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BAGHOUZ, Syria — U.S.-backed forces declared military victory over the Islamic State group in Syria on Saturday after liberating the last pocket of territory held by the militants, marking the end of a brutal self-styled caliphate the group carved out in large parts of Iraq and Syria in 2014.
The nearly five-year war that has devastated cities and towns across north Syria and Iraq ended in Baghouz, a minor border village where the cornered militants made their last stand, under a grueling siege for weeks.
On Saturday, the Syrian Democratic Forces raised their bright yellow banner from a shell-pocked house where the militants once flew their notorious black flag. Below it stretched a field shattered by the battle, pitted by trenches and bomb craters and littered with scorched tents, twisted wreckage of burned out vehicles, unspent explosives and few remaining corpses.
"Baghouz is free and the military victory against Daesh has been achieved," tweeted Mustafa Bali, a spokesman for the Kurdish-led SDF, referring to ISIS by its Arabic acronym.
The fall of Baghouz brings to a close a nearly 5-year global campaign against the Islamic State group that raged in two countries, spanned two U.S. presidencies and saw a U.S.-led coalition unleash more than 100,000 strikes. The campaign has left a trail of destruction in cities in Iraq and Syria, likely killed tens of thousands and drove hundreds of thousands from their homes.
The campaign put an end to the militants' proto-state, which at its height four years ago was the size of Britain and home to some 8 million people. But the extremist group still maintains a scattered presence and sleeper cells across Syria and Iraq. It's not known whether the group's leader, Abu Bakr al-Baghdadi, is still alive or where he might be hiding.
ISIS affiliates in Egypt's Sinai Peninsula, Afghanistan and other countries continue to pose a threat, and the group's ideology has inspired so-called lone-wolf attacks that had little if any connection to its leadership.
The "caliphate's" end also marks a new phase in Syria's civil war, now in its ninth year. The country is carved up, with the Iranian- and Russian-backed government of President Bashar Assad controlling the west, center and south, the U.S.-backed Kurdish-led forces holding the north and east, and Turkish allies controlling a pocket in the north. The fear now is of new conflict among those players.
At a ceremony held later Saturday at the nearby al-Omar oil field base, a senior U.S. diplomat, William Roebuck, said the territorial defeat of the Islamic State group is a "critical milestone" that delivers a crushing and strategic blow to the extremist group. But he stressed it remains a significant threat.
"We still have much work to do to achieve an enduring defeat of IS," he said.
The commander in chief of the SDF, Gen. Mazloum Abdi, appealed for continued assistance to his group until the full eradication of the extremist group. He spoke at the ceremony during which fighters marched to a military band.
The victory declaration sets the stage for President Donald Trump to begin withdrawing most of the 2,000 U.S. troops stationed in northern Syria, as he abruptly announced in December that he would do. Trump, however, later agreed to leave a small peacekeeping force of 200 soldiers in Syria to ensure Turkey will not get into a conflict with the SDF. Turkey views Kurdish members of the SDF as terrorists.
The Kurds fear being abandoned by the Americans. They are squeezed between a belligerent Turkey from the north, which regards them as a national threat and Syrian President Bashar Assad's forces from the south.
Saturday's announcement came a day after Trump declared that Islamic State militants no longer control any territory in Syria, a victory he had been teasing for days.
Associated Press journalists in Baghouz on Saturday, however, reported hearing mortars and gunfire directed toward a cliff overlooking the village, where U.S.-led coalition airstrikes were carried out a day earlier. SDF spokesman Kino Gabriel said Friday there were ISIS fighters hiding in caves near Baghouz and that clearing operations were still underway.
The site of ISIS's last stand was centered on a tent encampment in Baghouz where, unknown to the besieging SDF forces, thousands of civilians were holed up. During the weeks-long siege, an estimate 30,000 men, women and children were evacuated from the pocket, most of them ISIS family members, a mix of Syrians, Iraqis and foreigners. They were exhausted, hungry, many of them wounded and traumatized by the loss of relatives, but some remained die-hard supporters of the "caliphate."
On Saturday, journalists were taken to the encampment — a wasteland of wrecked vehicles, torn tents and scorched trees. A few bodies could be seen and a faint smell of rotting corpses hung in the air.
Scattered across the dirt amid empty foxholes and trenches were personal belongings, blankets, generators, oil barrels, water tanks and satellite dishes. Cars and motorcycles were turned to rusted, twisted heaps of metal. There were unused rockets, mortars and grenades, as well as a pile of suicide vests.
Ciya Kobani, an SDF commander, announced the end of the operation from the roof of the building with the SDF flag: "We have been victorious against Daesh," he declared.
At its height, the Islamic State group ruled a third of both Syria and Iraq, holding millions hostage to its harsh and violent interpretation of Islamic law. The group carried out massacres and documented them with slickly produced videos circulated online. It beheaded foreign journalists and aid workers and burned alive a captured Jordanian pilot. During a rampage through Iraq's Sinjar region in 2014, it captured thousands of women and girls from the Yazidi religious minority and forced them into sexual slavery. Many remain missing to this day.
The group also used its caliphate as a launchpad for attacks around the globe, including the assaults in Paris in 2015 that killed more than 130 people.
French President Emmanuel Macron tweeted that "a major danger to our country is now eliminated, yet the threat remains and the fight against terrorist groups must continue." France has been a member of the coalition fighting the ISIS since 2014.
While it imposed its unforgiving interpretation of Islamic law through public beheadings and crucifixions, the group also carried out the mundane duties of governance in its territories, including regulating prices at markets and repairing infrastructure.
Cornered in Baghouz, the group fought fiercely and desperately to hang on to the last shred of territory it controlled, using thousands of civilians, including women and children, as human shields. In the final weeks, they streamed out of Baghouz, bedraggled, angry and hungry, overwhelming Kurdish-run camps in northern Syria where they are being held.
Aid organizations say more than 100 people have died in the journey from Baghouz to the al-Hol camp in Hassakeh province, or soon after arriving.
Associated Press writer Zeina Karam in Beirut contributed to this report.


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Legacy Grove
My name is Ali and I'm a lifetime dog lover. I have been training dogs for over 20 years, raised guide dogs for the blind for a decade
My name is Ali and I'm a lifetime dog lover. I have been training dogs for over 20 years, raised guide dogs for the blind for a decade
Hey everyone! I'm Erin and I live in Madison in the Kelly Woods subdivision. I am a stay-at-home mom, so rest assured your pups will get all the love and attention they deserve!
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Hello there! I am Mike Cox and I am the owner of Petz Pack and manage all the Petz Pack locations.
We live in 5 Points off of Bankhead. We have a spacious home, a large fenced in yard, and very big hearts.
This badge indicates the host has completed the highest level of behavior training available. This host speaks dog. This host can interpret the emotional state of the dogs in their care and create a stress free environment. This host has mastered proper canine introductions and can develop healthy social skills. This host completed these pre-requisites before they earned this badge.
We are here for you 24 hours a day and we are local.
This badge indicated this host is more than a dog watcher. This host is learning to properly introduce dogs and reduce stress in order to keep a calm pack.
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I scored a A on all my canine body language and behavior quizzes
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This badge indicates that your host has completed the steps necessary to ensure they are covered by Petz Pack's 24 hour emergency protection plan .
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Your host is dedicated to making each visit an enjoyable experience for your pup. We want them to be excited to come back! If a host observes acute stress behaviors from any of the chosen amenities, the amenity will be cancelled with no charge. Some amenities are subject to cooperation and weather conditions. Heavy matting incurs additional charge.
One set of client's dog per given set of dates is OK to begin, note how they do not overlap.
Overlapping a set of client's dogs int his manner would require this host to have the 'introducing dogs' skill.
For a complete list, visit ASPCA.org

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Airports as Engines of Economic Development: Great Airports Are Critical for a Region
A great airport fuel regional economic growth. But if you build it, will they come? Only if you build it the right way.
If the claim that "all roads lead to Rome" was the key indicator of that city's economic greatness in ancient times, a modern city's equivalent claim would have to be "all airlines land here."
