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By Brent Masica and Hudson Brothen, Industrial Brokers
The Twin Cities industrial market has been among the strongest drivers of commercial real estate growth in the most recent economic cycle.
In fact, since the beginning of 2011, nearly 15 million square feet (sf) of multitenant industrial space has been absorbed throughout the Minneapolis-St. Paul market, according to Cushman & Wakefield's Compass report. That number – which doesn't include the several massive, recent build-to-suit projects accommodating only one tenant – makes up more than 14 percent of today's multitenant universe.
With growth continuing at a frenzied pace, and the fight for labor getting more intense than ever, leasing has become competitive for both landlords and the companies using space. So what factors are attracting users to the most successful properties, and how can landlords leverage those factors?
This is part two of a blog series digging into recent trends in occupier decision-making.
Factor Two: The bottom line
If your business is primarily in the Twin Cities, it makes sense to be near your customers. But if not, or if you're running a large distribution or logistics operation and need a Twin Cities outpost, suddenly that location takes a backseat to cost.
Simply put, some users are more attracted to a lower rent than they are a top-tier location. In the most recent edition of our Compass report, we noted that Rogers, an exurb in the northwest Twin Cities, saw 500,000 sf of absorption in the second half of 2017 and could witness another 500,000 sf or more absorption in the first half of this year. That would be a dramatic turnaround for the market, which has been lagging behind the rest of a bullish industrial market for several quarters now.
So, what changed? Basically, congestion and lack of land availability in other submarkets made Rogers a cheaper option. While competition heated up in Shakopee and Brooklyn Park, asking rents fell in unoccupied Rogers properties, some of which were built speculatively.
Why does Rogers suddenly work? For a distributor, perhaps sending food or another product to the Dakotas, western Wisconsin, Iowa and other nearby markets, what's another six or seven miles per drive if you're paying $1.50 per square foot less – or maybe even more? That bottom line savings can be applied to anything from on-site amenities to employee pay and benefits, both of which can help attract the workforce you're looking for.
We've seen that happen with FedEx, who's occupying a large distribution center in Rogers, and will see a couple more tenants make similar decisions in early 2018. And once Rogers gets more competitive? You may see other outer markets with great interstate access start landing distributors.
Brent Masica and Hudson Brothen are industrial brokers in Cushman & Wakefield's Minneapolis-St. Paul office. The two are part of a team specializing in industrial landlord and tenant representation, property sales and consulting. Visit their site at http://industrialmn.com.


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Gertrude Prince Ledyard
Date: 1851 - 1905
Remarks: Gertrude Prince was the daughter of Colonel William E. Prince (d. 1880) of the U.S. Army. In 1878, She married Lewis Cass Ledyard, a prominient New York lawyer and president of the Bar Association of New York City at one time. The couple had one child, Lewis Cass Ledyard, Jr. also a lawyer.

subset: commoncrawl


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Just like your workouts, you should shake up your nutrition every now and then to keep your body guessing! Carb cycling is a great way to break a plateau and get extra lean. I love the "Countdown to Competition" plan from 21 Day Fix EXTREME because it allows me to customize it and is easy to follow. The main difference between this style and the regular 21 Day Fix EXTREME Eating Plan is that there is no fruit, less carbs & a little less fat.
Don't be too intimated. The amount of meals makes it easy to say on track & you still get some carbs in the morning with your oatmeal & sweet potato. I use Flavor God seasonings on my meals to keep it interesting since you're not supposed to have much sodium. Also, make sure to drink A LOT of water. Here's a sample day:
Meal 1 (not shown): Oatmeal w/ 1 tsp coconut oil and Egg Whites (1 red, 1 yellow, 1 tsp)
Meal 2: 4 oz. baked chicken w/ lemon @flavorgod seasoning & sweet potatoes (1 red, 1 yellow)
Meal 3: 4 oz. baked chicken w/ lemon @flavorgod seasoning and zoodles (1 red, 1 green)
Meal 4: 4 oz baked chicken w/ broccoli (1 red, 1 green)
Meal 5: 4 oz baked chicken w/ lemon @flavorgod seasoning & zoodles (1 red, 1 green)
Meal 6: 4 oz baked chicken w/ garlic @flavorgod seasoning & broccoli (1 red, 1 green)
Meal 7 (if I'm hungry – not shown): @shakeology, cucumbers & handful of cashews (1 red, 1 green, 1 blue)
I stuck with chicken this time because I wasn't feeling any fish or another form of lean protein but feel free to sub that in! Here's to being pool party ready all the time. Typically you would eat 2 days this style and then 1 day regular 21 Day Fix EXTREME style if you are following the plan. The guide book recommends doing it up to 3 weeks. It's best to get your copy & find out what calorie bracket aka how many meals you would fall in a day.
Q: Where do you get the black containers?
A: Click here to buy the same containers from amazon. My friend is also creating an even better container system with customizable sections. Click here to find out more and sign up to be the first to find out about it!
Q: Do you get bored of eating the same thing every day?
A: No at all! I switch it up on a weekly basis and choose my healthy favorites that I don't mind eating often. I also add different seasonings to keep things interesting.
Q: Do you pre-cook all your food at the beginning of the week or do you just cut it up and package it? Does the food stay fresh all week?
A: I personally like to pre-cook all my food! I keep it properly refrigerated and find that it stays fresh up to 5 days. If you prefer, you can totally freeze the last 2 days or cook 2-3 days at a time.
Q: Can you put any of these meals in the freezer?
A: I personally don't but I know people who do but just remember to thaw it in time.


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Have you been looking for an original buddyseat for your Zundapp moped? You can find them at JMPB Parts! In our webshop, buddyseats and moped saddles are available in all types, sizes and colors so that also for your Zundapp the right buddyseat in available. Everything is in stock and will be delivered quickly. P>
A buddyseat is really a moped part that lets you make a statement. So you can choose a sober black model, but we also have a choice in nice red/crème and gray/crème buddyseats for model year 1965. Also for model year 1973 there are specific buddyseats available in red and black. The 517 buddyseat is applicable to Zundapps of fashion years 1968 to 1976. P>
As with all other moped parts, our buddyseats and other moped saddles are as much as possible original. If this is not possible, there is always an affordable aftermarket alternatives. These parts provide reliable quality for an attractive price. Need help choosing the right parts? Let us know, we would like to advise you on the best purchase for your Zundapp moped. P> Hide…
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Recently, writer Amy Tara Koch visited Telluride with her family and got to see much the resort has to offer for people of all ages. During their time here, Amy and her family stayed at the Madeline Hotel and Residences , and got to experience minimal lift lines (even on President's Day Weekend), fine dining and countless activities for the family to enjoy.
"Compared to the buzz of Beaver Creek, Telluride feels like a well-kept secret, and it its faithful flock, this is a good thing. Area hotels are luxe but relaxed. Lift lines are nonexistent, and there is a noticeable lack of crowds (it's far from any metropolitan area, so there's not glut of day skiers) in and around the slopes…
…The two towns are linked by gondola, which for kids is more entertainment than transport. Skiing is the main attraction, with 24 percent of the mountain devoted to beginner skiing and boarding – a key selling point for parents." – Amy Tara Koch
Read the entire article: " Five Ski Resorts Perfect for Families " – Travel + Leisure
Discovering Telluride - Family from Telluride Ski Resort on Vimeo .


