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Transform your '97-'06 Wrangler in minutes with our complete selection of stylish yet functional body cladding from Bushwacker. Installation is fast & easy with high-bond 3M double-sided adhesive tape. Rear Corner & Side Rocker Panels will work with either factory custom styled fender flares. Dura-Flex diamond textured plastic material can b easily custom painted or the attractive UV-protected black finish can be left alone. The Rear Corner Kit features an integrated license plate mount molded directly into itself. Side Rockers have that Rubicon version look and are sold pairs. Front Frame Cover features the Bushwacker oval logo and comes with the Rear Tailgate Valence piece. The newest Trail Armor pieces, the Hood Protector and Front Fender Guards Set completes this awesome & stylish look all the while protecting your Jeep from dings and dents both on and off the trails!
Front Corner Stone Guards - Black.
- Features: Plastic
- Color: Black
- Armor Type: Front Fenders
- Material: Plastic
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SPACE INVADERS Sweater - monochrome black and white dress with space invaders print, a change of perspective made of organic cotton. | ||
base color | black and white | |
composition | 95% organic cotton, 5% elastane | |
sizeguide | click here for sizeguide | |
certification | GOTS, oekotex 100 | |
handling | maschine wash 40° | |
production | Poland | |
origin | Berlin | |
dispatch time | 1-2 working days after payment | |
shipping time | Germany | 1-2 days |
Europe | 2-5 days | |
World | 3-9 days |
The SPACE INVADERS Sweater
…is created and designed by Berlin based Little Man Happy. A view from outer space directly into your soul. Monochrome print that trends out those pixel worlds we all once encountered and now hand over to the next generation. Truely following new Autumn Winter 016 topic "THE SKY IS MY LIMIT".
The sweater embodies uniqueness, rich of casual coolness and style. Wear it with in combination with the matching SPACE INVADERS Sweatpants or any other plain pants and get some booties or high top sneakers with it.
Additional Information
Shipping | Germany 1-3 days |
Material & Handling | The material keeps it all cosy and warm. The sweat has a very soft feeling through its brushed surface on the inside and contains 95% organic cotton and 5% elastane. Highest qualities guaranteed by excellent material and production standards. The sweater is assembled at our friends and partners close to Warsaw, Poland. The fabric is printed and produced by our partners in Turkey. It holds the independent Global Organic Textile Standard (GOTS). Only textile products that contain a minimum of 70% organic fibres can become GOTS certified. All chemical inputs such as dyestuffs and auxiliaries used must meet certain environmental and toxicological criteria. The choice of accessories is limited in accordance with ecological aspects as well. A functional waste water treatment plant is mandatory for any wet-processing unit involved and all processors must comply with minimum social criteria. The handling of the SPACE INVADERS Sweater is fairly easy: Wash it up to 40°C with similar colours. But please note, the fabric may shrink up to 5%. |
SKU: lmh-sw-085...089 - Need Help? Contact Us Leave Feedback
Categories: AW016, Sweater, All.

subset: commoncrawl


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Smaller than your smartphone, Mophie's Spacestation gives you up to 128GB of external storage, 600mAh of universal power for virtually any USB device & WiFi Space Portal to access, back up, and transfer files with your Mac, PC and portable devices.
The Nomad battery pod is small enough to fit in your pocket & features an 1800 mAh lithium polymer battery with enough power to charge your Apple Watch 4 times. It will also charge other USB devices with its integrated Type A & Type C USB ports.
This tiny, 1-inch cube could save your phone's life. It offers Lightning & USB connection, a slot for a micro SD card, an LED flashlight, & even a port to plug in a common 9-volt battery when your phone is about to die & plugs or power supply are not available.
This compact, rugged USB power supply from Brunton is both shockproof & weatherproof & provides up to 2.5 charges for your device. It also includes a 3-in-1 Adapter Cable with Micro USB, Lightning, & 30-Pin to USB connection.
Samsung's T1 portable is only slightly larger than the average thumb drive yet offers up to a hefty 1TB of storage space. It also supports data encryption and works with both Mac and Windows.
Blue Freedom is the world's smallest hydropower plant; a pocket-size power supply that charges up with the power of moving water. Drop the little turbine into the brook by your campsite and in one hour underwater it generates 10 hours of power for your smartphone, camera, & other electronics.
When you're off the beaten path, your phone & other gadgets are doomed to dead battery status. But if you've got a fire going or a campstove & you've got a Flamestower in your pack, you'll be back in business lickety-split. The compact portable device draws heat from the fire & converts it into electricity to power your USB electronics.
Powered by lighter gas or camping fuel, the Kraftwerk power supply uses fuel cell technology to offer off-grid power for your USB devices—anywhere, anytime. One filling supplies 11 iPhone charges and Kraftwerk is FAA approved for aircraft cabin use. Another fully funded Kickstarter project.
Dropping your iPhone in the toilet, or worse, out the car window, is now preventable. Highline is a security leash and protective case system that keeps your iPhone attached to you. The removable leash utilizes the iPhone's Lightning port and a special notch in the case to create a secure attachment. An attachment loop keeps it connected to your wrist, belt, bag, or 'biner.
Typing anything longer than a tweet on your touchscreen can be a real drag, especially if you were blessed with sausage fingers like us. The TextBlade solves the problem—it's a compact mini keyboard that uses a patented multitouch key technology. Weighing just 42.5 grams and a third of the size of an iPhone 6, it's the slimmest full QWERTY design to date.


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Can lines create three-dimensional optical effects? Here is a new example with three snakes trying to camouflage themselves between the lines … With students of the sixth grade we experienced the 3D effect created only through parallel lines. Before we drew the snakes with pencil and then we filled the sheet of horizontal lines with a sequence of four colors felt-tip pen. Whenever our line "meets" the serpent, we must draw a "bump", trying to keep the lines parallel.
1. drawing paper
2. pencil
3. colored felt pens
The activity takes 1 hour
Op Art Snakes
November 12, 2015 by 4 Comments
I love these snakes! Such a great subject matter for this technique. My son will love this project.
I've seen this done with hand prints. It's a fun technique!


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'Expres Succes! Midland Pullman, Britain's Most Exciting Train'. Poster produced for British Railways (BR), London Midland Region (LMR), promoting the Midland Pullman locomotive, which ran weekday expres services between London, Manchester and Nottingham. Printed by Sanders Phillips & Co Ltd, London. Dimensions: 1016mm x 635mm.
© NRM / Pictorial Collection / Science & Society Picture Library


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Sci fi/Fantasy image by
Madison Woods* Gordon-ForbesUh, this is my characters Suzu and Yumi, along with Amber's character Bakura (from Yugioh). On Bakura's shoulders are Mini Devil and Mini Angel. Yumi appeared out of no where on Suzu's back pissing Suzu off and Yumi is all like ' Yo Shane! 'Sup?' and Mini Devil is like ' Kill Yumi, kill kill kill!' and Mini Angel is like ' I must agree with Mini Devil'. Bakura is all like standing there gawking.
Published More than a year ago
Category Fan art
Be the first to favourite this image.


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Born in Vernon, B.C., first played with such well known western clubs as the Trail Smoke Eaters, Nanaimo Clippers and Red Deer Wheelers. In 1946-47, he came east and registered 37 points in 47 games for the New York Rovers of the EHL in 1946-47.
Following his appearance with the Rangers, Kwong played with the Rovers' EHL franchise before moving on to the team the organization had entered in the Quebec Senior League. Content in the QSHL, Kwong spent the next seven years with the league's Valleyfield Braves. He topped the 20-goal mark six times and led the Braves to the league championship in 1951. That year he was presented the Vimy Trophy as the most valuable player in the league. Kwong retired in 1958 after spending a year with the Nottingham Panthers of the British League.


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Spectrum Consultants
Strengthening Communities. Enriching Lives.Spectrum Senior Living Projects
Spectrum Consultants has been privileged to represent over 275 senior living communities since 1978. Our mission is to foster successful relationships with Life Plan Communities serving together to enhance value, fulfill missions, and enrich the lives of seniors. We celebrate successes with some of our past and current clients.Spectrum Senior Living Philosophy
It's All About Relationship and Community.Guiding Principles
Innovation. Energy. Integrity. Interdependence. Empowerment.Resident Focus
Enriching the lives of seniors is why we love the work we do. Helping to create an environment where residents and future residents can thrive is what matters most.
Mission Driven
Spectrum Consultants fosters successful relationships with senior living communities to fulfill their missions by enhancing value and enriching the lives of seniors.
Alignment with Client Intentions
You come first. We work directly with Executive Directors and their teams to help achieve short-term and long-term objectives and goals.
Integrated & Diverse Services
Your community will benefit from Spectrum's array of disciplines, skill sets, connections, and big-picture focus.
Industry Leadership
With clients like you, we want to put the Senior Living Industry on the map. Innovation, imagination, and implementation create progressive change.
Continuous Improvement
We promote learning of relevant knowledge and skills to keep our team (and your team) progressive, effective, and sharp.
Discover life in senior living
Spectrum Consultants and ClientsEnabling senior living communities to reach their highest potential by building value (real estate assets, cash and intangible assets such as brand recognition and good will), filling residences (through effective planning, marketing, communications and sales), and delighting residents (with the highest standards of holistic wellness, hospitality, housing and healthcare).


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300+ pronájmů · Podgórze
300+ pronájmů · Podgórze
Excellent aparment in a good location! Great communication with Witalij and Nika.
JakubMarch 2017Everthing was ok. I recommend this place.
BartekMarch 2017Typ pokoje
Soukromý pokoj
Typ nemovitosti
Filip was a wonderful host, offering great tourist advice and any support we needed. The apartment had a wonderful atmosphere like advertised and is very central - we did not have to take any form of public transport to explore within Krakov during our stay. Would definitely stay again!
EmmaFebruary 2017Super miejsce ,nie dale love centrum! Blizko sklepow:) Fajnie bylo sie zrelaksowac po dlugiej podrozy(dziekuje za maseczke i srodki do kapieli ) Napewno kiedys wrocimy!!
AnnaFebruary 2017El apartamento estaba en perfectas condiciones, todo parecía nuevo y limpio, cuenta además con muy buenas instalaciones, sobretodo en el baño y cocina. La pareja que nos recibió fue encantadora y muy servicial, en todo momento estuvieron atentos a posibles dudas y tuvieron muchos detalles a la hora de aconsejaros, recibirnos y hospedarnos. Repetiría sin duda, fue una estancia muy agradable.
CarlesMarch 2017Musiałem szybko znaleźć nocleg na niespodziewaną noc w Krakowie, a Filip odpowiedział bardzo szybko i zaoferował dobrą cenę. Mieszkanie jest super zaprojektowane i wygodne, no i lokalizacja jest znakomita - szybko dotarłem do mieszkania, a także na dworzec następnego dnia rano. Z pewnością wrócę, bo Filip i Ada to świetni gospodarze i widać, że znają się na tym, co robią! :)
DawidFebruary 2017Perfect location. Great owners. Great communication. Everything was great and we enjoyed every minute in the apartment!
