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Education and the Cloud Leaflet
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- 1. School on the Cloud: Connecting Education to the Cloud for Digital Citizenship Education and the Cloud What is School on the Cloud? School on Cloud is a Key Activity 3 ICT network that addresses three key questions: 1. How should education respond to the potential of Cloud-based tools and technologies? 2. What is the impact on education stakeholders? 3. What might the situation be like in the future? What is the aim of Working Group 1 Can education organizations take advantage of the potential offered by the Cloud? What prevents innovative leadership from pushing for change? What barriers are there to implementing the use of the Cloud in education? Working Group 1 (WG 1) brings together organizations dealing with these questions. Thegoalistoidentifyandsharetechnological,social, economic,culturalandotherexperiencesindifferent educationalcontexts. 543221-LLP-1-2013-1-GR-KA3-KA3NW Toexplorethesequestions,thenetworkhas4WorkingGroups: i-Manager (WG1) Transition from ground to Cloud: infrastructure, mentality, innovation and change i-Teacher (WG2) The innovative teacher: the role of the teacher, teacher training i-Learner (WG3) Integrating the Cloud: personalised learning, formal and informal education, special needs i-Futures (WG4) Future prospects: visions on open education, interactivity, impact and communicating the Cloud
- 2. Is Cloud Computing useful for Education? Cloud computing Cloud Computing involves storing and accessing data and programs over the Internet instead of your computer's hard drive. IT services are shared rather than having local servers or software. Why is the Cloud important? Cloud computing is rapidly becoming a very important delivery method for IT services across Europe. For education, the Cloud provides: the ability to share resources and information great speed, makes IT operations faster improved accessibility increased capacity independence of location more opportunities reduced costs safety for users security of information Benefits such as customised solutions, great cost effectiveness and increased efficiency make Cloud Computing an extremely attractive prospect for education. Its appropriate use requires careful management. anything from anywhere in anytime on any device by anyone Cloud offers a different kind of mental and physical strategies to access education materials (eg. personalized learning by anyone, also by disabled - handicapped - marginalized individuals).
- 3. Are you a leader in Cloud education? Cloud leadership is focused on strategies to transform, accelerate and benefit from using the Cloud. Do you recognize that Cloud Computing involves unprecedented mobility for users, increased scalability and speed of deployment for your organization? Is your Organization on the Cloud? Description of the Cloud leader characteristics by taking account of... Cloud leader teachers parents students interacts with... the wider community has specific attitudes toward... adopts use of... technological tools/services Managing the Cloud Cloud Computing presents a new environment to manage and new situations to master. The purpose is to monitor the applications, data and services being used. Tools are provided to help ensure Cloud Computing- based resources are working optimally and properly interacting with users and other services. Cloud management normally involves monitoring performance and security, auditing compliance and overseeing recovery and contingency plans. Characteristics of Cloud leaders in education Build an inspiring vision Create a positive environment Exert influence Foresee future problems in the transition Give clear guidelines Give direction and set stretch goals Lead reforms Set clear expectations Manage resistance to change Monitor progress, but don't micromanage Win respect and trust
- 4. DoukasSchool, Innovative Learning Network Ltd., EUROGEO, GO! onderwijs van de Vlaamse Gemeenschap, Istituto Comprensivo Assisi 3, KOKEGA School *form noton google drive*, Department of Sciences of Education andCultural andFormative Processes, University of Florence, Technische Universitt Dortmund, Sozialforschungsstelle, National Technical University of Athens, ATiT, bit media e-Learningsolution GmbH & Co KG, UNEP/GRID-Warsaw Centre, Branch of the National Foundation for Environmental Protection, ITEC Incorporated CompanyContinuous Vocational Training Centre, Vyara Foundation, Kantonsschule Solothurn Digital Earth Centre of Excellence Switzerland, Mary Immaculate College, Ministero dell'Istruzione, dell'Universit e della Ricerca, Bundesgymnasium andBundesrealgymnasium Waidhofen an derThaya,National College, University of the Aegean,EuropeanCentre of Studies andInitiatives, Univerza vLjubljani, Fundatia Professional, Universidad Complutense deMadrid, IES SAN ROQUE, Geodetic Institute of Slovenia, 3rd Primary School of Agia Paraskevi, REALSOCIEDAD GEOGRFICA, Universidade daBeira Interior, Universidad de Leny, GhentUniversity, Teachers' training college of the dicese Linz, State University of Library Studies andInformation Technologies, Goethe University Frankfurt am Main, Aristotle University of Thessaloniki, University of Cologne, Escola Bsica Integrada de Santa Maria , University of Education Heidelberg, Research Groupfor Earth Observation, Faculty of Earth Sciences Nicolaus Copernicus University, University of Porto, Paris LodronUniversitt Salzburg, EuropeanAssociation of CareerGuidance, Thales Foundation, Centre for the Advancement of R&D in Educational Technology(CARDET), National and University Library, Social Innovations Centre, Komunikujeme, o.s., EuropeanUniversity Cyprus, P.M.F. S.r.l., ASSIST Software SRL, E-Ludo Interactive di Salvatore Mica & C. s.n.c., Kecioren District Directorate of National Education, TRAINING 2000, Companhia de Ideias - Media, Lda., Basisschool Zavelberg ICTKeyAction3EuropeanProjectwiththesupportoftheLifelongLearningProgrammeoftheEuropeanUnion www.schoolonthecloud.eu , linkedin.com/groups/schooloncloud-7426807,twitter.com/school_cloud , facebook.com/schoolonthecloud This leaflet provides information and guidance for Managers and Leaders in terms of the education potential of Cloud Computing in education. It is the result of a workshop in Lithuania in November 2014. Information about Working Group 1: Karl Donert, firstname.lastname@example.com WiththesupportoftheLifelongLearningProgrammeoftheEuropeanUnion.ThisprojecthasbeenfundedwithsupportfromtheEuropeanCommission.This publicationreflectstheviewsonlyoftheauthor,andtheCommissioncannotbeheldresponsibleforanyusewhichmaybemadeoftheinformationcontainedtherein.
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Cloud Computing Delivers Education White Paper to community and deploying the ICT education curriculum. ... Cloud Computing Cloud computing includes three ... Cloud Computing Delivers Education White Paper to Millions ...
Health education leaflet - ?· Health education leaflet The Health education leaflet should be given…


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Public Charity
View our WEBSITE
View our GUIDESTAR PROFILE
View our GUARDIAN PROFILE
View our PHOTO GALLERY
Our Mission/How we are involved with horses:
Rising Hope is a non-profit therapeutic equine center in Centre County, Pennsylvania. Our mission is to provide recreational and therapeutic riding contributing positively to the physical, cognitive, social and emotional well-being of individuals through equine assisted activities.
Primary Focus involving horses (Horse Welfare, Public Service, Sport & Recreation): Public ServiceOur organization is directly responsible for the care and shelter of horses.
Our organization conducts Equine Assisted Activities and Therapies (EAAT) programs with instructors, specialists, counselors, trainers and/or facilitators who have certified training for their scope of practice applicable to the people participating in the programs and specific to the program offerings - serving as staff (full-time or part-time), as independent contractors, and/or as service providers, serving in a volunteer capacity, or accompanying clients when participating in our programs.
Our organization provides community outreach and/or public education programs involving horses.
100% of our total programs and services are horse-related.
Our organization conducts its horse-related programs at one facility.
Sidewalker VolunteerMinimum Age: 14Volunteers are extremely valued and appreciated in the Rising Hope program. Without dedicated volunteers, our program could not operate and serve the community and its individuals.
Rising Hope is looking for Sidewalker Voluteers to walk beside the individual receiving therapeutic riding instruction. Training is mandatory.
Wish List Tack1 draft saddle approximately 900 18 inch
2 English saddles, one 16 inch and one 18 inch
Surcingle 360 used with bareback pad and allows participant to have hand holds for balance
Therapeutic hippo-helper provides support for people who cannot sit upright and need to gain strength 200
Adjustable reins 70 helps set position for hands and gives solid hold
Ladder reins 70 easier hand hold position

subset: commoncrawl


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(Host) Journalist Stephen Kiernan says Vermont has a lot to learn when it comes to dying.
His book, Last Rights: Rescuing the End of Life from the Medical System, was published a year ago. And since then the Vermont writer has traveled all over the country talking about the need for more holistic end of life care.
Tonight, Kiernan addresses the issue in Rutland.
VPR's Nina Keck has more.
(Keck) Americans used to die more suddenly from things like heart attacks, strokes and car accidents. But thanks to dramatic improvements in medical technology, better drugs, air bags and 911 emergency services – Americans are living longer and, according to Stephen Kiernan, dying more slowly.
(Kiernan) "In some ways that's terrifying – we're watching our mortality walking toward us step by step. But on the other hand we have this interval of time when we're ill, but we're still very much alive."
