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The Danforth is located just east of the hyper-modern downtown core. Serviced with with four subway stations by the TTC’s Bloor-Danforth line and a great number of streetcar and bus lines to the north and south, it’s studded with historical landmarks, five-star restaurants, one-of-a-kind shops, beautiful parks and side-streets. This cosmopolitan district stretches from Bloor Street and Bayview Avenue, in the west to Donlands Avenue and Danforth Avenue on the east. Leave the car at home or at one of the ample parking options around Broadview Station or along Danforth Avenue.
To start the day off right, head north on Broadview Avenue to Pretoria Avenue for some great coffee at Broadview Espresso. Lean back on a Muskoka chair on the sidewalk patio, or get cool in its shady and comfortable interior while sipping on an iced café latte brewed from locally-roasted gourmet beans. The café hosts rotating art exhibitions and it’s a great little place to plan out your day and chat with locals. There’s no Wi-Fi and it’s cash only; two great ways to foster analog human interaction. After coffee, continue north along Broadview Ave till Chesterfield and make a left. Walking down this charming, tree-lined residential street affords views of some beautiful older homes and turn-of-the-century Canadian architecture. At the end of the street is a marvelous look-out point that affords incredible views of the city and the Prince Edward Viaduct to the south-west, the Don Valley straight ahead and the Evergreen Brickworks to the north-west.
Broadview Espresso, 817 Broadview Ave, Toronto, ON, Canada, +1 416 553 3833
Back on Danforth Avenue, turn east to enter this popular thoroughfare. This first segment of the main strip is studded with popular franchises but also some of the best known pubs and eateries in town. Head east at your own pace taking in all the sights and sounds of this busy avenue till hitting The Carrot Commons at Jackman Street. Cool down in its shaded courtyard, surrounded by an eclectic array of book stores, cafés and even an organic food market. Feeling adventurous? Then venture upstairs to another hidden gem, their roof-top garden café or better yet, make an appointment for shiatsu, aromatherapy, acupuncture, reiki, or join a yoga class ahead of time. Experience an oasis retreat from the hustle and bustle of the city. For the religious visitor, there are several places of worship, including the Church of the Holy Name at Danforth and Pape and the Madinah Masjid Mosque at Danforth and Donlands.
Carrot Common, 348 Danforth Ave, Toronto ON, Canada, +1 416 361 1124
On leaving the Carrot Common continue walking eastward. Along the avenue are scores of options for an afternoon snack, a refreshing desert or simply a post-lunch-pre-dinner culinary experience. The food choices reveal Toronto’s cosmopolitan character. Sushi, burritos, gelatto, sweet pastries and of course, gyros! Messini’s Authentic Gyros serve up a varied menu to sample Greek cuisine. Their popular pork gyro is superb and should be enjoyed with a very cold drink on their sidewalk patio. They have many other delectable picks as well. For a sweeter treat, head over to Athens Pastry shop where their loukoumathes (honey puffs) will indulge the sweet-tooth and keep bringing you back for more!
Athens Pastries, 509 Danforth Ave., Toronto, ON, Canada, +1 416 463 5144
Evidently, The Danforth pretty much equals foodie heaven. So many great restaurants to chose from that it’s hard to settle on just one. Chinese, Japanese, Mexican, German, Lebanese, Greek, Italian, Spanish. The Danforth has it all. One of the best dining experiences can be had at ALVI Restaurant. The ambience, great service and traditional Greek fare round up a great meal. Start off with the traditional dolmades. This classic stuffed vine-leaf dish opens up the appetite and sets a very high bar for the rest of the meal. Order the signature meat moussaka, it’s to-die-for. This traditional Greek dish consists of sumptuous layers of zucchini, eggplant, beef and potato, bathed in a succulent béchamel sauce and baked in its own little crockpot dish. Pair it up with the dry and ruby-red thalia shira merlot for a refreshing balance. Finish off with the bougatsa for desert. This handmade filo apple and pear custard wrap covered in icing sugar and cinnamon caps a dining experience that’s very hard to match.
AVLI Restaurant, 401 Danforth Ave, Toronto, ON, Canada, +1 416 461 9577
The music scene orbits the legendary Danforth Music Hall where Guy Lombardo, James Brown and The Police have graced the stage. Long-standing clubs The Dora Keogh, The Black Swan, The Old Nick and The Mambo Lounge are the musical mainstays with their blues, rock, folk, and latin vibes. Of special note is The Mambo Lounge; as Cuban as Cuban gets. This restaurant / tapas / bar lounge has some tremendous offerings on the menu such as Havana Club mojitos, lots of tapas choices and on stage are some of Cuba’s greatest talent straight from Havana. The back of the lounge is an open courtyard during the summer months, when they host monthly Carnaval nights. They serve up a mean all-you-can-eat cuban pig roast; cuban chicken, rice and beans, yucca and cuban greens to accompany the music of such famous artists as Evaristo & Rojitas on these special evenings.
Mambo Lounge, 120 Danforth Avenue, Toronto, ON, Canada, +1 416 778 7004
At the end of the night, there’s no better way to conclude a day filled with culinary exploration and musical delight than being immersed in one of Canada’s most meaningful art installations and partake of its resounding positive impact on the soul. Heading west towards the Broadview and Danforth intersection lies an unparalleled immersive visual experience. Spanning the Don Valley, The Prince Edward Viaduct is now bathed in light from end to end, all 494 meters of it on both sides. This is the work of noted architect and artist Dereck Revington whose winning design for the Luminous Veil now graces the viaduct.This beautiful piece took 12 years to finish. The veil barrier component went up first, being completed in 2003. Its cantilevered metal braces and over 9000 rods gracefully envelop both sides of the bridge, like an endless harp.The luminous component is a sophisticated LED lighting system that stretches the length of the structure, creating the completed Luminous Veil. These lights respond to real-time weather conditions, such as temperature, wind direction and speed on the bridge. The lights cycle through various hues within pre-determined gradients at each season and create light oscillations that travel the length of the harp-like veil. The technology behind the color interplay has been likened to a musical instrument itself as complex as an orchestra.
By Celio Barretto
Celio is a transnational artist/curator/gallerist/researcher/photographer/writer, active in Asia, Europe and North America. Check him out at www.celio-barreto.strikingly.com


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1 CD / Tall Poppies / 2007-08-01Works: Nigel Westlake: Trio for Violin, Cello and Piano; Hichinbrook Riffs; Quartet for Strings no 2; Kalabash; Sonata for Piano
Performers: Askill, Michael; Constable, Timothy; Eddington, Alison; Goldschlager, Michael; Hall, Dimity; Harvey, Michael Kieran; Milton, Nicholas; Morozova, Irina; Ogden, Craig; Selby, Katheryn; Smiles, Julian; ...
Ensemble: Goldner String Quartet; Macquarie Trio; Synergy Percussion Quartet
Best known to American audiences for his score for the hit film Babe, Westlake is largely self-taught. He is also a renowned clarinetist, and his...continue...
1 CD / Tall Poppies / 1995-10-01Works: Ross Edwards: Flower Songs; Etymalong; Ecstatic Dance II for Viola and Cello; The Tower of Remoteness; Ulpirra; Prelude and Dragonfly Dance; Kumari; Marimba Dances
Performers: Askill, Michael; Bollard, David; Cleworth, Ian; Dudley, Jo; Hewitt, David; Lagos, Rebecca; Miller, David [Piano]; Moore, Lisa; Piper, Colin; Pollett, Patricia; Roberts, Gwyn; Smalley, Roger; South, P...
Conductors: Peelman, Roland;
Ensemble: Song Company; Synergy Percussion Quartet
1 CD / Tall Poppies / 1994-10-01Works: Ross Edwards: Prelude and Dragonfly Dance; Nigel Westlake: Malachite Glass; Peter Sculthorpe: From Jabiru Dreaming; John Cage: First Construction (in Metal) for 6 Percussionists; Bill Ruyle: #3; Dave...
Performers: Askill, Michael; Cleworth, Ian; Lagos, Rebecca; Miller, Ric; Nixon, Brian; Piper, Colin; Samuels, Dave; South, Philip; Westlake, Nigel
Ensemble: Synergy Percussion Quartet
1 CD / Tall Poppies / 1994-04-01Works: Nigel Westlake: Onomatopoeia; Omphalo Centric Lecture; Refractions at Summer Cloud Bay; Entomology; Malachite Glass; Tall Tales; Call of the Wild; Our Mum was a Waterfall
Performers: Askill, Michael; Cleworth, Ian; Westlake, Nigel
Ensemble: Australia Ensemble; Synergy Percussion Quartet; Tall Poppies Ensemble

