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LSA Resources Centre
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Work Health and Safety policies developed by Turfgrowers should look at including a robust and clear-cut policy around drugs and alcohol in their workplace according to Turf Accreditation organisation AusGAP's program manager, Nick Dorney. Speaking on the need to regularly review such policies, Dorney saysREAD MORE
NEW FARMSAFE INDUCTION TOOL ONLINE The new Farmsafe Australia Safety Induction Tool is now available online. It's free and seeks to further improve the safety induction of new workers –a great tool for your WHS system – check it out at www.induction.farmsafe.org.auREAD MORE
QUAD BIKE SAFETY TIPS The Australian Farmers Assn. has produced new tips aimed at keeping employees and family safe on farm with quad bikes – the leading cause of death on Australian farms for the past five years – Read more at www.bit.ly/2m1HyHEREAD MORE
Research by the Australian Centre for Agricultural Health and Safety based on media coverage from 2016, indicates there were 63 on-farm injury deaths last year. The main causes were tractors (9), other farm machinery (9) and quads (6). These three factors accounted for almost 40% of allREAD MORE
We're serious about forking safety, and you should be too. This guide (hit link above or below) prepared by Worksafe NSW will help you hold toolbox talks with your workers about the three main causes of forklift deaths and serious injuries, which are: 1. pedestrians being hit byREAD MORE
LSA Safety Alert 02-2017: LOOK AFTER NEW WORKERS – Turfgrowers are reminded of the importance of looking after new workers and ensuring proper training and inductions on farm and on site. Maintaining a safe workplace should be a priority and proper safety procedures should beREAD MORE
Dear All Many farms I have inspected have genuine power line hazard issues. Whether irrigation, spray or cropping plant and equipment potentially striking the lines, cattle & sheep trucks hitting powerlines or workers breaching excluding zones; it is an issue nearly every farm business operatorREAD MORE
The saying 'Familiarity breeds contempt' can have life-threatening consequences, especially at busy farming & transport operations. Fatigue, distraction & heat issues need to be managed with good processes says Turf Accreditation organisation AusGAP. Turfgrowers and Lawn Solutions members are being advised to review their safetyREAD MORE
LSA Safety Alert 43: MORE WHS TOOLS – If you need Toolbox Talk subjects or other Safety tools then Safe Work Australia broadcasts a series of free online seminars and podcasts that showcase the latest thinking, innovation, research and developments in work health and safetyREAD MORE
LSA Safety Alert 42: NEW WHS E-TOOLS have been launched by Worksafe Qld assist you improve work health and safety. The five eTools are easy to use and can be accessed on a range of devices and include a Heat Stress Calculator and Hazardous ManualREAD MORE
LSA Safety Alert 41: SAFE WORK MONTH – Safe Work Australia's Safe Work Month is nearing to an end, but it's not over yet! How has your workplace been participating? Test your WHS knowledge and tap into great WHS resources with Safe Work's online FactREAD MORE
LSA Safety Alert 40: Safe Work Australia has launched a new video website for Safe Work Month featuring free virtual seminars that showcase the latest research, developments and best practice in work health and safety. Hear from experts in workplace mental health, job design, youngREAD MORE
LSA Safety Alert 39: GET INVOLVED IN SAFE WORK MONTH – Safe Work Month is about improving work health and safety awareness and remembering the most important reasons for staying safe at work. Safe Work Australia has developed new resources for businesses to help getREAD MORE
GET INVOLVED IN SAFE WORK MONTH National Safe Work Month is held every October and aims to improve WHS awareness and discussion at work. National Safe Work Month, also encourages discussion about safety at work and share positive workplace stories from across Australia. In 2016READ MORE
"Employers should prioritise safety discussions and training to reduce young workers' risk of injury," is the message from WorkSafe Victoria which has released startling new safety statistics. Read more www.bit.ly/2cv2VerREAD MORE
CHAIN OF RESPONSIBILITY (CoR)– IT'S EVERYBODY'S BUSINESS A new fact sheet has been released from NHVR detailing responsibilities for everyone involved in transport to be aware of new Chain of Responsibility laws. Keep up with the latest information & read more at www.bit.ly/2cofApp &nbsREAD MORE
National Safe Work Month is held every October and aims to improve WHS awareness and discussion at work. Safe Work Australia has developed new resources for businesses to help get involved at your workplace. Get involved in National Safe Work Month National Safe Work MonthREAD MORE
Turfgrowers often deliver to tricky construction sites and careful assessment of hazards and communication is important. Worksafe Vic has developed new guidance to support safe work near roadways. Read more at www.bit.ly/2crwwdcREAD MORE
The National Road Safety Partnership Program (NRSPP) has launched a new national Mobile Phone Use in Vehicles Policy Guide – Read more at http://bit.ly/2bB2HHF &nbsREAD MORE
Installing reflective tape on trucks to improve their visibility could reduce some types of accidents between trucks and cars by up to 44 percent, the Australian Trucking Association's Senior Engineering Adviser, Chris Loose, said last week. Mr Loose was releasing the ATA's updated Technical AdvisoryREAD MORE
Heavy vehicle health checks ongoing Australia's heavy vehicle fleet will have their roadworthiness checked in a two-month survey which has commenced this month. Federal Minister for Infrastructure and Transport Darren Chester said the National Roadworthiness Baseline Survey would be the first time the same inspectionREAD MORE
LSA Safety Alert 30-2016: TAKE FORKING SAFETY SERIOUSLY – Forklifts continue to cause workplace deaths and injuries in workplaces around Australia. Workcover NSW has addressed this with a new safety campaign with a great range of downloadable resources. If you use or work near forkliftsREAD MORE
A new system of chemical classification is coming into effect and you need to be ready. It's called the Globally Harmonised System (GHS) of Classification and Labelling of Chemicals. Watch the video from NSW Workcover that shows simple steps to help you get there www.bit.ly/2ak3cSdREAD MORE
Great Farm Safety Resources . . . Go to the farmsafe.org.au site or http://bit.ly/2abLFPg or: Ag Health resources at http://sydney.edu.au/medicine/aghealth/farmers/index.php or http://bit.ly/2a7b6yF National Farm Safety Week National Farm Safety Week is an annual event held across Australia during July and aims to highlight the importance of safety on farms. TheREAD MORE
LSA Safety Alert 27-2016: MANUAL HANDLING RISKS VIDEO – Workcover Qld has produced a new short video that shows how businesses from various industries identify and manage hazardous manual tasks. Watch now with your team to see how you can help eliminate any similar hazardsREAD MORE
LSA Safety Alert 26-2016: SAFETY VIDEOS TO WATCH – Safe Work Australia has released a number of Safety Videos for small businesses on their Youtube channel recently. Take the time to check them out and see that you're up to date in your operation –READ MORE
LSA Safety Alert 25-2016: HIGH RISK WORK (HRW) LICENSING – It is crucial all staff who operate high risk machinery (including forklifts) hold a current HRW license. Heavy penalties do apply if an operator is caught without a current HRW license. More info at http://bit.ly/29dn6MWREAD MORE
The Working safely in Australia Information sheet provides new and migrant workers with current information on work health and safety and workers' compensation in Australia. This Information sheet explains that in Australia, employers must look after the health and safety of workers and that aREAD MORE
LSA Safety Alert 23-2016: 5 STEPS TO PREVENT STRAINS & SPRAINS – Watch this short video from Worksafe to help address some of the issues behind strain and sprain injuries that exceed 80,000 in NSW alone in the last three years from manual tasks –READ MORE
LSA Safety Alert 22-2016: Outdoor & Farm Workers are exposed to many hazards depending on type of work, geography, season & length of time spent outside – A Safety Alert has been issued by Worksafe Victoria following a snakebite fatality as an example of suchREAD MORE
LSA Safety Alert 21-2016: Quieter times on turf farms provide an ideal opportunity to assess & review Workplace Safety Consultation. Consultation is a legal requirement and an essential part of managing health & safety risks and can take many forms such as toolbox talks –READ MORE
Turfgrowers should be mindful of the dangers inherent in farm machinery and equipment following the tragic deaths of a number of farmers last week; with tractor and quad-bike incidents behind the fatalities. In a real wake-up call for all farmers, the three deaths in three days in Victoria last week has prompted WorkSafe toREAD MORE
Farmers are handy at a range of skills but electrical work is something that unlicensed people should ever attempt. That's the message from the new Energy Safe Campaign – read more at www.bit.ly/1U6OgEt Farmers are being urged not to attempt dangerous do-it-yourself electrical work asREAD MORE
Online assistance for small business Small businesses account for more than 95 per cent of all Australian businesses and are responsible for the health and safety of approximately 4.8 million workers. State and territory work health and safety regulators have developed resources to assist smallREAD MORE
LSA Safety Alert 18: LOOK UP AND LIVE Farmers are being urged to learn more about what to do if they contact powerlines, after recent electrocutions on farms in the past six weeks have resulted in two farmers dying after accidentally coming into contact withREAD MORE
No time to sit: Keeping active at work is best for your health Turf Growers are advised to keep abreast of a new report from Safework Australia on the risks of health problems around sedentary work – the type of work that doesn't involve much movementREAD MORE
LSA Safety Alert 16-2016: 10 steps to site inductions – Turf work off farm can present safety hazards for even the most seasoned workers and for those unfamiliar with the site the risks are multiplied. Simply 'showing them the ropes' isn't always enough to avoidREAD MORE
LSA Safety Alert 15-2016: New First Aid Model Code of Practice – A new code of practice has been developed by Safework Australia to provide guidance to better manage health & safety risks under the WHS Act in order to provide adequate first aid facilitiesREAD MORE
LSA Safety Alert 14-2016: NEW 'ALIVE AND WELL' WEBSITE – Over 5,000 NSW farmers have been injured at work over the last 3 years and Worksafe have put together a new website to enable farmers to share their safety stories and lessons learnt – CheckREAD MORE
LSA Safety Alert 13-2016: FARMS URGED TO PRIORITISE SAFETY – Farmers are more prone to workplace death & injury than any other workers in Australia according to the latest figures from WorkSafe that has prompted a new Farm Safety awareness campaign– Read more at www.wp.me/p74DQl-60READ MORE