SimonFebruary 2017Staying at Filip' s place was great! He was very friendly, kind and he always replied really fast and to the point. The apartment was at great location and well communicated. We' d totally stay again at Filip' s :)
SylvanaMarch 2017I can just recommend this place, we had no problem with anything. The flat was really nice and clean. Filip's responded very fast and gave to us recommendations what to do in the beautiful city Krakow!
MartinFebruary 2017The apartment was the best choice for our trip to Krakow. You can walk to every part of the city easily. Near to the apartment you find different pubs, restaurants or bars and some supermarkets. Filip is a very friendly person and the communication was perfect all the time. Always again!
KristinaMarch 2017Typ pokoje
Celý dům/byt
Typ nemovitosti
She is nice and kind host, easy and quick in communication. The apartment is well located and cozy.
AmirJanuary 2017This is a wonderful apartment. The location couldn't have been better. We could walk everywhere. It was clean and check in was easy.
CassieFebruary 2017urocze i czyste mieszkanko niedaleko centrum Krakowa :)
MajaJanuary 2017Comfortable room in nice apartment, well located close to historical center of the city and main sights. Host Anna operatively will give you all information about arrival.
RomanJanuary 2017Great experience! The room was clean and comfortable, furnished with good taste. In the kitchen there was everything to cook and the bathroom was clean. Apartament's location is fantastic close to every point of interest in Krakow. Anna was very kind and helped us in every situation. Highly recommend this place and Anna!!!
PatrizioJanuary 2017A nice place for having a nice time
LivioJanuary 2017Place clean and comfortable, exactly as on the pictures:) The host was not there but the communication was easy and we received all the necessary information to get there.
JustynaJanuary 2017Excellent localization - 10 min walking distance to Old Town; mini markets and nice restaurants around; walking distance (or quick tram journey) to Central Train Station. The room is cozy, comfortable, quiet. The whole structure is great. Anna is very easy to communicate and the place is so nice I wanna live there :)
ThaísFebruary 2017Typ pokoje
Soukromý pokoj
Typ nemovitosti
Mohu vřele doporučit. Skvělá lokalita, krásný byt, super komunikace s hostitelem. Děkujeme!!!
LuciaMarch 2015I cant recommend Jamie's apartment enough. Jamie went above and beyond to be as attentive and accommodating as possible, from restaurant recommendations to arranging a taxi to collect me on departure day. The apartment was super clean, and it was the smaller touches that I appreciated like the extra banket, bathroom essentials and the artistic feel of the apartment. Best location as well, easy to get around by foot and close to public transport. Excellent choice. I cant thank you enough Jamie, my stay was amazing!!
SereenaJuly 2016Exelent host, beautiful and cozy apartment. Everything you could want for your stay in Kraków.
EwelinaMarch 2017Great stay at Jamie's apartment this weekend in Krakow! It's ideally placed to explore the Jewish district on foot and easy to get to the old town via tram. Also very quick and easy local train links to the salt mines from the small train station near the Schindler factory musuem! Jamie was very helpful prior to and during our stay and provided us with lots of useful info about the area which helped us to make the most of our stay. Apartment was very clean and spacious-the photos really don't do it justice! It was also lovely and warm in the flat which we weren't really expecting in the cold Polish winter! Jamie was also really helpful in terms of getting to the apartment from the airport and it wasn't an issue that we arrived late at night. We had a slight misunderstanding around check out times but Jamie was able to arrange for us to store our bags at a local restaurant so we could make the most of our final day exploring Krakow! I would definitely recommend a stay in Jamie's apartment!
MelissaDecember 2014Fantastic flat in great location, Jamie couldn't have been more helpful in making sure we had everything we needed.
MoragJune 2016We really felt at home in this cosy and functional flat and the corner shop right across the street was very convenient for food shopping. The neighborhood isn't very touristy (yet relatively close to the center), so you kind of feel like a local, living a life of your own in Krakow. This stay was very enjoyable and Jamie is a very caring host. Just go and try :)
MathildeOctober 2015From the outset Jamie was a great host, providing all the information that we needed and even going to the trouble of booking excursions for us toAuschwitz and the Salt Mine. The apartment was warm and cosy and we loved the location. There's easy access to buses and trams but walking into the centre of Krakow is a great way to get to know the city.
NikkiOctober 2015Great appartment in a great city. Very clean and stylish.
ronaldAugust 2014Typ pokoje
Celý dům/byt
Typ nemovitosti
Perfect place to stay in Kraków.
DorotaOctober 2016Superrr!!! :) jakosc i klimat adekwatne do zdjec ❤❤❤
PawełFebruary 2017Me and my boyfriend had a great time at Monika's apartment. Great location very close to the main market Square and old town. The apartmant itself is on a very quiet residential street. The little cafe across the street is a must try - amazing dumplings! The apartment was very quirky, nicely decorated and clean. Monika was very quick to respond to any of our questions and gave lots of useful information before our arrival. I would recommend the apartment highly and would definitely stay again. Thanks for a lovely stay.
AmyOctober 2016This was my first experience in airbnb and I might say it was amazing. The location is very close to Stare Miasto, and also you only walk a few blocks to get the to the Train Station. The building is beautiful and the street is very safe to walk, you will need to climb more stairs than you expect, but it is all worthy. The loft is exclusive for you, you dont share bathroom, kitchen or anything. The two beds are very very comfortable, the place is unbelievably clean, equiped and cozy. You will get more than you expect and the price is more than fare.
AleOctober 2016This is the BEST place to stay when visiting beautiful Krakow! It's fun, funky and functional. The apartment is beautifully equipped, with well thought out lighting, loads of sockets and great wifi. The location of the apartment is perfect - minutes walk from the old town. Communication with Monika was very prompt and full of useful information. Directions to the apartment were really easy and straightforward. Without a shadow of a doubt we will definitely be coming to stay again. Many thanks Monika and Alex.
RachelOctober 2016This place is terrific: small but perfectly formed. Really nice touches like that fantastic bike above the bed and a spotless and powerful shower. Yes, there are a few stairs and yes there's some building work in the neighbouring block, but these are minor quibbles in what is a fantastic place to anchor your visit to the city. Not only are you a few minutes walk from the main square, but a there are tasty and inexpensive food options within a few feet from the main door (the 'sausage man' - wow!) and tours to Auschwitz leave a few metres away. I didn't meet Monika, but friendly Alex picked me up and dropped me off in a seamless and informative transfer service. Once in the apartment he took the time to go through a map and suggest things to see, do and taste. I heartily recommend this wonderful and stylish pad.
RobertOctober 2016Süßes kleines Apartment. Top Lage zwischen Altstadt und Ausgehviertel. Gutes Preis-Leistungs-Verhältnis. Sehr zufrieden.
RobertSeptember 2016Tha apartment is very centrally located , comfortable and great design It has everything i needed, i wish i would have stayed longer Easy instructions and all was explained I thank you for letting me stay at your place last minute
RaSeptember 2016Typ pokoje
Celý dům/byt
Typ nemovitosti
Joanna's apartment exceeded our expectations. It was immaculately clean and the decor was beautiful. It was perfectly placed to be able to walk everywhere around Krakow. What was really amazing, however, was how accomodating Joanna was. Our flight didn't arrive until 23:30 but even at that time she was waiting to meet and greet us and made sure we were settled before she left. A perfect host and a perfect weekend!
AbbiFebruary 2017Great apartment and location. Joanna is very kind and helpfull. We enjoyed our stay!
MariekeDecember 2016This air B n B is without a doubt one of the best I have ever stayed in. As my partner said the pictures really don't do it justice. It is clean, welcoming, comfortable and huge. The host was very accommodating and informative on arrival and very quick as responding to messages. Even booking our taxi to the station for us. Overall this made out experience in Kraków even better. Would highly recommend!
AlexAugust 2016Despite arriving in Krakow around midnight after a very late flight, Joanna welcomed me at her apartment. Joanna is very kind and helpful and was easy to contact. The newly renovated flat is beautiful with high ceilings and parquet floors and fabulous views of Wawel castle. It is located within easy walking distance of the old city- Stare Miasto and the Jewish quarter in Kazimierz. There are also grocery shops and cafes just out the door as well as anything else you might need. A great place to stay in Krakow!
NickJuly 2016Piękne mieszkanie. Czysto i schludnie, świeżo wyremontowane. Miłym zaskoczeniem było wyposażenie, wybór pysznych herbat i kawy. Właściciele nie zapomnieli o soli i cukrze, których zazwyczaj się nie ma w walizce jak się wpada gdzieś na weekend :) Jak do tego dodasz świetną lokalizacje 10 min piechotą od Wawelu to na prawdę nie pozostaje nic jak tylko zarekomendować pobyt u Joanny.
MartaOctober 2016Amazing apartment in an amazing location. Couldn't have asked for anything more really. Very close to the Jewish district and only a 5 or so minute walk to the old town. Joanna was a lovely host and gave us some good information when we arrived about what areas are best to explore. Will definitely look to stay here again next time we visit Krakow.
AdamNovember 2016Beautiful apartment in great location. Joanna is really friendly, welcoming and made everything really easy. It was a wonderful weekend. Thanks Joanna!
ilonaSeptember 2016Great place !! I cannot even describe how sad I was leaving that apartment. Great location 5 minutes walk away from Kazimierz, 10 minutes walk from Main Square !! Super cosy and charming apartment with amazing host Joanna who will as a real Concierge give directions and tips about the city !! The best Airbnb I have ever stayed !! Really top class !
MaciejOctober 2016Typ pokoje
Celý dům/byt
Typ nemovitosti
It was really nice to be hosted in Monika&Hubert's place. This is a fantastic place to stay in. Convenient to get to from the airport using public transit, and great location only about a 10 minute walk to the main square. Accommodation was clean and quiet, with modern finishing. Highly recommend this place. Super clean apartment with everything you need. Thank you so much!! :)
AnnaFebruary 2017Beautiful flat (decoration, space, really perfect for two persons) with lot of practical equipments. We lacked nothing, everything was there. The place is very quite and close to the Old Town. Amazing stay in the Monika&Hubert's flat, thank you !
CeliaFebruary 2017Cosy flat but enough room to move around comfortably. Very quiet. Close to local shops and only 10-20 minute walks from Old Town, the main square and train/bus station. Highly recommend
TaraFebruary 2017We are very pleased with our stay in Monika&Hubert's apartment. It looks exactly the same as in the photos and is well equipped, there are all the things you may need. The biggest advantage is that it is located in thereabouts of the city centre. Monika and Hubert were also very helpful and we could easily contact them with any problem. It is a very good place to stay. :D
Gabriela January 2017Monika&Hubert are kind and sympathetic. They provided me wonderful place to stay in Krakow. Everything was perfect. Thank you so much one more time :)
KristinaJanuary 2017It is a nice place to stay in Kraków, is right in the middle of the city center ( old town and kazimirz). Good access to the night life and supermarket is just few steps away, in the apartment you will find everything you need.
MaryMarch 2017The place is very nice and worth every penny. We stayed here for 3 days. It is located up to 10 minutes by foot to the Rynok Square and close to the main train station. We mainly walked around the city, besides using trams to get to museums. Huge advantage of this apartment is the supermarket and outdoor market right on the corner. The hosts were very communicative. We met Hubert exactly on time, although it was his working time. I'd strongly recommend staying in this apartment.
