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, in cooperation with the New York State Office of Parks, Recreation and Historic Preservation- Central Region, the 9th annual Green Lakes Endurace Races.
As the Race Director, Thank You for your patience in our delayed opening this year. I was strongly considering career relocation options over the past 6 months and wasn't sure I would have the opportunity or privilege to RD 2015 GLER and held off on opening registration until those issues were resolved.
We anticipate that our GLER Team will hold another highly competitive and enjoyable set of trail ultra-marathons again late this August.
Ultrasingup.com at:
Green Lakes Endurance Races
100 km & 50 km trail races
Saturday August 6 BOTH RACES START AT 0600AM
Affiliated with the Road Runners Club of America
Green Lakes Endurance Runs
201 W. Genesee St.
Fayetteville, NY 13066
United States
My 2013 GLER 50K Race Report......Let's see, where do I begin....
My 2013 GLER 50K Race Report begins with the Annual UM meeting last August 26th, 2012. Since GLER had been cancelled for 2012, a FatAss Run and Annual UM meeting were held on that date. At the meeting, I won one of the drawings which was for the entry fee into any one of the UM races for 2013. Originally, I had planned on using it on the Mind The Ducks (MTD) 12 Hour Endurance run. I knew I had more miles in me than what I had run at my USATF age group record run in 2012 (I had trained to average 5 miles per hour for that race which I felt was doable based on my 2011 MTD total miles of 57.675 and I was on track (no pun intended!) to do that - But I didn't train for the heat! Big mistake! - 4 hours into the 2012 MTD run, the heat got to me and I was bent over on the side of the course - SICK! - I lost valuable time and pace working through this issue and, as a result, I could not get back to my 5 miles per hour pace, but I was still able to complete the race and set the American age group (65-69) record that day. I broke the record of 48.7198 miles at 11:03 hours into the race. I had run 48.7898 miles, but I wasn't done yet! I continued on and broke my record 5 more times. I stopped with 12 minutes left in the race and 51.471 miles completed.) Unfortunately, the MTD race for 2013 was cancelled earlier this year and my plans to try and beat my American record this year ended! I was so disappointed,...but not for long!...I signed up for the 2013 GLER 50K instead and decided that I would try to better my 2011 GLER 50K time of 6:54:32. (When I looked at what Ultra Signup predicted as my finish time, I was even more determined to beat my 2011 time. They predicted that I would finish over 7 1/2 hours (can't remember the exact time now but I know it really got to me). I realized that I was 2 years older - I was now 66 years old, but what the computer didn't account for was that I have not peaked as a runner yet :) - I started running at 60 years old and ran my first Ultra at 63 years old.
Friday night before the race, I had 6 runners from out of town (Rochester & NYC) stay at my house. Katherine Fleming, Dave Farrands, Egils Robs, Mary Harvey, Joe Delano, and John MacKenzie...I already knew Ultra runners are nice, but being able to spend this time with these runners was extra special. And, they were so nice to my dog - Morrie (who thinks anyone who comes to my house is there to be with him) and my two cats - Terra (very social cat) & Cotta (who bonded with Katherine as they shared a bedroom together). Can't wait to do this again. The 3 runners from NYC even stayed over until Sunday morning. We had fun socializing and getting to know the new runners Friday night before the race, and then we were up, ate, and ready to head out the door by 4:00 AM Saturday morning to Green Lakes State Park for the race - we were all signed up for the 50K....There is so much more I could write about here about the time spent with these runners, but I will stick to my "race" report - I will just say I really enjoyed spending this time with my "new" friends and my "old" friends.
My training for this race included running 1 loop training runs of the GLER course after deciding where I would walk and where I would run and where the tricky spots were on the course, down hill path, etc. I would do these 1 loop runs in ~1:25 (I would do the first 5 miles in just under 1 hour and then relax a little and recover during the last 2.75 miles.) Then I did some 2 loop runs, always running the first loop around the same time (1:25), and then I would do the second loop much slower between 1:45 - 1:55. I never ran 3 or 4 loops together. I was thinking that on race day I would try to start off with one of these 1:25 loops and then slow down and be reasonable with my pace - but I also knew that if I started out that fast that it might come back to "bite" me since I had not done anything close 4 loops back to back during my training. By Wednesday, prior to the race, I ran my last training loop run in my Hokas and I noticed I was tripping in the grass on the Serengeti - (I had worn the Hokas to the PGA tournament at Oak Hills in Rochester on Aug 6th and noticed that when I walked in the short rough on the course which was similar to the length of the grass on the Serengeti - the Hokas were getting stuck in the rough and would cause me to trip slightly - but they were great as far as being on your feet all day at the PGA) - since I wasn't sure if the grass on the Serengeti would be cut some by Saturday, I decided not to run in the Hokas and left them in the car race day. Instead, I decided to run in my Newton Gravity running shoes (which aren't waterproof) and put my other Newton Waterproof trail shoes in my drop bag.
Start of the race: 100K (20 runners) & 50K (100 runners) started together this year.
BTW - I left my "Darth Varder" rain outfit that I had on at the start of GLER in 2011 at home this year (although in 2011, we were running in Hurricane Irene - 5" rain fell during that race) - I learned very quickly that day in 2011 that it is better to be colder and wet than being comfortable at the start of an Ultra. It doesn't take long for the body temperature to rise. Saturday, at the start of the race, I had my hydration vest half filled with water and I carried Endurolytes and Shot Bloks and a banana in my vest.
My 1st two loops were paced just right (for me that was - I'm sure Katherine and Ken might have wanted to be moving a little faster though) and I felt great. Katherine, Ken, and I were running together - the weather was perfect. When we got up onto the Serengeti, I noticed that the grass had been cut (could have worn my Hokas but too late - they were back in my car and I wasn't going to go get them) and there was a lot of dew on the grass - I should have started out running in my waterproof Newtons but too late now. The view on part the Green Trail was so beautiful on the first loop with the fog in the distance (Katherine had her iPhone and got a picture of it). Stopped at aid station #2 for some "sugar" - said hi to Greg and off we went. While running, I took Endurolytes every 1 to 1.5 hrs and Shot Bloks every 3 miles, and at aid station #1, I would also have 1 packet of Salted Caramel Gu (awesome) and grab a cookie. During the 2nd loop I was feeling some hot spots from my wet socks and wet running shoes so I decided to change socks and put on my waterproof Newtons when we finished the 2nd loop. Katherine changed her shoes and socks and put on her Hokas. I made a "pitstop" at bathroom in the Great house at this stop. I had a little trouble getting my wet socks off and changing into a pair of dry socks and dry Newtons. After the 3 of us "sugared" up at the aid station, we headed out on the 3rd loop. I got down the stairs in back of the Great House, and my right thigh muscle right above my knee started pulsating (I could actually see it) - it was pretty painful - I would have to slow down and try to rub it out while running. At this point, I wanted Katherine and Ken to go on ahead - I didn't want them to hang back for me - they had PRs they were going for...They wouldn't run on ahead - they stayed with me (with hindsight, I wish had made them run on) ...I tried to run through the pain and occasionally it would feel better, but then the pulsating would come back. We got to aid station #2 (4 miles away from when this first started) and Ryan O'Dell gave me 2 Salt Sticks to take to help me with my muscle problem. He told me they would eventually kick in and help, and Greg filled my water vest and off we went. The eventually, the Salt Sticks helped lessen the pain of the "charlie horse" in my right thigh. When we got to the campgrounds and the big down hill portion of the loop, I decided to run the downhill in back of Katherine and Ken (the previous 2 loops - I ran in front of them down the hill portion ( I love downhills) and I had clear view of the trail and saw all the roots and stuff on the trail (and, more importantly, I was focused on the trail). Unfortunately, on the last part of this downhill coming around the corner and down to Round Lake, I got a little to close to Ken, and in addition to that I was distracted by acknowledging one runner running up that hill, and I tripped and barely caught myself - pulling some back muscles and my right calf muscle. I am so thankful that I didn't fall, because I would have wiped out both Ken and Katherine, and it would have been entirely my fault --- running to close to a runner while running downhill - VERY BAD.... (In all my practice runs on this down hill section, I never had anyone running ahead of me and I learned a very valuable lesson Saturday. Someone was watching over me! (Was that you Linda? - she is one of my angels in heaven)...I don't even want to think of what could have happened on the hill....Well needless to say - I'm mentally, as well as physically, struggling at this point...I knew I was slowing Katherine and Ken down and it wasn't fair to them...Finally after finishing the 3rd loop - got to the aid station and got more water in my hydration vest - I knew I had to have Katherine and Ken leave me and go run that final loop with out an "anchor" (ME). We got down the stairs and I said goodbye to them and I watched them disappear ahead of me - I felt relieved that they had gone on, but now I was really hurting - both legs had different problems now and I had a pulled muscle in my side. I did versions of running then walking until I got to the hill portions going up from Round Lake to the Serengeti...Then I went back to my planned loop (although a little slower pace) - unfortunately, on the last section of this uphill almost to the power line - I fell "UP HILL" - my weight landing on my left arm and left knee but at this point felt most of the pain in my left hand - I just whined a little bit, picked myself up and headed up to Serengeti to get to the aid station - I was able to keep to my plan run and walk sections for the Serengeti and when I got to aid station #2 - I sat down just for a very short time because I knew that could cause me to stiffen up - Actually my plan is always to get in and out of aid stations as quick as possible. Greg asked me if I needed any water and I said no, that I got water back at aid station #1 and so off I went - The Green Trail (except for the portion along the hedge row) is my favorite part of the GLER loop and also the big downhill from campgrounds to Round Lake and that was still ahead of me and I felt better knowing that. Well, I knew I didn't like the hedge row, and this time on it I ran out of water - I should have gotten water back aid Station #2 but I thought I had enough and didn't even check it there. So now on top of everything else, I have 2.75 miles left to cover with no water - one good thing was that I would be off the Serengeti in a few minutes...I got down to Round lake without needing any water, and now I started looking at my watch trying to calculate whether or not I had time enough to get to the finish line and beat my 2011 time of 6:54/6:55 (couldn't remember exact time). (Now this may not make any sense to you reading this, but at this point in the race, I have this scene from "Monty Python and the Holy Grail" running in my head, where two guys were sword fighting and the one guy would get an arm cut off and he would put the sword in his other hand, and he would start fencing again, and he also got his legs cut off, but he kept coming back for more)....well this is what I felt like at this point - my right leg, my left leg, my hand, my arm, and now no water.....and I'm still thinking I can do it...set a PR in this race....needless to say - I walked - I ran, etc, etc, came out to the beach with less than 1/2 mile to go, panting like my dog "Morrie after he comes in from chasing his Orange Peanut", still thinking I can do it, and when I finally came around the path to where the "Chalk Messages" (loved them) were on the pavement, I saw the time of 6:42:59 change to 6:43:00 on the clock at the finish line, and I "sprinted" to the finish line because now I had a new race going on in my head and that was to get to the finish line before the 43 on the clock turned to 44...and crossed finish line at 6:43:49 .... PR!!! (2011 time 6:54:32)...Katherine and Ken, your PR should have been a much faster time!!!! Thanks So Much for Helping Me Get Mine!!!
On race day, before, during and after, it was great seeing so many of my running friends and new running friends running GLER. Christine (thanks for delivering the Endurolyte tabs to me before the race), Deb, Nicole, Eric (met him during a training run at GLER - this was going to be his 1st ultra - he was doing ~ 1 hr loops in training and he looked very strong as he flew by me Saturday - lapping me of course), Roger (Good Luck at Oil Creek this year - doing the 100 miler, again - the 50K was tough enough for me), Tom, Bill, Ken, Luana (way to go 100K finisher) - and of course, my house guests, Mary (the only person I know that can get stung by a bee at the same spot on the course during two separate loops - once on her stomach and once on her tongue - and she kept going even continuing the "down the slide at the playground" routine as she and John passed it on the course during each loop), John, Joe, Dave, Gil and Katherine (her conversation during the 3 loops we did together made it so easy to keep going - the loops seemed to fly by - I always thought that if you talked while running that it would sap your energy faster. But not her - she never tired - it was just so much fun to run with her - and she even did the 14 miler at Letchworth State Park the next day with Christine and Joe - according to my "Fitbit", I was averaging 5500 steps per day for the next 4 days - after my 65,000 steps on Saturday).
I want to thank everyone involved in this day: The race director, Tim Hardy - thanks for taking over the duties as RD of GLER for without you GLER might have ended forever; all the wonderful volunteers at Packet Pickup and manning the aid stations - they are pros - they know how to get you in and out as fast as possible with everything you need to keep going - a special thanks to Ryan O'Dell for the Salt Sticks on the 3rd loop - my day might have ended too soon without them; Leone timing (Sue Leone - it was so great seeing you as I finished my 1st loop) ; Doug Hardy for taking all the photos of the finishers; Greg - thanks for all the training runs & the support during the race at AS #2 (and for getting the Endurolytes to me). I hope I didn't forget to thank anyone !!!
Congrats to all the 100K runners and the 50K runners!
Mary DaSilva
Brewerton, NY
gleruns.org, Green Lakes Endurance Runs, a.k.a. GLER. All rights reserved.
"Dedicated to the preservation and enjoyment of Green Lakes State Park."
Green Lakes Endurance Runs
201 W. Genesee St.
Fayetteville, NY 13066
United States


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Two goals from Andre Gray saw the Clarets come from behind to beat Bolton and go top of the Championship for the first time this season.
Burnley fell behind with 20 minutes remaining as David Jones was dispossessed by Darren Pratley, who found substitute Gary Madine, and he rolled the ball across goal for Liam Feeney to turn in at the far post.
But the Clarets again showed they have the strongest chin in the division.
Gray levelled four minutes later as Matt Lowton slung over a low cross, and though Paul Rachubka pulled off a stunning save, the Championship's top scorer lifted the loose ball over the keeper.
And 11 minutes later, Fredrik Ulvestad, with his first touch after coming on as a substitute, lifted the ball over the top for Gray, who went clear and finished unerringly.
Burnley had to thank Tom Heaton for clawing the ball out of the top corner at the death, as a defender inadvertently flicked on a Feeney free kick, but the Clarets held out to go top.
Neither keeper was otherwise tested in a tense game.
In the first half, Josh Vela flashed a volley across the face of goal from a Feeney cross, while George Boyd's shot was deflected wide of the near post by Rob Holding.
Wanderers started the second period the better and deserved their lead, but Burnley did what they do, found a way to win, to leapfrog Hull at the top


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(CNN) — The U.S. Army has appointed a two-star general to investigate how and why Army Sgt. Bowe Bergdahl left his base in Afghanistan, resulting in his capture, a senior defense official said Saturday.
Bergdahl spent five years in captivity until his release May 31, in exchange for five Taliban figures being held at a U.S. military detention facility in Guantanamo Bay, Cuba.
Bergdahl returned to the United States — specifically to an Army medical facility in San Antonio, Texas — early Friday.
The investigating officer looking into the circumstances surrounding how Bergdahl went missing is expected to begin working on the case next week, though that doesn't necessarily signal anything about when the sergeant will undergo formal questioning.
The senior defense official declined to name the general who will investigate until there is a formal announcement.


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I wrote most of a story for NaNoWriMo. That is to say, I hit the 50,000 word goal, but the story isn't finished. I do plan on continuing it. It's nowhere near good enough to get published - real published, I mean, not self-published or blog-published. That, I can do. After all it's free. No risk. And if no one likes it, who cares? They didn't pay for it.
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Category: emerson
Kershaw Emerson CQC-2K Knife Review
The Kershaw Emerson collaboration series features classic Emerson style knives with the production quality of a Kershaw. With the release of the CQC-2K stinger knife, you get a quick deploying blade, a comfortable handle that ensures a solid grip, as well as a unique opening system.