(Keck) Kiernan says that window of time presents a huge opportunity for people to get their affairs in order; mend relationships, visit with loved ones and find personal or spiritual peace. But all too often, he says, a patient's physical or emotional pain is not controlled well enough to do that.
(Kiernan) "Medical people – doctors and nurses – are largely untrained in how to care for people who are dying slowly. They are incredibly expert at people who are in critical situations. But when it comes to sitting down and listening – and saying what do you need? Saying you're pain is getting bad now, but if we manage it you're going to be asleep all day – how do you want to balance it? And listening. . . That's not a skill that they're taught."
(Keck) Stephen Kiernan says Vermont is way behind when it comes to providing good end of life care, and patients pay the price.
(Kiernan) "Pretty hard to mend a troubled relationship if you're in a lot of pain. Pretty hard to attain spiritual calm if we can't get a decent breath. So we really need to change the care so the medical part is right. Then that enables all sorts of terrific opportunities at the end of life."
(Keck) Doctors point out that even if they want to provide good care, it's hard to find time for emotional end-of-life conversations. Still, health care providers say things are improving in Vermont. Rutland Regional Medical Center, for instance, has created larger and homier comfort suites for seriously ill patients and their families. They also have a designated palliative care team, as does Fletcher Allen hospital. It's a good start, says Kiernan. But he says patients and doctors, alike, need to do more to ensure that a person's last days are as fulfilling as possible.
For VPR News, I'm Nina Keck in Rutland.
(Host outro) Vermont Author Stephen Kiernan will speak Thursday evening at 7 at the College of St. Joseph's in Rutland. The event, which is free of charge, is sponsored by the Rutland Area Visiting Nurses and Hospice.


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Sport / Motorbike trials first for West Burrafirth
THE FIRST national motorbike trials event in Shetland is set to take place at West Burrafirth at the end of June.
Aberdeen based Bon Accord Motorcycle Club is hosting the Simmer Dim Two Day National Trial on 29 and 30 June with the assistance of local riders and enthusiasts.
Not all local residents, however, were supportive of the prospect of 100 motor bikes racing up the Brindister hills, with artist Janette Kerr, in particular, voicing her opposition.
According to local organiser Brian Gray, the event – which is run according to Scottish Auto Cycle Union (SACU) rules – will prove a boost to the Westside economy as well as local charities Michaelswood, Mind Your Head and the MRI scanner appeal.
Gray said: "With riders, observers, organisers, vendors and their families travelling up for the weekend, there will be approximately 200 extra people on the West Side of Shetland for a few days bringing a welcome boost to the local economy.
"Additionally, three local charities were selected to be beneficiaries of fund-raising that will be running during the event.
"The trial organisers are grateful to have received sponsorship, both financial and practical, from local companies and individuals. The kind words of support and cooperation from West Burrafirth and Brindister residents is also greatly encouraging."
For some years local riders Gary McMillan and Keith Leslie have been travelling to the Scottish mainland to compete in motorcycle trials.
Unlike scrambling, where participants start en-masse to speed against one another round a course, the trials involve riders setting out singly against the clock with assessments made of how they handle technically challenging parts of the course.
These sections contain obstacles which must be navigated without stopping, rolling backwards or placing a foot down on the ground.
Scoring at each section is carried out by a trained observer who returns the scores at the end of each day to the event organisers, who then collate the results to determine which rider has scored the fewest points and who has won.
The bikes used are lightweight, nimble machines designed to make the slow speed balancing required as easy as possible.
Trials on the mainland have been run in places as varied as forests, mountains and quarries and include the flagship event of the trials calendar: the Scottish Six Days Trial held in the Fort William and Lochaber area covering 100 miles a day over the hills and moors around and on Ben Nevis.
According to the duo, a frequent question encountered during their travels flying the flag for Shetland has been "when is Shetland going to host a trial? with the idea for the event being bandied about for six years.
Gray added: "Organising a trial is a massive undertaking requiring a lot of management, assistance and good old-fashioned hard elbow grease.
"Without enough people on the island to form a club, membership of the nearest trials club (the Bon Accord Motorcycle Club) provided the necessary accreditations, insurances and organisational structures and experience.
"Locally though, with the assistance of a growing group of trials riders, the first possibility of hosting a trial came to life with the support of West Burrafirth resident Gibby Fraser who was kindly able to provide a venue.
"Scouting and planning suggested there were ample rocky obstacles to be able to set out a route in the region of 10 miles long with 15 assessed sections.
"Guidance from the RSPB, Scottish Natural Heritage and Amenity Trust bird recorder Paul Harvey have helped to ensure that the route would be placed so as to avoid disrupting important bird species."
Gray was finalising the trials routes on Tuesday after a site visit from Harvey to help avoid any nesting birds.
News of the Shetland trial was so well received that it was decided that it should be held at national level trial – open to riders from throughout the UK.
"The Mid-Summer date was chosen to offer a different element to any other trial – no need to start and finish early each day due to dark nights. People who had long been interested in visiting Shetland now had that last reason to take the leap. Enquiries and entries quickly followed," Gray said.
In order to help promote and grow the sport, Scottish champion Andy Anderson will be attending to offer tuition sessions.
Part-time resident Kerr said that the event would disturb wildlife including breeding birds. She had seen scrambler bikes racing on ground near where the event is to be held.
Kerr added: "There are nesting birds nearby, the oyster catchers were going mad, and a golden plover running around anxiously. There was also a brood of geese making for the sea as fast as they could."
She said that the trials would impact nesting birds including greater skuas, black backed gull, golden plovers, and geese.
She added: "The land is pretty soft and boggy up there and will be completely churned up and wrecked…we don't want this to take place."
Walls and Sandness Community Council chairman Ian Walterson said that the community council had no position as it had never been discussed.
Personally, he welcomed the event, and said that the local organisers had gone to a great deal of effort to plan it in order to minimise disruption to birds and wildlife.
Shetland Islands Council said that the event could go ahead without a public entertainment licence as it was a private event.


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Cost accounting midterm exam solutions
Which the following costs does not change when. Costs expensed period incurred identified with accounting periods ex. Reported pfizer had used replacement cost accounting. Midterm1solution temple cost accounting accounting 2521 spring 2011 midterm multiplechoice questions 2. Posts about acct 505 midterm solutions written by. Bezig met 6012b0237y management accounting intermediate aan universiteit van amsterdam. Book solutions cost accounting chapter 3. Cost accounting course syllabus fall 2014 instructor hugh. Study flashcards cost accounting final exam review cram. Production and marketing costs. Managerial accounting designed for use a. Uploaded patricia tumbocon. Read this essay solutions midterm exercises principles accounting 13e. Acc 3200 second midtermfall 2011 cuny baruch cost accounting acc 3200 spring 2013 second midterm examination ex. The sarbanesoxley act 2002. Printed book your hand. Midterm exam cost accounting points problem financial statements morton buildings manufacturer steel buildings. Indicate the effect each transaction the statement cash flows scf. Accounting 201 practice midterm covering chapters 1. Quickly memorize the terms phrases and much more. Conservatism improves the process estimation allowing accountants assign values certain transactions. Angryface collected student exam answers the end class noticed brenda was clearly peeved. The solutions the suggested problems will made. Browse and read cost accounting midterm exam solutions cost accounting midterm exam solutions undergoing this life many people always try and get the best. Bus 2230 midterm review questions winter 2010 managerial accounting midterm review questions. Fall 2010 midterm main1. What the adjusted value debt for chipotle 2005 after accounting for solutions. Academic year 1415. Solutions browse and read cost accounting midterm exam solutions cost accounting midterm exam solutions give minutes and cost accounting midterm exam solutions cost accounting midterm part cost accounting midterm view notes cost accounting midterm part find more books about managerial accounting midterm exam. The exam questions b. Study accounting 301 practice midterm solutions notes. Acct222 mock midterm exam solutions. Acc 700 milestone guidelines and rubric. Manufacturing costs typically consist a. Direct materials direct labor and manufacturing overhead. These costs related primarily the closing of. Solutions all test items are also included. Solutions practice midterm 200. You can get the soft file cost accounting midterm exam solutions ebooks pdf your gadget. Acc 410 not course about cost accounting journal entries detailed calculations of. This one read this essay acct 504 midterm solution.What responsibility accounting what cost center. Browse and read cost accounting midterm exam solutions cost accounting midterm exam solutions one day you will discover study flashcards cost accounting midterm cram. In the acct 5002 course there will two individual problem based assignments week and and one group case. Joborder cost accounting system for the first month the new fiscal year exam complete. But not financial accounting. Acct2005 managerial accounting for applied accounting. Ascm 632 midterm exam instructions each essay. Class presentations lecture notes old midterms and final exams can also.. Degrees international business economics ibe. Start learning today for free view notes cost accounting midterm part from acct 434 devry kansas city. Acct 505 midterm exam. The content and all things are same. Cost accounting 15e. Datar george foster madhav v. Of cost accounting information for managerial decisionmaking and control purposes. Questions and are five points each. Click the button below add the acct 505 managerial accounting midterm exam answers 2017 your wish list. Lived asset cost accounting. Midterm exam fundamentals managerial accounting february 2012 questions and answers. Direct materials direct labor and administrative costs. Study flashcards cost accounting midterm cram. General instructions you may. Which the following statements concerning users accounting
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Pronunciation Teacher Resources
Find Pronunciation lesson plans and worksheets
Showing 1 - 24 of 1,898 resources
The Pronunciation of Regular Verbs in the Past Exercise
6th - 12th
Give your class experience with pronunciation. This worksheet has learners place the given verbs ending in /-ed/ into columns based on the final sound, then state the rules for pronunciation. This is a more advanced activity and is very...