LSA Safety Alert 12-2016: DESIGNING GOOD WORK – Safework Australia has recently issued a new handbook on the principles of good work design. Well-designed, healthy and safe workplaces allows for greater productivity to be achieved if hazards and risks are eliminated through good design –READ MORE
LSA Safety Alert 11-2016: WARNING ON GRINDERS & GUARDS – Worksafe has issued a safety alert around the correct use of grinders and their guards after a Queensland worker received fatal injuries while operating a 9 inch angle grinder. Ensure your gear is safe andREAD MORE
LSA Safety Alert 10-2016: WHAT SAFETY INSPECTORS LOOK FOR – Worksafe has bought together a number of resources on a new website that helps you identify and rectify risks in your workplace. Take a look for your own operation to see how you stack-up. ReadREAD MORE
LSA Safety Alert 09-2016: If your workers aren't safe, then neither are you – Worksafe – There's a strong message in Worksafe's latest ad campaign that emphasises the effects that injuries pose on the workplace and it's aimed squarely at employers. Read more at http://wp.me/p74DQl-4LREAD MORE
LSA Safety Alert 08-2016: WORKING WITH HERBICIDES SUCH AS GLYHOSATE – Worksafe Victoria has responded to recent WHO reports around herbicides such as glyphosate, and how to minimise risks to employees and others when using this chemical. For more info see fact sheet http://bit.ly/1VM4BkB GlyphosateREAD MORE
LSA Safety Alert 07-2016: WORKING WITH SUBMERSIBLE PUMPS ON FARMS WARNING – SafeWork has issued a reminder on working safely around submersible pumps after a recent death on a Victorian farm. Measures must be in place when around pumps as electricity is present. For moreREAD MORE
LSA Safety Alert 06-2016: SPATE OF FALLS PROMPTS SAFEWORK WARNING – SafeWork has issued a reminder of working safely at heights after two workers were killed and eight others seriously injured in falls from heights since the start of the year in NSW alone. MoreREAD MORE
LSA Safety Alert 05-2016: STAY SAFE AS IT HEATS UP AGAIN – SafeWork has issued a reminder of the importance of working safely this summer. Falls, higher chemical exposure, burns & heat stress are issues to be considered during hot days and heatwaves. More infoREAD MORE
LSA Safety Alert 04-2016: LOOK AFTER NEW WORKERS – Turfgrowers are reminded of the importance of looking after new workers and ensuring proper training and inductions on farm and on site. Maintaining a safe workplace should be a priority and proper safety procedures should beREAD MORE
LSA SAFETY ALERT 03-2016 – Spate of Tractor incidents prompts warning – Turfgrowers are reminded of the dangers of working around machinery and farm vehicles especially tractors following a number of on-farm accidents recently. Maintaining a safe workplace should be a priority and proper maintenanceREAD MORE
Turfgrowers can expect a Worksafe Inspection sometime soon on the back of recent announcements. Maintaining a safe workplace should be a priority and proper record-keeping and procedures should be in place. Read full AlertREAD MORE
Risks of workplace injuries increase in holiday periods with a casual workforce, family and friends sometimes on the farm and regular employees away can contribute to tragic outcomes on farms not managed properly. LSA-Safety-Alert-01-2016-STAY-SAFE-IN-HOLIDAYS.pdfREAD MORE
SafeWork has issued a reminder to celebrate end-year events safely. WH&S responsibilities at work functions are the same as the workplace- why not hold a tool-box-safety-talk prior to your shutdown? LSA Safety Alert 16-2015 – CELEBRATE END OF YEAR SAFELYREAD MORE
Risks of workplace injuries increase in extreme weather research has found. Falls, higher chemical exposure, occupational burns & heat stress are issues to be considered during hot days and heatwaves.READ MORE
Farms have been singled out as the most dangerous workplace in Victoria after a spate of deaths on regional properties over the past four weeks. Read full AlertREAD MORE
Recent breaches by transport operators, including turf businesses has increased the importance of safety in transport.READ MORE
The saying 'Familiarity breeds contempt' can have life-threatening consequences, especially at busy farming & transport operations. Fatigue, distraction & heat issues need to be managed with good processes.READ MORE
Approx 1.2M Aussie workers are exposed to diesel exhaust and Safe Work Australia released guidance material last week to help workplaces manage the risks of continued exposure.READ MORE
Research shows that the most safety-minded organisations are also among the most profitable and developing a safety culture pays off more than just reducing fatalities and injuries. Check out & download Safe Work Australia's latest Safety Stats Factsheet.READ MORE
National Safe Work Month continues – individuals and workplaces are encouraged to raise safety awareness. See the Virtual Seminar Series online – this week Supply Chains & Construction Industry.READ MORE
Risks of workplace injuries increase in extreme weather research has found. Falls, higher chemical exposure, occupational burns & heat stress are issues to be considered during hot days and heatwaves.READ MORE
A number of recent workplace injuries and a Qld fatality have involved falls from flatbed trucks. Such falls can be serious and sometimes fatal, but there are several ways to stay safe loading & unloading.READ MORE
BE SAFE, BE HEALTHY, BECAUSE is this year's theme for National Safe Work Month for October '15 and encourages everyone to raise awareness of work health & safety. Check out the extensive electronic information kit available from Safe Work Australia.READ MORE
Incidents involving quads are now the leading cause of injury death on Australian farms. Most deaths are due to crush injury and/or asphyxiation associated with quads rolling over, or by injury associated with the victim being flung onto a hard surface as a result of a crash.READ MORE
Start planning for safety discussions for your workplace. WorkSafe is encouraging employers and workers to a new public awareness campaign which began last week to help prevent injuries with safe work environments.READ MORE
Many recent workplace injuries have involved vehicles or mobile plant. An Industry Alert on Friday from WA Commission for Occupational Safety & Health reinforces the message to be alert around moving machinery.READ MORE


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The Greatest Olympian EVER!
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The Greatest Olympian EVER!
Yes Sir! Truly amazing... :patriot: USA USA USA!!!!
Swimming is definitely grueling, but I think the argument can be made that Carl Lewis excelled in a wider variety of events. Yes, Phelps has medaled in events with a variety of strokes and distances, but it's all still swimming for speed. Lewis on the other hand medaled in running (sprinting only) and the long jump.
Plus Lewis was dominant over a longer period in his best event. He won the gold in long jump in 4 consecutive Olympics.
Either way it's splitting hairs. They're both outstanding Olympians. Phelps accomplishments are amazing, and I don't know if we'll see them surpassed in my lifetime.
I'm not as knowledgeable on Owens or Thorpe so I can't really speak to them.
Am I the only one a bit disappointed about Phelps this year?
Admitting he didn't train as hard...Teammates being critical of his training.
Maybe I am just hating on the guy because he comes off as a dick but he makes it hard to be excited for him this time around.
Sent from my PC36100 using Tapatalk 2
It would have been nice to see him be truly dominant again, but he's basically said that he's gotten tired of swimming. I'm not going to hold that against him. IMO he's already accomplished such incredible things that his legacy is untouchable.
Actually I was a bit peeved at the way NBC seemed to center so much of their early Olympic coverage on how Lochte was going to "dethrone" Phelps. Then after Phelps finished 4th in his 1st final they seemed to crank it up even more. I almost felt like they were hoping for the guy to fail so they could drag him through the mud.
Yes, he may come off as a bit of a prick, but he accomplished amazing things while representing our country. I still think that's something to be proud of. Shame on NBC for being so eager to tear down one of our Olympic heroes.
And Lochte may be a better swimmer at this point, but he will never come close to Phelps accomplishment. Phelps was never going to be dethroned no matter what happened at this Olympics.
If he was going to go he still should strive for the gold in every event. Losing sucks! I get 2nd gets the silver but how much sweeter is it to win and have even more Golds?
I'm proud of Phelps but it bugs me a little that he don't have the "I want to dominate" attitude he once had.
Ray Lewis has a Super Bowl ring and has yet to quit and trains harder and harder every year. I guess Phelps ain't built that way.
Sent from my PC36100 using Tapatalk 2
Track and field has long been the dominant sport of the olympics. It is the one where you see the best athletes compete.
No one cares about swimming unless their boat is getting ready to sink.

subset: commoncrawl


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Comfort food has taken on a new meaning over the past fortnight at our school.
The making, receiving, sharing and eating of kai has played a significant part in showing support, aroha and kindness among students, staff, families and the wider community following the Paritutu tragedy.
In the classroom we have had many more practical lessons than we normally would, as the students take comfort in the food- making process. A hands-on approach has been emphasised to produce nutritious finger food. Making food has been therapeutic and has helped to lift their spirits.
The delicious bread cases are a fantastic way to produce a healthy savoury. Slices of bread are pressed into muffin pans and baked into a golden, slightly crisp bread case.
The bread cases are a healthy alternative to pastry and provide a good source of energy, fibre and minerals and are virtually fat free compared with pastry, which is high in fat and low in fibre. Bread cases are a good way of using up bread which is not fresh enough for school lunches, but fresh bread is also suitable.
Choose a wholemeal or wholegrain bread for an even healthier option to add more nutrition, especially fibre, and to provide longer-lasting energy. Each case is filled with a prepared filling and baked for a further 10-12 minutes to heat through.
We developed two fillings - one using lean mince, chilli beans and mixed vegetables and the other has a white sauce base with smoked fish, corn and spring onion. Both have a little grated cheese and chopped parsley sprinkled over the top for extra flavour and garnish, added before baking.
The addition of parsley not only boosts the flavour and adds colour, it is also rich in vitamin C which is essential for our general health and wellbeing. Add more than two tablespoons if you have access to plenty of parsley growing in your vegetable garden. Parsley is a really easy herb to grow.
Another suitable and very simple bread case filling could be to add a spoonful of either spaghetti, baked beans or creamed corn, followed by a sprinkle of grated cheese and chopped parsley.