Just as in the past shipping, railway and then highway systems have played vital roles in determining a city's economic power, global air transportation systems will do so in the future for cities, regions and countries. Rome's Caesar had it relatively easy. When a new road was needed, he commanded it to be built. Modern leaders do not have that luxury. To become an international hub, a city must first have sufficient demand for air travel, the right geographic location and a highly developed infrastructure to handle passengers and freight. Yet having all three in place does not guarantee success.
Today, local or even national aviation policy decisions can make or break a city's vision of becoming an international hub, and good policy- making is not easy. It is a complex process requiring insight into more than local political, socioeconomic and environmental issues - often the overriding concerns of policy-makers. Sound policy also requires extensive understanding of global marketplace dynamics, the economics of airline operations and the long-term impact of policy decisions on local business and industry and consumer behavior - factors more complicated than policy-makers may think.
Some cities seem to have the right formulas. Amsterdam has clearly prospered as one of the best connecting hubs in Europe. Singapore has been the leading hub in Southeast Asia for some time. Hong Kong decided to invest billions of dollars in air transportation facilities and infrastructure to sustain the city's status as an international trade center.
Others have lost opportunities as a result of faulty or misguided policies. Paris has thus far failed to emerge as one of Western Europe's leading international gateways, in part as a result of its decision to split hub traffic between Orly and Charles de Gaulle airports. Montreal faltered similarly with its domestic/ international split between Dorval and Mirabel. In Washington, D.C., Dulles has never developed into the international connecting hub it could have been.
At the heart of the matter is how well the airport system serves its customer base. Local passengers - those traveling to and from the hub - provide the backbone of the system; connecting passengers provide the volume to "double frequencies" and significantly increase the number of cities served. By illustration, since 60 percent of passengers at a United States hub are typically connecting, it only takes 40 percent local passengers to support a decent-sized flight. A non-hub airport will only support such a service with 80 percent to 90 percent local passengers (10 percent to 20 percent connecting passengers). The threshold for service from a non-hub city is consequently much higher than for a hub city and the frequencies that can be supported much lower.
The key to efficient aviation policy is to create a system that serves the local and connecting passengers well. Splitting the hub system between two airports in the same city does not do this. For example, the international connecting passenger arriving in Dulles (27 miles west of Washington) does not want to take a taxi to Ronald Reagan National Airport (very near the city center), where most North American flights are concentrated. Consumers in central Washington do not want to take a taxi to Dulles when they can use the more conveniently located Ronald Reagan National Airport. This is one of the key problems with attempts to split a hub: given the choice, the local consumers will choose the more conveniently located (old) airport, and the distant, new airport will stand unused.
It is economically prohibitive for an airline to develop a hub solely for connecting passengers, because these are much less profitable than local passengers. In the 1980's, a few airlines attempted to establish hubs principally for connecting passengers - e.g., Raleigh-Durham and Nashville - and failed. Restrictions are often imposed on the old airport to provide traffic for the new. The problem with this is that the component of the local traffic that is allowed to stay at the old airport remains there and the city ends up with one airport focused on, say, the long-haul traffic, and the other on short-haul traffic. This leaves the aviation system uncompetitive as a hub.
In effect, that is what has happened in New York and Washington; what may still happen in Milan, and what occurred in Montreal. In Montreal the new Mirabel Airport opened in 1975 about 35 miles north of the city, with the objective of becoming the leading international gateway in Canada. Most North American flights, however, remained at Dorval, the original airport just 20 minutes from downtown Montreal, severely limiting the connections available at Mirabel. Consequently, Mirabel's projected high volume of international traffic never materialized because of the lack of an adequate connecting structure. Montreal lost its status as an international gateway, and spent an estimated $4 billion to develop an airport that has now reverted to cargo and charters.
Going forward, Frankfurt and Amsterdam stand to lose their positions as leading European hubs if they fail to expand their airports effectively. Amsterdam appears further along with its expansion plans and is causing some concern in London, where the main airports need to expand to keep pace with competition, but where progress is slow and painful.
Many cities are currently wrestling with policy decisions that will directly affect their futures as international hubs. Kuala Lumpur has recently developed an international airport, but domestic travelers have found the airport too far from the city and taxis too expensive. Sydney is considering developing a second overflow airport and Seoul is planning to retain its old airport, focused on domestic services, when its new international airport is opened. Chicago, which has the potential to give New York stiff competition as North America's premier international gateway, is embroiled in a struggle that will determine if it will emerge as one of the world's great international metropolitan centers in the 21st century. The key to achieving that ambition is to have the preeminent international air transportation hub in North America. Chicago and Illinois are in an intense political debate over whether or not to restrict growth at O'Hare (which is 14 miles northwest of the city center and surrounded by residential and commercial districts) and split its traffic with a proposed airport 35 miles south of the city center.
The evolution of the airline industry over the past two decades from point-to-point air travel to hub-and-spoke operations (in which a high volume of air traffic is concentrated in a few large hub airports with spoke connections to numerous lower- volume destinations) has produced significant benefits for most of the stakeholders.
The airlines have reaped the economic benefits of scope and scale in their operations. Local economies of hub cities have seen upturns because of increased employment, more visitors who spend more money locally and a heightened attractiveness to new businesses that consider convenient, frequent and cost-effective air travel when deciding where to locate. Airports are magnets for business and trade. Extensive and frequent air services are critical to attracting conventions and trade shows, and play a major role in the location of corporate and regional headquarters, service companies, research and development facilities and manufacturing sites.
Great benefit has also accrued to consumers - business travelers in particular - in terms of greater choice of flights and destinations, frequency of service, flexibility in re-scheduling and a general lowering of ancillary costs related to travel, such as avoiding the time and cost of an overnight stay. Although in the United States the rise of hub-and-spoke operations coincided with airline deregulation in the late 1970's, marketplace dynamics have been the true drivers of the concept's acceptance and success worldwide. Simply put, a hub-and-spoke system works better for nearly everyone in Europe, the United States and Asia.
In the United States, the airline economy is still primarily domestic. The future will be tied to becoming an international hub. Some European and Asian communities have already figured this out and acted accordingly.
"Hubbing" in Europe is not about forcing passengers to connect via Frankfurt when traveling from Stockholm to London. It is about providing frequent and convenient one-stop connections to medium-sized international destinations that cannot support direct service from cities such as Stockholm (plus connecting smaller and medium-sized European cities). In Europe, a few major interior cities have emerged as the key European and international hubs. Frankfurt, for example, has direct service to more than 100 destinations outside Europe. In the United States, the key international connecting points are on the coasts: New York, Los Angeles and Miami. Chicago, by contrast, has direct service only to some 25 to 30 destinations outside North America. If a passenger wants to go to Chicago from Vienna, a stopover in New York or a European connecting point is required.
Chicago's potential for economic growth does not lie in the domestic market; it already provides nonstop services to more North American destinations than any other United States airport system. The economic growth potential is in international service, where Chicago ranks fourth in the United States, far short of New York and Miami and somewhat behind Los Angeles. Chicago is not missing out on Cleveland's business; it is missing out on business from Europe and Asia. Consider the economic impact of this relatively low level of international service. A recent Booz-Allen & Hamilton study conducted for the Chicagoland Chamber of Commerce found that the total value to the local economy of a single international passenger at Chicago's O'Hare International Airport is five to six times greater than that of a North American connecting passenger: $2,310 compared with $430. (See Exhibit I.)
The message for Chicago and for the many cities worldwide with similar ambitions to capture the economic value of international air travel and to become global trade centers is the same: aggressively pursue international hub status.
WHO WILL OR CAN WIN? Policy-makers should realize that there are at least three basic requirements for becoming a major hub, whether domestic or international: sufficient local consumer demand, good geographic location and the necessary infrastructure to support high-volume traffic. When these three conditions exist, the difference between cities that succeed and those that fail often boils down to which city can craft and execute sound aviation policy.
What goes into sound aviation policy? Policy-makers must consider the priorities of and their policies' impact on the four Cs:
- The consumer who wants diverse and frequent services at low prices.
- The community that seeks both a high quality of life and jobs.
- The country that can suffer balance of trade and commercial isolation problems from poor policy.