MyVocabulary.com: Word Roots NAT, TRACT, SEQU Beginner Context Story
6th - 9th
A great way for Language Arts or English Lanuage Learners to get more exposure to vocabulary terms, this resource provides a short passage containing 12 vocabulary words with the roots NAT, TRACT or SEQU. Print this resource and have...
Word Roots 1: Dict, Vent, Duct Intermediate Context Story 2
8th - 12th
Play this audio recording for your class to improve pronunciation and reinforce context for the given vocabulary words. Consider having classmates repeat each vocabulary word out loud after the recording has pronounced it once. You might...
Word Roots 2: FIN, SED, FER Beginner - Context Story 1
7th - 12th
Promote understanding of vocabulary words with this audio recording. You or your learners click on a character image to hear a vocabulary passage read out loud. The audio recording repeats each bold word twice, giving your class a chance...
Word Roots 4: GRAD, MOT, CAD Advanced Context Story 3
8th - 12th
Simply click on the image of "Al Literation" to hear this paragraph read out loud and pronounced correctly. The paragraph includes twelve vocabulary words that are connected by context and three word roots: GRAD, MOT, and CAD. Learners...


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Mexican Healing Broth Packet
Mexican Healing Broth Packet
A herbal spice blend packet to make Mexican inspired soup or chili and enhanced with medicinal herbs. A beautiful blend of smoky and aromatic chili spices, blend well for a deep flavor without too much heat. Makes a fabulous bowl of chili or pozole soup. Add in pastured pork, beef, or chicken to make a robust meal or just add beans!
The medicinal component of the herbs have been shown to provide great antioxidant protection for the body, strengthen the immune system, seaweed has been shown to help those who have difficulty with bean digestion when cooked with beans, and may help improved cellular function. Additionally, the capsaicin in the chili powders may help improve cognitive function, keep your eyes healthy, support the digestive system and maintain healthy blood pressure.
Recipes included in pack.
Makes about 8-10 servings of broth.
Organic & NonGMO Ingredients: smoked paprika, chili powder, ancho chili powder, garlic and onion granules, cumin, chipotle powder, cayenne, oregano, bay leaves, reishi mushroom, burdock root and kombu seaweed.
Chili peppers capsaicin gives peppers their intense heat but has been shown to fight inflammation, treat sensory nerve fiber disorders. They have been shown to reduce blood cholesterol, triglyceride levels, and platelet aggregation, while increasing the body's ability to dissolve fibrin, a substance integral to the formation of blood clots.
Reishi Mushroom medicinal use dates back over 4 ,000 years. In ancient China, Reishi was referred to as the Mushroom of Immortality and eaten exclusively by royalty due to its rarity. This medicinal mushroom has been shown to enhances the body's immune system, improves blood circulation and is excellent for many heart conditions.
Kombu Seaweed. The glutamic acid found in this seaweed provides its pleasantly savory flavor while the fiber helps digestion overall. It may offer cancer-preventing benefits by providing inflammatory relief and lower the cumulative estrogen secretion. Seaweed is high in iron, which helps the body to carry oxygen through the blood as well as contribute to healthy cells, hair, skin and nails. It is also one of the most iodine rich foods in the world which is important for healthy hormone function.
Burdock Root has been used for centuries in holistic medicine to treat a variety of different conditions. Traditionally, it was most commonly used as a diuretic and a digestive aid. It has been shown to be a powerhouse containing multiple types of powerful antioxidants, including quercetin, luteolin, and phenolic acids. It has been shown to inhibit some types of cancer, remove toxins from the blood and be an aphrodisiac.


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"There's a new upscale restaurant now open on Main Street in Snyder.
Jazzboline is attached to the Reikart House hotel, and officially opens today at 5 p.m.
According to the Buffalo News, Jazzboline, 'will seat 168, with the ballroom able to accommodate anywhere from 10 to 200 people for weddings and special events...and 24 taps will be features of the lounge.'"
Reikart House announces chef, renderings for restaurant in former Sonoma Grille
"With the Reikart House entrenched as an established boutique hotel in Amherst, at 5000 Main St., plans for an adjacent restaurant and event space have now been updated.
Iskalo Development has announced Jazzboline restaurant and the Reikart Ballroom will open in spring 2019, and that Grand Island native Michael Litzel will handle executive chef duties for the Reikart campus."
The Gettys Group reveals unique vision for Reikart House in Amherst, NY
"With warm and welcoming appeal, Reikart House offers 92 guestrooms and 12 suites, all with a wider profile that resembles bedrooms versus typical hotel accommodations. Partnering with the Buffalo Niagra Heritage Museum, each of the 12 suites are themed around local influences and landmarks to symbolize Amherst's history. A boardroom, fitness room, spa and soon-to-open restaurant, Jazzboline (named after an instrument Frank Reikart invented), add to Reikart House's Tribute Portfolio-worthy guest experience.
CORE - Northtowns: Jazzboline restaurant to open next year
"Jazzboline is the final piece of Iskalo Development's hospitality campus at the site of the former Lord Amherst hotel in Snyder.
The $6.3 million, 14,000-square-foot restaurant and banquet center is being built on the former site of Sonoma Grille on Main Street. The restaurant will seat 168 and the banquet area will serve up to 200.
Iskalo Development spent more than $40 million on the campus that includes the 137-room Hyatt Place Hotel, which opened in November 2015, and the Reikart House, a 93-room boutique hotel that recently opened.
Site Work to Start This Fall on Restaurant at Reikart House in Snyder
Replacement for Sonoma Grille in Snyder to open by next fall
"The developer behind the Reikart House, (the 92-room boutique hotel that is the first in New York State to operate as part of Marriott International's Tribute Portfolio, a network of "upper upscale" independent hotels), and the Hyatt Place hotel on the same campus in Snyder decided months ago to tear down the former Sonoma Grille building and to construct a new restaurant on the site.
Building from scratch on the property allows Iskalo Development to construct a restaurant that makes better use of the available space for the new restaurant, named Jazzboline, said David Chiazza, Iskalo's executive vice president."
New upscale hotel opens in Amherst
Reikart House hotel in Amherst opens to guests
Reikart House aligns with Marriott's Tribute Portfolio group
"Reikart House has aligned itself with Marriott International's Tribute Portfolio grouping of upscale, independent hotels.
While the Reikart House — the former Lord Amherst Hotel, a Snyder landmark — will remain an independent, boutique hotel when it opens in June, by being part of Marriott's Tribute Portfolio, it allows the hotel to secure bookings from the Marriott's vast hospitality network."


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Watch Unlimited
Passion Fish
Mary-Alice Culhane is the star of a popular daytime soap opera who finds her life change completely after a car accident that leaves her in a wheelchair. No longer able to work, she retires to her family home in Louisiana and wallows in self-pity, bitterly lashing out at a series of caretakers who don't last long in her employment. But when she hires Chantelle, a nurse with her own problems and a desperate need for the job, and finally meets her match.
| 1992 | 2 hr 14 min | 10 /
- Cast
- Mary McDonnell, Angela Bassett, Lenore Banks, Will Mahoney
- Studio
- Sony Pictures Home Entertainment
- Director
- John Sayles
- Language
- English
Also directed by John Sayles
Also starring Mary McDonnell
Also starring Angela Bassett
Watch Passion Fish Trailer
Passion Fish Trailer 1992|2:21
Passion Fish Trailer 1992|2:21


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- Published: 11 April 2019
- We tried drawing YouTubers from memory! Tried. ¯\_(ツ)_/¯
SUBSCRIBE ►► bit.ly/2FB4N5P
SUBSCRIBE TO OUR BRAND NEW SMOSHCAST: bit.ly/2I4tXwJ
SMOSH: cepnet.mobi/user/smosh
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SMOSH en Français: cepnet.mobi/user/thefrenchsmosh
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#SmoshPit #DrawingYouTubersFromMemory #Challenge
Comments • 1 219
- Winter 2 days back
I like y'all
- Lumen Allison 3 days back
Wait, is Ian wearing Teddy fresh?