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Here's a video of Miami's own Hemlock playing a song called "Sweet Sweet Music," and sounding like a disco version of the Allman Brothers. The movie appears to be a shoddy film to digital transfer. Click the HQ button at the bottom of the player to watch it in high quality. According to the YouTube description, Hemlock released a single called "Disco Break," apparently through Warner Bros. Here is that song.
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Get your bowls of popcorn & your favorite wine ready for the most dramatic season finale of The Bachelor yet! Who will Nick choose?!
This post is a little different than what I normally talk about, but I just had to write about one of my favorite topics. The Bachelor. I love it! And when I saw the SkinnyPop wine & popcorn pairing graphic at the end of the post, I was inspired to share 3 of my loves - The Bachelor, wine, & popcorn!
As much as it is lame reality TV, there is just something about the Bachelor franchise that gets me hooked & I tune in every Monday night, season after season. With the season finale coming up on the 13th, I thought it would be the perfect time to indulge in a little girl talk. Plus, a Bachelor viewing party is not complete without wine & popcorn! So, I've rounded up some lovely dietitian's favorite popcorn recipes to pair with your wine.
Let's start off with my feelings about this season. I love to hate Nick. He went from being America's most hated contestant after calling Andi out after the final rose, then our hearts slightly warmed towards him on Kaitlyn's season, until they did some not so cool things during the MIDDLE of the season! But then, we saw a total transformation on this past Bachelor in Paradise, & I found myself actually liking the guy.
After this season, I don't really know how I feel about him though. I secretly was kind of hoping he would pick Corrine. I think Raven & Vanessa both seem like sweet, relatively normal girls, but I just can't help but feel like they might be too good for him. I mean let's face it, it's Nick's 4th Bachelor franchise show & he's still single at 36....something's a little weird to me. I really like both Raven & Vanessa, so I'd be happy with either pick.
The Bachelor always leaves me with some serious travel envy, though. I really want to visit Finland now, it truly seems like the "most romantic place to fall in love." With that being said, the Women Tell All....cray cray. Like where was Chris Harrison? Was he even present during half of it, because he just let the girls blabber overtop of one another! It was kind of awful. The whole Corrine vs. Taylor thing I have no words for. Kristina was so so sweet & just seems like the most amazing person. My heart goes out to Kristina! She deserves such happiness in life! And totally over the whole Liz, Jade & Tanner Wedding ordeal. I loved her little speech on it's not what you did, but who you are though.
Can we also talk about how they announced Rachel as the Bachelorette when she was still a front runner contestant?! Like, what?! Why did you do that to us?! I think she's going to be an amazing Bachelorette & I really loved her this season, so I'm excited for May!
I truly can't wait to see what goes down on Monday. There's definitely going to be tears (mostly from Nick) & the drama will be on point! But we can't have a Bachelor viewing party without appropriate snacks! Side note: I just found out the Bachelor franchise has their own line of wines, & I kind of really want to buy it.
Wine & popcorn are the perfect Bachelor watching duo. While I'm all for just eating plain popcorn straight from the bag, why not jazz it up a little bit with some toppings?! You have to give these snack mixes a try!!
Spicy Snack Mix by The Nutritionist Reviews
Super Bowl Sriracha Popcorn by Kara Lydon, The Foodie Dietitian
Honey Spiced Popcorn by Judy Barbe of LiveBest
Salted Caramel & Dark Chocolate Ancient Grain Snack Mix by Shaw Simple Swaps
Spring Snack Mix by The Nutritionist Reviews
LiveBest Popcorn by Judy Barbe of LiveBest
Savory "Cheesy" Popcorn by RDelicious Kitchen
Garlic Dill Parmesan Popcorn by Salubrious RD
If you're curious as to what wines will go best with your popcorn of choice, check out this graphic below so you can get to sipping & munching in no time! Cheers!
I was not compensated for this post. All opinions & promotion of product are my own.
3/10/2017 10:50:28 am
Although I am not a fan of the Bachelor I am most definitely a fan of all these snacks and wine of course! ;)
3/14/2017 10:59:41 am
haha perfect! Wine & snacks are the best!
9/23/2017 11:48:36 pm
shut up, you stole my man from me you she-witch! :(
3/10/2017 11:38:28 am
im not into Bachelor either but do love me popcorn and wine. i will have to refer to that tutorial next time. how fun!
3/14/2017 11:00:22 am
Yeah, I love the little pairing graphic! So fun!
3/10/2017 03:28:43 pm
I cannot bear to watch the Bachelor for even a second but I do love those snack options. Did not know Kind made snacks :0
3/14/2017 11:01:16 am
Yeah, I've been seeing the snacks recently! They look great!
3/10/2017 08:40:01 pm
So many good snacks!!!
3/14/2017 11:01:43 am
Never can have too many snacks!
3/10/2017 08:46:03 pm
Sounds like fun and tasty way to enjoy! How fun!
3/14/2017 11:02:22 am
Thanks Jess!
3/11/2017 02:12:36 pm
Fun post. Not a Bachelor fan, but popcorn is my jam!
3/14/2017 11:03:14 am
Popcorn is the best!
3/11/2017 04:30:03 pm
I love KIND products. How did I not know about the popped bites? I must find them!
3/14/2017 11:03:51 am
Yeah! They're such a fun snack!
3/12/2017 08:33:15 am
I love snacking popcorns but I never thought of pairing it with a wine :) Thanks for tips and good infographic. I'm definitely saving this... and sharing ;)
3/14/2017 11:04:35 am
Thanks Natalie, I appreciate that! :) Love the graphic, too!
3/12/2017 01:19:25 pm
I must say - Wine tastes amazing with anything, but I don't think I have ever tried it with popcorn before! Now I must try it with this popcorn to see what I'm missing - any excuse to open a bottle is ok for me ;) The garlic dill version looks amazing!
3/14/2017 11:05:28 am
haha yes, any excuse to open a bottle is okay with me too! I like sweet wines, so that sweet & salty combo is really great!
3/12/2017 06:54:55 pm
Great ways to serve up popcorn. And open for any excuse to open up some wine.
3/14/2017 11:05:58 am
Definitely with you on that one Lauren!
3/12/2017 09:04:41 pm
Never though about popcorn and wine but these suggestions are fantastic!
3/14/2017 11:06:54 am
Thanks Lauren! You'll love the two together!
3/13/2017 12:02:29 pm
This was such a great idea for a blog post!!
3/14/2017 11:07:30 am
Thanks Lindsey! :)
3/13/2017 01:02:06 pm
YES! You had me at wine! Love the pairings- so creative!
3/14/2017 11:09:11 am
haha I knew we'd get along!
3/13/2017 01:08:59 pm
Oo love the snack mixes!
3/14/2017 11:10:04 am
Yes! Perfect snacks!
3/13/2017 02:40:17 pm
Those KIND popcorn snacks look so cute! I haven't seen them yet!
3/14/2017 11:11:05 am
Yeah! They look great!! :)
Leave a Reply.
Hey everyone! I'm Emily - a Registered Dietitian & food lover! I love sharing simple, tasty recipes & mindful nutrition tips here on my blog. You can browse my site for other services I offer & learn how to work with me.
January 2020
Follow @emily_the_rd


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The Sunflower Portable Treatment Couch is a light but tough folding table ideal for physios, sports therapists and masseurs who need a couch they can carry with them or who simply suffer a lack of space. Although this couch weighs only 15kg itself, it can hold individuals weighing upto 150kg. It is very quick and easy to put up and take down, and has wipe-clean surfaces.
When errected, the Sunflower Portable Treatment Couch measures 64-80cm(H) x 184cm(L) x 66cm(W). Can be supplied with an optional carrying case (please select above, add £37.80). Available in black, navy or white.
Be the first to write a review!


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Avalanche's Downie had shoulder surgery
[media-credit name="Doug Pensinger, Getty Images" align="alignright" width="490″][/media-credit]
For those wondering if Steve Downie was bothered by a shoulder injury in the final month of the season, the answer is: yes, very much so. In fact, Downie recently had surgery for it.
The Avs confirmed that Downie underwent shoulder surgery to repair a separation in the joint, but that he his doing well in his rehab. The exact timetable of his rehab remains unclear, but it's expected he would be ready to return by the start of training camp.
The injury, suffered March 3 against Pittsburgh, clearly affected Downie's play. He missed the next game, at Minnesota, but decided to play on starting the one after that against the Wild. Though he posted three assists in that first game back, he managed only two points the rest of the way in 13 games – both assists. He did not score a goal in his final 14 games.


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After exhibiting in the bustling capitals of Denmark and Sweden, photographer Peter Farago and his stylist wife Ingela Klemetz-Farago are taking Northern Women in Chanel, their ethereal portfolio of Baltic and Scandinavian models, a little farther afield. The location? A remote spot on a tiny island off the coast of Norway called Verdens Ende, which literally translates into English as the end of the Earth. "When we found out the name of the place, we almost fainted—it was so perfect," he says. The stony curvilinear landscape and magical rock pools are an otherworldly setting for Farago's images of bewitching Chanel-clad muses like Freja Beha Erichsen, Helena Christensen, and Carmen Kass. The Faragos have been known to cross icy glaciers and ancient forests in their quest for the perfect backdrop, and the latest leg of the book tour brings their work to an entirely new place: Each picture is silicone mounted without a frame so that the landscape creates a tableau in and of itself. "The light during these summer months is so beautiful," says Farago, who with the help of Chanel is celebrating the opening tonight with a private party and dinner on the islets that make up Verdens Ende. "It can be pink one moment and then orange the next, so the exhibition looks different depending on the day and time." Clearly a sight worth traveling to the end of the Earth to see.
"Northern Women in Chanel" opens June 30 and will be on view through September 30 at Verdens Ende on the island of Tjøme.
Learn more about Northern Women in Chanel.


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Kalamazoo, Mich., Sept. 21, 2018 – The Washington University in St. Women's tennis battled 20-mile per hour winds all day and had three singles players and four doubles teams advance to the Round of 32 of the Intercollegiate Tennis Association (ITA) Central Region Championships held at Kalamazoo College in Kalamazoo, Mich.
Sophomores Ashley Lessen, the No. 8 seed in the 128-singles draw, advanced with a pair of victories. Also posting a pair of victories was senior Lisa Chionis and sophomore Laurel Wanger.
In doubles, the Bears had four teams that picked up a win on day one: No. 4 seed Lessen and sophomore Ally Persky, No. 9 seed Chionis and freshman Stephanie Ren, No. 9 seed freshman Emma Verpoucke and Wanger, and sophomore Grace Hederick and senior Brigitte Hodge.


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Disclosing a disability
Deciding when (and if) to disclose your disability in applications and the selection process can be difficult. In some cases, disclosure may not be necessary if your disability will not impact your performance in the role.
Tips for disclosing
- Be honest - if a disability question is asked directly in an application, you may need to weigh up how serious you are about applying and if you would be prepared to disclose up front.
- If disclosing at an interview, stay positive and point out the abilities your disability has enabled you to develop which may be of benefit in the role (resilience, initiative etc).
- Be prepared to answer any objections you may foresee the employer having if you disclose. Also, be prepared to discuss any accommodations that may be necessary for you to do the job and how/where these can be provided.
- Try to keep information on your disability job specific. Steer discussion/content to show how you can do the job rather than the focus being on the problems that may arise.
Some resources to help
- Choosing Your Path -Disclosure: It's a Personal Decision
- Education to Employment provides great tips for university students and employers on transitioning to employment and employing students with a disability.
- Australian Employers Network on Disability (AEND) is a not-for-profit organisation focused on advancing employment opportunities for people with a disability.
- Disclosure Pros and Cons is a comprehensive article from GradAustralia on disclosing in the application or acceptance phase of a new job
- Stepping into... is a paid internship program designed specifically for university students with a disability.
For further help:
Contact the Disability Service to discuss your individual situation, what else to consider when preparing for employment, and the support services available to you while at uni.
You can also contact the Career and Employment Service for assistance.


