text:
Grafting tape- black rubber stretchy stuff?
A short while ago someone described their success with non-adhesive rubber tape. I bought a roll years ago for that purpose but never used it. Now I'd like to try on my apple very soon.
Can't find the post, though. Could somebody point me to it, or could the writer please repeat his advice?
This may be the post. Brady
Here is a link that might be useful: affect of electric tape on grafts
Thanks to you all, both for the help and for the promptness.
As much as I like parafilm I'm up for anything, and I suspect that, given the variable weather we get around here, the black tape might help overcome the cold snaps (30 F here this AM, with fresh snow, 50F at the moment.) I'll wait another week.
Surprised by takes on a couple of last year's grafts that I had all but given up on. A bud back up that never calloused-in properly looked like it was going to fall out of the bark, but a nice leaf is emerging now. The Belmont sprouted last year and then withered, but new growth is poking. Two apricot grafts calloused properly, but only one actually has emerged so far. It ain't much but it's my first 'cot success. The other isn't dead, just not going anywhere yet. We'll see.
The weather seems to be turning. I just hope we get some insect activity this week, or all those lovely pear blossoms will disappoint.
Just to be clear, I don't use the splicing tape INSTEAD of parafilm. I use with WITH parafilm. I think the two perform entirely different functions.
The parafilm is for sealing in moisture so the scion (and the graft union area) does not dry out during the knitting process. The splicing tape takes the place of grafting rubbers, rubber bands, green tape, etc. It is used to reinforce the graft area and hold everything tightly and motionless until knitting occurs and even after while the scion has begun to push but the union is still physically weak.
This post was edited by steve_in_los_osos on Wed, May 1, 13 at 20:58
Appreciated. Well said and very clear.
I usually wrap things up tight with rubbers and cover with parafilm, but I like the idea of the somewhat self-adhesive nature of the splicing tape. Makes me wish I had more grafting to do this year so I could experiment more!

subset: commoncrawl


text:
Hotel Caron de Beaumarchais
No availability found through our partners. Please contact the business directly or check some of our recommended alternatives.
How has this hotel rated in the past?
- Shuttle bus service
- Free High-Speed Internet
- Pets allowed
Photos of Hotel Caron de Beaumarchais
Travelers also recommend:
TravelPod Member ReviewsHotel Caron de Beaumarchais Paris
Okay, it is small. But, really, what do you expect in Paris? And though I am a person with the means to travel to Paris, I am not a person with the means to travel high end to Paris. For a moderate price, this hotel has all the charm and ambiance one would hope to find in the City of Love. In fact, my husband and I loved this hotel so much, we stayed there in 2007 and again in 2010.
What did I like? First of all, the decor...brilliant reds and blues; the windows, french, of course, allowing all of the fresh air into the room daily; the breakfast, pain au chocolat, hard boiled eggs, tea, cheese, kiwi, delish; the staff, always kind and willing to help, not once condescending towards us because of our American-ness; the location, in the hip Marais, we were within walking distance from the Louvre, the Notre Dame Cathedral, and my favorite place to shop in Paris, BHV!
This review is the subjective opinion of a TravelPod member and not of TravelPod.com.
Historical Traveler Reviews Hotel Caron de Beaumarchais Paris
Great Paris Location!
My husband and I just returned from a wonderful six-night stay at the Hotel Caron de Beaumarchais over Christmas 2003. The location was fabulous - 10 minute walk to Notre Dame, 15 minutes to Place des Voges, 3 minutes to the nearest Metro, and all the wonderful Marais shops begin just outside your door. We initially stayed in a third floor room and then moved to room 61 which was smaller (and yes, the rooms are small, but I believe they all conveniently laid out and have lovely wooden ceiling beams) but which had an outdoor balcony, a view over the Marais rooftops, and a shower. The rooms are quiet, the beds are very comfortable, the staff is professional and friendly (not overly personal - but I tend not to prefer that anyway), and it's great to be able to order either a breakfast or just coffee/tea in your room. I did considerable research about hotels in the Marais and St. Germain areas, and though we passed many of them in our long walks, our location couldn't have been better nor our trip more restful. We will definitely return another time.
Just another hotel
I stayed at Caron de Beaumarchais for a few nights in March 2002.
Whilst everything was as it should be in a hotel, it was nothing special. Negatives: The room was tiny, furniture bordering on kitsch, tiny lift. Positives: Modern well designed bathroom, the service was very efficient.If you are expecting a fabulously warm little hotel with a heart of gold I would stay elsewhere, I felt like I was paying a premium because they appeared in Cond� Nast. I would equate the Caron de Beaumarchais to the Warwick Hotel in San Francisco.
We loved this hotel
My husband and I stayed here and loved it. The room was typical for Paris, small but functional. Being winter, we couldn't eally use our balcony, but the view over the rooftops was beautiful. Our concierge was very polite and helpful. We really loved the breakfasts - what wonderful coffee. We will definitely be staying there again for Easter.
Good location
Just returned from a 4 night stay here. Initially a bit disapointed with the small 'courtyard' room at the back when we had been quoted for a larger room at the front - no doubt we got this because of the late arrival of our easyjet flight. However, the room soon proved to be well equipped and with everything to hand. Great location in the Marais and we would also recommend the Colimacon Restaurant just a few doors up the street - great food and atmosphere - absolutely no need to trail the streets looking for something further away.
Very Tiny rooms
Rooms are extremely small, staff not very helpful with directions, would not stay here again.
Shame about the departure
After the initial shock of how tiny our room was, we did setttle nicely into Caron de Beaumarchais. Everything was comfortable and clean and nicely presented. The breakfasts were a real treat and kept us nicely filled until lunchtime and we had the added bonus of a balcony which made a perfect setting from which to enjoy it. The morning newspaper was a nice touch too. We stayed for four nights and it was disappointing however that by the third day our bed had not had a linen change. Our departure was tumultuous to say the least with the gentleman at the desk verbally abusing my boyfriend and shouting and throwing his arms in the air over a disagreement with the payment, we wanted to pay with visa, he insisted it was cash only and that we should have known better ( No- one had informed us of this at any stage) We felt terribly embarrassed and so following a cash payment left swiftly. Unfortunately, this spoiled what had been a pleasant experience to that point and so we will definitely not be returning to this hotel
A honeymoon hotel!
After researching for many months for the right hotel, I found Tripsadvisors and found the Hotel Caron de Beamarchais. It was as wonderfull as people described it and for a european not as tiny as for a american. There were everything on the room and especially the served breakfast was wonderfull!!! We thought that it was very tastefull decorated and clean and the idea about stepping into a livingroom and not a reception is perfect. You felt at home right away. It�s a very honeymoon like hotel. Not especially made for people with children. Too small in that sense.
Charming hotel with some history
Had a wonderful 5 day stay here in early December, 2002. The hotel is well situated for The Bastille, Marais, Notre Dame, Louvre, with everything else only a metro ride away. The rooms are small by even european standards, but very modern and well appointed with TV, internet capable phone lines, and a very well designed bathroom with shower/tub. Try to get one of the 2nd floor balcony rooms, particularly if the weather is decent (which it was not during our stay, but who cares, since you are in Paris!) The son and father team are very gracious, and will help book restaurants, etc. We can enthusiastically recommend Le Repair de Cartouche (sp?) in the Bastille/Marais and La Regalade in the 14th arr. for great food at reasonable prices(75-80 euro for 2 incl. wine). The wine lists were good as well.
Overall an excellent stay(which we rate an 8-9/10), and we plan to return on our next Paris trip.
A really fine place to stay
My husband/dance partner stayed here for 15 nights in November, 2002. I did 2 months of research before choosing the Caron. Was my work worth it? Yes! This hotel is managed perfectly. Utterly and uniformly clean, uncompromised plumbing, umbrellas in a stand near the door for you to borrow. Fresh linen every single day, and and a new live flower posey on your hand-painted desk every day; comfortable beds with real wool blankets (not that space age unresilient cheap material substitute sold in North America). Staff who ran to BHV and bought a new iron for our use, the moment they heard that theirs had broken. Coffee at our door every morning within 4 minutes of our request. People who answered all my prior e-mails and queries in a timely way; who didn't treat us like tourists; who answer you in French if that's what you initiate. A small room, like most of Paris, of course, and yes, eighteenth century-style upholstered chair styles aren't comfortable to relax in, but there are a zilllion hang-out places just outside your door, and the decor is beautiful and distinctly not kitsch. On a lively, trendy, but non-touristy street. French windows on the front rooms completely block out noise (like the wonderful peal of bells from Notre Dame). The Caron is very good value, though not budget. I'd only suggest that they instal shower curtains because it's a shame to soak the whole floor and toilet seat in the classy bathroom when you shower. To avoid this, we took baths only. A pity because the inclusion of both a shower AND bathtub is one mark of a 3-star hotel. Except for this, this hotel is like a perfect townhouse.
We can't stop staying at this Parisian hotel
The Hotel Caron de Beaumarchais, 12 rue Vielle du Temple, is a most wonderful place to stay. So wonderful, that we can't seem to stay anywhere else whenever we visit Paris. The Marais neighborhood is not only charming and full of interesting things to do, it is friendly and easy to find your way around in. The hotel's staff is friendly and helpful and the rooms and common areas are superbly kept. The decor couldn't be better and the hotel couldn't be more conveniently located as a base from which to visit the rest of Paris. On our last visit, we promised ourselves we'd make an effort to scout out other neighborhoods and hotels for subsequent trips but the more we think about it, it is unkilely we will stay anywhere else.
TripAdvisor Reviews Hotel Caron de Beaumarchais Paris
Travel Blogs from Paris
... in the first place. The area we ended up lost in was nice and full of shops and a younger, non-tourist crowd. After a bit of wondering, we found the store, grabbed our dinner and a bottle of wine to drink from the plastic cups in the hotel room (yeah we're classy) and went downstairs to the train station.
The train was delayed significantly and since there was a delay a large group of people tried to get on the next one that came through. The people looked ...
Today's the day
Well sleeping was difficult last night. I woke up at 2 and had to peed woke up at 4:50am just because I guess. I got up at 5am. I heard the kid across the hall making noises, I think he was playing video games. I showered and go ready to head to the train station.
Well of course it had to be pouring down rain as I walked to the station at 5:45am. I was not a happy camper. Even better, the bus was over 15 minutes late. So I was worried ...
Walt Disney Studios and Disneyland Paris
... most rides would be in French, some with English parts, and some with subtitles opportunity permitting. Unfortunately some rides were just French, making it tough to know what was going on.
Straight off this ride, next door, the Armageddon special effects show was starting in 1 minute. Perfect. This allowed you to experience the effect of being in a space station, just before being hit by a meteor! No problem. After, just accross from the exit, the big car stunt show ...
London To Paris
We have a 10.30 flight but have to return the car, so Ron advises to leave early in case of traffic on the M25. We have a faultless run in and the car handover is quick ( they don't spot the damage to the back bumper ) and we are at the airport 2 hours early. It ...