The 2 3/4″ blade on this knife boasts a modified clip point with a slight recurve. The recurve makes pull cuts a breeze especially when cutting straps, rope and string. The outward curve of the belly "holds" the item to be cut and allows the blade to slice through it with greater ease when making pull cuts. The clip point gives greater strength to the tip of the blade when making piercing cuts.
The blade on this Kershaw knife is 8Cr13MoV stainless steel with a black oxide coat that gives even more corrosion and wear resistance to an already great blade steel. The blade will be relatively easy to sharpen—I would call it an 9 of 10 on ease of sharpening scale– and should keep a fine edge under heavy use for a reasonable amount of time. Sharpening the blade will require a small bit of skill to sharpen along the recurve edge. The recurve isn't overly aggressive and shouldn't present much of a problem to any but the absolute novice knife sharpener.
Blade locks in place with a seriously secure frame lock. The pivot pin can be adjusted with a normal flat screwdriver. The knife comes a bit stiff out of the box. I actually prefer this on a manual folder so that the blade doesn't flop open without cause. You can loosen the pivot a bit and make it for a "looser" open if you prefer. The blade does have a ball detent that keeps it "locked" in place when the blade is in the closed position.
To open the blade with the Emerson "wave feature" you just the knife out of your pocket and at the same time pull it backwards toward the area behind you. As you do this, the "wave feature" hook catches on the edge of your pocket and pulls the blade into the open and frame locked position. Done properly, this method of pocket retrieval® is simple and quick. In fact, done right this knife opens faster than most automatic knives because the blade is deployed as soon as you have it fully out of your pocket as opposed to most auto knives that require you to withdraw them from your pocket and then press the fire button.
The handle has a black G10 front scale and a 410 black oxide finished back scale. There is a nice, deep yet gentle finger groove for your forefinger that is followed by a long curve for the rest of your fingers. This is a relatively small knife which means that for someone with extremely large hands it may feel too small. For average to large hands the size should be just right. Some mild jimping is found on the spine of the handle scales for a bit of extra grip.
Tip up right or left pocket clip. Lanyard hole for alternate carry.
This knife is specifically shaped for serious slicing and piercing. A fantastic EDC knife for anyone who wants a well built knife that is easy to use and has serious power. Check out the Kershaw Emerson CQC-2K on our website here and let me know what you think of it below.
- Designed by Emerson, built by Kershaw
- Thumb disk; "waved shaped opening feature"
- Manual opening
- Frame lock
- Reversible pocketclip (left/right)
- Steel: 8Cr13MoV, black-oxide coating
- Handle: Textured G-10 front, 410 black-oxide coated back
- Blade length: 2.75 in. (7 cm)
- Closed length: 3.6 in. (9.1 cm)
- Weight: 2.8 oz. (79.4 g)
Kershaw Emerson CQC-4K Knife Review
Kershaw and Emerson have just collaborated to release a line of knives built by Kershaw Knives based on the classic Emerson features. Each of these knives boast the "wave feature" that has made Emerson so popular over the past several years.
The CQC-4K is a slim, ready for action manual knife that is built for serious daily carry or tactical use. The precision engineered knife has a modified drop point blade with a standard edge. Finished black for maximum wear resistance and glare control, the blade opens smooth and easy. The best part is it opens with the "wave feature" as you pull it from your pocket.
The "wave feature" is a small hook built into the blade. As you pull the knife from your pocket, if you pull it back at the same time, the hook catches on your pants pocket and opens the blade. By the time you have the knife fully withdrawn from your pocket, the blade is open, locked and ready for action.
The blade is 8Cr13MoV stainless steel. You can expect solid, workmanlike performance from a blade like this. This stainless steel is generally tempered to a Rc56-58 range. Generally comparable to AUS-8 stainless steel, the 8Cr13MoV has slightly more carbon but performs simliarly. The blade is going to give solid corrosion resistance, keep a good edge and be easy to resharpen when the time comes. The black oxide coating on the blade adds a bit of corrosion resistance.
Let's move to the handle. A solid frame lock system, the front scale is textured, coyote brown G-10 on a 410 stainless steel handle frame. Lock up is solid with the frame lock achieving a nice secure lock every time.
The pocket clip is tip up, reversible for right and left.
The blade reads Emerson and has the Emerson Skull logo and the pocket clip also displays the Emerson Skull logo. The back of the blade reads Kershaw and then the model number.
This knife is currently selling for around $36. Considering a standard Emerson will set you back well over $100, this new Kershaw Emerson knife is a definite bargain. Check them out on our site and let me know what you think of yours below.
- Designed by Emerson, built by Kershaw
- Thumb disk; "waved shaped opening feature"
- Manual opening
- Frame lock
- Reversible pocketclip (left/right)
- Steel: 8Cr13MoV, black-oxide coating
- Handle: textured G-10 front, 410 black-oxide finish back
- Blade length: 3.25 in. (8.3 cm)
- Closed length: 4.2 in. (10.7 cm)
- Weight: 4.1 oz. (116.2 g)
Kershaw Emerson CQC-3K Knife Review
Just hitting the shelves is the much-anticipated Kershaw Emerson collaboration knife, the CQC-3K. This folder boasts the classic "wave feature" from Emerson that allows you to open the knife as you pull it from your pocket. Easily one of the coolest structural mechanisms to hit the knife market in the past few decades, the "wave feature" is quite simply a small curved integral hook that sits at the spine of the blade where it meets up with the handle. When you withdraw the knife from your pocket, if you pull it outwards also, the hook snags the edge of your pocket from the inside and the force of your pull draws the blade from the closed position to the fully open and locked position. Not only does this look awesome when done properly, it allows you to pull the knife out and have it ready to use in an instant. Although not an auto knife, you may actually feel like it is one. This "wave feature" was designed to allow ranchers and farmers to pull their knives out and have them ready for action immediately. It makes for easy one hand operation.
What else is great about this knife? All kinds of things. First, it is being manufactured by Kershaw Knives which means you can count on high quality production. Second, because it is being produced by Kershaw, you can get what is essentially an Emerson knife for well under $100. In fact, you can pick this one up for just a hair under $40–an unbelievable price for an Emerson.
The knife has a black finished tanto blade that can also be opened with the thumb disc that sits atop the blade spine. This means the knife operates as a truly ambidextrous model. The tip up pocket clip gets into the act by being right/left reversible. The handle is comfortable to hold and provides plenty of grip with its front G10 scale. The framelock back scale is 410 steel with a black oxide coat. It functions flawlessly and keeps the blade open when you want it that way.
This is a spectacular collaboration that provides a fantastic every day carry knife at a price that won't destroy your budget. Find the Kershaw Emerson CQC-3K on our site here. Let me know what you think of yours down below.
- Designed by Emerson, built by Kershaw
- Thumb disk; "waved shaped opening feature"
- Manual opening
- Frame lock
- Reversible pocketclip (left/right)
- Steel: 8Cr13MoV, black-oxide coating
- Handle: Textured G-10 front, 410 black-oxide coated back
- Blade length: 3.25 in. (7 cm)
- Closed length: 4.2 in. (9.5 cm)
- Kershaw Product Code: 6014TBLK
- Weight: 3.8 oz. (107.7 g)
Emerson Roadhouse Knife
Emerson continues to knock the ball out of the park with their knives. Each one is built for serious, heavy use. The Roadhouse knife is no exception. Consider the black G-10 handle scales. Built for comfort, grip and durability, the scales have the classic Emerson texture that makes for a solid, anti slip grip. On the spine of the handle, right close to the blade, there are several jimping ridges that give your thumb a nice, extra solid grip when you choke up on the knife for close cutting work. The same jimping ridges can be found right where your pinkie finger sits. All in all, the handle is built for use. An oversized finger groove gives your forefinger a comfortable seat and it keeps your hand from slipping up onto the blade during heavy cuts. Now let's look at the 154cm tanto blade. Built with the patented "wave" feature, with practice you can have the blade open and ready for work as soon as it leaves your pocket. The tanto shape makes for an extra sturdy blade that is perfect for slicing, slashing, as well as piercing cuts. The 154cm is going to stay sharp for a long time–which means you can spend more time on the road and less time in your shop getting your knife sharp. And to top it all off, this knife is made in the USA and carries a limited lifetime warranty. Check out the Emerson Roadhouse–you'll be glad you did.