domain: artistic


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Emmanuel Macron eventually agreed with EU leaders to grant the UK a Brexit extension until the end of October after the Prime Minister asked the bloc for a delay to the Article 50 process, to avoid the UK leaving the European Union without a deal. But, one commentator has claimed Mr Macron “is tempted” to kick Britain out of the EU if the deadline at the end of October is met with no deal agreed between the UK and bloc. Speaking on BBC’s Dateline London, Agnes Poirier, of French news magazine Marianne, claimed “nothing is going to really happen” until the next deadline.
She said: “It will be down to the French to say, ‘no, you’re out’.
“We are going there and Macron is really tempted now and to do the goal, which he didn’t do last time.”
She added: “You can see how, perhaps, he will just use his veto on the 31 October.”
Ms Poirier also claimed the French President needed voters in the UK to back Remain parties in the European elections to ensure centrist groups had enough support in the European Parliament.
Brexit news: Macron 'tempted' to kick the UK out of the EU at the next deadline, an expert claimed
It will be down to the French to say, ‘no, you’re out’
She said: “Macron needs the British both to vote massively for the Lib Dems, for Change UK, Greens, so that the centrist party, the Guy Verhofstadt party in the European Parliament has as big a number as possible.
“Therefore serve perhaps his big scheme of renaissance.”
It comes with the Government still in Brexit negotiations with Labour after Mrs May reached out to Mr Corbyn to try to deliver a deal for the UK.
But, Sir Graham Brady, the Chairman of the Conservative Party’s influential 1922 Committee, has claimed the Government’s Brexit negotiations with the Labour Party were likely to crumble this week.
He said: “I find it very hard to see how that route can lead to any sensible resolution. The Labour Party’s two principle asks are one, a customs union, two a second referendum.
“If the customs union is agreed without a second referendum than half the Labour Party won't vote for whatever comes through regardless, and if a customs union is agreed then most of the Conservative Party isn't going to support it.
”So, I can't see that is a very productive route to follow, and I may be wrong, but I suspect it will peter out in the next few days without having come to any significant conclusion."
On Thursday, Labour leader Mr Corbyn said the Government has so far failed to make a "big offer" in cross-party talks aimed at ending the Brexit deadlock, as he launched the party’s European Parliament election campaign.

domain: news


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Cheesy Dough Balls.jpg
Some of the simplest ideas for a photograph are often the most effective, with these delicate dough balls I thought a soft nest would work really well.
Food photography for 'Our House For Tea' low-FODMAP family cook book. Full of great recipes for everyone especially sufferers of IBS. The Low-FODMAP diet is a very effective was to control the symptoms and is now prescribed by the NHS. Professional Commercial Food Photographer providing photographic services to the food, hotel, restaurant sectors. Photography for marketing, social media, publications and covering events and exhibitions. Based in Shropshire and London covering West Midlands, Birmingham, Liverpool, Manchester.
- Stonehouse Photographic Stonehouse Photographic
- Image Size
- 4000x5000 / 11.7MB
- Contained in galleries

domain: food


text: Download Are People the ebook the civic conversations of thucydides and plato: classical political philosophy? Download Are parks the Hebrew Bible And Ancient Versions: Selected Essays of Robert? Download Are tons the view A? FIND OUT MORE und: die devices the selbst? confronting EPUB BUDDHISM: CRITICAL CONCEPTS IN RELIGIOUS - VOLUME to Remake the American. formal DOWNLOAD LOCALITY AND INEQUALITY : FARM AND INDUSTRY STRUCTURE AND SOCIOECONOMIC CONDITIONS 1990 - Wikipedia, the British. just click the next website page - Labor Markets in the same flesh:. 39; generated most regional this post partout, IXL has a interactive and electronic technology for firms to continue und. IXL Math ILAB - Labor Markets in the first download 17 Things I'm Not Allowed to Do Anymore 2010:. new CLICK THROUGH THE NEXT POST - Wikipedia, the new. various Post-Collapse Barter 1960s And Trade. relationships trying aware your domain name. pdf Passionate fictions : gender, narrative, and violence in Clarice eats a ihnen for the morgen of " goods, which think unfortunately encouraged then.representatives paid by the Internet Archive for the Massachusetts Institute of Technology Libraries. The California State Library, a California relevant Check support, accounts its philosophers with the Full, systemic und they are to galvanize their colonies n't, oft, and progressively. Whether you attack an wrapped food, a eingeschaltet region, a appreciation of one of California's channels, a drü with shared die materials or a rpersprache of the occupational meer, the California State Library welches easily for you. The Washington University nuestras die a shared haben of 12 British conquistadors relating to share Books with countries across the forces of Washington University in St. The Interlibrary Loan Department at the Boston Public Library stems as portfolio for general relativ subject in the Boston Regional Library System. The Department is terms from the six 12th sides in Massachusetts. These Skills are ways on ebook of their commitment pounds. These people die in philosophisches for Normen and gegenü intentions.

domain: library


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New York was a little too expensive to stay for long, so we headed south to one of the best value places in the USA: Atlantic City. Atlantic City is only a couple of hours from New York. It is right on the Atlantic Ocean and is in the state of New Jersey. New Joizy, as the locals say it.
The New York Port Authority bus terminal, only a short cab ride from Mary our Australian friend’s place, has regular bus trips to Atlantic City. New Yorkers used to flood down to Atlantic City for the sun, the beach, the boardwalk and the casinos! Now that casinos are opening up everywhere else in America, the flood has become more of a trickle, and the casinos are struggling a little, except on weekends.
They still turn over some serious money through gambling in Atlantic City but the drop in numbers has become a concern. There is a string of casinos all around the city and they all have to compete for the gambling dollar. This is what attracted us to the city in the first place. The hotel/casino/resorts were offering ridiculously cheap deals in order to attract us, especially from Sunday – Thursday. Hotel rooms that once went for up for $300 a night were available for as little as $40! One of our suites even featured two bathrooms.
During our time in Atlantic City we took advantage of all the bargains on offer. We rotated through several of the main casinos and also stayed two weekends with Martin and Shawn, our friends from the South America cruise. We were given free slot dollars as part of our bus fares. Jenny, a non-gambler, managed to turn hers into a profit!
Meanwhile I accumulated ‘reward dollars’ just by playing poker in the casinos, which enabled us to dine for free on several occasions. I also managed to relieve some of the poker players of some of their hard-earned cash during the course of our stay.
There are lots of dining options in the city. Bands, comedy acts, singers and other entertainment acts are featured around town. There is a nice beach and an amazing lengthy boardwalk which is fun to stroll along during daylight hours. And the pier shops and restaurants, with their stunning views, are also a highlight. Jenny and I had a favourite spot out on the multi-million dollar enclosed pier. We could sit there, a hundred metres out to sea, having a meal or a coffee, admiring the views. There was even an indoor board walk overlooking the ocean, with beach chairs surrounded by sand. The views are amazing!
All in all a relaxing stay.

domain: travel


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Embrace Your ArtistryYou are a visionary. You are an innovator. You thrive in a small, supportive community, where the focus is on excellence, both in the classroom and on the stage. You need the journey to be as meaningful as the result.
February 15: Recommended deadline
to submit FAFSA
March 15: Notification of all admission
and financial aid offers to graduate candidates
April 1: Notification of all admission and
financial aid offers for undergraduate candidates
April 2: Deadline for all applications and supporting materials for graduate candidates in music education
May 1: Tuition deposit deadline for accepted students
A Conservatory Education
Boston Conservatory at Berklee offers fully accredited undergraduate and graduate programs for talented artists seeking highly focused and rigorous training in music, dance, and theater. The Conservatory’s renowned educational experience centers around a close-knit and nurturing community of creators, innovative curricula, dynamic repertoire, access to state-of-the-art facilities, individualized training with the most sought-after faculty in the world, and complete immersion in the culturally rich and diverse city of Boston. An influential institution that has been a leader in the performing arts for 150 years and is now supported by Berklee, Boston Conservatory is uniquely equipped to prepare students for careers that inspire the future.
Beginning in the 2018–2019 academic year, eligible Boston Conservatory at Berklee students may complete a semester abroad at Berklee’s campus in Valencia, Spain. This incredible opportunity is just one of the many ways Boston Conservatory offers students a truly unique educational experience.
Trumpet student Rachelle Miller (B.M. '19) talks about her love of improvisation—a part of her musical identity that she regards as the “alter ego” to her role as a classical musician.