text:
Report Release: Unleashing Impact Investing in Ontario and the Ro...
Impact investing and the shifting landscape in OntarioRead More ›
SocialFinance.ca produces a weekly round up featuring social finance related news, insights, job openings, and events. We source the content for these round ups from Twitter, an RSS reader, and directly from our community of social finance practitioners. Below is our round up for the week of June 18, 2012.
Recently on SocialFinance.ca
Canadian and International News
Social Finance Learning and Best Practices
Photo credit: http://www.flickr.com/photos/benimoto/603815615/
Impact investing and the shifting landscape in OntarioRead More ›
The British Council has commissioned a survey to understand what support services are offered to social enterprises in the UK and around the world.Read More ›
Let's help Canada "B the Change"!Read More ›


text:
2008 BMW 328i Coupe (VIN: WBAWB335X8P134365), black/black leatherette, 56,500 miles, 6-spd. Steptronic auto trans. with paddle shifters, 3.0L chain driven DOHC 24V inline-6 cyl.... More
2014 Range Rover Autobiography LWB Supercharged FOR SALE!!! Finished in Fuji White Exterior over Red Leather interior. This Rover is As New with only 700 ... More
Luxurious California two owner 2010 Mercedes Benz S550 sedan powered by a 382 horsepower 5.5 liter V-8 engine matched to a 7 speed automatic... More
We are pleased to present this 1 owner 2002 Rolls Royce Silver Seraph Last of the Line Edition, with an amazingly low mileage of... More
Here is a beautiful rare 2008 Roush Black Jack Edition. Only 100 Black Jacks were built, of that only 16 were convertibles. This car... More
1987 Ferrari Testarossa VIN. ZFFSG17A9H0072207 U.S. Version Testarossa with Knock Off Wheels Striking Original Color Combination Clean CARFAX History Report Complete with ALL Books & Tools Sold New to Texas -... More
FINANCING AVAILABLE! Exotic Classic USA has relationships with banks and credit unions throughout the country to assist with your financing needs. Get pre-approved quickly through our secure... More
2014 Range Rover Autobiography Supercharged FOR SALE!!! Finished in Fuji White Exterior over Espresso/Almond Leather interior. This Rover is As New with only 50 MILES. Options... More
The Classic Car Gallery is proud to offer this 2003 Hummer H2. The truck is in excellent condition, and has traveled only 13,000 miles!!!... More
***2005 CADILLAC STS SEDAN*** ONLY 19,000 MILES!!! THIS STS IS LIKE BRAND-NEW,TOTALLY LOADED WITH OPTIONS AND THE NICEST AVAILABLE ANYWHERE...PERIOD! CARFAX CERIFIED & DEALER SERVICED THROUGHOUT OWNERSHIP! PREFERRED EQUIPMENT GROUP... More
***2012 MAYBACH 57S SEDAN*** "BALANCE OF FACTORY WARRANTY UNTIL JANUARY 2017" "TRUE ELEGANCE, LUXURY, PERFORMANCE AND EVERY CONCEIVABLE OPTION FROM ONE OF THE WORLDS MOST DESIRABLE... More
They only made 7547 of the 50th Anniversary Red convertibles and this one we have here is a real beauty. It has 36K miles... More
Sold new to Owner #1 of Bayonne, New Jersey in August 2005. After three years of ownership, it was sold with about 4,200 miles to... More
Lexus of North Miami is pleased to offer from our ever growing exotic motorcar inventory this pristine 2009 Audi R8 finished in its most... More
Lexus of North Miami is proud to offer this Stunning 2012 Aston Martin Rapide finished in its most desirable Morning Frost White Pearl over... More


text:
NHL Hockey - Preview
|Montreal Canadiens vs. Pittsburgh Penguins
The fans at Consol Energy Centre will be treated to a game between the Montreal Canadiens and the Pittsburgh Penguins when they take their seats on Wednesday. Last time out for Montreal, they were a 5-3 loser as they battled the Maple Leafs on the road. Moneyline bettors who got the Maple Leafs at -110 were rewarded, while the 8 combined goals moved the game OVER for totals bettors. In their last action, Pittsburgh was a 5-1 loser at home against the Panthers. Bettors on Florida at +255 on the moneyline collected their winnings from that game, while the total score (6) sent OVER bettors home happy as well. Pittsburgh:
Team record: 34-13-2 SU, ATS
The total has gone OVER in 5 of last 5 games at home
When playing on Wednesday are 9-1
Team record: 27-17-5 SU, ATS
The total has gone OVER in 4 of last 5 games on the road
When playing on Wednesday are 3-7
Montreal at Detroit, Friday, January 24
Pittsburgh at NY Islanders, Thursday, January 23


text:
The 12 Worst PETA Ads Of All Time
The animal rights group does some really great work. And some really horrible advertising.
The animal rights group does some really great work. And some really horrible advertising.
copyranter 2 years ago 242 responses
This just happened earlier today. The vandals did the job in the daytime.
copyranter 2 years ago 69 responses
Over two years after the disastrous BP oil spill wreaked havoc on the Gulf, Greenpeace has received photos of the destruction inflicted on marine life in the area. They're shocking and upsetting.
The Huffington Post 2 years ago respond
Well isn't this fun news to wake up to. A pipeline in Alaska "ruptured during testing and spilled a mixture of methanol and oily water onto the tundra." It was apparently a small spill, but come on BP, get it together. (via news.yahoo.com) Read More ›
Jack Moore 3 years ago 21 responses
Is this a few of the side effects of the BP oil spill on humans? Watch Video ›
Presenting BuzzFeed's picks for the top videos that defined 2010. Whether we were amazed or appalled, emotions ran high in a year that the line between viral and mainstream virtually disappeared. In no particular order, here are the top 20. How many have you seen? View List ›
Chris Menning 4 years ago 52 responses
Don't dig in the beaches! Don't Question Authority! Watch Video ›
cybergata 4 years ago 14 responses
The man behind the genius @BPGlobalPR Twitter has finally been unmasked.
Amanda Dobbins 4 years ago 4 responses
Well this is awkward. View Image ›
Rebecca E. 4 years ago 26 responses
BP has not only destroyed our oceans and shores, but it's going after our childhoods now! Watch Video ›
Brian Feldman 4 years ago 85 responses
Awwww. Shame on you BP. All little Carter wants to do is go to the beach and play in the water but he can't because it's covered in oil. His childhood is ruined. Watch Video ›
Dmo 4 years ago 18 responses
The rest of this pie fell victim to the 2010 Gulf Coast oil spill. View Image ›
Rebecca E. 4 years ago 7 responses
Here's your step-by-step guide to cleaning up your oiled pelican. It goes without saying that you shouldn't try this at home. But if you decided to volunteer for animal rescue in the Gulf, here's what your process would be like! View List ›
Scott Lamb 4 years ago 126 responses
This is what happens when BP spills coffee. Watch Video ›
MelisBuzzFeed 4 years ago 15 responses
More than 50% of this sign is factually accurate. View Image ›
Amanda Dobbins 4 years ago 102 responses
If the vast amounts of oil unleashed in the Gulf could be used to power things, what could we do? Happy World Ocean Day, everyone! You might be surprised just how much that amount of oil could power, if it weren't being used to kill pelicans and ruin fishermans' lives. Read More ›
Scott Lamb 4 years ago 44 responses
"I'm With Coco" artist, Mike Mitchell has certainly been on a roll with his recent illustrations of BP Oil Sponge Bob, and now his portrait of a BP executive. View Image ›
MelisBuzzFeed 4 years ago 2 responses
The BP station on Houston and Layfayette in New York has been slimed with a mud ball. Who ever did this has great aim. View Image ›
Jenni Leder 4 years ago 83 responses
In 1979, an oil well in the Gulf of Mexico operated by Transocean erupted and an Alaska pipeline cracked. They tried the top kill, the junk shot, booms, chemical dispersants, and mud. Oil gushed out for 9 months until relief wells were dug. Watch Video ›
DarthVader 4 years ago 44 responses
If you haven't been following the fake BP Public Relations twitter account, you need to now because they're finally starting to get to BP a little bit. BP has even recently asked Twitter to shut down the fake account. (Twitter refused.) View Image ›
Ricky 4 years ago 86 responses
Today's new phrase that news anchors love to repeat is: Top kill. Read More ›
Scott Lamb 4 years ago respond