JulianaMarch 2017Very good location. Walking distance to city center and main touristic attractions. Totally recommended
MariusFebruary 2017Typ pokoje
Celý dům/byt
Typ nemovitosti
Oh what a fantastic apartment this was! All top class amenities. We think we got a lot more than what we expected. The building itself looks very modern. There is a bus stop right in front of the building (we never really needed public transport to explore old town. but we needed it to reach airport and the train station). Our hosts made sure that every little detail is taken care off (for example, even the pencils were sharpened and kept ready for us!) Kitchen had adequate supplies (coffee, tea, sugar, salt, pepper etc). The apartment looks exactly as described.
MadhumithaMarch 2016Dina and Mirek have been great hosts! Dina even took me fom the train station because she was around when I arrived and showed me the apartment. The flat was fully equipped, everything as seen in the pictures and as described. It is an amazing flat, spacious and very well designed, my parents and me felt very comfortable. Also there is a map with recommendations for restaurants and places to go provided- we tried nearly every place and every single one was worth it! Thank you very much for this awesome experience :)
MaikeMay 2016Apartment location is just perfect. 5 minutes walking distance from main square. Dina and Mirek have prepared anything you might need including a lot of tourist information and maps. Apartment is very well designed and furnished! Recommended 100%
JesusSeptember 2016Dina and Mirek's apartment is really lovely, it is spotlessly clean , stylish and modern. The location is excellent so near the heart of the old town and its attractions . Maps , guide books etc are provided in the flat and even some umbrellas !! Communication before and during our stay was smooth and efficient . Thankyou Dina and Mirek.
carolynNovember 2016If you love good design and short ways into the city: that is the place to be! Wonderful ideas together with great personal atmosphere. We loved our time in Dina and Mireks cosy-stylish apartment. Everything you could wish was there. Thanks for being so nice!
SilkeDecember 2016It was our first Airbnb experience and it seems to us that we got the jackpot. The apartment was great. Just the perfect size for the two of us and stylish decorated. The apartment was fully equipped but unfortunately we were not able to take advantage of it since we were out all day. Just behind the university the apartment was an ideal starting point for all our activities in Kraków. There is absolutely nothing to complain about our stay maybe with the exception of the elevator. The door was opened with a crazy signal tone. Awful
UweMay 2016Dina and Mirek's apartment is absolutely beautiful. Modern, clean and well decorated. Located perfectly for us, a short walk from the main square and wawel castle. Dina and mirek were extremely helpful our entire stay, offering their personal recommendations for krakow and answering any questions we had. Check in was super easy (I worried it would be difficult) everything exceeded our expectations and we would return here in a heartbeat. Absolutely perfect. Krakow is a wonderful city! Thanks again D&M!
NikkiMarch 2017This apartment is INCREDIBLE and the best airbnb we have ever stayed in! The location is perfect and the easy check in/out is a huge bonus so thank you! Can i also say as we appreciated everything being so CLEAN you can tell the hosts put in a lot of effort and it shows so thank you so much we would love to come back! The location is ideal, it is a 15 zloty ride to the train station, and can easily walk into the old town for some amazing polish cuisine. The apartment is well heated and the interior design is next to none! A true home away from home and perfect for our visit to Krakow in order to see Auschwitz. Thanks again D&M! Kind regards, Keyorra and Shaun
shaunNovember 2016Typ pokoje
Celý dům/byt
Typ nemovitosti
The apartment is very cozy and is close to the center (you can get the center by walking around 7 minutes). The bed clothes weren't very clean!
GiacomoJanuary 2017Polecam gorąco to miejsce. Wybraliśmy się z dziewczyną do Krakowa, i szukaliśmy czegoś w tym rodzaju. Apartament wysokiej jakości, internet, TV i co najważniejsze kilka minut do głównego rynku Krakowa, wszystko w zasięgu ręki.. Również bardzo dobry kontakt z osobą wynajmującą, nie było żadnego problemu jak spóźniliśmy się w dzień przyjazdu, odpowiedź na wiadomości w ciągu kilka minut, polecam naprawdę to miejsce :)))
KrzysztofOctober 2016Wszystko zgodne z opisem, wspaniale miejsce i dokonały kontakt z Gospodarzem. Polecam
SebastianNovember 2016The place and location was amazing would definitely rev omen staying here it was a pleasure :D
CatherineSeptember 2016We had a nice staying in this room! It was very clean and equipped with everything that you would eventually need for a comfortable staying. Also is close to the centre and the owners were very kind and waited until late night to do our check in on Friday since we were traveling from the Czech Republic. Only downside the room is -1 floor and you don't really have a view outside.
ElenaSeptember 2016Pani Katarzyna była bardzo pomocna podczas przyjazdu. Czekała już na nas w apartamencie. Wszystko pozostałe również było w porządku. Lokalizacja super.
PawełNovember 2016Polecam ten apartament na spędzenie miło czasu ;)
KlaudiaFebruary 2017Wir waren drei Tage in dem Apartment es ist nur zum empfehlen. Denn in dem Apartment verbringt man gerne Zeit da es liebevoll gestaltet ist. Katzyna war eine tolle Gastgeberin und hat ihre Hilfe angeboten.
MalgorzataSeptember 2016Typ pokoje
Celý dům/byt
Typ nemovitosti
Genialnie położony apartament dla miłośników Kazimierza i jego klezmerskiej atmosfery. Bezproblemowy kontakt z gospodarzem lokalu, czyli Natalią, która pomocne informacje podaje od ręki lub w mailu/sms. Sam apartament dokładnie tak jak w opisie i na załączonych zdjęciach. Idealny na pobyt o każdej porze roku. Świetny dla pary lub pary z dzieckiem.
KasiaJanuary 2016Absolutely stunning place, beautifully decorated and looked after. Wonderful and very helpful landlord too. Very convenient location, close to delicious food and lots of fun places. We will definitely come back again
PiotrMay 2016Fabulous time in a beautiful apartment
GrainneMay 2016Natalias apartment was clean, comfortable, and very well supplied. Decorated well with a washing machine, dish washer, and large balcony. Keys were on site which made it simple to gain entry.
LisaJune 2016Natalia's apartment was beautiful, especially the deck overlooking the courtyard. We loved cooking dinner and then sitting outside. Natalia herself was extremely helpful. She had great recommendations for where to go and what to do. Also, Natalia not only let us check in early to drop off our stuff, but was very kind in letting us use her storage facility to leave our things for a few hours before our train when checking out. Both Natalia and her apartment were fantastic. Exactly what we were looking for and exactly where we were looking for it.
JessicaJune 2016Nice little apartment on a great location. Located in center of fun part of Krakow, old Jewish part. Restaurants and bars are literally few minutes away. Old town is some ten minutes away by foot. Apartment feels very cozy, has all we needed for a four days stay. It is brand new and the terrace is nice addition. Natalia was a very polite host. To summarize, we can definitely recommend it.
NevenaJanuary 2016Lovely flat in a fantastic location. Lots of bars and restaurants close to the flat, with the flat being close to everything the city has to offer. Great host who was very helpful. 100% would return.
NatalieApril 2016The communication was excellent, we had no difficulties finding the apartment. Everything was very tidy and clean. The recommendations for local restaurants were great as were people of Krakow. We had a great time and would highly recommend a stay here.
BrianMarch 2017Typ pokoje
Celý dům/byt
Typ nemovitosti
Прекрасная квартира. Все новое, свежее, чистое. Очень заботливые хозяева. Чай, кофе, какао и сладкий сюрприз ждали нас в квартире. Удобное месторасположения. Все в пешей доступности. Много кафе и ресторанов поблизости. Окна выходят во внутренний двор, поэтому в квартире тихо. Находится на 3 этаже без лифта, но для нас это не было проблемой.
Mariya VlJuly 2016Staying at Aga and Simons place was absolutely perfect. They were great hosts - organising a cab from the airport for us and really informative about the city.
LouiseAugust 2016My first time in Krackow with my girlfriend and we couldn't have enjoyed it more what a great city. And agas apartment is right in the middle of it all in the Jewish quarter her apartment has everything you need and is very modern . And aga is always contactable if you have any questions I would definitely come back and stay again
AndreOctober 2016Simon and Aga have been really wonderful hosts! I definetely would like to come back to meet these two very kind and generous people. The flat is very beautiful and clean. Wonderful experience!
AlexJuly 2016Agnieszka and Simon were very welcoming and helpful. The apartment itself was clean and finished to a high standard. Will definitely stay here again next time I'll be visiting, highly recommended!
DamianOctober 2016En nyrenoverad och fräsch lägenhet med bra läge mitt i Kazimierz men ändå lugnt och tyst.
MariaAugust 2016The whole experience with Agnieszka and het boyfriend was really great. She was very careful since the very beginning of our trip. She wondered where and what time we arrived and she provided us with very detailed information how to get to her apartment with many great tips of local bistros, restaurants, pubs etc. She was also reachable and very helpful during the whole stay, always responded very quickly. We simply fell in love with Krakow and Agnieszka apartment gets a huge credit for that. The apartment is located right at the center of the best street ever - Jozefa, in beautiful district of Kazimier. The street is reachable from every single corner of Krakow downtown, very easy to access and it´s full of very cool bistros, restaurant, shops etc. The apartment looks just like on the pictures, very cozy and fully renovated. I would definitely come back again and thank you Agnieszka for such a lovely stay.
KláraSeptember 2016We had an excellent stay! The apartment is very beautiful and modern. The location is great as well, we mostly just traveled around the city on foot. Many good resturants and bars nearby :) Would definetely recommend!
MarinJanuary 2017Typ pokoje
Celý dům/byt
Typ nemovitosti
Hela was a fantastic host to us in Kraków! We arrived earlier than the check in time but she allowed us to leave our bags in the apartment so we could begin exploring the city. She was helpful with suggesting places to eat and sights to see. The apartment was very clean and a great size. It was also in a nice quiet location right by the river. Easy to walk to everything--we never used public transportation or cars except to get from the airport and to the train station. Hela and her husband even arranged a taxi to pick us up to go to the train station! Definitely recommend for anyone staying in Kraków.
MarcAndMelissaJune 2016Our stay with Hela was a lovely experience! The flat was a quaint modern and clean space where we felt very much at home. Hela's warm personality and friendly advice was a big help with sightseeing and the general lay of the land. If you fancy a wonder nearby, there are some awesome places to visit on the ground floor of the apartment building, which also have great food and drink. We would definitely recommend her flat to anyone wanting to stay in Kraków!
ShelleySeptember 2015What a fantastic break away! We were greeted at Hela's place after really great communication. We went up to the apartment which was immaculate and had everything we needed and more. The kitchen is well equipped and the living space is really comfortable. The bedroom is lovely with a very comfortable bed and big windows to open up onto the balcony. The bathroom, again, is perfect with a brilliant shower and all towels provided. Everything is so clean. I especially loved all the artwork on the walls! Some really interesting stuff. The apartment itself was in the best location. A 5 minute walk to the old Jewish quarter where there's some great restaurants which were recommended to us by our host. It is also only a 20-30 minute walk to the main square in the centre. I strongly recommend staying out of the centre though as you see so much more of Kraków. This apartment is in a quiet location but there are a few bars and restaurants right next to the apartment block which are perfect for a pre dinner or post dinner drink. We would definitely come back to Kraków and definitely rebook with Hela! We didn't want to leave!! The host was also great with recommending where to book tourist trips/visits to places like the salt mines and auschwitz. If your want to visit Kraków- this is the perfect apartment to stay in! Thanks so much!