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Imagine walking with Jesus Christ and being able to converse with him about the end. When the disciples asked the Lord about his return, what was his first sign? Jesus gave an important sign that is before the Apostle John's visions in Revelation. This first sign concerns future leaders who would appear and take his place (Mt. 24:4, Lk. 21:8).
When Christians study the writings of other apocalyptic groups, this point emerges. One simple lady once said that she did not join an apocalyptic group when she heard the members continually praise and exalt the role of their prophet. In practice, they emphasized their leader more, not the Lord Jesus.
While reading Manhee Lee's book, I thought about this point too. Does the revelation to Mr. Lee put Mr. Lee on a level that takes the Son of Man's place? To find answers to this question, we need to analyze the specific signs Jesus reveals about final leaders in the Olivet discourse (Mt. 24, Mk. 13, Lk. 21).
1. ¨For many will come in my name¨ (Mt. 24:4). The Lord says that a leader will come in his name (i.e. claim to be his authority and representative on earth). In Shinchonji, Manhee Lee claims to come in Jesus' name. ¨The next advocate, the holy spirit of the advocate who comes from heaven at the second coming, comes in Jesus' name¨(Creation of Heaven and Earth, p. 437).
2. ¨Many will come in my name, saying I am he,¨ (Mk. 13:5). Jesus says that the leader will announce to everyone that he is the one everyone was waiting for in the end. He is linked to the Messiah's presence. In the same way, Manhee Lee teaches that he is the body/flesh that people see when Jesus' spirit returns to earth.
¨Jesus promised that when the gospel of heaven is spread to the ends of the earth, he will return in spirit to unite with his promised pastor¨ (Creation of Heaven and Earth, p. 143). Manhee Lee states that he is "the flesh" through whom Jesus appears in Rev. 19. ¨John sees heaven open and someone called 'Faithful and True' riding a white horse leading the armies of God (Rev. 19:11)...The spirit chooses one flesh as its horse and works through that person. At the second coming, Jesus chooses the one who overcomes (Rev. 3:12) as his horse and works through him (Rev. 6:2)¨ (Creation of Heaven and Earth, pp. 246,247).
3. ¨I am he and the time is at hand,¨ (Lk. 21:8). Jesus says that a leader not only proclaims to be the savior-Messiah's presence, but he announces the coming of the end of the age. In Manhee Lee's book, he writes that he is witnessing the end of the age and that the time is at hand. ¨...the prophecies in the New Testament exist to testify about the promised pastor who acts as a savior¨ (Creation of Heaven and Earth, p. 177). ¨Today the time that was appointed for Revelation's fulfillment has finally come¨ (p. 564).
4. ¨...they will appear and perform great signs and miracles to deceive even the elect.¨ The Lord teaches that final leaders will perform signs to convince people, almost convincing the elect (Mt. 24:24). A sign is necessary to give the leader credibility and convince many. Manhee Lee states that mastery of the Bible's prophecies is a spiritual sign that he is the chosen pastor (i.e. explanations of Revelation).
5. ¨At that time if anyone says to you, Look, here is the Christ...There he is, out in the desert, do not go out... or here he is in the inner rooms, do not believe it.¨ Jesus states that some will announce how the Lord returns. They will point to a hidden or secret return (Mt. 24:26,27, Lk. 13:21). In Shinchonji's article on Rev. 1:7, Shinchonji teaches that Jesus comes back in an invisible way and the final pastor is the one everyone sees.
When thinking about these signs from the Lord Jesus, we see that he expects us to wait for him, not a leader who comes in his name or embodies a spirit return of Christ. When leaders of apocalyptic movements appear, they say they come as servants of the Lord but end up ruling, judging, and saving the Christian world in place of the Lord. In Manhee Lee's book, the emphasis is noticeably on Mr. Lee and his final role.


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Beware of the company Vita Nordica
The Swedish Consumer Agency have received many reports from angry consumers on the matter.
The reports are all about consumers who has ended up with a subscription that is hard to get out of, after ordering what they believed was a sample package.
Read more on the Swedish Consumer Agencies website. You can find the link in the column on the right hand side of the page.


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Optimize computer performance with Driver Booster
In order to keep your computer performing optimal it is necessary to keep your drivers updated just like you keep it updated to stay secure online.
Driver Booster keeps your drivers updated
Most people know it is important to keep software updated in order to be secure from hackers, malware and viruses. In order to keep your computer performing optimal you should also keep your drivers updated. To help you with that, IObit has developed a small tool to help you keep your drivers updated. If you are a gamer that love to play heavy games, updating graphic card, network and disk drivers updated.
I tested Driver Booster on my own computer and was a bit surprised that I had that many drivers that was not up to date. I knew that my graphic card driver was not the newest one, because Nvidia updated all the time, but that my audio and net Card driver was very old was a surprise for me. Maybe you should test your own system to see if your drivers are up to date. Driver Booster automatically makes a Windows restore point, making it easy to recover if something goes bad updating a driver.
How does Driver Booster work?
After installing Driver Booster, it will scan your computer to check if you have drivers that is not running on the newest version. If the scan finds devices that is not running the newest version it presents you with a list of devices you should updated. You can choose yourself what drivers you want to update. You can choose to automatically reboot the PC when the update has completed. Reboot is required for most updates to work. In case you find that an updated driver is not working stable you also have an option to restore to an older driver. Driver Booster automatically keeps a backup of the drivers you update (Pro Edition only).
Enter below to win a copy of Driver Booster 6 Pro:
About Driver Booster
Driver Booster 6 controls and updates more than 2.500.000 device drivers from Intel, Nvidia, AMD etc. to keep you running on the best and most stable drivers on your computer. The software also has a feature you can turn on to boost your games. Game Boost stop unnecessary app/services for a better gaming experience. Driver booster also cleanup old leftovers that many driver installers leave behind after updating drivers.
Driver Booster from IObit is also available in a Pro edition with even more features.
Gallery of Driver Booster from IObit
Download Driver Booster 6
To test Driver Booster from IObit you can download the free version here:
Download Driver Booster Free here (19.3 MB)


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Monthly Archives: June 2016
Doncaster Electronic Foundation Live #15 3rd Birthday
Filed under event news
Doncaster Electronic Foundation Radio 28th June 2016 – Battery Operated Orchestra interview
Track list below: (more…)
Filed under podcast
Pilosa – Live in Sheffield 25th June 2016
Pilosa are a three piece electro outfit from Sheffield who wear their LCD Soundsystem influences quite proudly on their sleeves. When they are wearing things with sleeves that is and not just t-shirts. Which they are here. Obviously.
We're not really normally quite into the more funky hip hop inspired sound that Pilosa do but yet there is something awfully infectious and appealing about it in this instance. There's a clear glee and enthusiasm bursting from them about what they're doing and frankly bags of musicianship and professionalism. Such qualities are hard to resist, alongside some actually really rather catchy tunes.
Here's a couple of videos we took of them from last saturday night so why not have a look for yourself to see the enjoyment that can be had.
You can find more Pilosa tunes on soundcloud and facebook and twitter:
Filed under gig review
Tokyo Witch Hunt at Live in Barnsley
It's long been the case that Tokyo Witch Hunt have been one of our favourite artists. There's just something incredible and masterful about the way maestro Izzie Kirk puts together a song that really gets into our bone marrow. Songs that are frequently as danceable as they are deep, as singalong as they are soulful. She's also got great style in the live performance too as you'll see here when Tokyo Witch Hunt headlined the K Box Stage at the Live in Barnsley Festival.
On this special occasion Ash, her usual bass player, was unable to make it so Faye of Berlyn Trilogy kindly stepped in on bass guitar duties to great effect.
Here she is joined by Faye of Berlyn Trilogy
Filed under feature, gig review
Night Shift Sheffield – The Gifted, Last July, Jan Doyle Band 24th June 2016
Filed under event news, Night Shift
Last July interview
Filed under Night Shift, podcast


