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... where visionaries, game changers, and challengers discuss business models
A group for faculty to share syllabi, relevant student reading citations, teaching pedagogy.
Location: University of Massachusetts Lowell
Members: 13
Latest Activity: Mar 22, 2015
Business Design
Manning School of Business
University of Massachusetts Lowell
M.B.A. Program
Fall 2012
Dr. Valerie Kijewski
Course Description: This will be a 'hands-on' course in which the students will identify either a new product to introduce to the market or a business to restructure. You will begin the course by examining existing business models – perhaps for a company for which you now work. You will then be required to develop either a new business model (for a new product) or innovate an existing business model (to restructure a business) in order to create new value for the market. Ultimately, business model innovation is about creating value, choosing which customers will be the targets of that value offering, deciding what activities you can/will do yourself or with whom you will partner, and finally – how you will capture your share of the value you create. Thus your task in this course will be to invent, design, and implement a new business model or challenge and transform old outdated ones. Projects may be either in the for-profit, non-profit, or social entrepreneurship arenas. You must anticipate that much of your effort in this course will be taking place in the field – not the library.
Text: Osterwalder & Pigneur, Business Model Generation, Wiley, 2010.
go to: http://www.businessmodelgeneration.com/book/order
Introduction to Course – the Canvas
Read Osterwalder 14 – 51
Visit: http://www.businessmodelgeneration.com (Visit Hub tab)
Develop an initial canvas for a simple organization of your choice. Due 9/18
The Value Equation
Read: Osterwalder 127-132 (Customer Insights)
Read http://faculty.uml.edu/vkijewski/priceperf.pdf
Watch: http://www.youtube.com/watch?v=s9nbTB33hbg&feature=player_embedded
BM Patterns
Unbundled Pattern: Osterwalder P56ff
Read: Treacy & Wiersema, Customer Intimacy and Other Value Disciplines, Harvard Business Review, Jan/Feb 1993.
Read: Kijewski/Powell, Implementing Value Disciplines (Unpublished)
BM Pattern
Long Tail / Multisided Patterns: Osterwalder
BM Patterns
Free & Open Patterns: Osterwalder
BM Patterns
Slywotzky & Morrison, Profit Patterns, Random House, 1999
Patterns: Value Chain Patterns & Customer Patterns
BM Patterns
Slywotzky & Morrison, Profit Patterns, Random House, 1999
Patterns: Mega Patterns
Student Preliminary Presentations
Make a business model presentation on a business of your choice – be sure to stress the concepts developed to date in the class.
SWOT & Business Model Assess
Osterwalder 200 -231
Prepare a comprehensive SWOT analysis for the Business Model you presented in class on 10/30
Scenario Analysis
Osterwalder 180-189
deGues, Planning as Learning
Ward & Audrey, Dynamic Scenarios
Mason, Future Mapping
Blue Ocean Strategy
Osterwalder 226-231
Kim& Mauborgne, Create New Market Space
Balanced Score Card
Final Presentations
Final Project Presentation
This group does not have any discussions yet.
Valerie. Thanks for your course syllabus. Will have some questions for you.
Suggestions for additions welcomed!
thank you
I am posting my course syllabus for suggestions/comments/discussion . . .
Download at: http://faculty.uml.edu/vkijewski/Business_Design_Syllabus.pdf


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Though not officially recognized as a holiday, May 4th marks "Star Wars Day,"
celebrated by fans of George Lucas' epic science-fiction franchise
Canada and space are a natural fit. - Marc Garneau
Now, young Skywalker... you will die. - The Emperor
For NASA, space is still a high priority. - Dan Quayle
What we need is Star Peace and not Star Wars. - Mikhail Gorbachev
Space ails us moderns: we are sick with space. - Robert Frost
It is the empty space which makes the room useful. - Lao-tzu
I only have two passions: space exploration and hip hop. - Buzz Aldrin
My husband said he needed more space. So I locked him outside. - Roseanne Barr
He had them as spellbound as a room full of Ewoks listening to C-3PO. - Cory Doctorow
Space is almost infinite. As a matter of fact, we think it is infinite. - Dan Quayle
Humor does not diminish the pain - it makes the space around it get bigger. - Allen Klein
Oh my God! Space aliens! Don't eat me! I have a wife and kids. Eat them! - Homer Simpson
If women can be railroad workers in Russia, why can't they fly in space? - Valentina Tereshkova
Great music is as much about the space between the notes as it is about the notes themselves. - Sting
Most whale photos you see show whales in this beautiful blue water - it's almost like space. - Brian Skerry
Don't let negative and toxic people rent space in your head. Raise the rent and kick them out. - Zig Ziglar
Just be yourself, and hopefully they can shape an epic space adventure around exactly who you are. - Chris Pratt
The way you can understand all of the social media is as the creation of a new kind of public space. - Danah Boyd
The larger office, the corner space, the extra window are the teddy bears and tricycles of adult office life. - Willard Gaylin
When walking, you see things that you miss in a motor car or on the train. You give your mind space to ponder. - Tom Hodgkinson
Be ruthless about your calendar - stick to it, hell or high water but create space for unstructured time as well. - Arjun Arora
We're all trying to keep up in this stupid race. But that won't be much fun when we're floating in space. - John Symeou
Hello. I don't believe we have been introduced. R2-D2? A pleasure to meet you. I am C-3PO, Human-Cyborg Relations. - C-3PO
Oh my. Space travel sounds rather perilous. I can assure you they will never get me on one of those dreadful Star Ships. - C-3PO
In most homes, the father is concerned with parking space, the children with outer space, and the mother with closet space. - Evan Esar
The real lover is the man who can thrill you by kissing your forehead or smiling into your eyes or just staring into space. - Marilyn Monroe
As I hurtled through space, one thought kept crossing my mind - every part of this rocket was supplied by the lowest bidder. - John Glenn
The space in a needle's eye is sufficient for two friends, but the whole world is scarcely big enough to hold two enemies. - Solomon Ibn Gabirol
The world, the race, the soul - in space and time the universes,
All bound as is befitting each - all surely going somewhere. - Walt Whitman
Alien Seating
Canada Strikes Back - Saskatchewan Anti-Missile System
Darth Fiddler
Darth Vader Dog
Darth Vader Driveway
Darth Vader Mailbox
Darth Vader Models
Darth VadeHer
Gingerbread Star Wars Walker
Ham Solo
Heineken Meets Star Wars
Luke FloorWalker
May The 4th Be With You
Pirate Star Wars
Star Trek Trike
Star Wars Baby
Star Wars Computer
Star Wars Dog Walk
Star Wars Eggs
Yoda Churchill

subset: commoncrawl


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Monday, January 31, 2011
K & C Come to Play!!