- The carriers that will succeed in, or fail at, emerging as leaders in their industry, taking their hub cities with them.
In the best of all possible worlds, policy-makers would maximize the benefits for all the stakeholders. In the process their policies would foster the creation of a hub so strong that any airline could fly there and that competition - not regulation - would control service levels and pricing.
We do not live in an ideal world. Policy-makers in cities around the world face a range of complex challenges: noise and pollution concerns, limited airport capacity, aging infrastructure and resistance to high fares. Typically, there are three scenarios for solving the problems: abandon an existing airport and build a new one; build a second point-to-point airport to handle local overflow from the existing airport without compromising its hub capabilities, or maintain and grow the existing airport into a single strong hub.
In some cases, building a new airport and closing or refocusing the old facility, as was done in Denver, may be the only rational alternative, but it is rife with both economic and social considerations. First, there is the issue of the enormous investment required just to build the new airport facility, not to mention the cost of the necessary infrastructure, such as roads and mass transit, to support it. Second, major economic dislocations can result:
- If the new airport is built far away from the old one, then hotels, convention centers and businesses that were developed near the old airport may become obsolete. Even apartments and houses built for people wanting locations convenient to the airport are impacted. Occupancy, lease rates and property prices can decline as the old location becomes less attractive.
- Economic development around the new facility is often relatively slow in coming.
- The new airport can be very distant from the city center and be very expensive to use (in terms of landing fees, taxi rides, etc.), concerns that have, for example, been raised in Denver.
Hubs are aviation systems with significant economies of scale and scope, and all prior attempts to split hubs have failed. There are, however, a number of cities with a two- or even three-airport system that are effective hubs. A clear distinction can be drawn between multi-airport cities with effective hubs, such as Chicago, Dallas and Houston, and those with ineffective hub structures, such as Washington, New York, London and Paris. The successful cities have one primary hub and a secondary airport focused on point-to-point traffic to and from the city. In each case, the local traffic base is large enough to support both airports; the primary hub is significantly larger than the secondary airport, and the secondary airport is focused on a different customer segment (i.e., it is not an overflow hub). The less successful multi-airport systems have two primary airports, often with legal or other restrictions imposed to separate traffic between them. As is clear from Exhibit II, the "multi-hub cities" have not become hubs at all, but have largely become focused on local traffic and have failed to attract a proportionate share of connecting traffic. Just imagine the traffic potential of London, Paris, Washington or New York if they could attract one connecting passenger for every local (i.e., 50 percent connecting traffic).
Splitting a hub is not an attractive policy alternative. What will tend to happen is that the old hub will become more and more focused on local traffic, and services to medium-sized locations will get crowded out, thereby curtailing growth. This is certainly what is happening in London and what may happen in Chicago. A constrained O'Hare would not emerge as the international hub it could become if allowed to expand. Flights from medium-sized international cities to Chicago can carry as much as 80 percent connecting passengers. With capacity limits, the effective cost of slots will go up and the availability of seats for connecting passengers will diminish, reducing the attractiveness of Chicago as a connecting point (this will be true whether the current changes in slot regulation come through or not).
The recent study that Booz-Allen & Hamilton conducted for the Chicagoland Chamber of Commerce demonstrates how this scenario would play out for Chicago, which now faces the choice of maintaining O'Hare as a single, strong hub or building a new, second airport farther south in Illinois to split traffic.
As is the case in many other cities, Chicago's growth will be tied to international service. Currently, Chicago has a relatively low share of international traffic. Passengers from cities such as Athens, Lisbon, Taipei and Beijing currently must connect through New York, Los Angeles or non-domestic locations such as London, Amsterdam, Frankfurt and Tokyo. Passengers from many of the international cities that O'Hare does serve are offered limited frequencies and often choose to connect to their North American destinations through other gateways because of inconvenient schedules or flights that are full.
A broad range of cities are close to the threshold traffic level required to support direct service to Chicago, provided a reasonable share of connections to the rest of the United States can be captured. Exhibit III (see next page) shows the forecasted traffic for the year 2015 between several major international cities and Chicago compared with the actual traffic between Chicago and those cities in 1996. Such growth would not only create direct airport and travel-related employment, but would also make Chicago more attractive as a center of international commerce. Booz-Allen's estimates indicate that such international growth could contribute $17 billion to greater Chicago's economic output by the year 2015.
The study concluded that because hub traffic is not divisible or transferable across airports, a single strong hub is a requirement for building international traffic and sustaining Chicago's position as a premier transportation center.
The Chicago study also found that Chicago's second airport, Midway (which focuses on meeting local point-to-point - not connecting - air travel demand), contributes significantly to the local economy and encourages price competition. Lower-priced airlines, such as Southwest and others that base their operations at Midway, stimulate local point-to-point demand and impose significant price discipline on O'Hare - similar to that imposed by low-priced carriers at other hubs. Current investments by Southwest and the airline's experience elsewhere suggest that growth may continue for some time. The study recommended that the city insure continued development of point-to-point traffic to maintain such market-driven price competition by adding capacity at Midway and other regional airports. What Chicago decides will certainly be critical to its future as a world-class trade center.
Aviation policy is difficult: Community pressures to reduce noise and control pollution are intense and well understood. The economic cost of the all-too-popular decision to constrain growth or develop impractical overflow airports is not understood. Similarly, consumer pressures for lower fares tend to be directed at carriers and their successful hubs, rather than policy-makers for building insufficient or incorrect airport capacity. Policies aimed at breaking up effective hubs may be more damaging to consumers and communities than policies aimed at providing effective additional capacity for point-to-point, low-priced hub carriers.
Airline carriers based in stagnating hubs can choose to stagnate themselves or refocus growth initiatives elsewhere, through capacity additions in another location or by leveraging alliance partners. Either way, carriers focused on constrained hubs are unlikely to become the global leaders of air transportation.
The prize is clear: Which communities, cities, carriers and countries will win? In North America, the question is which community will emerge as an international metropolitan center of the 21st century. In parts of Europe and Asia, the question is which countries will enjoy the greatest economic growth - for air transportation will remain a magnet for business and commerce.
Reprint No. 99308


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When she got out of college and moved to New York, Elizabeth Cline liked to shop at vintage-clothing stores. They were the kinds of places tucked away on side streets in Manhattan and Brooklyn, where a lot of hunting and a little luck might reward you with a great, inexpensive cocktail dress that no one else had.
Then she discovered the world of "fast fashion" — chains like Forever 21, H&M and Zara — and it redefined her whole notion of bargain shopping.
"The products are very, very cheap," says Cline, author of Overdressed: The Shockingly High Cost of Cheap Fashion. "The design is pretty attractive. And if you walk into the store, I think, for a lot of consumers, it's virtually impossible to walk out empty-handed."
You see some products and it's just garbage. It's just crap, and you sort of fold it up and you think, yeah, you're going to wear it Saturday night to your party — and then it's literally going to fall apart.
'Selling An Ocean Of Clothing'
Over time, Cline had amassed 354 items of clothing, some of which she never wore. And such excesses aren't all that unusual, she notes. Chains like H&M are constantly turning over their merchandise, introducing ever-trendier clothing and feeding their customers' desire for novelty.
"We want to surprise the customers," says Margareta van den Bosch, the company's hugely influential style adviser. "We want to have something exciting. And if it's all the time hanging the same things there, it is not so exciting, I think."
Much of H&M's clothing is so inexpensive — a $10 leopard-print top or a $15 sweater, for example — that consumers can afford to buy it in quantities that wouldn't have begun to fit in our grandparents' armoires. It's so cheap that it isn't even worth returning if we get home and decide we don't like it, Cline says.
But despite the low prices, fast fashion chains can be enormously profitable. Sales at H&M's parent company rose by 11 percent in 2012. Its chairman and largest shareholder, Stefan Persson, is the 17th richest person on the planet, with a net worth of $26.3 billion, according to Bloomberg. Amancio Ortega, founder of Zara, another highly successful chain, is the third richest, worth $58.3 billion.
How can these stores make so much money selling $10 shirts? Mostly because of volume.