text:
BALTIMORE (AP) — Using their own brand of baseball, the St. Louis Cardinals showed power-hitting Baltimore they can score a bunch of runs, too.
Cardinals beat Orioles 8-3 to avoid sweep
Rookie Kolten Wong had four hits and scored twice, Peter Bourjos homered and St. Louis beat the Orioles 8-3 Sunday to avoid a three-game sweep.
After allowing nine home runs in losing the first two games of the series by a collective 22-5 score, the Cardinals amassed a season-high 17 hits — 14 of them singles.
St. Louis came into the game with 80 home runs compared to 147 for Baltimore, but the Cardinals' style of little ball produced a big win.
"We walked in here today and that's all the conversation was, we've got to win this, we've got to figure out a way to get this one," manager Mike Matheny said. "We felt good about what our offense could do. The guys, they were taking good at-bats all day long. We got a couple big hits when we needed them; that's usually the difference."
Bourjos capped the barrage with a three-run drive in the ninth off Zach Britton, ending the left-hander's run of 27 straight scoreless appearances at home.
The additional runs seemed to be unnecessary, but against the Orioles it's hard to determine how much offense is enough.
"We saw what they can do the last couple nights and we had to keep pushing to keep pace with them and keep the lead," third baseman Daniel Descalso said.
Wong's four hits, all of them singles, matched a career high and lifted his batting average 11 points to .253.
St. Louis right-hander Lance Lynn (12-8) gave up three runs and nine hits over 5 2-3 innings, only the second time in his last 12 starts that he allowed more than two runs.
"They've got some guys that can hit the ball all the way up and down the lineup, and I knew that going in today it was going to be a grind," Lynn said. "I was able to make enough pitches when I needed to and get out of some jams."
Nick Markakis had four hits for the Orioles, who went 2 for 13 with runners in scoring position. Caleb Joseph's streak of consecutive games with a home run ended at five, one short of the club record.
Continue reading this story on the...