Overall Length 8.9 in.
Blade Length 3.8 in.
Blade Thickness .125 in.
Hardness 57-59 RC
Weight 6.2 oz.
Handles Black G-10 epoxy / glass laminate
Lock Aerospace grade Titanium
Blade 154 CM
Blade Style Tanto, Plain Edge
Finish Black
Grind Conventional V Grind
Emerson Knives Mini Roadhouse
If you need a tough folder knife that is built for the roughest of work–you can always rely on an Emerson knife. The Mini Roadhouse is no exception. Hard work, heavy duty choppers and late nights is what this little knife is all about. Built USA tough with G-10 handle scales and a 154cm stainless steel tanto blade, the Mini Roadhouse has attitude that just cannot be corralled. The blade can be opened easily via the thumb plate or you can use the "wave" feature. As you pull the knife from your pocket, just snag the "wave" on the edge of your pocket–by the time the knife is clear of your pocket, the blade will have snapped into the fully open position. It locks up solid with the aerospace grade titanium liner lock and stays ready to take care of whatever cutting needs to be done. Check out the Mini Roadhouse and find out what all the fuss is about.
Emerson Commander v. Super Commander Knives — Video Review
ProTech CQC7 Automatic Knife
This Pro-Tech CQC7 Automatic knife was built as a collaboration between Ernest Emerson and Pro-Tech Knives. This fantastic auto knife features a tanto blade with a chisel tip. Built with the famous Pro-Tech coil spring, this knife opens fast and hard. The lock up is tight. Built at the Pro-Tech facility, the knife features all the high quality manufacturing that you would expect from a Pro-Tech built knife. I especially like the handle on this knife. It is basic. Made of 6061 T6 black aluminum, the shape gives your hand and extremely comfortable hold. And it has just a bit of jimping on the spine of the handle right where it meets the blade–which gives you a great spot for extra leverage if you need it. The blade also has a spot right near the junction of the blade and the handle where your thumb fits perfect and gives you even more leverage. This knife is built to be used. This collaborative effort stands tall–well made, top quality materials, and an extremely useful shape make the Pro-Tech CQC7 auto knife perfect for every day carry.
Overall: Pocket clip on back side matches blade finish – drilled for tip up or tip down carry. Comes complete with nylon pouch.
Weight 4.1 oz
Handle: T6 6061 Aluminum / 4.67″ Long / 1.09″ Wide / .45″ Thick
Blade: 154-CM Stainless – 3.25″ Long / .96″ Wide / .120″ Thick Chisel ground Tanto with integral thumb grip.
Emerson Commander Knife
Every once in a while, a knife comes along that really wows you. The Emerson Commander has been out for a couple of years now. But it is definitely one of those knives. Originally, it won the "Best Overall Knife of the Year" at the International Blade Show in Atlanta. And if you have ever held the Commander, you quickly can see why. The knife is reasonably big. It is rugged. And it is built strong. Made with a 154CM stainless steel blade with an excellent V grind, the Emerson Commander works like a charm. It is easy to open. You can even use the WAVE feature and open it as you pull it out of your pocket. The G10 scales make it easy to grip and hold onto. It is easy to see why so many elite forces around the world like the Commander knife. Strong, built to last and to perform, and easy to use. The Emerson Commander is a definite must have knife.
Overall Length: 8.75 in.
Blade Length: 3.75 in.
Handle Length: 5.0 in.
Blade Thickness: 0.125 in.
Hardness: 57-59 RC
Weight: 4.9 oz.
Made in USA


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King of the castle. Mancave. Nah, not for me. Home is where I don't have to think…okay that came out wrong. Home is what makes everything I do outside of it, worth it. Within its walls is where I recharge. Home is my family's sanctuary.
Home is family. Family is home.
Home is my family. It's the hub of my family's lives. Within its walls is our private sanctuary.
My space.
Mine and my husband's space. Where we are free to be everything for each other.
It's also where I nursed my babies. Care for my sick children. Sooth nightmares. Wait out thunderstorms.
Home is family. Family is home.


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4 Ways to Rise Above the Noise & Generate Leads OnlinePosted in Book Reviews, Consumer, Marketing, Outreach, Professional Development, Social Media, by Doug Devitre on February 19, 2015
Are you drowning in the endless supply of data? Chances are your customers and clients are too. Search engines are quick-loading when it comes to giving advice. And too often, that advice is automated, over-opinionated, and misinformed. The buzz of social media is quietly fading and the scream for demonstrating value is taking on new forms of creativity that promote the customer's best interest, not just sell a solution.
So how do you lend a helping hand without coming across as a salesperson who is just looking for a commission check? In his new book, YouTility for Real Estate: Why Smart Real Estate Professionals are Helping not Selling (Portfolio | Penguin in November, 2014), Jay Baer really lives up to his subtitle. This shortened version of his New York Times best-selling book YouTility provides practical case studies on how real estate agents are succeeding with this approach.
Here are four elements of Baer's new book that you can implement in your marketing right away.
"Friend of Mine" Awareness
The best source of business is via trusted referrals and past clients. The way to achieve this in a social media world is by getting personal. An agent who shares an undifferentiated, company-centric messages will find their marketing goes unseen, unshared, and un-referred. The more targeted the message and the more value it offers to a specific customer type, the more likely people are to share the message with others because they can easily see how everyone can benefit.
Self-Serve Information
Customers are starving for the right answers, not just any answers. If you can post authoritative, easy-to-understand solutions to potential clients' online queries, you're building trust before you ever meet them. And sometimes a helpful tip will require the customer to contact you to get more specific details. Baer calls these information-packed nuggets "knowledge snacks." If you don't feed your customers, they might go searching for another meal elsewhere.
Real-Time Relevancy
Even more rare than accurate information is an accurate understanding of what the data represents. Outdated statistics, legal information, and accounting principles that don't automatically update can easily mislead a customer. In order to combat this problem in a constantly changing world, you need to make yourself available. Increase your accessibility by opening up your communications on several mobile-friendly channels. Then, when a customer has questions you can quickly respond to their answers according to their preferred method of communication.
Radical Transparency
Have you ever publicly given a potential customer a good reason not to hire you? What might seem to be a self-destructive maneuver is actually a brilliant tactic in disguise. A post or video that outlines the type of real estate professional you aren't can be a real differentiator in your marketing. One of my favorite examples of this comes from the BREL Team in Toronto. They say customers who "just want someone to tell you what you want to hear" or who are "looking for a discount agent" should seek services elsewhere. This tactic works to both introduce your style to unknown prospects and to help you find clients who are looking for the specific types of service you provide.
Doug Devitre
Companies bring in Doug Devitre, CSP, when they want to improve sales and marketing using the latest technology with quantifiable metrics. He is a member of the National Association of REALTORS® Business Specialties Hall of Fame and earned the Certified Speaking Professional award, which is bestowed upon the top 10 percent of professional speakers worldwide. His new book, Screen to Screen Selling—published by McGraw Hill and available in October 2015—helps executives and sales managers increase sales, productivity, and customer experience without being physically present.
An interesting article and refreshing approach to people.


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News View All News »
LHS Musicians Selected for Syracuse Youth Orchestra
Tuesday, October 3, 2017 -
Five Liverpool High School students recently were honored with selections to the Syracuse Youth Orchestra.
Receiving selections were senior Andrew Phan, senior Katherine Meluni, junior Gianna McManus, junior Jingwen Ou and senior Taylor Fennelly.
Syracuse University created the Syracuse Youth Orchestra and the Syracuse Youth String Orchestra in 2011. Central New York middle and high school student-musicians are selected for the orchestras after an audition process. Participation helps students grow musically and intellectually, as well as learn discipline and teamwork that will benefit them throughout life.


