jackpots prefer to receive their winnings in the form of annual payments.
However, in this case, they also have to pay taxes, the Internal Revenue Service of the United States (IRS) very strictly follows this. Subtract from the total amount of the jackpot another 40%, because such winnings are taxed at the maximum rate. So, the next time you hear that someone has won ten million in Megabucks and immediately took all the money, you know that the lucky guy got a little over three and a half million at his disposal.The Curse of the Megabucks Jackpot
As already mentioned above, there are a lot of urban legends about the Megabucks slot and its jackpot, mostly of a gloomy nature. For the most part, they describe the tragic fate of players who managed to win a huge jackpot. It is believed that almost all the lucky people either perish or suffer numerous woes. The cause of their numerous misfortunes is the so-called Curse of the Megabucks slot.
Of course, in these stories, there is much more fiction than the truth. However, there is no smoke without fire — some winners, really, seriously suffered after they won the jackpot. In particular, the further life of the waitress Cynthia J. Brennan, who won $34.9 million in 2000, was sad. A month and a half after the win, Cynthia and her sister were hit by a drunk driver. The sister died on the spot, and Cynthia was forever paralyzed. The guy who drove the car in a state of intoxication was imprisoned for twenty-eight years.
But the rumors about the curse of Megabucks spread even before the year 2000. Simply, this accident was widely covered in the press and made people remember about other similar events, which at that time did not become so resonant. In 2003, many media published a story about a 25-year-old player who became the owner of the Megabucks jackpot and either died from a drug overdose in a casino hotel or was killed in a street shootout. IGT companies had to work hard to convince the public of the falsity of these statements.
There are also a lot of rumors about underage players and employees of different casinos who won the Megabucks jackpot but could not get it due to existing rules. 7000 free games. But none of these rumors received documentary evidence.
Many experts in the field of gambling suggest that ITG recently made relevant changes to the Megabucks system, which makes the jackpot play less often, but with larger amounts. Although officially the company claims that nothing of the sort has happened, this opinion remains very popular.Where Could You Play Megabucks?
Most fans of slot machines and large jackpots are not afraid of the curse of Megabucks and are willing to play in this slot. You can find this slot in almost all real casinos on the Las Vegas Strip, as well as in other establishments in Nevada, California, New Jersey, Mississippi, and some Indian reservations. Each state has its own separate network of Megabucks slots, but the biggest progressive jackpots are expected in Nevada. In other states, jackpots are much smaller.Why do Experts Consider Megabucks a Bad Slot?
Experts do not believe in the curse of the Megabucks slot, but this does not stop them from considering this gambling machine not worthy of attention. The fact is that this slot is very unprofitable for the player. Firstly, it has an extremely high percentage of the casino advantage, which reaches 10-15% (for comparison, many slots in the Las Vegas casino are limited to 2-3%). Secondly, the procedure for paying a jackpot is extremely inconvenient. The winner either loses 40% of the amount or gets it in parts for 25 years. But the progressive jackpots of most other slots are paid immediately and in full.
All this suggests that Megabucks is a mediocre slot, which gained its popularity only thanks to record payments and a masterly organized PR campaign.Slots At Vegas AirportSee AlsoLas Vegas Progressive Jackpots
As a disciple to the math that surrounds all forms of gambling, there are only a few good things I have to say about the slot machines.
They require no thought, can provide a short-term jackpot that’s unattainable in most other games, and they are undeniably fun.
In the end though, they will take all of your money and are physically programmed to return about 90 cents of every dollar put into them, but that’s doesn’t mean I’m totally immune to their temptations.
A recent layover in Las Vegas provided two hours to hit the machines because, hey, it’s all they have inside the airport (although a poker room would be a huge hit). And it provided a scenario that allowed an opportunity to actually answer one of the most common questions to hit my inbox.
Can you ever win at McCarran International?
The machines have a notorious reputation as that last ounce of blood money to be squeezed from the wallets of outgoing tourists. At certain casino properties, the slot payout percentages are openly advertised, although this is getting rarer by the day. The airport staff won’t tell you theirs either, because, frankly, they have no idea because there are more than 1,300 units spread throughout the facility. All the attendant could tell me was they were regularly inspected by state regulators.
I’ve probably spent more than 40 hours waiting for flights inside the terminals without ever hearing the rings of a super jackpot.
But they do happen.Mjg Airport Slots Las Vegas
According to a report from winthebet.com, six-figure wins aren’t overly rare, and a record $3.9 million jackpot was hit on a “Wheel of Fortune” progressive machine inside a terminal. The same attendant who couldn’t tell me the payouts admitted she did witness a $350,000 win her third month into the job.
There is a teeny, tiny bit of bad news that comes with winning big, though. You’ll probably miss your flight and have to book another one after doing the required paperwork.