- Parsley The Herb 6 days back
Shmame dawnswon
- Gacha thing For fun 2 weeks back
In the thumb nail thought Ian was Noah
- Ben Hair 2 weeks back
- SyntecTK 2 weeks back
Wow, Ian. Great moves, keep it up. Proud of you!
Nice Hoodie
- Megan M. 2 weeks back
Ian and Anthony should guest star on each other's channels! Anthony can maybe interview Ian for his current series, and Smosh can have Anthony back for an episode of Try not to laugh or squad vlogs.
- Susana Quezada 2 weeks back
Why was the sims FreePlay music in this video
- Noel Rodriguez 2 weeks back
I'm loving the Teddy Fresh representation Ian :)
- iicxkyy 2 weeks back
U: Unhappy
W: Without
Uwu: Unhappy Without U
- VinnyI6420 3 weeks back
Courtney is pretty talented at drawing
- xevozmaster360 3 weeks back
Why doesn't Shayne just take salt with him everywhere X3
- erm4gundr 3 weeks back
Courtney just giving up and drawing Ray William Johnson is a whole mood
- Daniel Deluxe 4 weeks back
w h a t s g o i n g o n t h e r e b u d ?
- Jacob M 4 weeks back
where did Ian get his hoodie
- JaeJae Noodles 4 weeks back
A,m I the only one who is scared of heart monitors?
- kastriot hykaj 4 weeks back
[0 w 0] uwu
- Kaelyn_ jaye 1 months back
Courtney looks like an art student in this vid. 😆🙂😂
- Layla Toomer 1 months back
Ian's hoodie looks like vereena's ☕
- Midnight! 1 months back
Is the back ground music from sims..... ;-;
Sorry. 🌚
- Sophia Grossman 1 months back
courtney is wearing shaynes hat
- Nigel Cooper 1 months back
4:02 sick burn, Ian
- Ryan Richardson 1 months back
Did anyone else see Courtney pick her nose at 11:06
- Addison Newby 1 months back
This was published on my birthday!!!!!!!!!!!!!!!!!!
- KittenAdventures :3 1 months back
Ian has an UNFAIR ADVANTAGE for the last one
- blood moon. 1 months back
No one at all:
Courtney: *UWU*
- That Artist 1 months back
( )
- greer kennedy 1 months back
6:38? why is there salt in the corner
- idkwhat imdoing 1 months back
Shayne: Besides Keith, Courtney is the best artist so she always wins at this
Continues to get an applause the next 2 rounds😂
- Megan Roderick 1 months back
Personally, I think courtney is a better drawer than Keith❤🖍📝
- Claire Stewart 1 months back
Courtney, you draw really good! (I'm being serious)
- Merete Brønfeld 1 months back
- Jenny Kisa Chalupa 1 months back
This was fun, you guys should do it again some time
- Christopher Scotts 1 months back
Shayne's Tana looks like Lele Pons
And damien no offence but kanck 2 didn't won game of the year for so many years super mario brothers 2 did
So glad they drew dunkey
- Lily Gordon 2 months back
- steamed_ bunz 2 months back
Courtney's really good when it comes to art damn
- Trikey 3326 2 months back
Shaynes Anthony looks like brian may
- Sara Kirkland 2 months back
Ah yes, tummy mongoose
- sunshinerr 2 months back
- Pine Apple 2 months back
Anyone else find Courtney hilarious? Yeah, me neither
- The Trixster gaming 2 months back
1:48 Damian's voice sounded different
- Alex Martin 2 months back
Is Shane gay? Not like it's a bad thing or anything I just want to know
- Crameron Games 2 months back
They always have to have Rhett and Link in every youtuber type video or else they will GMM will leave them jk lol
- Russianwhite 37 2 months back
Is Damien now part of the squad
- Lay Rewis 2 months back
My name is garrett and when courtney said "Give it to me Garrett" I was like 'SHE KNOWS ME!?


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Are you in need of porn addiction treatment? Do you continually look at porn in one way or another? Movies, pictures, books, whatever if it is always about porn you may need to seek out help. After all there have been people who found themselves breaking the law because of these problems they have had with porn.
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April 23, 2010 Published ~ 9 years ago.
Do You Need Porn Addiction Treatment?Are you in need of porn addiction treatment [1]? Do you continually look at porn in one way or another? Movies, pictures, books, whatever if it is always about porn you may need to seek out help. After all there have been people who found themselves breaking the law because of these problems they have had with porn. Depending on just how much you have to seek out porn and what you do to get it, you may have a problem. But that does not mean it should equal to an excuse to use because you have gone and done something bad either. Though it seems a bit ludicrous that it could actually be used for a defense in the case of rape. It has been used and most likely will be used in the future too. So look at it this way if you are addicted to porn, you surely do not want to go down that route and be ending up in jail for rape. Seek out the help you need before you have gotten to this point. Actually it may seem like a problem or situation that has been used like many other cases. A new way that someone can blame a crime they have committed on something else. After all it must have been the porn that has driven them to this situation. But why did you not just stop looking at the porn? But it is not just a problem that comes up for normal people or the common folk out there. It was not many years back that David Duchovny would head off for treatment for his addiction. No not to drugs, but to porn, and at that time I still thought it was a joke. However, it seems that it must be a real problem; after all you see so many treatment programs that come up online. There are many people out there that profess they have an addiction to porn or other sexual problems. But there is little to lead you to realize that you may have the problem. Again it must be that feeling when the only thing that you want to do is look at porn that you know you have a problem. When you spend all your time on the computer looking up x-rated porn sites and nothing else. This is when you know that you have a problem and really need to seek out treatment. These are really questions that only the person who feels they have a problem can really answer. Seek out the options you find online to see if you are addicted to porn and seek out treatment. Looking to find the most comprehensive information on porn addiction treatment [2]? [1] http://www.resolutioncounseling.org [2] http://www.resolutioncounseling.org
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The 15 shortlisted entries in this year's Art of Building photography competition have been revealed
Herzog & de Meuron's 'Bird's Nest' stadium in Beijing; Alvaro Siza Vieira's Municipal Library in Viana do Castelo, Portugal; and the Sheikh Zayed Grand Mosque in Abu Dhabi are among the buildings photographed by the finalists in the annual contest.
Other entries depict a multi-exposed photograph of a German housing block, a shot of the construction site of Amsterdam's new metro line and an image of children playing in a cemetery in Manilla.
The photography competition – now in its fifth year – is run by the Chartered Institute of Building, with the winner chosen by public vote and announced on 5 February 2015.
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1 of 99
840 North Lake Shore Drive Unit 2601, Chicago IL 60611
Enjoy postcard perfect lake & city views from the expansive terraces of Chicago's most iconic penthouse. Sited in the best locale and encompassing 8800 sqft of interior living + 1135 sqft of outdoor living, this jaw dropping full floor home has no equal. Acquired as raw space, it was custom designed & built with no expense spared by the ultimate dream team of designers & craftsman. With soaring twelve foot ceilings & the ultimate in tastefully curated design and timeless finish selections, there is truly not a more spectacular residence. Featuring six en suite bedrooms, eight baths & multiple living/dining areas, this home performs perfectly for both grand scale entertaining & casual everyday living. Stunning great room w/ rotunda sitting area has mesmerizing views, large bar & expansive dining area w/ fireplace. Custom Boffi eat-in kitchen w/ showcase wine cellar. Game & media rooms. Sumptuous office adjoins master suite. Five-star home automation. Three prime garage spaces included.
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Victor SALESINI
Graphic Design
He is currently a student at the Politehnica University Timișoara. Most of his professional experience comes from volunteering projects. He's passionate about diving and volunteering.
1. He loves making himself wallpapers.
2. He enjoys making short and badly-made descriptions.
3. He is half Italian, half Romanian.


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The benefits of Touring on the Cruise Ship
Cruising is the newest getaway fad, and lots of persons are deciding on to spend their time absent from home on the cruise ship.
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Some cruise traces even supply motion picture theaters, ice skating rinks, and placing programs!
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Also, there are a lot of social occasions, this means you have loads of possibilities to satisfy new buddies if you would like!


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aThese are the top 3 reasons for not meeting inclusion criteria. There were 1140 patients who were excluded for other reasons.
bThe first 12 patients randomized to the control group served as controls for the intra-aortic filtration group only and the other 120 patients served as controls for both the suction-based extraction group and the intra-aortic filtration group.
Panels A and B depict the cumulative distribution of observed infarct volume up to the 90th percentile for each treatment group compared with the control group. The y-axis gives the percentage of patients with an observed total infarct volume less than or equal to that of the corresponding infarct volume on the x-axis. IQR indicates interquartile range; MRI, magnetic resonance imaging.