text:
Radiotherapy Introduction One third of people in Britain will develop cancer at some time during their lives and about half are cured. Opportunities for active treatment are increasing, with improvements in radiotherapy and chemotherapy and the development of novel biological and molecular treatment approaches. Of all cancer patients - 22% are cured by surgery, 18% by radiotherapy and 5% by chemotherapy alone or in combination with surgery or radiotherapy. Radiotherapy remains the most effective nonsurgical treatment modality forming a central provision of treatment in Cancer Centres and is solely responsible for or significantly contributes to cure in 40% of the long-term survivors of cancer. 40-45% of all cancer patients will require radiotherapy at some point during their illness. In two thirds of these cases radiotherapy is given with curative intent, either alone or in combination with surgery and/or chemotherapy. Palliative radiotherapy offer many patients relief from symptoms associated with advanced cancer. As with surgery, radiotherapy is a locoregional treatment modality. The main aim of radiotherapy is to maximize tumour control, whilst minimizing damage to normal tissues. Over the last 20 years, major technological advances have helped greatly to improve the accuracy of treatment with resulting improvements in outcome. The radiotherapy department Radiation oncology is a multidisciplinary speciality that requires a skill mix of clinicians (radiotherapists and radiologists), physicists, dosimetrists, technicians (workshop, electronic, mould room), therapy radiographers, specialist nursing staff and IT specialists. A wide variety of technical equipment and machinery is required and includes linear accelerators, simulators, treatment planning systems, brachytherapy and afterloading facilities, portal imaging systems, CT/ MRI scanners linked to 1 planning systems, computer networks and software upgrades. The enormous capital costs and specialist staffing necessitate radiotherapy departments to serve a large population to be cost-effective and most centres serve at least a population of a few million. SJIO serves a population of 2.8 million. Clinical use and indications for radiotherapy Radical treatment. Radical radiotherapy is treatment delivered with intent to produce a high rate of local tumour control. It accepts a defined rate of normal tissue complications and demands a certain level of technical sophistication. Radiotherapy may be curative as a single modality or when combined concurrently with chemotherapy. Radical radiotherapy involves complex planning and a protracted fractionated course of treatment. Most radical treatments are given over 4-6 weeks, in 1.8 – 2.75 Gray fractions to a total dose of 55 - 74Gy. Many of the currently used treatment practices and regimes are based on outcome measures obtained by analysing results from individual centres. For many tumours there is a wide range of currently acceptable practice. Concurrent chemoradiotherapy requires scheduling of chemotherapy during the course of radiotherapy. Toxicity is often a significant problem and patients should be monitored closely throughout treatment. Adjuvant treatment. Radiotherapy is commonly used in the adjuvant setting following initial surgery or chemotherapy. The aim of treatment is to eradicate loco-regional residual microscopic disease. Adjuvant radiotherapy doses are usually slightly less than the doses used for radical treatment of macroscopic disease, but treatment planning may be just as complicated. The following cancers may require adjuvant radiotherapy following surgery: breast cancer, sarcomas, endometrial cancer, and head and neck cancer. 2 Neoadjuvant treatment. Radiotherapy or chemoradiotherapy may be given prior to surgery either to increase operability by downstaging the disease and/or to treat locoregional microscopic disease. Examples include the treatment of locally advanced rectal cancer and vulval cancer. Palliative treatment. Radiotherapy has a crucial role in the palliative setting and is effective for a variety of symptoms: 1. Pain - especially pain from bone metastases, but also visceral pain. 2. Bleeding – haematuria, haemoptysis, PR bleeding, bleeding/fungating ulcers 3. Tumour obstruction of a hollow viscera e.g bronchus, oesophagus, rectum. 4. Superior vena cava obstruction (SVCO) 5. Spinal cord compression 6. Symptoms from brain metastases and leptomeningeal disease 7. Skin metastases 8. Symptomatic nodal disease Palliative radiotherapy is given over a shorter period of time with larger fraction sizes but a lower overall dose. Patient set up and radiotherapy techniques are often very simple. Treatment may be given as a single fraction (e.g 8-10 Gy) or as a short fractionated course (eg: 20 Gray in 5 fractions, 30Gy in 10 fractions). High dose/radical palliation Sometimes it is appropriate to offer higher doses of fractionated palliative radiotherapy to achieve local control of the primary tumour and possibly improve survival. Radical palliation is most commonly used in head and neck cancer treatment, where control of 3 local symptoms is particularly important. Other examples include locally advanced pelvic cancers, locally advanced lung cancer and brain tumours. External beam radiotherapy planning Treatment planning is a multi-step process. The complexity of this process depends upon the treatment intent, the site of the tumour, the equipment/facilities available and the desired accuracy of treatment (including reproducibility and verification). The aim of radiotherapy in the radical setting is to deliver the maximum possible dose of radiation to the tumour to achieve local tumour control, whilst trying to spare surrounding normal tissue. In the palliative setting, the aim is to control the symptoms and the treatment is usually shorter, simpler and of lower dose for patient convenience and reduced side effects. 1. Pre-planning. Prior to planning, it is essential that patients should be given adequate information relating to their disease and its proposed management. Specifically, they should be made aware of the diagnosis, the natural history of their tumours and different treatment options. They should be given practical explanation of the treatment and planning processes and be advised of side-effects of the therapy. Radiotherapy treatment planning can be a complex and resource intensive process. In order to make best use of the resources at their disposal and to avoid redundancy and delays, it is important that at an early stage of the process the planning clinician formulates a strategy for the subsequent planning and treatment process. The strategy should be based on all the relevant clinical data available from the staging procedures. It should include consideration of the intended level of treatment complexity which will determine the subsequent stages of the process. 4 2. Planning. Treatment planning is the most crucial part of the radiotherapy process, comprising of a number of activities which follow from the decision to treat a patient with external beam radiotherapy and from the stated objectives of that treatment. These activities include: definition of treatment volumes prescription of the radiation dose (schedule) the production of a treatment plan and the associated dataset needed for its implementation 3. Method of patient positioning and immobilisation. Another parameter to be established at an early stage is the positioning of the patient for planning and treatment and whether there is a requirement for a customised immobilisation device. Patients must be treated in the same position everyday that is technically sound, comfortable and reproducible. This minimises the risk of a geographical miss that may compromise tumour control and increase surrounding normal tissue damage. To help in this process various immobilisation devices are available, which include vacuum moulded bags of polystyrene beads, and foam blocks and wedges, which can be used for trunk and limb immobilisation. Higher degrees of precision are required for treatment of CNS and head and neck tumours due to the close proximity of critical structures such as the spinal cord, eyes and optic chiasm. This can be achieved with immobilisation devices such as custom made perspex/plastic moulded shells (masks) that can be fixed to the treatment couch 5 4. Choice of target volume. This has been revolutionised with the advent of CT and MRI imaging. The volumes to be irradiated have to include the demonstrated tumour (Gross Tumour Volume – GTV), and the predicted sub clinical spread of disease (Clinical Target Volume – CTV). In order to make sure that the entire CTV receives the prescribed dose a further margin is required to account for day to day variations due to patient and organ movement (e.g respiratory movements, bladder filling, bowel emptying etc). This is known as the Planning Target Volume (PTV). The palliative treatment of cancer may include the total tumour burden (e.g T4 bladder cancer) or only the symptomatic areas of widespread disease (e.g a single painful bone lesion in a patient with multiple bone metastases). Treatment planning volumes (International commission on radiation units and measurements (ICRU) 62 definitions) Treated PTV Volume CTV GTV Sub clinical disease GTV – Gross tumour volume CTV – Clinical target volume PTV – Planning target volume Irradiated volume – tissue volume which receives a dose that is considered significant in relation to normal tissue tolerance. 6 Organs at risk – are normal tissues whose radiation sensitivity may significantly influence treatment planning and/or prescribed dose. 5. Target volume localisation and simulation. The planning clinician is responsible for defining gross tumour volume (GTV) and clinical target volume (CTV). These processes require consideration of all available clinical data and may involve close cooperation with a diagnostic radiologist. In order to accurately treat the required target volume on a daily basis, the target volume needs to be localised within the patient in relation to external reference points (marked with ink and/or tattoos). This allows the radiographers to set up the patient in exactly the same treatment position every day. Tumour localisation is achieved with diagnostic imaging information (X-rays. MRI, CT etc) and the use of a simulator. The Simulator There are no standard simulators at SJIO. The simulator is a diagnostic X-ray machine that also has the facility for real-time screening with an image intensifier linked to a closed circuit TV. It duplicates a radiation treatment unit in terms of its geometrical, mechanical and optical properties. Surface markings and tattoos can then applied, which help radiographers to reproduce the same field on each day of treatment. Simulation X-rays/vidifilms are taken for each treatment beam to allow verification of the field position and also serve as a permanent record of treatment. These films also allow the clinician to make any changes to the field or mark areas that require shielding. Within SJIO there are only CT-Simulators. The CT-simulator allows the clinician to identify the tumour on CT images and mark appropriate radiation fields on screen. A laser system allows radiographers to mark and tattoo the patient for treatment set-up. 7 Target volume localisation For simple radiotherapy planning the target volume can be defined by radiographic visualization. Appropriate adjustments of field sizes can be made to encompass the tumour/target volume. This process can be aided by using metal markers for palpable disease and barium/contrast to define the tumour or critical normal structures. For some very simple palliative treatments, a simulator may not be required, as a field can be marked directly onto the patient by the clinician. Examples include treatment of skin cancers and whole brain irradiation. CTV / PTV may also be defined on radiographs (orthogonal films- lateral and AP or PA) obtained at a simulator planning session or on an appropriate CT section. These treatments have to be planned and will involve the physics department. For more complex treatment (Level 3) planning, volumes are defined on a CT study at a graphics terminal. At this level, the GTV, CTV and PTV can be defined in one or more planes (sections), using a series of CT and/or MRI sections. It is also assumed that the complete dose distributions are computed in the central plane and in other planes (sections) and with inhomogeneity corrections, when appropriate. The computer planning system can develop digitally reconstructed radiographs (DRRs) that give beams-eye-views of the radiation fields. 6. Dosimetry. Dosimetry is calculation of the amount of radiation dose absorbed by the patient. Beam data for treatment units are available as depth dose charts that allow simple dose calculation For simple field arrangements (single fields and parallel opposed fields), it is assumed that the dose at the ICRU Reference Point and an estimate of the maximum and minimum doses to the PTV can be determined using central axis depth dose tables. Radical treatments often require multiple and complex field arrangements 8 to achieve the optimum dose to the tumour with normal tissue sparing, and modern computer planning systems are required to carry out the very complex dosimetric calculations. 7. Treatment Delivery. The patient is placed on the couch of the treatment unit in exactly the same position as during simulation with the aid of set up instructions (produced from simulation) and the reference skin marks and tattoos. The beam parameters are then set (gantry angles, beam collimation to set field size etc). Any further modifications with shielding blocks or wedges are also made. The prescribed dose is then checked and the amount of time (number of monitor units) each radiation beam needs to be turned on for to give the required dose is calculated. Treatment can then be given. 8. Verification. To ensure the accuracy of treatment, check X-ray films are taken with the first fraction of radiotherapy treatment. These films show the anatomical landmarks that the radiation beam has passed through and they can be compared to the simulator films to confirm patient positioning is correct. Further check films may be required to confirm reproducibility of the field throughout the course of radiotherapy. Most machines now have portal imaging systems that utilize computer software programs to produce images of the treated area to help assess for deviations of the treatment field. 9 Basic physics Radiation is a term for the emission, propagation and absorption of energy. This includes high energy electromagnetic radiation such as X-rays, gamma rays and particulate radiation such as electrons, protons and heavier particles (e.g alpha particles). Ionising radiation produces biological effects when ionised atoms cause breakage of chemical bonds leading to the formation of highly reactive free radicals, which react with and damage biomolecules such as DNA. X-rays, gamma rays and electrons are the most widely used forms of ionizing radiation in the clinical setting and the typical energies used, vary from 50 kilovolts (kv) to 25 megavolts (MV). The unit of absorbed radiation dose is the Gray (Gy) (1Gy = 1 joule per kilogram (J/KG)) Production and delivery of therapeutic radiation Clinically useful radiation is produced both artificially and naturally and can be delivered by three main methods – external beam radiation, brachytherapy, and systemic isotope therapy. External beam radiation (teletherapy). This involves delivery of radiation from a unit located external to the body. The most commonly used external beam units are: Superficial X-ray machines Differing energies can be produced. X-rays with energies of 10-150 kV are known as superficial X-rays and are useful for treating skin cancers. X-rays with energies of 200- 10 500kV are known as orthovoltage and can be used to treat thicker skin lesions and superficial bone lesions such as rib metastases. 60 Co machines. Gamma rays with energies of 1.17 and 1.33 MeV are emitted from the artificially 60 produced radionuclide Cobalt-60. A source of Co can be placed within a heavily shielded (lead and uranium) treatment head and moved mechanically over an aperture to produce a beam of radiation that can be aimed at the patient. Some of these machines are still in use, but most have been replaced by linear accelerators. Linear accelerators These machines can produce very high-energy megavoltage X-rays (photons) (4-40 MV) and electrons. The design of the machine allows the treatment head to rotate 3600, allowing treatment of the patient at any angle. This type of high-energy radiation has the advantages of good tissue penetration coupled with a skin sparing effect. Linear accelerators can also produce electron beams by simply removing the tungsten target and replacing it with thin copper foil, which is virtually transparent to the incident electron beam. Electrons are very useful for treating superficial tumours as they have a rapid fall off in dose and can thereby spare underlying tissues such as lung and spinal cord. The effective treatment depth in cms is approximately equal to 1/3 of beam energy (e.g 12MeV electrons have an effective treatment depth of ~ 4 cms). Brachytherapy This involves placement of radioactive sources within tissues/tumours (interstitial therapy) or body cavities (intracavitary therapy). Very high doses of radiation can be delivered directly to the immediate area where the sources are placed, with a rapid fall 11 off in dose intensity with increasing distance from the sources (inverse square law). Therefore, accurate placement of the radioactive sources is required to achieve an adequate dose distribution to eradicate the tumour and minimise normal tissue damage. Brachytherapy may be used radically with curative intent (e.g cervical cancer, prostate cancer, tongue cancer), adjuvantly (e.g breast "boost") or in the palliative setting (e.g recurrent head and neck cancer). permanent interstitial temporary brachytherapy intracavitary Interstitial therapy. This involves implanting radioactive sources into tissue which contains the tumour. Sites that can be treated include the head and neck (tongue, floor of mouth, neck nodes), breast, prostate, vagina, anal canal and skin. Permanent implants 125 Iodine 125 seeds are commonly used to treat early prostate cancer. I has a half-life of 60 days and emits low energy (27-35 kV) gamma rays, which do not penetrate far into tissue. A very good dose distribution can be obtained by implanting 50-120 seeds under ultrasound guidance. Temporary implants. 