So with my two hours to burn, I plopped a $50 bill into a “penny” machine that is legally allowed to be grossly mislabeled when the minimum bet was 80 cents per spin (that increased in those increments) with the option for as much as $3.20 max-bet spin.
I forget the name of the game, but it had a vibrating seat and was Aztec themed, had 3-D graphics and a tree frog shot balls out of its mouth at targets while the traditional slot reels churned combinations.
The minimum was wagered the first 10 spins as I settled into the game, with only a few free spins won. But it looked like something was about to happen, so I pressed to the 160 bets to chase the losses and my $50 was down to about $10.
That was when the first good payout hit, about $35, getting almost back to even.
I pressed again to the 240 after another dose of nothing spins. The machine went slightly insane, spewing coins into my till at a feverish pace.Las Vegas Airport Slot Machines
I applied my gambling math wits and cashed out for about $100. A small profit that’s nothing to brag about, but in the world of notoriously stingy airport slots, any win is a win.
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*Arboreal herbivory is rare among mammals. The few species with this lifestyle possess unique adaptions to overcome size-related constraints on nutritional energetics. Sloths are folivores that spend most of their time resting or eating in the forest canopy. A three-toed sloth will, however, descend.
*The lifestyle of the Sloth has so many lessons for human survival in the 21st century. If we continue to promote the dominant paradigm of infinite growth with our ’faster, bigger, stronger’ behavior; the economic system pushing mass-production, mass-consumption and a scientific, reductionist view of nature it is clear that we will.
*Sloths are classified as Folivora, meaning leaf eaters. They are fond of eating buds, shoots and leaves. However, the two toed sloths feed on insects, reptiles and even birds. Though these animals have well adapted to the trees, leaves do not provide enough nutrition and energy and also make digestion difficult.
Sloths have no problem taking life slowly. In fact they rarely move more than 100 m (328 ft) in a day and their average speed does not exceed 0.5-0.6 kph (0.31-0.37 mph) (Billet et al., 2012). Okay, you don’t have to slow down that much but it is a good reminder to take a moment to breathe and look at the world around you.
Native to Central and South America, sloths eat, sleep, mate, give birth and raise their young while hanging upside-down in trees. The slowest mammals in existence, they can walk on the ground but only with extremely awkward and unwieldy movements. They’re much better swimmers. Some of their adaptations differ slightly, but both sloth families -- two-toed and three-toed -- are uniquely suited to their slow-paced, arboreal lives.Camouflage
Three-toed sloths have tan coats, while two-toed sloths usually have gray-brown fur. While these tones match tree trunks and branches, the animals have another layer of camouflage: Green algae grow from their hair, enabling them to better blend into the leaves and vines of the treetop canopy. Their extremely slow movements might also help conceal them from predators that rely on vision to hunt.Defense
With their slow speed, sloths might seem like easy prey for anacondas, boas, wild cats, eagles and hawks. However, they use their long, sharp claws -- normally used to hold onto branches -- and very sharp teeth to fiercely defend themselves. Casino map pa. When they’re in the trees, special adaptations help them spot potential threats. Two-toed sloths can tilt their heads 45 degrees backward to watch for predators. Three-toed sloths have nine cervical vertebrae -- four more than their relatives -- that enable them to rotate their heads 270 degrees to scan for threats.Sloths LifespanWeather Adaptations
Sloths’ thick, dense coats help keep them dry during the rainy season. An undercoat guards their skin, while the longer, outer hairs hang down at an angle, providing a natural path for water to flow off the animal. C plotting library. Two-toed sloths can vary their body temperature from 75 to 91 degrees Fahrenheit, allowing them to adapt to various weather conditions. Three-toed sloths raise their body temperature by basking.Metabolism
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Conventional thrombolytic drugs for vascular blockage such as tissue plasminogen activator (tPA) are challenged by the low bioavailability, off-target side effects and limited penetration in thrombi, leading to delayed recanalization. We hypothesize that these challenges can be addressed with the targeted and controlled delivery of thrombolytic drugs or precision drug delivery.
Ischemic stroke occurs when a blood clot obstructs or narrows the arteries that supply blood to the brain. Currently, tissue plasminogen activator (tPA), a thrombolytic agent, is the only United States Food and Drug Administration (FDA)-approved pharmacologic treatment for ischemic stroke. Thrombolytics are medicines that may be used for the emergency treatment of an ischemic stroke (a stroke caused by a blood clot), a heart attack (myocardial infarction), or a massive pulmonary embolism (PE). They may also be used for other indications. TPA works by dissolving blood clots. That helps to restore blood flow to the brain after a stroke, potentially preventing additional brain cells from dying. TPA is only recommended if it can be.