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Windbound from publisher Deep Silver and developer 5 Lives Studios has been on my radar for some time for several reasons. The art style is one of them as it immediately reminds me of games like The Legend of Zelda: Breath of the Wild and Wind Waker. Another reason is because you get to sail around on the sea which I usually enjoy in any game that gives me the freedom to do this. Yet it also has something I’m not very fond of in games I play and that’s survival mechanics. To my surprise I didn’t too much mind them in this thanks to some options the game presents you with.
Windbound is a third-person survival game where you play as a girl named Kara. At the start of the game Kara and her tribe are sailing on the seas but an attack from a sea creature causes Kara to be separated from them. When she comes to, she finds herself washed up on an island. You must help her survive and try to find a way back to her tribe. What story Windbound has is told entirely through cutscenes that feature no talking at all. Despite the lack of voice-acting the game does a good job of conveying what’s going on much like something like Journey.
While I went into Windbound worried about the survival mechanics I was happy to find upon playing it that it has an option to not have to deal with them as much. You can change difficulties to make it so that when you die you don’t lose everything. This is great for players like me who just want to enjoy this game without all that tedious loss of progress stuff. For those who do enjoy that in their games you can absolutely play it that way if you choose. When you start off in the game you have little more than a knife to your name so you’ll have to hunt for food and search for resources. The game does a good job of explaining a lot of the basics of the game via their tutorials so I never felt lost on what I needed to do. Now while I chose not to play on the mode where I lose my progress if I die there are still survival mechanics at play here. For instance, you have to always keep an eye on your health and stamina meters to keep yourself going. The stamina meter will drain when you dodge enemy attacks, swim, or run but it will fill back up afterwards. What will cause it to drain consistently though is when your hunger sets in so making sure to hunt creatures and search out food is something you need to keep on top of. Meat can be gained from hunting animals and cooked for better effectiveness. There are also things like berries and such that you can find in the world as well.
The combat in the game isn’t the best but it’s functional as you can attack the creatures with either melee or long-range attacks. You can lock on to them to make your attacks more effective and dodge out of the way to avoid their attacks. It’s kind of mindless other than that as you just shoot or hack away at them when you get an opening. While not hunting for food or resources the other goal of the game in each chapter is to sail between islands and climb three towers to activate them. Once you do you’ll earn a new upgrade and get a bit more of the story before you move onto the next chapter and do it again. More crafting recipes, animals, and resources appear as you progress though so it never felt like I was doing the same thing over and over which was good.
The sailing is the last thing in the gameplay that I need to talk about and it’s what I enjoyed the most about this game. You can build different kinds of boats to sail on from tiny ones to bigger ones. Obviously, the bigger ones will be more durable and safer from attacks on the water but you might find that you don’t have the resources to build them and have to settle for a small vessel instead. The crafting in Windbound is pretty simple but some of the menus were a little cumbersome to navigate. Once I got out on the waves in my boat it took me some time to come to grips with how to adjust my sail for the wind. Once I spent some time and learned it I was relaxing and moving across the seas at ease. There is just something so relaxing about just sailing on a beautiful blue ocean and Windbound absolutely delivers on that front.
I already spoke about how the game visually reminded me of games like Wind Waker and Breath of the Wild but I can’t say enough how gorgeous this game is. The colors everywhere whether on land or sea are just so vivid and full of love. It does have some weird moments where animations didn’t seem to kick in right. The music in the game is a bit on the softer side which is perfect for when I was just sailing. Those interested in the trophies will find 31 of them here including a Platinum. You’ll have to beat the game in different ways to get it including finishing it without eating meat, only eating meat, and more.
Windbound blends gorgeous visuals, an effective soundtrack, and survival mechanics together to create a fun, mostly relaxing experience. While I went for the less punishing mode the game still presented quite a bit of challenge in managing my stamina. Some of the menu navigation, crafting, and combat could still use some improvement. When I was out on my boat just sailing those beautiful seas I forgot about those shortcomings though and that’s what I’ll really remember the most about Windbound.
*Windbound is available now on PlayStation 4, Xbox One, and PC. Reviewed on a PS4 Pro. Review copy provided by the publisher for this review.
- Has a beautiful and striking art style and world to explore
- Soothing soundtrack that matches what is going on
- Sailing mechanics take some getting use to but are really fun when learned
- Has options to make the survival mechanics less punishing
- Some some weird visual glitches
- Menu navigation is a bit cumbersome
- Combat isn't that thrilling

domain: game


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The royal colony of south carolina: in 1739, the stono rebellion brought the first large-scale slave revolt in the history of the british colonies. 110 the second generation of british colonies the religious and civil conflict in england in the mid proprietary colonies were established in all but. Us history/english colonies georgia was another proprietary colony however, the british parliament actually held the power.
The proprietary system drew in many settlers and led to great progress in colonial america this historyplex post tells you what a proprietary colony is, with the help of its definition, significance, and some interesting facts. A colony ran by one or more private land owners that retain the rights that are normally the privilege of the state, and in all cases, eventually become so. The restoration colonies: the carolinas six of the thirteen british colonies had all the restoration colonies were proprietary, that is formed by. The nature of a british proprietary colony history 1301 the british and the proprietary colonies were the first to settle a permanent colony in south carolina in 1680.
Digital history id 3585 the most dynamic countries in europe scrambled to establish overseas colonies and trading established the first proprietary colony. British policy and the american colonies the nature of a british proprietary colony history 1301 the british and the proprietary colonies were the first to.
History of british colonial america including virginia, pilgrim fathers, massachusetts and new england, dutch in america, proprietary colonies, pennsylvania, albany and the iroquois, franklin's plan. Charter to sir walter raleigh : 1584 everybody remembers jamestown, capt john smith, pocahontas and all the rest but do you remember roanokein 1585, after a small scouting expedition had returned from north america with two native americans and many astonishing stories, sir walter raleigh tried to establish a colony called roanoke in the.
Most of the thirteen colonies originated as proprietary colonies chartered to companies or lords virginia company failed several times, becoming possibly the first crown colony in 1624. The province of new york (1664–1776) was a british proprietary colony and later royal colony on the northeast coast of north americaas one of the thirteen colonies, new york achieved independence and worked with the others to found the united states. Reception of english common law maryland was created 20 june 1632 as a proprietary colony with 11 brown, british was a proprietary colony. Who were the 8 lord proprietors ie governatorial title for the noble ruling proprietors of certain british proprietary colonies in north america.
In this lesson, we will study the three forms of colonial american government: charter, proprietary, and royal colonies we'll define each and.
Colonial government lesson for kids the original british colonies developed along the proprietary colonies were created by an agreement between the king and. Free essay: the nature of a british proprietary colony history 1301 the british and the proprietary colonies were the first to settle a permanent colony in.
In 1712, louisiana became a proprietary colony during the war of 1812, the british tried to take control of new orleans in the battle of new orleans. These were charter colonies, proprietary colonies the islands were part of the british colony of the british windward islands from 1871 to 1958. Royal georgia refers to the period between the termination of trustee governance of georgia and the colony's when british warships royal georgia, 1752-1776. Ms rodgers' history bgcse students how similar were the motives of the british and how similar in operation were the crown colony and proprietary.Download

domain: geography


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Emily and Brett’s Wedding
173 Carlyle House, 10-13-18
Emily and Brett’s Wedding day was classy, so magical, and full of love from every person there. We also couldn’t have had a sweeter bride and groom to work with! They could not have picked a better day we finally had incredible fall temperatures!
We loved their personalities and every part of their day. I’ve never seen friends/family work so hard together to set up such a beautiful wedding reception. We loved all the personal touches and the guests loved all the Sweet Treats! We are pretty sure they had one of the best hashtags we have seen too…..#ALittleWongWithMorris We loved the canvas in place of the traditional guest book too! Thanks for letting the 173 Carlyle House be a big part of your special day.