12 Iridium 192 is the most commonly used temporary implant. It has a half-life of 74 days and emits gamma rays with a relatively high energy of 300-612 kV. Wires or seeds may be directly implanted into the target volume and then removed after a specified time when the required dose is delivered. (e.g tongue and floor of mouth tumours). Afterloading techniques may also be used. This involves inserting hollow tubes/catheters into the target volume and then loading them with radioactive sources either by remote control or manually afterwards. This method reduces radiation exposure to the staff. Intracavitary therapy. This involves placement of hollow applicators into body cavities and then using afterloading techniques to introduce radioactive sources safely. The main use is in gynaecological oncology and various techniques are in clinical use. For treatment of cervical cancer, an intrauterine tube and vaginal applicators (ovoid or ring) are inserted 192 and connected to a remote afterloading machine. This automatically loads an Ir source to predetermined positions within the tubes to achieve the best dose distribution. This is a high dose rate (HDR) system that allows large doses of radiation (upto 7 Gy) to be given within minutes. Low dose rate systems (e.g with Caesium137) can also be used but require 2-3 days of inpatient treatment. For endometrial cancer in the adjuvant setting, a vaginal applicator is applied and then connected to an afterloading system. Systemic Isotope Therapy. Involves the oral or intravenous administration of radionuclides. The best example is the use of iodine-131 in the treatment of thyroid cancer and thyrotoxicosis. Other examples include the use of Strontium 89 to treat bone metastases, Phosphorous-32 for the treatment of polycythaemia and MIBG for neuroblastoma. The use of 13 monoclonal antibodies conjugated with radionuclides for cancer therapy (radioimmunotherapy) is under investigation. Side effects and toxicity of radiotherapy. Radiotherapy causes a broad spectrum of normal tissue reactions that limit the total dose of radiation that can be delivered safely to a tumour. The severity and time course of the reactions depends on the total dose of radiation, the fraction size, overall treatment time, tissue type, the volume of tissue irradiated and the clinical state of the patient. The achievable tumour control rate depends on the radiation tolerance of normal tissues. Radiation effects on normal tissues can broadly be divided into early/acute, subacute and late reactions: Early/acute reactions These occur during, immediately after or within a few weeks of the end of treatment. Acute effects are due to depletion of stem cells and therefore the tissues most affected tend to be the rapidly proliferating tissues such skin, mucosal tissue and haemopoietic tissue. The intensity of the reaction reflects the difference between stem cell loss and clonogen renewal. Acute reactions are usually self-limiting and normally settle within a few weeks of treatment completion. Subacute reactions (early delayed). These reactions occur between one and 6 months after completion of radiotherapy and are usually self-limiting over a period of a few weeks or months. Examples include: a. Radiation pneumonitis. Often responds well to a course of oral steroids. 14 b. Lhermitte's sign. This is an electric shock-like pain that shoots down the spine and represents a reversible type of demyelination injury following spinal cord irradiation. c. Somnolence syndrome. Occurs following brain irradiation and manifests as a transient period of severe exhaustion, lethargy and anorexia lasting typically for a few weeks. Acute effects of radiotherapy Tissue Acute Reaction Management skin Erythemas, dry desquamation, Moisturising creams, dressing, moist desquamation, ulceration antibiotics and hydrocortisone GI Tract and hair loss Oral hygiene, mouthwashes, Oropharyngeal mucositis analgesia, and treat infections Mucaine liquid, analgesia, Oesophagitis/gastritis antacids Gastroenteritis Antidiarrhoeals, antiemetics Lung Proctitis Stool softeners, steroid enemas Bladder Pneumonitis Steroids. Bone Marrow Cystitis – frequency and dysuria Fluids, analgesia Eye Suppression of erythropoiesis Transfusions and growth factors Ear Conjunctivitis, dry eye Treat infections, artificial tears Acute otitis externa, serous otitis Treat infections. topical steroids media or myringotomy Late reactions These effects develop over months or many years following irradiation and are usually progressive. The late effects of radiation are usually the dose limiting factor and tends to affect slowly proliferating tissues such as nervous tissue, lung, kidney, liver and 15 heart. See the table below with organ specific late effects. Pituitary or thyroid irradiation may cause endocrine dysfunction. Late effects are dose related and the risk is greater with high radiation doses, large fraction sizes and larger treatment volumes. Damage to stromal tissue (vasculature and connective tissue) and reduced proliferative capacity of stem cells are thought to be the main mechanisms for the late effects of radiotherapy. Carcinogenesis is also a late complication following radiotherapy. The latency period for solid malignancies is around 20 years. Leukaemia may occur between 7-12 years following radiotherapy. Late tissue effects Tissue Clinical manifestations of late effects Brain Lethargy, cognitive impairment, dementia, pituitary dysfunction. Spinal cord Spinal cord and peripheral nerve injury may lead to myelopathy and neuropathies respectively. Eye Dry eye, cataracts and retinopathy Gastrointestinal Bleeding, diarrhoea, malabsorbtion, strictures, obstruction, Liver perforation, Bladder and urethra Veno-occlusive disease, hepatitis, ascites and liver failure Bladder spasms, reduced bladder capacity, haemorrhagic cystitis, Kidney obstructive uropathy, Lungs Hypertension, renal impairment, renal failure Heart Fibrosis, restrictive lung disease Pericarditis, cardiomyopathy, coronary artery disease, valvular Head and neck disease (mainly aortic valve), arrhythmias (due to conduction 16 Female organs system fibrosis), Xerostomia, laryngeal necrosis, hypothyroidism, Male organs Osteoradionecrosis Vaginal strictures and dryness, early menopause, infertility, Skin, muscle, bone telangectasia and bleeding, lymphoedema, fistula formation Infertility, impotence, low volume ejaculate, Telangiectasia, hair loss, lymphoedema, fibrosis, contractures, mobility problems, growth problems (mainly in children), dysmorphia NORMAL TISSUE TOLERANCE DOSE The tolerance dose is an attempt to express minimal and maximal injurious dose acceptable to clinician and also measured as normal tissue complication probability (NTCP) Minimal tolerance TD5/5 - the dose in given population exposed under standard set of treatment conditions resulting in no more than 5% severe complication rate within 5 years treatment. Maximum tolerance TD50/5 - dose that results in a 50% severe complication rate 5 years after treatment. The following are examples of NTCP for various organs in specific conditions: Megavoltage treatment(1-10 MeV) Dose delivery of 2 +/- 10% Gy per day, 5 fractions weekly, or 10Gy, with 2 day rest intervals Completion of treatment in 6-8 weeks Doses conditioned by partial volume organ iiradiation These values are based on current data and clearly should be taken as a guide only. 17 Target cells Complication end point TD5/5 to TD5/50 (Gy) 2 – 10Gy Lymphocytes aand Lymphopenia 2-10 lymphoid Testes.spermatagonia Sterility 1–2 Ovarian,oocytes Sterility 6 – 10 Diseased bone Severe 3-5 marrow leukopenia,thrombocytopenia 10 – 20Gy Lens Cataract 6 -12 Bone marrow stem Acute aplasia 15-20 cells 20 – 30Gy Kidney :glomeruli Arterionephrosclerosis 23 – 38 Lung: type 2 cells, Pneumonitis or fibrosis 20 - 30 vascular connective, tissue stroma 30 – 40Gy Liver: central veins Hepatopathy 35 – 40 Bone marrow Hypoplasia 25 -35 40 – 50Gy Heart(whole organ) Pericarditis or pancarditis 43-50 Bone marrow Permanent aplasia 45-50 microenvironments 50 – 60Gy Gastrointestinal Infarction necrosis 50 -55 Heart (partial organ) Cardiomyopathy 55 – 65 Spinal cord Myelopathy 50 - 60 60 – 70Gy Brain Encephalopathy 60 – 70 Mucosa Ulcer 65 – 75 Rectum Ulcer 65 – 75 Bladder Ulcer 65 – 75 Mature bones Fracture 65 – 70 Pancreas Pancreatitis >70 18 Basic radiobiology The most important biological effect of radiation is DNA damage; especially double strand (DS) breaks in DNA. Damage to DNA occurs by both direct and indirect means. Direct damage occurs from ionisation of atoms within the DNA molecule itself, but the majority of DNA damage occurs indirectly by reactions with free radicals produced from the hydrolysis of water molecules (e.g hydroxyl (OH.) free radical). The presence of molecular oxygen (O2) enhances radiation induced DNA damage by binding to short-lived reactive free radical sites in cellular DNA, thus chemically fixing the damage. This explains why hypoxic (low levels of O 2) cells are more resistant to radiation. Cellular events following radiation exposure are complex, but involve activation and expression of many genes. Depending on the amount of damage, cells may die immediately or after several cell divisions, have delayed growth (temporarily or permanently ), or continue to divide. Fractionation In order to achieve cure, all cancer cells capable of dividing (clonogenic cells) must be killed. Higher doses of radiation kill more clonogenic cells increasing the chances of cure, but also increase the risks of normal tissue damage. Hence, as tumour tissue is not that different to normal tissue, there is often a small therapeutic window between tumour cure and normal tissue damage. However, it was realised by French radiotherapists in the 1920's that an overall higher dose of radiation could be given to tumours with less damage to normal tissue if it was divided into smaller fractions and given over a longer period of time. This is known as fractionation and the biological 19 factors that influence normal tissue and tumour responses to fractionated radiotherapy can be summarised in the five "Rs" of radiotherapy: Intrinsic radiosensitivity. This is a measure of the extent of cell damage caused by a particular dose of radiation. It varies greatly between different types of tumours and normal tissues. The radiosensitivity of some tumours may reflect the radiosensitivity of the normal tissue they were derived from. For example, lymphoid and germ cell tissues are very radiosensitive and so are lymphomas and germ cell tumours. Bone, muscle and neuronal tissue are radioresistant and so are sarcomas and gliomas. Cells are most sensitive to radiation in the M (mitosis) and G2 (second gap before mitosis) phases of the cell cycle and therefore tissues with a high proportion of dividing cells are usually more radiosensitive e.g lymphoid tissue, gut and skin. Repair and recovery. The majority of cell damage induced by radiation is sub-lethal and can be repaired. Repair increases cell survival (recovery). Most of the repair in normal tissues occurs within 6 hours of radiation exposure and if a second dose of radiation is given within this period, there is increased risk of normal tissue damage. By allowing adequate time for repair between doses of radiation, a much greater overall dose of radiation can be given with sparing of normal tissues. Fractionation of treatment leads to much less late radiation-induced tissue damage because repair of DNA prevents genetic errors being passed onto daughter cells. Differences in repair rates between normal tissue and malignant tissue contribute to the therapeutic ratio of effective radiotherapy i.e if cancerous cells have less ability to repair damage, there will be far less sparing of cancerous tissue than normal tissue. 20 Repopulation. Prolonged courses of treatment allow time for cellular proliferation, repopulation and recovery of irradiated tissue. However if the repopulation rate of the tumour is higher than that of normal tissue, then protracted courses of radiotherapy or delays in treatment may allow time for tumour regrowth thus decreasing the chances of tumour control. This is most likely to occur in some anaplastic tumours with large growth fractions and short cell cycle times (e.g head and neck cancer). Reoxygenation. Hypoxic cells are much more radioresistant than well-oxygenated cells (see above). Thus, tumours with inadequate blood supply due to poor vasculature, clotting abnormalities and fast tumour growth are more likely to be radioresistant. Increasing the fraction time allows surviving hypoxic cells to re-oxygenate after the better oxygenated (more radiosensitive) cells have died off. The re-oxygenated cells are then more radiosensitive to the next fraction of radiotherapy. The exact mechanism of reoxygenation is not clear, but death and damage of the oxic cells reduces the oxygen consumption rate of the tumour and as the tumour shrinks, diffusion of oxygen is also increased Reassortment/ redistribution. This occurs when cells in the more radiosensitive phases of the cell cycle (M/G2) die off and the surviving radiosensitive cells redistribute into the more sensitive phases of the cell cycle. Subsequent fractions of radiation may then be more efficient at killing these cells. In clinical practice, the dose of radiation that can be given safely is determined mainly by the tolerance of surrounding normal tissues. For radical radiotherapy treatments, most centres use once daily fractionation schedules during weekdays without 21 treatment at the weekends. (The usual daily doses are 1.8-2.75 Gy over a 4-6 week period). This is not the optimum fractionation according to the above radiobiological principles, but is standard practice for logistical reasons. However, there has been much research into defining the optimal radiotherapy fractionation regimens and the following are some examples Altered fractionation regimens 1. Hyperfractionation. This aims to decrease late effects of radiotherapy on normal tissues and improve tumour control by using smaller more frequent fraction sizes. This allows an overall higher dose to be given over a similar period of time as conventional regimens. Typically, 2-3 daily fractions <1.5 Gy are used. 2. Accelerated hyperfractionation (AH) and Continuous Hyperfractionated Accelerated Radiotherapy (CHART). Accelerated hyperfractionation aims to overcome tumour repopulation by reducing overall treatment time. This can be achieved with the same dose and fraction number as conventional treatment by using multiple daily fractions of radiotherapy 6-8 hours apart. CHART is similar, but patients are also treated at weekends to decrease the overall treatment time even further. CHART has recently been shown to improve survival in lung cancer patients compared to standard fractionation. However, both AH and CHART increase acute side effects of treatment and due to logistical problems in terms of implementation, they are not in wide use in the UK. 3. Hypofractionation. A smaller number of fractions are given, but the dose per fraction is higher. The overall dose given must be lower than with conventional radiotherapy, due to the increased risk of late side effects. Hypofractionation is particularly useful in the palliative situation as the overall treatment time is short and the large daily doses can be particularly effective in fast growing, aggressive, symptomatic cancers. 22 4. Split-course irradiation. Large doses per fraction are used daily increasing the risk of late side effects, therefore a treatment gap of a few weeks rest is allowed before continuing. Mainly used in the palliative setting as not as effective as conventional radiotherapy due to the problem of tumour repopulation during the treatment gap. Other ways of improving the therapeutic ratio include 1. Radiosensitizers and radioprotectants. Drugs that enhance tumour radiosensitivity or protect normal tissues radiation damage have been the focus of much research. Oxygen is the most important radiosensitizer known. Positive results have been seen with hyperbaric oxygen as a radiosensitizer, but logistical difficulties of treating patients in hyperbaric chambers have restricted its use to the experimental setting. Other drugs that can mimic the properties of oxygen have been tried (e.g misonidazole, nimorazole) but toxicity problems have limited their use. The radioprotectant amifostine is a free radical scavenger and has shown much promise in clinical trials, but also has significant side effects. 2. Hyperthermia. Moderately heating tissues to 42-45 0C can destroy malignant and normal cells. The combination of hyperthermia with radiotherapy is particularly attractive because radioresistant tissues with poor blood supply and hypoxia are more responsive to hyperthermic damage than well-oxygenated tissues. In addition, hyperthermia increases tissue radiosensitivity. Many clinical trials have shown hyperthermia alone and in combination with radiotherapy to be effective in a wide variety of malignant diseases, but logistical problems such as the treatment of deep-seated tumours and cost have restricted its use to research institutes. Microwave and ultrasound are the most commonly used heating techniques. 23 Concurrent Chemoradiotherapy. Concurrent chemoradiotherapy has become a major treatment modality in the treatment of many cancers including head and neck, cervix, rectum, anus, lung and oesophagus. The simultaneous administration of chemotherapy during a course of radiotherapy may enhance the tumour response by a variety of mechanisms that include inhibition of cellular repair, reduction in the number of hypoxic tumour cells, redistribution of cells into the more radiosensitive phases of the cell cycle and treatment of microscopic systemic disease. Unfortunately, this is often at the expense of increased normal tissue toxicity. Commonly used drugs with radiation include cisplatin, 5FU, gemcitabine and mitomycin C. 3-Dimensional Conformal Radiotherapy Planning. Most radical radiotherapy planning now utilises this technology. Conformal radiotherapy can help maximise tumour dose and minimise dose to normal surrounding tissue. CT scans are taken of the patient in the treatment position and the images are transferred into the treatment-planning computer. The clinician can then mark on each CT slice the required volume to be treated. The computer generates a 3- D image of the volume to be treated and critical structures at risk can be highlighted. This helps define the best beam arrangement and the computer then calculates the optimum dose distribution. A beam's-eye view can be generated digitally (digitally reconstructed radiograph- DRR) to give an image of how the simulation film should look and this is also used in treatment verification. Critical structures can be shielded by beam shaping, which can be achieved with customised lead blocks or the use of multileaf collimators (MLCs- computer controlled motorised movable lead leaves within the treatment machine which can block part of the radiation field). The radiation field can therefore be conformed to the shape of the volume to be treated. 24 Intensity modulated radiotherapy – IMRT. This is an exciting recent development in 3-D conformal radiotherapy made possible by technical advances in computer technology. IMRT is based on the concept of inverse treatment planning which means than the clinician defines the treatment volume and surrounding normal tissue volumes and specifies certain dose restrictions on these volumes. The computer then calculates optimisation of beam parameters. With this information the computer is then able to control the shape of the radiation beam and modify its intensity by moving multi-leaf collimators in and out of the treatment field. This process can produce additional sparing of critical normal tissues allowing further dose escalation to the tumour and is especially useful for volumes with concave surfaces. It is used to treat prostate cancer and head and neck cancers. However, there are disadvantages to IMRT. There is very little room for error in patient set-up and any organ movements or patient movements may drastically alter the dose plan. For these reasons IMRT requires precise patient set-up each day as well as excellent immobilisation techniques. The other main disadvantages are cost and increased treatment time for the patient. Stereotactic radiotherapy and radiosurgery. This modality of treatment is a technique of high precision localised radiotherapy allowing high-dose radiation to the target volume with minimal dose to surrounding normal tissue. Its main use is in the treatment of brain metastases. One very large fraction (stereotactic radiosurgery) or 2-3 smaller fractions (stereotactic radiotherapy) are usually given. Proper immobilisation with a stereotactic frame attached to the skull is required to ensure very accurate delivery of the high dose radiation, which can be 60 delivered by the Co Gamma Knife or a linear accelerator with specialised collimators. 25 Both techniques rely on the production of multiple thin (pencil) radiation beams focused on a small volume (maximum tumour size usually 3-4cms). 26
Pages to are hidden for
"4 Principles of radiotherapy"Please download to view full document