Plastic bronchitis (PB) is a rare, most often pediatric disease characterized by the formation of obstructive airway casts primarily composed of fibrin. There is presently no FDA-approved pharmacotherapy for PB, but acute exacerbations of the illness are often treated with inhaled tissue plasminogen activator (tPA). To date, this is done somewhat anecdotally because there has been no safety or efficacy testing of this treatment. In addition, there is presently no reliable surrogate marker of adverse drug events. Nevertheless, in the absence of inhaled tPA treatment, PB-induced respiratory distress can be severe, often warranting urgent or emergent bronchoscopy for cast removal, or can sometimes result in respiratory failure. As such there is a significant unmet need for safety and efficacy testing of inhaled tPA and for biomarkers of drug response.
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This is the documentation to Matplotlib for C, a C wrapper for Python’s matplotlib (MPL) plotting library. The code is organised in this GitHub repository, which is a fork of that repository. ScottPlot is a free and open-source plotting library for.NET that makes it easy to interactively display large datasets. Line plots, bar charts, pie graphs, scatter plots, and more can be created with just a few lines of code. ScottPlot Demo

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Grantville
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Bensalem
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*Gplots Bioconductor DOI: 10.18129/B9.bioc.Linnorm
This package is for version 3.8 of Bioconductor;for the stable, up-to-date release version, seeLinnorm.Linear model and normality based transformation method (Linnorm)
Bioconductor version: 3.8
Linnorm is an R package for the analysis of RNA-seq, scRNA-seq, ChIP-seq count data or any large scale count data. It transforms such datasets for parametric tests. In addition to the transformtion function (Linnorm), the following pipelines are implemented: 1. Library size/Batch effect normalization (Linnorm.Norm), 2. Cell subpopluation analysis and visualization using t-SNE or PCA K-means clustering or Hierarchical clustering (Linnorm.tSNE, Linnorm.PCA, Linnorm.HClust), 3. Differential expression analysis or differential peak detection using limma (Linnorm.limma), 4. Highly variable gene discovery and visualization (Linnorm.HVar), 5. Gene correlation network analysis and visualization (Linnorm.Cor), 6. Stable gene selection for scRNA-seq data; for users without or do not want to rely on spike-in genes (Linnorm.SGenes). 7. Data imputation. (under development) (Linnorm.DataImput). Linnorm can work with raw count, CPM, RPKM, FPKM and TPM. Additionally, the RnaXSim function is included for simulating RNA-seq data for the evaluation of DEG analysis methods.
Gplots: Various R Programming Tools for Plotting Data. Various R programming tools for plotting data, including: - calculating and plotting locally smoothed summary. Bioconductor version: Release (3.12) This workflow package provides, through its vignette, a complete case study analysis of an RNA-Seq experiment using the Rsubread and edgeR packages. The workflow starts from read alignment and continues on to data exploration, to differential expression and, finally, to pathway analysis.
Author: Shun Hang Yip <shunyip at bu.edu>, Panwen Wang <pwwang at pwwang.com>, Jean-Pierre Kocher <Kocher.JeanPierre at mayo.edu>, Pak Chung Sham <pcsham at hku.hk>, Junwen Wang <junwen at uw.edu>
Maintainer: Ken Shun Hang Yip <shunyip at bu.edu> Plots Bioconductor
Citation (from within R, enter citation(’Linnorm’)): 888 casino live help.Gplots BioconductorInstallation
To install this package, start R (version ’3.5’) and enter: Slots empire review.
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Follow Installation instructions to use this package in your R session.Source Package Linnorm_2.6.1.tar.gzWindows Binary Linnorm_2.6.1.zip (32- & 64-bit) Mac OS X 10.11 (El Capitan) Linnorm_2.6.1.tgzSource Repositorygit clone https://git.bioconductor.org/packages/LinnormSource Repository (Developer Access)git clone git@git.bioconductor.org:packages/LinnormPackage Short Urlhttp://bioconductor.org/packages/Linnorm/Package Downloads ReportDownload Stats
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A slotting fee, slotting allowance,[1]pay-to-stay, or fixed trade spending[2] is a fee charged to produce companies or manufacturers by supermarket distributors (retailers) in order to have their product placed on their shelves.[3] The fee varies greatly depending on the product, manufacturer, and market conditions. For a new product, the initial slotting fee may be approximately $25,000 per item in a regional cluster of stores, but may be as high as $250,000 in high-demand markets.[4]
*Slotting/listing fees: Slotting fees (or listing fee) is the amount of money a manufacturer pays a retailer to appear on the shelves. This transaction typically takes place after a range review process once the retailer is convinced about a product’s potential to generates sales and profit. Slotting fees average $1500 per store per SKU.