Delirium was measured by Confusion Assessment Method assessment at baseline and at days 1, 3, and 7. The probability of delirium over time was modeled using generalized estimating equations. The interaction term between days from surgery and randomization group was statistically significant (P < .05), indicating that the incidence of delirium over time was significantly different between the treatment groups and the control group.
Trial protocol
eAppendix 1. Devices and their Deployment
eAppendix 2. Outcomes and Ascertainment
eAppendix 3. Statistical Information
eFigure. Relative Risk of "Large Volume" Infarcts for Each Treatment Device Compared to Control
eTable 1. Baseline and operative characteristics
eTable 2. Incidence of Clinical or Radiographic CNS Infarction at 7 Days Post procedure Assuming Various Missing Data Mechanisms
eTable 3. Unadjusted and Adjusted Odds Ratios of Clinical or Radiographic CNS Infarction at 7 Days Post procedure
eTable 4. Neurocognitive Decline at 90 Days by Domain
Customize your JAMA Network experience by selecting one or more topics from the list below.
Mack MJ, Acker MA, Gelijns AC, et al. Effect of Cerebral Embolic Protection Devices on CNS Infarction in Surgical Aortic Valve Replacement: A Randomized Clinical Trial. JAMA. 2017;318(6):536–547. doi:10.1001/jama.2017.9479
© 2019
Can cerebral embolic protection devices reduce the incidence of stroke after surgical aortic valve replacement?
In this randomized clinical trial that included 383 patients, there was no significant difference in freedom from central nervous system infarction between suction-based extraction and a standard aortic cannula (32.0% vs 33.3%, respectively) or between intra-aortic filtration and a standard aortic cannula (25.6% vs 32.4%, respectively).
The incidence of central nervous system infarction after surgical aortic valve replacement was not altered by either of the 2 cerebral embolic protection devices.
Stroke is a major complication of surgical aortic valve replacement (SAVR).
To determine the efficacy and adverse effects of cerebral embolic protection devices in reducing ischemic central nervous system (CNS) injury during SAVR.
Design, Setting, and Participants
A randomized clinical trial of patients with calcific aortic stenosis undergoing SAVR at 18 North American centers between March 2015 and July 2016. The end of follow-up was December 2016.
Use of 1 of 2 cerebral embolic protection devices (n = 118 for suction-based extraction and n = 133 for intra-aortic filtration device) vs a standard aortic cannula (control; n = 132) at the time of SAVR.
Main Outcomes and Measures
The primary end point was freedom from clinical or radiographic CNS infarction at 7 days (± 3 days) after the procedure. Secondary end points included a composite of mortality, clinical ischemic stroke, and acute kidney injury within 30 days after surgery; delirium; mortality; serious adverse events; and neurocognition.
Among 383 randomized patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), the rate of freedom from CNS infarction at 7 days was 32.0% with suction-based extraction vs 33.3% with control (between-group difference, −1.3%; 95% CI, −13.8% to 11.2%) and 25.6% with intra-aortic filtration vs 32.4% with control (between-group difference, −6.9%; 95% CI, −17.9% to 4.2%). The 30-day composite end point was not significantly different between suction-based extraction and control (21.4% vs 24.2%, respectively; between-group difference, −2.8% [95% CI, −13.5% to 7.9%]) nor between intra-aortic filtration and control (33.3% vs 23.7%; between-group difference, 9.7% [95% CI, −1.2% to 20.5%]). There were no significant differences in mortality (3.4% for suction-based extraction vs 1.7% for control; and 2.3% for intra-aortic filtration vs 1.5% for control) or clinical stroke (5.1% for suction-based extraction vs 5.8% for control; and 8.3% for intra-aortic filtration vs 6.1% for control). Delirium at postoperative day 7 was 6.3% for suction-based extraction vs 15.3% for control (between-group difference, −9.1%; 95% CI, −17.1% to −1.0%) and 8.1% for intra-aortic filtration vs 15.6% for control (between-group difference, −7.4%; 95% CI, −15.5% to 0.6%). Mortality and overall serious adverse events at 90 days were not significantly different across groups. Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; P = .02) and cardiac arrhythmias (57 vs 30; P = .004).
Conclusions and Relevance
Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up.
Trial Registration
clinicaltrials.gov Identifier: NCT02389894
Quiz Ref IDThe prevalence of aortic stenosis increases with aging and the expanding number of US patients requiring surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) is estimated to be 100 000 per year.1,2 Steady improvements in patient selection, surgical techniques, and perioperative management have improved survival and quality of life for these patients. However, concerns remain about the incidence of central nervous system (CNS) infarction, a serious complication of SAVR. Studies documented a high incidence (up to 60%) of radiographic brain infarcts on postoperative magnetic resonance imaging (MRI) scans, although the vast majority are subclinical.3,4 In a cohort study, 17% of patients undergoing SAVR (enrolled from 2008-2012) experienced clinical stroke, about 25% of which were moderate or severe.5 The effect of perioperative stroke on survival, quality of life, and cost is well established,6,7 whereas the effect of silent (nonsymptomatic) cerebral infarcts on these outcomes is unknown.
These concerns stimulated the development of cerebral embolic protection devices. Currently 2 devices are approved in the United States. The Embol-X (Edwards Lifesciences) intra-aortic filtration device has been shown to be safe and capture emboli (with a heparin-coated polyester mesh filter), but not reduce stroke in a mostly low-risk population undergoing coronary artery bypass graft surgery.8 The CardioGard (CardioGard) device extracts both particulate and gaseous emboli through suction-based extraction. A small trial of this device among patients undergoing SAVR reported a significant reduction in the total volume and number of radiographically detected brain lesions, but the effect on cognitive outcomes was not evaluated.9 More rigorous data are needed on the value of cerebral embolic protection devices in reducing ischemic CNS injury documented by clinical and radiographic means.10
This trial evaluated the efficacy and adverse effects of these cerebral embolic protection devices among patients undergoing SAVR, which is a high-risk setting for CNS infarction. It included clinical, radiographic, and cognitive outcomes within 90 days.
We conducted a randomized clinical trial at 18 North American centers that compared each of 2 approved cerebral embolic protection devices vs a standard aortic cannula (control) in patients undergoing SAVR. This trial had a coordinating center, an events adjudication committee, and a data and safety monitoring board appointed by the National Institutes of Health (NIH) overseeing the trial. Participating institutional review boards approved the protocol and all patients gave written informed consent (the trial protocol appears in Supplement 1).
The overall aim of the trial was to establish the effectiveness of embolic protection devices vs standard of care. At the time the trial was initially designed, patients were to be randomized to the treatment group to receive the intra-aortic filtration device or to receive a standard aortic cannula in a 1:1 ratio. Within 6 weeks after initiating the trial, the suction-based extraction device became available, and patients were then to be randomized to receive the intra-aortic filtration device, the suction-based extraction device, or standard aortic cannula in a 1:1:1 ratio. The trial was not designed to directly compare devices, which would have required a substantially larger sample size.
The trial randomized patients aged 60 years or older undergoing SAVR for aortic stenosis with minimal or no deficits within 7 days of randomization according to the preoperative scores on the NIH Stroke Scale (NIHSS; score ≤1) and the modified Rankin Scale (score ≤2). Quiz Ref IDKey exclusion criteria included clinical stroke during the 3 months prior to randomization; cardiac catheterization; cerebral or aortic arch angiography within 3 days of planned SAVR; and active endocarditis. Patients were randomized immediately after sternotomy and stratified by center and procedure (isolated aortic valve replacement vs aortic valve replacement and coronary artery bypass graft with or without mitral valve repair). The intra-aortic filtration device uses a heparin-coated polyester mesh filter. Filter size was determined by measuring the size of the distal ascending aorta (using computed tomography or an intraoperative measurement). The suction-based extraction device has a suction sideport located posterior to the main port of an aortic perfusion cannula. In the control group, a standard aortic perfusion cannula was used (eAppendix 1 in Supplement 2). Patients underwent SAVR between March 2015 and July 2016. The end of follow-up was December 2016.
Patients were assessed at baseline and at postoperative days 1, 3, 7, 30, and 90; the investigators were blinded to the end point data. Quiz Ref IDThe primary end point was freedom from clinical or radiographic CNS infarction at 7 days (± 3 days) after the procedure. Radiographic CNS infarcts were identified using a diffusion-weighted 1.5-T or 3.0-T MRI scanner.
Imaging-based stroke ascertainment was supplemented by serial neurological assessment using the NIHSS (score at postoperative days 1, 3, and 7) and reporting of ischemic stroke adverse events detected during hospitalization. All MRIs were read by a core laboratory and stroke events with clinical findings (NIHSS score ≥2) were adjudicated by an events adjudication committee composed of vascular neurologists.