text:
Trócaire stalwart Sally O'Neill to retire in April
- Social Affairs
- March 30, 2015, 13:26
Tributes have been paid to Sally O'Neill, Trócaire's head of region for Latin America, who is to retire next month. Ms O'Neill has been at the heart o(...)
Irish Aid calls for volunteers to join Rapid Response Corps
- Social Affairs
- March 23, 2015, 22:06
Irish Aid is calling for skilled and experienced volunteers to consider joining the Irish Rapid Response Corps as part of the Government's programme f(...)
Trócaire programme brings climate change into the classroom
- Education
- March 17, 2015, 05:00
'Do you think you do a good job at looking after the planet?" The group of third-year students from Loreto Secondary School in Navan shuffle th(...)
Human history pushed back 400,000 years by new discovery
- Africa
- March 4, 2015, 21:41
Human history has been pushed back 400,000 years with the discovery of a fossil jawbone dating back almost three million years.The lower jaw, uncovere(...)
Teagasc signs agreement to use its work to help developing countries
- Africa
- February 20, 2015, 15:54
Teagasc and Irish Aid have signed an agreement to use agricultural research and training to help developing countries.The agricultural research body a(...)
Irish firm bids to improve banking services in Ethiopia
- Technology
- February 6, 2015, 01:10
Ethiopian banks and microfinance firms are launching mobile money services, helping reach swathes of the population that now have little access to bra(...)
Sisi cuts short Ethiopia visit after 26 killed in Sinai attacks
- Africa
- January 30, 2015, 09:41
Egyptian president Abdel Fattah al-Sisi cut short a visit to Ethiopia for an African Union summit on Friday, following a wave of deadly attacks in the(...)
1984: the year that brought Ronald Reagan and Dunnes strikers
- Politics
- December 26, 2014, 06:00
It was a time when a Labour party in coalition with Fine Gael took a kicking in European elections, two cases involving the deaths of babies shook the(...)
Let us sing a song of praise to . . . the Irishry
- Editorial
- December 16, 2014, 00:01
It's the season of goodwill, so let's attempt it. That honest Staffordshire man Dr Samuel Johnson once said "the Irish are a fair people: they never s(...)
Credit where it's due: the Christmas gift of microfinance
- Life & Style
- December 12, 2014, 06:00
Agnes Phiri isn't looking for charity. The 24-year-old mother-of-one runs a grocery store in Katete, eastern Zambia. Although Zambia is the poorest co(...)