"A store like H&M produces hundreds of millions of garments per year," Cline says. "They put a small markup on the clothes and earn their profit out of selling an ocean of clothing." H&M has 2,800 stores in 48 markets and it's growing fast, especially in China and the United States, according to the company's website.
The success of chains like H&M and Forever 21 represents a paradigm shift in the retail world, one that has affected every corner of the industry.
In the 1960s, people generally bought their clothing from large retailers like department stores, which in turn bought from manufacturers. But in the 1970s, retailers began to manufacture clothing themselves, giving them direct control over the manufacturing and distribution process.
Among the pioneers of the change was Les Wexner, founder of the Ohio-based women's clothing chain The Limited, says Frank Bober, CEO of Stylesight, a company that helps retailers and designers spot trends.
"He was the guy that recognized that, 'Hey, I can do this myself. I can understand what my clients want, what my customer wants, and then I can go make that for them. I don't need to go to a bunch of manufacturers to do that,' " Bober says.
The End Of The Two-Season Shopping Calendar
Meanwhile, computer technology transformed the entire process, enabling retailers to design, manufacture and ship products much faster and more efficiently. At one time, the fashion industry worked around a two-season calendar that unfolded at a predictable pace.
"I remember my mother would take me shopping in August for the fall, and I would just be dying, putting on these itchy sweaters when it was 90 degrees outside," recalls Sharon Graubard, Stylesight's design director. "Nobody does that anymore."
A relentless drive for speed now characterizes the industry. Chains like Zara are so fast, they can design, manufacture and get clothing onto store shelves in a month. Customers can now easily see the latest fashions online and have become conditioned to expect a constant stream of trendy new styles from retailers.
This focus on speed has affected every kind of retailer, even those not generally considered fast fashion.
"What that has done is made the industry move faster and work faster and have to produce more product," says Ed Filipowski, president of KCD, a public relations firm that represents some of the biggest and best-known brands in fashion. "It's created a sort of year-round calendar for fashion as opposed to a biannual calendar for fashion. It's made our job a lot harder and it's made creativity a constant challenge."
But now that retailers have whetted customers' demand for novelty, they have to keep their products affordable — a big challenge. That means manufacturing in low-wage countries like China, but it also means using cheap, synthetic materials and rudimentary manufacturing processes.
The simple fact is that much fast fashion doesn't survive more than a few washings. Simon Collins, dean of fashion at Parsons The New School for Design, likes the way fast fashion has brought a level of style to the masses, but he laments how poorly made it can be.
"You see some products and it's just garbage. It's just crap," he says. "And you sort of fold it up and you think, yeah, you're going to wear it Saturday night to your party — and then it's literally going to fall apart."
Author Elizabeth Cline remembers buying a shirt at Old Navy, a chain she used to frequent. "I had this tank top that had two flowers, kind of like on the strap, and ... after I started writing the book, I just started looking at my clothes, and the flowers were actually affixed with some sort of tape. They weren't even sewn on."
'Landfill Fashion'
Poor quality has turned the fast fashion label into something of a pejorative, so much so that chains like Uniqlo and H&M now reject the term altogether.
And the chains have other image problems as well. Cline says there's a growing public consensus that the mass production of so much cheap clothing is an enormous waste of resources such as fuel and water. While many people donate their clothing to charities and consignment shops, fast fashion tends to be so cheaply made that no one wants to buy it, she notes. Instead, it gets recycled into industrial rags and insulation, or even thrown out altogether — generating the term "landfill fashion."
The fast fashion model may be cracking in other ways, too. Factory workers in China, where a lot of clothing is manufactured, are increasingly pressing for higher wages.
Companies have responded by moving production into places where wages are even lower, like Bangladesh. But such countries lack the sophisticated manufacturing infrastructure of China, and in the rush to fill the void, tragedy has sometimes ensued. A fire at a clothing factory on the outskirts of the capital, Dhaka, killed 112 people in November.
The industry will no doubt adapt over time, but the days when fashion gets faster and cheaper every year are probably at an end.
Copyright 2021 NPR. To see more, visit https://www.npr.org.


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Here you can find all your transfer and excursion requirements at the most competitive prices. All vehicles used by our company are licensed public service vehicles and all our drivers are holders of a professional driving license.
Our company offers to you transfers all over an ireland of  Cyprus. Starting from airport either is Larnaka or Paphos airport or as well as Limassol port. Book your transfer online without prepayment and you can be assured that there will be a vehicle waiting for you at the place. Even if your flight is delayed, we do not charge you extra.  No matter how many of you there are in your party you can always be assured of the best discounts throughout the year. By clicking on our Excursions link. You will find a large selection of trips available on the island of Cyprus, together with advice as to how best to spend your time here, what to visit and what to do, so as to get the most out of your holiday.
Company Information | |
Number of Employees | 1-50 |
Stadiou 78 , Floor: 1st, Flat/Office: 14 , Larnaca 6020 , Cyprus
info [ at ] taxi-cyprus.com
+357 99 445 027; +357 99 496 335
+357 24 621 423
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Dry eye is a common ocular condition that occurs when the eyes do not produce enough tears or when the tears evaporate too quickly. This can lead to discomfort, redness, blurred vision, and even damage to the surface of the eyes. Understanding the causes and symptoms of dry eye is crucial provide early detection and effective treatment.
Early detection of dry eye is crucial for preventing further progression of the condition and improving patient outcomes. Without proper diagnosis and treatment, dry eye can cause significant discomfort and affect daily activities. Additionally, chronic dry eye can lead to corneal ulcers, infections, and even vision loss. By accurately identifying and addressing dry eye in its early stages, optometrists can provide timely interventions and prevent complications.
One of the advanced diagnostic tools available for dry eye is TearLab. TearLab is a non-invasive test that measures the osmolarity of tears, which is an indicator of tear film stability. This test provides valuable information about the quality and quantity of tears, allowing healthcare professionals to accurately diagnose and monitor dry eye. By analyzing the osmolarity of tears, TearLab helps identify the severity of dry eye and guides treatment decisions. It is a quick and painless procedure that can be performed in a clinical setting.
Inflammation plays a significant role in dry eye, and identifying the presence of inflammation is crucial for effective treatment. InflammaDry is a diagnostic tool that detects elevated levels of matrix metalloproteinase 9 (MMP-9), an inflammatory marker, in tears. By measuring MMP-9, InflammaDry helps optometrists differentiate between inflammatory and non-inflammatory dry eye. This information is essential for tailoring treatment plans and determining the most appropriate therapies for each patient.
Meibomian gland dysfunction (MGD) is a common contributor to dry eye. The meibomian glands, located along the eyelid margins, produce an oily substance that helps prevent tears from evaporating too quickly. When these glands become blocked or dysfunctional, the tear film becomes unstable, leading to dry eye symptoms. Meibomian gland photography is a diagnostic technique that allows eye doctors to assess the structure and function of the meibomian glands. By evaluating the health of these glands, optometrists can develop targeted treatment strategies to address MGD and improve dry eye symptoms.
Advanced diagnostic testing for dry eye provides optometrists with valuable information about the underlying causes and severity of the condition. This allows for a more targeted and effective treatment approach. By identifying the specific factors contributing to dry eye, optometrists can tailor treatment plans to address each patient's unique needs. Whether it's prescribing lubricating eye drops, recommending lifestyle modifications, or performing in-office procedures, advanced diagnostic testing enhances the precision and success of dry eye treatment.
If you are experiencing symptoms of dry eye, consult our optometry team who can perform advanced diagnostic testing to accurately diagnose and develop a personalized treatment plan for your dry eye condition.


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Free sewing tutorial: Geek Chic iPad Case
Hello, everybody! I'm back from my travels. I hope last week's orange round-up didn't scald the retinas of those who prefer other hues. I've got a freebie for you today, and you can make it in any color you like (though I do recommend orange).
The Geek Chic iPad Case is a sewing project from Lisa Lam's book A Bag for All Reasons. You might know Lisa from her site U-handbag.com. Since I have a bag addiction, this book with 12 different sewing patterns makes me super happy. They're modern, clean, and make smart use of hardware. I've seen tons of bag and purse patterns that combine appliques, ruffles, and patchwork in a crazy mess. Cool if you like that sort of thing, but I prefer simplicity. Let the fabric be the star, I say! So I'm a fan of Lisa's lovely patterns. Want to try out a free project from her book, compliments of the publisher?