The day we got home from Puerto Rico I could not have been more depressed, it was gloomy and freezing and I had nothing fun to look forward to........and then I got a phone call from Celina and Kristen!! They called to tell me they were going to get tickets and come to Denver the last weekend in January. My awful mood was immediately turned right around! I have been so excited for weeks. So this past weekend they came to visit and it was incredible to see them! We had so much fun eating and talking and laughing. Friday night we went out to dinner in Boulder to a pizza place that was on Man vs Food. (I don't know what our obsessiong with that show is but I would go just about anywhere Adam tells me to) The pizza was huge with giant crust but it was delicious! Saturday we had a lazy morning...late breakfast...and went to get pedicures then to lunch. That night we went into Denver to a famous hamburger place, put our names in and during the wait we went to the Northface store. They were running a special promotion where you could pose in front of a green screen and they would print off your poster.
The restaurant mostly served hamburgers and there was list of about 20 ingredients that you could choose to put on your burger. Mine was a cheeseburger with a fried egg and bacon. Incredible!! It was the Best burger I have ever had! When Ryan was ordering he asked the waiter what he reccomended and he said the peanut butter with a fried egg! He said everyone is always hesistant but ends up loving it......so that's what Ry got. And I was sceptical but it was surprisingly good.
The other perk was the giant cups!
These are our posters, they probably will be framed and hanging in our home next time you come to visit!
I have the best friends and it was good to see them! I'm sad I didn't more pictures but I was so distracted by food and laughing all weekend I just forgot. Thanks so much for coming you two!
Posted by aclark at 11:16 AM 2 comments:
Thursday, January 27, 2011
Time for a Haircut!
For quite a while now I have been wanting to cut my hair, but I have held off because who chops their hair when they're 29 weeks pregnant and not feeling so hot about the way you look to begin with? I just don't care anymore....I love this haircut and I am ready(I think?) . Ryan thinks I should do it and when I saw my engagement picture at my mom's house the other day I thought it was so much more flattering than what I have now. So, what do you think? Should I do it, or will I hate myself weeks later when I have swollen up like a balloon?
Posted by aclark at 9:05 PM 5 comments:
Happy Belated Birthday!
We made it to Colorado a couple weeks ago and we are as settled as we can be. All of our furniture is still in Utah and we can't get it until the first weekend in February. Ryan's birthday was on the 13th (yes I know I am really late posting this) and for his birthday he got a new tv and a messenger bag. Since we have no furniture, we went got some cheap lawn chairs to tide us over. I realized how silly this must have looked to the cable guy when he came to set up our cable and internet, so I made sure he knew that our other furniture was on its way. We can't wait until we can get all of our stuff, but for it's kind of funny. Happy Birthday Ryan!
Posted by aclark at 8:56 PM 1 comment:
Tuesday, January 18, 2011
Puerto Rico continued.....
When Ryan and I first saw the movie Avatar, he told me on the way home that part if it reminded him of a place in Puerto Rico called the Bioluminescent Bay. So, one night around 8pm we went to the marina and got in kayaks and went through a channel that was surrounded by mangrove trees. As we were going through the channel it was pretty dark except whenever the water was disturbed, it glowed. Every time we rowed, the water glowed, if a fish swam by, it glowed. None of it seemed real, it was like a movie. The explanation behind it is there are dinoflagellates in the water that have the same properties as a firefly, so they glow. It's hard to explain in words, and unfortunately cameras can't capture it either but it was one of the coolest experiences of my life!