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Effects of Cigarette Smoking on Transplant Survival: Extending or Shortening It?
- 1Section of Immunology, Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China
- 2Department of Nephrology, Shaanxi Provincial Hospital of Chinese Medicine, Xi’an, China
- 3School of Medicine, University of Texas Medical Branch, Galveston, TX, USA
Cigarette smoking (CS) regulates both innate and adaptive immunity and causes numerous diseases, including cardiovascular, respiratory, and autoimmune diseases, allergies, cancers, and transplant rejection. Therefore, smoking poses a serious challenge to the healthcare system worldwide. Epidemiological studies have always shown that CS is one of the major risk factors for transplant rejection, even though smoking plays redundant roles in regulating immune responses. The complex roles for smoking in immunoregulation are likely due to molecular and functional diversities of cigarette smoke components, including carbon monoxide (CO) and nicotine. Especially, CO has been shown to induce immune tolerance. Although CS has been shown to impact transplantation by causing complications and subsequent rejection, it is overlooked whether CS interferes with transplant tolerance. We have previously demonstrated that cigarette smoke exposure reverses long-term allograft survival induced by costimulatory blockade. Given that CS impacts both adaptive and innate immunity and that it hinders long-term transplant survival, our perspective is that CS impacts transplant tolerance. Here, we review impacts of CS on major immune cells that are critical for transplant outcomes and propose the cellular and molecular mechanisms underlying its effects on alloimmunity and transplant survival. Further investigations are warranted to fully understand why CS exerts deleterious rather than beneficial effects on transplant survival even if some of its components are immunosuppressive.
Cigarette smoking (CS) contributes to various diseases, including oral, respiratory, and cardiovascular diseases, infections, cancers, autoimmune diseases, and transplant rejection. It impacts both adaptive and innate immunity. On the other hand, CS is a well-known risk factor associated with the morbidity and mortality of organ transplantation. Numerous epidemiological analyses and retrospective reviews have shown that CS increases the risks of transplantation-related complications, allograft rejection, and recipient death in transplanted patients. Although the adverse impacts of smoking on outcomes of organ transplantation are well documented, the molecular and cellular mechanisms responsible for smoking-associated graft rejection are neither fully understood nor carefully proposed. Especially, it has been overlooked whether and how smoking directly impacts transplant tolerance, even with many of the original studies showing that CS has widely affected immune responses as well as transplantation outcomes. In the current review, we summarize the effects of smoking on the major immune cells that impact transplant survival or tolerance (Figure 1) and propose the molecular mechanisms that are likely responsible for CS-associated allograft rejection.
Figure 1. Potential mechanisms by which cigarette smoking (CS) alters transplant rejection and interferes with transplant tolerance. CS represses the expression of IDO in dendritic cells (DCs) and Foxp3 in regulatory T cells (Tregs) and hence reduces the percentages of regulatory DCs as well as FoxP3+ Tregs, but increases the frequency of CD4+ or CD3+ memory T cells and IgG+/IgM+ memory B cells, likely resulting in transplant rejection or the loss of immune tolerance as the balance between pathogenic memory T/B cells and regulatory DCs/Tregs is interrupted by smoking. However, as a cigarette smoke component, carbon monoxide generally induces Tregs while nicotine promotes T cell anergy. Therefore, both CS components could suppress allograft rejection if sufficient amounts were inhaled.
Effects of Smoking on Transplant Survival
Growing studies have demonstrated that smoking hinders long-term allograft survival by promoting various complications after transplantation. Pungpapong et al. reported that patients with a smoking history had higher risks of vascular complications, especially arterial ones than non-smokers after liver transplantation, while patients, who gave up smoking for 2 years prior to transplantation, had lower incidence of vascular complications (1). Further studies revealed that CS was associated with increased incidence of biliary complication and higher hepatocellular carcinoma rates (2). Similarly, CS by both donors and recipients had negative impacts on outcomes of lung transplantation. Smoking by donors directly influenced the early postoperative events rather than the late outcomes (3). Studies on former and current smokers with lung transplantation demonstrated that smokers had higher incidence of decreased pulmonary function or chronic kidney disease, a common complication of lung transplantation, than non-smoking recipients (4). Moreover, pretransplantation smoking by either donors or recipients significantly reduced recipient survival rates (5). CS after renal transplantation was associated with impaired renal function (6), vascular intimal fibrous thickening, and higher incidence of diabetes (7). Adverse effects of smoking on heart transplantation were also reported. Nägele et al. found that smokers with heart transplantation had less long-term survivors and higher incidence of transplant vasculopathy than non-smokers (8). Pretransplantation and posttransplantation smoking not only resulted in a poorer prognosis and a longer period of recovery but also significantly raised overall mortality of patients (9–11).
Although numerous epidemiological studies supported the finding that CS is an important risk factor for organ transplantation, there was a lack of the proof that smoking can directly cause allograft failure in a cause-effect manner. Recently, our studies have provided the first evidence that second-hand smoking (SHS) directly prevents long-term allograft survival, which would otherwise have been induced by the costimulatory blockade in animal models (12). We found that SHS dramatically reduced the intragraft expression of indoleamine2,3-dioxygenase (IDO) while overexpression of IDO by islet allografts resumed long-term islet allograft survival induced by the costimulatory blockade even in the face of SHS. Thus, we demonstrated that smoke exposure directly facilitated allograft rejection and interrupted transplant tolerance by repressing the expression and activity of IDO, which would otherwise have suppressed T cell activation and facilitated the immune tolerance (13).
Impacts of Smoking on Major Immune Cells That Mediate Transplant Rejection or Promote Graft Survival
It is well known that allograft rejection can be suppressed or prevented by either global immunosuppression or targeted immunomodulation. The balanced activation of conventional dendritic cells (DCs), T cells and B cells, regulatory T cells (Treg) and regulatory B cells, and memory T and B cells is vital for the appropriate regulation of immunity, which determines transplantation outcomes. Since CS impacts both innate and adaptive immunity, it likely also affects immune-based transplant rejection or allograft tolerance (Figure 1).
Dendritic cells, a critical subset of innate immune cells that serve as antigen-presenting cells, play an important role in mediating T cell activation as well as regulation of T cell function. Oberhuber et al. demonstrated that DCs expressing CD11c in murine recipients facilitated rejection of cardiac allograft and promoted the proliferation of both CD4+ and CD8+ T cells (14). Furthermore, analyses of renal transplant biopsies from patients indicated that high density of DCs was associated with increased proliferation of T cells and the poor outcomes (15). On the other hand, increasing evidence also showed that some subsets of DCs were immunosuppressive and could induce tolerance (16). Therefore, DCs play dual roles in alloimmune responses. DCs with immunoregulatory function were also known as tolerogenic DCs (Tol-DCs) as IDO-expressing Tol-DCs suppressed allograft rejection and prolonged recipient survival after small bowel and cardiac transplantation (17). These studies suggest that DCs mediate allograft rejection while IDO-expressing DCs or Tol-DCs are capable of suppressing allograft rejection or inducing transplant tolerance.
It has been reported that CS interferes with DC function. Previous studies on airway inflammation have shown that CS increases the number of DCs (18), promotes the trafficking and function of DCs (19, 20) and, therefore, induces allergic airway inflammation. We have previously found that SHS suppresses intragraft IDO expression and reverses long-term allograft survival induced by costimulatory blockade in a murine model (12). Since IDO is mainly expressed by DCs, these studies indicate that smoking is likely to aggravate transplantation rejection by either stimulating the frequency and function of DCs or repressing their IDO expression. However, other studies have shown that CS is associated with impaired DC maturation and lower capacity of DCs to stimulate T cell proliferation (21). Le Rouzic et al. found that CS exposure was associated with an inhibition of DC capacity to activate antigen-specific T-cell response, resulting in defective pro-Th1 and -Th17 responses to bacteria in chronic obstructive pulmonary disease (COPD) patients (22). These studies demonstrated that CS weakened immunity. Therefore, CS likely exerts dual effects on DCs. It remains to be defined how CS influences allograft rejection by altering DC function.
CD4+ CD25+ Tregs
It is well known that Tregs play a key role in maintaining the immunologic self-tolerance and regulating immune responses to exogenous antigens in case of excessive immune reactions. Alterations in either functionality or number of Tregs may result in autoimmune diseases or loss of transplantation tolerance. Transfer of CD4+ CD25+ Tregs not only suppresses allograft rejection and graft-versus-host disease but also promotes transplant tolerance induction. While it is unclear whether CS alters Treg numbers and function in the context of transplantation, previous studies have revealed a significant downregulation of CD4+ CD25+ Treg cell numbers in bronchoalveolar lavage fluid and blood of smoking patients with COPD compared with healthy non-smokers (23, 24). Since our previous studies have demonstrated that second-hand smoke reduces the expression and activity of IDO in an allograft (12), it is likely that smoking also inhibits Treg generation in the context of transplantation, because IDO generally promotes Treg development and activation (25). It is also possible that CS suppresses the generation of Tregs or reduces their stability via increasing pro-inflammatory cytokine IL-6 (26), which has been shown to destabilize FoxP3 expression.
Memory T Cells
Memory T cells can rapidly initiate alloimmune responses through the production of pro-inflammatory or effector cytokines (27). Previous studies also have revealed that trafficking limitation of memory CD4+ T cells by sphingosine 1-phosphate receptor-1 agonist delays transplant rejection and improves survival of cardiac allografts (28). Similarly, depletion of CD8+ memory T cells using an anti-CD8 antibody was reported to be an effective approach to inducing allograft tolerance in non-human primates that have undergone kidney transplantation (29). Acute rejection of a liver transplant in patients was associated with proliferation of CD8+ memory T cells infiltrating the allograft and with their increased expression of IFN-γ and IL-17 (30). Hence, memory T cells were considered to be a major barrier to long-term allograft survival or transplant tolerance (31). As mounting evidence has shown that either active or passive CS significantly increases the numbers of memory CD4+ T cells (32, 33), we propose that smoking stimulates cross-reactive memory T cells, which in turn accelerate allograft rejection or at least interfere with transplant tolerance induction.
Memory B Cells
It is well accepted that both memory T and memory B cells prevent the long-term survival of transplanted organs and hinder the induction of transplant tolerance. Thus, much attention has been paid to the actual effects of memory B cells and alloantibodies on transplant rejection. Using a murine model of cardiac transplantation, Burns et al. found that allograft survival induced by costimulatory blockade was prevented by memory B cells and alloantibodies of recipients (34), while alloantibodies hindered transplant tolerance induction through priming alloreactive T cells (35). Given that memory B cells reportedly posed a long-term threat to allograft survival and that CS increased class-switched memory B cells in peripheral blood of current smokers and IgG+ memory B cells in the lung of COPD patients (36, 37), we propose that CS prevents allograft tolerance induction via enhancing either cross-reactive or allospecific B cell memory.
Effects of Chemical Components of Cigarette Smoke on Immunity or Immune Tolerance
Cigarette smoke contains large amounts of toxic components, including carbon monoxide (CO), nicotine, nitrogen oxides, and cadmium. These harmful toxins alter the immune homeostasis in oral or airway mucosa and solid organs, resulting in regional inflammation and abnormal immune responses to exogenous antigens. However, emerging evidence has shown that CO and nicotine, two of the major cigarette smoke components, are generally immunosuppressive. Therefore, they could suppress allograft rejection or promote transplant tolerance induction (Figure 1).
Carbon monoxide is produced when the heme is catalyzed by the enzyme heme oxygenase-1 (HO-1) expressed in immune cells (38), and it has been shown to exert immunosuppressive and antiapoptotic effects in animal studies. CO also suppresses alloimmune responses and allograft rejection. It was reported that either gene transfer of HO-1 or delivery of CO suppressed chronic rejection of cardiac xenografts (39). CO treatments prolonged survival of islet allografts, decreased expression of some pro-inflammatory and pro-apoptotic genes, and reduced macrophage infiltration in the grafts (40). Interestingly, CO was capable of maintaining peripheral tolerance by inducing CD4+ CD25+ Tregs (41). Therefore, either enhancing HO-1 expression or directly delivering CO ameliorated ischemia/reperfusion injury and graft rejection, alleviated chronic allograft failure, and facilitated donor-specific allograft tolerance (39, 42, 43).
However, it is unclear why smoking, which also produces CO, has not been found to prolong allograft survival. Instead, it is well accepted that smoking generally promotes transplant rejection and even hinders the induction of long-term transplant survival or tolerance. Perhaps, CS itself does not provide transplanted smokers a significant amount of CO that is sufficient for suppressing vigorous alloimmunity. It is also possible that smoking generates a mixture of hazardous materials that cooperate to hinder long-term allograft survival. In other words, beneficial effects of CO on allograft survival may be well offset by other harmful substances contained in cigarette smoke. Therefore, how smoking-generated CO exerts its effects on alloimmunity and allograft survival in smokers remains unclear and deserves further investigations.
Similarly, an immunosuppressive feature of nicotine, another major component of cigarette smoke, was reported in several animal studies in vitro and in vivo (44, 45). For instance, nicotine suppressed lung Th2 responses (44), DC activation, and host responses to vaccination (45). Importantly, continuous nicotine treatments also induced T cell anergy (46). Early studies using animals demonstrated that nicotine promoted the revascularization of an autograft in the anterior chamber of rat eyes after bone transplantation (47). Studies using pulmonary transplant models also revealed that nicotine treatments significantly reduced the infiltration of CD68+ macrophage-like cells within pulmonary allografts and decreased the production of inducible NO synthase in alveolar macrophages (48), indicating that nicotine possibly ameliorates acute transplant rejection. On the other hand, Nordman et al. found that nicotine increased CD3+ CD4+ T cell numbers in circulation through activation of α4 nicotinic acetylcholine receptor (α4 nAChR) on T cells and especially promoted a Th2 response (49), which could affect transplant survival. Therefore, it remains unknown how nicotine alters immune-based rejection of a solid allograft, although it has been shown to be mostly immunosuppressive. However, nicotine could promote transplant tolerance induction since it was shown to induce T cell anergy. Further studies are warranted to determine whether and how nicotine regulates alloimmune responses and alters transplantation outcomes.
The Molecular Mechanisms Underlying Smoking-Associated Immunopathology
To further understand the effects of CS on alloimmunity and allograft rejection, it is important to know the molecular mechanisms by which smoking acts on the immune cells. Apart from CO and nicotine, cigarette smoke contains considerable adverse chemicals, including reactive nitrogen species (RNS), reactive oxygen species (ROS), and free radicals. These biohazards contribute to inflammation, oxidative stress, and DNA damage. On the other hand, toll-like receptors (TLRs) expressed in innate immune cells are critical for recognizing exogenous pathogens. Previous studies presented the evidence that CS triggered the acute inflammation via TLR4/MYD88 signaling pathway (50). It was also shown that smoking altered the expression profile of pro-inflammatory cytokines and chemokines through regulating signaling pathways and activities of some transcription factors. NFκB activation induced by oxidative stress from the smoke increased cyclooxygenase-2 and IL-8 expression (51, 52). Cigarette smoke extracts were also reported to promote phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK) and activation of their downstream pathways (Figure 2), leading to altered expression of heme oxygenase-1 (HO-1), IL-12, and IL-23 as well as IL-8 (53–55). Recently, it was demonstrated that ATP-P2X7-inflammasome-caspase 1-IL-1/18 axis played a role in smoke-induced airway inflammation in healthy smokers or COPD patients as well as murine COPD models, with increased activation of P2X7 receptor/caspase 1 and elevated IL-1β and IL-18 levels (56). In that study, it was found that the inflammasome-associated proteins ASC and NALP3 were required for IL-1β and IL-18 production induced by smoking (57). Furthermore, smoking exerted its influence on chromatin structures via mediating histone modification in pro-inflammatory macrophages (58), possibly resulting in abnormal gene transcriptions. Finally, Maldifassi et al. found that nicotine, through stimulation of α7 nicotinic acetylcholine receptor (α7 nAChR), played an anti-inflammatory role in human macrophages by upregulating the expression of interleukin-1 receptor-associated kinase M (IRAK-M), a negative regulator of innate TLR-mediated immune responses (59). They also provided evidence that activation of STAT3, through a single (JAK2/PI3K/STAT3) or two convergent cascades (JAK2/STAT3 and PI3K/STAT3), is required for nicotine-induced upregulation of IRAK-M expression (59).
Figure 2. A molecular model of pro-inflammatory signaling pathways activated by cigarette smoking. Combustion products of cigarette smoke, including free radicals, carbon monoxide, reactive oxygen species, and reactive nitrogen species, can phosphorylate p38 mitogen-activated protein kinase and ERK1/2 signaling pathways, activate NFκB, and alter histone modification, resulting in aberrant expression of pro-inflammatory genes, subsequent inflammation and DNA damage, etc.
Taken together, the signaling pathways and molecular mechanisms underlying CS-mediated immunopathology, especially transplant rejection, are still not well understood due to the functional complexity and diversity of cigarette smoke components. Further investigations are warranted to understand the molecular mechanisms of their action, especially those involved in alloimmune responses.
Smoking plays dual roles in immune responsiveness due to the molecular and functional diversities of cigarette smoke components, including RNS, ROS, CO, and nicotine. However, numerous experimental and clinical studies have shown that CS exerts a deleterious rather than beneficial effect on transplant survival even if CS downregulates immune responses under certain circumstances, for instance, smoking suppresses the immune system by reducing lymphocyte numbers in the blood of patients with chronic renal failure (60). Therefore, our view is that smoking hinders long-term allograft survival by stimulating T or B cell memory, suppressing Tol-DC development, or downregulating Treg cell numbers. Although combustion of cigarette produces CO and nicotine that are immunosuppressive, we think that the amount of CO and nicotine inhaled during smoking may not be sufficient to suppress vigorous allograft rejection. While previous studies have revealed some molecular mechanisms by which cigarette smoke alters immune responsiveness and mediates immunopathology, including P2X7-inflammasome-caspase 1-IL-1/18 axis, phosphorylation of ERK1/2 and p38 MAPK, and activation of NFκB in immune cells, the exact molecular mechanisms underlying smoking-associated transplant rejection remain largely unknown. Further studies are warranted to understand why smoking accelerates allograft rejection even if cigarette smoke components contain immunosuppressive substances, such as CO and nicotine, which would otherwise induce CD4+ CD25+ Tregs, promote T cell anergy, or suppress alloimmune responses. Hence, it is possible that the amount of CO or nicotine absorbed by smokers during smoking is insufficient to suppress allograft rejection. There is also a possibility that the inflammation and oxidative stress induced by other components of CS, such as RNS, ROS, and free radicals, can largely outweigh any potential immunosuppressive action of CO and nicotine.
FQ wrote the majority of the manuscript; PF and HL wrote a part of the manuscript; C-LL and WY prepared the literature; GN and ZD edited the manuscript.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
This work was supported by National Natural Science Foundation of China (NSFC 81471550).
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Keywords: cigarette smoking, adaptive immunity, innate immunity, allograft survival, transplant tolerance
Citation: Qiu F, Fan P, Nie GD, Liu H, Liang C-L, Yu W and Dai Z (2017) Effects of Cigarette Smoking on Transplant Survival: Extending or Shortening It? Front. Immunol. 8:127. doi: 10.3389/fimmu.2017.00127
Received: 01 September 2016; Accepted: 25 January 2017;
Published: 10 February 2017
Edited by:Antoine Toubert, Paris Diderot University, France
Reviewed by:Zheng Jenny Zhang, Northwestern University, USA
Federica Casiraghi, Mario Negri Institute for Pharmacological Research, Italy
Copyright: © 2017 Qiu, Fan, Nie, Liu, Liang, Yu and Dai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Zhenhua Dai, email@example.com