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Stockdale Technologies, Inc., is guided by the following Values. We want our decisions and actions to demonstrate these Values. We believe that putting our values into practice creates long-term benefits for shareholders, customers, employees, suppliers, and the communities we serve.
Stockdale Technologies, Inc. implemented a Corporate Social Responsibility program (CSR) in 2010. Stockdale aspires to meet the highest standards obtainable for Corporate Social Responsibility. Our goal is to achieve business excellence and at the same time challenge our employees, customers and suppliers to share these values. To ensure that our manufacturing partners provide safe and healthy working conditions, and engage in fair and ethical employment practices which include:
We are committed to protecting our environment as well as our employees, customers, and people in the communities in which we operate. Stockdale follows the standards and guidelines established by the Fair Labor Association through its published "Code of Conduct". We have been affiliated with the Fair Labor Association as a category C licensee, since 2000.


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Are you looking for a beautiful font free that make your designs look unique, this font is for you.
Cortes is an excellent and very unique modern font for techno, tech type of logo designs.
We hope these fonts are very useful and looks great printed at any size. If you want to feature the Free Cortes Font, please link back to this article. It is free for personal and commercial use
Find the best free fonts for your project!


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Tired of all the Bad News
Fr. Bryan Shortall ofm.capuchin
Tired of all the bad news
While we can't deny the difficulites for so many people at home and overseas, it's important to take account of the positives, and to spread the Good News. I don't know who said this but; "No-one ever injured their eyesight by looking on the bright side
Tuesday, 1 May 2012
Line to pray before the casket of John Paul II snakes through Rome
Line to pray before the casket of John Paul II snakes through Rome
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Bryan Shortall
Tuesday, May 01, 2012
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Every great book was once a hidden gem. Browse through the books below and start your own discovery!
|Book Discovery - newly-published and overlooked books!
|The Zee Brothers : Zombie Exterminators (Non-Illustrated Edition): Curse of the Zombie Omelet!, by Grivante
|Orgasms, Chocolate & Zombies? Just an average day for Jonah, Judas & JJ.
This is for the non-illustrated version. For the illustrated version, look here http://www.amazon.com/dp/B013M5DXGC
The Zee Brothers have a strange and dangerous vocation. While some hunt rodents or pests in the dark, Jonah and Judas tackle much larger prey… Zombies. Equipped with a well-loved artillery gun, DeeDee, and a much used and somewhat abused pickup truck called Sasha, the duo clear the night of undead pests, keeping the ever present threat of a Zombie Apocalypse at bay.
When the slap happy pair receives an after hours call for extermination that ends in a gurgle, they head out, guns locked and catch...
|Ship the Kids on Ahead: Short Stories by Bill Stokes, by Bill Stokes
|We all have that one older funny family member. You know the one, he tells stories from his experiences and usually has people rolling in the eyes. Bill Stokes is that person! He presents a delightful collection of memories that are truly life lessons even today! Stokes, through his memories and wit provides opportunities to learn through laughter, sharing of memories and love.
Many will shake their heads in remembrance of similar experiences and crack a smile if not a full on belly laugh!
From chapters on "The Hammer is in the Petunias" to "Merry Christmas" one cannot help but feel warm and comforted in those memories he shares that are full of life lessons. His writing style is comfortable, breezing a...
|All The Lonely Spirits: Journal 1 of The Sun and Moon Archives, by Jane J. Henri
|(Each book in this series is a full-length, complete, stand-alone novel.)
Medium Abby Nelson joins a small team of Marines to investigate paranormal problems at top secret locations around the country.
On their first mission together, Brigadier General Matthew Jackson and his team of three Marines are only there to supervise and keep Abby on track while she attempts to reclaim an abandoned but essential Army building from an overwhelming number of boisterous spirits who've taken control of it.
It sounded easy enough in the beginning, but they soon find that the job is far more dangerous and shocking than anyone ever dreamed. The fact that every day brings more discoveries about a defunct hellhole of an orp...
|The Gossip of an Earl (The Widows of the Aristocracy Book 1), by Linda Rae Sande
|Extra! Extra! Read all about it ...
The Earl of Fennington has a secret identity—that of Mr. Pepperidge, editor of London's premiere gossip rag, The Tattler. While attending a garden party as Fennington, he meets and falls in love with an earl's daughter. The attraction is mutual, for despite knowing better, Lady Emelia allows him to kiss her behind a hedgerow. Who will know but them?
When the earl asks permission to marry Emelia, her father denies him, requiring him instead to court Emelia for eight weeks. He's only allowed to see her once each week, however. Desperate to spend more time with her, Fennington devises a scheme in which he'll be able to do just that, but in disguise. Emelia will have to meet Mr. Pepper...
|Lethal Code (A Lana Elkins Thriller Book 1), by Thomas Waite
|America's worst nightmare has come true: a "cyber–Pearl Harbor" attack by unknown terrorists has crippled the nation's power grid—and brought the land of the free to its knees. As widespread panic and violence ravage the country, its ruthless captors issue their ultimatums…and vow an apocalyptic reckoning.
A defenseless nation scrambles to fight an invisible invasion. Chief among America's last line of defense is Lana Elkins, head of a major cyber-security company—and former top NSA operative—who returns to her roots to spearhead the Agency's frantic efforts to combat the enemy's onslaught on its own terms. While she and her superiors take action to infiltrate a terrorist hotbed overseas, much closer to home...
|The Cruisers: A Travel Writer Mystery, by Jeff Soloway
|In award-winning author Jeff Soloway's second Travel Writer Mystery, quick-witted Jacob Smalls and his outrageous mother cruise into highly dangerous waters.
Jacob Smalls manages to land the ultimate freebie: a two-berth stateroom on a cruise to a private tropical island. To everyone's surprise, Jacob invites as a guest his prickly mother, an olive branch from son to mother after years of ill will. Once aboard, Jacob is determined not to let her characteristically scathing sarcasm spoil his trip. But her relentless prying proves much more dangerous to swallow.
Their journey begins ominously: they discover the ship's trumpet player has just died under mysterious circumstances. Ever curious, Jacob qu...
|Beloved Beast (The Ravenswood Chronicles), by Karyn Gerrard
|If a man can live forever . . .
A lifetime ago, the debauched Viscount Ravenswood lost his life, only to be revived as as new man with a new name…and a new desire for love. Now, scarred and monstrous of visage, Luke Madden has outlived his beloved wife. Crushed by loss and despair, he swears to never feel such a love again. For such a perfect mingling of souls could never happen twice in one lifetime. Especially for a beast such as Luke believes himself to be . . .
. . . how can he love forever?
Gillian Browning is a bold woman of action. But her spy activities in pre-war Germany have made her a target. Now in London, she is being hunted by ruthless Nazi opera...
|The Girl From The Tea Garden (The India Tea Series Book 3), by Janet MacLeod Trotter
|In the dying days of the Raj, Anglo-Indian schoolgirl Adela Robson dreams of a glamorous career on the stage. When she sneaks away from school in the back of handsome Sam Jackman's car, she knows a new life awaits—but it is not the one she imagined.
In Simla, the summer seat of the Raj government, Adela throws herself into all the dazzling entertainments 1930s Indian society can offer a beautiful debutante. But just as her ambitions seem on the cusp of becoming reality, she meets a charming but spoilt prince, setting in motion a devastating chain of events.
The outbreak of the Second World War finds Adela back in England—a country she cannot remember—without hope or love, and hiding a shameful secret. Only exceptional...


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Country/Date of Origin: France/1500s
The Beauceron is one of the best-known sheepdogs in France. Like some of its compatriot breeds, the Beauceron has double dewclaws that enabled it to get a good grip in the sheep's wool when it climbed across their backs to get across a flock. Although it has been used as a herding dog for centuries, it is thought the original use was as a hunting dog. The Beauceron is also used successfully as a police dog.
FCI Group: 1 (Herding)
About This Breed:
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Berger de Beauce, Bas Rouge
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Access Surveys
Since the issuance in 1978 of the Pastoral Statement of U.S. Catholic Bishops on People with Disabilities, a number of Ordinaries have published statements directed at the programs and facilities of their own dioceses. Numerous dioceses have likewise issued policy statements and synod statutes relating to access and welcome for Catholics with disabilities.