*Products are called “pay-to-stay” fees. See discussion and definition in Chapter I.B, infra at 5, n. 14 and in Chapter II.E, infra at 19-20 and n. 92 (definition). Although the FTC study maintains a clear distinction between slotting fees (for new products) and pay-to-stay fees (for continuing products), some researchers and others use the term.
In addition to slotting fees, retailers may also charge promotional, advertising and stocking fees. According to an FTC study, the practice is ’widespread’ in the supermarket industry.[5] Many grocers earn more profit from agreeing to carry a manufacturer’s product than they do from actually selling the product to retail consumers. Fees may serve to efficiently allocate scarce retail shelf space, help balance the risk of new product failure between manufacturers and retailers, help manufacturers signal private information about potential success of new products, and serve to widen retail distribution for manufacturers by mitigating retail competition.[6] For vendors, slotting fees may be a move by the grocery industry to profit at their suppliers’ expense.[7]A Slotting Fee Is A Payment That A Dependent
Some companies argue that slotting fees are unethical as they create a barrier to entry for smaller businesses that do not have the cash flow to compete with large companies. The use of slotting fees can, in some instances, lead to abuse by retailers such as in the case where a bakery firm was asked for a six figure fee to carry its items for a specific period with no guarantee its products would be carried in future periods.[8]
The same practice is common in major bookstore chains in the US as well, as far back as the mid-nineties.[9]
Slotting fees are consideration given to a retailer to obtain space on the retailer’s shelves or in the retailer’s catalog, and payments for brand development or new-product introduction. In a buydown program, a vendor reimburses or issues credit memos to a retailer for decreased revenue during a promotion period. Historically, many supermarkets, as well as retailers like bookstores, have charged ‘slotting fees’ which are essentially a pay-for-shelf space arrangement. Slotting fees have been controversial, for obvious reasons, and are banned in some places, but there is a reasonable argument to be made that because brick-and-mortar stores have.References[edit]
*^’The Use of Slotting Allowances in the Retail Grocery Industry | Federal Trade Commission’(PDF). Ftc.gov. 2003-11-14. Retrieved 2015-08-18.
*^’H.J. Heinz Company and Milnot Holding Corp | Federal Trade Commission’(PDF). Ftc.gov. Retrieved 2015-08-18.
*^Sparks, Brian. ’Slotting fee battle continues.’ American Fruit Grower. January, 2001. Retrieved on August 1, 2006.
*^Copple, Brandon. ’Shelf-Determination.’ Forbes. April 15, 2002. Retrieved on August 1, 2006.
*^’FTC Releases Grocery Industry Slotting Allowance Report’. Federal Trade Commission. 2003-11-14. Retrieved 2020-01-17.
*^Innes, Robert; Hamilton, Stephen F. (2013). ’Slotting Allowances under Supermarket Oligopoly’. American Journal of Agricultural Economics. 95 (5): 1216–1222. doi:10.1093/ajae/aat023. ISSN0002-9092. JSTOR24476902.
*^Aalberts, Robert J.; Jennings, Marianne M. (1999). ’The Ethics of Slotting: Is This Bribery, Facilitation Marketing or Just Plain Competition?’. Journal of Business Ethics. 20 (3): 207–215. doi:10.1023/A:1006081311334. ISSN0167-4544. JSTOR25074132.
*^[1]Archived April 2, 2010, at the Wayback Machine
*^In Bookstore Chains, Display Space Is for SaleNew York Times. January, 1996. Retrieved on August 22, 2012.Retrieved from ’https://en.wikipedia.org/w/index.php?title=Slotting_fee&oldid=953086444’
Slotting allowances refer to fees that suppliers pay for some type of preferential treatment from their distributors. There are a number of benefits that suppliers can receive from paying a slotting allowance, such as eye-level shelf placement of their products or the opportunity to introduce new ones. This practice is widely used in the grocery store industry. The need for these fees is supported by the risks and costs that are associated with stocking a store’s shelves and replacing failed products with new products.
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Consumers tend to be most familiar with the practice of distributors purchasing products for their stores from various suppliers. Many are unaware that slotting allowances refer to a practice where suppliers pay the distributors to take some type of action. The prevalence of this practice greatly varies. Some distributors may require certain suppliers to make these payments or may require these fees for certain products. Slots empire review. In other instances, suppliers may offer to pay slotting allowances to motivate a store to invest in a new product, to place a product in a prime location on the shelves, or to motivate a distributor not to drop a product from its stock.
The amount paid for slotting allowances also varies. Instead of decisions being made on an industry-wide basis, fees are often negotiated on a case-by-case basis. Different suppliers may be charged different fees, and it is even possible that one supplier may be subject to different fees for different items.