Any leftover filling could be heated and added to a panini or toasted sandwich or served on a slice or two of toast.
The savoury scone or "quick bread" is another example of a nutritious, high-energy food.
The addition of ham, onion, parsley and cheese boosts the protein, calcium and vitamin content. They are easy and quick to make and bake.
Use tasty cheese as it gives a lot of flavour in baking. Diced red capsicum would also be a suitable vegetable to add.
Eaten hot and straight from the oven with a little margarine or butter spread between the two layers really hits the spot of culinary pleasure. Just the ideal high-energy food for hungry teenage students to make on a blustery winter's day.
If you wish to buy the first two years' worth of Kai with Soul, there are limited stocks still available at Mitre 10 Mega, The Crafty Fox and the Finance Office at Spotswood College. The book would make an ideal Fathers' Day gift and encourage dads to cook in the kitchen.
Ham and Cheese Savoury Scones
Makes 6 large scones
1 cups flour
1 Tbsp baking powder
tsp salt
Pinch of cayenne pepper
25g cold butter
cup milk + 2 Tbsp extra milk
onion, diced
cup tasty cheese, grated
1 slices ham, chopped into small pieces
2 Tbsp parsley, chopped
1. Preheat the oven to 200 degrees C on Fan Bake.
2. Sift the flour, baking powder and salt into a large bowl.
3. Cut the butter into small pieces, add to the flour and rub into the dry mixture with your fingertips, until the mixture resembles coarse breadcrumbs.
4. Add the diced onion, grated cheese, chopped ham and parsley and stir together with a bread and butter knife.
5. Make a "well" in the centre of the flour mixture and pour in the milk.
6. Mix with the knife to form a soft dough. Cut across the dough instead of using a circular motion. The mixture will be dry to start with but will combine to form a moist dough.
7. Turn the dough on to a lightly floured bench.
8. Lightly handle and press the dough into a rectangle shape about 2cm in thickness. (A thin dough will produce a crusty scone, and a slightly thicker dough a softer product.)
9. Cut the dough into 6 even- sized rectangular pieces with a sharp knife.
10. Place the scones on the oven tray (no greasing or flouring required) about 2cm apart.
11. Bake for 12-15 minutes or until the scones are well risen and slightly golden in colour.
12. Cut each rectangle in half to make 12 small scones.
Bread Cases
Makes 20 cases:
20 slices of sandwich wholemeal bread
Margarine for spreading
1. Preheat the oven to 200 degrees C on Fan Bake.
2. Cut the crusts from the bread slices, using a serrated knife.
3. Spread one side of each slice lightly with margarine.
4. Position each bread slice, margarine side down, in a muffin pan. Ease the sides into the pan. Each slice will take on its own shape.
5. Place the muffin tray in the middle of the oven and bake for 10-15 minutes until the bread cases are crisp and golden.
6. Remove from the oven. The cases are now ready for adding your filling.
Creamy Smoked Fish and Corn Filling
Makes filling for 18-20 bread cases
60g butter
cup flour
tsp salt
Freshly ground black pepper
2 cups milk
1 cups smoked fish, drained and flaked
cup spring onion (green part), chopped
1 cup corn kernels
1 cup grated cheese
1-2 Tbsp chopped parsley
1. Melt the butter in a medium saucepan.
2. Add the flour, salt and pepper. Stir while cooking for 1 minute, until the mixture bubbles.
3. Add the milk and stir gently until the sauce thickens.
4. Add the drained and flaked smoked fish, chopped spring onion and corn. Stir and cook for another 1-2 minutes.
5. Place spoonfuls of the creamed mixture into the baked bread cases. Sprinkle each with a little grated cheese and chopped parsley.
6. Bake at 200 degrees C for 10-15 minutes, until the cheese has melted. Canned or fresh smoked fish work equally well.
Best served hot, straight from the oven.
Savoury Mince and Bean Filling
Makes filling for 20 bread cases
500g mince
1 tsp canola oil
1 small onion, finely chopped
1 Tbsp soy sauce
1 cup frozen mixed veges
1 cup mild chilli beans
1 cup water
2 Tbsp flour
tsp salt and freshly ground black pepper
2 Tbsp chopped parsley
1 cup grated cheese
1. Preheat the oven to 200 degrees C on Bake.
2. Preheat a non-stick frying pan with 1 tsp canola oil. Add the mince and stir with a wooden spoon, breaking up the lumps until lightly browned.
3. Add the onion, stir and cook for 1-2 minutes.
4. Add the soy sauce, chilli beans, vegetables, parsley and water. Stir together, then simmer on a low heat for 15 minutes with the lid on the pan.
5. Stir in the flour to thicken the mixture. If the mixture is still thin, continue simmering until it is thickened, without the lid.
6. Place spoonfuls of the mince into the prepared bread cases and top each one with a little grated cheese and a sprinkle of extra chopped parsley.
7. Place into the preheated oven and cook for 10-15 minutes or until the cases are golden and the cheese is melted on top.
8. Serve hot from the oven.
- Taranaki Daily News
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Cornell University, The Methodist Hospital Research Institute, Weill Cornell Medical College, Department of Systems Medicine and Bioengineering, Houston, Texas 77030
Chroma Technology, 10 Imtec Lane, Bellows Falls, Vermont 05101
Rice University, Department of Electrical and Computer Engineering, Houston, Texas 77005
Cornell University, The Methodist Hospital Research Institute, Weill Cornell Medical College, NCI Center for Modeling Cancer Development, Houston, Texas 77030
Cornell University, Weill Cornell Medical College, The Methodist Hospital, Department of Pathology and Genomic Medicine, Houston, Texas 77030
* Authors contributed equally to this work.
The advent of molecularly targeted therapies requires effective identification of the various cell types of non-small cell lung carcinomas (NSCLC). Currently, cell type diagnosis is performed using small biopsies or cytology specimens that are often insufficient for molecular testing after morphologic analysis. Thus, the ability to rapidly recognize different cancer cell types, with minimal tissue consumption, would accelerate diagnosis and preserve tissue samples for subsequent molecular testing in targeted therapy. We report a label-free molecular vibrational imaging framework enabling three-dimensional (3-D) image acquisition and quantitative analysis of cellular structures for identification of NSCLC cell types. This diagnostic imaging system employs superpixel-based 3-D nuclear segmentation for extracting such disease-related features as nuclear shape, volume, and cell-cell distance. These features are used to characterize cancer cell types using machine learning. Using fresh unstained tissue samples derived from cell lines grown in a mouse model, the platform showed greater than 97% accuracy for diagnosis of NSCLC cell types within a few minutes. As an adjunct to subsequent histology tests, our novel system would allow fast delineation of cancer cell types with minimum tissue consumption, potentially facilitating on-the-spot diagnosis, while preserving specimens for additional tests. Furthermore, 3-D measurements of cellular structure permit evaluation closer to the native state of cells, creating an alternative to traditional 2-D histology specimen evaluation, potentially increasing accuracy in diagnosing cell type of lung carcinomas.
Lung carcinoma is the most prevalent type of cancer in the world, and it is responsible for more deaths than other types of cancer.1 Across the globe, five-year survival rates for lung cancer patients range from 6% to 14% for men and 7% to 18% for women.1,2 Forover 50 years, lung cancer has been viewed as a relentlessly progressive, overwhelmingly fatal disease, essentially because the utility of radiological screening remains unproven and pathologists have had only limited success in differentiating small cell from non-small cell carcinoma and staging resection specimens.3 This has led to the use of the term non-small cell lung carcinoma (NSCLC),as a reflection of this difficulty.3
The 21st century has given birth to a revolution in the treatment, classification, and detection of lung cancer that promises to radically enhance survival of lung cancer patients for the first time in decades.4 In particular, the advent of molecularly targeted therapies makes identification of the various histologic cell types and subtypes of lung cancer more important. For example, adenocarcinoma patients should be tested for epidermal growth factor receptor (EGFR) mutations as an indication of responsiveness to EGFR tyrosine kinase inhibitor.5–7 In addition, an exclusion of a squamous cell carcinoma diagnosis is required for NSCLC patients prior to treatment with bevacizumab because of potential life-threatening hemorrhage.8,9 As a result, additional molecular tests are frequently involved in reaching a definitive diagnosis for targeted therapies.10,11 However, most lung carcinomas are not resected and are diagnosed and classified using small biopsies or cytology specimens.12,13 Hematoxylin and eosin (H&E) stain of tissue sections, which is currently the gold standard for histologic diagnosis, requires hours to days for tissue transfer, processing, sectioning, and staining, and it still cannot always differentiate NSCLC cell types and subtypes. Cytology results are typically faster, but the material is even more limited in volume, and reliably separating adenocarcinoma from squamous cell carcinoma is sometimes impossible. Finally, immunochemistry may be useful in helping to make this distinction, but this method adds more time to the diagnostic process and consumes tumor cells. Therefore, the ability to rapidly recognize different cell types and subtypes of lung cancer with minimal tissue consumption will not only facilitate the diagnostic process, but also enable maximum preservation of tissue samples for subsequent molecular testing for targeted therapy.11 Given the risks and cost of lung biopsy, it would therefore be beneficial to develop techniques that enable fast examination of excised biopsy samples as a preliminary test for separating general cell types of lung cancer before a follow-up molecular analysis, with the aim of reducing the number of required biopsies and providing equal or greater accuracy relative to existing testing methods.
As a label-free imaging technique, CARS microscopy14,15 holds great potential for this type of diagnostic application by significantly minimizing sampling error and realizing maximum preservation of specimen for follow-up molecular tests. By capturing intrinsic molecular vibrations to create optical contrast, CARS enables cellular imaging with submicron level spatial resolution, as well as video-speed imaging.16–18 Two laser beams are commonly used to probe designated molecular vibrations and produce CARS emission through a four-wave mixing process.19 Because of its high resolution and label-free imaging capability, CARS microscopy has been used to visualize various tissue structures, such as skin20 andbrain,21 as well as DNA backbone structures.22 Nevertheless, to realize the diagnostic value of CARS, we must extract and analyze quantitative information from the digital CARS images in order to meet the rigorous evaluation criteria required for objective diagnosis.