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This is Jim Breitfeller's journey into the Maze of Melanoma. Jim Breitfeller has gathered medical information for the patient and the caregiver. As Lance Armstrong would say "Lets stand Up to Cancer" Jim's Battle with the Beast July 2005 to present.
Thursday, October 28, 2010
The Accelerator..IL-2 Therapy..Melanoma Cancer..Jim Breitfeller
Ipilimumab, by contrast, is a more general immune booster. It blocks a protein called CTLA-4 that acts as a brake on T cells, the soldiers of the immune system. It is already also being tested against lung and prostate cancer.
Still, if a tumor does not elicit a strong immune response to begin with, then just keeping the response going longer would not help much, just as lifting one's foot from the brake usually will not make a car go faster if the accelerator is not pressed. The accelerator needed is Interluekin-2 (IL-2.
IL-2 induces inflammation at tumor sites(Danger Signal) with three predominant secondary effects:
1)activation of antigen-presenting monocytes.
2) massive production of chemoattractants that may recruit other immune cells to the tumors.
3) activation of cytolytic mechanisms in monocytes (calgranulin, grancalcin) and NK cells NKG5, NK4.
The take away; systemic combinatorial therapy is one of the best ways to utilize the immune system to induce an immune response to Melanoma Cancer.
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change."
~Charles Darwin~
Take Care,
Jimmy B
Tuesday, October 26, 2010
Tumors shut down the Third Signal needed for T-cell Activation..Melanoma Cancer..Jim Breitfeller
STAT-3 signaling from the tumors blocks the pro-inflammatory cytokines, so no danger signal is sent to the immune system.
The Missing Link in T-cell activation using a Vaccine, "The Danger Signal"
DCs leads to enhanced induction of Th17-1 cells. These data demonstrate the capacity of DCs to induce expansion of polyfunctional IL17-producing T cells in humans, and suggest a role for DCs in the enrichment of Th17-1 cells in the tumor bed.
Tumor bed is heavily infiltrated by DCs, which, as shown here, are the most efficient inducers of human Th17 cells. The data supports a model in which Th17 cells are recruited to the tumor bed by Th17-attracting chemokines (eg, CCL20, recently shown to be enriched in the melanoma tumor bed) and activated to a Th17 phenotype locally by tumor-infiltrating DCs. The capacity of DCs to induce Th17 cells may be further enhanced by the uptake of apoptotic tumor cells, as well as inflammatory cytokines (eg, IL1, IL6, TNF) in the tumor bed. This gives rise to T-cell activation and the inflamed response leading to immune response.
For the tumor to survive the immunologic suppression system, it must turn on pathways (such as Stat3) that inhibit production or sensing of proinflammatory danger signals that activate innate and adaptive immune responses. Tumors that successfully accomplish this can shift the balance of immunity from activation to tolerance induction. Pardol et al But what if, the production of Proinflammatory cytokines can over come the suppressive function of the tumor's microenvironment? Could the differentiation of the CD4+ T-cells into Th17 be the path to activation and immunity responses? If that is the case, then Anti-CTLA-4 blockade (ipilimumab) plays more of a major factor in adaptive immunity then we originally thought.
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change."
~Charles Darwin~
Take Care,
Jimmy B
Monday, October 25, 2010
The Future of Immunotherapy.. Emerging concepts in biomarker discovery.Melanoma.Jim Breitfeller
Take away: Get your blood and tumors profiled for Biomarkers. It could lead you to the right therapy to do.
A table of:
Emerging biomarkers potentially useful for the immunotherapy of cancer.
A Table of:
Emerging biomarkers potentially useful for the immunotherapy of cancer.
Source:Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology
Dr. Kirkwood give his honest opinion on the clinical trails to date and where they are heading in the future incliding Biomarkers.
Please take an hour out of you day to view and listen, It may save you or your love one from doing the wrong therapy.
Dr. Kirkwood talks about autoimmunity through out the presentation
NIH Scientists Discover Secrets Of Helper T Cells Involved In
Autoimmunity.... Th17 cells!!!!!!
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.
"~Charles Darwin~
Take Care,
Jimmy B
Friday, October 22, 2010
Questions and Answers from Jim In Denver Co..Melanoma..Jim Breitfeller
First of all thank you for replying to my post. I usually don't get many replies. When I talk to my wife about this, within the first five minutes she is telling me "I am loosing her." It has taken me close to three years to get to where my knowledge on melanoma and the immune system is today. I don't mean to talk over patient heads. It is just the scientist in me. I worked at Eastman Kodak's Research laboratories for 25 years.
Now to answer you first question:
You have said that the most effective durable treatment for advanced melanoma would consist of Ipilimumab combined with IL2 - is that correct?
Based on my research today, IL-2 and Anti-CTLA-4 (Ipilimumab) are most durable as we speak. A new phase I therapy is showing great promise with less side effects. That is anti-PD-1 Therapy. These therapies don't need a specific HLA type to get into the trials.
There is also a very, very ,very new therapy that is still in translational stage. Translational research is a way of thinking about and conducting scientific research to make the results of research applicable to the population under study and is practised in the natural and biological, behavioural, and social sciences. It is usally conduted with animals like rats, mice, monkeys.
Anyway this therapy combines the Anti-CTLA-4 and Anti-PD-1. It has shown synergistic results.
If you have c-Kit or BRAF mutations, then targeted therapy may used but may not be durable.
If you are HLA-02 Positive, You have the option of ACT therapy with Dr. Rosenberg or Dr. Patrick Hwu at NCI or MD Anderson. They have gotten 72 % response rate with I think about 36 % complete response is I am not mistaken.
Second Question:
There are no studies currently availble that combine Ipi and IL2, is that correct?
Define combine? There was a clinical study done by Dr. Rosenberg and colleages.
As you can see in the graph above, IL-2 was added prior to the maximum propagation of the CD4+ T helper cells. IL-2 is known as a growth factor. So what I believe happened in this trial, they grew the Tregs.
IL-2 treatment during the expansion phase was detrimental to the survival of rapidly dividing effector T cells. In contrast, IL-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of Tumor-specific T cells. IL-2 treatment also increased proliferation of resting memory T cells in the host that controlled the disease. A tumor-specific T cell in chronically infected Host also responds to IL-2 resulting in decreased tumor burden. Thus, timing of IL-2 administration and differentiation status of the T cell are critical parameters in designing IL-2 therapies (Blattman et al., 2003).
So what I am trying to say is you do the Ipilimumab therapy first. Wash out for about 50 days, and then start IL-2 Therapy.
Take away: It is a systemic combination with dosing and timing involved. Systemic Combinatorial Therapy.
Question 3:
If someone were to choose to do a combination treatment on their own (i.e. get IL2 following a course of Ipi through one of the clinical trials), would there be an advantage
to starting IL2 as soon as possible after stopping Ipi? Is there a time frame after which there would be no advantage to having received Ipi prior to taking IL2?
Base on papers from ITOH etal and others, 49 days after activation is at the maximum growth phase for the CD8- T-cells that mature into Cytotic T Lymphocytes.
Results: Graph setup
Kinetic Study of rIL-2-induced Expansion. In all 12 metastatic melanomas tested, a substantial proportion of TIL was present in tumor cell suspensions.
The ratio of lymphocytes to tumor cells ranged from 0.03 to 1.25 with an average ratio of 0.40 t 0.37. By fluorescence analysis,
TIL consisted of 78 days 11% CD3
T cells, 33 days 10% CD4+
T cells, 49 days 17% CD8+
Their CD4/CD8 ratio was 0.67.
(ITOH et al., 1988)
It was also reported that there is a time factor involved.
Our results show that T4 + human T cells differ substantially from T8 + cells with respect to their IL-2 responsiveness. T4 + cells cease to proliferate well before T8 + cells during a primary response. (GULLBERG AND SMITH et al.,1986)
Is there a time frame after which there would be no advantage to having received Ipi prior to taking IL2?
Yes, Ipilimumab has a half life of 15 days. So say you get one dose at 3.0 mg/Kg.
Days-- concentration
0-- 3
15-- 1.5
30-- 0.75
45-- 0.375
60-- 0.1875
75-- 0.09375
90-- 0.04687
105-- 0.02343
120-- 0.01171
135-- 0.00587
150-- 0.00292
165-- 0.00146
180-- 0.00073
It gets more complicated when you get multiple doses. Four dose regiment.
Days-- concentration
0-- 3
15-- 1.5
30-- 3.7
45-- 4.85
60-- 5.425
75-- 2.7125
90-- 1.35625
105-- 0.68
120-- 0.34
135-- 0.17
150-- 0.08
165-- 0.04
180-- 0.021
I am not sure where the limited threshold is but, at day 49 you have close to the maximum concentration of Ipilimumab in your body.
Since I used Tremelimumab with Half Life = 21 days and did 15mg/Kg
I had at day 50 approximately 2.17 mg/Kg anti-CTLA-4 level in my body
If I had to venture an educational guess, I would say after a four dose regime, you have 75 days to do the HD IL-2.
To back this theory up, we will use a chart from Dr. Wolchok experience the Ipilimumab.
It is a chart with the Absolute Lymphocyte count. (ALC). It is the CD4+ T-cells and CD8+ T cells combined.
As you can see from the graph, the maximum ALC was about week 7.
Week seven correlates to 49 days. That is when CD8+ T cells are at their maximum growth.
Question 4:
Last, is there any evidence that IL2's efficacy is enhanced by combining it with other agents (i.e. Biochemotherapy), either with or without first receiving Ipi?
This my take on the situation. You need the tumor-specific antigen to presented to the T-cells as signal 1. That could be a vaccine, radiation therapy or chemo to shed the antigen.
Secondly you need the costimulation of the CD28/B7 interface. By using Ipilimumab that blocks the CTLA-4 receptor from binding to the B7 molecule and shutting down the response.
Anti-CTLA-4 (ipilimumab) also blocks the CTLA-4 receptor on the Treg cells subduing their surpress function.
Third you need a "Danger Signal" to get the cell to migrate to the tumor site. This may be done with inflammatory Cytokines like IL2, IL17, IL-1,IL-12,IFN gamma that act directly on the T-cells. This signal was found to optimally activate the Th1 differentiation and lead to the clonal expansion of the T-cells.
It has come to light recently that Ipilimumab helps also in the differentiation by tilting the balance towards Th17 cells. These cells secrete IL-17 which recruite the neutrophils. This all takes place at the tumor's microenviroment. The neutrophils secrete chemokines that are chemoattractants.
These chemokines, MIP-1alpha, MIP-1beta, and MCP-1 are recently reported to serve as chemoattractants for Th1 cells. MIP-1alpha and MCP-1 are also reported to enhance antigen-specific (CTL) Cytotoxic T Lymphocyte induction. Studies revealed that MIP-1alpha /beta released from neutrophils are involved in recruitment of macrophages, T cells, monocytes, dendritic cells (DC), neutrophils and NK cells.
MIP-1 attracts predominantly CD8+ T cells while MIP-1 attracts CD4+ cells, although there is some overlap between subsets in response to both chemokines.
The other Chemokine MCP-1, binds to CCR2 to accumulate monocytes/macrophages, DC, T cells, and NK cells, thereby playing an important role in innate and adaptive immunity. CCR2 is Chemokine receptor that is key determinant of leucocyte trafficking.
IL-2 strongly upregulates expression of CCR2. With the MCP-1/CCR2 interface, the cells can traffic towards the tumor's microenvironment. The trafficking of the cells and inflammatory cytokines present the perfect storm in the tumor's microenvironment to induce the right immune response to eradicate the cancer, Melanoma.
So to answer your question, is there any evidence that IL2's efficacy is enhanced by combining it with other agents (i.e. Biochemotherapy), either with or without first receiving Ipi? yes if you know and take a systemic approach. You need to activate the t-cells before introducing IL-2. IL-2 can be the activator for small patient population.
As for Ipilimumab going it alone, like IL-2 can be the activator for small patient population. But when you do a systematic combinatorial therapy, there can be a synergetic result, complete response.
I hope I answered you questions, and please don't hesitate to ask them. I do all this time by requesting reseach papers from around the world. Each question is a learning tool. There are no stupid questions. Knowledge is power to make an educated decision. Your Life may depend on it. There are many paths to take. Just follow the yellow brick road to complete response.
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change."
~Charles Darwin~
Take Care,
Jimmy B
Thursday, October 21, 2010
NIH Scientists Discover Secrets Of Helper T Cells Involved In Autoimmunity..Melanoma..Jim Breitfeller
October 21, 2010
A race for a cure!!!!!!! Let the games begin!!!!!
WHATScientists at the National Institutes of Health have redefined the roles of several cytokines involved in the generation of immune cells implicated in severe autoimmune diseases. The study in mice showed that development of Th17 immune cells can occur without the presence of transforming growth factor (TGF)-beta, a mediator thought to be required for Th17 cell development. The study demonstrates that the interaction of three inflammatory cytokines (proteins that influence the behavior of cells) - interleukin-6 (IL-6), IL-1-beta and IL-23 - is responsible for the creation of Th17 cells that are more active in promoting autoimmunity than Th17 cells generated with IL-6, IL-1-beta and TGF-beta. These findings reemphasize the separate roles of IL-23 and TGF-beta in immunity and autoimmunity, and open up possibilities for the development of new therapies. The study appears in the current issue of the journal Nature.
The immune systems of mice and humans mainly consist of B cells and T cells. While B cells fight infections and can induce autoimmunity by producing antibodies that directly target foreign antigens or a person's own tissue, T cells are involved in overall cell-mediated immunity. Importantly, how a T helper (Th) cell differentiates (develops from an immature, unspecialized cell into a mature, specialized cell) determines how it mediates immune responses. Th17 cells produce IL-17, a powerful inflammatory cytokine, and have been implicated in multiple autoimmune diseases, including rheumatoid arthritis, psoriasis and multiple sclerosis. The established belief has been that Th17 cells initially differentiate in response to activation by IL-6 and TGF-beta. However, previous research has shown that TGF-beta is primarily associated with suppressing immune functions and promoting regulatory T cells (Treg), which can produce inhibitory cytokines that dampen inflammatory immune responses.
In the present study, the NIH scientists first looked at the conditions to differentiate Th17 cells from naïve T cells outside of the mouse (in vitro) and tried several different cocktails of cytokines to see which combinations would promote Th17 development. They found two combinations that efficiently induced Th17 differentiation. As previously described, IL-6, IL-1-beta, and TGF-beta-1 together created Th17 cells. Surprisingly, IL-6, IL-1-beta, and IL-23 without TGF-beta also created Th17 cells. Most interestingly, the action of Th17 cells generated with IL-23, designated Th17(23), was different from the action of Th17 cells generated with TGF-beta (Th17(beta)). The researchers compared transcription factors, receptors and mediators of the two Th17 subtypes and looked at the pathogenic activity of both Th17 subtypes in mice during experimental autoimmune encephalomyelitis (EAE), a common model of autoimmunity that mimics some aspects of multiple sclerosis. They found that Th17(23) cells provoked significantly more severe disease than did Th17(beta) cells.
These findings suggest a new model for Th17 generation and the existence of functionally different subtypes of Th17 cells. This study also provides a better understanding of the array of immune components involved in autoimmunity and suggests possibilities for new targeted therapies.
NIH scientists contributing to this study are affiliated with the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute of Dental and Craniofacial Research (NIDCR), and the National Institute of Allergy and Infectious Diseases (NIAID). Additional support was provided by Merck Research Laboratories (Schering-Plough Biopharma), Palo Alto, Calif.
Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, Konkel J, Ramos HL, Wei L, Davidson T, Bouladoux N, Grainger J, Chen Q, Kanno Y, Watford WT, Sun HW, Eberl G, Shevach E, Belkaid Y, Cua DJ, Chen W, O'Shea JJ. Enhanced Pathogenicity of Th17 cells Generated in the Absence of Transforming Growth Factor-ß Signaling. Nature. 2010 October 21;467(7318): 967-971.
John J. O'Shea, M.D. Scientific Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, is available to comment on this article.
To schedule interviews, please contact Trish Reynolds, 301-496-8190, .
About National Institute of Arthritis and Musculoskeletal and Skin Diseases
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information, visit http://www.niams.nih.gov.
About The National Institute of Dental and Craniofacial Research
The National Institute of Dental and Craniofacial Research (NIDCR) is the Nation's leading funder of research on oral, dental, and craniofacial health. For more information, visit http://www.nidcr.nih.gov/.
About National Institute of Allergy and Infectious Diseases
The National Institute of Allergy and Infectious Diseases (NIAID) conducts and supports research -- at NIH, throughout the United States, and worldwide -- to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. For more information, visit http://www.niaid.nih.gov.
About National Institutes of Health
The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information, visit www.nih.gov.
SOURCE: National Institutes of Health
NIH Scientists Discover Secrets Of Helper T Cells Involved In Autoimmunity
October 21, 2010
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change."
~Charles Darwin~
Take Care,
Jimmy B
Tuesday, October 19, 2010
Dilated capillaries at the melanoma tumor's microenvironment caused by inflammation cytokines is the beginning of the "Danger Signals".Jim Breitfeller
Three major events must occur to induce CD8+ T cell–mediated, tumor-protective immunity against melanoma.
First, the T-cell receptor must be triggered by a (or multiple) self antigen–derived peptide MHC class I complex. Therefore, this event depends entirely on appropriate antigen presentation, which is most efficiently provided by mature dendritic cells. Peripherally tolerant or "ignorant" self-reactive T-cell clones, once properly activated, may serve as tumor-specific effector T cells.
Second, simultaneously with T-cell receptor triggering, a distinct second costimulatory signal must be delivered, mediated by IL-2, B7-1, or B7-2, which engage IL-2 receptors and CD28 on the surface of the T cell, respectively (17). A source of these cofactors for effective CD8+ T-cell stimulation can be provided by CD4+ T cells that release critical amounts of IL-2, or by mature dendritic cells that display an increased level of B7-1/B7-2 costimulatory molecules on their cell surfaces.
Third, inflammatory cytokines, including IL-1, IL-6, IL-12, and IFN-γ provide a third signal that acts directly on T cells, referred to as the "danger signal". This signal was found to optimally activate TH1 differentiation and lead to clonal expansion of T cells.1
The inflammatory cytokines act to promote T cell responses. They include IL-1, IL-6, IL-12, TNF-α, and IFN-g produced by macrophages and/or dendritic cells. Th17 cells also plays a part by secreting IL-17 and others. The most notable role of IL-17 is it involvement in inducing and mediating proinflammatory responses. Neutrophils are the earliest cells to arrive at the inflammatory site.
While TGF-β is a critical differentiation factor for Treg cells, IL6 completely inhibits the generation of Treg cells induced by TGF-β. Instead, IL6 and TGF-β together induce the differentiation of pathogenic Th17 cells. With IL-6 missing in the microenvironment, Treg Cells flourish.
If the CD4 + T cells differentiate into TH2 cells that produce IL-4, the other cells inhibited to produce IL-6. IL-4 was found to inhibit TNF-α and IL-1β by activated monocytes almost 100 %. The Secretion of IL-6 was decreased by approximatly 80 % in the presences of IL-4 Cytokine. TE Velde et al 1990
Neutrophil recruitment can also be induced by cytokines such as IL-17 and Tumor necrosis factor (TNF). Among the family of IL-17 cytokines, IL-17A and IL-17F are able
to promote the recruitment of monocytes and neutrophils via the induction of other cytokines and chemokines such as G-CSF and IL-8 by various cell types.
IL-17 appears to be involved in promoting neutrophil influx into the tumor site. With the influx of neutrophils in the tumor's microenvironment and the inflammatory cytokines, capillaries at the melanoma tumor's microenvironment become dilated, making room for the recruitment of immune cells.
Neutrophils also play an important role in promoting or suppressing the Th1 immune response, which is mediated partly by induction of cytokines or chemokines. Depending on the compositional makeup of the microenvironment, the neutrophils can promote the right immune response. Studies revealed that these neutrophils secreted three different chemokines. Some of these chemokines are known as chemoattractants. A chemoattractant is a chemical (chemotactic) agent that induces an organism or a cell, a leukocyte, to migrate toward.
These chemokines, MIP-1alpha, MIP-1beta, and MCP-1 are recently reported to serve as chemoattractants for Th1 cells. MIP-1alpha and MCP-1 are also reported to enhance antigen-specific (CTL) Cytotoxic T Lymphocyte induction. Studies revealed that MIP-1alpha /beta released from neutrophils are involved in recruitment of macrophages, T cells, monocytes, dendritic cells (DC), neutrophils and NK cells.
MIP-1 attracts predominantly CD8+ T cells while MIP-1 attracts CD4+ cells, although there is some overlap between subsets in response to both chemokines.
The other Chemokine MCP-1, binds to CCR2 to accumulate monocytes/macrophages, DC, T cells, and NK cells, thereby playing an important role in innate and adaptive immunity. CCR2 is Chemokine receptor that is key determinant of leucocyte trafficking.
IL-2 strongly upregulates expression of CCR2. With the MCP-1/CCR2 interface, the cells can traffic towards the tumor's microenvironment. The trafficking of the cells and inflammatory cytokines present the perfect storm in the tumor's microenvironment to induce the right immune response to eradicate the cancer, Melanoma.
Neutrophils circulate in the bloodstream and must be signaled to leave the bloodstream and enter tissues. The signal often comes from the bacteria themselves, from complement proteins, or from damaged tissue, all of which produce substances that attract neutrophils to a trouble spot. (The process of attracting cells is called chemotaxis.)
The combination of chemoattractants and inflammatory cytokines, in the tumor's microenvironment, helps to send out a Danger Signal which in turn invokes the right immune response to eradicate the Melanoma tumors.
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change."
~Charles Darwin~
Take Care,
Jimmy B
Friday, October 15, 2010
It takes two (IL-2) to Tango! Melanoma..Jim Breitfeller
Immune responses involve multiple cell-cell interactions within lymphoid tissues, the
trafficking of activated cells to sites of effector function, and the migration of such effector cells within peripheral tissues. To gain a more detailed appreciation of the dynamics of such cell behavior and the relationship between cell dynamics and function, I have put together a series of events that take place during the activation phase of the immune response.