Posted by aclark at 6:48 PM 4 comments:
Friday, January 14, 2011
Puerto Rico Day 1
After Christmas this year, the whole Clark family headed to Puerto Rico for a little sun and adventure. Ryan lived there a few years ago so he was a pretty good tour guide. To start our trip off Nana, Papa, Sean, Tanner, Matt, Kate, and Averi got delayed in Columbus and weren't able to fly until much later. So, Ryan and I met Nic, Steff, Kendyl, Camryn, and Brooklyn in the airport in San Juan. It was adventure enough just getting our rental cars and finding our way to our house, but in the middle of downtown San Juan on the free way I got a text from Steff, who was behind us in the 14 passenger van, that their brakes and power steering had gone out. Thank heavens they were able to get safely off the freeway and coast into a gas station parking lot! Apparently these belts are supposed to be connected somewhere!! Who knew!
The next day we had wonderful weather and our house was right on the beach, so we spent the morning hanging out and playing on the beach. Here's Sean and Matt.
Nic, Steff, and Kendyl.
Now before I go any further I must say that Steff, Kate and I are all pregnant, so please keep your judgements to a minimum. I'm due April 12, Steff May25 and Kate June 15
(I think these are correct dates, I may be a little off)
Now before I go any further I must say that Steff, Kate and I are all pregnant, so please keep your judgements to a minimum. I'm due April 12, Steff May25 and Kate June 15
(I think these are correct dates, I may be a little off)
Brooklyn played with this coconut all day long throwing it in the ocean and laughing when the tide brought it back up. It was so fun to play with all the little girls on the beach.
Later we wandered around Old San Juan to try to find some where to eat dinner. We found the cutest little pizza place in a plaza with all these cool Christmas lights (Mel was then on a mission to try and find the same lights to take home)
Posted by aclark at 8:47 AM 2 comments:
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From http://www.nswwriterscentre.org.au
The Blake Poetry Prize 2008
$5,000 prize for new national poetry competition on the theme of 'Bliss, blasphemy and belief'
The NSW Writers' Centre is delighted to announce that it is joining the Blake Society, Leichhardt Municipal Council and Wet Ink magazine in sponsoring a new national poetry prize to be known as the Blake Poetry Prize, which calls for entries on the theme of 'Bliss, blasphemy and belief'.
The Chairwoman of the NSW Writers¹ Centre, Máire Sheehan,said: 'The aim of the competition is to give Australian poets another opportunity to achieve national recognition and a financial reward for their efforts.'
This new competition was made possible by the generosity of Leichhardt Municipal Council, which has a strong commitment to supporting the arts, and especially writing through the NSW Writers' Centre.
"This grant of $5,000 continues our longstanding commitment to the NSW Writers' Centre and the development of arts through the written and spoken word," Mayor of Leichhardt Council Cr Alice Murphy said.
The NSW Writers' Centre is pleased to develop this partnership with the Blake Society which awards the annual Blake Prize for Religious Art. Blake Chairman, the Reverend Rod Pattenden, said: 'This exciting new initiative links visual art and literature, and offers new possibilities for poets to explore the nature of spirituality in the twenty-first century.'
Australia's newest literary magazine Wet Ink will join the partnership by providing the judges for the competition and publishing the winner and commended entries in Wet Ink, which is distributed nationally and internationally. Co-managing Editor of Wet Ink, Dominique Wilson, said: 'We are very excited to be part of this important new prize. Wet Ink is dedicated to promoting new writers, and this prize enables us to further support emerging poets through recognising their talents and exposing their work to a broad audience, both within Australia and overseas.'
Download an entry form and conditions at the NSW Writers Centre link above.
Entries close Friday 27 June 2008
Entry fee: $15


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Climbing Trees
There is something magical about climbing a living thing. Sure, clambering up the back of the sofa is okay, but much better to climb up daddy, grappling onto handfuls of shirt and digging toes into any crevasse hoping for traction. This weekend I was happy to have Toddler Harbat forgo her daily summit of Mount Babbo and instead try her hand at arboreal vertical locomotion. This beauty of a live oak has probably entertained thousands of children (and lovesick teenage couples with pocketknives) over its many years.
Were you wondering about the outfit? The Liz Taylor glasses and headwrap that look stuck in limbo between Shriner's tassled hat and Gypsy fortune teller turban? The striped pants with floral shirt that together make your retinas smolder? The red socks because, after all, one does want a hint of color? You can guess who picked out this outfit. Really I think it's the perfect tree-climbing garb because even if she scampered fifty feet up into the canopy like a spider monkey I'd still be able to see that outfit. Hell, they could even see her from space with that traffic cone orange carrot hat. Here then, is the full ensemble as shown by my little spider monkey.


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October 3, 2009
OSK-UOB declares distribution for 3 funds
OSK-UOB Unit Trust Management Berhard (OSK-UOB) has declared interim distribution of 5.666 cents per unit for OSK-UOB Kidsave Trust fund, 5.6275 cents per unit for OSK-UOB Emerging Opportunity fund, and 9.7815 cents per unit for OSK-UOB Smart Treasure fund based on the NAV of the funds on September 30, 2009.