Accordingly, we reported a pattern recognition and classification strategy that integrates CARS imaging with quantitative image computing techniques for cancer diagnosis.23–27 This strategy is based on extraction and calibration of a series of pathologically related features for disease identification, thus providing meaningful diagnostic information with reproducible results. The developed platform has been successfully demonstrated using a number of disease models, including lung, breast, and prostate cancers.23–27 In spite of this progress, the developed platform has thus far shown limited accuracy (around 70% to 75%)25 for separation of adenocarcinoma from squamous cell carcinoma, two major cell types of NSCLC. This difficulty is not surprising and it corresponds with the clinical difficulty in differentiating these two cell types using morphology alone.28 However, as discussed above, definitive diagnosis of these cell types is increasingly required.29 Accordingly, we have further exploited the potential of CARS for the identification of cancer cell types by extending the previously developed two-dimensional (2-D) image analysis framework into a three-dimensional (3-D) nuclear segmentation, feature extraction, and classification system. As a nonlinear multiphoton imaging method, CARS provides superior optical sectioning capability, enabling acquisition of individual 2-D images from the same field of view but different imaging depths.16,30 Such an image stack is usually called a z-stack. Using appropriate interpolation methods, a z-stack can be reconstructed into a 3-D volume. Throughout the remainder of the discussion, the terms z-stack and volume will be used interchangeably, as they both refer to a 3-D data structure. Such 3-D data analysis system is capable of extracting cell morphology information that accurately captures cells in their native state, thus effectively eliminating certain artificial effects posed by 2-D data analysis. For example, using 2-D data analysis, the same cell nucleus can be measured as different dimensions, depending on where the 2-D sectioning of the cell takes place. This sectioning artifact leads to confusing measurements, as a nucleus will be imaged several times, in several slices, and will have a different size in each of these slices. Taking this effect onto a whole image scale, where many cells are imaged in the same image plane. Only a small portion of these cells will be measured at the correct sizes, while the remaining cells will be measured as a different size rather than their real maximum cross-sectional dimension. We treat this effect as a sampling noise, which can hide the real size of a cell, rendering reliable analysis difficult. In contrast, a 3-D measurement would provide access to the nucleus as a whole and allow measuring real nuclear size represented by volume, potentially improving the classification accuracy between non-small cell carcinomas.
In the present work, we focus on developing a CARS-based 3-D diagnostic imaging system for nuclear segmentation and cancer cell type classification. Different mouse lung cancer models were developed by injecting human lung cancer cell lines, including adenocarcinoma and squamous cell carcinoma, as described below, into the lungs of nude mice. CARS images were acquired from normal lung tissues and different cell types of cancer lesions ex vivo. By stacking all image slices from one z-stack, as mentioned above, into a single data structure, a 3-D volume is formed. The generated volumes show cell nuclei as dark, roughly ellipsoidal structures surrounded by brighter cytoplasm tissues richer in CH2 structures.
For the purpose of this study, it is imperative that the volume be automatically partitioned, or segmented, into small regions, or clusters, whose boundaries adhere to image edges as accurately as possible. If this requirement is achieved, isolating those regions containing nuclei and extracting their physical characteristics for classification become trivial tasks. This partitioning, or segmentation, could be achieved by a myriad of well-established data clustering methods that utilize image location and intensity information, such as the k-means algorithm31 or image statistics like the expectation maximization algorithm.32 However, these classical segmentation approaches pose a major limitation in that they minimize global energy functions, meaning they operate on the dataset as a whole and generate clusters that satisfy global conditions, which frequently results in under segmentation error.33 Undersegmentation results in image points belonging to different objects lumped into single clusters; for example, a cluster contacting a cell nucleus will have a boundary that does not adhere to nuclear boundaries but also encompasses parts of the image background. As such, this would not be an efficient method of accurately segmenting cell nuclei, which are often too small with respect to the size of a volume. The use of a global clustering approach on such a large dataset also requires large memory capacity and computing power, a requirement that might hinder efficient execution of segmentation and follow-up diagnosis.
To circumvent these problems, superpixel-based local clustering was used to perform segmentation and generate clusters that capture real image boundaries with great accuracy in 2-D images33 and then finally extended to 3-D images in which they are called supervoxels. We designed a modification of the simple linear iterative clustering (SLIC) algorithm to compute 3-D supervoxels.34 Additionally, we expanded the definition of the feature vector used in clustering to include the entropy of information in 3-D volumes; this amplifies image edges and circumvents the low contrast in CARS images. In this clustering process, the 3-D volume is partitioned into small regions based on local affinity information, and voxels are grouped into one cluster according to the similarity of their features. In this method, unlike k-means, a data point is not assigned to a cluster unless it falls within a small region of interest around that cluster's center. The clustered dataset is used to extract pathologically relevant features about the cell nuclei, such as volume and spatial configuration, which are then used to perform classification of lung cancer cell types.
Our results showed that the refined 3-D strategy can accurately delineate nuclear structures and has significantly improved the diagnostic accuracy between adenocarcinoma and squamous cell carcinoma. As such, these findings hold substantial potential to provide fast diagnosis with minimal tissue consumption while effectively preserving tissue specimens for follow-up molecular tests.
The schematic of the setup was previously described.24 One z-stack was imaged for each mouse, and a total of 40 (30 from tumor-bearing mice and 10 from normal control) z-stacks were examined. The imaging depths of these stacks range from 35 to 50 μm with 1 μm separation between images. For this study, a60x, NA1.2 water immersion objective (IR UPlanApo, Olympus, Melville, NJ) with a lateral resolution of 0.6 μm and a axial resolution of 1.5 μm was used.35 After CARS imaging, all specimens were marked to indicate the sampled locations, sectioned through marked positions, and finally stained with H&E to be examined for the type of lesion as a standard histology control.
Human lung cancer cell lines, A549 adenocarcinoma and NCI-H226 squamous cell carcinoma, were obtained from the American Type Culture Collection (ATCC, Manassas, VA). A549 and NCI-H69 were maintained in DMEM (Invitrogen, Grand Island, NY) medium. Both media were supplemented with 10% FCS, 100 units/mL penicillin, and 100 μg/mL streptomycin. Cancer cells were cultured in a 37 °C humidified incubator with a mixture of 95% air and 5% CO2. All experiments were performed on exponentially growing cells with a cell population doubling time of approximately 24 to 36 h. Forty BALB/c nude mice (12-week-old females, Charles River, Wilmington, MA) were ordered for this study. Fifteen mice were assigned to each cancer group, e.g., adenocarcinoma and squamous cell carcinoma, while 10 mice were used as controls. Animals were anesthetized by Ketamine and Xylazine injection. A right posterolateral thoracic incision was made, and the thoracic wall was exposed by blunt dissection of the muscles. The tip of a 0.5-inch, 27-gauge needle was advanced by 3 mm under visual control through the translucent pleura at the third intercostal space at the dorsal midaxillary line into the pleural cavity where A549 or NCI-H226 cells (1 million/20 μL PBS) containing 1 mg/mL Matrigel (BD Biosciences, Bedford, MA) were injected. The same volume of PBS containing 1 mg/mL Matrigel without cells was injected for the control group. This group only serves as a control for the mouse tumor model but not for the diagnostic analysis. The implanted tumors were allowed to grow for two weeks before the mice were sacrificed for imaging of tumor tissues in their lungs. CARS imaging was performed close to the surface of the tumors. All processes were performed according to the guidelines of The Methodist Hospital Research Institute (TMHRI, Houston, TX).
Mouse lung tissues were placed on a cover slip, which was reversely placed on the chamber to keep the samples from being pressed as described in 27. The beating frequency was tuned to 2845 cm−1 to probe the CARS signals originating from symmetric CH2 stretching bonds.16 The CARS signal at around 663 nm was collected by the same objective using the backward (Epi-) detection scheme.
We developed a clustering and labeling pipeline based on superpixels,36–38 which are small image patches produced by applying a clustering algorithm to localized regions of a volume. Figure 1 shows the overall process of image segmentation, feature extraction, and classification. The benefit of superpixels lies first in their ability to capture fine image details such as edges and generate patches that adhere to natural boundaries. The boundary of a superpixel containing a cell nucleus, for example, adheres very well to the boundary of that nucleus. Second, the computational load of analysis tasks farther down the data analysis pipeline is reduced by the reduction in the number of data points, as analysis will be performed on clusters of pixels rather than individual pixels. For the remainder of this paper, the terms supervoxel and cluster carry the same meaning and are used interchangeably.
Schematic illustration of the 3-D imaging, image analysis, and classification strategy. M: mirror, OPO: optical parametric oscillator, DL: delay line, DM: dichroic mirror, L: lens, MO: microscope objective, BT: breast tissue, BPF: band-pass filter, PMT: photomultiplier tube. CARS output was collected in the epi-direction. Stacking all image slices from one z-stack into a single data structure formed a 3-D volume. A SLIC superpixel-based local clustering approach was developed for 3-D segmentation of these nuclear structures. Segmented nuclei were then fitted with ellipsoids, enabling consistent measurements of image features related to nuclear morphology and distribution. Using these disease-related features, a classification system was developed for separation of lung cancer cell types.
Multiple algorithms for creating superpixels exist, such as Refs. 33, 39, and 40, but the SLIC algorithm has shown superior performance in terms of segmentation errors, image boundary detection, and computational recourses.32 SLIC operates as a modified k-means algorithm that performs clustering in a subset of clusters confined to small regions of interest in the volume, rather than partitioning datasets into k clusters to which any data point can belong. Thus, a pixel does not potentially belong to any of the k clusters, but instead to a small subset of clusters in its immediate neighborhood. In this strategy, pixels having similar characteristics are grouped together, but the limited search area ensures that pixels distant from each other, such as very similar pixels belonging to two different nuclei, are never in the same cluster. This reduces under segmentation error, and at the same time supports the assumption that later processing steps can treat a cluster as a single nucleus. Although this definition of SLIC superpixel clustering applies to datasets consisting of 2-D images, it can be easily extended to 3-D image stacks, or volumes, where data points are voxels instead of pixels. In this case, the clustering outcome is a volume partitioned into small 3-D clusters called supervoxels. In this report, we present the operation of SLIC in 3-D volumes and our extension to the feature vector used in clustering.