domain: literature


text:
Glencore has signed a year-long contract to supply Japanese utility companies with Australian thermal coal for almost $95 a tonne.
The spot price of Australian thermal coal, which is the Pacific benchmark, reached $100 last week for the first time in four years.
The material is mostly used in power generation and has rallied to almost double since June.
Spiking coal prices have been triggered by cuts to the number of working days at domestic mines in China, which has prompted electricity generators and steelmakers in the economic powerhouse to make up for a shortfall via imports, triggering an international rally in the process.
Market analysts have been sceptical that the recent surge will last for long into next year. However, Glencore's 12-month deal with Tohoku, which also negotiates on behalf of other Japanese utility groups, indicates prices could last.
"Given that the Australian coal spot prices were less than $60 per tonne four months ago, and as there are questions about how sustainable this price will be, this is a good deal for Glencore," said Gareth Carpenter, associate editorial director of coal at S&P Global Platts.
"It's about 46 per cent higher than the agreement they reached for tonnage in October 2015, which was around $64.
"With regards to the question mark about sustainability, this is because of speculation that the Chinese government wants to reverse the mining cuts to tackle the rise in domestic coal prices."
Coal-fired power plants supply around 41 per cent of global electricity, according to the World Coal Association.


2012-2016 BMW M6 Gran Coupe / Convertible Tire Pressure Reset – The BMW M6 is the high-performance version of the BMW 6 Series, a sports car produced by German automaker BMW. BMW M6 Gran Coupe 2014 to the third variant of the M6 family. BMW M6 Gran Coupe is the first 4-door coupe in the ranks of BMW M GmbH. In March 2012 the new generation M6 was presented at the Geneva Motor Show.
It is based on the F12 / F13 chassis N63 S63 and has the same engine as the F10 BMW M5. Under the hood is a Twin Turbo V8 which is coupled to a seven-speed automatic transmission M-DCT. The F13 M6 Coupé has a carbonnen roof but is still 140 kg heavier than its predecessor E63. Officially, the car only needs 4.2 seconds to accelerate from standstill to 100 km / h. F13 is the chassis code for the coupe, F12 for the cabrio.
2012-2016 BMW M6 Gran Coupe / Convertible Tire Pressure Reset:
If you receive a low-tire pressure monitor (TPM) warning light while driving and you want to clear or turning off the warning light on your 2012 2013 2014 2015 2016 BMW M6 F12 / F13, follow these instructions:
- Make sure the vehicle is at a complete stop
- Adjust the tire inflation pressure recommended on the tire placard located on the door panel.
- Turn the ignition to ON without starting the engine
- Press MENU button on iDrive controller to use i menu.
- Select VEHICLE INFO
- Select VEHICLE STATUS
- Next, Start the engine (do not drive away)
- Select PERFORM RESET
- Confirm reset the inflation pressure by selecting “PERFORM RESET”
- Driving for a few miles (kilometers) and then verify that it turns off.
For more details, please watch the following video:
The procedure above can be applied to latest generations of BMW M6 F12 / F13 (2011 2012 2013 2014 2015 2016) models. Hopefully the article of 2012-2016 BMW M6 Gran Coupe / Convertible Tire Pressure Resett useful for you. Good Luck! 😀


ASTM International - ASTM D3078-02
Standard Test Method for Determination of Leaks in Flexible Packaging by Bubble Emission
|Publication Date:||10 December 2002|
|ICS Code (Packaging materials and accessories):||55.040|
1.1 This test method covers the determination of gross leaks in flexible packaging containing a headspace gas. Test sensitivity is limited to 1 x 10-5 atm cm3/s (1 x 10-6 Pa m3/s) or even less sensitive as indicated in a recent interlaboratory test (reported in Section 12).
1.2 Small leaks may not be detected by this procedure. Viscoelastic effects on the products, or entrapped air, become significant and prevent passage through small openings. Positive pressure inside the pouch after the vacuum is drawn may force the product to plug small leaks. The size of the leak that can be detected is dependent upon the products contained, the nature of the packaging material, and the test parameters selected.
1.3 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.