Download the Geek Chic iPad Case tutorial here.
Download the flap template here.
If you dig it, you can purchase the whole book here. Happy sewing!
(Photos from A Bag for All Reasons.)


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Consumer's Choice
Ralinksi Six Drawer Dresser
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With its clean-lined look and modern attitude, this dresser is a fresh style awakening. A warm gray hue over replicated oak grain easily complements other furniture finishes. Smooth drawer fronts with antiqued pewter-tone handles complete the aesthetic.
Height | 36.46in | |
Width | 59.53in | |
Depth | 15.59in | |
Details | Made with engineered wood (MDF/particleboard/plywood) and decorative laminate for the right balance of affordability and durability, Rustic warm gray finish over replicated oak grain with authentic touch, Large scale pewter-tone handles, 6 smooth-gliding drawers, Safety is a top priority, clothing storage units are designed to meet the most current standard for stability, ASTM F 2057 (ASTM International), Drawers extend out to accommodate maximum access to drawer interior while maintaining safety | |
Material | Wood Products and Other | |
Lifestyle | Casual | |
Dimensions | 60''W x 16''D x 37''H |
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« Prev | How the married and the single are to be… | Next » |
Chapter XXVII.
How the married and the single are to be admonished.
(Admonition 28.) Differently to be admonished are those who are bound in wedlock and those who are free from the ties of wedlock. For those who are bound in wedlock are to be admonished that, while they take thought for each other's good, they study, both of them, so to please their consorts as not to displease their Maker; that they so conduct the things that are of this world as still not to omit desiring the things that are of God; that they so rejoice in present good as still, with earnest solicitude, to fear eternal evil; that they so sorrow for temporal evils as still to fix their hope with entire comfort on everlasting good; to the end that, while they know what they are engaged in to be transitory, but what they desire to be permanent, neither the evils of the world may break their heart while it is strengthened by the hope of heavenly good, nor the good things of the present life deceive them, while they are saddened by the apprehended evils of the judgment to come. Wherefore the mind of married Christians is both weak and stedfast, in that it cannot fully despise all temporal things, and yet can join itself in desire to eternal things. Although it lies low meanwhile in the delights of the flesh, let it grow strong in the refreshment of supernal hope: and, if it has the things that are of the world for the service of its journey, let it hope for the things that are of God for the fruit of its journey's end: nor let it devote itself entirely to what it is engaged in now, lest it fall utterly from what it ought stedfastly to hope for. Which thing Paul well expresses briefly, saying, They that have wives as though they had none, and they that weep as though they wept not, and they that rejoice as though they rejoiced not (1 Cor. vii. 29, 30). For he has a wife as though he had none who so enjoys carnal consolation through her as still never to be turned by love of her to evil deeds from the rectitude of a better aim. He has a wife as though he had none who, seeing all things to be transitory, endures of necessity the care of the flesh, but looks forward with longing to the eternal joys of the spirit. Moreover, to weep as though we wept not is so to lament outward adversities as still to know how to rejoice in the consolation of eternal hope. And again, to rejoice as though we rejoiced not is so to take heart from things below as still never to cease from fear concerning the things above. In the same place also a little afterwards he aptly adds, For the fashion of this world passeth away (v. 31); as if he had said plainly, Love not the world abidingly, since the world which ye love cannot itself abide. In vain ye fix your affections on it as though it were continuing, while that which ye love itself is fleeting. Husbands and wives are to be admonished, that those 57bthings wherein they sometimes displease one another they bear with mutual patience, and by mutual exhortations remedy. For it is written, Bear ye one another's burdens, and so ye shall fulfil the law of Christ (Galat. vi. 2). For the law of Christ is Charity; since it has from Him bountifully bestowed on us its good things, and has patiently borne our evil things. We, therefore, then fulfil by imitation the law of Christ, when we both kindly bestow our good things, and piously endure the evil things of our friends. They are also to be admonished to give heed, each of them, not so much to what they have to bear from the other as to what the other has to bear from them. For, if one considers what is borne from one's self, one bears more lightly what one endures from another.
Husbands and wives are to be admonished to remember that they are joined together for the sake of producing offspring; and, when, giving themselves to immoderate intercourse, they transfer the occasion of procreation to the service of pleasure, to consider that, though they go not outside wedlock yet in wedlock itself they exceed the just dues of wedlock. Whence it is needful that by frequent supplications they do away their having fouled with the admixture of pleasure the fair form of conjugal union. For hence it is that the Apostle, skilled in heavenly medicine, did not so much lay down a course of life for the whole as point out remedies to the weak when he said, It is good for a man not to touch a woman: but on account of fornication let every man have his own wife, and let every woman have her own husband (1 Cor. vii. 1, 2). For in that he premised the fear of fornication, he surely did not give a precept to such as were standing, but pointed out the bed to such as were falling, lest haply they should tumble to the ground. Whence to such as were still weak he added, Let the husband render unto the wife her due; and likewise also the wife unto the husband (v. 3). And, while in the most honourable estate of matrimony allowing to them something of pleasure, he added, But this I say by way of indulgence, not by way of command (v. 6). Now where indulgence is spoken of, a fault is implied; but one that is the more readily remitted in that it consists, not in doing what is unlawful, but in not keeping what is lawful under control. Which thing Lot expresses well in his own person, when he flies from burning Sodom, and yet, finding Zoar, does not still ascend the mountain heights. For to fly from burning Sodom is to avoid the unlawful fires of the flesh. But the height of the mountains is the purity of the continent. Or, at any rate, they are as it were upon the mountain, who, though cleaving to carnal intercourse, still, beyond the due association for the production of offspring, are not loosely lost in pleasure of the flesh. For to stand on the mountain is to seek nothing in the flesh except the fruit of procreation. To stand on the mountain is not to cleave to the flesh in a fleshly way. But, since there are many who relinquish indeed the sins of the flesh, and yet, when placed in the state of wedlock, do not observe solely the claims of due intercourse, Lot went indeed out of Sodom, but yet did not at once reach the mountain heights; because a damnable life is already relinquished, but still the loftiness of conjugal continence is not thoroughly attained. But there is midway the city of Zoar, to save the weak fugitive; because, to wit, when the married have intercourse with each other even incontinently, they still avoid lapse into sin, and are still saved through mercy. For they find as it were a little city, wherein to be protected from the fire; since this married life is not indeed marvellous for virtue, but yet is secure from punishment. Whence the same Lot says to the angel, This city is near to flee unto, and it is small, and I shall be saved therein. Is it not a little one, and my soul shall live in it (Gen. xix. 20)? So then it is said to be near, and yet is spoken of as a refuge of safety, since married life is neither far separated from the world, nor yet alien from the joy of safety. But the married, in this course of conduct, then preserve their lives as it were in a small city, when they intercede for each other by continual supplications. Whence it is also rightly said by the Angel to the same Lot, See I have accepted thy prayers concerning this thing also, that I will not overthrow the city for the which thou hast spoken (v. 21). For in truth, when supplication is poured out to God, such married life is by no means condemned. Concerning which supplication Paul also admonishes, saying, Defraud ye not one the other except it be with consent for a time, that ye may give yourselves to prayer (1 Cor. vii. 5).