To perform supervoxel clustering, each voxel (v) in a volume is represented by a vector of features fv=[Lv,Av,Bv,xv,yv,zv,Hv]T where Lv, Av, and Bv represent CIELAB colorspace values at v. xv, yv, and zv represent the coordinates of v within a volume, and Hv represents the entropy of information value at v. The entropy of a voxel is computed by calculating the entropy of the dataset represented by voxel v and all its immediate neighbors using 8-connectivity and the equation Display Formula
Clustering was initialized by distributing cluster centers at uniform spatial intervals in the volume; the values of the feature vectors f at each cluster center served as the initial centers of those supervoxels. The algorithm searches for potential data points to associate with each cluster center based on the distance, measured as the Euclidean distance in the 7-D space of the feature vectors, between the data point and the cluster center. The search region of interest is limited to the cube whose vertices are the immediate neighboring cluster centers and the cluster center of interest at its center. For each iteration, the algorithm associates each data point to the closest cluster. At the end of an iteration, a new cluster center for each supervoxel is computed as the mean of all voxels assigned to it. Clustering terminates when the residual error computed as the sum of all L1 distances between new cluster centers and old cluster centers is below a preset threshold; in this study, the threshold was set at 0.2.
Following the partitioning of the volume into supervoxels, a program with a simple user interface was created to perform labeling of those supervoxels that correspond to cell nuclei. This program operates in two repeating steps (Video 1) during which all cell nuclei can be manually selected. It is worth mentioning that labeling is an efficient process, as labeling an entire 512×512×80 volume consumes about five min.
Demonstration of nuclear labeling process. (MOV, 3.7 MB) [URL: http://dx.doi.org/10.1117/1.JBO.17.6.066017.1]
Thus far, the focus has been on sifting through a very large dataset of three-dimensional images to find a small subset of data that contains information relevant to diagnosis, namely the voxels corresponding to cell nuclei. Hereafter this subset of data is used to compute physical features that contain enough information to represent the cell nuclei and build a classifier that can perform automatic identification of cancer cell types.
To ensure consistency in extracted features across different volumes, we assumed a cell nucleus to be roughly ellipsoidal in shape, and, as such, an ellipsoid was fitted to each contiguous set of 3-D points representing a nucleus. The features we used for each nucleus were the physical features of the ellipsoid that best fitted the convex hull of the points comprising that nucleus; in other words, the ellipsoid that best fitted the smallest region in space that could enclose all the points comprising a nucleus. Computed features were the volume and the lengths of the major and minor axes of the fitted ellipsoid. Furthermore, features representing the spatial position of a nucleus relative to its neighbors were computed to incorporate information about the distribution of cell structures. We constructed the Delaunay triangulation41–43 to define the connectivity of nuclei in the sample. Using the triangulation, four features were computed for each nucleus, including the distance to the farthest neighbor, distance to the nearest neighbor, mean distance to neighbors, and orientation relative to the nearest neighbor. These distances were respectively represented by: the length of the longest edge of the Delaunay triangulation structure attached to the nucleus of interest, the length of the shortest Delaunay edge attached to the nucleus, the average length of all Delaunay edges attached to a nucleus, and the angle between the major axis of a cell and the major axis of its nearest neighbor.
We performed segmentation, labeling, and feature extraction from 15 volumes corresponding to adenocarcinoma and another 15 volumes from squamous cell carcinoma. In addition, because we wanted to demonstrate the superiority of information extracted in three dimensions over that extracted from two dimensions, we used three slices from each image stack and extracted the same features from those to serve as a 2-D benchmark. It is worthnoting that all features can be mapped to any dimension, e.g., an ellipsoid mapped to two dimensions becomes an ellipse; volume becomes area. The major difference between 3-D and 2-D representation of the features is that an ellipse has only two equatorial radii, one major and one minor axis, as opposed to an ellipsoid that has three such radii. Compared to 2-D, 3-D measurements resulted in one more feature as minor axis length since there are three axes in a 3-D ellipsoid.
Since each volume was identified by the statistics of its features, mean, standard deviation, skewness, and kurtosis of the distribution function were calculated for each of the seven (in 2-D) or eight (in 3-D) features in a given volume. These quantities constituted the 32 features used to build a classifier capable of characterizing a volume as either an adenocarcinoma or squamous cell carcinoma cell type. The leave-one-out approach, also used for differential diagnosis of lung carcinoma cell types by 24, was utilized to demonstrate that the designated statistical features could be used to perform automatic diagnosis. We detail this method through the following example. If samples from each cell type were labeled 1 through 15, A1 through A15 for adenocarcinoma samples and S1 through S15 for squamous cell carcinoma, samples A1 and S1 would be excluded on the first iteration, and the remaining 28 samples would be used to train the a classifier, with the two excluded samples (A1 and S1) used to validate that classifier through testing whether it can assign them to their correct subtype. On the second iteration, sample A1 would be left out with sample S2, and the training/model testing process is repeated. This process is repeated over enough iterations to exhaust all possible parings of excluded samples. As a benchmark in this study, the process was performed both in 2-D and in 3-D datasets.
Figure 2 shows representative CARS images and corresponding H&E results of normal lung tissue and two cell types of non-small cell lung cancers. Tissue structures were clearly identified on the cellular level. The normal lung tissue sample is predominantly composed of well-organized fibrous and matrix structures, consisting of the bronchi and supporting matrix for alveoli [Fig. 1(a) and 1(b)]. Cancerous regions showed much denser cellularity compared with normal regions, and the size and configuration of the cells corresponded with these parameters, as shown by H&E staining [Fig. 1(c) through 1(h)]. Commonly used pathological features were also identified for individual cell types of cancers, including vesicular nuclei, prominent and moderately abundant foamy cytoplasm44 for adenocarcinoma [Fig. 1(c) and 1(d)], and pleomorphic malignant cells containing keratin with abundant cytoplasm and formation of intracellular bridges45 for squamous cell carcinoma [Fig. 1(e) and 1(f)].
CARS images of mouse lung tissues taken at Raman shift of 2845 cm−1 and their corresponding H&E stained images: (a) (b) normal lung, (c) (d) adenocarcinoma and (e) (f) squamous cell carcinoma derived from the same mouse, respectively. Scale bars: 50 μm.
Segmentation of each volume, or z-stack, resulted in new volume data, which were partitioned, or segmented, into supervoxels. For all subsequent processing steps, we considered a supervoxel to represent one data point. This is possible based on the assumption that a well-performing clustering algorithm will generate supervoxels in which all individual voxels belong to the same class. Indeed, as illustrated by Fig. 3, all voxels in a supervoxel only represent either cell nuclei or background. A sample slice of a segmented volume is presented in Fig. 3(a), and the same slice after clustering is shown in Fig. 3(b). The red regions represent the boundaries of supervoxels. The boundaries in certain regions appear as surfaces rather than lines because the chosen slice passes through the boundary of the 3-D supervoxel. It is notable that those supervoxels enclosing nuclei are completely separable from those enclosing background and that supervoxel boundaries accurately capture nuclear boundaries. It is this preliminary segmenting of the volume into clusters belonging to either nuclei or background that allowed us to proceed to the next step in the image analysis framework, namely, labeling of those supervoxels that represent nuclei. Figure 3(c) further shows the outcome of labeling the clustered volume where the boundaries of the labeled supervoxels accurately capture the boundaries of the nuclei, while the 3-D boundary of a representative cell nucleus is illustrated in Fig. 3(d). It is worth mentioning that an accurate boundary was determined in all three dimensions as a result of a smooth segmentation process. Video 2 shows representative reconstructed nuclei after segmentation in a whole squamous cell carcinoma volume.
Superpixel-based 3-D nuclear segmentation process. A sample slice of a volume is presented (a), where all voxels in a supervoxel represent either cell nuclei or backgrounds. The same slice after clustering is shown (b), in which the red regions represent the boundaries of supervoxels. (c) shows the outcome of labeling the clustered volume where the boundaries of the labeled supervoxels accurately capture the boundaries of cell nuclei. The 3-D segmented structure of a cell nucleus is illustrated in (d). The YZ and XZ cross sections are presented in the right and bottom panels, which were constructed from the depth stack along the blue and green lines, respectively.
Reconstructed cell nuclei in a whole squamous cell carcinoma volume. (MOV, 3.5 MB) [URL: http://dx.doi.org/10.1117/1.JBO.17.6.066017.2]]
As described in the Methods section and shown in Fig. 3(c) and 3(d), the segmented cell nuclei were fitted with ellipsoids for consistent extraction of feature information. Figure 4 illustrates a representative case of the fitting results on all the nuclei in a squamous cell carcinoma volume, where all ellipsoids are plotted with their color representing different depths within the z-stack. This mesh in Fig. 4 is representative of the real size and distribution of nuclei within the imaged tissue, and it was used to extract pathologically relevant information, namely, the features defined in the Methods section, to be utilized in automatic differential diagnosis. As such, the above-defined features were measured across different volumes consistently following the same procedure. Since multiple cell nuclei existed in each volume (Figs. 3 and 4), the measurement resulted in a probability distribution function (PDF) for each measured feature in a given volume. We found that distributions of five out of eight measured features showed significant difference between 2-D and 3-D measurements using data from all studied volumes through both 2-D and 3-D computation (Fig. 5).They were mostly related to the size, shape, and orientation of nuclear structures. We note here that features related to nuclear size and shape failed to show a clear separation between the two cancer cell types in 2-D measurements [Fig. 5(a) through 5(c)]. In contrast, 3-D measurements effectively captured the difference between the two cell types by showing clear separations of their peak positions [Fig. 5(e) through 5(g)]. While nuclear orientation shows a clear peak with 2-D measurement [Fig. 5(d)], this peak turns into an even distribution across different angles in 3-D [Fig. 5(h)]. The presented PDF curves were estimated from the measured data, i.e., they represent the histograms of the features processed with a smoothing kernel causing the curves in some cases to have tails in the negative side of the number line. Measurements related to the remaining three feature distributions, which carry information on the distance between individual cell nuclei, failed to show clear separations between cancer cell types both in 2-D and 3-D data and thus are not illustrated here.