Grocery stores tend to operate differently than many other retail establishments, which operate on consignment. On the contrary, stocking grocery stores involves substantially greater risks because store owners purchase their merchandise outright. Any merchandise that does not sell or that must be deeply discounted results in losses for the grocery store owner. Annual product failure rates are generally high, supporting the need for slotting allowances in this industry.A Slotting Fee Is A Payment That Applies
These allowances allow stores to cover their costs. In addition to helping to compensate for the financial losses, the fees paid by suppliers also help to cover other categories of expenses, such as the costs of setting up displays and applying labor to remove unsold products from the shelves. Other costs associated with acquiring, selling, or replacing a product include warehousing, programming new items into vendor systems, and producing new shelf labels.A Slotting Fee Is A Payment That A
There are debates about the fairness of slotting allowances. It is commonly argued that this practice is anti-competitive because large suppliers have an obvious advantage. Some small suppliers cannot afford to pay these fees at all. This may keep their products out of certain stores or may prevent them from ever receiving preferential placement on the shelves.
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Between 1993 and 2003, ACST randomized 3120 patients with 60% mainly asymptomatic carotid stenosis (12% had symptoms at least 6 months previously) to immediate endarterectomy plus medical treatment versus medical treatment alone or until the operation became necessary. 17 Surgeons were required to provide evidence of an operative risk of ≤6% for their last 50. Acas carotid trial definition. North American Symptomatic Carotid Endarterectomy Trial (NASCET), the European Carotid Surgery Trial (ECST), and the trial by the Veterans Affairs Cooperative Studies Program. Symptomatic Carotid Stenosis. Moderate stenosis, 50 to 69%. ‒In NASCET, the 5-year risk of fatal or nonfatal ipsilateral stroke among patients was 22.2% in the medical group and 15.7% in. Purpose: Since the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the Asymptomatic Carotid Artery Stenosis Study (ACAS) established the efficacy of carotid endarterectomy at large academic centers, there have been two community-based studies of outcomes after this operation. The purpose of this study was to perform a statewide survey to evaluate postoperative morbidity and mortality after carotid. Purpose: Proponents of carotid angioplasty and stenting suggest that “high risk” patients, defined as patients excluded from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and Asymptomatic Carotid Atherosclerosis Study (ACAS), may have a significantly higher risk of stroke with carotid endarterectomy (CEA).
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Purpose: Proponents of carotid angioplasty and stenting suggest that “high risk” patients, defined as patients excluded from the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and Asymptomatic Carotid Atherosclerosis Study (ACAS), may have a significantly higher risk of stroke with carotid endarterectomy (CEA). North American Symptomatic Carotid Endarterectomy Trial (NASCET), the European Carotid Surgery Trial (ECST), and the trial by the Veterans Affairs Cooperative Studies Program. Symptomatic Carotid Stenosis. Moderate stenosis, 50 to 69%. ‒In NASCET, the 5-year risk of fatal or nonfatal ipsilateral stroke among patients was 22.2% in the medical group and 15.7% in. Acas carotid trial training. Between 1993 and 2003, ACST randomized 3120 patients with 60% mainly asymptomatic carotid stenosis (12% had symptoms at least 6 months previously) to immediate endarterectomy plus medical treatment versus medical treatment alone or until the operation became necessary. 17 Surgeons were required to provide evidence of an operative risk of ≤6% for their last 50. Purpose: Since the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the Asymptomatic Carotid Artery Stenosis Study (ACAS) established the efficacy of carotid endarterectomy at large academic centers, there have been two community-based studies of outcomes after this operation. The purpose of this study was to perform a statewide survey to evaluate postoperative morbidity and mortality after carotid. Abstract Background and Purpose —This study reports the surgical results in those patients who underwent carotid endarterectomy in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). Methods —The rates of perioperative stroke and death at 30 days and the final assessment of stroke severity at 90 days were calculated.
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*Acas Carotid Trial Procedure
*Acas Carotid Trial Definition
*Acas Trial Carotid StenosisPlain English Summary
*The NASCET and ECST trials have shown benefit for symptomatic patients from carotid endarterectomy. ACAS demonstrated that the incidence of cerebral infarction can be reduced by endarterectomy, and forms the foundation for current clinical guidelines for asymptomatic patients.
*With asymptomatic carotid stenosis come from the Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST; Current Controlled Trials number, ISRCTN26156392).1,2 Although stroke may be the most feared consequence of carotid disease, the most common adverse event in these studies was.
*Two landmark RCTs, the Asymptomatic Carotid Atherosclerosis Study (ACAS) and the Asymptomatic Carotid Surgery Trial (ACST), determined that CEA conferred a small but significant benefit over BMT in patients with an ipsilateral 60%–99% ICA stenosis.30 31 Unlike in NASCET and ECST, it was more difficult to identify subgroups of patients who.