But, on the other hand, those who are not bound by wedlock are to be admonished that they observe heavenly precepts all the more closely in that no yoke of carnal union bows them down to worldly cares; that, as they are free from the lawful burden of wedlock, the unlawful weight of earthly anxiety by no means press them down; that the last day find them all the more prepared, as it finds them less encumbered; lest from being free and able, and yet neglecting, to do better things, they therefore be found deserving of worse punishment. Let them hear how the 58bApostle, when he would train certain persons for the grace of celibacy, did not contemn wedlock, but guarded against the worldly cares that are born of wedlock, saying, This I say for your profit, not that I may cast a snare upon you, but for that which is comely, and that ye may attend upon the Lord without hindrance (1 Cor. vii. 3, 5). For from wedlock proceed earthly anxieties; and therefore the teacher of the Gentiles persuaded his bearers to better things, lest they should be bound by earthly anxiety. The man, then, whom, being single, the hindrance of secular cares impedes, though he has not subjected himself to wedlock, has still not escaped the burdens of wedlock. The single are to be admonished not to think that they can have intercourse with disengaged women without incurring the judgment of condemnation. For, when Paul inserted the vice of fornication among so many execrable crimes, he indicated the guilt of it, saying, Neither fornicators, nor idolaters, nor adulterers, nor effeminate, nor abusers of themselves with mankind, nor thieves, nor covetous, nor drunkards, nor revilers, nor extortioners, shall possess the kingdom of God (1 Cor. vi. 9, 10). And again, But fornicators and adulterers God will judge (Heb. xiii. 4). They are therefore to be admonished that, if they suffer from the storms of temptation with risk to their safety, they should seek the port of wedlock. For it is written, It is better to marry than to burn (1 Cor. vii. 9). They come, in fact, to marriage without blame, if only they have not vowed better things. For whosoever has proposed to himself the attainment of a greater good has made unlawful the less good which before was lawful. For it is written, No man, having put his hand to the plough, and looking back, is fit for the kingdom of God (Luke ix. 62). He therefore who has been intent on a more resolute purpose is convicted of looking back, if, leaving the larger good, he reverts to the least.
« Prev | How the married and the single are to be… | Next » |


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ManHood Beginner Bundle - Gold
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Not sure where to start with retaining during foreskin restoration? We can help. This special bundle lets you try two of our most popular styles, the ManHood Original in Gold Skin Tone and ManHood Restorer in Gold Member. Wear the Restorer for more active daytime movement and the Original for sleeping.
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29 years later + thousands of happy customers
ManHood® was a breakthrough innovation for restoring penis sensitivity when it was invented in 1995. In the past 27 years, thousands of satisfied customers have experienced a smoother, more sensitive glans penis after wearing ManHood® daily.
Wearing ManHood® is simple and painless, without any complicated tapes, straps, or cones that look like medieval torture devices! All you do is insert your penis between the two layers of fabric and secure it with the built-in velcro strip. Your glans will be safely and comfortably protected all day. Removing it is simple too. Soon you will know how great it feels to be intact!
manhood® benefits for circumcised men
When you're circumcised, ordinary daily activities irritate your glans because there is a great deal of movement in your groin area. Manhood® will solve this problem by protecting the head of your penis the same way a foreskin would.
Your glans was not meant to be exposed to outside elements. It was intended to be soft and smooth, for maximum sensitivity. But over time, because it's been exposed to harsh outside elements, the glans had to toughen up to survive. This caused it to dry out, which is why you'll notice a circumcised penis usually has lines and ridges on the head. This is from the damage.
Once you start wearing Manhood®, your glans will begin to recover. You'll notice more softness and more shine. After about a month of daily use, you should notice an increase in sensitivity as well. This means your sex life will improve, the intensity of your orgasms will be evident, and your glans will finally begin to "feel" the way it was supposed to.
manhood® feels like heaven for your penis
Each ManHood® is carefully hand-made without inside seams to ensure it stays smoothly against your glans. It has two layers of silky soft 100% polyester material that rub together, absorbing friction that would normally irritate your glans. Place your index finger inside the ManHood® and your thumb on the outside, then rub together and you will feel how it works.
From the moment you put on ManHood®, you'll begin to notice the comfort of having a glans that's protected, just like with a real foreskin. By keeping your glans covered, you'll begin the dekeratinization process. Within 30 days, you'll experience a smoother, more sensitive glans, just like intact men have. This can increase the intensity of your orgasms and bring you more pleasure than you've ever felt before.
what is the dekeratinization process?
The glans is made up of a soft, spongy tissue with thousands of nerve endings. The foreskin protects this tissue by covering it when the penis is flaccid. When you're circumcised, you lose the protection of the foreskin, and this affects the glans.
Let's use your tongue to demonstrate the damage. Ordinarily your tongue stays inside your mouth, where it's warm, moist, and safe from outside damage. Now let's try sticking your tongue out for a minute or two. What happens to your tongue? It dries out and even starts to get numb.
The damage to your glans is very similar. Without the protection of the foreskin, it dries out and loses some of the feeling. As a result, you may encounter decreased sensations during sexual activity and less satisfaction overall. Your partner may also suffer from friction caused by the rough texture of your glans.
That's where dekeratinization comes into play. When you wear ManHood®, your glans will once again have the protection it was intended to have. That dry, rough surface will gradually flake away from the head of your penis to reveal a smoother, shinier glans.
Within a month of regular usage, you will begin to notice an improvement in sensitivity. An easy way to test it is to go running without your ManHood® on. You'll feel itchy and uncomfortable, and that's how you'll know the dekeratinization process has begun.
Continue to wear ManHood® daily so your glans remains protected, just like it would with a real foreskin.
will manhood® slip off?
If the velcro strip is properly fastened around the base of your penis, it takes a great deal of movement to make ManHood® slip off. However, since it is an undergarment and isn't attached to the skin, it is possible for it to dislodge. This is true with all retainers. As long as it's properly fastened, and you've ordered the correct size, you should be fine on a day to day basis.
here are some tips to maximize the comfort of wearing manhood®:
Make sure you have accurately measured your penis before ordering. You should measure when flaccid, around the base of the penis (the area where your pubic hair usually ends, not including the testicles), and measure it in a circle. The sizing is based on the girth of your penis, not the length.
Wear briefs or boxer briefs because they usually hug the body more than traditional boxers. The fabric will hold your penis against your body, which will minimize the amount of movement against Manhood®. The less movement, the less likely it will slip off. Also, if it does slip off, it will mostly likely get caught inside the brief, which will prevent you from losing it.


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Logo Maker
What do I get when I purchase a logo?
- The logo you designed in the SVG format
4 variations in the SVG format
- A full black logo
- A full white logo
- The logo you designed without any background
- The logo designed with the background and font colors exchanged
- A guide on how to use & edit SVG files
- Social Media Kit - When you purchase a logo from us, we try to make sure that you have everything to start using your logo immediately.
- Here is your logo in the PNG format, in all the sizes required by various social media sites.
- Favicon Set - ICO and PNG files in various favicon sizes
- Brand Guide - All the information on your logo you require to ensure that it is consistent in everywhere it is used
Why the SVG format?
- It is the preferred file format for designers and professionals
- The file sizes are small so it is easy for you to share & host
- It scales to any size without losing quality
- It looks great on retina displays
- It can be edited further
Can I edit the logo after I purchase it?
In those tools you can edit everything from the symbol, font, color etc.
Unfortunately, you cannot use our tool for editing the logo after purchase.
Is there a limit to the number of logos I can generate and edit?
Is my logo package price a one-time or a recurring fee?


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Badger Power
Wherefore Art Thou, Badger?
Badger is an application toolkit designed to simplify the process of building object-oriented Perl applications. It provides a set of foundation classes upon which you can quickly build robust and reliable systems. Convenience, convention and consistency are key in our ongoing quest to increase the Kwalitee™ of our code and make it more Skimpy™ (aka skimmable).
An Introduction to Badger
Andy Wardley gave a talk about Badger at the London Perl Workshop on 29th November 2008. The slides are available here complete with extended footnotes culminating in an extended rant about how hard it is to write extensible, generic software.
The Badger source code is now being managed using git. The new repository is at http://github.com/abw/Badger. More...


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US Pharm. 2013;38(1):35-39.
ABSTRACT: Epilepsy is a disorder comprising a collection of seizures that differ in cause, symptoms, severity, and treatment. Seizures are assigned to one of two major categories: partial or generalized. Epilepsy cases can involve more than one type of seizure. Epilepsy may be classified into etiologic types and then further defined by presenting features. Drug therapy is based on type of seizure, age, gender, comorbidities, adverse-effect potential, drug interactions, and cost. Once treatment is initiated, about 60% of patients achieve adequate seizure control with monotherapy. Monitoring of serum concentrations is beneficial when suspecting toxicity, assessing medication adherence, or making dose adjustments. Pharmacists can improve patient outcomes through dose recommendations, drug interaction surveillance, adherence counseling, and adverse-effect monitoring.