OliviaApril 2016Nous avons passé quelques jours à Cracovie, l'appartement est vraiment spacieux, très propre et correspond totalement aux photos et la réalité est encore meilleure. Nous nous sentons vraiment chez nous, tout est à disposition, quelques bonnes adresses nous sont fournies, ainsi que des plans de la ville et tous ce qu'on peut y faire. L'appartement est situé près de la Vistule que l'on a juste à traversé pour se retrouver au quartier juif, il est également pas loin de la fabrique de Shindler. Nous n'avons pas retrouvé notre téléphone en partant de l'appartement mais c'est quand on cherche quelque chose qu'on ne le trouve souvent pas surtout quand on est pressé par le temps. Le téléphone a été retrouvé et va nous être renvoyé. Notre hôte est vraiment super, merci de nous avoir aussi bien accueillit.
MathieuMay 2016We had lovely stay in Hela's flat. It was a very modern.beautiful flat with everything we could possibly need. It was in a very nice area close to all transport. It could not be improved upon. Perfect!.
MaureenSeptember 2016Great apartment, brilliant location (close to Shindler's factory, 5 min walk from the Jewish quarter where all the best bars and restaurants are. Beautifully furnished, everything you could possibly need and more. Also a great host, very easy meeting and leaving the apartment. Would happily stay again! :)
LewisNovember 2015Hela was a very warm and friendly in her welcome. The apartment was modern and for us well situated. We would return to the apartment if we returned to Krakow.
AnnyJuly 2015The apartment is perfectly located, spotless, well furnished and brand new. A wonderful place for discovering Krakow! Hela was flexible with our check-in and check-out time. Dziękujemy bardzo!
ElenaJuly 2015Typ pokoje
Celý dům/byt
Typ nemovitosti
Mieszkanie bardzo czyste w świetnej lokalizacji. Wszędzie było blisko. Ponadto profesionalizm gospodarza jest na bardzo wysokim poziomie. Jeśli ktoś się zastanawia nad tym mieszkaniem to polecam z czystym sercem bo naprawdę warto :)
SebastianFebruary 2017Studio było urządzone praktycznie i z pomysłem, bardzo przytulnie i miło. Mieszkanie zgadzało się z opisem na stronie i tym co można było zobaczyć na zdjęciach. Lokalizacja bardzo dobra, serce Kazimierza, puby, restauracje, sklepy, rzut beretem na Wawel czy starówkę. Właściciele to bardzo miła, bezproblemowa i kulturalna para. Mieszkanie godne polecenia każdemu kto lubi nocne życie a przy okazji chce mieć blisko do atrakcji turystycznych. Na pewno skorzystam z niego podczas kolejnej wizyty w Krakowie :)
KarinkaOctober 2016Its the perfect little place to stay, quiet but have all the good restaurants and cafes just around the corner. Its small but has everything you need. Me and my 14 year old son thouroghly enjoyed our Kraków visit.
HelenFebruary 2017Great flat, great lokation. Recommended
RafMarch 2017Okolica piękna, dobra lokalizacja. Samo studio bardzo czyste i pomysłowo urządzone. Gospodarz pomocny i uprzejmy, wszystko jak należy. Zdecydowanie polecam.
AgataOctober 2016Wspaniałe miejsce, piękne, małe mieszkanko, ale bardzo czyste i niezwykle zmyślnie urządzone! Bardzo blisko do Dworca, w świetnie skomunikowanym miejscu. Rewelacja :)
AgnieszkaOctober 2016We stayed at Tomasz's appartment a few days and it was perfect for us ! It is well located, there is everything close by (groceries and restaurants) and the Rynek is about 15 min by walk. Also, Tomasz was always available when we had questions. We'll definetely stay there again when we'll visit Krakow next time :)
GavinFebruary 2017От апартаментов Томаша осталось самое приятное впечатление: очень чисто, уютно, я впечатлена аурой места - старинный дом, прекрасный дворик, собственный выход. Отдельно хотелось бы сказать о районе Казимерц - старинный, "Еврейский", с сотней достопримечательностей, барчиков и ресторанов на каждом шагу. И в пешей доступности от главных достопримечательностей Кракова. Я влюблена в это место и в город. Спасибо Томашу за гостеприимство, очень рекомендую!
YuliaDecember 2016Typ pokoje
Celý dům/byt
Typ nemovitosti
Все было здорово, и расположение, и условия, и цена, хозяин был рядом и при необходимости сразу приходил на помощь. Центр города, все рядом пешком, единственное неудобство - платная парковка в рабочий день, но тут не вина хозяина - центр города, ничего, нашел в километре бесплатную, был повод прогуляться.
OlegFebruary 2017Conrad was incredibly welcoming and helpful. Beautiful, comfortable apartment. Highly recommend.
MikeMarch 2017Rewelacyjna lokalizacja- można się zrelaksować spacerując wzdłuż rzeki zaraz obok apartamentu. 5 min piechotką do krakowskiego rynkowo-knajpowego życia :-) naprawdę polecam!
MarcinMarch 2017Typ pokoje
Celý dům/byt
Typ nemovitosti
Magdalena is very quick to respond any question and is a very helpful host. The apartment is in a great location, easy accessible by foot and car. She also made sure that we had everything and we could just enjoy our stay.
DominiqueJanuary 2017Magdalena's appartment is located near all sites, nearly everything is within walking distance and for all the rest she offers a bike. She gave us a warm welcome and clear instruction about the building & facilities. It was also very easy to communicate with Magdalena during and before our stay. The room was very clean and spacious. We really enjoyed our stay!
karlijnFebruary 2017Everything was perfect! The apartment was modern and clean, located close to the City Center and equipped with everything needed for a short stay. Magda is an excellent host, responds within minutes and made our stay in Cracow even more memorable.
JacobDecember 2016Fantastic place!
RafałFebruary 2017Everything was perfect. Magdalena was very helpful and the apartment was beautiful, just like in the pictures (or even better)! It was very clean and perfectly equipped, even the last tiny detail. The kitchen is very modern and easy to navigate, and the bathroom is cozy and very warm. The apartment has underfloor heating, which is really nice when outside temperatures are well below 0ºC. We had a lovely week, we plan to go back to Krakow soon, and we would definitely go back to this apartment.
BritaJanuary 2017Typ pokoje
Celý dům/byt
Typ nemovitosti
Všechno bylo naprosto perfektní. Darek na nás trpělivě čekal před domem, i když jsme měli trochu zpoždění, byl velice milý, přátelský, nápomocný a dal nám spoustu užitečných tipů. Ubytování zcela odpovídá popisu a zveřejněným fotkám, byt má velice originální design, je světlý, čistý, moderní, útulný a plně vybavený. Úžasná je hlavně vana uprostřed pokoje, která přesně zapadá do celkového vzhledu bytu a dotváří jeho originalitu. Ubytování se navíc nachází na perfektním místě v centru, ze kterého se snadno dostanete pěšky jak na Hlavní náměstí, tak i do židovské čtvrti. Pokud někdy znovu navštívíme Krakow, tak se rádi vrátíme právě na toto místo. :)
LindaDecember 2015Poloha apartmánu mezi hlavním náměstím a Kaziměří byla fantastická. Všude se dalo dojít pohodlně pěšky. Apartmán čistý, vybavení dostačující. Dariusz nám dal užitečné tipy, kde se dobře najíst. Vyzkoušejte pirohy hned naproti apartmánu! Za návštěvu stojí muzeum Fabrika Schindlera nebo krakovské podzemí. Komunikace byla bez problémů. Doporučujeme!
PetraJune 2016Serdecznie polecam skorzystanie z oferty Pana Dariusza. Apartament bardzo przyjemny, wygodne łóżko, urządzony z gustem, dodatkowym atutem oferty jest bardzo dobra lokalizacja. Przesympatyczny gospodarz, służący pomocą. Pan Dariusz doradził na temat atrakcji turystycznych, co warto zobaczyć a także o miejscach gdzie można smacznie zjeść. Na pewno wrócimy jeszcze do Krakowa i do wspaniałego gospodarza P. Dariusza.
MartynaApril 2016Świetny gospodarz, wszystko zgodnie z opisem, pełna kultura , a nawet gotowość na ustępstwa. Dzięki uprzejmości Pana Dariusza mogliśmy zostać o 2h dłużej niż przewidywała to "hotelowa" doba. Dziękujemy i wszystkim polecamy!
BartłomiejJanuary 2015Mój pobyt w Krakowie był po prostu idealny, złożyło się wszystko: piękna pogoda, cudowne oczekiwanie Świąt bożego narodzenia i najważniejsze pobyt w uroczych apartamentach Lili w Centrum Krakowa. Mieszkanie jest świetna, stylowa, oryginalna, niezwykła. Z mieszkania po prostu nie chciało się wychodzić na spacer. Z przyjemnością pozostał tam jeszcze przez jakiś czas!!!! Silnym wrażeniem Krakowa stał nocny świąteczny koncert w kościele (informacje o nim mi łaskawie udzielił Pan Dariusz). Dziękuję bardzo. Z przyjemnością polecam i gospodarza i apartamenty do wszystkich swoich znajomych.
ЕвгенияDecember 2015Kontakt szybki i bardzo miły! Apartament zgodny z opisem i tym, co widzimy na zdjęciach. Bardzo blisko do Rynku, świetna okolica. Szczerze polecam!
PawełApril 2015Super miejsce na weekendowy lub kilkudniowy wyjazd do Krakowa! Apartament jest taki jak na zdjęciach i ma swój niezapomniany urok. Do rynku jest stosunkowo blisko i również blisko do dzielnicy Kazimierz. Dariusz świetnie nas przyjął i podrzucił kilka świetnych pomysłów i miejsc, które warto odwiedzić! Polecamy to miejsce wszystkim znajomym!
PawelJuly 2015A nice apartment in the city center, right between the 2 main districts: Old Town and Kazimierz. Great stay!
KyryloDecember 2015Typ pokoje
Celý dům/byt
Typ nemovitosti
Gorąco polecam to miejsce na Kazimierzu, wspaniały klimat, opiekuńczy przemiły gospodarz, zainteresowany swoimi gośćmi, czekał na nas o umówionej godzinie, na powitanie przygotował butelkę pysznego wina oraz owoce, wszystko nam pokazał i wyjaśnił, w czasie kilku dni naszego pobytu dzwonił kilkakrotnie. Niezwykle udany wyjazd, mieszkanie dokładnie takie, jak na zdjęciach, bardzo dobrze wyposażona kuchnia, duży telewizor, czyściutka łazienka. POLECAM!!!
MagdalenaNovember 2016We had the best time in Poland. Jays apartment was perfect. Beautifully decorated, super modern and clean. Best location, we loved being able to walk out to dinner/bars. Old Jewish quarter is definitely the hip and happening area. Communication was great, they were super accommodating. Help recommend places to go. Highly recommend this apartment.