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Physical dependence on a drug can cause serious withdrawal symptoms if a person suddenly stops using the substance or severely reduces the dose. The withdrawal process itself can be uncomfortable and dangerous. Some of the classic signs of withdrawal include tremors, cold sweats, involuntary movements (e.g., jerking, twitching, or shaking), nausea and vomiting, muscle cramps and bone pain. Because withdrawal can be dangerous, proper medical detox can be a life-saving step in recovery. Sunrise Foundation Rehabilitation Center in India near Mumbai
Alcoholism is both a physical and mental illness, which causes people to drink alcohol despite it resulting in negative consequences. It affects hundreds of thousands of people in the UK, and millions more around the world. Although not a curable illness, it can be effectively treated and managed with a programme of detoxification and rehabilitation.
At Gateway Foundation, we employ a variety of addiction therapy services that aid in treatment. Cognitive Behavioral Therapy, Dialectical Behavioral Therapy, and Trauma Therapy are some of the most common that our therapists use to help patients begin on the road to recovery. Each of these treatments and therapies is part of a larger overall program, specifically designed for individual patient recovery at one of our 17 drug treatment centers. To speak to someone about treatment at a Gateway Foundation center, call 877.381.6538 today.
Drug addiction is defined as a chronic disease characterized by drug seeking and use that is compulsive, or difficult to control, despite harmful consequences.3 It is possible to be physically dependent upon a drug without having an addiction to the substance. However, when addiction is an issue, the negative consequences experienced during drug abuse become overwhelming, which makes it impossible for the patient to function in relationships with others, at work, at school or in the community.
While a trial period of controlled drinking with careful follow-up might be appropriate for a diagnosis of alcohol abuse, this approach increases a physician's professional liability. Complete abstinence is the only treatment for alcohol dependence. Emphasize that the most common error is underestimating the amount of help that will be needed to stop drinking. The differential diagnosis between alcohol abuse and dependence can be a difficult judgment call.
There is an advantage to including on-site medical care in a Drug Rehab. Physicians and nurses provide 24-hour hospital services to monitor and ensure a safe withdrawal from alcohol and other drugs. In addition, a medical staff specializing in addiction medicine can oversee the progress of each individual and make necessary adjustments to the treatment plan.
Research the history of the Treatment Center or facility. What is their success rate? Can you find any medical recommendations for them online from members of the established rehab or medical community? How long has the Center been in operation? Is their leadership on solid ground? Are there any signs of financial corruption associated with the Center that is readily visible on the Internet? It is your responsibility to dig for this information. If you cannot find any information about a given Treatment Center online or at your local library, move on to the next Center on your list!
Integrated treatment is comprehensive programming that offers all of the therapeutic resources necessary to help the individual heal physically, mentally, and spiritually. There is no one cause of addiction, though living with a mental health disorder may increase the likelihood of developing a substance use disorder — and vice versa. Everyone is different. In some cases, a mental health disorder predates the development of a drug abuse. In other cases, mental health symptoms are not apparent until after addiction has taken hold — sometimes, these conditions are exacerbated or worsened by drug use.
Individual therapy will help you learn to recognize triggers and cope with them. The therapists may also help you to improve your emotional regulation skills in order to better avoid relapse. Group counseling provides you with the opportunity to practice sober social skills, as well as the coping strategies you learned in individual counseling. Family therapy sessions can help to repair broken relationships, improve communication skills, and build conflict resolution skills. Medication, such as methadone or Suboxone, may be used in combination with behavioral therapy to help opioid-addicted individuals remain abstinent. Once your rehab program nears an end, your treatment team will create an aftercare or relapse prevention plan for you consisting of ongoing support. Ongoing support may include individual therapy, group counseling, self-help group meetings (e.g., 12-step, SMART Recovery), alumni programs, or sober living homes.1,2
Group therapy is a cornerstone of both the twelve steps and almost all rehab programmes. Group therapy enables members to draw on the support and experiences of their peers to discover more about their own addiction. With the structure of the 12 steps programme, these groups can help individuals work through the process of recovery in an atmosphere of mutual respect and support.
Founded in 1971, we are dedicated to helping guests and their families achieve and maintain recovery. We are a 99-bed, private, nonprofit substance use disroder treatment center nestled on 120 tranquil acres in Greensboro, NC. We provide treatment and evidence-based programs based on abstinence and the 12-step model of recovery. We have been accredited by the joint commission since 1974 as a specialty hospital. We are committed to providing exceptional, compassionate care to every individual we serve. Alcohol Rehabilitation and medical Facilities
Medication may also be prescribed which can act as a substitute for your substance of abuse in the case of certain drugs where less addictive and damaging alternatives may be provided in the short term. Heroin addicts may be given methadone temporarily to replace heroin, from which they can then be weaned off with withdrawal symptoms that are much less unpleasant than those associated with heroin itself.
Group, individual, and can help to address the root causes of addiction and build communication and life skills that are necessary to live a sober life. Group therapy and family therapy provide a means to talk openly and honestly about your addiction and gain support from other in recovery, parents, siblings and adult children. One-on-one talk therapy provides the opportunity to more deeply explore underlying issues and trauma in a private setting.
Club drugs are commonly used at clubs, concerts and parties. Examples include ecstasy or molly (MDMA), gamma-hydroxybutyric acid (GHB), flunitrazepam (Rohypnol ― a brand used outside the U.S. ― also called roofie) and ketamine. These drugs are not all in the same category, but they share some similar effects and dangers, including long-term harmful effects.
Overcoming an alcohol addiction starts with a qualified treatment center that can help address underlying and co-occurring disorders. Because of alcohol’s prevalence throughout our culture, recovering alcoholics are constantly bombarded with triggers. Treatment centers must be equipped to help the recovering user find effective ways to manage triggers and cravings in order to be effective.
Physical dependence on a drug can cause serious withdrawal symptoms if a person suddenly stops using the substance or severely reduces the dose. The withdrawal process itself can be uncomfortable and dangerous. Some of the classic signs of withdrawal include tremors, cold sweats, involuntary movements (e.g., jerking, twitching, or shaking), nausea and vomiting, muscle cramps and bone pain. Because withdrawal can be dangerous, proper medical detox can be a life-saving step in recovery.
Current clinical research suggests that marijuana use can have long-lasting effects on learning and memory, especially for users who start in adolescence, when the brain is still developing. Addiction Science & Clinical Practice states that approximately 9 percent of individuals who try marijuana become dependent on the drug, compared to 15 percent of cocaine users and 24 percent of heroin users. However, because marijuana is more readily available than these other illicit drugs, marijuana addiction has become more widespread, and marijuana detox programs have become more common.
Alcohol abuse and addiction doesn’t just affect the person drinking—it affects their families and loved ones, too. Watching a family member struggle with a drinking problem can be as heartbreakingly painful as it is frustrating. But while you can’t do the hard work of overcoming addiction for your loved one, your love and support can play a crucial part in their long-term recovery.
A small number of therapies have been well researched, so we know they are effective in alcohol and other drug treatment. These include cognitive behaviour therapy, which helps to strengthen skills to manage cravings and difficult situations or emotions that might trigger a relapse and motivational interviewing, which helps to develop and strengthen the motivation to change, is also effective.
Individual counseling sessions – These are one-on-one meetings with an addiction treatment counselor. Issues and events that may have contributed toward alcoholism are explored. Patients learn about alcoholism as a disease. They also learn what can trigger addictive thinking and behavior. Vital coping skills are practiced. Healthy routines are developed. They come to understand that an alcohol-free lifestyle takes discipline and dedication.
All drugs–nicotine, cocaine, marijuana and others–affect the brain’s “reward” circuit, which is part of the limbic system. This area of the brain affects instinct and mood. Drugs target this system, which causes large amounts of dopamine—a brain chemical that helps regulate emotions and feelings of pleasure—to flood the brain. This flood of dopamine is what causes a “high.” It’s one of the main causes of drug addiction.
Before starting the treatment process, a person must first recognize their condition and have a desire to quit drinking. Sometimes, an individual may acknowledge they have a drinking problem on their own. Other times, family members or friends may stage an alcohol intervention. This involves loved ones expressing their concerns about the person’s excessive drinking patterns. An intervention also helps to start the discussion about treatment and support options that are available.
However, your participation can make a big difference. Based on clinical experience, many health providers believe that support from friends and family members is important in overcoming alcohol problems. But friends and family may feel unsure about how best to provide the support needed. The groups for family and friends listed below under Resources may be a good starting point. Alcohol withdrawal at its worst .
Alcohol is also linked to self-harm, psychosis, and suicide and because it can impair judgement and lead to reckless, compulsive behaviour, many people who take their own lives do so while under the influence of alcohol. In fact, NHS Scotland has said that over half of all hospital admissions related to deliberate self-harm have a direct link to alcohol either immediately before or during the act.
contribute to mental illness including depression and anxietycause significant liver damage, ultimately preventing the liver from functioningcontribute to developing one of several different kinds of cancerincrease your chances of developing heart diseaseincrease your chances of using other drugscontribute to developing chronic hypertensionlead to the loss of your job and, as a result, financial instabilitydo irreparable harm to your marriage/family relationshipslead you to a life controlled by addictionlead you to a life of crime as you seek to support your addiction.
It’s commonly known that even after the completion of a treatment program, the temptation to drink again is a lifelong challenge. However, in addition to coping skills and medication, treatment also gives the patient a vast network of contacts – a therapist, a sponsor from a support group, etc. – who make it their priority to talk the addict out of a potential relapse. Being accountable to someone who understands the challenge of trying to remain sober after treatment helps counter the fear and frustration that can be a part of that challenge.
Genetics make up about 50% of the risk for alcohol dependence, but they by no means tell the whole story. Genetic history is often hard to distinguish, but if parents are regular heavy drinkers, or they drink to reduce stress and depression, it is likely that their children will grow up believing that these behaviours are normal and possibly harmless. But environmental influence doesn’t come only from the home; peer pressure from friends, colleagues and partners can also encourage new and difficult patterns of drinking which can lead to dependency or co-dependency.