October 2, 2009
Pacific Mutual declares distribution for 5 funds
Pacific Mutual Fund Bhd has declared income distribution of 4 cents per unit for Pacific Premier Fund, 3.3 cents per unit for Pacific Income Fund, 3 cents for Pacific Focus18 Fund, 0.38 cents per unit for Pacific Cash Fund, and 0.1 cents per unit for Pacific Protected Islamic Cash Fund, for the year ending September 30, 2009. These distributions represent a yield of 5.58%, 5.8%, 5.48%, 0.75%, and 0.1% respectively, based on the NAV per unit.
Subscription allocation of AS1M extended
Permodalan Nasional Bhd (PNB) has extended the subscription allocation of AS1M to ethnics group until December 31, 2009. As of September 27, 2009, 2.5 billion units out of 10 billion units have been sold to 165,661 investors.
AS1M is opened for purchased by all Malaysians with 50% quota allocated to Malays, 30% for Chinese, 15% for Indians, and 5% for other ethnic groups.
0 comments Labels News, Unit Trusts
Income distribution for RHB Bonds
RHB Investment Management has declared income distribution of 3.00 cents per unit and 5.00 cents per unit for RHB Islamic Bond and RHB Bond respectively on September 30, 2009
October 1, 2009
PRUequity Income Fund Distribution - 3.18 cents per unit
Prudential Fund Management Berhad (PFMB) declared 3.18 cents per unit distribution for PRUequity income fund. This distribution is equivalent to 5.39% based on the NAV on 28 September 2009.
The fund has charted a YTD return of 26.67% and recorded a return 33.67% since its inception in October 2004. For full press release statement of the distribution news, please click the link here.
September 30, 2009
Why Should You Invest in Amanah Saham 1Malaysia (AS1M)?
Continuing from previous article, we talked about some of the reasons for the poor response to AS1M from the public. Let's look at the reasons again and here's why i think these reasons are not very important deterrent factors for you to invest in AS1M:
September 28, 2009
Top 3 Reasons for Amanah Saham 1Malaysia (AS1M) Poor Response
Amanah Saham 1Malaysia (AS1M), a 10 billion fixed price unit trust fund, launched by Permodalan Nasional Berhad (PNB) in August, has received very poor response from Malaysians. As of current date, the fund is only 30 - 40% sold out, as compared to some other fixed price unit trust funds like ASM and ASW 2020, when the funds were sold out in a matter of hours.
Based on the feedback that I've gathered, here's the top 3 reasons why Malaysians are not responding well to the AS1M fund:
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Impaired Coronary Collateral Growth in the Metabolic Syndrome Is in Part Mediated by Matrix Metalloproteinase 12–Dependent Production of Endostatin and AngiostatinSignificance
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Objective—We have previously shown that transient coronary artery occlusion stimulated coronary collateral growth (CCG) in healthy (Sprague Dawley) but not in metabolic syndrome (JCR:LA-cp [JCR] ) rats. Here, we sought to determine whether matrix metalloproteinases (MMPs) negatively regulate CCG in the metabolic syndrome via release of endostatin and angiostatin.
Approach and Results—Rats underwent transient, repetitive left anterior descending occlusion and resultant myocardial ischemia (RI) for 0 to 10 days. CCG was measured in the collateral-dependent and normal zones using microspheres, MMP activation by Western blot, and endostatin and angiostatin by ELISA on days 0, 3, 6, 9, or 10 of RI. Endostatin and angiostatin were increased in JCR but not in Sprague Dawley rats on days 6 and 9 of RI. Increased endostatin and angiostatin correlated with increased MMP12 (≈4-fold) activation in JCR but not in Sprague Dawley rats on days 6 and 9 of RI. Inhibition of MMP12 in JCR rats nearly completely blocked endostatin (≈85%) and angiostatin (≈90%) generation and significantly improved CCG (collateral-dependent zone flow was ≈66% of normal zone flow versus ≈12% for JCR RI).
Conclusions—Compromised CCG in the metabolic syndrome is, in large part, because of increased MMP12 activation and consequent increased generation of endostatin and angiostatin, which inhibits late-stage collateral remodeling.
Transient repetitive coronary artery occlusion and resultant myocardial ischemia (RI) stimulate adaptive enlargement of preexisting high-resistance arterioles with minimal to no blood flow to conduit arteries in a process termed coronary collateral growth (CCG).1 Well-developed coronary collaterals provide an alternative source of blood supply and can help preserve myocardial function in the setting of total coronary occlusion.1 Clinically, patients with stable angina have decreased incidence of fatal myocardial infarction, which is associated with better developed collateral networks.2 However, the development of collateral networks is severely impaired in patients with metabolic syndrome.3–7 Similarly, CCG is impaired in our metabolic syndrome rat model (JCR:LA-cp or JCR).8 JCR rats mimic the complex pathology of human metabolic syndrome. By 8 weeks of age, the rats develop obesity with fatty liver, insulin resistance with glucose intolerance, complex dyslipidemia (high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein), and vasculopathy characterized by decreased endothelium-dependent and endothelium-independent vasorelaxation and intimal lesions morphologically identical to early atherosclerotic lesions in humans. By 12 weeks of age, JCR rats exhibit wide-spread atherosclerosis and evidence of myocardial and cerebral (micro)infarctions. In addition, like the development of metabolic syndrome and cardiovascular disease in humans, the apparent complexity of the cardiometabolic phenotype exhibited by JCR rats is suspected to be multifactorial and polygenetic in pathogenesis, arising from a combination of environmental and genetic factors.9 Thus, the JCR rat acts as an unparalleled rodent model for the study of CCG in the metabolic syndrome.