ElizaSeptember 2016First, the apartment: Jay and Mariola's place ticks all the boxes: pretty, comfortable, well located... You name it! You'll find yourself in a calm, residential area just a stone's throw from the Vistula river, but also from Kazimierz (the old Jewish neighbourhood filled with small cafes and restaurants). There's a tram stop just round the corner and you can take any tram to get to the Old Town. Secondly—and most importantly—the experience! The contact was superb; Jay met us just outside the building and showed us everything we might need in the apartment, as well as gave us recommendations about Kraków. It felt like he was always available to help—he even reached out during our stay to make sure all is well, which was really nice! All in all, it was one of the best (if not THE best!) Airbnb experiences and we thoroughly recommend staying at Jay and Mariola's apartment! :)
AniaOctober 2016Jay and Mariola were great hosts! Before our arrival, they provided us with very detailed options for getting to their apartment. Jay met us at the apartment exactly when we arrived and gave us a very warm welcome, complete with everything we would need to know about Krakow! The apartment was perfect for the two of us and within walking distance to everything (a 30 min walk at the most to anything). We would definitely stay here again!
JessicaSeptember 2016Well, what can we say?! We stayed in Jay and Mariola's apartment for one week over New Year. Beautiful, well-equipped apartment in a great location, only a short walk to the centre of Kazimierz and everything that has to offer. The old town is a short, lovely walk (either down the river, or down the main street) with plenty of shops along the way for supplies. As hosts, Jay and Mariola were kind, helpful and checked in with us regularly, suggesting recommendations for places to visit, eat etc. This is the perfect base for your stay in Kraków, and we will definitely be returning!
SarahJanuary 2017Mariola & Jay are great hosts, very kind & caring about their guests wellbeing - thank you guys. Without any hesitation we would highly recommend their lovely apartment! Really enjoyed our stay & we will be back!
IlonaDecember 2016Este apartamento es tal y como se muestra, coqueto y acogedor con una localización fantástica. Jay es muy amable y comunicativo, accesible y colaborador y absolutamente recomendable. Si volviéramos a Cracovia su apartamento sería nuestra primera opción.
VictorOctober 2016Super pobyt w super mieszkaniu ! Jay przywital nas bardzo przyjaznie ! Idealne miejsce pod wzgledem lokalizacji , cichutko, spokojnie ... Wisla w zasiegu reki , serce Kazimierza 5 min od mieszkania . Było nam bardzo wygodnie , niczego w mieszkaniu nie brakuje, jest super wyposażone, czyste, ladne ! Napewno jeszcze kiedyś tam wrócimy !
Iza & RaphNovember 2016Typ pokoje
Celý dům/byt
Typ nemovitosti
Great place to stay
PavloJanuary 2017Great location and communication between me and my host. The place was clean and neat but cold and dark. It was very cold in Krakow but I couldn't warm up because the place was cold too. It's a good value overall.
MikeFebruary 2016Studio cosy, très bien situé , très proche du centre ! Katarzyna s'est montré très disponible :) très bon séjour
ophélieOctober 2015Apartamento bem localizado, bem próximo à cidade velha de Cracóvia. Limpo, espaçoso e Katarzyna sempre atenciosa.
ArturApril 2016Apartamento correcto en buena ubicación. Anfitriona muy atenta a dudas. A mejorar la limpieza y estado de algunos elementos del apartamento, no funcionaban o estaban rotos
DanielMay 2016Location is great, just under the Wawel castle, very close to city center. The appartment is charming, just as it looks on the pics, has everything one needs - iron, hair dryer, dishes, coffee machine. Katarzyna was out of town for holidays but assisted us with every question we had, was very friendly and helpful! We enjoyed our stay in this place and hope to return some day for more time in Krakow! Thank you Kasia!
KylaApril 2016Great location within walking distance from the city center and Wawel castle... close to transit... cozy apartment wifi could be faster for video calls but no further complaints there... Missing siad and shampoo for shower it was too late when I realized like. I had to use liquid hand soap... great communication great host
KajMay 2016Katazyna was a wonderful host during my short trip to Krakow. My friend and I felt like home and the apartment was very clean and close to the main town area. I would recommend staying in her apartment for your next trip to Krakow.
VeronicaJune 2016Typ pokoje
Celý dům/byt
Typ nemovitosti


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What is Santa's Party with Québec Pub Crawl?Santa is done distributing gifts all over the world. Disguise in Santa or Mrs. Claus and make new friends from bar to bar while partying and enjoying the city at night. Did you know Québec Pub Crawl is actually Québec's #1 nightlife experience? And that the Crawl has been run only by locals for 3 years now! Come discover the whole vibe !
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Women's Karhu Strong Fulcrum RideItem #KRW103
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Charles J. St. Angelo, 92, Bristol
Posted 3/14/17
Charles J. "Charlie" St. Angelo, 92, passed away Sunday, March 12, 2017. He was the husband of the late Mary E. (Gomes) St. Angelo, to whom he was married 54 years before her passing in …
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Wednesday, October 24, 2007
scaredy crap
the past few days i've played with candy. here is a photo of some children of the (candy) corn.
and a semi edible interpretation of a lilo hair accessory.
i also took a photo of my favorite skull. see?
but all i really wanted to do was laugh at the pumpkins.
(please tell me that i'm not the only person who's heard that old ween song.)
you wanna' know what's really scary? sideshow bob is running for snohomish county auditor!
i would totally vote for him.
anyway, the scariest thing by far this week occurred when i ate this.
i have to tell you, despite what other people have claimed, i did not find the elvis reese's to be tasty. scary in that "what the fuck did i just eat?!? fuck me, why is there fake banana in this!?!" kind of way? yes. but tasty? no.
ok, *insert term of endearment here*, my fried brain wants me to watch this or this over and over again. they make us happy, our preciouses.
6 comments:
- The Mincing Mockingbird said...
Your blog rocks.
Were you in the Human Pixel project? - 10:50 PM
- r4kk4 said...
thanks!! :D!
i was! i did the "8bit evil" guys. i loved your birds in the humal pixel project!! - 10:29 AM
I love Elvis; but I, too, think this would NOT be tasty.
- r4kk4 said...
it was like they packaged some of elvis' 30 year old soul inside. seriously gross.
- Shannon said...
I have to agree with ya, the banana sucks. I've been avoiding it for weeks, then I just had to breakdown and try it. Huge disappointment! Who knew Elvis tasted so damn bad. I should have known that anything edible with Elvis on the wrapping could never be good.
- r4kk4 said...
the sad thing is that i LIKE fake banana even better than real banana. (well, in candy, anyway.)
elvis always messes things up. i say this after having lived in memphis on and off for seven years. ;D - 9:45 AM


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Camelot Motor Lodge is in the heart of Christchurch, walking distance from Hare Krishna Temple and Victoria Street. This 4-star motel is within close proximity of Southern Cross Hospital and St. Mary's Merivale.
Make yourself at home in one of the 34 guestrooms, featuring kitchenettes with refrigerators and microwaves. Digital programming and DVD players are provided for your entertainment, while complimentary wireless Internet access keeps you connected. Conveniences include desks and minibars, and housekeeping is provided daily.
Don't miss out on recreational opportunities including an outdoor pool and a spa tub. Additional amenities at this motel include complimentary wireless Internet access, tour/ticket assistance, and barbecue grills. If you're ready for some gaming fun, you can hop on the casino shuttle (surcharge).
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Featured amenities include a business center, complimentary newspapers in the lobby, and luggage storage. A shuttle from the hotel to the airport is provided for a surcharge (available on request), and free self parking is available onsite.
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Acute Leukemia Is The Commonest Malignancy In Children Biology Essay
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Acute leukemia (AL) is the commonest malignancy in children less than 15-years of age {{664 Anonymous 2010}}. Approximately 3000 new cases of AL occur annually in the United States, of which 80% are acute lymphoblastic leukemia (ALL). The five-year survival rates for childhood AL, and especially ALL has dramatically improved from 61% in 1975-1978 to 89% in 1999-2002 {{663 Smith,M.A. 2010; 655 Pulte,D. 2008; 563 Johnston,W.T. 2010; }}. The remarkable success story of pediatric ALL is attributed to the exponential increase in knowledge of the molecular mechanisms of the disease and the impact of well-designed clinical trials adapted to risk -stratified subgroups based on prognostic indicators, including evaluation of early response to the treatment (minimal residual disease detection). This has been accomplished by genomic studies employing a host of modern techniques, for example, conventional cytogenetics, fluorescent in-situ hybridization (FISH), DNA and gene expression arrays, and proteomics. Many of these methodologies have moved from the research bench to clinical molecular diagnostics allowing their routine use in the diagnosis, classification, prognostication, and follow-up of acute leukemia. In this chapter we discuss the clinical features of acute leukemia and describe the evolution of the modern classification of acute leukemia as it reflects a transition from morphological to molecular genetic approaches. The subsequent chapter on AL in this volume describes molecular techniques routinely used in the diagnosis and prognostication of acute leukemia.
Clinical Features
AL is the commonest childhood malignancy with an age-adjusted incidence of 44.3 per 1,000,000 persons (ALL 36.8; AML 7.5){{484 Linabery,A.M. 2008; 664 Anonymous 2010}}. ALL is four times as common as AML, and occurs more often in male rather than female children {{484 Linabery,A.M. 2008; 664 Anonymous 2010}}. Since 80% of all childhood AL is ALL, the major discussion will be devoted to ALL, especially precursor B-ALL (80-85% of ALL). The applications of genomic studies to precursor B-ALL are similarly relevant to precursor T-ALL and AML; features specific to the latter will be highlighted separately. AL of infancy is biologically and clinically different from that in older children. Unlike older children, ALL and AML occur with nearly equal frequency in infancy, and there is a female rather than male preponderance {{1431 Schlis,K.D 2009; }}. The infant AL very often have high white blood cell counts and presence of the t(4;11)(q21;q23) putting them in the clinically high-risk category with poor outcome.
Clinical symptoms of AL are related to replacement of normal hematopoietic cells in the bone marrow by the leukemic cells, and to organ infiltration by blasts. Fever, pallor, weakness, bleeding manifestations, and bone pains are the most common presenting symptoms {{746 Chessells,J.M. 2002}}. Nearly 40% of affected children complain of joint aches, presumably from leukemic infiltration of the joint capsule {{1432 Sinigaglia, R. 2008;}}. Massive organomegaly and central nervous system (CNS) involvement at presentation are characteristic of AL in infancy {{1431 Schlis,K.D 2009; }}.. Extramedullary solid tumor masses or chloromas are seen at presentation in a small number of patients, mostly AML with monocytic differentiation; orbits, paranasal sinuses, and skin are the usual sites for chloromas. Isolated testicular masses are more a feature of relapse than primary presentation in acute leukemia. Nearly 10% children, almost always with precursor T-lymphoblastic leukemia/lymphoma, present with a life-threatening tracheobronchial or cardiovascular compression syndrome due the leukemic infiltration of the thymus and other mediastinal structures, requiring prompt intervention by systemic corticosteroids, or local radiation {{1430 Silverman,L.B. 2009}}.