We know based on research that once the CD4+ T cell is activated, within two hours the IL-2 expression and IL-2 receptor are unregulated. IL-2 is secreted 45 minutes into this activation phase.
Experimental work has shown that IL-2 signaling in the first 10 hours is critical for the proliferation decision of T cells in culture. The spacial resolution of the Tregs and the T helper cells during this phase plays a major part in the immune response.
Secreted IL-2 is competed for by the Tregs and the activated CD4+ and CD8+ T-cells. If the Tregs are in close proximity of the T effector cells that are secreting the IL-2, the Tregs will create an IL-2 sink in the microenvironment. This will cause the proliferation and survival of the Tregs which suppresses the effector cell function. The IL-2 sink is where all the IL-2 that is secreted by the T helper cells is adsorbed by the IL-2 receptors on the Treg cells. Tregs don't have the capability to produce IL-2 so they must scavenge the IL-2 out of the microenvironment of the CD4+ T helper cells. In Treg cells, the IL-2 gene is silenced and IL-2Rα is constitutively expressed through the action of the Treg-lineage-specifying transcription factor FoxP3.
The model proposed by Dr. Dorothea Busse and colleages predicts that the IL-2 secretion rate must exceed a threshold value Theta (θ) to switch IL-2Rα expression to the activated state and permit extensive autocrine IL-2 signaling.
This is just like the three little bears. You need the microenviroment conditions just right to activate T Helper cells.
As you can see in the above diagram, you don't need high concentration of IL-2, you need spacial distance from one cell to the other. That can be achieved by Anti-CTLA-4 Blockage. By blocking the CTLA-4 receptors, the spacial distance between the T helper cell and the Treg cells increases and it also helps to differentiate the niave CD4+ T cells into Th17 cells.
IL-2 is mainly captured by the Treg cell, whereas autocrine reuptake by the T helper cells predominates when the cells are further apart. So we want to introduce IL-2 before the tumor recruites the Tregs to the Tumor Microenviroment and or when the Treg population is in the contration phase of the CD4+ T-cell cycle.
Cellular signal response is potentially controlled by ratio between ligand (IL-2)
number and surface receptor (IL-2R) number per cell.
Ligand n. An ion, a molecule, or a molecular group that binds to another chemical entity to form a larger complex.
Suboptimal amounts of IL-2 during priming promoted apoptosis, little proliferation and cell cycling, yet the CD8+ effectors generated produced high levels of cytokines and proliferated autonomously. Although IL-2 deprivation caused apoptosis and little proliferation initially, the effectors generated under these conditions possessed optimal effector functions. This low IL-2 concentration, allows the T help cell to activate and proliferate.
This is the reason why it takes a while for the tumors to begin to shrink because of little proliferation at first. It takes time for the immune system to assemble an army of Cytotoxic T Lymphocytes.
So how can we minimize the proliferation of the Tregs which are a subset of CD4+ T-cell subset without doing a full blown depletion of the CD4+ T-cells?
1. Anti-CTLA-4 Blockage
2. Local IL-21 Promotes the Therapeutic Activity of Effector T cells by
Decreasing Regulatory T Cells Within the Tumor Microenvironment
3. Anti-PD-1 Blockage
4. A combination of the above three.
This is the future of Melanoma Therapy, Combinatorial Therapy.
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change."
~Charles Darwin~
Take Care,
Jimmy B
Tuesday, October 12, 2010
ASCO 2010 Long Term Survival Benefit in Melanoma...Jim Breitfeller
As you can see the combinatorial therapy of Anti-CTLA-4 and Interluekin-2 give the best complete response. I am convince that if they adjust the timing and dose, they will see an even higher response rate in overall survival.
The Making of an Immune Response by Combinatorial Therapy Using Anti-CTLA-4 Blockade and Interleukin-2
The paper that I am about to present to you is a culmination of research that was done base on my own experience as a stage IV Melanoma Patient. I wanted to know why my immune system responded and prove to myself and my doctors that it was not a statistical fluke. I dedicate this paper to all my fellow Melanoma Patients that lost their battle with the Beast, especially Bob Luker who fought so bravely but was unable to obtain Anti-CTLA-4 blockade due to the shortage proclaimed by Bristol Myer Squibb which halted compassionate drug use on 9-12-2008.
Most Melanoma tumors are accepted by the host's immune system and progress even when they contain potentially antigenic proteins. This may be due to the tumor secreting immunosuppressive Cytokines like, TGF-Beta, IL-10, IL-4 and IL-6. TGF-β inhibits the proliferation and functional differentiation of T lymphocytes. TGF- Beta accelerates the expression of CTLA-4 by stimulated CD4+CD25– T cells. TGF- Beta requires CTLA-4 early after T Cell Activation to induce FoxP3 and generates adaptive CD4+CD25+ (Treg) Regulatory Cells. The tumor cells secrete TGF-Beta.
The Making of an Immune Response by Combinatorial Therapy Using Anti-CTLA-4 Blockade and Interleukin-2
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change."
~Charles Darwin~
Take Care,
Jimmy B
Friday, October 8, 2010
Activating the Danger Signal with Anti-CTLA-4 Blockade..Melanoma..Jim Breitfeller
Initial Diagnosis: May 2003
Current Stage: Stage 4
Depth of Primary: Up to 1 mm
Treatment Stats
Doctor: Mario Sznol MD
Treatment Center: Yale New Haven
Clinical Trial(s): Ipilimumab
Treatment History
February, 2003 my wife noticed a dark spot on my balding head.
April 2003 Punch biopsy read asmelanoma, 0.76mm deep.
May 2003 Wide Local Excision
May-Sept - Multiple dysplastic nevi excised
Sept 2003 - Second primary, this time in situ, on my chest
PET scan, MRI and CT all negative
Oct 2003 - University of Pennsylvania Pigmented Lesion clinic in Philadelphia they reread my slides and reclassified it to a Breslow's depth of 0.86 and Clark's level 4 and told me I have Stage 1B with a specific note that there appeared to be no immunologic response by my body to the melanoma.
October 2003 - October 2006 Derm exam every 3 months. Many dysplastic nevi excised. Doing well, no more primaries, no problems.
October 2006 coughed up blood CT, PET showed a 5cm mass in my L lung. MRI negative for brain mets. No other lesions found.
October 30, 2006 - Thoracotomy at St. Peter's Hospital in Albany NY with removal of the lower lobe of my left lung. Did well after surgery.
November, 2006 - Local oncologist offers interferon but suggests I look into trials
December, 2006 - Accepted into University of Pennsylvania trial of Anti-CTLA4 if my scans remain clear
December 12, 2006 - Had MRI and CT for study and found I has a previously undiagnosed.
met to my brain
December 13, 2006 - Radiation oncologist suggests neurosurgery unless it is not safe to resect. Also heard I may have micro-mets in the lungs. Put on decadron. Seeing neurosurgeon on 12/14
December 14, 2006 - Neurosurgeon says "take it out"
December 20, 2006 - Craniotomy. Second major surgery in 7 weeks! Another stint in the ICU. Woke up unable to move my left leg
December 24, 2006 - One week in a rehabilitation hospital. Intense physical therapy and I walk out
January 2007 - Planned on SRS but more brain mets found. Underwent 15 sessions of WBR
March 2007 - More lung mets found - multiple, disseminated in both lungs, tiny
April 2, 2007 I start IL-2 at Deaconess Beth Isreal in Boston
June, 2007 Brain tumors bleed - emergency craniotomy
July, 2007 - Stereotactic radiation
Sept, Oct waititg for a trial...and waiting...and waiting
October 2007 Accepted in compassionate use trial WITH Ipilimumab (MDX-010 at Yale New Haven Hospital under the care of Dr. Sznol
October 31, 2007 First dose of Ipilimumab at Yale-New Haven Hospital.
November 20, 2007 Second Infusion of Ipilimumab
December 11, 2007 Third dose of Ipilimumab
December 18, 3007 Severe reaction to IPI
Admitted to YNHH with uncontrolled vomiting, dehydration, hyponatremia and weakness. Discharged December 23, 2007 to home. Began 4 mg oral steroids.
January 22, 2008 began to notice double vision, nausea and vomiting as steroids were tapered from 3mg to 2 mg. Steroids increased to 2.5 mg
January 23. , increased to 3mg
anuary 25, increased to 4 mg
January 28, 8 mg January 29 . Nausea and vomiting disappeared. Double vision improvement noted
February 4th…Have lost all peripheral vision.
March 2008 increased weakness noted in lower extremity resulting in confinement to
Wheelchair and walker. MRI noted area of increased swelling on right parietal lobe at site of June 2007 surgery. Not metastatic disease.
April 2008 prescribed high dose (40mg) oral steroids to reduce swelling and manage side effects until planned surgery May 2008.
May 8 2008 planned craniotomy (#3) to remove necrotic tissue iAfter 5 day inpatient stay, walked out of hospital without assistive device. Began taper of steroids.
May-June 2008 unable to tolerate steep taper, steroids increased and taper resequenced at much slower rate.
December 2009 Tumors still visible on scans in brain and lungs but no growth since 2008, Stable. No evidence of active disease.
UPDATE written October 7 2010
October 7, 2010. Four years after my diagnosis with Stage IV Melanoma I continue to show no evidence of active disease. I do have problems elated to treatmens: Simple Partial Seizures, Visual problems (Double and blurred) Short term memory loss, Episodes of fatigue. Symptoms that remind me about what I went through these past four years, but definitely things I CAN LIVE WITH. A hell of a lot better than I thought when I started to fighting the beast/
Mark, Catskill, NY
Activating the Danger Signal with Anti-CTLA-4 Blockade
Was it the combination Radiation, IL-2 plus the Anti-CTLA-4 blockage?
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change."
~Charles Darwin~
Take Care,
Jimmy B
Invoking an Immune Response without causing an Autoimmune Response..Melanoma ..Jim Breitfeller
Challenges in immunotherapy
• Immunotherapy has yet to fulfil its clinical potential.
• Historically, responses have only been observed in a minority of patients.
• Recent trials of new immunotherapies in oncology have shown that patients receiving treatments such as anti-CTLA-4 therapy respond differently, and sometimes later, compared with those receiving chemotherapy or some of the existing immunotherapies such as interleukin-2 and interferon.
Some of the investigational immunotherapies act as T-cell mediated immunopotentiators. That is, they may regulate and potentially enhance the body's own immune response, and consequently there may be a delay in stimulating the immune system to fight disease.
"Another patient's measured tumor burden in 7 pulmonary metastases is shown as a percent of their baseline size. Tumor remained stable during 4 doses of ipilimumab administered without symptoms, but regressed promptly after patient experienced a bout of biopsy documented enteritis." Yang et al
en•ter•i•tis ( n t -r t s). n. Inflammation of the intestinal tract.
Inflammation is the "Danger Signal" that is needed to hone in on the cancer itself.
Currently it is difficult to select patients who might benefit from specific immunotherapeutic approaches, and tailored immunotherapy regimens will have to be created in order to provide the most appropriate and effective treatment. Each Patient is at a different stage of his or her disease. It will take a trained Melanoma Oncologist to provide the guidance.
T-cell activation video from Andrew Lamb on Vimeo.
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change."
~Charles Darwin~
Take Care,
Jimmy B
Tuesday, October 5, 2010
Helper T Cell (Th17) Guides Killer Cells to Melanoma Cancer..Jim Breitfeller
Helper T Cell Guides Killer Cells to Cancer
An important mechanism by which Melanoma cancer avoids antitumor immunity is by recruiting regulatory T cells (Tregs) to the tumor microenvironment. Recent studies suggest that suppressor Tregs and effector Th17 cells share a common lineage and differentiate based on the presence of certain cytokines in the microenvironment. Because IL-6 in the presence of TGF-β has been shown to inhibit Treg development and induce Th17 cells, they hypothesized that altering the tumor cytokine environment could induce Th17 and reverse tumor-associated immune suppression.
CTLA-4–B7 Interaction on the activated T-cell suppresses Th17 Cell Differentiation.Using anti-CTLA4 blocking antibody (Ipilimumab or tremelimumab) increases Th17 cells in peripheral blood of patients with metastatic melanoma. The Th17 cells can then migrate to the tumor's microenviroment. This sends the Danger Signal in the form of pro-inflammatory cytokines including IL-17. This is the third signal that is needed in the initiating of an immune response.
One of the mechanisms proposed is that CTLA-4 inhibition of T cell activation is due to antagonism of CD28-mediated costimulation. Both CD28 and CTLA-4 share the ligands B7.1 (CD80) and B7.2 (CD86); however, the affinity of the CTLA-4:B7 interaction is 10 times higher than the affinity of the CD28:B7 interaction. Although studies using CD28-deficient mice have shown that negative signaling through CTLA-4 is independent of CD28 expression, it is plausible that CTLA-4 interacts with B7 and prevents its interaction with CD28.
It is possible that T-cell activation can't start until the level of CTLA-4 is block or decreased.
In my own experience, I did not get any activation until tremelimumab was introduced
If you Block the CTLA-4 and B7 with Ipilimumab or tremelimumab It will also take the brakes off the immune system and shift it towards activation.
I hypothesized that Th17 cells induce Th1-type chemokines, and in turn recruit Th1-type effector T cells into tumor microenvironment.
Recent data supports the notion that Th17 cells induce Th1-type chemokines through IL-17 and IFN- , and in turn recruit Th1-type effector T cells and NK cells into tumor microenvironment.
Increased tumor-associated IL-17 predicts improved patient survival
Mechanistically, Th17 cell–derived IL-17 and IFN- synergistically induced the production of CXCL9 and CXCL10, and in turn promoted effector T-cell migration toward tumor. The levels of CXCL9 and CXCL10 were directly correlated with tumor-infiltrating CD8+ T cells and NK cells. The data suggest that Th17 cells may play a role in promoting effector T-cell and NK-cell tumor trafficking and retainment, and the polyfuctional cytokine profile (IFN- +IL-17+) of Th17 cells is essential for synergistically inducing Th1-type chemokines.
"It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change."
Friday, October 1, 2010
Tregs Rule Unless Anti-CTLA-4 Blockage is Used!!! Melanoma.. Jim Breitfeller
The first step is to relieve the immune system from the tumor-dependent immune tolerance mediated by Treg, which prevents the development of an efficient antitumor immune response.
The second step is the activation of the immune response.
"It is not the strongest of the species that survives,
nor the most intelligent, but the one most responsive to change."
~Charles Darwin~
Take Care,
Jimmy B
Greetings to One and All
It was he, who showed me How to live and give back. He was wise beyond his years.
Jimmy and Dee
Carepage: Jimmybreitfeller
Jimmy Breitfeller
My Profile as of 2009
- jimmy_B
- Last July (2005)I was riding my bicycle to work at the Eastman Kodak Research Labs about 3 miles from home. I was wearing a knapsack to carry my things to and from the labs. I started noticing an ache on my back. So I decide to go to the dermatologist. To make the long story short, it was cancer. I knew from my research that I would be needing adjuvant therapy. So I started communicating with Sloan Kettering, University of Pittsburgh Cancer Center, and a couple of others including the Wilmot Cancer Center at Strong. I realized that by telling my story, I might help someone else out there in a similar situation. So to all who are linked by diagnosis or by relation to someone with melanoma, I wish you well. Stay positive, read as much as you can (information helps to eliminate the fear associated with the unknown), and live for today, as no one can predict what tomorrow may bring. Jimmy B. posted 12/15/08
Only your physician/Oncologist can make medical decisions and treatment plans that are appropriate for you. But, An Educated Consumer is a Smart consumer.
As Dr. Casey Culberson Said:
"The BEST melanoma patient is an ACTIVE PARTICIPANT in his or her treatment
(not a PASSIVE RECIPIENT)"
Melanoma and the "Magic Bullet" (Monoclonal Antibodies)
It is 33 pages long and may help you in your quest for the Yellow Brick Broad. Just to let you know it is only the first draft. Revisions are sure to come. I wanted to get it to the people that need it the most, the Melanoma Patients.
So, where does Interluekin-2 (IL-2) come into play? According to Byung-Scok et al and recent reports, IL-2 is not needed for developmental CD4+ CD25+ Treg cells in the thymus but does play an important role in the maintenance and function in the peripheral.18 Peripheral is defines as secondary system outside the bone marrow and thymus. It entails the site of antigen, immune system interaction. IL-2 is required for the peripheral generation of Tregs based Abbas's and colleagues research.19
IL-2 prevents the spontaneous apoptosis of the CD4+ CD25+ Treg cells. It has been reported that patients with multiple advance-stage tumors have elevated levels of Tregs within the tumor microenviroment.20 Interluekin-2 is the survival factor for CD4+ CD25+ Treg cells.21 If the addition of IL-2 is on or before the maximum propagation of the CD4+ T cells, the Tregs population can increase 5-fold in a 96 hour period based on certain growth mediums.
By controlling the addition of the endogenous IL-2, one has a knob to turn and can lead to the control of the expansion of the Tregs. When you combined this control with the anti-CTLA-4 blockage, you can shift the balance of the immune response.
Now here is the catch. The maintenance and function of the CD8+ T-cells require CD4+ cells which secrete IL-2. So we don't want to deplete the CD4+ cells, we want to control the expansion of the Tregs which are a subset of the CD4+ cells. It has been postulated by some researchers that the Anti-CTLA-4 blockage also suppresses the Treg function in a different mechanism. By using IL-2 as the rate limiting factor, we can suppress the CD4+ CD25+ Treg cell expansion by controlling the concentration and timing of the Inerluekin-2 at the tumor microenvironment.
The Interluekin-2 plays another role in this Melanoma Maze. In a study by Janas et al, Il-2 increases the expressions of the perforin and granzyme A, B and C genes in the CD8+ T-cells. This increase expression causes the CD8+ T-cells to mature into Cytoxic T Lymphocytes (CTLs). The exogenous IL-2 is required for the granzyme proteins. As stated previously, CTLs have cytoplasmic granules that contain the proteins perforin and granzymes. A dozen or more perforin molecules insert themselves into the plasma membrane of target cells forming a pore that enables granzymes to enter the cell. Once in the tumor cell, these enzymes are able to breakup (lyse) the cell and destroy it. This is the beginning of the end for the cancer cells. The tumors begin to shrink and the rest is history,
On the other hand, prolong therapy with Il-2 can result in causing apoptotic death of the tumor- specific CD8+ T-cells.23
Clearly in a clinical setting, timing, dose, and exposure to these drugs play a major roll in the immunotherapy, and can have dramatic effects on the outcome.
All it takes is that one magic bullet to start the immune reaction..
Melanoma And The Magic Bullet (Monoclonal Antibodies)
Public Service Announcement
"We continue to see a high rate of clinical responses in our cell transfer immunotherapy treatments for patients with metastatic melanoma", Dr. Rosenberg said.
"We are actively seeking patients for these trials and any note of that on a patient-directed web site would be appreciated."
If you would like to apply for his trials, here is the website and information.
Dr. Rosenberg's information
Dr. Rosenberg's Clinical Trials
The Melanoma Research Alliance has partnered with Bruce Springsteen, the E Street Band, and the Federici family to alleviate suffering and death from melanoma. Please view Bruce Springsteen's public service announcement inspired by Danny Federici. Danny was the E Street Band's organist and keyboard player. He died on April 17, 2008 at Memorial Sloan-Kettering Cancer Center in New York City after a three year battle with melanoma.
Source Fastcures blog
Join the Relay for Life!!!
Dear Family and Friends,
I've decided to take a stand and fight back against cancer by participating in the American Cancer Society Relay For Life® event right here in my community! Please support me in this important cause by making a secure, tax-deductible donation online using the link below.
To donate on line now, click here to visit my personal page.
Jimmy B AKA Melanoma_Missionary
Relay For Life® is a life-changing event that brings together more than 3.5 million people worldwide to:
CELEBRATE the lives of those who have battled cancer. The strength of survivors inspires others to continue to fight.
REMEMBER loved ones lost to the disease. At Relay, people who have walked alongside people battling cancer can grieve and find healing.
FIGHT BACK. We Relay because we have been touched by cancer and desperately want to put an end to the disease.
Whatever you can give will help - it all adds up! I greatly appreciate your support and will keep you posted on my progress.
Keep the Fire Burning!!!
Jimmy Breitfeller
Signs of Melanoma Carcinoma Skin Cancer
Delcath Systems Granted Orphan-Drug Designations for Cutaneous and Ocular Melanoma
Delcath is actively enrolling patients in a Phase III clinical trial testing its proprietary drug delivery system, known as Percutaneous Hepatic Perfusion ("PHP"), with melphalan for the treatment of ocular and cutaneous melanoma metastatic to the liver.
This NCI-led trial is enrolling patients at leading cancer centers throughout the United States. Commenting on these orphan-drug designations, Richard L. Taney, President and CEO of Delcath, stated, "These favorable designations are important steps in our efforts to secure Delcath's commercial position upon conclusion of our pivotal Phase III trial for metastatic melanoma. We remain steadfast in our commitment to become the leader in the regional treatment of liver cancers and we continue to enroll patients in this study, and advance our technology and the promise that it offers to patients with these deadly forms of melanoma and other cancers of the liver, all with limited treatment options."
Orphan drug designation, when granted by the FDA's Office of Orphan Products Development, allows for up to seven years of market exclusivity upon FDA approval, as well as clinical study incentives, study design assistance, waivers of certain FDA user fees, and potential tax credits.
Current Trial Centers
Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using
Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies
James F. Pingpank, Jr., MD, FACS
Associate Professor of Surgery
Division of Surgical Oncology
Suite 406, UPMC Cancer Pavillion
5150 Centre Avenue
Pittsburgh, PA 15232
412-692-2852 (Office)
412-692-2520 (Fax)
Blog Archive
- ► 2012 (32)
- ► 2011 (47)
- The Accelerator..IL-2 Therapy..Melanoma Cancer..Ji...
- Tumors shut down the Third Signal needed for T-cel...
- The Future of Immunotherapy.. Emerging concepts in...
- Questions and Answers from Jim In Denver Co..Melan...
- NIH Scientists Discover Secrets Of Helper T Cells ...
- Dilated capillaries at the melanoma tumor's microe...
- It takes two (IL-2) to Tango! Melanoma..Jim Breitf...
- ASCO 2010 Long Term Survival Benefit in Melanoma....
- Activating the Danger Signal with Anti-CTLA-4 Bloc...
- Invoking an Immune Response without causing an Aut...
- Helper T Cell (Th17) Guides Killer Cells to Melano...
- Tregs Rule Unless Anti-CTLA-4 Blockage is Used!!! ...
- ▼ October (12)
- ► 2009 (332)
- ► 2008 (26)
- ► 2007 (65)
Call For Melanoma Patients!!!!
Dr. Rosenberg Has a New Clinical Trial.
Our latest treatment has a 72% objective response rate with 36% complete responses.
We are currently recruiting patients for our latest trial.
Is there some way to post this "Call for Patients" on the web site?
Steve Rosenberg
Dr. Rosenberg's Clinical Trials
(For a copy of the research paper.. see My Shared files)