Temporally regulated reorganization of the extracellular matrix (ECM) is an integral part of collateral remodeling. First, the ECM acts as a mechanical barrier to the migration of endothelial cells (ECs) and vascular smooth muscle cells, which must be removed to allow for effective cell proliferation and migration in the early stages of CCG then reformed to allow for collateral vessel maturation in the late stages of CCG. In addition, the ECM also acts as a repository for proangiogenic growth factors, such as the vascular endothelial growth factor (VEGF) and the fibroblast growth factor, and for antiangiogenic peptides, such as angiostatin and endostatin. The extent of CCG depends on the balance between the proangiogenic growth factors and the antiangiogenic peptides. Therefore, ECM degradation, through the release of the above-mentioned angiogenic factors, can either promote or impede collateral development.
Angiostatin and endostatin have been negatively associated with coronary collateral development in patients with coronary artery disease10 and type II diabetes mellitus.11 Chronic hyperglycemia was also shown to inhibit CCG via an increase in angiostatin in a dog model.12 Angiostatin is a 38-kDa cleavage product of plasminogen,13 which has been shown to exert its antiangiogenic effects via induction of EC apoptosis14–17 and impairment of EC proliferation,18 migration, and tube formation.19 Endostatin is a 20-kDa cleavage product of collagen XVIII.20 It also functions to induce EC apoptosis thorough multiple signaling pathways21,22 and diminish endothelial cell migration, adhesion, and proliferation.23,24 Targets of angiostatin and endostatin in collateral growth have not been investigated but are presumed to also be ECs.
Several proteases, including matrix metalloproteinases (MMPs), have been shown to be able to generate angiostatin and endostatin by cleavage of plasminogen and collagen XVIII, respectively, in vitro and in cell culture studies. MMP225 and MMP1226 have been shown to release angiostatin in an in vitro model of lung metastasis. MMP12 has also been shown to inhibit microvascular EC proliferation in vitro by generating angiostatin.26,27 MMP3,28 MMP7,29 and MMP929 have been shown to be able to release angiostatin in in vitro studies in which human plasminogen was incubated with various MMPs. In an in vitro assay, MMPs 1, 2, 3, 9, 12, 13, 14, and 20 were able to release endostatin from a fragment of human collagen XVIII.30 One study showed that MMP12 releases endostatin to inhibit VEGF-induced chemotaxis of osteoclasts.31 Very little is known about MMP8 and its ECM substrates; however, the other 2 collagenases, MMP1 and MMP13, have been shown to generate endostatin in in vitro assays.30 The ability of these MMPs to generate these antiangiogenic peptides in vivo, especially during collateral development, has not been evaluated. MMP2 and MMP9 are the only MMPs that have been studied in collateral growth. One study correlated their increased expression with actively remodeling collaterals.32 However, their decreased activation has been correlated with decreased CCG in humans with type II diabetes mellitus.11 Furthermore, we have recently definitively shown that they are required for CCG and that they are not activated in metabolic syndrome,33 and several studies demonstrated lack of correlation between increased angiostatin and endostatin levels and increased MMP2 or MMP9 activation in humans with impaired CCG,10,11 suggesting that MMP2 and MMP9 are not the MMPs responsible for the generation of angiostatin and endostatin associated with decreased coronary collateral development. The role of the other members of the MMP family has not been studied in association with collateral development. Moreover, it is not known whether their activation is altered in metabolic syndrome.
Our results in this study demonstrated that elevated angiostatin and endostatin levels in the metabolic syndrome rat model (JCR) correlated with enhanced MMP12 and MMP8 activation. Therefore, the goal of this study was to determine whether MMP12 and MMP8 were involved in the corruption of CCG in the metabolic syndrome via upregulation of angiostatin and endostatin in the later stages of CCG.
Materials and Methods
Materials and Methods are available in the online-only Supplement.
MMP12 and MMP8 Activation Is Increased in the Later Stages of CCG in the Metabolic Syndrome but not in the Normal Rat Model
Of the MMPs which have been shown to be able to generate angiostatin and endostatin in in vitro or cell culture studies, MMPs 1, 2, 3, 9, 12, 13, and 14, we have found MMPs 2, 9, and 14 (membrane type 1-MMP) to be activated in response to RI and required for CCG in the normal rat phenotype (Sprague Dawley [SD] rat33; Figure I in the online-only Data Supplement). Importantly, of these MMPs, we have found only MMP12 to be activated in the metabolic syndrome (JCR) rats in response to RI. Moreover, in our screen of MMPs, which are known to be expressed in the cardiovascular system,34 by expression of the pro and active forms of the MMP proteins, we have found only 1 additional MMP to be activated in response to RI, MMP8 (Figure 1; Figure I in the online-only Data Supplement).