Below are sample access surveys, and accessibility plans developed by dioceses, to implement the vision of the Pastoral Statement.
|Access Survey of Parish and Diocesan Facilities
|Parish Accessibility Surveys
(Note: The parish accessibility survey is on two pages and is a modified version to be duplicated back-to-back and folded in a booklet format.)
|Access Survey of the Archdiocese of Washington
|Accessibility Plan of the Archdiocese of Detroit
|Accessibility Plan of the Archdiocese of Springfield in Illinois
|Parish Physical Accessibility Survey of the Diocese of Toldeo


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**** Click Orange "MENU" Button For More Options ****
The Clerk of the Superior Court is an elected officer established by the Arizona Constitution. Duties and responsibilities are prescribed in state statute, court rule, and case law. Supreme Court Administration order also provides that the presiding judge may prescribe additional powers and duties of the Clerk of the Court, in addition to those prescribed by the Supreme Court. State law was amended to clarify the clerks authority to manage her own staff and operations.
The Clerk of the Superior Court officially maintains all civil, domestic, criminal, juvenile and probate records. The Clerk issues writs and warrants; takes and transcribes all court minutes for all court proceedings; is the Registrar of Probate matters; maintains all court exhibits used as evidence; is the Jury Commissioner, providing qualified jurors for trials from the lists of all registered voters and holders of drivers licenses; accepts passport applications, issues and records marriage licenses; and prepares and forwards appeals to the Court of Appeals and State Supreme Court.
The Clerk also collects all fees, fines, bonds and restitution for the court. Monies collected are transmitted monthly to the county treasurer. The Clerk also receives monies to be held in trust in a fiduciary capacity for the Court.
Superior Court, Bisbee


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Hypnobabies for Birth Partners
When expectant mothers have supportive partners that want to be involved in the preparation for their baby's birth, Hypnobabies Childbirth Hypnosis classes provide the tools for them to do so with confidence!
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Hypnobabies for Birth Partners
When expectant mothers have supportive partners that want to be involved in the preparation for their baby's birth, Hypnobabies Childbirth Hypnosis classes provide the tools for them to do so with confidence!
It's not unusual for Birth Partners to be skeptical at first about childbirth hypnosis, or concerned that the expectant mother will simply listen to hypnosis tracks, leaving him/her without a significant role during the babies birth.
Hypnobabies Birth Partners soon learn that their concerns are unfounded when they discover in Class One that hypnosis is a normal state of mind that people experience every day, and that they have a very hands-on role in the process of preparing the mother for an easier, more comfortable birth.
The first Hypnobabies lesson dispels the misconceptions that many have about hypnosis. Birth Partners experience hypnosis along with the expectant mother during Class One's "Learning Self-Hypnosis" script. They are surprised to learn that hypnosis is actually quite pleasant, very relaxing, and even fun. "That's it?", and "All I felt was very relaxed.", and "I enjoyed it a lot…it wasn't weird at all!" are the excited comments our instructors hear from our Birth Partners at the end of that first script.
What Will the Birth Partner Learn in Hypnobabies Classes?
Birth Partners that attend Hypnobabies Classes are also provided with resources:
What are Birth Partners saying about Hypnobabies?
Hypno-Dad, Daryl weighs in about his wife's much easier second birth, and his own participation in their baby's birth with Hypnobabies:
Our doula friend suggested that we try Hypnobabies, self-hypnosis for childbirth. My wife and I attended a six week hands-on course that taught my wife how to produce anesthesia from her thoughts. No, seriously! Through a series of hypnotic scripts, affirmations, and relaxation music my wife actually learned how to create mental anesthesia during birth. And I learned how to help her do it. During the entire six weeks I felt like we were preparing for this upcoming momentous and spiritual event together. We were truly a team this go-around, ready to welcome our second child in a calm, peaceful way. No drugs. No screaming. No anxiety.
Hypno-Dad, Brad adds to his wife's Hypnobabies birth story:
Even though I wasn't always the biggest fan of it through the pregnancy, it was GREAT for April when she was in labor. It is because of Hypnobabies that I will from this point on call the contractions, birthing or pressure waves. Once she started listening to the CD she was able to focus on her breathing and relax her body and mind. Where she was a moment ago crushing my hand with her vice grip, she was now peaceful and serene. She got to the point where I seriously couldn't tell when she was having a pressure wave at all.
Hypnobabies® – Natural Childbirth at its best!
Join our Hypnobabies Community and receive 10% off of all Hypnobabies pregnancy, birth, doula and postpartum products.


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- Research
- Open Access
Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib
- Lokesh Jain†1, 2,
- Tristan M Sissung†1, 3,
- Romano Danesi4,
- Elise C Kohn3,
- William L Dahut3,
- Shivaani Kummar3,
- David Venzon5,
- David Liewehr5,
- Bevin C English6,
- Caitlin E Baum6,
- Robert Yarchoan7,
- Giuseppe Giaccone3,
- Jürgen Venitz2,
- Douglas K Price3, 6 and
- William D Figg1, 3, 6Email author
© Jain et al; licensee BioMed Central Ltd. 2010
- Received: 10 May 2010
- Accepted: 14 July 2010
- Published: 14 July 2010
Hypertension (HT) and hand-foot skin reactions (HFSR) may be related to the activity of bevacizumab and sorafenib. We hypothesized that these toxicities would correspond to favorable outcome in these drugs, that HT and HFSR would coincide, and that VEGFR2 genotypic variation would be related to toxicity and clinical outcomes.
Toxicities (≥ grade 2 HT or HFSR), progression-free survival (PFS), and overall survival (OS) following treatment initiation were evaluated. Toxicity incidence and VEGFR2 H472Q and V297I status were compared to clinical outcomes.
Individuals experiencing HT had longer PFS following bevacizumab therapy than those without this toxicity in trials utilizing bevacizumab in patients with prostate cancer (31.5 vs 14.9 months, n = 60, P = 0.0009), and bevacizumab and sorafenib in patients with solid tumors (11.9 vs. 3.7 months, n = 27, P = 0.052). HT was also linked to a > 5-fold OS benefit after sorafenib and bevacizumab cotherapy (5.7 versus 29.0 months, P = 0.0068). HFSR was a marker for prolonged PFS during sorafenib therapy (6.1 versus 3.7 months respectively, n = 113, P = 0.0003). HT was a risk factor for HFSR in patients treated with bevacizumab and/or sorafenib (OR(95%CI) = 3.2(1.5-6.8), P = 0.0024). Carriers of variant alleles at VEGFR2 H472Q experienced greater risk of developing HT (OR(95%CI) = 2.3(1.2 - 4.6), n = 170, P = 0.0154) and HFSR (OR(95%CI) = 2.7(1.3 - 5.6), n = 170, P = 0.0136).
This study suggests that HT and HFSR may be markers for favorable clinical outcome, HT development may be a marker for HFSR, and VEGFR2 alleles may be related to the development of toxicities during therapy with bevacizumab and/or sorafenib.
- Vascular Endothelial Growth Factor
- Overall Survival
- Bevacizumab
- Progression Free Survival
- Sorafenib
The process of angiogenesis is crucial for carcinogenesis, invasiveness and metastasis in several tumor types including prostate, ovary, kidney, non-small cell lung and colorectal cancer [1–3]. This process is governed by an array of growth factors; however, vascular endothelial growth factor (VEGF) and its major receptor in the endothelium, VEGFR2, are predominant regulators of this process [2]. Rising interest in angiogenic modulators has led to the design and synthesis of several new molecules that target the VEGF signaling pathway, such as sorafenib, bevacizumab and sunitinib, which are currently approved for various solid tumors. There is wide inter-individual variation in toxicity and clinical outcome following treatment with agents targeted at the VEGF pathway suggesting that predictive markers of these outcomes could be clinically useful.