The two randomized controlled studies mostly referenced on the subject of “asymptomatic” carotid stenosis are the Asymptomatic Carotid Atherosclerosis Study (ACAS) with 1662 and the Asymptomatic Carotid Surgery Trial (ACST) with 3120 patients 5, 6. Table 1 summarizes the most important results of the aforementioned studies 3–6, 33–38.
Background and study aimsCarotid stenosis is a condition where one or both of the carotid arteries (the main blood vessels that supply the head and neck) become narrowed due to a build-up of fatty deposits (plaque). This increases the risk of having a stroke, when the blood supply to part of the brain is cut off. The aim of this study is to compare carotid surgery (carotid endarterectomy or CEA) with the best medical treatment (BMT) in patients with carotid stenosis but no symptoms. The aim of this study is to find out whether CEA and BMT together improve stroke-free survival time when compared to BMT alone. The study also aims to identify high-risk groups for whom the benefits of surgery and of BMT are increased and the long-term follow-up is looking at whether carotid endarterectomy reduces the risk of dementia in the long-term.Who can participate? Patients whose carotid stenosis has not caused symptoms for at least 6 months, and who have no past history of stroke What does the study involve? Participants are randomly allocated to be treated with either CEA plus BMT or BMT alone, unless symptoms develop requiring a CEA. Fatal and non-fatal stroke and death rates are compared between the two groups. For long-term follow-up the UK and Swedish participants’ health records are also analysed for rates of stroke, death and dementia in the long-term. Relatives or friends of the UK participants are also asked to complete a postal questionnaire about the participant’s cognitive (mental) function.What are the possible benefits and risks of participating? There is no direct benefit to taking part but the information gained may help doctors to treat patients with asymptomatic carotid disease better in the future. There is no additional risk to taking part in this study. Long-term follow-up: there is no direct benefit to taking part but this follow-up may contribute to a wider benefit if carotid surgery is found to reduce the risk of developing later memory and thinking problems. The long-term follow-up does not involve any additional physical risk to the participants or does not provide any risk in relation to loss of anonymity.Where is the study run from? John Radcliffe Hospital (UK)When is the study starting and how long is it expected to run for? April 1993 to October 2019Who is funding the study? 1. Medical Research Council (MRC) (UK)2. Alzheimer’s Society (UK)Who is the main contact?Alison Hallidayacst@nds.ox.ac.ukTrial websiteContact informationType
Scientific Primary contact
Prof Alison Halliday ORCID IDContact details
ACST Trials Office Level 6 West Wing John Radcliffe Hospital Headley Way Oxford OX3 9DU United Kingdom +44 (0)1865 617975acst@nds.ox.ac.ukType
Public Additional contact
Ms Mary Sneade ORCID IDContact details
ACST trials office Richard Doll Building Old Road Campus Roosevelt Drive Oxford OX3 7LF United Kingdom +44 (0)1865 617978acst@nds.ox.ac.ukAdditional identifiersEudraCT numberClinicalTrials.gov numberProtocol/serial number
G9408332 Study informationScientific title
Asymptomatic Carotid Surgery Trial (ACST-1) Acronym
ACST-1 Acas Carotid Trial ProcedureStudy hypothesis
The aim is to determine whether CEA and BMT improve stroke-free survival time when compared to BMT alone. The trial will also help identify high-risk groups in whom the benefits of surgery and of BMT would be increased.Added 21/02/2017:Primary objective: In participants with carotid stenosis, does carotid endarterectomy reduce the long-term risk of dementia, stroke or death related to carotid stenosis?Secondary objective: In patients with carotid stenosis, does the long-term risk of dementia, stroke or death in recorded electronic records vary by duration of follow up, or participant characteristic recorded at baseline?Updated 28/09/2018:Primary objective: In participants with asymptomatic carotid stenosis, does carotid endarterectomy reduce the long-term risk of stroke, dementia or death, related to carotid stenosis?Secondary objective: In patients with carotid stenosis, does the long-term risk of dementia or stroke in recorded electronic health records vary by duration of follow-up, or participant characteristic recorded at baseline? Ethics approval
London Research Ethics Committee, 11/11/1998, ref: 98/2/92 Study design
Randomised controlled trial Primary study design
Interventional Secondary study design
Randomised controlled trial Trial setting
Hospitals Trial type
Treatment Patient information sheet
Not available in web format, please use contact details to request a participant information sheet Condition
Carotid stenosis Intervention