Basal MMP12 expression was ≈2-fold higher in the JCR phenotype; however, there was no difference in its basal activation between the 2 phenotypes. RI resulted in a significant increase in pro-MMP12 on day 3 of RI in the SD rats (≈5-fold), but this did not translate into an increase in its activation on any day of the RI protocol in the SD animals. Pro-MMP12 was also increased in the JCR rats on days 3 (≈3-fold), 6 (≈5-fold), and 9 (≈5-fold) of RI. However, in contrast to the SD rats, MMP12 was also highly activated beginning at day 6 of RI (≈4-fold versus baseline) in the JCR animals. This activation remained sustained for the duration of the RI protocol (Figure 1A). Increased RI-induced MMP12 expression and activation in the heart did not translate into increased RI-induced MMP12 expression or activation in the plasma of JCR rats (Figure III in the online-only Data Supplement). Basal expression of MMP8 was ≈2-fold higher in the JCR animals; however, RI did not significantly alter MMP8 expression in either phenotype. MMP8 activity was increased ≈2-fold on day 3 of the RI protocol in the SD rat. In the JCR rat, MMP8 activation was greater in magnitude and the timing of activation was shifted from the early to the later staged of CCG. MMP8 was maximally activated on days 6 (≈4-fold) and 9 (≈3-fold) of RI (Figure 1B). All changes were observed in the collateral-dependent zone (CZ) only. RI did not induce any changes in MMP12 or MMP8 expression or activation in the normal zone (Figure 3; data not shown)
Elevated Myocardial Angiostatin and Endostatin Levels in the Later Stages of CCG in the Metabolic Syndrome Correlate With Increased MMP12 and MMP8 Activation
Basal angiostatin and endostatin levels were similar between the 2 phenotypes. RI did not alter either angiostatin or endostatin in the CZ of the SD rats. In contrast, both angiostatin and endostatin levels were markedly upregulated on days 6 (≈3-fold and 2-fold, respectively) and 9 (≈2-fold and 2-fold, respectively) of RI in the CZ of the JCR rats. Because the angiostatin and endostatin fragments are inaccessible to the respective antibodies within the tertiary structures of intact plasminogen and collagen XVIII in the ELIZA assays, the observed increases specifically represent cleaved angiostatin and endostatin. Neither endostatin nor angiostatin was altered by RI in the normal zone of either rat phenotype (Figure 2A and 2B). Thus, increased angiostatin and endostatin levels correlate with the increased activation of MMP8 and MMP12 in the later stages of CCG in the metabolic syndrome animals.
To determine whether the concentrations of angiostatin and endostatin generated by RI in JCR rats induced the classical endothelium-specific antiangiogenic effects of these peptides, we examined whether they decreased VEGF-induced human coronary artery endothelial cells proliferation and survival. Although neither angiostatin (750 pg/mL) nor endostatin (1000 pg/mL) alone was able to significantly decrease the VEGF-induced increase in human coronary artery endothelial cells number or survival (data not shown), results in Figure 2C demonstrate that their combined effect on both parameters was significant.
Inhibition of MMP12 Activation Decreased Myocardial Endostatin and Angiostatin Levels and Partially Restored Coronary Collateral Growth in the Metabolic Syndrome
To determine whether MMP12 activation alone was responsible for the increased level of angiostatin and endostatin in response to RI in the metabolic syndrome, JCR rats were treated with the specific MMP12 inhibitor (3.5 mg/kg per day, 1/d, IP) on days 6 to 9 of the RI protocol. Complete inhibition of MMP12 activation was confirmed by Western blot analysis of the active (molecular weight=22 kDa) MMP12 band (Figure 3A). MMP12 expression was not affected. MMP8 activation was not affected (Figure 3A) confirming the specificity of the inhibitor. MMP12 inhibition resulted in a significant reduction in both endostatin and angiostatin levels (85% and 90%, respectively) at day 10 of RI (Figure 3B). Moreover, inhibition of MMP12 partially restored CCG in JCR rat as evident by increased artery/arteriolar density (≈2 50 µm arteries/mm2 versus ≈1 20 µm arteriole/mm2 in JCR RI versus ≈3 60 µm arteries/mm2 in SD RI) and increased collateral-dependent flow (CZ/normal zone flow ratio was 0.66±0.05 versus 0.12±0.02 in JCR RI versus 0.87±0.04 in SD RI)33 and completely restored RI-dependent angiogenesis as indicated by an increase in capillary density equivalent to that observed in normal animals (Figures 3C and 5). Nearly identical results were obtained when MMP12 expression was decreased (≈80%) using shRNA, delivered to JCR rats via a lentiviral vector (Figure 3). Control-Lnv, carrying a nontargeting shRNA, had no effect (data not shown).
To determine whether additional inhibition of MMP8 would have an additional beneficial effect on CCG in the metabolic syndrome, in addition to the specific MMP12 inhibitor to inhibit MMP12 activity, we used the MMP8 inhibitor (0.25 mg/kg per day, 1/d, IV) to inhibit MMP8 activity at days 6 to 9 of RI in JCR rats. The MMP8 inhibitor may inhibit the other collagenases, MMP1 and MMP13, at similar doses; however, because neither MMP1 nor MMP13 is activated at these time points in the JCR rat (Figure I in the online-only Data Supplement), the nonspecific effects on the other collagenases were not a concern. The collagenase inhibitor successfully and completely inhibited MMP8 activation without effecting MMP8 expression and did not alter the effectiveness of the MMP12 inhibitor on MMP12 activity (Figure 4A). Concomitant inhibition of MMP12 and MMP8 resulted in a slightly greater but statistically insignificant reduction in endostatin levels (90% versus 85% with MMP12 inhibition alone), whereas the extent of reduction in angiostatin levels remained unchanged (Figure 4B). The additional inhibition of MMP8 likewise did not have any greater effect on CCG recovery or angiogenesis than MMP12 inhibition alone (CZ/normal zone flow ratio was 0.62±0.08; Figure 4C).