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The Nuclear Jazz Quarktet's debut CD is now available. Price: $9.99 plus shipping and handling.
Tracks (hear them using the Our Music link at the top of the page):
1. Bouncing with Bud
2. Day by Day (Vocal)
3. All For One
4. Ally
5. Midnight Sun (Vocal)
6. Beatrice
7. Lullaby of Birdland
8. I Concentrate on You (Vocal)
9. Nothing Personal
10. From This Moment On (Vocal)
11. Bright Mississippi


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Friday, October 29, 2010
Brady's Halloween Party!
Well, tomorrow is the big day for my little guy. He wanted another Halloween party this year. At current count, I have 20 kids coming over for an afternoon of fun. Just wanted to share some of my decorations...
I got this idea from here it was just too cute to pass up.
One of my club members had a similar frame for our monthly club night on Tuesday. Great idea Jeanne :)
This guy is a spider, but kinda hard to see in the picture
And, of course, no goodie bag is complete without pumpkin poop
Have a Happy Halloween
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When I participated in a live chat about grant-writing a few weeks ago, I was surprised at the widespread – and forcefully expressed – view that HE managers want academics to write reams of pointless grant applications which face inevitable rejection. So I was delighted last week to encounter a presentation by Phil Ward, Research Funding Manager at the University of Kent, that shows what we really want.
The presentation (the slides are available here) describes how the Grants Factory at Kent has produced a perfect storm of goodness. The numbers of RCUK grant awards won by Kent are rising while application numbers fall because success rates are going through the roof. They have more than doubled in the four years since the first Grants Factory was organised by Jacqueline Aldridge, who is now research manager at Kent Business School.
The basic principle of the Grants Factory is that experienced academics share their insights with junior colleagues in workshops, master-classes and mock panels. In the inaugural event in 2009, Jacqueline and I developed an approach to writing research grants that was designed to exploit the specific conditions under which funding decisions are made. We describe it in the book, The Research Funding Toolkit, published last year by Sage. More of how it works below.
Grants Factory masterclasses and workshops are designed to improve grant-writing skills but the effect they have on morale is probably just as important. Attendees learn how to respond to referees, write a 'pathways to impact' statement, or calculate a budget. They discover the intricacies of European funding or applying for fellowships. Attendees value what they learn but, more than that, they value the sense that they are being supported by their senior, more experienced colleagues.
The Grants Factory events with the biggest impact on attendees are mock panels. The mock panel teaches you that a research grant application is completely unlike any other piece of academic writing. Its task is to give a committee of people who are expert about, and interested in, other areas of research the confidence that your research is worth the money it will cost to do it. No matter how many times you tell somebody that fact, they don't really get it. However, when they participate in a mock panel, they get it straight away.
A mock panel mimics the events of a grants' committee at high speed. Panel members evaluate draft proposals written by each other. A senior academic, experienced in grants' committee work, chairs the panel. Panellists discover how difficult it is to give a coherent explanation of what research an applicant will do, why it is important and what will be done with the results, on the basis of 30 minutes spent reading their proposal. The realisation that it is even more difficult for a colleague to explain what research you will do after reading your proposal is truly a lightbulb moment.
Once the lightbulb goes on and people realise how hard it is to write a good grant proposal they become eager for the research funding toolkit. Tools in the toolkit help them to write a document that can be speed-read, that is easy to read completely, that is memorable and easy to reconstruct. There are also tools that will convince a grants' committee of the four propositions: importance (of the research problem), success (of the proposed research project), value (of the project) and competence (of the research team). Phil Ward's presentation contains a brilliantly witty pictorial exposition of the main tools and is worth viewing for that alone.
For me though, the best is kept till last. Success rates for RCUK grant applications at Kent have increased from 15% to 35%. Fewer grant applications are being submitted and more grants are being won. That was my dream when I started the first grants factory and that is what HE managers really want!
Phil Ward blogs and tweets about research policy and research funding.