CEA and best medical treatment (BMT) vs BMT aloneAdded 19/08/2008: follow-up is a minimum of 5 yearsAdded 21/02/2017:No further treatment interventions are planned as part of the long-term follow-up study. Phase 1: Analysis of long-term data from UK and Swedish ACST-1 participant’s health records through electronic data linkage (NHS digital, UK; Socialstyrelsen, Sweden) for specific outcomes of incident stroke, death and dementia (16/SC/0406). The trialists will also be applying to the equivalent regulatory authorities in Scotland and Northern Ireland.Phase 2: A relative or friend of the ACST-1 UK participants will be invited to complete a postal questionnaire (Informant Questionnaire on Cognitive decline in the Elderly-IQCODE) on the participant’s cognitive function. Updated 28/09/2018:No further treatment interventions are planned as part of the long-term follow-up study. Phase 1: Phase 1: Analysis of long-term data from UK and Swedish ACST-1 participant’s health records through electronic data linkage (NHS digital, UK; Socialstyrelsen, Sweden) for specific outcomes of incident stroke and dementia (ethics approved 16/SC/0406).Phase 2: A relative or friend of the ACST-1 UK participants will be invited to complete a postal questionnaire (short form of the validated ‘Informant Questionnaire on Cognitive decline in the Elderly’ - IQCODE) on the participant’s cognitive function. Intervention type
Procedure/Surgery PhaseDrug namesPrimary outcome measure
Fatal and non-fatal stroke and death ratesAdded 10/03/2017:Long-term follow-up to determine specific outcomes of stroke and cognitive decline:1. Long-term risk of dementia, stroke or death, measured using participant’s health records through electronic data linkage (NHS digital, UK; Socialstyrelsen, Sweden) at least 14 years post enrolment2. Cognitive function, measured using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), MoCA and TICS-N, at least 14 years post enrolmentUpdated 28/09/2018:Long-term follow-up to determine specific outcomes of stroke and cognitive decline:1. Long-term risk of dementia, stroke or death, measured using participant’s health records through electronic data linkage (NHS digital, UK; Socialstyrelsen, Sweden) at least 14 years post enrolment2. Cognitive function, measured using the short form of the validated Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), at least 14 years post enrolment Secondary outcome measures
Subsidiary analyses in an effort to identify high and low risk groups will include the effect of risk factors such as presence or absence of silent cerebral infarction on clinical outcome Overall trial start date
01/04/1993 Overall trial end date
01/10/2019 Reason abandoned (if study stopped)EligibilityParticipant inclusion criteria
1. Patients whose carotid stenosis has not caused symptoms for at least 6 months2. No past history of ipsilateral disabling or severe contralateral stroke3. No clear indications or contraindications to carotid endarterectomy (CEA) Participant type
Patient Age group
Adult Gender
Both Target number of participants
3120; 1601 for long-term follow-up Participant exclusion criteria
1. Patients with a small likelihood of worthwhile benefit e.g. those with major life-threatening disease. 2. Patients who have had recent myocardial infarct, intracerebral neoplasia or aneurysm, or restenosis of an artery following previous CEA Recruitment start date
19/04/1993 Recruitment end date
01/05/2003 LocationsCountries of recruitment
Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Cyprus, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Netherlands, New Zealand, Norway, Poland, Portugal, Russian Federation, Slovenia, Spain, Sweden, Switzerland, Tunisia, United Kingdom, United States of America Trial participating centre
John Radcliffe Hospital Oxford OX3 9DU United KingdomTrial participating centre
123 other centres - United KingdomSponsor informationOrganisation
Medical Research Council (MRC) (UK) Sponsor details
20 Park Crescent London W1B 1AL United Kingdom +44 (0)20 7636 5422clinical.trial@headoffice.mrc.ac.ukSponsor type
Research council WebsiteOrganisation
University of Oxford Sponsor details
Research Services Clinical Trials and Research Governance (CTRG) Joint Research Office 1st Floor Boundary Brook House Churchill Drive Headington Oxford OX3 7GB United Kingdom -ctrg@admin.ox.ac.ukSponsor type
University/education WebsiteOrganisation
University of Oxford Sponsor detailsSponsor type
Not defined WebsiteFundersFunder type
Research council Funder name
Medical Research Council (MRC) (UK) Alternative name(s)
MRC Funding Body Type
government organisation Funding Body Subtype
National government Acas Carotid Trial DefinitionLocation
United Kingdom Funder name
Alzheimer’s Society Alternative name(s)Funding Body Type
private sector organisation Funding Body Subtype
Associations and societies (private and public) Location
United Kingdom Results and PublicationsPublication and dissemination plan
The long-term follow-up results are anticipated to be presented at relevant scientific forums and conferences in the spring 2019 and published end of 2019 in peer-reviewed scientific journals.IPD sharing planThe datasets generated during and/or analysed during the current study are not expected to be made available. Intention to publish date
31/10/2019 Participant level data
Not expected to be available Basic results (scientific)Publication list
2004 results in: http://www.ncbi.nlm.nih.gov/pubmed/151355942010 results in: http://www.ncbi.nlm.nih.gov/pubmed/208700992013 results in: http://www.ncbi.nlm.nih.gov/pubmed/236329802016 results in: http://www.ncbi.nlm.nih.gov/pubmed/274352052016 results in: http://www.ncbi.nlm.nih.gov/pubmed/273223792016 results in: http://www.ncbi.nlm.nih.gov/pubmed/271118092016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26725253Publication citations
*
Results
Halliday A, Mansfield A, Marro J, Peto C, Peto R, Potter J, Thomas D, , Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial., Lancet, 2004, 363, 9420, 1491-1502, doi: 10.1016/S0140-6736(04)16146-1.