To confirm that MMP12 but not MMP8 plays the major role in the regulation of angiostatin and endostatin production and CCG in metabolic syndrome, we also inhibited MMP8 alone. Complete inhibition of MMP8 activation had no effect on RI-induced angiostatin or endostatin production (Figure 4B), CCG or angiogenesis in JCR rats (Figure 4C).
Angiostatin and Endostatin Infusion Decreased Coronary Collateral Growth in Normal Animals
Finally, we tested the effect of the amounts of angiostatin and endostatin produced in the JCR rats on CCG in the normal animals to provide proof-of-concept and examine the physiological relevance of these amounts. Infusion of 750 pg/mL per day angiostatin and 1000 pg/mL per day endostatin (days, 0–10 or 6–9 of RI) moderately but significantly decreased RI-induced angiogenesis and CCG in SD rats, while having predictably no effect on preexisting collaterals and capillary networks (Figure 5). These results suggest that angiostatin and endostatin amounts produced in JCR rats are physiologically significant. The caveat to these conclusions is that ECs of SD rats are normal, whereas JCR rats display marked endothelial dysfunction9; thus, these antiangiogenic peptides would be predicted to more severely impact the already apoptosis-prone JCR ECs.
The most important novel findings of this study are that (1) MMP12 and MMP8 are differentially regulated in the normal versus the metabolic syndrome phenotype during the process of CCG; (2) the temporal pattern of MMP12 and MMP8 activation in the later stages of CCG correlates with elevated levels of angiostatin and endostatin in the metabolic syndrome; and (3) inhibition of MMP12 but not MMP8 activation blocks RI-induced generation of angiostatin and endostatin and significantly improves CCG in the metabolic syndrome.
Proteolysis of ECM and plasma proteins is a common theme in inhibition of angiogenesis. Many inhibitors of tumor angiogenesis, such as angiostatin, endostatin, serpin antithrombin, tumstatin, canstatin, vasostatin, restin, and arrestin, are proteolytic fragments.20,35–43 Of these, angiostatin and endostatin have been investigated in collateral growth. Results in our study demonstrating elevated levels of angiostatin and endostatin during the later stages of repetitive ischemia in the metabolic syndrome are in agreement with previous studies which showed that these antiangiogenic peptides were increased in hyperglycemic dogs with impaired CCG during the later stages of repetitive ischemia12 and in humans with type II diabetes mellitus and impaired coronary collateral development.10,11
The mechanism by which angiostatin and endostatin inhibit collateral growth has not been investigated, but is inferred from a related process of tumor angiogenesis. It has been shown that angiostatin directly targets only EC proliferation and survival and does not affect either tumor cells or other cells of non-endothelial origin in vitro.44 In agreement with these findings, results in this study show that the concentrations of angiostatin and endostatin generated in the metabolic syndrome animals can suppress EC proliferation and survival. It was shown that angiostatin directly induces apoptosis of ECs without a compensatory increase in proliferation, resulting in a net reduction of viable ECs via altering focal adhesion kinase signaling and disrupting normal focal adhesion turnover.45,46 Second, angiostatin directly reduces EC migration, proliferation, and tube formation by inhibiting fibroblast growth factor–dependent and VEGF-dependent extracellular signal–regulated protein kinases 1 and 2 activation.47 Finally, angiostatin may mediate its antiangiogenic effects by binding to the cell surface ATP synthase and depriving ECs of ATP.15 Like angiostatin, endostatin does not affect the in vitro proliferation of tumor cells nor other non-endothelial cell lines; thus, its actions seem to be EC specific.20,21 Endostatin increases EC apoptosis by reducing the expression of antiapoptotic proteins, Bcl-2 and Bcl-XL,21 and by inducing Caspase 3 activation.48 Furthermore, endostatin inhibited extracellular signal–regulated protein kinases 1 and 2 phosphorylation in VEGF-stimulated and fibroblast growth factor–stimulated primary arterial EC cultures without interfering with growth factor receptor binding.49 Our unpublished observations suggest that extracellular signal–regulated protein kinases 1 and 2 activation is also impaired in the metabolic syndrome during CCG (P. Rocic, unpublished data, 2008).