Diagnosis and Classification of AL
In addition to establishing the diagnosis, the aim of physicians and laboratorians is to stratify patients according to the risk for optimal management. Risk-stratification is determined by 1) clinical features at presentation (age, white cell count, sex (in some protocols)), 2) cytogenetics (or molecular abnormalities), and 3) response to treatment (minimal residual disease). Laboratory methods are directed towards the latter two.
Morphology, immunophenotyping, and cytogenetic analysis form the cornerstone of diagnosis and risk-stratification in acute leukemia. The white cell count is usually high; counts exceeding 50,000/µL denote high-risk and are seen in 20% of the children at presentation, more often in infants. About 10% children present with hyperleukocytosis (leucocyte count >100,000/ µL ){{1433 Majhail,N.S. 20041434 Lowe,E.J. 2005}}. Circulating blasts are present in the peripheral blood in most patients, even those with normal white cell counts, although about 1%, may have an aleukemic or pancytopenic presentation. Anemia and thrombocytopenia may be mild or critically low.
The diagnosis of AL based on cytomorphology and cytochemistry has undergone a drastic change in the last three decades. The initial French-American -British (FAB) classification of ALL {{68 Bennett,J.M. 1976 }} based on nuclear morphology (nuclear heterogeneity, contour, nucleoli), or the FAB classification for AML{{68 Bennett,J.M. 1976}} based on morphology, degree of maturation, and cytochemistry, are insufficient for prognostication and risk-stratification {{1317 Vardiman, J.W. 2009; 1318 Vardiman,J.W. 2002; 520 Brunning,R.D. 2003; }}. Still, morphological assessment is the first step towards diagnosis and guides subsequent investigation. In many instances, morphology provides a clue for the underlying genetic abnormality, for example blasts with cytoplasmic and nuclear vacuoles (Burkitt-like) are consistent with mature B-ALL and t(8;14), and abnormal heavily granulated promyelocytes are consistent with acute promyelocytic leukemia (APL) and t(15;17) (Figure 2-1A and 2-1B). Bone marrow evaluation is useful for diagnosis when the presentation is aleukemia or subleukemic. Bone marrow aspiration is however necessary in the initial estimation of cellularity and leukemic burden in order to obtain sample for karyotyping and molecular studies, to assess response to induction chemotherapy, and for predicting outcome based on early response to chemotherapy thereby predicting likelihood of relapse. Extensive necrosis in the bone marrow at presentation is not common {{1900 Invernizzi, R. 1995; 1901 Inoue, S. 2007; }}, but when necrosis is present it can make the morphological and immunophenotypic characterization very challenging.
The immunological classification of AL introduced in 1985 by the European Group on Immunological Classification of Leukemia (EGIL) was based on use of antigen panels for lineage determination and the hierarchical sequence of antigen expression by cells {{518 Bene,M.C. 1995 }}. The 2008 WHO classification system has proposed a simpler algorithm that relies on fewer markers for lineage determination and categorization as mixed phenotype acute leukemia (MPAL). Table 1 (adapted from the 2008 WHO classification), shows the critical antigens required for lineage delineation as myeloid, precursor B, precursor T-lymphoid, or MPAL.
B-Acute Lymphoblastic Leukemia
Based on the presence of antigens that reflect degree of differentiation, precursor B-ALL has been subclassified as early or pro-B-ALL (TdT+, CD10-, CD19+, CD22+/-), intermediate stage or common ALL with expression of CD10 (CALLA), and pre-B-ALL (positive for cytoplasmic immunoglobulin (cIg)). Historically, the immunophenotype was used to predict outcome in ALL, for example the better outcome in ALL with expression of CALLA (CD10), and worse outcomes in CALLA (-) ALL, or ALL with a cIg + phenotype {{1324 Crist,W.M. 1990}}. Correlation of simple and complex phenotypes determined by multiparameter flow cytometry (MFC) with genotypes is well described {{1438 Paietta,E. 20041437 De,J. 20071435 Hrusak,O. 20021436 Kozlov,I. 2005}}. Later studies demonstrated that the phenotypes, and hence the outcomes, were highly associated with specific chromosomal anomalies {{829 Borowitz,M.J. 1990; 1321 Pui, C.H. 1990; }}. A higher representation of hyperdiploidy (>50 chromosomes) in the CD10 (CALLA)+ pre-B ALL, and of t(4;11) in the CD10 (-) ALL {{1332 Pui,C.H. 1991; 1329 Pui,C.H. 1998; }} were correlated with the observed favorable and unfavorable outcomes in these phenotypes, respectively. Likewise the presumed unfavorable outcome associated with co-expression of myeloid antigens in newly diagnosed ALL could be ascribed to presence of the associated MLL (11q23) and BCR-ABL1 [t(9;22)] translocations {{690 Seegmiller,A.C. 2009; 719 Khalidi,H.S. 1999; 1326 Vitale,A. 2007; 1332 Pui,C.H. 1991; }}. The early reports on the unfavorable outcome in ALL expressing cIg {{1324 Crist,W.M. 1990}} found a high correlation with t(1;19)(q23;p13) translocation, 90-95% of which have this phenotype {{829 Borowitz,M.J. 1990; 1321 Pui, C.H. 1990}}. In subsequent studies several authors showed that with intensive chemotherapy programs the negative impact of t(1;19) could be offset {{1322 Raimondi,S.C. 1990; 1323 Pui,C.H. 1994; }}. More recently, gene expression studies (GEP) have validated specific immunophenotypes predictive for different leukemia subtypes {{ 763 Haferlach,T. 2010; 767 Buldini,B. 2010; 1901 Basso, G. 2007; }}. MFC can suggest the underlying genetic aberration and guide the choice of appropriate panels for FISH studies if conventional cytogenetics is non-contributory (Tables 2 and 3).
Genetic abnormalities
ALL is genetically heterogeneous. Multivariate analyses in several large clinical studies have clearly established that genetic abnormalities are the most important determinants of response to chemotherapy and outcome in ALL {{819 Sutcliffe,M.J. 2005;749 Schultz,K.R. 2007;732 Moorman,A.V. 2010;737 Moorman,A.V. 2007742 Moorman,A.V. 2003;553 Harrison,C.J. 2010;1285 Harrison,C.J. 2001;1302 Harrison,C.J. 2009;1302 Harrison,C.J. 2009;1291 Forestier,E. 2000;1291 Forestier,E. 2000;1188 Forestier,E. 2003;751 De Braekeleer,E. 2010}} . Their relevance is likely to increase as targeted therapies are introduced. The genetic abnormalities, which currently have the most significant impact on treatment and management are t(9;22)(q34;q11)/BCR-ABL1, t(4;11)(q21;q23)/MLL- AFF1, and near-haploid/low hypodiploidy that are poor prognostic markers, and to a lesser extent, t(12;21)(p13;q22)/ETV6- RUNX1 and high hyperdiploid that are favorable prognostic markers {{553 Harrison,C.J. 2010; 1303 Konn,Z.J. 2009; 737 Moorman,A.V. 2007; 732 Moorman,A.V. 2010; 1186 Harrison,C.J. 2010}} . The genetic abnormalities that are considered mandatory in the evaluation of ALL, and for which clinical testing is available, are shown in Table 2 along with their prognostic implication and the various genetic techniques for their determination. These and other novel genetic aberrations are discussed below.
Numerical chromosomal aberrations
The clinically significant numerical aberrations seen in ALL are high-hyperdiploidy (HeH) (51-65 chromosomes), near-haploidy (24-29 chromosomes), and near-diploidy (31-39 chromosomes) {{736 Moorman,A.V. 2007; 585 Kowalczyk,J.R. 2010; 585 Kowalczyk,J.R. 2010; 553 Harrison,C.J. 2010; 751 De Braekeleer,E. 2010 }}. HeH, which is present in 23-42% of newly diagnosed precursor B-ALL, results from gain of specific non-random chromosomes (4, 6, 10, 14, 17, 18, 20, 21, and X) and is grouped as those with 47to 50 or more than 50 chromosomes {{823 Ito,C. 1999; 819 Sutcliffe,M.J. 2005; 742 Moorman,A.V. 2003; }} . HeH with 51-65 chromosomes is considered a favorable risk factor when associated with other types of chromosomal gains, such as trisomy of chromosomes 4, 10, and 17 (Figure 2-2) {{742 Moorman,A.V. 2003; }} . HeH cells are more sensitive to apoptosis with certain drugs (especially methotrexate, mercaptopurine, and l-asparaginase) than non-hyperdiploid cells {{1284 Whitehead, V.M. 1998; }}. Low hypodiploidy, and near hypoploidy have a poorer outcome compared to near diploid chromosomes {{1067 Heerema,N.A. 1999; 965 Nachman,J.B. 2007; 1289 Harrison,C.J. 2005}}. Low hypodiplody often undergoes duplication, which can be misdiagnosed as hyperdiploidy; the distinction is crucial for prognostication. Analysis of metaphase chromosomes by G-banding is the gold standard and best method in the clinical laboratory to evaluate numerical abnormalities as it provides a global overview of the genome and a baseline to trace the evolution of the disease.
Common structural aberrations
t(9;22)(q34;q11)/BCR-ABL1 translocation/Ph+
The Philadelphia (Ph) chromosome results from the balanced translocation t(9;22)(q34;q11) and is the hallmark of chronic myelogenous leukemia (CML). Three to five percent of childhood and 25% of adult ALL have the Ph chromosome {{1895 Aricâ , M. 2010; }}. Until recently, the Ph+ ALL have been consistently considered as a very high risk group with dismal outcome {{734 Ribera,J.M. 2002; }}. Addition of specific tyrosine kinase inhibitors, such as imatinib to chemotherapy regimens have changed the traditional outlook of Ph+ ALL as a "hallmark high-risk" requiring stem cell transplantation {{749 Schultz,K.R. 2007}}, to one with a good outcome {{1440 Schultz, K.R. 2010; 1895 Aricâ , M. 2010; }}. There are two major forms of BCR-ABL1 translocations depending on the breakpoints on the BCR gene (Figure 2-3(A)). The translocation consistently involves exon 2 of the ABL gene, but occurs in different exons of the BCR gene. The fusion involving the major breakpoint region (MBR) between exons 12 and 13 or 13 and 14 leads to expression of an 8.5 kb transcript coding for a 210kD fusion protein (p210BCR-ABL1) that characterizes adult CML, and about 30% of ALL. In 70% of Ph+ ALL, the breakpoint in the BCR gene is in between alternate exon1 and exon 2 (minor breakpoint region/m-BR), resulting in a smaller 7.5 kb transcript coding for a 190 kD protein (p190 BCR-ABL1 ) {{1439 Verma, D. 2009; 1896 Westbrook,C.A. 1992; }}. Other less common fusions {{1441 Melo, J.V. 1997;}}, and co-expression of the p210BCR-ABL1 and p190 BCR-ABL1 encoding transcripts as a result of alternative splicing in the M-BR of BCR, have been reported {{1880 Lemes,A. 1999; 1887 Volpe,G. 2007; 1879 van Rhee,F. 1996; 1883 Solves,P. 1999; 1890 Saglio,G. 1996; 1888 Lichty,B.D. 1998; 1888 Lichty,B.D. 1998; 1875 Kunieda,Y. 1994; }} . rtPCR (reverse transcriptase polymerase chain reaction) and conventional cytogenetic analysis readily detect the BCR-ABL1 fusion transcript/t(9;22)(q34;q11); in those cases with a failed, cryptic, or normal karyotype result, FISH provides a reliable alternative method (Figures 2-3(B) and 2-3(C)){{1289 Harrison,C.J. 2005;}}. Dual-color, dual-fusion FISH probes have high specificity and can also detect associated deletions of derivative chromosome 9, and complex or variant translocations {{1308 Primo,D. 2003; 1367 Robinson,H.M. 2005; }}.