3-D nuclear distribution of a squamous cell carcinoma volume after supervoxel-based nuclear segmentation. All ellipsoids are plotted with their color representing different depths within the volume.
Distribution of four representative features extracted from the segmentation results. PDF curves are fitted to the distributions to illustrate the data structure. Left panels, (a) through (d), show results from 2-D segmentation, while right panels, (e) through (h), show results from 3-D segmentation. Data from adenocarcinoma and squamous cell carcinoma are plotted in red and green, respectively.
Using the calculated features, a classifier was built, as described in the Methods section, and classification was performed to separate cancer cell types. Figure 6 and Table 1 illustrate the automatic classification results. In Fig. 6(a) and 6(b), results of classification using 2-D data are presented, where each point represents one tissue sample, specifically the one that was left out during a particular iteration. The threshold for classification is the straight line y=0.5. Points with y≥0.5 were classified as adenocarcinoma, while points with y<0.5 were classified as squamous cell carcinoma. For better presentation, the graph is separated into two separate subfigures, respectively representing adenocarcinoma samples [Fig. 6(a)] and squamous cell carcinoma samples [Fig. 6(b)]. Classification from 2-D data resulted in a true positive rate of 71.98% and 65.05% for adenocarcinoma and squamous cell carcinoma, respectively (Table 1). False positive rate, in the same order, was 28.02% and 34.95%. Classification results from the 3-D data analysis are plotted in Fig. 6(c), where clear separation between cell types allows for data visualization on the same graph. As shown in Table 1, quantified classification accuracies were a 99.56% and 97.78% true positive rate for adenocarcinoma and squamous cell carcinoma, respectively. False positive classification was 0.45% and 2.22% in the same order. The results showed that features extracted from 3-D data analysis provided information that significantly enhanced the classification accuracy and thus demonstrated proof of concept that information extracted from 3-D image analysis and segmentation can be used for the automatic diagnosis of lung cancer subtypes.
Visualization of 2-D and 3-D classification results. (a) and (b) present adenocarcinoma and squamous cell carcinoma results with 2-D data analysis, respectively. Each point represents one tissue sample. The threshold for classification is the straight line y=0.5. Points with y≥0.5 were classified as adenocarcinoma while points with y<0.5 were classified as squamous cell carcinoma. Similarly, classification results from the 3-D data analysis are plotted (c), where clear separation between cell types allows for data visualization on the same graph.
Rapid advances in optical imaging technologies have led to substantial contributions to advancing diagnostic strategies and improving care delivery in cancer research. To exploit the diagnostic value of acquired images for clinical diagnosis, an effective imaging and image analysis platform should be developed to allow accurate evaluation of imaging data in a repeatable manner. Thus far, several studies have explored the diagnostic potential of CARS,23–27 promoting the translation of this label-free technique for clinical use. These strategies were based on extraction and calibration of a series of disease-related morphology features for diagnosis. From this, the CARS technique has been successfully bridged to clinical evaluations. However, similar to the commonly used H&E stain technique, the morphology-based classification system encounters difficulties in distinguishing certain diseases, such as separation of the cell types of NSCLC. The problem originates from the fact that these cancer cell types often show a similar morphology, especially in poorly differentiated areas, preventing accurate characterization.
Taking aim at this problem, this study proposed a strategy to increase the accuracy of NSCLC characterization by extending 2-D analytical strategies to a 3-D analytic platform. By taking advantage of the optical sectioning capability provided by CARS, our strategy allows analysis of cellular features in 3-D, a setting closer to the microenvironment in which the cells reside. As illustrated in Fig. 5, five of the eight disease-related features (volume, major axis length, lengths of the two minor axes, and the orientation relative to the nearest neighbor) showed clear separation in 3-D measurements when compared to their four equivalent features from the 2-D benchmark.
In this strategy nuclear volume was first measured in 3-D to provide size information. As discussed in the introduction, this effectively allowed suppression of the sampling error posed by measurements from 2-D slices. As a result, a clear separation of adenocarcinoma from squamous cell carcinoma was observed. In contrast, the 2-D analysis showed much broader distributions for both cell types without clear separation of peak positions, potentially caused by the sampling noise. Second, the sampling error in 2-D also obscured identification of the nuclear size difference between examined cell types. It is worth mentioning that the peaks of the major axis lengths of adenocarcinoma and squamous cell carcinoma were about 6 and 5.5 μm [Fig. 5(f)], respectively. Although they were well separated in 3-D measurements, 2-D measurements of the same parameter did not show a clear difference. More importantly, both cell types showed the peak value of major axis length between 4 and 5 μmin 2-D [Fig. 5(b)], values that were substantially smaller than the resulting values in 3-D. These data strongly indicated that such 2-D measurements combined values associated with both sampling noise and real axis lengths. Specifically, if, in a given plane, we assume that all cell nuclei have the same axis length, then the measured axis length for a given nucleus can range from zero to its actual length, depending on the selection of the plane. This effect is true for every cell nucleus in that plane, resulting in a distribution of the measured value from zero to the actual length, especially when the spatial locations of individual nuclei are unrelated. As such, a sampling noise is created that lowers the peak position of the distribution curve away from the real value and also broadens the distribution curve if there are variations in the axis length among individual nuclei [Fig. 5(b)]. In contrast, 3-D measurement of the same parameter resulted in much narrower curves with clear separation of peak positions. The same observation was supported by minor axis lengths, as well [Figs. 5(c) and 5(g)]. Third, the relative orientation angle between neighbors showed a broad peak around 25 deg [Fig. 5(d)]. This peak was weakened in the 3-D results [Fig. 5(h)], where a more even distribution was observed across the spectrum of all angles, indicating a lack of orientation in such tumors. This distribution could be caused by the use of animal models, instead of human tumor samples, as it is well-known that adenocarcinomas tend to form glandular structures, while squamous cell carcinomas tend to form well-oriented cell sheets.45,46 Consequently, by showing more random cellular distribution patterns, the mouse tumor model could be more poorly differentiated compared to human tumors. Cell lines also tend to be relatively poorly differentiated, since these tumors tend toward immortalization. We therefore expect a much more prominent difference of their PDF curves in human tumors, especially when measured in 3-D. In another sense, this difference also supports the utility of the 3-D approach since this method even worked well on mouse models, which are harder to separate. However, the tremendous heterogeneity of human tumors, as compared with only two cell lines in this study, may pose challenges for classification that are difficult to capture in this model system. Finally, compared to the aforementioned features, a clear distinction between 2-D and 3-D approaches could not be found relative to measurements of distance-related features. This was expected because the sampling noise posed by 2-D does not affect the center position of cell nuclei, which are the major determinants of cell-cell distance.
With increasing attention to development of CARS-based microendoscopy to support label-free, in vivo, molecular diagnosis,47–52 another benefit of the proposed 3-D image quantitation system lies in its potential for in vivo differentiation of lung carcinoma cell types and possibly subtypes during biopsy.Specifically, it has long been known that most lung cancers are histologically heterogeneous and that most adenocarcinomas have more than one histologic subtype.44 With the advent of molecularly targeted therapies, avoiding sampling errors to allow complete identification of the various histologic cell types and subtypes within a given lung cancer becomes even more important. CARS allows selecting biopsy sites within a mass or nodule to minimize sampling error. Blind aspiration biopsy or fluoroscopic guided biopsy may sample surrounding tissues rather than the cancer and may not sample different cell types or subtypes within a cancer; thus, they may not be representative of the cancer as a whole. This is particularly important for targeted therapy since any adenocarcinoma component may respond to EGFR tyrosine kinase inhibitor therapy, but the adenocarcinoma component may not be sampled in a mixed cancer, such as an adenosquamous carcinoma, using current techniques. Reducing sampling error improves the accuracy of obtaining tissue and increases the useful sample size for biomarker testing. Since adenocarcinoma subtypes are associated with different biomarkers, future research into CARS microscopy could greatly enhance complete sampling of the different subtypes within an adenocarcinoma. It will not only ensure sampling of all cell types and subtypes within a heterogeneous lung cancer for molecular analysis at the time of biopsy, but also facilitate the whole diagnostic process while providing more abundant biopsy samples of the correct tissues for biomarker studies.
In conclusion, we demonstrated a 3-D analytical strategy in conjunction with the CARS imaging technique for fast and accurate determination of NSCLC cell types. By stacking multiple image slices from a z-stack into a single data structure, 3-D nuclear segmentation, labeling, and measurements were realized for extraction of disease-related features using SLIC-based supervoxel segmentation. Classification was then performed using the extracted features. Compared to a 2-D approach, the 3-D strategy showed much higher efficacy with greater than 97% accuracy and specificity for separation of NSCLC cell types. Collectively, this strategy effectively takes advantage of the superior optical sectioning capability of the CARS technique; meanwhile, it enables quantification of image features in a configuration closer to the natural arrangement of tissues. By doing so, a significant accuracy improvement was achieved for separation of lung cancer subtypes. In addition, since no tissue consumption or sectioning was required, the combination of CARS and the 3-D analytical approach offers an alternative strategy to the widely used H&E staining technique for lesion evaluation with faster analysis times. Therefore, the developed 3-D diagnostic platform promises to provide a new modality that combines advanced nonlinear optical imaging methods with quantitative bioinformatics techniques for label-free delineation of tissue pathology, thus holding the potential to facilitate diagnosis while effectively preserving tissue specimens for follow-up diagnostic tests.