Sorafenib and bevacizumab have some common toxicities, such as hypertension (HT), diarrhea, and gastrointestinal perforation [4, 5]. However, sorafenib confers frequent cutaneous side effects, including hand-foot skin reaction (HFSR; palmar-plantar dysesthesia; acral erythema) and rash in many individuals while bevacizumab confers HFSR in a limited number of individuals. Both in-vitro and in-vivo evidence support that HT, results directly from the pharmacologic activity of VEGF inhibitors [6]. Recently, we demonstrated that sorafenib-induced HFSR was directly related to cumulative sorafenib dose, that HT and HFSR development coincided, and that HFSR is more prevalent in individuals being treated with a combination of sorafenib and bevacizumab targeting the VEGF receptor and the VEGF growth factor, respectively. A pharmacokinetic interaction was not observed [7]. Taken together, these results suggest that HFSR and HT may both be related to the activity of anti-VEGF and anti-VEGFR therapy; thus, HT and HFSR may also be markers for a greater degree of response in patients treated with sorafenib and bevacizumab. Inter-individual genetic variation in the VEGF pathway may also alter both the toxicity and response to these agents.
The VEGFR2 gene contains two SNPs that are located in exons 7 and 11 and result in nonsynonymous amino acid changes at residues 297 Val>Ile and 472 His>Gln in the third and fifth immunoglobulin like (Ig-like) domains of VEGFR2 receptor, respectively. The Ig-like domain 3 is critical for binding to the VEGF ligand [8], while domains 4-7 contain structural features that inhibit VEGFR2 signaling in the absence of VEGF [9]. HEK293 s cells that were transfected with VEGFR2 V297I SNP had significantly low VEGF binding efficiency regardless of VEGFR2 H472Q genotype, while variant VEGFR2 H472Q allele had minimal effect on VEGF binding efficiency [10].
We hypothesize that 1) the development of HT and HFSR following anti-VEGF therapy with bevacizumab and sorafenib is a marker for response to these drugs; 2) that since both toxicities are related to the activity of these agents, the development of a single toxicity (i.e. HT) would increase the risk of developing the other toxicity (i.e. HFSR); and 3) that functional SNPs in VEGFR2 could alter antiangiogenesis treatment response or outcome by affecting the VEGF signalling pathways. To this end, we determined if HT and HFSR were associated with progression free survival or overall survival, and if development of HT increased the risk of developing HFSR in patients with various solid tumors being treated with sorafenib and/or bevacizumab. We also determined if genetic polymorphisms in the VEGFR2 gene modified the relationship between toxicity and survival endpoints as well as the relationship between coincidence of HT and HFSR.
Patients and treatment
Summary of patients included in analysis
Tumor type
Treatment (s)
Frequency of Toxicity [n= (%)]
Median PFS (months)
HT ≥ grade 2
HFSR ≥ grade 2
HT < grade 2 vs. ≥ grade 2
Log-Rank P =
HFSR < grade 2 vs. ≥ grade 2
Log-Rank P =
Bevacizuamb + Thalidomide + Docetaxel
15 (25.0)
4 (6.7)
14.9 vs. 31.5
Sorafenib + Bevacizumab
15 (55.6)
13 (48.1)
3.7 vs. 11.9
3.7 vs. 12.6
9 (19.6)
7 (15.2)
3.7 vs. 1.8
2.0 vs. 3.1
9 (40.9)
10 (45.5)
1.9 vs. 4.6
2.9 vs. 3.7
Sorafenib + Cetuximab
1 (5.6)
2 (11.1)
4.7 vs. 8.7
Sorafenib +/- Protease inhibitor
3 (37.5)
2 (25.0)
The most severe grades of common, sorafenib treatment associated toxicities, namely rash, desquamation, diarrhea, HFSR, HT and fatigue were used for analysis. Toxicities were graded based on the National Cancer Institute common toxicity criteria version 3.0. This retrospective genotyping analysis was approved by the National Cancer Institute Institutional Review Board.
DNA was extracted from plasma or whole blood using QiaBlood extraction kit (Qiagen, Valencia, CA). Genotyping for two VEGFR2 loci was performed by single/nested PCR using the following primers at an annealing temperature of 60°C: rs1870377 (T/A) F1:5'-CAGAATCACCCTACACAGATGC-3', R1: 5'-TTCCCAGAATAGCTGCTTCC-3', F2: 5'-TGGTACTGCTAAAAGTCAATGG-3', R2:5'-GGCTGCGTTGGAAGTTATTT-3'; and rs2305948 (C/T) F4: 5'-GGTTTGAACCCAAGTTCCTG-3', R4: 5'-CACTTTCACCACGTGAGGTTT-3', F5: 5'-TGGCCTCCCTAACAAGAAAA-3', R5: 5'-TGGTGTCCCTGTTTTTAGCA-3'. The details of the genotyping procedure are described elsewhere [15]. The sequencing PCR was carried out with Big Dye (v3.1, Applied Biosystems, Foster City, CA) using the following PCR primers: rs1870377 (T/A) F3: 5'-CCTGGAAGTCCTCCACACTT-3', R3: 5'-AACCAAAGTCTGAATCTTTTCCTT-3'; and rs2305948 (C/T) F6: 5'-CCCTGACAAATGTGCTGTTC-3', R6: 5'-TGCTGTGCTTTGGAAGTTCA-3'. The PCR products were then sequenced on an ABI Prism 3130xl Genetic Analyzer (Applied Biosystems) as per the instructions from the manufacturer.
Statistical considerations
The progression free or overall survival based on genotype or toxicity groups (grade ≥ 2/grade < 2) was estimated by the Kaplan-Meier method [16] and compared by the exact log-rank test. Deviation from Hardy-Weinberg equilibrium was tested separately for different ethnic groups, using the Chi-squared test. The impact of genotypes on treatment-associated toxicities and the association between toxicities were assessed by Fisher's exact test. All statistical analyses were two-tailed at a pre-specified significance level of < 0.05. In view of the exploratory nature of analysis, P-values were not formally corrected for multiple testing. SAS for Windows version 9.1.3 was used for these statistical analyses.
Genotyping data
Genotype and allele frequencies for SNP in VEGFR2 loci for patients treated with sorafenib and/or bevacizumab, with or without other agents
Allelic variant
Genotype frequencies, N (%)
Allelic frequencies
HT and HFSR as phenotypic markers for PFS and OS
As is indicated in Table 1, incidence of ≥ grade 2 HFSR was also associated with PFS in patients with colon cancer treated with sorafenib (P = 0.0065) with those patients having HFSR (n = 2) having a significantly longer response to sorafenib (8.7 months) than those without HFSR (4.7 months, n = 16). HFSR and PFS were either marginally not associated in patients on BAY-BEV (P = 0.094), or were not associated on BAY-NSCLC and BAY-CRPC (P ≥ 0.29). However, since each group treated with sorafenib had a similar trend (i.e. patients with HFSR always had a longer median PFS) with a small number of patients in each group (n ≤ 46), we pooled survival data obtained from the above trials to analyze the relationship between HFSR and PFS with greater statistical power. The pooled analysis significantly improved the relationship between PFS and HFSR with patients who developed HFSR following treatment with sorafenib, either as single agent or in combination with bevacizumab or cetuximab (n = 32), having a median PFS of 6.1 months compared with 3.6 months in patients without these toxicities (n = 81; P = 0.0003, Figure 1C). However, this pooled analysis should be interpreted with caution given that it is present only when heterogeneous groups of data obtained from patients are combined together. Association of these toxicities with OS was not significant with a single striking exception where those patients receiving the BAY-BEV combination had a significantly longer survival (P = 0.0093) if they developed hypertension during therapy (29 months, n = 14) when compared to those that did not develop hypertension (5.7 months, n = 12; Figure 1D). No other toxicity (i.e., rash/desquamation, diarrhea, or fatigue) was related to PFS (P > 0.05) for either drug.