Chromosomal translocation between the C-terminal of MLL gene at chromosome band 11q23 and AF4 on chromosome 4p13 results in the MLL- AF4 fusion (Figure 2-4(A) and 2-4(B)). t(4;11) demonstrates an age-dependent distribution- it is observed in 50-70% of infant ALL and roughly 5% of pediatric and adult cases. Clinically it is associated with high-risk ALL. Most patients have a CD10-, CD19+ (pro-B) profile with co-expression of myeloid antigens. Breakpoints on MLL gene are dispersed over a wide region, and clustered differently in infant versus other patients. To date, 104 translocation partners are known of which 64 have been molecularly characterized {{1444 Meyer,C. 2009; }}. The biological behavior and distribution of the different MLL translocations depends on the translocation partner, for example t(4;11) AF4/MLL is almost exclusively seen in infants and has the worst outcome; t(11;19) ENL/MLL {{1025 Jansen,M.W. 2005}} occurs in both ALL and AML , and has a poor prognosis; whereas t(9;11) AF9/MLL present in AML has a favorable prognosis. At present, the combination of cytogenetic and molecular techniques, including FISH, specific rtPCR and genomic PCR methods, seems to be the best approach to identify MLL rearrangements, notably unusual, complex and cryptic chromosomal rearrangements IS THIS COPIED AND PASTED DIRECTLY FROM JOURNAL??? {{1442 De Braekeleer, E. 2010;1025 Jansen,M.W. 2005; }}. A systematic evaluation starting with a commercially available MLL split signal FISH probe is recommended for screening as a first step. Should an abnormality be detected, karyotype or genomic PCR-based molecular methods can be used to further delineate the recombination {{1442 De Braekeleer, E. 2010}}.
t(1;19)(q23;p13)/TCF3-PBX1 (E2/PBX1)
t(1;19) is detected in 5-6% of childhood ALL and can occur as a balanced or an unbalanced translocation. It occurs almost exclusively in pre-B ALL expressing cytoplasmic ï (CD10+, CD19+, cIg+) {{829 Borowitz,M.J. 1990; 1321 Pui, C.H. 1990}}. Initially considered to have an unfavorable prognosis {{1324 Crist,W.M. 1990}}, an outcome similar to that for standard risk ALL was demonstrated in subsequent studies for TCF3-PBX1 ALL when patients received intensive chemotherapy regimes {{1322 Raimondi,S.C. 1990; 1323 Pui,C.H. 1994; }}.
t(12;21)(q21;q22)/ETV6-RUNX1 (TEL/AML1)
This is the most frequent structural abnormality in pediatric ALL. It is present in 25% of patients and is associated with a favorable outcome. ETV6/RUNX1 is a cryptic translocation and cannot be detected by conventional metaphase cytogenetics (Figures 2-5(A) and 2-5(B)) {{1365 Nordgren,A. 2002; 1364 Mathew,S. 2001; 1363 Douet-Guilbert,N. 2003}}.
The translocation, t(8;14)(q24;q32), and the variant forms t(2;8)(p13;q24) and t(8;22)(q24;q11), are found in Burkitt lymphoma, some diffuse large B cell lymphomas, and some ALLs. Mature B-cell ALL or Burkitt-like ALL are rare, comprising 1-2% of pediatric ALL {{717 Navid,F. 1999; }}. With a few exceptions, ALL blasts with translocations involving MYC have a FAB-L3 morphology and demonstrate a mature B cell phenotype, with clonal expression of immunogobulin light chain {{1449 Davey,F.R. 1992;1451 Hammami,A. 1991; 1450 Kaplinsky,C. 1998; 1447 Komrokji,R. 2003; 1446 Navid,F. 1999; 1448 Gupta,A.A. 2004; 1285 Harrison,C.J. 2001; }}. These translocations juxtapose the oncogene, MYC, located at 8q24, to the immunoglobulin heavy chain (IGH) at 14q32, kappa (IGK) or lambda (IGL) light chain genes at 2p12 and 22q11 respectively. Despite the low incidence of this type of leukemia and its poor response to conventional treatment for B-precursor ALL, it is recognized that patients with B cell ALL have an improved survival when treated with very intensive chemotherapy {{1446 Navid,F. 1999}}.
Precursor T-cell leukemia/lymphoma
About 10-15% of pediatric ALL have a T-cell immunophenotype. In comparison with precursor B-ALL, they are more frequent in the older children and adolescents, and present with a higher tumor burden {{1076 Pui,C.H. 2004; }}. Historically, T-ALL have been considered as high-risk with increased incidence of relapses, although the outcome has greatly improved with more intensive protocols {{1053 Goldberg,J.M. 2003; 1079 Pui,C.H. 2004; }} .
Genetic aberrations
In approximately 50% of T-ALL, structural chromosomal aberrations can be identified by conventional karyotyping {{1081 Rubnitz, J.E. 1999; 1080 Raimondi,S.C. 1999; 1117 Graux,C. 2006}}. Numerical changes are rare, except for tetraploidy seen in approximately 5% of cases, and are without prognostic significance {{1117 Graux,C. 2006; }}. Translocations involving the TRA and TRD (14q11) and TRB (7q34) are seen in 35% of patients {{715 Szczepanski,T. 2000; 1113 Ellison,D.A. 2005; 1117 Graux,C. 2006; 1116 Bellido,M. 2000; 1115 Cauwelier,B. 2006; }}, and result in upregulation of oncogenic transcription factors involved in T-cell differentiation. Other rearrangements include fusion translocations not involving the T-cell receptor loci, for example, the cryptic interstitial deletion of TAL1 at 1p32 resulting in the SIL/TAL1 chimeric gene (~30% T-ALL), t(10;11)(p13;q14)/ CALM-AF10 {{ 1048 Asnafi,V. 2003; }}, and t(5;14) (q34;q32) {{ 1051 Bernard,O.A. 2001; }} both of which are cryptic, and translocations involving the MLL gene {{1035 Raimondi,S.C. 1993; }}. Specific signatures obtained by GEP analyses can segregate the major oncogenic pathways, to which different genetic lesions converge. The major oncogene clusters are NOTCH1 {{1453 Aster,J.C. 2005; 1455 Rao,S.S. 2009; 1454 Real,P.J. 2009; }}; HOXA {{1035 Raimondi,S.C. 1993; 1456 Ferrando, A.A. 2003; 1457 Speleman,F. 2005; 1460 Dik,W.A. 2005; 1459 Soulier,J. 2005; 1458 Van Vlierberghe,P. 2008; }}; TLX1 (HOX11) AND TLX3 (HOX11L2) {{1098 van Grotel,M. 2006; 1099 van Grotel,M. 2008; 1100 Ballerini,P. 2008; 1101 Ballerini,P. 2002; 1088 Ferrando,A.A. 2004; 1042 Cave,H. 2004; 1121 Berger,R. 2003; }}; beta-helix-loop-helix (SCL/TAL1) {{1461 Kikuchi,A. 1993; 1462 Janssen,J.W. 1993; }}, LYL1{{ 1124 Ferrando,A.A. 2002; }}; ABL1 {{1057 Graux,C. 2004; 1043 De Keersmaecker,K. 2005}}; JAK1 {{1464 Flex,E. 2008; }}; and JAK2 {{1463 Peeters,P. 1997}}.
Similar to precursor B-ALL, the outcome in T-ALL is associated with molecular and cytogenetic abnormalities {{1038 van Grotel,M. 2006; 1045 van Grotel,M. 2008; }}. T-ALL with translocations involving the TAL1 gene [t(1;14) (p32;q11) or submicroscopic interstitial deletion resulting in the SIL-TAL1 fusion and HOX11 [ t(10;14)(q24;q11) or t(7;10)(q35;q24) ] have a better outcome, and those involving HOX11L2 [t(5;14)(q35;q32) and CALM-AF10 t(10;11)(p14;q14)], JAK1, and ABL1 do poorly independently, or in combination {{1461 Kikuchi,A. 1993; 1462 Janssen,J.W. 1993; 1037 Attarbaschi,A. 2010; 1042 Cave,H. 2004; 1100 Ballerini,P. 2008; 1038 van Grotel,M. 2006; 1045 van Grotel,M. 2008; 1104 Ferrando,A.A. 2004; 588 Szczepanski,T. 2010; 1464 Flex,E. 2008; }}.
Unlike precursor B-ALL, the clinical significance of immunophenotypic subtyping based on surface antigen expression in T-ALL is less clear {{1059 Pullen,J. 1999; }}, except for some recurrent chromosomal rearrangements that are associated with the expression of specific antigens suggesting a developmental stage of T-cell. For example, TAL1 translocations commonly have a surface CD3+, TCRï¡/ï¢+, mature phenotype, and translocations involving HOX11 are frequently CD1a+, representing a cortical or intermediate stage of development. Early precursor T-ALL (ETP-ALL), a recently described distinct biological subtype by GEP, with high risk of remission induction failure or relapse, has a distinctive immunophenotype - (CD1a-, CD8-, CD5 (weak), and presence of stem-cell or myeloid markers, consistent with its origin from early T-cell precursors {{773 Coustan-Smith,E. 2009; }}. Table 3 shows the clinically important genetic abnormalities in precursor T-ALL and the recommended method for their evaluation.
About 50% of the abnormalities in T-ALL can be detected by conventional cytogenetics, and the common translocations are detectable by FISH {{1117 Graux,C. 2006; 1044 Gorello,P. 2010; 588 Szczepanski,T. 2010; }}. A high percentage of cryptic abnormalities, such as cryptic deletions at 9p21 and 1p32, and translocations with breakpoints near terminal regions of chromosomes, for example 9q34 breakpoints, t(5;14)(q35;q32), and rearrangements of TRB at 7q34 are often disclosed only with appropriate FISH probes {{1117 Graux,C. 2006}}. A recent study established a novel Q-rtPCR assay for detection of NUP214-ABL1 {{1465 Burmeister, T. 2006}}. Although risk-stratified protocols have not been employed commonly in T-ALL, the recent discoveries of involvement of NOTCH1, ABL1, and JAK kinases in T-ALL have the potential for translation into novel targeted therapies {{1465 Burmeister, T. 2006; 1455 Rao,S.S. 2009; 1454 Real,P.J. 2009; 1057 Graux,C. 2004; 1464 Flex,E. 2008; }}.
Acute Myeloid Leukemia (AML)
Compared with ALL, AML is less common in the pediatric age group, accounting for 16% of AL in children less than 15 years of age, and 36% in adolescents and young adults in the 15-20 years age group. A bimodal distribution is observed, with increased frequency of AML in children less than 2 years compared to older children.