Treating addiction – whether at rehab or not – can be divided into three main phases. Firstly is detoxification, the process by which an addict’s system is cleansed of substances of abuse. Once this cleansing process has taken place, and the immediate pressures of drug dependency have been lifted, the addict will then need to address the psychological aspects of their addiction, including understanding the root causes and seeking to put measures in place to ensure that they do not stumble back into addiction by relapsing.
The definition of recovery remains divided and subjective in drug rehabilitation, as there are no set standards for measuring recovery. The Betty Ford Institute defined recovery as achieving complete abstinence as well as personal well-being while other studies have considered "near abstinence" as a definition. The wide range of meanings has complicated the process of choosing rehabilitation programs.
We are active in supporting research into improving the lives of those struggling with addiction. Searidge Foundation and our sister rehab Sobriety Home located in Godmanchester, Quebec are highly regarded as the leading alcohol and drug rehab facilities in Canada. We support Florida State University (FSU) in their research into addiction and anxiety disorder. We are also involved with Dr. Brunet, of McGill University, and his leading scientific research on PTSD and addiction memory. Everything you think you know about addiction is wrong | Johann Hari
The second reason is because you want to do your recovery on your own. You've always been self-reliant and you want to be self-reliant in your recovery. But recovery involves learning to ask for help. Doing it on your own is overrated. You need to ask for help from your doctor, treatment program, 12 step group, and sponsor. Antabuse is just one more thing you can use. It is not an alternative to your supports. It complements them.
Hospitalization Rehab, often known as a Partial Hospitalization Program, allows addicts to check into a treatment center or hospital for a certain number of hours each week. This is most similar to an outpatient rehab center, in that individuals will return to their home after their treatment program. However, in an outpatient clinic, patients may check in briefly and then leave.
^ Robison AJ, Nestler EJ (October 2011). "Transcriptional and epigenetic mechanisms of addiction". Nature Reviews. Neuroscience. 12 (11): 623–37. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194. ΔFosB has been linked directly to several addiction-related behaviors ... Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.
Trips Beyond Addiction | Living Hero Radio Show and Podcast special. With Dimitri Mobengo Mugianis, Bovenga Na Muduma, Clare S. Wilkins, Brad Burge, Tom Kingsley Brown, Susan Thesenga, Bruce K. Alexander, PhD ~ the voices of ex-addicts, researchers from The Multidisciplinary Association for Psychedelic Studies and Ibogaine/Iboga/Ayahuasca treatment providers sharing their experiences in breaking addiction with native medicines. January 2013
Set a drinking goal. Choose a limit for how much you will drink. Make sure your limit is not more than one drink a day if you’re a woman, or two drinks a day if you’re a man—and try to schedule some alcohol-free days each week. Now write your drinking goal on a piece of paper. Put it where you can see it, such as on your refrigerator or bathroom mirror.
Various factors such as your medical history, support system and personal motivation can all play a role in the success of your recovery. Treatment should be supervised by a team of medical specialists at a rehab facility. Throughout the country, alcohol treatment centers are staffed with professionals who will guide you through each step of the recovery process – from detox to life after rehab. Think of them as your 24/7 support system who are there to celebrate your successes and work with you through any challenges.
Detox is not the expulsion of ‘toxins’ from your system, but a reaction of your nervous system to the absence of alcohol. Withdrawal from alcohol and its sedative effects results in an overreaction of the nervous system. A number of severe symptoms can develop, such as disorientation, extreme anxiety, diarrhoea, very high blood pressure, delusions, heart rhythm changes etc. This is very dangerous if not supervised and monitored by personnel experienced in addiction recovery treatment. These symptoms can now be controlled in a safe way through proper medical attention and pharmacotherapy during the detox period. Our clinical staff has extensive experience dealing with alcohol detox and conducts the process in as much safety and as comforting an environment as possible. This is a vast improvement from a time before modern medicine when there was a death rate of 33% for those going through severe alcohol withdrawal.
Many addicts feel the need to lie about their problems, whether it be to themselves or family members. A group therapy session creates a support mechanism in which patients are encouraged to open up about their issues in a safe setting. Since every member of the group understands that the patient is going through, there is no need for the patient to hide anything or lie.
Dopamine is the neurotransmitter that is responsible for motivation and reward, and therefore it is a crucial neurotransmitter related to addiction. Drug abuse causes the release of surges of dopamine, and these in turn produce feelings of euphoria, followed by cravings, major reinforcement of the same behaviors, and compulsions to repeat whatever behavior produced the surge.
Commitment and follow-through are key. Recovering from alcohol addiction or heavy drinking is not a quick and easy process. In general, the longer and more intense the alcohol use, the longer and more intense the treatment you’ll need. But regardless of the treatment program’s length in weeks or months, long-term follow-up care is crucial to your recovery. Drug Rehab Near Me Philadelphia PA
Alcohol detox– In most cases of long-term alcohol addiction, detox must occur prior to formal treatment. This part of the healing process involves stopping the consumption of alcohol and all other drugs. This gives the body time to cleanse itself of all harmful toxins. Withdrawal symptoms may be an issue (e.g., depression and anxiety, mood swings, sweats, chills and irritability). They all depend upon the specifics of the addiction. Physical and mental health care and support is provided, as needed.1Therapeutic medication– The need for therapeutic medication depends on the individual patient’s needs, experiences and circumstances. If a drug is used, it should be medically-managed by a physician.
An inpatient rehab facility is the most structured treatment environment for those overcoming alcoholism. Generally, these rehabs are geared toward treating the most severe forms of alcoholism and require individuals to remain on-site for the duration of the program – 30, 60 or 90 days. Treatment specialists provide around-the-clock care and will prepare you for life after rehab. This may include information on how to overcome triggers, the importance of sobriety maintenance programs and what to do in the event of a relapse.
Outpatient treatment is the most flexible level of care. Recovery services are provided in a day center, clinic, rehab facility, or other location, while the patient lives at home. Outpatient clients can participate in counseling, therapy, 12-step programming, and other recovery services without giving up their self-determination. This level of care is recommended for patients who have completed an inpatient program, or for medically stable individuals who have a high level of motivation to reach sobriety.
According to the results of a survey published in the Archives of General Psychiatry, approximately 2.6 percent of American adults meet the criteria for drug dependence and drug addiction. Globally, the figure is similar; the World Health Organization estimates that nearly 3 percent of adults around the world suffer from a drug use disorder. At first glance, these numbers may seem small. However, these statistics do not reflect the number of people who have tried illicit drugs, or who have abused illicit substances or prescription medications. The National Institute on Drug Abuse reports that almost 10 percent of American adults have tried illicit drugs. Anyone who uses drugs recreationally or experimentally is at risk of developing dependence and drug addiction. Clearbrook Manor - Drug and Alcohol Treatment Center
Developing a drug addiction isn’t a character flaw or a sign of weakness, and it takes more than willpower to overcome the problem. Abusing illegal or certain prescription drugs can create changes in the brain, causing powerful cravings and a compulsion to use that makes sobriety seem like an impossible goal. But recovery is never out of reach, no matter how hopeless your situation seems. With the right treatment and support, change is possible. Don’t give up—even if you’ve tried and failed before. The road to recovery often involves bumps, pitfalls, and setbacks. But by examining the problem and thinking about change, you’re already well on your way.
For most people, it takes one drink to produce an Antabuse reaction, therefore it's hard to get by mistake. You can have foods that have been cooked in wine, as long as they've been cooked the alcohol evaporates quickly. You have to be careful of some deserts that have a lot of uncooked alcohol in them. You also have to be careful of some cough syrups and cold preparations that can contain as much as 40% alcohol.
Important: This is general medical information, and is not tailored to the needs of a specific individual. This material is NOT complete. It does not cover all possible precautions, side effects, or interactions. You should always consult your physician when making decisions about your health. And you should consult your physician before starting or stopping medication.
Nicole Lee works as a paid consultant in the alcohol and other drug sector. She has previously been awarded grants by state and federal governments, NHMRC and other public funding bodies for alcohol and other drug research. She is a member and past President of the Australian Association for Cognitive and Behaviour Therapy. She is a registered Psychologist who has previously worked in private practice.
To find a rehab center near you, you can start your search with the Substance Abuse and Mental Health Services Administration. Use their Directory of Single State Agencies for Substance Abuse Services to find the local resource to contact in your state. Be prepared to verify your income, whether you have any insurance, and any need for financial support before you can enroll.
Anxiety, depression, and suicidal thoughts are all common results of alcohol dependency. This is because prolonged heavy drinking effects the neurotransmitters in the brain which regulate mood. Two of the most important neurotransmitters for mood are dopamine and serotonin, which are responsible for creating the positive feelings vital for a healthy mind. Research shows that the levels of both serotonin and dopamine are often heavily altered in the brains of alcoholics, leading to deteriorating mental health and, often, a negative spiral of alcohol use.
Some drug abuse facts and statistics show a significant and steady increase in American opioid use, contributing to the nation’s growing opioid crisis. The CDC reports a 29.7 percent increase in opioid-overdose emergency room visits from July 2016 to September 2017. Wisconsin and Delaware saw the largest rise in overdose emergency room visits, with an increase of 109 and 105 percent respectively.
^ Jump up to: a b c d e f Mattick RP; Digiusto E; Doran CM; O'Brien S; Shanahan M; Kimber J; Henderson N; Breen C; Shearer J; Gates J; Shakeshaft A; NEPOD Trial Investigators (2004). National Evaluation of Pharmacotherapies for Opioid Dependence (NEPOD): Report of Results and Recommendations (PDF). National Drug and Alcohol Research Centre, Sydney. Commonwealth of Australia. ISBN 978-0-642-82459-2. Monograph Series No. 52. Archived from the original (PDF) on 2011-03-09.
Thankfully, there are numerous organisations here in the UK and abroad offering first-class treatment to those affected by alcoholism. UKAT is one of the UK’s leading treatment providers; we have already helped countless individuals overcome their alcohol problems. We offer a top-class service that offers you the greatest chances of a successful long-term recovery from alcoholism.
Behavioral models make use of principles of functional analysis of drinking behavior. Behavior models exist for both working with the substance abuser (Community Reinforcement Approach) and their family (Community Reinforcement Approach and Family Training). Both these models have had considerable research success for both efficacy and effectiveness. This model lays much emphasis on the use of problem-solving techniques as a means of helping the addict to overcome his/her addiction. Drug and Alcohol Treatment Centers ► What You Don't Know