Increased risk of developing HFSR along with HT
We next hypothesized that since HT and HFSR originate from the activity of bevacizumab and sorafenib, the development of a single toxicity (i.e. HT) would increase the risk of developing the other (i.e. HFSR). Analysis of association between toxicities revealed that individuals with HT grades < 2 had a lower risk of developing HFSR grades ≥ 2 (19 of 126 patients, 15.1%) than those patients with HT grades ≥ 2 (19 of 52 patients, 36.5%, OR (95%CI) = 3.2 (1.5-6.8), P = 0.0024). Therefore, increased HT grade conferred a significantly increased risk of also developing HFSR.
VEGFR2 H472Q and V297I genotypes vs. treatment associated toxicities and survival following sorafenib and/or bevacizumab therapy
Comparison of toxicities between wild type and variant allele groups for VEGFR2 SNPs
Toxicity grade ≥2
wt allele
var allele
Wt allele
var allele
22 (21.4)
26 (38.8)
38 (29.0)
12 (30.8)
16 (15.5)
22 (32.8)
28 (21.4)
10 (25.6)
17 (25.0)
13 (28.9)
23 (27.7)
9 (30.0)
14 (20.6)
7 (15.6)
19 (22.9)
3 (10.0)
12 (17.7)
6 (13.3)
14 (16.9)
4 (13.3)
To determine whether the aforementioned association between HT and HFSR is confounded by VEGFR2 H472Q, the association between any two of the factors (i.e., HT, HFSR and VEGFR2 H472Q) with stratification by the remaining factor were tested. The results were consistent with the hypothesis that the associations are independent of each other. Genotype-toxicity relationships for other toxicities and studied VEGFR2 SNPs were not significant (Table 3). The VEGFR2 V297I SNP was not related to toxicity, and neither VEGFR2 genotype was related to any survival endpoint in any of the individual clinical trials in spite of the relationship with toxicity.
We hypothesized that 1) increased HT and HFSR were markers for increased response duration in individuals treated with bevacizumab and/or sorafenib; 2) that since these toxicities are likely derived from the activity of bevacizumab and sorafenib, the development of HT would increase the risk of also developing HFSR; and 3) that VEGFR2 genotypic variation may be responsible for alterations in the activity of bevacizumab and/or sorafenib therapy that would manifest in associations with toxicity or clinical outcome following treatment with these agents. The results of the present study confirm a previously published study where HFSR development was noted to be related to PFS in patients with various solid tumors receiving doses of sorafenib between 300-600 mg bid [17], and a small study that HT is related to bevacizumab response [18]. Moreover, those receiving combination therapy with bevacizumab and sorafenib that developed hypertension enjoyed a greater than 5-fold increase in overall survival following therapy initiation. Consistent with our previous results [7], the development of HT was also directly related to the incidence of HFSR, further suggesting that these two toxicities are markers for the activity of anti-VEGF therapy. This study is the first to evaluate VEGFR2 H472Q status; carriers of 472Q alleles were more likely to experience HT and HFSR, although the relationship between genotype and toxicity was independent of the relationship between the two types of toxicity, and was not related to any of the studied survival endpoints.
The physiological basis for bevacizumab- and sorafenib-induced HT and HFSR is currently unknown although they most likely originate from the activity of these drugs altering signaling through several targets (i.e., VEGF, Raf-1, wild-type B-Raf, mutant b-raf V599E, VEGFR2, VEGFR3, PDGFR-β, Flt3, c-KIT and p38) [19, 20]; recent data suggests that the VEGF pathway directly contributes [6, 7]. Once these pathways are altered, HT may develop because of decrease in vascular surface area [6], and HFSR may develop due to inefficiency of the repair of microtrauma originating from use of the hands and feet [21]. In spite of the unknown origin of these toxicities, our data are consistent with the hypothesis that HT and HFSR are related to the activity of these drugs. The data also suggest that these toxicities are markers for prolonged response, and in the case of sorafenib and bevacizumab coadministration, prolonged survival benefit from these therapies. Others have also observed that the severity of rash in patients with NSCLC is directly related to EGF-RTK inhibition by tyrosine kinase inhibitors, and that this cutaneous toxicity is also a marker for increased survival [17, 22]. Moreover, it has also been suggested that rash brought on by EGF-pathway inhibitors could be useful for optimal dose titration [17]. Therefore, future studies directly evaluating the development of HT and HFSR as markers for effective dosing of these bevacizumab and sorafenib are warranted in order to decrease the incidence of toxicity and improve response.
Interestingly, VEGFR2 genotype may also be related to the incidence of both HT and HFSR independently, but does not confound the relationship between the two toxicities. These data suggest that the development of these toxicities is related to signaling through the VEGF pathway, at least in part, although the polymorphism in VEGFR2 is not the sole factor responsible for the relationship between HT and HFSR. Given the heterogeneity of the clinical trials under study, the lack of a relationship between VEGFR2 genotype and PFS may be due to low statistical power and it is hoped that future studies in homogeneous populations will validate the relationship between VEGFR2 polymorphism and survival.
The present analysis is inconsistent with a previous report where it was determined that patients with breast cancer reported significantly longer OS for patients who developed HT on bevacizumab and paclitaxel combination than patients without this toxicity [23]. The present data were obtained retrospectively from clinical studies that were not designed to retain patients on the basis that toxicity was a marker for efficacy. Indeed, a greater proportion of patients carrying the 472H/Q substitutions were removed from the trials due to toxicity (14%) than those carrying wild-type or variant genotypes (9%), although this was not statistically significant (data not shown). This is not surprising given the association of VEGFR2 variants and toxicity. However, since those carrying this genotype also had a better response in general, it is possible that the desirable long-term benefit of the treatment may not have been enjoyed in patients being removed from therapy prior to tumor progression due to toxicity.
In conclusion, our data indicate that HT and HFSR are markers for prolonged progression free survival in patients treated with bevacizumab and/or sorafenib, patients receiving a combination of both agents that develop HT have a large increase in treatment-related survival, and that the development of HT on these agents increases the risk of also developing HFSR. The association with toxicity was not significant with respect to overall survival. When VEGFR2 genotypes were considered, the present data suggest that those carrying 472Q alleles at H472Q are at an increased risk of developing both HT and HFSR following bevacizumab, although the SNP is not related to either progression free survival or overall survival. Given the exploratory pilot nature of this study, it is hoped that future studies will validate these results and provide a mechanism by which toxicity is related to PFS and VEGFR2 genotypic variation is related to toxicity.
This study was supported in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Bethesda, MD. We thank our data managers Cynthia Graves, Sonja Crandon, Qinghua Ge (Roger), Shveta Tiwari, and Kathleen Wyvill, and most of all, our patients who participated in these trials. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U.S. Government.
Authors' Affiliations
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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I love how excited they are when they first experience the joy of creating Zentangle® art.
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Shortly after the class, Jen Dagenais sent me a photo of the tangled cupcakes she made. I spy some tasty looking patterns in there including Static, Bunzo, Indyrella, Diva Dance, Umble, 'Nzeppel, Keeko, Huggins, Poke Leaf, Jetties, Schway, Poke Root, Zingers, Cadent, Quib, Printemps, Flux, Sand Swirl, Crescent Moon, Florz, and more.
Wow, we've learned a lot of great patterns in our classes together, Jen! :-) Thanks for sharing your frosting art!


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GOLD for the week of Feb 6th 2017
Initial Resistance (1st tier) 1245-1255 (2nd Tier) 1272-1282
Initial Support (1st tier) 1207-1219 (2nd Tier) 1190-1197
Our last update listed resistance (2nd Tier) at 1222-1232 and the high was 1225. Support was listed at 1172-1182 and the low was 1197.
Gold Short Term (Bullish since 1134) Goes Bearish on close below 1197
Resistance this week and the odds favored targets are 1245-1255 and 1272-1282.
Support 1207-1219 & 1192-1197. The Trend is up. Close below 1192-1197 puts short term bearish. There's minor resistance at the 1235-1238 area at the red line.
Pivot is the 1218-1222.
As long as we're above that, we're heading for the resistance areas. There's a minor resistance near 1235-1238 we need to get above (at the red line). The trend remains up into this week & then we'll see.
Technical Analysis :: Gold & Silver
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JCHS Band
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