Genetic aberrations
Cytogenetics is the most important predictor of outcome in childhood AML {{1335 Kaspers,G.J. 2007; 1336 Rubnitz,J.E. 2008; 1337 Pui,C.H. 2004; 1152 Manola,K.N. 2009; 1186 Harrison,C.J. 2010; }}. Cytogenetic abnormalities, seen in 70-85% of pediatric AML, is higher than in adult AML {{1152 Manola,K.N. 2009; 1186 Harrison,C.J. 2010; }}, and form the basis of classification {{239 Swerdlow, S.H. 2008}} and risk stratification of childhood AML {{1186 Harrison,C.J. 2010; 1212 Lange, B.J. 2008; 1215 Meshinchi, S. 2007; }}. The cytogenetic and molecular subtypes of adult AML carry the same prognostic significance in pediatric AML but with a difference in age distribution. For example, the frequency of MLL (11q23) translocations decreases from nearly 40% of AML in infants to 10% in older children {{1152 Manola,K.N. 2009; }}. Certain cytogenetic and molecular abnormalities such as t(1;22)(p13;q13) translocation with aberrant expression of OTT-MAL fusion gene occurs exclusively in non-Down syndrome-associated AMkL in infants {{1283 Bernstein, J. 2000 ;}}.
INSERT FIGURES 3a, 3b, 3c???
Others such as NPM1 and FLT3 mutations are less commonly observed in childhood AML. NPM1 mutations in childhood AML occur in 8-10% of AML cases and in approximately 25% of those with a normal karyotype {{1170 Brown,P. 2007; 1158 Hollink,I.H. 2009; }}, as opposed to adult AML (overall frequency 35% ; normal karyotype AML 60%) {{1342 Thiede,C. 2006; 1338 Verhaak,R.G. 2005; }}. The frequency of FLT3 internal tandem duplication (FLT3 ITD) is 10-15% in children versus 20-30% in adults {{1350 Zwaan, C.M. 2003; 1351 Meshinchi, S. 2001; 1352 Schnittger, S. 2002;}}. NPM1 and FLT3 mutations have similar prognostic implications in childhood AML as in adult patients {{1344 Gale,R.E. 2008; 1350 Zwaan, C.M. 2003; 1351 Meshinchi, S. 2001; 1353 Meshinchi,S. 2006; }} - presence of NPM1 mutation in normal karyotype AML is associated with a favorable outcome when not associated with FLT3-ITD; coexistence of NPM1/FLT3-ITD is associated with an intermediate prognosis; whereas FLT3 ITD alone predicts the worst outcome for the patient {{1351 Meshinchi, S. 2001; 1170 Brown,P. 2007; 1346 Rau,R. 2009; }}. NPM1 mutation is stable during disease evolution, and represents a possible marker for minimal residual disease detection. Table 4 lists the cytogenetic and molecular genetic abnormalities common to and of prognostic importance in pediatric AML.
Therapy-related AML/MDS (t-AML/MDS)
Use of intensive treatment protocols for childhood cancers has improved outcome for the primary tumors at the cost of increase in t-AML/MDS. It has been estimated that tMDS/tAML affects at least 1% of childhood cancer patients {{1501 Tucker, M.A. 1987; }}, with a 2% cumulative incidence at 15 years for secondary myeloid neoplasms. The frequency of t-AML/MDS in children depends on the nature of primary tumor, nature of therapy {{1606 Cohen, R.J. 2005; 1609 Bhatia,S. 2002; 1612 Pui,C.H. 1991}}, duration of therapy, and the underlying genetic predisposition {{1615 Bogni,A. 2006; }}. A higher incidence is seen in children treated for Hodgkin disease, sarcomas, especially Ewing's sarcoma, and ALL patients who received topoisomerase-II inhibitors, {1605 Kushner, B.H. 1988; 1606 Cohen, R.J. 2005; 1611 Neglia,J.P. 1991; 1612 Pui,C.H. 1991; 1608 Leung,W. 2001; 1610 Kreissman,S.G. 1992; 1609 Bhatia,S. 2002; }}. A higher incidence is also observed for children with neurofibromatosis 1 (NF1) and other germline DNA repair disorders {{1606 Cohen, R.J. 2005}} , or those with polymorphisms in drug metabolizing enzymes {{1613 Chen, H. 1996; 1614 Blanco, J.G. 2002; }}. An increased risk of t-AML was also observed in children who received granulocyte colony-stimulating factor (G-CSF) following ALL induction chemotherapy {{1616 Relling, M.V. 2003}}.
Most of the therapy related leukemias are t-AML. Therapy-related ALL comprises 5% of secondary leukemias. Molecular detection of IGH and TCR- gene rearrangements has facilitated the identification of t-ALL from the primary ALL. The outcome for t-myeloid neoplasms is very poor. Cytogenetic abnormalities are a major determinant of outcome. Abnormalities of chromosome 5, 7 or 21q22 translocation are commonly observed; the frequency of classical recurrent non-random translocation t(8;21), t(15;17), 11q23, and inv 16 are common in pediatric t-AML/MDS due to the frequent use of topoisomerase II inhibitors, especially in ALL. Developing individualized treatment protocols based on the genetic framework of the patient and targeted to a specific antigen or genetic pathway in the specific tumor is the goal for molecular medicine to check the increase in second neoplasms.
Acute leukemia associated with Down syndrome
Children with Down Syndrome (DS) have a 150-times greater risk of developing AML {{1227 Fonatsch,C. 2010;1259 Hasle,H. 2000; }}than those without DS. The most common AML subtype in DS is acute megakaryoblastic leukemia (AMkL), and the risk in DS is increased 500-fold {{1258 Zipursky,A. 2003}}. DS-AML has an excellent cure rate of nearly 80% compared to the non-DS AML . Virtually all children with DS- AMkL have somatic mutations in the GATA1 gene {{1265 Wechsler,J. 2002}}. The mutations result in a truncated GATA1 protein (also referred to as GATA1s) that contributes to uncontrolled megakaryoblastic proliferation. Somatic GATA1 mutations are specific to AMkL occuring in trisomy 21 patients {{1265 Wechsler,J. 2002}}; the underlying mechanism of this association is as yet unresolved.
DS children also have a 20-fold increased risk for developing ALL {{1259 Hasle,H. 2000; 1235 Xavier,A.C. 2009; }}. In contrast to DS-AML, DS-ALL is of very high-risk and has a worse outcome compared to non-DS ALL {{1275 Tigay,J.H. 2009; 1280 Whitlock,J.A. 2005; 1274 Maloney,K.W. 2010; }}. GATA1 mutations are not present in DS-ALL {{1273 Whitlock,J.A. 2006}}. Recent studies have shown presence of a R683 somatic mutation in JAK2 in 18-28% of DS-ALL patients {{1277 Kearney,L. 2009; 1281 Bercovich, D. 2008; }}. Aberrantly increased expression of cytokine receptor CRLF2 is present in the majority of DS-ALL with R683-mutated JAK2 {{1276 Hertzberg,L. 2010; 753 Russell,L.J. 2009; }}, suggesting a synergistic effect between the two mutations. The activation of the CRLF2-JAK-STAT signaling pathway in the majority of DS-ALL suggests a therapeutic potential for JAK inhibitors.
Conventional cytogenetics and FISH are important in detection of trisomy 21, the latter is especially useful in DS mosaics {{1226 Kudo,K. 2010; }}. GATA1 mutation testing may play a useful role in the initial stratification of AMkL into chemosensitive or chemoresistant groups (Stepensky P, Fuster). GATA1 mutation can be detected by sequencing and can be employed in follow-up for MRD. Down-syndrome related myeloid proliferations and their link to AL is discussed in greater detail in the chapter on pediatric myelodysplasia and myeloid proliferation.
Blastic Plasmacytoid dendritic cell tumor (BPDCN)
BPDCN, formerly known as blastic natural killer (NK)-cell lymphoma and CD4+/CD56+ hematodermic neoplasm {{1129 Jegalian,A.G. 2009; }}, is a rare subtype of AL, even less frequent in children{{1126 Jegalian,A.G. 2010; 1127 Hama,A. 2009}}. Based upon phenotypic (CD4+, CD56+, CD123+ BDCA-4 +, CD303/BDCA-2+, TCL1+,CD68-), functional, and genetic features, the cell of origin is believed to be the hematopoietic precursor committed to a plasmacytoid dendritic cell (PDC) lineage {{1129 Jegalian,A.G. 2009; 1128 Garnache-Ottou,F. 2009; }}. A leukemic presentation in the absence of skin lesions is described more often in the pediatric patients. Pediatric BPCDN are reported to have a fairly uniform and "lymphoblast"- like appearance and S-100 positivity in neoplastic cells compared to a variability of morphologic features and S-100 negativity seen in adult cases IS THIS COPIED {{571 Jegalian,A.G. 2010; 1485 Cota, C. 2010; }}. Two-thirds of BPDCN have complex, non-random cytogenetic abnormalities {{571 Jegalian,A.G. 2010; }}. GEP studies have identified a set of genes expressed in BPDCN not described in other hematopoietic cells, but highly expressed in neuronal cells and implicated in neurogenesis {{1486 Dijkman, R. 2007;}}.
Hereditary disorders with predisposition to AL
An increased predisposition for development of AML has been observed in children with inherited disorders that include disorders of DNA repair and increased chromosomal fragility, for example Fanconi's anemia and Bloom's syndrome; bone marrow failure syndromes, such as Kostmann's syndrome, Diamond-Blackfan anemia, familial platelet disorder and Shwachmann-Diamond syndrome; and in Neurofibromatosis type I {{1358 Shimamura,A. 2006; 1360 Rosenberg,P.S. 2008; 1362 Dror,Y. 2008; 1361 Alter,B.P. 2010; 1361 Alter,B.P. 2010; 1357 Alter,B.P. 2007; 1356 Jongmans, M.C. 2010}}. The development of leukemia in these disorders often occurs in adulthood. Highly sensitive and specific diagnostic tests based on the mutations identified for many of the inherited disorders are available {{1357 Alter,B.P. 2007}} for confirmation of the underlying germline genetic disorder and in investigation of family members of the affected individual. These tests and the different laboratories offering them are available at http://www.genetests.org


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When: Wed., Jan. 16, 6:30 p.m. 2013
PlayMakers Repertory Company behind-the-scenes preview with Clybourne Park playwright Bruce Norris. RSVP via phone or website.
Price: Free
120 Country Club Rd (Orange County)
April 5-30
UNC Campus: Paul Green Theatre - Orange County
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Genre/Form: | Criticism, interpretation, etc |
Additional Physical Format: | Online version: Wilson, H.H. (Horace Hayman), 1786-1860. Drāmās. Varanasi, Chowkhamba Sanskrit Series Office [1962] (OCoLC)572631516 |
Document Type: | Book |
All Authors / Contributors: |
H H Wilson |
OCLC Number: | 6561586 |
Notes: | "A reprint of the learned introduction of Professor H.H. Wilson's celebrated work Hindu theatre." |
Description: | 112 pages 17 cm. |
Series Title: | Chowkhamba Sanskrit studies, v. 18. |
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Hi all,
when data is read from disk, is the whole extent read into the buffer cache or is it only the blocks ?
I am guessing the answer is only the blocks, but just wanted to make sure.
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