The composite secondary end point was mortality, clinical ischemic stroke (including newly MRI-detected CNS infarcts associated with focal findings by the NIHSS before postoperative day 7), or acute kidney injury within 30 days after surgery. Other secondary end points included volume and number of radiographic brain lesions; delirium (assessed using the 3-minute Diagnostic Interview for Confusion Assessment Method [CAM] or CAM for use in patients in the intensive care unit) at baseline and at postoperative days 1, 3, and 7; modified Rankin Scale score; Barthel Index score; Geriatric Depression Scale score; survival; serious adverse events; and hospital readmissions within 90 days.
Quality of life (physical and mental subscales from the 12-Item Short-Form Health Survey) and cognition in 6 domains (verbal memory, visual memory, executive functioning, visuospatial or constructional praxis, attention, and information processing speed) were assessed at 90 days. Additional details regarding the definition and assessment of outcomes appear in eAppendix 2 in Supplement 2.
Patients were randomized with equal allocation to 1 of 2 cerebral embolic protection device groups or to the control group. Random permuted block sizes of 3, 6, and 9 were used. The randomization sequence was generated by a trial statistician and randomization assignment was controlled centrally through a web-based data collection system and performed in the operating room. A sample size of 165 patients in each group ensured that each comparison had a power of approximately 90% to detect a between-group difference of 17.5% from an assumed control rate of 50% in the incidence of postoperative CNS infarcts, which corresponds to a 35% reduction in risk.
A single interim analysis was prespecified and performed and was based on group sequential monitoring with Lan-DeMets efficacy boundaries defined by an O'Brien-Fleming spending function.11,12 The consideration of halting for futility was prespecified if conditional power was below 20% (eAppendix 3 in Supplement 2). Intention-to-treat χ2 tests performed at the nominal .05 level (2-sided) were used to test hypotheses about differences between the intervention devices and the control intervention.
No adjustment was made to the type I error rate because these 2 planned comparisons are separate comparisons of each device group vs a shared control. Based on the recommendation of the data and safety monitoring board at the interim analysis, randomization but not follow-up was halted due to low conditional power of observing any between-group differences for the primary end point. At that point, 383 patients had been randomized.
The primary end point analysis used an iterative hot-deck multiple imputation approach, assuming a nonignorable missing data mechanism (eAppendix 3 in Supplement 2). The proportion of patients who experienced the composite clinical end point was compared using χ2 tests. The volume of brain infarcts was compared by permutation test.
Negative binomial models were used to analyze the number of brain infarcts (instead of protocol-defined zero-inflated Poisson regression models) because model fit was better. All-cause mortality was analyzed using the log-rank test and differences in adverse event rates were tested using Poisson regression. The incidence of delirium at postoperative days 1, 3, and 7 were compared using χ2 tests and the trajectory of delirium incidence over time was compared using generalized estimating equation logistic regression models.
The decline in scores for cognitive domains (decrease of 0.5 SD at 90 days) was compared between groups using logistic regression models, adjusting for baseline scores. Quality of life was assessed using t tests. Depression (presence vs absence), modified Rankin Scale scores (>2), and Barthel Index scores (≤80) were assessed using χ2 tests. All statistical analyses were conducted using SAS version 9.4 (SAS Institute Inc).
A total of 870 patients were screened and found eligible (Figure 1). Among 383 patients (mean age, 73.9 years; 38.4% women; 368 [96.1%] completed the trial), 118 were randomized to the suction-based extraction group, 133 to the intra-aortic filtration group, and 132 to the control group. Of the 132 patients randomized to the control group, the first 12 served as controls for the intra-aortic filtration group only because the suction-based extraction device was not yet clinically available and the other 120 served as controls for both the suction-based extraction group and the intra-aortic filtration group.
The randomized groups had similar baseline characteristics (Table 1 and eTable 1 in Supplement 2). Preoperatively, 36.3% of patients randomized to the suction-based extraction group had severe cognitive impairment (≥2 SDs below the mean of an age-standardized population) in 1 or more of the domains specified in Table 1 vs 25.7% of patients in the control group and 29.8% of patients in the intra-aortic filtration group vs 25.8% of patients in the control group.
Most patients underwent either isolated SAVR (58%) or a combined SAVR and coronary artery bypass graft procedure (41%). Cardiopulmonary bypass times were similar in both device groups and in the control group. Three patients randomized to intra-aortic filtration and 2 patients randomized to suction-based extraction did not receive the designated device due to anatomic constraints and hemodynamic instability. Embolic debris was captured in 99% of patients in the intra-aortic filtration group and in 75% of patients in the suction-based extraction group (Table 1).
Quiz Ref IDFreedom from CNS infarction at postoperative day 7 (using imputation for missing data) was not significantly different between the suction-based extraction group and the control group (32.0% vs 33.3%, respectively; between-group difference, −1.3% [95% CI, −13.8% to 11.2%]) nor between the intra-aortic filtration group and the control group (25.6% vs 32.4%, respectively; between-group difference, −6.9% [95% CI, −17.9% to 4.2%]). Sensitivity analyses assuming different missing data mechanisms appear in eTable 2 in Supplement 2. Among patients who met the primary end point, the majority did not show clinical evidence of stroke (91% in suction-based extraction group vs 90% in control group; and 87% in intra-aortic filtration group vs 90% in control group). End point analyses stratified by procedure and site are provided in the eTable 3 in Supplement 2.
The proportion of patients in the suction-based extraction device group (with or without an MRI) who had clinically apparent stroke was 5.1% vs 5.8% among patients in the control group (between-group difference, −0.7%; 95% CI, −6.5% to 5.1%). The proportion of patients in the intra-aortic filtration group with stroke was 8.3% vs 6.1% among patients in the control group (between-group difference, 2.2%; 95% CI, −4.1% to 8.4%). Seventy-six percent of clinically apparent strokes were detected by postoperative day 3, and there were fewer cases of severe stroke among patients who received a cerebral embolic protection device within this 3-day window in a post hoc analysis (Table 2).
Patients frequently showed evidence of multiple new CNS infarcts. The number of infarcts was not significantly different between patients in the suction-based extraction group and the control group (mean, 2.4 vs 2.3, respectively; between-group difference, 0.1 [95% CI, −0.8 to 1.0]; P = .88), nor between patients in the intra-aortic filtration group and the control group (mean, 2.8 vs 2.7, respectively; between-group difference, 0.1 [95% CI, −0.8 to 1.1]; P = .78). Total lesion volume was not significantly different between patients in the suction-based extraction group and the control group (mean, 178.5 mm3 vs 476.4 mm3, respectively; between-group difference, −297.9 mm3 [95% CI, −741.3 to 145.6 mm3]; P = .28), nor between patients in the intra-aortic filtration group and the control group (mean, 321.3 mm3 vs 484.4 mm3, respectively; between-group difference, −163.1 mm3 [95% CI, −586.0 to 259.8 mm3]; P = .49).
Figure 2 depicts the cumulative distribution of total lesion volume up to the 90th percentile. Infarct volumes were larger in patients with a clinically apparent stroke (mean, 1688 mm3) than in those without a clinically apparent stroke (mean, 236 mm3) (between-group difference, 1451.9 mm3 [95% CI, 883.0-2020.8 mm3]; P = .001). Data on the risk of large volume infarcts appear in the eFigure in Supplement 2.
The proportion of patients experiencing the composite end point of death, clinically apparent ischemic stroke, or acute kidney injury within 30 days of surgery was 21.4% in the suction-based extraction group vs 24.2% in the control group (between-group difference, −2.8%; 95% CI, −13.5% to 7.9%) and 33.3% in the intra-aortic filtration group vs 23.7% in the control group (between-group difference, 9.7%; 95% CI, −1.2% to 20.5%). The individual components of the composite 30-day end point were not significantly different across groups (Table 2).
Mortality, composite neurological events, and overall serious adverse events at 90 days were not significantly different across groups (Table 2). Patients in the intra-aortic filtration group vs patients in the control group experienced significantly more acute kidney injury events (14 vs 4, respectively; between-group difference, 2.7 [95% CI, 0.4-4.9]) and cardiac arrhythmias (57 vs 30, respectively; between-group difference, 7.2; 95% CI, 2.3-12.1).
The length of stay during the index hospitalization was not significantly different between patients in the suction-based extraction group and in the control group (mean, 9.8 days vs 10.3 days, respectively; between-group difference, −0.5 days [95% CI, −2.1 to 1.1 days]) nor was length of ICU stay (mean, 4.0 days vs 4.2 days, respectively; between-group difference, −0.1 days [95% CI, −1.0 to 0.7 days]). Similarly, length of stay during the index hospitalization was not significantly different between patients in the intra-aortic filtration group and in the control group (mean, 10.4 days vs 10.3 days, respectively; between-group difference, 0.1 days [95% CI, −1.5 to 1.7 days]), nor was length of ICU stay (mean, 4.5 days vs 4.1 days, respectively; between-group difference, 0.4 days [95% CI, −0.5 to 1.2 days]). Hospital readmission rates were not significantly different between both intervention groups and the control group.