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Communicable Diseases: Clean Hands Are Happy Hands
What is a communicable disease?
A communicable disease is any infectious agent that can be spread from person-to-person or from animal-to-person. These diseases often occur as airborne viruses or bacteria; however, they can be spread through blood or other bodily fluids.
What actions can I take to avoid being infected by a communicable disease?
To reduce your chances of being infected by a communicable disease, it important to take advantage of opportunities to receive vaccinations which will help your body guard against a particular infections disease (Ex: Flu).
Another method that is extremely effective is to wash your hands often. You should wash your hands for at least 20 seconds with warm water and soap and while washing rub your hands vigorously together. Make sure to scrub surfaces under nails and between fingers. You should wash your hands after or before the following situations:
- Before preparing, cooking, and eating food
- After using the restroom
- After blowing your nose
- After touching or handling animals
- Frequently when someone is sick in your house or in your office
After washing your hands, you will want to avoid touching your T-Zone which includes:
- Eyes
- Nose
- Mouth
Here are some other tips for staying healthy and reducing your odds from contracting a communicable disease:
- Get plenty of sleep
- Be physically active
- Manage stress levels
- Drink plenty of water
Also, if you are sick, do NOT come in to work or school as it will result in the zombie apocalypse. Instead, use your sick leave (Employee), or let your professor/instructor know you will be out sick (Student).
For more information about communicable disease and prevention please go to the following websites:
Page last updated 10:17 AM, May 28, 2019