Commonly referred to as seizure disorder, epilepsy is a disorder comprising a collection of seizures that differ in regard to cause, symptoms, severity, and treatment.1 Approximately 2 million people in the United States have epilepsy, and it is estimated that about 140,000 people develop the disorder every year.2 Despite advances in technology and treatment, epilepsy still remains a huge economic burden, with an estimated health care cost of $2.7 billion per year.3
Seizures occur when there is a disturbance in the balance of excitation and inhibition in the central nervous system (CNS).4 Many different mechanisms can cause neuronal hyperexcitability and lead to the development of seizures. These factors include changes in ion channel conduction, membrane receptor response, messenger systems, and gene transcription. Imbalances between excitatory (glutamate) and inhibitory (gamma-aminobutyric-acid, or GABA) neurotransmitters, as well as excessive acetylcholine, norepinephrine, and serotonin levels, may also precipitate seizures.1
Excitatory and inhibitory currents are primarily mediated by different channels including voltage- and ligand-gated channels. Voltage-gated channels include sodium and calcium channels. Ligand-gated channels include GABA and glutamate channels. Most of the pharmacologic agents used in treating epilepsy target these different channels.1
Seizures represent the clinical manifestations or symptoms of disturbed electrical activity, while epilepsy is a disorder of recurrent seizures. A patient is considered to have epilepsy when he or she has had two or more unprovoked seizures.1 Patients with an isolated seizure or seizures secondary to a reversible cause (e.g., hypoglycemia, alcohol withdrawal, high fever) are not considered to have epilepsy.
Seizures are classified according to the classification scheme proposed by the International League Against Epilepsy (ILAE).5 It is recommended that seizures be assigned to one of two major categories: partial seizures or generalized seizures. Partial seizures are further classified into simple partial seizures (patient has no loss of consciousness) or complex partial seizures (patient has loss of consciousness).5
The classification of epilepsies is more complex. Since epilepsy cases can involve more than one seizure type, specific classification of epilepsies is less meaningful. Rather, the newly recommended approach is to refer to epilepsies in regard to etiology—genetic, structural/metabolic, or unknown. The epilepsy can then be further characterized based on different presenting features (e.g., age of onset, EEG findings, neurologic examination).6
Seizures involve abnormal electrical activity that can produce changes in consciousness, motor and sensory activity, and behavior. The symptoms that occur can vary significantly from patient to patient and generally depend on the type of seizure or epilepsy. Generally, partial seizures originate in one hemisphere and can involve disturbances in motor function, sensory perception, autonomic function, and behavior. Sensory symptoms include paresthesias, abnormal tastes or smells, flashing lights, and hearing changes. Patients can report different autonomic symptoms, like sweating, epigastric sensation, or piloerection. Some patients can experience psychic symptoms including dysphasia, fear, and hallucinations. Automatisms, or repetitive movements, can be described in some patients and often present as chewing, swallowing, or sucking. A number of patients can experience an aura or warning symptoms minutes to hours before a seizure. Aura symptoms can differ significantly; examples include irritability, nausea, headache, and fear. Loss of consciousness and memory loss may also occur with partial seizures. Partial seizures may not terminate and can evolve into secondary generalized seizures.5,7
Generalized seizures involve both hemispheres and typically include bilateral motor symptoms and loss of consciousness.5 The many different types of generalized seizures (absence, myoclonic, tonic, clonic, tonic-clonic, atonic) will vary in motor symptom characteristics.
Antiepileptic drug (AED) therapy may or may not be indicated after a patient experiences a first seizure. AED therapy is generally reserved for patients diagnosed with recurrent, unprovoked seizures or epilepsy and is typically not indicated in patients who have experienced an isolated seizure or seizures secondary to a reversible cause.
With the many different types of seizures and epilepsy syndromes, there really is no specific agent that is considered the drug of choice. Rather, specific AEDs are generally more effective and useful for certain types of seizures or epilepsy syndromes compared to others. A number of studies have compared agents for different types of seizures. The VA Cooperative Study compared carbamazepine, phenobarbital, phenytoin, and primidone in the treatment of partial and secondarily generalized tonic-clonic seizures.8 Based on the results, carbamazepine and phenytoin had the greatest treatment success. However, this study was conducted in the early 1980s and does not consider the use of newer AEDs. More recent studies have compared newer AEDs as initial monotherapy and have shown little difference in efficacy, but these studies are limited in duration (<1 year) and do not evaluate long-term efficacy.9-11
One of the latest studies, the Standard and New Antiepileptic Drugs (SANAD) trial, followed patients for 3 years.12 Results demonstrated that for partial seizures, lamotrigine and oxcarbazepine had the longest time to treatment failure in comparison to carbamazepine, topiramate, and gabapentin. For time to 12-month remission, lamotrigine and carbamazepine were significantly better versus oxcarbazepine, topiramate, and gabapentin.12 For generalized seizures, valproate and lamotrigine had the longest time to treatment failure, while valproate and topiramate had the shortest time to 12-month remission.13
The ILAE guidelines summarize evidence for efficacy of initial monotherapy for the treatment of newly diagnosed or untreated epilepsy.14 The American Academy of Neurology has issued guidelines assessing the efficacy, tolerability, and safety of newer AEDs in the treatment of newly diagnosed epilepsies.15 Although these guidelines make general recommendations on which AEDs should be considered for use based on efficacy or safety, they do not make specific recommendations on which AED is the clear drug of choice.14,15 With limited data and lack of specific recommendations from evidence-based guidelines, drug therapy is individualized, and selection of the most appropriate AED is based on a number of important considerations including seizure or epilepsy type, age, gender, comorbidities, potential adverse effects, drug interactions, and cost.14 Once treatment is initiated, approximately 60% of patients achieve adequate seizure control with monotherapy.16
Treatment Considerations
Seizure Type: Each AED is generally effective for certain types of seizures and can be classified as either broad or narrow spectrum. Broad-spectrum agents are effective for many different types of seizures. Narrow-spectrum agents are effective for only specific types of seizures. Determining seizure and epilepsy type is important in selecting the most appropriate agent (TABLE 1 lists specific agents and dosing).17
Adverse Effects: Since treatment of epilepsy is long-term and medication adherence is crucial for treatment success, drug tolerability is a major issue. AEDs can cause various adverse effects, and this is an important factor to consider when selecting therapy. Although most AEDs can cause common CNS side effects (dizziness and drowsiness), some agents are more tolerable compared to others. Impaired cognition is one major concern for many patients and family members. In general, newer agents like gabapentin and levetiracetam appear to have the least effects on cognition and may be better options.18
Patients with renal dysfunction should have dosage adjustment performed for topiramate, oxcarbazepine, levetiracetam, pregabalin, and lacosamide to avoid accumulation of the drug or its metabolites.19
A number of agents can affect the liver. Carbamazepine, phenytoin, and valproic acid can cause elevations in liver enzymes and thus should be avoided in patients with liver disease. Although these agents have also been known to cause hepatotoxicity, more severe liver problems are rare.19
AEDs may also cause different dermatologic reactions. Phenytoin can cause skin rash. Rare, fatal skin reactions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported with most agents, but appear to be more common with carbamazepine, valproic acid, phenytoin, phenobarbital, and lamotrigine.20,21