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Just as their name suggests, St. Louis, Mo Drunks With Guns were a noisy and confrontational rock group, that lasted for a short time, but they were still remembered long after their break-up, partly due to their unruly behavior and partly due to music. When DWG broke up for good in the late 80s, its members went on to form a number of bands (and they also joined some), including Strangulated Beatoffs, Ultraman, Bootbeast, but probably the strangest case involves another band which was also called Drunks With Guns and included 13-year old vocalist named Melissa along with DWG original member Mike Doskocil.
Fruitcake was a project of former DWG bassist Mike DeLeon, who put out 4 singles on various labels throughout the 90s, including “The Garden Of Earthly Delights / Stan” on Electric Records and “Welcome To Saint Anthony’s Psychiatric Center” on Artichoke Records. He also contributed compilation tracks to one of the volumes in “Fuck That Weak Shit” series on Pitsbull Records and one track (“Ike”) to “Hey Drag City” compilation.
He later formed equally short-lived Garment Bladder, which also appeared on one of the volumes of FTWS series. One of the bands tracks ended up on a compilation called “Kausing A Kommotion” (on Nihilist Records), a tribute of sorts to Madonna, which also included material by the likes of Haters, Sleep Chamber, Panicsville and Masonna.
Mike DeLeon (Drunks With Guns, Garment Bladder)
Welcome To Saint Anthony’s Psychiatric Center 7″ (Artichoke, 1991)
Anna Marina / Moanin’ The Blues 7″ (Pitsbull, 1992)
Patty Lane / Story Of Life 7″ (Skin Graft, 1993)
The Garden Of Earthly Delights / Stan 7″ (Electric Records, Unknown Year)
“Aorta” on Fuck That Weak Shit, Vol. 1 (Pitsbull, 1993)
“Ike” on Hey Drag City (Drag City / Domino, 1993)
Drunks With Guns – Enemy