text:
Fringe News
News on Fringe continually updated from thousands of sources around the net.
John Noble Recalls His Time on Fringe, 24, Sleepy Hollow and More
Friday Mar 27 | TVLine | Comment?
'Agents of SHIELD': Where you've seen those new faces before
Tuesday Mar 24 | Entertainment Weekly | Comment?
Syfy Greenlights Season Two of Adventure Thriller 12 MONKEYS
Thursday Mar 12 | BroadwayWorld.com | Comment?
The CW Announces Season Finale Dates for The Vampire Diaries, Arrow and More
Wednesday Mar 11 | The Hollywood Gossip | Comment?
How to Watch Leonard Nimoy's Most Memorable Performances Online
Feb 27, 2015 | Time | Comment?
Trending Now
Updated: Fri Mar 27, 2015 04:53 pm
Copyright © 2015 Topix LLC


text:
Kentucky is suing Purdue Pharma on claims that the company misrepresented its prescription painkiller, resulting in a wave of addiction and increased medical costs across the state. Kentucky officials filed theirs, which included claims that Purdue Pharma lied about the addictiveness of the drug to doctors, who then overprescribed it to an unwitting...» Read More
Copycat biotech drugs in the U.S. market could cut prices of expensive medications by 40 percent to 50 percent, said a top CVS Health exec.
The move happened after the Irish Court of Appeal found the 1977 Misuse of Drugs Act was unconstitutional.
Raghuram Selvaraju, managing director, Healthcare equity research at MLV & Co, discusses whether AbbVie's acquisition of Pharmacyclics for about $21 billion is a good move.
JUPITER, Florida, March 2- In October 2003, Jeb Bush unveiled one of the largest economic projects in Florida history: a $500 million plan to bring Scripps Research Institute to the state and build a biomedical hub he said would generate nearly 50,000 jobs in 15 years. As governor, he described it as a "seminal moment," comparable to Walt Disney World's arrival in...
With all the fibbers we've outed lately, Turney Duff takes a look at the top 10 lies told on Wall Street.
Marijn Dekkers, CEO of Bayer, says the company plans to increase its R&D budget this year, after strong earnings.
Marijn Dekkers, CEO of Bayer, talks about the company's plans to separate themselves from their material science unit, saying they will focus on life sciences businesses going forward.
Arthur Mondella, president and CEO of Dell's Maraschino Cherries, killed himself Tuesday during a drug raid.
LONDON, Feb 10- Global health charity Medecins du Monde launched a legal challenge on Tuesday to a European patent held by U.S. drugmaker Gilead Sciences Inc which it accused of charging "exorbitant" prices for a hepatitis C drug. According to World Health Organization data, as many as 150 million people worldwide live with chronic hepatitis C infection, most of...
Turney Duff, now five years sober, talks about how cocaine crushed his trading skills—and cost him and his firm millions.
Cocaine users seem to not to feel the losses associated with bad predictions, and this may mean their brains have more trouble learning from mistakes.
NEW YORK, Feb 3- A U.S. prosecutor sought on Tuesday to dissuade jurors from believing that the man who created the underground website Silk Road and is facing drug trafficking charges abandoned the venture long before it was shut down. Ross Ulbricht, who is on trial in Manhattan federal court, has acknowledged creating Silk Road, where drugs and other goods could...
Sanofi launched an inhalable insulin in the U.S. in a potential boost for its flagging diabetes drug sales and for patient quality of life.
Marvina is a premium cannabis provider that offers a monthly delivery service of marijuana to consumers in San Francisco.
Regeneron Pharmaceuticals CEO Dr. Leonard Schleifer told CNBC on Tuesday that benefits companies should not try to practice medicine.
The Justice Department kept a secret database of incoming and outgoing U.S. international calls for more than a decade.
"Any event in life changes one. That was an event that probably changed me in many ways. I think I am a better person," biotech company founder Sam Waksal.
Rather than pay so much out-of-pocket, many skip checkups and scrimp on care, USA Today reports.
This flu season is ramping up earlier than last year's, NBC News reports.
Hallucinogenic mushrooms have been discovered on the grounds of Buckingham Palace in London, NBC News reports.


text:
- Brucies Races - Grand Theft Auto 4
Back to Grand Theft Auto 4 Guide Index
More for this game: PS3 | Xbox 360|
After the "No.1" mission, you can call Brucie to participate in street races taking place around the city. There are a total of 9 races, and each consisting of 3 or 5 laps around a different part of the city. There are three tracks in Dukes/Broker, three in Algonquin, and three in Alderney, so once Brucie tells you that there aren't any races going on, move on to one of the other islands and call him from there.
There really isn't much to these races; get a fast car, meet the others at the start point, follow the waypoints around the track, and be ahead of the pack when the final waypoint is reached. A Comet, Infernus, Turismo, Banshee, or Super GT is best suited for these races. You can use motorcycles too, but they aren't recommended. The quality of your opponents' cars will improve as you win more races, but either way, once you get a good lead you should be able to keep it the whole way through as long as you keep your eyes on the road. You're not trying to break any records here, so once you're in first, just concentrate on avoiding crashes—which can set you back quite a bit—rather than reaching the finish line blazingly fast.
Note: The races can be replayed; just call Brucie a couple of times after he tells you that there aren't any more races, and he will set you up with one of the previous race. Though winning yields little reward in terms of money, replaying these races is a must to unlock the "Genetically Superior" achievement on the Xbox 360 version for which a total of 20 races must be won.
Added 27th Feb 2015, ID #521703
Added 2nd Jan 2015, ID #494732
Added 13th Jun 2014, ID #399123
Added 20th Sep 2013, ID #310321
Added 20th Oct 2012, ID #198655
Added 24th Jul 2012, ID #167808
Added 22nd Jul 2012, ID #167387
Added 19th Jun 2012, ID #154283
Added 5th Jun 2012, ID #149073
Added 24th May 2012, ID #144857
Added 16th May 2012, ID #142668
Added 13th Mar 2012, ID #122772
Added 22nd Dec 2011, ID #97652
Added 20th Nov 2011, ID #88760
Added 11th Aug 2011, ID #66093
Added 8th Aug 2011, ID #65164
Added 30th Apr 2011, ID #40650
Added 8th Feb 2011, ID #28502
Added 14th Jul 2010, ID #4463
Added 14th Jul 2010, ID #4397
Added 1st Jul 2010, ID #2609


text:
Staatsburg Senior Care
4 senior care providers near you. The average senior care rate is: $13.00. Share this rate and result with friends.
Staatsburg, NY
I have took care of my grandmother for a year, and I have to say patience is the most important item. I love doing it because I care so I try my best and it makes me see myself in the future.
1 yr of exp.
24 years old
Full Time Caregiver Available — Staatsburg, NY
Although my employment history does not show continuous care jobs, it starts in my home. I am a single mother of 2 children. I have worked in a nursing home before in the past and have also worked wit...
3 yrs of exp.
35 years old
Staatsburg, NY
I absolutely love dogs and cats and have been pet sitting for many years. I am an experienced daycare provider and have had my own family daycare business for 16 years. I am very interested in serving...
10 yrs of exp.
61 years old
Dependable, Energetic, and Loving Individual Dedicated to Taking Care of Children and/or Senior Citizens — Staatsburg, NY
I have volunteered in two nursing homes and absolutely loved it. Some of my responsibilities included transporting individuals to and from their rooms, assisting in meal times, participating in variou...
0 yrs of exp.
31 years old
More Care Options
Senior Care Near Staatsburg
- Senior Care New York, NY
- Senior Care Hyde Park, NY
- Senior Care Rhinebeck, NY
- Senior Care Pleasant Valley, NY
- Senior Care Poughkeepsie, NY
- Senior Care New Paltz, NY
- Senior Care Highland, NY
- Senior Care Hurley, NY
- Senior Care Wappingers Falls, NY
- Senior Care Salt Point, NY
- Senior Care Clinton Corners, NY
Additional Senior Care Resources
Join free today
Sign up now! It only takes a few minutes.
I'd like to...
Who needs care?
What type of ?
When do you need ?
What services do you offer?
What best describes you?
Last, but not least...
Fill in the blanks to create your account.
Thanks—you're almost there.
Create your login below.