Suicidal behavior or ideation has been reported in numerous studies evaluating the use of AEDs for epilepsy and psychiatric conditions. Due to the potential risk, a black box warning has been added to the labeling of all AEDs, and distribution of medication guides is required. It is generally recommended to monitor patients on AEDs for any new or worsening thoughts of suicidal behavior.22
Childbearing Plans: Because of significant concerns for teratogenicity, AED selection is also affected by a woman's childbearing plans. Possible birth defects include intrauterine growth retardation, major malformations, and postnatal developmental delay. Since there is no consensus on the safest agent during pregnancy, the most effective agent is generally used at the lowest effective dose. However, because studies do demonstrate a greater risk for birth defects with valproic acid, it is commonly avoided.23 Women on oral contraceptives should be educated about the potential interaction between enzyme-inducing oral contraceptives and AEDs. When necessary, alternative contraception should be recommended.23
Drug Interactions: Many AEDs are metabolized through the CYP450 system in the liver and can be either enzyme inducers or enzyme inhibitors. Phenytoin, phenobarbital, carbamazepine, and primidone are well-known enzyme inducers, while valproic acid is the only major enzyme inhibitor. Enzyme inducers can enhance the metabolism of warfarin, oral contraceptives, antibiotics, and antidepressants resulting, in decreased serum concentrations and effects. Valproic acid can decrease the metabolism of warfarin, statins, and tricyclic antidepressants, resulting in increased serum concentrations and effects (TABLE 2).24 Carbamazepine is metabolized through CYP3A4 and can interact with CYP3A4 inhibitors, resulting in increased carbamazepine levels (e.g., erythromycin, diltiazem, cimetidine). Combination AED therapy is sometimes necessary, but drug interactions between AEDs are possible too. Since these agents can cause drug interactions with other medications and concomitant AEDs, it is important to screen for potential drug interactions prior to drug selection.24
Therapeutic Drug Monitoring
Therapeutic drug monitoring for AEDs is commonly used to help guide and assist clinicians with optimal dosing in patients. Monitoring serum concentrations can allow clinicians to achieve seizure control while minimizing adverse effects. Established drug levels for various AEDs should be primarily viewed as reference ranges and not therapeutic levels (see TABLE 1 for agents with established reference ranges). A serum concentration that falls below the reference range is unlikely to result in a therapeutic response, while a serum concentration that falls above the reference range is likely to result in toxicity. Yet it is important to recognize that because of individual variation and patient response, many patients can still achieve adequate seizure control at concentrations outside established reference ranges or develop toxicity at concentrations that fall within reference ranges. Thus, reference ranges serve merely as a guide, and each patient will have an individualized therapeutic level. Monitoring serum concentrations is most beneficial when suspecting toxicity, assessing medication adherence, or assisting with dosing in patients with altered pharmacokinetics.25
Epilepsy and the Pharmacist's Role
Epilepsy is a chronic disorder that continues to be a huge economic burden. Although newer AEDs aim to increase treatment success and decrease the risk for adverse effects, there is still a strong need for improving patient outcomes. Pharmacists can play a significant role in optimizing therapy for patients with epilepsy. Patient counseling on the potential adverse effects of AEDs is important. Patients and family members should be educated on expected CNS and cognitive side effects, potential skin reactions, and the risk for suicidal behavior. Patient education should also address the importance of medication adherence. Patient medication profiles should be reviewed for possible drug interactions, and dosage adjustments or alternative agents should be recommended if necessary. Additionally, pharmacists can advise clinicians on appropriate therapeutic drug monitoring.
1. Rogers SJ, Cavazos JE. Chapter 65. Epilepsy. In: Talbert RL, DiPiro JT, Matzke GR, et al, eds. Pharmacotherapy: A Pathophysiologic Approach.
8th ed. New York, NY: The McGraw Hill Companies; 2011.
www.accesspharmacy.com/content.aspx?aID=7985219. Accessed August 22,
2. Hirtz D, Thurman DJ, Gwinn-Hardy K, et al. How common are the "common" neurologic disorders? Neurology. 2007;68:326-337.
3. Vivas AC, Baaj AA, Benbadis SR, Vale FL. The health
care burden of patients with epilepsy in the United States: an analysis
of a nationwide database over 15 years. Neurosurg Focus. 2012;32:E1.
4. Lowenstein DH. Chapter 369. Seizures and epilepsy. In: Fauci AS, Kasper DL, Jameson JL, et al, eds. Harrison's Principles of Internal Medicine.
18th ed. New York, NY: The McGraw Hill Companies; 2012.
www.accesspharmacy.com/content.aspx?aID=9145219. Accessed August 20,
5. Commission on Classification and Terminology of the
International League Against Epilepsy. Proposal for revised clinical and
electroencephalographic classification of epileptic seizures. Epilepsia. 1981;22:489-501.
6. Berg ET, Berkovic SF, Brodie MJ, et al. Revised
terminology and concepts for organization of seizures and epilepsies:
report of the ILAE Commission on Classification and Terminology,
2005–2009. Epilepsia. 2010;51:676-685.
7. Symptoms of a seizure. About epilepsy. www.epilepsy.com/101/ep101_symptom. Accessed December 5, 2012.
8. Mattson RH, Cramer JA, Collins JF, et al. Comparison of
carbamazepine, phenobarbital, phenytoin, and primidone in partial and
secondarily generalized tonic-clonic seizures. N Engl J Med. 1985;313:145-151.
9. Brodie MJ, Richens A, Yuen AW. Double-blind comparison
of lamotrigine and carbamazepine in newly diagnosed epilepsy. UK
Lamotrigine/Carbamazepine Monotherapy Trial Group. Lancet. 1995;345:476-479.
10. Chadwick DW, Anhut H, Greiner MJ, et al. A
double-blind trial of gabapentin monotherapy for newly diagnosed partial
seizures. International Gabapentin Monotherapy Study Group 945-77. Neurology. 1998;51:1282-1288.
11. Privitera MD, Brodie MJ, Mattson RH, et al.
Topiramate, carbamazepine and valproate monotherapy: double-blind
comparison in newly diagnosed epilepsy. Acta Neurol Scand. 2003;107:165-175.
12. Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD
study of effectiveness of carbamazepine, gabapentin, lamotrigine,
oxcarbazepine, or topiramate for treatment of partial epilepsy: an
unblinded randomised controlled trial. Lancet. 2007;369:1000-1015.
13. Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD
study of effectiveness of valproate, lamotrigine, or topiramate for
generalised and unclassifiable epilepsy: an unblinded randomised
controlled trial. Lancet. 2007;369:1016-1026.
14. Gluaser T, Ben-Menachem E, Bourgeois B, et al. ILAE
treatment guidelines: evidence-based analysis of antiepileptic drug
efficacy and effectiveness as initial monotherapy for epileptic seizures
and syndromes. Epilepsia. 2006;47:1094-1120.
15. French JA, Kanner AM, Bautista MD, et al. Efficacy and
tolerability of the new antiepileptic drugs. I: Treatment of new onset
epilepsy. Report of the Therapeutics and Technology Assessment
Subcommittee and Quality Standards Subcommittee of the American Academy
of Neurology and the American Epilepsy Society. Neurology. 2004;62;1252-1260.
16. Brodie MJ, Kwan P. Staged approach to epilepsy management. Neurology. 2002;58(suppl 5):S2-S8.
17. Fisher RS. Summary of antiepileptic drugs. Epilepsy.com. September 2009. www.epilepsy.com/epilepsy/newsletter/sept09/aeds. Accessed September 6, 2012.
18. Meador KJ. Cognitive and memory effects of new antiepileptic drugs. Epilepsy Res. 2006;68:63-67.
19. Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug Information Handbook 2011-2012. 20th ed. Hudson, OH: Lexi-Comp; 2011.
20. Rzany B, Correia O, Kelly JP, et al. Risk of
Stevens-Johnson syndrome and toxic epidermal necrolysis during first
weeks of antiepileptic therapy: a case-control study. Study Group of the
International Case Control Study on Severe Cutaneous Adverse Reactions.
Lancet. 1999;353:2190-2194.
21. Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600-1607.
22. Suicidal behavior and ideation and antiepileptic
drugs. FDA. May 5, 2009.
Accessed December 5, 2012.
23. Tomson T, Perucca E, Battino D. Navigating toward
fetal and maternal health: the challenge of treating epilepsy in
pregnancy. Epilepsia. 2004;45:1171-1175.
24. Diaz RA, Sancho J, Serratosa J. Antiepileptic drug interactions. Neurologist. 2008;14(suppl 1):S55-S65.
25. Patsalos PN, Berry DJ, Bourgeois BF, et al.
Antiepileptic drugs—best practice guideline for therapeutic drug
monitoring: a position paper by the subcommission on therapeutic drug
monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia. 2008;49:1239-1276.
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