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The Fund's investment objective is to achieve a total return over the medium term (3-5 years) by investing at least 80% in the shares of European companies, not including the UK, listed on European stock exchanges. The Fund's performance target is to outperform the FTSE Europe ex-UK Index (the "Index") over rolling 5-year periods. For further information on the Fund's index, please refer to the Prospectus, available via the fund information section of this website.
Steve Bolton has worked on the European funds since October 2016. Steve joined RLAM in August 2013 following the acquisition of The Co-operative Asset Management by the Royal London Group where he worked as Assistant Fund Manager on the Sustainable funds. Steve previously worked as an Investment Research Analyst covering both equities and investment grade credit. After graduating with a Law degree, Steve became a CFA Charterholder in 2012.
Since joining RLAM in 2014, Sebastien Beguelin has worked on the European funds initially as an Equity Analyst and as Assistant Fund Manager since April 2017. Before joining RLAM, he worked in Paris as an Equity Analyst at Sycomore Asset Management and prior to that was an Equity Analyst at Comgest. Sebastien holds a Bachelor in Economics from the University of Savoy, a Master in Management from the Toulouse Business School in France and is a CFA Charterholder.
The Fund is a balanced portfolio of European companies that the Managers have identified as having growing cashflows. The Managers focus on bottom-up analysis with a top-down risk overlay for portfolio construction. Stock selection is central to the investment process. The Managers utilise a range of internal screens and external sources to identify potential investments, and will typically look to meet with the company prior to investment and regularly afterwards. The Managers prefer businesses with products or services that they believe are able to grow faster than the broader economy, that operate in markets with high barriers to entry, and generate strong cashflows. A range of quantitative risk tools are utilised to monitor factor exposures and ensure consistency with the Managers' macroeconomic views.
Past performance is not a guide to future performance. The value of investments and the income from them is not guaranteed and may go down as well as up and investors may not get back the amount originally invested. For funds that use derivatives, their use may be beneficial, however, they also involve specific risks. Derivatives may alter the economic exposure of a fund over time, causing it to deviate from the performance of the broader market. All rights in the FTSE World Europe ex UK Index (the "Index") vest in FTSE International Limited ("FTSE"). "FTSE®" is a trade mark of the London Stock Exchange Group companies and is used by FTSE under licence. The Royal London European Growth Fund (the " Fund") has been developed solely by Royal London Asset Management. The Index is calculated by FTSE or its agent. FTSE and its licensors are not connected to and do not sponsor, advise, recommend, endorse or promote the Fund and do not accept any liability whatsoever to any person arising out of (a) the use of, reliance on or any error in the Index or (b) investment in or operation of the Fund. FTSE makes no claim, prediction, warranty or representation either as to the results to be obtained from the Fund or the suitability of the Index for the purpose to which it is being put by Royal London Asset Management.
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