There were significant differences in the trajectories for delirium occurrence (baseline to day 7) among patients in the suction-based extraction group vs the control group (P = .03) and among patients in the intra-aortic filtration group vs the control group (P = .02; Figure 3). At postoperative day 7, 6.3% of patients in the suction-based extraction group experienced delirium vs 15.3% of patients in the control group (between-group difference, −9.1%; 95% CI, −17.1% to −1.0%) and 8.1% of patients in the intra-aortic filtration group vs 15.6% of patients in the control group (between-group difference, −7.4%; 95% CI, −15.5% to 0.6%).
The 12-Item Short-Form Health Survey composite physical and mental health scores were not significantly different between the 2 device intervention groups and the control group (Table 2). Moreover, no differences were observed in the overall cognition scores for the 2 device intervention groups and the control group (Table 2). However, the decline in overall cognition scores was greater for patients experiencing clinically apparent stroke than for other patients (71.4% vs 28.0%; between-group difference, 43.5% [95% CI, 19.2%-67.7%]). With the exception of executive function, which showed less decline among patients in the intra-aortic filtration group vs patients in the control group, there were no differences among the neurocognitive domain comparisons (eTable 4 in Supplement 2).
Quiz Ref IDDespite the fact that debris was captured in most patients who received a cerebral embolic protection device, rates of clinical and radiographic infarction were not reduced. Nearly 69% of patients who underwent SAVR experienced clinical or radiographic stroke. However, the majority of these events was only detectable by postoperative diffusion-weighted MRI, with just 9% of patients exhibiting clinical findings. Neither the number of MRI lesions nor total lesion volume differed between patients receiving either of the cerebral embolic protection devices and the patients in the control group. However, the infarct volume pattern suggested a possible differential effect of devices compared with the control intervention, with larger volume infarcts more numerous in patients in the control group. This observation may be important because the risk of clinically evident stroke increases with infarct volume.
The reported incidence of newly detected clinical and radiographic infarcts after cardiac surgery has varied across observational studies likely in relation to cohort size, patient characteristics, approaches to clinical assessment, and imaging techniques.3,4,14-18 The volume of radiographic infarcts seen in this study (the majority of which were small with a median infarct volume of 48.7 mm3) is concordant with that reported in prior studies using MRI after patients underwent SAVR.5,9,19 Imaging studies in the general population have reported that clinically silent brain infarction (including microinfarction <3 mm) is associated with dementia, mortality, and risk of future stroke and death; however, it is not clear whether these same associations pertain to periprocedural infarcts that are clinically silent.10,17,20-23
The proportion of patients with clinical stroke findings at day 7 (with or without MRI evidence of infarction) were not significantly different between patients in the suction-based extraction group and the control group (5.1% vs 5.8%, respectively) nor between patients in the intra-aortic filtration group and the control group (8.3% vs 6.1%, respectively). However, the majority of clinical stroke findings were detected by postoperative day 3, suggesting that many cases of perioperative stroke may be preventable with use of a cerebral embolic protection device.
In a post hoc analysis, there were numerically fewer patients with severe clinical stroke (NIHSS score >20) among patients receiving a cerebral embolic protection device compared with patients in the control group at days 0 through 3. Given that severity (defined by NIHSS score) at onset is one of the strongest predictors of long-term outcome after acute stroke, a reduction in the risk of severe stroke during the early perioperative period might be a tangible benefit of cerebral embolic protection device use during SAVR, and may justify a larger trial.24
The rate of clinically apparent stroke (6.5%) in this trial is much higher than the 7-day stroke incidence of 1% to 3% reported in several prior studies,25,26 and is most likely attributable to active ascertainment with early repeated neurological assessments. However, there was a lower incidence of stroke with clinical findings than the 17% seen in a previously reported cohort study,5 perhaps related to a treatment shift from SAVR to TAVR among high-risk patients that occurred during the course of this trial. There was a large difference in this trial between observed cases of stroke during the course of clinical care and cases of stroke detected through protocol-specified, routine NIHSS screening, suggesting that many clinical events are undetected or underreported in practice.
Delirium (defined as a disturbance of consciousness and cognition that can develop acutely after surgery) is common and occurs in 11% to 46% of patients after surgery.27 Prior studies have shown that cerebral embolization is associated with delirium, a condition that is costly and associated with poor outcomes, including prolonged hospitalization, readmissions, long-term cognitive decline, and mortality.28-30 Longitudinally (over 7 days postoperatively), there was a significant difference between patients who received one of the device interventions and patients in the control group. At day 7 (when perioperative medications are less of a factor), fewer patients who received a device experienced in-hospital delirium than patients in the control group and the difference achieved statistical significance with the suction-based extraction device. This difference may be related to the fact that, in addition to particulate matter, the suction-based device also extracts gaseous microemboli, which have been shown to affect neuropsychological functioning early during the postoperative phase among patients undergoing cardiac surgery.31
More than 25% of patients had severe cognitive impairment on baseline testing in 1 domain compared with age-adjusted norms, especially in verbal memory and executive functioning. These domains are associated with late-onset Alzheimer-related pathology and cerebrovascular disease. Similar findings have been reported with TAVR.32 Given the advanced age of patients with aortic stenosis and the increased incidence of cerebrovascular disease, higher rates of postoperative cognitive impairment in populations undergoing SAVR and TAVR is not unexpected. These findings underscore the importance of evaluating cognitive impairment during risk assessment given its association with postoperative delirium and late-onset dementia.21,30
Baseline performance-adjusted cognitive outcomes at 90 days were not significantly different between the patients in the device groups and the control group with the exception of a reduced decline in executive functioning in the intra-aortic filtration group. This finding requires more investigation, but might relate to the lower incidence of delirium observed among patients in the device treatment groups compared with patients in the control group.
There was evidence of an increased incidence of acute kidney injury and a higher rate of cardiac arrhythmias among patients in the intra-aortic filtration group compared with the control group. These findings merit further investigation, but need to be interpreted in the context of multiple statistical comparisons for adverse events, which increases the likelihood of finding abnormalities due to random variation alone.
This trial has several limitations. First, even though the trial subscribes to the latest imaging recommendations for assessing neurological outcomes in the postcardiac surgery setting,33 the significance of the many small and clinically silent lesions identified by diffusion-weighted MRI cannot be established. Second, although the optimal time frame to assess the effectiveness of an intraoperative cerebral embolic protection device is within the first few postoperative days, 7-day imaging is more feasible for patients undergoing cardiac surgery. As a result, this study may have captured radiographic and clinical CNS infarctions not related to intraoperative embolization (eg, from postoperative atrial fibrillation), thus overestimating the infarct burden, whereas smaller lesions may have normalized by 7 days, underestimating the infarct burden.
Third, although the NIHSS score has been validated as a measure of stroke severity, it does not inherently inform whether a clinical stroke has occurred. However, clinical stroke end point adjudication was performed by experienced vascular neurologists who reviewed trial data to determine whether an event occurred. Fourth, randomization was halted due to low conditional power for the primary end point, diminishing the power to detect differences for the secondary end points. In addition, the long-term effects on cognition may not have been fully evident within the 90-day follow-up of the trial. Fifth, the trial was not designed to directly compare devices, which would have required a substantially larger sample size.
Among patients undergoing SAVR, cerebral embolic protection devices compared with a standard aortic cannula did not significantly reduce the risk of CNS infarction at 7 days. Potential benefits for reduction in delirium, cognition, and symptomatic stroke merit larger trials with longer follow-up.
Corresponding Author: Annetine C. Gelijns, PhD, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1077, New York, NY 10029 (email@example.com).
Accepted for Publication: July 6, 2017.
Author Contributions: Ms Overbey and Dr Parides had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Mack and Acker are both first authors.
Concept and design: Mack, Acker, Gelijns, Parides, Browndyke, Moskowitz, Ailawadi, Thourani, Moquete, Iribarne, Perrault, Bowdish, Davatzikos, Winkle, Miller, Taddei-Peters, Rose, Weisel, Furie, Bagiella, Moy, O'Gara.
Acquisition, analysis, or interpretation of data: Mack, Acker, Gelijns, Overbey, Parides, Browndyke, Groh, Moskowitz, Jeffries, Ailawadi, Moquete, Iribarne, Voisine, Perrault, Bilello, Davatzikos, Mangusan, Smith, Michler, O'Sullivan, Taddei-Peters, Rose, Weisel, Bagiella, O'Gara, Messé.