text:
ON NPR: UDC David A. Clarke School of Law Professor Andrew G. Ferguson has been visible in the media quite a bit lately on the strength of his recent book, Why Jury Duty Matters, and as a go-to expert on juries with regard to the high-profile Zimmerman murder trial.
In this National Public Radio story, however, Ferguson is called on to discuss the implications of increasing police use of crime predictive software. To read a (surprisingly inexact) transcript of the NPR story or to listen to it, click HERE.
In The Economist: Prof. Ferguson was also quoted by The Economist on "predictive policing." To read more, see Story
_ _ _________________________________________________ _ _
The University of the District of Columbia David A. Clarke School of Law, www.law.udc.edu, is among the nation's most racially, ethnically, class and age-diverse law schools. Its minimum of 740 hours of clinical public interest legal service - a sum exceeded by most of its students - is clear evidence that the UDC David A. Clarke School of Law is America's preeminent public interest law school.
3/25/2015Jessica Watkins, '14, in BNA's Personal Tax Ins...
Remember Me
Forgot your password?
Haven't registered yet?
4/2/2015Law School Admission Information Session
4/8/2015Is the Exelon Takeover of PEPCO in the Public Interest?
4/9/2015Law School Admission Information Session
4/15/2015NPR 'Morning Edition' Producer Ricardo Sandoval-Palos


text:
Unless children can get to school on time and safely, the world's best teachers can't help dig South Carolina out of its educational slough.
And unless the House-passed budget's allocation for new school buses grows a lot, it will be increasingly difficult for students to do just that.
Why? Because the oldest and most polluting school bus fleet in the country will continue to break down more, frequently require more maintenance, use more gas and fail more often to get children to school on schedule.
But the real cost of using buses that are too old even to be under warranty is the risk of a serious accident in which children are injured or killed.
State Superintendent of Education Mick Zais has demonstrated that he is fiscally conservative. Last year he didn't even ask for an increase in his department's budget.
This year, he says he needs $46 million for new school buses — $34 million from the state's capital reserve fund and $12 million from unclaimed lottery prize money to replace old, unreliable buses.
Instead, the House budget includes only $10.5 million from the capital reserve fund and not one dime in unclaimed lottery prize money.
Besides being woefully inadequate ($1.7 million less than last year), the allocation would be non-recurring revenue, meaning it would not be guaranteed in subsequent budget years.
And it fails to meet the General Assembly's own mandate that a portion of unclaimed lottery prize money be used for school bus purchases.
A 2007 state law also requires the fleet to be replaced every 15 years. It was enacted after The Post and Courier reported on the sorry state of South Carolina's school bus fleet.
Dr. Zais' budget request would begin the replacement cycle established by the Legislature — and then ignored. School buses should not be shorted as if they are somehow not essential.
Earlier this year, the state received 342 new buses to be distributed statewide. They are to replace some that are 28 years old, and they were paid for ($24.6 million) mostly by lottery funds and unclaimed lottery prizes. It was the first time since 2006 that unclaimed lottery money was applied to school bus purchases.
We shouldn't expect help from the governor. Her budget includes no money for school buses. Last year, she vetoed the $12 million school bus allocation. Instead, she advocates transferring responsibility for buses to individual school districts.
The experience of threatened bus driver strikes in Charleston, Beaufort and Dorchester counties suggests that might not be the best model. In contrast, public employees could not legally go on strike.
Older buses can have safety problems and are prone to catching fire. Some have holes in the floor which can allow exhaust fumes to waft in and be inhaled by children. Most lack standard safety features and equipment found on new buses to transport students with disabilities.
The Legislature is ignoring its responsibility by failing to replace school buses on a regular cycle and by failing to provide lottery money on a regular basis for that purpose.
Worse, lawmakers are failing the state by playing fast and loose with students' safety.
Notice about comments:
The Post and Courier is pleased to offer readers the enhanced ability to comment on stories. Some of the comments may be reprinted elsewhere in the site or in the newspaper. We ask that you refrain from profanity, hate speech, personal comments and remarks that are off point.
We do not edit user submitted statements and we cannot promise that readers will not occasionally find offensive or inaccurate comments posted in the comments area. If you find a comment that is objectionable, please click the X that appears in the upper right corner when you hover over a comment. This will send the comment to Facebook for review. Please be reminded, however, that in accordance with our Terms of Use and federal law, we are under no obligation to remove any third party comments posted on our website. Read our full terms and conditions.


text:
I don't know much about any of this, but, from what i understand about conical fermenters, they use the cylindrical shape of the cone/fermenter to create a convection current in the fluid in order to get to the yeast and turb that would accumulate in the bottom most part of the cone. Would a square cone allow the same process?
Reading this thread got me interested in the mathematics of making a cone from a flat piece of metal, so I amused myself by working out some equations which may be of use to those who need to make a cone. In the link above (How to Build a Conical Fermentor Cheap) the cone was made from a semicircular template. This gives a fixed angle between the sides of the cone and the centerline of 30 degrees, for the end dimensions specified. I don't know what the standard is for conical fermentors, but it is easy enough to make a template to give whatever angle is desired; i.e., either a taller, more slender cone, or a shorter, fatter cone.
All cones can be made from a sector of an annulus - the area contained between two concentric circles, and between two radii extending out from the common center, cutting through both circles. Call the radius of the smaller circle r1 and the radius of the larger circle r2, and let theta be the angle between the two radii extending out from the center. The problem is, given the cone dimensions, to determine the values of r1, r2, and theta so you can cut the flat piece of metal for the cone.
D1 = the diameter of the small end of the cone
D2 = the diameter of the large end of the cone
H = the height of the cone, along its centerline
L = the length of the cone measured along the cone from end to end
phi = the angle which the side of the cone makes with the center line of the cone
NOTE: all angles in the following equations are measured in radians - multiply by 57.3 to convert to degrees, or divide by 57.3 to convert from degrees to radians.
Typically you will know D1, D2, and either H or phi. If you know H, then:
L = H^2 + ((D2-D1)/2)^2 and phi = arccos(H/L)
If you know D1, D2, and phi, then H = (D2-D1)/(2*tan(phi)), and L can then be determind as above, or also by L = H/cos(phi).
Now from D1, D2, and L, we can easily find r1, r2, and theta:
theta = (PI*(D2-D1))/L
r1 = (PI*D1)/theta
r2 = (PI*D2)/theta
Another useful calculation is to determine the minimum dimensions of the rectangular sheet from which the cone can be cut. These numbers can easily be obtained from r1, r2, and theta. There are four cases, depending on the value of theta:
Call the length of the two sides of the rectangle S1 and S2.
Note - angles here are in degrees
* theta < 90 degrees
S1 = r2 - r1*cos(theta)
S2 = r2*sin(theta)
* 90 <= theta <= 180
S1 = r2*(1+cos(180-theta))
S2 = r2
* 180 <= theta <= 270
S1 = 2*r2
S2 = r2*(1+sin(theta-180))
* 270 <= theta < 360
S1 = S2 = 2*r2
Disclaimer - I believe these equations are right, but the calculation was kind of "quick and dirty", so before you use them to cut an expensive piece of metal, remember - "Measure twice, cut once."
Interesting idea but, how bout this. Make it out of any metal you want, either round or square and instead of welding the joints use lead free silver solder. You could get your smooth inner joints without grinding them smooth. You could also leave a lip on the outside of the cone/cylinder/pyramid/square that could be used to clamp the joints together while soldering.
Heck be the first to have a transparent fermenter, you can do it with plastic and one of those plastic solvent glues, silicone or food grade epoxy. They have been building aquariums that way for years. It would be like caulking a bath tub.
The hardest part is going to be getting an air tight seal on what ever you use as a lid. How much pressure builds up inside a fermenter anyway? 5 to 10 psi?
Just my 2 cents, Pinworthy.


text:
Jinnah Garden (Bagh-e-Jinnah), Lahore
2 Reviews
2 Reviews
If you would like to visit "garden of the gardens" or want to enjoy the most pleasant walk in Lahore, then go to historical park "Jinnah Garden". Established in 1862 over a large area of 140 acres. At that time thousands of saplings of hundreds of different species from every corner of the world were brought here. The very first tree was planted by the daughter of the commissioner of Lahore during January of 1862.
There are several entertainment and sports facilities within the garden that comprise of an open-air theatre, a restaurant, tennis courts and kids play land. But the pride of the entire garden is the cricket ground, Mughal garden and Gulshen Fatima. There is also a mosque and a huge library there.
A must visit place in Lahore.
Surronding the librarey are the spacious Jinnah Gardens laid out in 1860 and originally known as Lawrance Gardens. This is a recommended place to stroll and admire the trees labelled with their Latin names. At one end is a small zoo, open 8am to 5pm, founded in 1872, which is worth a visit if you have childern.
Get an instant answer from local experts and frequent travelers
Sponsored Links
Sponsored Links


text:
Workaholism In America Is Hurting the Economy 710
from the being-productive-vs.-looking-productive dept.
We've improved Slashdot's video section; now you can view our video interviews, product close-ups and site visits with all the usual Slashdot options to comment, share, etc. No more walled garden! It's a work in progress -- we hope you'll check it out (Learn more about the recent updates).
Dear team,
After coming back from my vacation in Aruba, I've decided that in these times of trouble we need to do more with less. We're in a troubled economy -- do you realize how much yacht gas has gone up in the past year? In addition, the Affordable Care Act has made it cost ineffective for our FTNE (Full Time Non-Employee) initiative to continue.
Moving forward, we'll need to tighten our belts and take on other responsibilities. Some of you will work longer hours than usual. My performance bonus is based on how much money we can save, so I'm simply going to let go anyone who refuses to comply with this iniative -- I'm sure I can find someone to replace you.
And what's up with this "In 1942, more than 80 percent of Americans slept seven hours a night or more. Today, 40 percent sleep six hours or less" part?
I had to do some mental math to convert those equilvent comparisons 20% got less than 7 hours in 1942, and today 40% get less than 6.
Why would they make me do mental math when they know I probably didn't get enough sleep last night?
Baaahhhhh says the sheep
But i'm addicted to workahol!