We would like to thank Drs. Kelvin K. Wong, Hong Zhao, Kemi Cui and Zhong Xue from Department of Systems Medicine and Bioengineering, The Methodist Hospital Research Institute for helpful discussions. The funding of this research was initiated and supported by the Department of Systems Medicine and Bioengineering, TMHRI, Weill Cornell Medical College, and the TT & WF Chao Foundation and John S. Dunn Research Foundation to STCW. Provisional patent filed.
Liang Gao ; Ahmad A. Hammoudi ; Fuhai Li ; Michael J. Thrall ; Philip T. Cagle, et al."Differential diagnosis of lung carcinoma with three-dimensional quantitative molecular vibrational imaging", J. Biomed. Opt. 17(6), 066017 (Jun 04, 2012). ; http://dx.doi.org/10.1117/1.JBO.17.6.066017
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"Discussion of US and Canada Trade Secret Protection and the recent EU Directive for the Protection of Trade Secrets"September 11, 2015 – Presentation
Licensing Executives Society International's Pan-American Young Members Congress
IP Litigation partner Julianne M. Hartzell participated in the panel, "Discussion of US and Canada Trade Secret Protection and the recent EU Directive for the Protection of Trade Secrets," at the Licensing Executives Society International (LESI)'s 1st Pan-American YMC (Young Members Congress) Event. The event was held on Friday, September 11, 2015, at TechNexus (20 N. Upper Wacker Drive, Suite 1200) in Chicago. Ms. Hartzell discussed trade secret protection in the USA, from an external counsel perspective.
Ms. Hartzell was joined on the panel by:
- Vincent Bergeron, Partner, Lawyer and Trademark Agent, ROBIC LLP
- Maitreya Jani, Senior Counsel – Patents, Fortune Brands Home & Security, Inc.
- Jean-Hyacinthe De Mitry, Lawyer, Gide Loyrette Nouel, and Chair of YMC


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Telescoping Casement Stays
These telescoping friction stays function very nicely as casement window stays. The friction is sufficient to hold against moderate wind. We have also found that they also make excellent chest stays and drafting table adjusters. Because these stays collapse into themselves, they require only minimal free space inside a chest and the internal friction provides a margin of safety against accidental closure. The locking varieties are ideal for drafting tables where a suitable angle can be found and held with just the friction, then locked for use.
5 products


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An exceptionally wonderful cruise
Sail Date: November 01, 2007
Reviewed: 9 years ago
Traveled As: Singles/Friends
Room Type: Inside
I did my research on the internet and found that offered the best deal. Their travel agent, Karen, was especially helpful to a first timer.
The ship was beyond my expectations. Our inside cabin was quite adequate in space. We could have used a lit up clock, as we didn't know whether it was day or night in the dark. I was impressed with the high calibre of entertainment offered, and goods in shops at very reasonable prices. The fitness centre contained state of the art equipment of which I availed myself...as well as the jogging track. I felt like I had died and gone to heaven after my spa treatment and massage.
One could never forget the plethora of not only delicious but also healthy food in every outlet on the ship. I felt like a small child let loose in a candy store.
All services were professional and friendly. The overall appearance of the ship as well as our cabin was always clean. Our waiter, Val, in the dining room made each one of us feel special and always remained pleasant despite unwarranted complaints. The photographers were of great assistance with my struggles in using a digital camera for the first time.
Embarkations and disembarkations were well handled and went smoothly.
Shore excursions packed alot of sightseeing into short periods of time. I will have to peruse my pictures now to see where I had been.
Thank you for making my 70th birthday special!
Pros: Being pampered
Cons: It was over too soon
Recommends Celebrity Century? Yes!
Category Ratings
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Watching your own TV, thousands of miles away
By Ben Berkowitz
AMSTERDAM (Reuters) - So you're moving from the United States to another country and the most important thing you can think of is how you can watch the new season of "American Idol"?
You're not alone -- "placeshifting" is one of the hottest new areas in TV technology. People no longer need to live in a country to see all of their local TV stations. In fact, they don't even need a TV anymore.
There are platforms for watching popular shows on the Internet and there is technology to actually make a full television feed available just like in the living room. Either way, it can be relatively cheap and surprisingly easy to keep up while on an overseas assignment.
The best-known technology for moving an entire TV feed from one place to another is the Slingbox, which came out a few years ago. Although the developer was later acquired by satellite company EchoStar, the device works with any platform, even an over-the-air antenna.
The Slingbox, which currently comes in two models starting at $180, connects to a video feed and to the Internet, and lets users watch that feed as though they were in the same room. It even offers an on-screen remote control for changing channels, pausing, opening menus, and so on.
The Slingbox is available for Windows and Mac, as well as the BlackBerry, iPhone, Windows Mobile, Symbian and classic Palm mobile platforms.
One downside of the Slingbox, is that it does not offer wireless support out of the box, meaning users need to put their Slingbox close to their Internet router or buy a separate wireless or home powerline adapter. Also, it is not designed to let users record video onto computers.
For those who want wireless or who want to record to a PC, Monsoon Multimedia's Hava Media Player offers many of those features. It leverages the Windows Media Center software to turn a PC into a personal video recorder, using a remote video stream from a Hava box. Hava has four models that start at $120. Continued...


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MODA™ Precision Contour
MODA™ Precision Contour
Stipple and blend concealer with this flat brush for a natural, flawless finish.
This beautifully bold, 100% vegan line includes water-resistant acrylic handles with a Silk-Touch™ coating for ultimate durability and ease of care. Collect all 36 brushes. In addition to the standard MODA™ line, check out our MODA™ EZGLAM Duo Kits and Flip Kits.


text: BUFORD, Ga., May 15, 2013 /PRNewswire/ -- OMNIMETRIX, LLC, an Acorn Energy company (NASDAQ: ACFN) and the global leader in wireless remote monitoring and diagnostics for emergency standby generators, has moved to its new, state-of-the-art corporate headquarters in Buford, GA. The new facility, located at 4295 Hamilton Mill Road, Suite 100 in Buford, GA not only hosts the heart of business operations, but also is home to OMNIMETRIX's recently launched Global Network Operation Center which provides 24/7 response capabilities to its customers. The new office, three times the size of the previous location, allows OMNIMETRIX to expand its core teams to support the growth it is experiencing and the rising demand for around-the-clock technical support for emergency back-up power generation systems. OMNIMETRIX's 24-hour services have risen to meet these demands, and it currently offers a wide range of technical support benefits, including support for new monitoring installations, set up and activation, and user interface support and technical support advice. Deena Redding, OMNIMETRIX's President and CEO, states, "The Global Technical Support Center is a tremendous enhancement to our customer experience. As we expand geographically across the world, we need to provide around-the-clock support for installation and technical support services." Redding adds, "The foundation of our product and service offering is that we dramatically improve the reliability of the emergency standby power systems since we proactively monitor the systems 24/7. However, in the event of a generator failure, our new support center helps to reduce the downtime considerably and significantly improves the proactive field service response time to correct problems." By providing a proactive rather than reactive product and service, OMNIMETRIX has maintained its status as the global leader in wireless remote monitoring solutions for emergency standby power generation and looks forward to continued growth and success in the new facility.


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15285 James Street, Holland MI, 49424
Sold Price:
3 beds , 1 Full baths
920 sqft
Status: Closed
Last Updated: 6/23/2017 12:11 PM
Description for 15285 James Street Holland, MI 49424
Location - Location - Location!! Walk or bicycle on the fantastic bike path to beautiful Lake Michigan! Adorable 3 bedroom ranch in desirable Park Township. Some recent updates include new kitchen countertops, some new flooring and fresh paint. Large family room in basement, many newer windows, glass slider and front door. Extra large 2 stall attached garage on a nice deep lot with underground sprinkling. Really cute home.
Sold Price:
Sold Date:07/10/2015
Park Twp
1 Full
920 (approx)
Listing Information
Park Twp
Public Water Service
Septic, Public Sewer
Cable TV, Electric, Natural Gas, Telephone
School Information
Room Information
Eat-In Kitchen
Interior Features
Dishwasher, Range, Refrigerator
Central Air, Ceiling Fan(s)
Gas Heat, Forced Air
Basement, Full
Exterior / Lot Features
2 Car Garage
Deck, Patio
In Ground Sprinklers
100 x 140
Paved Road, Wooded, Acreage
Driving Directions
James St W of 152nd to address
Financial Considerations
Listing Price History
Holland Real Estate
Holland is located in Michigan. Holland, Michigan 49424 has a population of 33,742.
The median household income in Holland, Michigan 49424 is $44,619. The median household income for the surrounding county is $58,160 compared to the national median of $53,482. The median age of people living in Holland 49424 is 29.7 years.
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text:
|Half Baths
|1,600 sq. ft.
|Property type
|Minimum Stay
|2 - 3 nights
Before you go any farther, read this! I just added a significant discount for a summer week at Loon. The rate is called the Summer Flash Sale, and I plan to have it available until June 11th, when our prices will go back up. Our normal rate is in the range of $1700 per week, but I'm in the mood to get all my bookings taken care of for the summer -- so, if you like what you see, please know that the rate is good through this weekend. Okay -- now that you know the deal, read on!
Four reasons to select this home!
1. It's immaculate! You'll not find a better maintained or cleaner home.
2. Fresh linens and towels, a great kitchen, with top quality supplies. Comfort and privacy.
3. The best location in Loon. Straight across from the ski mountain, in a community of single-family and two-family homes. Unlike places with six-unit buildings, you have room, peace and quiet. Nobody above or below you. Coolidge Falls is the nicest community at Loon.
4. Exceptional mountain views, even from the first floor.
Check under the rates to see how you can make a gift to the Jimmy Fund -- at no cost!
First floor: two bedrooms, one queen bed, one with double bed and bunks - perfect for kids. A large full bath and washer and dryer. Foyer with plenty of room for skis and gear, plus a very large closet.