*
Results
Halliday A, Harrison M, Hayter E, Kong X, Mansfield A, Marro J, Pan H, Peto R, Potter J, Rahimi K, Rau A, Robertson S, Streifler J, Thomas D, , 10-year stroke prevention after successful carotid endarterectomy for asymptomatic stenosis (ACST-1): a multicentre randomised trial., Lancet, 2010, 376, 9746, 1074-1084, doi: 10.1016/S0140-6736(10)61197-X.Additional filesEditorial Notes 02/10/2018: The intention to publish date was changed from 01/10/2018 to 31/10/2019.28/09/2018: The following changes were made to the trial record:1. The study hypothesis, interventions and primary outcome measure fields were updated.2. The overall trial end date was changed from 31/12/2018 to 01/10/2019.3. Contact and sponsor details updated.18/09/2017: Contact details updated.21/02/2017: The following changes were made to the trial record:1. The overall trial end date was changed from 31/03/2004 to 31/12/2018.2. The target number of participants was changed from ’3120’ to ’3120; 1601 for long-term follow-up’.3. Alzheimer’s Society was added as a funder for the long-term follow up.4. The acronym was changed from ACST to ACST-1.5. Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Cyprus, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, New Zealand, Norway, Poland, Portugal, Russia, Slovenia, Spain, Sweden, Switzerland, Netherlands, Tunisia and USA were added to the countries of recruitment.6. University of Oxford was added as a sponsor.27/01/2017: Publication references added. Perspective:
The following are 10 points to remember about asymptomatic carotid stenosis: 1. With modern intensive medical therapy, the risk of stroke in patients with asymptomatic carotid stenosis is now much lower than it was when the earlier trials, ACAS (Asymptomatic Carotid Atherosclerosis Study) and ACST (Asymptomatic Carotid Stenosis Trial), were conducted. 2. In contrast to symptomatic carotid stenosis, in asymptomatic carotid stenosis, the severity of stenosis does not predict risk. 3. It is disturbing that in the United States, the indication for approximately 90% of carotid endarterectomy and stenting is asymptomatic carotid stenosis based on extrapolation from CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial), a modern study of stenting versus endarterectomy without a medical arm of therapy, to historical results from the medical arms of early studies of carotid endarterectomy, which were performed during a time when medical therapy was much less effective. 4. This extrapolation is not valid, because with modern medical therapy, the risk of stroke in patients with asymptomatic carotid stenosis is much lower than it was in the two historical trials that are used to justify this practice. 5. The risks of stroke or death in CREST cannot legitimately be used to justify stenting or endarterectomy in unselected patients with asymptomatic carotid stenosis. 6. Transcranial Doppler embolus detection may identify the 10% of patients who would be at high enough risk to benefit from endarterectomy or stenting. 7. Additional indications of high-risk asymptomatic carotid stenosis include ulceration of carotid plaques on three-dimensional carotid ultrasound, intraplaque hemorrhage on magnetic resonance imaging, and echolucency of carotid plaques. 8. We need randomized controlled trials with a medical arm that compares stenting, endarterectomy, and modern intensive medical therapy in patients with asymptomatic carotid stenosis to assess true safety/efficacy of revascularization. 9. The proposed CREST-2 trial proposes exactly that comparison. 10. With asymptomatic carotid stenosis, patients clearly warrant intensive medical therapy to reduce their high risk of coronary events in addition to their risk of stroke.
Clinical Topics:Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Vascular Medicine, Interventions and Imaging, Interventions and Vascular Medicine, Magnetic Resonance Imaging
Keywords:Stroke, Endarterectomy, Carotid, Carotid Artery Diseases, Constriction, Pathologic, Embolism, Carotid Stenosis, Magnetic Resonance Imaging, United States, Stents< Back to ListingsAcas Trial Carotid Stenosis
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