Drafting of the manuscript: Mack, Acker, Gelijns, Overbey, Browndyke, Moskowitz, Moquete, Iribarne, Bowdish, O'Sullivan, Bagiella, O'Gara.
Critical revision of the manuscript for important intellectual content: Mack, Acker, Gelijns, Overbey, Parides, Browndyke, Groh, Jeffries, Ailawadi, Thourani, Moquete, Iribarne, Voisine, Perrault, Bowdish, Bilello, Davatzikos, Mangusan, Winkle, Smith, Michler, Miller, Taddei-Peters, Rose, Weisel, Furie, Bagiella, Moy, O'Gara, Messé.
Statistical analysis: Overbey, Parides, Browndyke, Jeffries, Iribarne, Perrault, Smith, Rose, Bagiella.
Obtained funding: Gelijns, Parides, Ailawadi, Bowdish, Michler, Miller, Rose, Weisel, Moy.
Administrative, technical, or material support: Acker, Browndyke, Iribarne, Voisine, Bowdish, Bilello, Michler, Miller, O'Sullivan, Taddei-Peters, Rose, Weisel.
Supervision: Mack, Acker, Gelijns, Parides, Groh, Moskowitz, Ailawadi, Thourani, Moquete, Perrault, Winkle, Michler, O'Sullivan, Weisel, O'Gara, Messé.
Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Mack reported having prior uncompensated research relationships with Edwards LifeSciences and Abbott Vascular; and serving on an executive board for Medtronic (uncompensated). Dr Browndyke reported receiving personal fees from Claret Medical Inc. Dr Bowdish reported receiving personal fees from Edwards Lifesciences. Dr Messé reported receiving personal fees from Claret Medical Inc; and receiving personal fees from the Yale Cardiovascular Research Group for serving on a clinical event committtee. No other disclosures were reported.
Funding/Support: The trial was supported by cooperative agreement U01 HL088942 funded by the National Institute of Neurological Disorders and Stroke, the National Heart, Lung, and Blood Institute, and the Canadian Institutes for Health Research. Additional support was provided by grant R01 AG014971 from the National Institutes of Health (Dr Davatzikos). Training in use of the Embol-X (Edwards Lifesciences) and CardioGard (CardioGard) devices was provided by the companies but they did not provide financial support for the study.
Role of the Funder/Sponsor: The representatives from the National Institutes of Health were involved in study design, management, and review of the manuscript. Edwards Lifesciences and CardioGard had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript or the decision to submit for publication.
Group Information: The members of the Cardiothoracic Surgical Trials Network (CTSN) are Dennis Buxton, Nancy L. Geller, Catherine Burke, Albert Lee, and Tyrone Smith (National Heart, Lung, and Blood Institute); Ilana Kogan Gombos (Canadian Institutes of Health Research); Kinjal Shah, Stephanie Pan, Alishba Aslam, Helena Chang, Melissa Chase, Kayla Dellefratte, Seth Goldfarb, Lopa Gupta, Katherine Kirkwood, Edlira Dobrev, Ron Levitan, Andrea Ratner, Milerva Santos, Nancy Sledz-Joyce, and Xia Ye (International Center for Health Outcomes and Innovation Research at Icahn School of Medicine at Mount Sinai; data coordinating center); Amanda Fenlon, Katherine Harrington, Kelly Hutcheson, Melissa Johnson, Jessica Jones, Megan Kolb, Sarah Lam, Lucy Miranda, Jackie Ward, Renessa Whitman, Brittany Zingler, William Ryan, Robert L. Smith, Pedro Nosnik, and Justin Whisenant (Baylor Research Institute); Edward G. Soltesz, Stephanie Mick, Irene Katzan, Brian Strippy, Shoi Smith, Michelle Garcia, and Mary Alice Bowman (Cleveland Clinic Foundation); Michael Argenziano (primary investigator), Michael Borger, Hiroo Takayama, Lyn Goldsmith, Nadia Sookraj, Talaya McCright-Gill, and Sowmya Sreekanth (Columbia University); Jock N. McCullough (primary investigator), Joseph P. DeSimone, Anthony W. DiScipio, Henry Stokes, Amanda St Ivany, Gaylin Petty, and Jim Hart (Dartmouth-Hitchcock Medical Center); John H. Alexander, Carmelo A. Milano, Donald D. Glower, Stacey Welsh, Sarah Casalinova, Victoria Johnson, Derek Smith, and Greg Tipton (Duke University); Robert Guyton, Omar Lattouf, Michael Halkos, Kim Baio, Tamara Prince, Natascha Cook, and Alexis A. Neill (Emory University); François Dagenais, Robert Laforce Jr, Kim O'Connor, Gladys Dussault, Manon Caouette, Hugo Tremblay, Nathalie Gagne, and Patricia Landry (Hôpital Laval); John G. Short, Reid D. Taylor, Tracy Nanney, Holly Aubart, Kristin Cross, Leslie McPeters, Christina Riggsbee, and Lucy Rixey (Mission Hospital); Joseph J. DeRose Jr, Daniel J. Goldstein, Ricardo A. Bello, William Jakobleff, Kathryn Kirchoff, Richard Zampolin, Rebecca Meli, Juan Garcia, Jon Goldenberg, and Lauren Kealy (Montefiore-Einstein Heart Center); Denis Bouchard, Michel Carrier, Jean François Tanguay, Pierre Pagé, Céline Odier, Filippo Codemartiri, Jonathan Lacharité, and Sophie Robichaud (Montreal Heart Institute); Keith A. Horvath (primary investigator), Philip C. Corcoran, Michael P. Siegenthaler, Mandy Murphy, Margaret Iraola, Ann Greenberg, Greg Kumkumian, Mark Milner, and Zurab Nadareishvili (National Institutes of Health Heart Center at Suburban Hospital); Bryan A. Whitson (primary investigator), Juan Crestellano, Xuan Nguyen, Mohit Datta, Asia McDavid, and Denise Fadorsen (Ohio State University Medical Center); Maral Ouzounian (primary investigator), Terry Yau, Cheryl Jaigobin, Narinder Paul, Walter Kucharczyk, Nishit Fumakia, and Shakira Christie (Toronto General Hospital); John C. Mullen (primary investigator), Asvina Bissonauth, and Alexandra Hripko (University of Alberta Hospital); Bradley Taylor (primary investigator), James Gammie, John Cole, Robert Morales, Kristen Mackowick, Stephanie Deasey, and Julia Collins (University of Maryland); Jesse Raiten, Cen Zhang, Mary Lou Mayer, Caitlin McDonald, Holley Fok, Breanna Maffei, Stephen Cresse, and Christine Gepty (University of Pennsylvania); Vaughn A. Starnes, David Shavalle, Christi Heck, Amy Hackmann, Craig Baker, Fernando Fleischman, Mark Cunningham, Meng Law, Edward Lozano, Michelle Hernandez, and Sylvia Ramos (University of Southern California); Irving L. Kron, Karen Johnston, Ravi K. Ghanta, Leora Yarboro, Joe Carrera, Nicole Chiota-McCollum, Sandra Burks, Mike Cosner, China Green, Samantha Loya, Helen Kim, Jennifer Phillips, and Rachel Simon (University of Virginia).
Additional Contributions: We thank David A. Bull (chair), Patrice Desvigne-Nickens (executive secretary), Dennis O. Dixon, Rebecca Gottesman, Mark Haigney, Richard Holubkov, Constantino Iadecola, Alice Jacobs, Eric M. Meslin, John M. Murkin, and John A. Spertus (protocol review committee); Frank Sellke (chair), Cheryl L. McDonald (executive secretary), John Canty, Neal Dickert, Dennis O. Dixon, John S. Ikonomidis, Kyung Mann Kim, David O. Williams, Clyde W. Yancy, Seemant Chaturvedi, and Marc Chimowitz (data and safety monitoring board); James C. Fang and Wayne Richenbacher (medical monitors); Vivek Rao (chair), Rachel Miller, Jennifer Cook, David D'Alessandro, Frederick Han, Sean Pinney, and Mary N. Walsh (overall event adjudication committee); David Greer (chair), Koto Ishida, and Christian Stapf (events adjudication committee neurology subcommittee); Judy Hung, Xin Zeng, David Hung, and Sudarat Satitthummanid (echo core laboratory at Massachusetts General Hospital); Guray Erus, Lauren Karpf, and Lisa Desiderio (MRI core laboratory at the University of Pennsylvania); Joseph P. Mathew, Michael L. James, Yanne Toulgoat-Dubois, and Rachele Brassard (neurocognitive core laboratory at Duke University Medical Center); and Renu Virmanu, Maria E. Romero, and Ryan Braumann (histopathology core laboratory at CVPath Institute).
Disclaimer: The views expressed in this article are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the US Department of Health and Human Services.
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