Second Floor: Full kitchen with everything you need. All utensils, pots and pans plus first-quality tableware/glasses etc. Microwave and dishwasher.
The bar-style window with two stools is ideal for quick breakfasts. Half bath. Dinner table seats eight. Living room with fireplace, cable TV/VCR, CD player is cozy and comfortable - perfect for apres ski fires, or access to the deck for summertime fun. A small library of movies, plus wireless Internet! Firewood is included! Enjoy sunrise to sunset from the deck lounge chairs. Grill steaks on the gas grill. Third floor: Master bedroom with private bath and double sinks, TV/VCR and mountain views. Hear the sounds of the river running through the valley on summer nights. Village of Loon Sports Club. Outdoor pools, year-round outdoor hot tub, indoor pools, two indoor hot tubs, a sauna, exercise room, tennis courts and game room.
Early Arrivals and Late Departures: We are often asked by guests if they can arrive early or stay late when they visit. Our check-in time is 4:00 PM and check-out is 10:00 AM. We need those six hours to fully clean the home in preparation for a guest arriving the same day as a departure. But! Often times we do not have a same-day turnaround, and we are happy to let our guests come as early and stay as late as possible in those situations. We usually can't confirm the extra hours when you reserve -- but we can give you a pretty good idea of the possibility of giving more time. And if we do need to stick to our standard times, you may take advantage of the sports club, and drop off the key later. (This means you could ski or hike all day after your departure -- head to the pool or hot tub at the end of the day, play, shower and head home whenever you like.) And that's an option for all guests all the time!
An important note about HomeAway and VRBO's 'Instant Quote' feature! The system quotes our full price for a standard one week or weekend stay. If you want to rent a weekend in ski season, or a full week, it is usually accurate. However! If you want to rent for, say four nights in ski season -- please contact me. I can almost always offer a discount from the listed rate. Similarly, if you have a stay that fits well with the arrival or departure of other guests, I can generally offer a discount from the automatically quoted rates. Thanks for reading... I look forward to hearing from you!
Still reading? Great. Many people write and ask if we rent our home for the full ski season, or if we will allow a family of 10 or more to stay. A funny new feature of this website you're on right now, is that it records the number of times people send me an inquiry, and compares it to the number of times I accept a reservation. Every time someone asks for something that we just can't provide, and we turn down that reservation, that hurts me by putting my home farther down the list of homes when the next person searches. So, to answer two of your most frequent questions:
Q: "Do you rent for the ski season?"
A: Generally, not. But the rate for a full season is $12,000 and you pay the utilities when you do this type of rental. If you want the full season, you know the price. If the calendar is open from November 1 to April 30, please inquire.
Q: "Can we bring more than eight people?"
A: The only time we accept nine people is when one of them sleeps in the crib you are bringing. We never accept ten. (And yes, everyone, regardless of age is a person!) If you have more than eight people, none of whom are infants, please do not inquire.
Hi Folks, We are Mark Krumm and Kathy Beitler. We live just south of Boston and purchased this wonderful home in 2000 when our two boys were little guys and we loved to ski and hike.
Kathy and Mark are both transplants from Ohio and have lived in the Boston area for about 30 years.
We have been renting our home since the year we bought it and have a pretty good idea of what makes a great vacation for you, our guests. Read on...
Mark Krumm purchased this townhome in 2000
If you asked me the three things that make our home different (and better) than most, it would be these:
1. The views. Everyone comments on the great views to the mountain. You get sunrise and sunset views from the decks. There's nothing better.
2. The condition of the home. We keep it spotless. From Mark's travel days, we learned that guests should feel like nobody has ever occupied the home before you. That mean it is super clean, the refrigerator --and everything else in the kitchen is perfectly clean. Bathrooms? Yes -- super-clean.
3. The value. Look around, you will no doubt find someone who has a lower price. But you will not find a better value. If our price is in the range you expect to pay, it's unlikely that you'll find anything as nice.
Okay, we can't resist -- one more thing to think about -- Coolidge Falls is one of the very nicest communities at Loon. We are not stacked on top of each other, in fact we share one common wall with one neighbor, and that's it. No one above or below. We are at the end of a dead-end street, and there is no through traffic, just you and your neighbors.
Aside from the home itself, your proximity to fun places is simply the best in the White Mountains. The famous Kancamagus Highway is at the end of our community. And that lead to great places for nature lovers like Sabdaday Falls, The Basin, The Flume, lake swimming, hikes of every distance and elevation... we are close to Lost River and Clark's Trading Post and easy drives to the Cog Railroad, Mount Washington Auto Road, Saco River Canoeing, Santa's Village, Storyland and the big city of North Conway for that shopping excursion.
You'll find brochures for all the area attractions and restaurants -- and even our favorite book the 'AMC's Guide to the Best Day Hikes in the White Mountains' -- a book that just about every summer guest has taken on the trail when they head out the door. And of course, at the end of the day, you can hit the pools (plural, there are four!) or hot tubs (yes, 'plural' again) at the health club, and fire up the grill or visit one of the many great restaurants in town.
Mark and Kathy,
This was the most beautiful place we have ever stayed! The Chalet is equipped with everything you could ever need. We loved the refrigerator with the water and Ice maker. The views are amazing from everywhere in the house. We did so many things on our vacation, including Storyland, The Flume, Cannon Mountain and Whale's Tale. We enjoyed the pools and the hottubs so much. This is a gorgeous place with so much around it. We loved the pools with no deep end to play basketball in. Every day was wonderful, even if it rained a little. I would definitely come back here and I would highly recommend it to everyone! Thank you for being great hosts and giving us the opportunity to enjoy your home.
We will be back soon.
Thanks again,
Doreen and Brian - Dracut, MA.
We stayed in summer of 2015, I believe, but the calendar won't go back that far. Thought I had written a review already but it doesn't seem to have gone through. Thinking of going again to the Loon Chalet, as it was a perfect place for my family! So much to do in the area and at the house, not to mention the pool area, and very easy to find everything you'll need. On top of that, the owners are kind and gracious. Really a wonderful place all around!!!
Our 4th time staying, we love it and will be back next year.
Mark, the owner is very nice, had a bottle of wine for us when we got there. The place is very nice, clean and so close to all the attractions and restaurants.
This place is exactly as advertised. It is a large, well equipped and appointed, clean condo, with wonderful views out most directions. It is an ideal location to stay during a vacation in the White Mountains, with easy access to lots of interesting things to do. We will certainly be back.
There were a number of things that I really liked about this place, but the most amazing was the view and the general location. The "chalet" is right across the Kakamangus Highway from Loon Ski area, so there is a very pretty view from the porches and decks. It was also an ideal starting point to go see the waterfalls and do small hikes and swimming with the kids. (It was a little chilly for the lake, but chasing minnows for a 4-year-old was pretty fun.
The house is very clean and well maintained. The bathrooms and kitchen (my two places that I generally want to re-clean when I go somewhere) were spotless. It's comfy, and with three levels, there's privacy for Grandpa in his room while the kids played in the living room.
We will be back, for sure, and are delighted to offer a positive review to others.
Activities: Skiing, boarding at Loon, with free shuttle bus to mountain, hiking the White Mountains, biking trails, golf, tennis, fitness center, miniature golf, Santa's Village, Clark's Trading Post, Storyland, Whale's Tail, fishing, moose viewing, horseback riding, shopping, restaurants, cinemas, sightseeing, cross-country skiing, snowmobiling.
|Rate Period
|Weekend Night
|Monthly *
Summer Flash Sale!
Jun 17 2017 - Sep 2 2017
Changeover Day: Saturday
3 night minimum stay
Winter Peak Season
Dec 17 2017 - Mar 31 2018
2 night minimum stay
My Standard Rate
2 night minimum stay
|Refundable damage deposit
|Tax Rate
We do our best to offer our home at the lowest possible price and give you no run-around or surprises with added fees. At our published prices, we generally sell out, and there is rarely a need to lower the price. If, though, you see some dates coming right up in a week or so that are empty, we'll do our best to rent the dates -- and may be able to take a little something off the price.
* Approximate monthly rate. Actual rate will depend on the days of the month you stay.


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Vampire Teeth Fangs
Product Number:Fm_22197
I vant to suck your blood! But vit vhat? Need some dentures to round out your vampire costume this Halloween? Then sink your teeth into these Vampire Teeth Fangs!
Vampire Teeth Halloween Fangs
In Stock!
Retail Price: $5.00
Our Price: $2.95


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Added 18/03/2017
Repair I had my house rewired several years ago and the wires from upstairs are clipped to...
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Needs electric fire checking for fault and fixing Property style: Suburban
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Wanting a light switch disconnecting for removing of internal wall and new switch and sockets...
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Outside light with sensor and also an external socket. Power shower stopped working and may...
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Install 1 x light fitting Additional information: Taken down existing light - only need 3...
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I have an outside light to replace. It is a like for like so should be straight forward and...
Made a really good job of a difficult re-wiring on an old house. Really friendly and efficient service, would recommend them.
Very pleased with the professional, friendly and helpful service provided.
Very helpful in explaining what was needed and why. Andy did a very professional job, very quickly, in installing the external circuit and sockets.
Faultless installation undertaken with great care and attention to detail. The cleanest tradespeople we have ever used - cleaning up as they went. No hesitation to recommend Dan.
Efficient, friendly and excellent value. I will use them again without question.
Very quick and efficient service. Darryl was very friendly and did a great job. No hesitation at all in recommending him. Thank you.
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text:
Bhopal, Sep 18 (UNI) BJP President Rajnath Singh is arriving in the state capital on September 20 in view of the three-day national executive meeting getting underway here on September 21.
Party sources said Mr Singh would arrive at the Raja Bhoj airport on September 20 where he would be welcomed. He would drive straight to party headquarters and review preparations for the meeting.
Sources said senior BJP leader Murli Manohar Joshi would reach the state capital in train on September 21.
Chief Minister Shivraj Singh Chouhan and state BJP President Narendra Singh Tomar today reviewed the preparations for the meeting.