MMPs, non-MMP elastases, and plasmin are capable of generating angiostatin from plasminogen, whereas a wide variety of MMPs are able to generate endostatin from collagen XVIII. Of the possible candidates relevant to the cardiovascular system, our results show that only MMP12 and MMP8 activation correlates with increased levels of angiostatin and endostatin in the later stages of CCG in metabolic syndrome. Our findings further indicate that MMP12 is the primary regulator of angiostatin and endostatin in the metabolic syndrome because its inhibition alone was sufficient to completely block their generation; additional inhibition of MMP8 had no further effect and MMP8 inhibition alone likewise had no effect. MMP12 has extensive activity against elastin but is also capable of degrading proteoglycans, fibronectin, laminin, nonfibrilar collagen, including collagen XVIII, heparin sulfate, plasminogen, and vitronectin. Importantly, it has been shown to be antiangiogenic in several studies in cancer angiogenesis. MMP12 was decreased in breast carcinoma compared with normal mammary cells, and these breast carcinoma lines were more efficient in capillary tube formation than the normal mammary cells.50 Decreased MMP12 expression correlated with decreased expression of angiostatin.51 MMP12 was also able to generate angiostatin from purified plasminogen in vitro27 and in an in vitro model of lung metastasis.26 MMP12 has also been shown to inhibit microvascular endothelial cell proliferation in vitro by generating angiostatin.26,27 One study showed that MMP12 can release endostatin, which inhibited VEGF-induced chemotaxis of osteoclasts.31
Not much is known about MMP8. Its role in collateral growth or angiogenesis is completely unknown, as are its substrates. However, MMP8 belongs to the family of interstitial collagenases, which in the cardiovascular system includes MMP1 and MMP13, and its active site is structurally identical to that of MMP1 and MMP13. Neither MMP1 nor MMP13 is activated during coronary collateral remodeling in either the normal or the metabolic syndrome rat phenotype. Thus, it is reasonable to propose that MMP8 may be the representative active interstitial collagenase under these circumstances. Interstitial collagenases cleave collagen types I and III, which are components of the myocardial interstitium and vascular adventitia. MMP1 has been shown to suppress angiogenesis in sarcoma; its silencing significantly increased mean vascular volume per unit volume of tumor.52 MMP13 has been found to have a direct role in the formation of endostatin. Because both MMP1 and MMP13 share the collagen XVIII cleavage site, MMP1 was also thought to mediate its antiangiogenic effects via endostatin production.52
Paradoxically, many of the same proteases that release antiangiogenic peptides are also capable of releasing proangiogenic growth factors and stimulate angiogenesis. For example, plasmin mediates cell invasion into neighboring tissues, which requires angiogenesis.53,54 MMP1 effectively releases proangiogenic growth factors, VEGF and fibroblast growth factor, from the ECM.55,56 This is interesting because in our study, in addition to being activated late in CCG in the metabolic syndrome animals, which fail to grow collaterals, MMP8 was also activated early during CCG in the normal animals. Thus, our data suggest that MMP8 may play a differential role in CCG in normal versus the metabolic syndrome phenotype. Depending on the timing of its activation, it may release either proangiogenic growth factors from their binding proteins in the ECM (early in CCG) or antiangiogenic peptides (late in CCG). The extent of collateral growth is determined by the balance of the proangiogenic growth factors and antiangiogenic peptides. Therefore, our results in this study further support the concept that ECM proteolysis within the context of collateral growth is a temporally tightly regulated process, which can be profoundly affected by the temporal regulation of MMPs.
Regarding the possible cause of the later and sustained increase in MMP8 activation in the metabolic syndrome, MMP8 is a neutrophil collagenase (collagenase-2). Although transient accumulation of a low number of neutrophils and other inflammatory cells early in collateral growth has been associated with beneficial effects on collateral remodeling,57 prolonged or excessive neutrophil accumulation and inflammation that characterize the vasculature of type II diabetes mellitus and metabolic syndrome are strongly negatively correlated with CCG.58,59 Also, increases in the expression, activation, and collagenase activity of MMP8 and MMP13 have been shown in response to angiotensin II administration.60 We have previously shown that infusion of a hypertensive dose of angiotensin II negatively affected collateral growth. Moreover and explicitly relevant to the scenario in the current study, angiotensin II type I receptor levels are increased in JCR rats and angiotensin II type I receptor blockade partially but significantly restored CCG in the JCR rat.61 Another possibility is that MMP8 upregulation in the late stages of CCG in metabolic syndrome may serve some other as of yet unknown function or be coincidental.
Our results suggest that increased angiostatin and endostatin production provide a very substantial impediment to coronary collateral development in the metabolic syndrome because their downregulation results in ≈65% recovery of coronary blood flow to the CZ. Upstream regulators of MMP12 activation in collateral growth are not known. The mechanisms responsible for impaired collateral remodeling in the metabolic syndrome have not been completely elucidated, but involve increased oxidative stress and altered redox-dependent signaling,8,62 which might provide an upstream activation mechanism. All MMPs have a disulfide bond in their hinge region,63 which makes them directly susceptible to oxidation by reactive oxygen species, which results in their activation.63,64 We have previously shown that oxidative stress is highly elevated in response to RI in the metabolic syndrome and that reduction in oxidative stress significantly improved CCG in the metabolic syndrome.8,62 Results in the present study are compatible with the idea that observed recovery of CCG in response to oxidative stress reduction was, in part, because of the downstream inhibition of MMP12 activation and the consequent decrease in angiostatin and endostatin generation.
A limitation of our study inherent to the rat model of coronary occlusion, where it is not possible to isolate collateral vessels from the heart tissue, is that we did not determine the cellular source of the active MMPs in this study. The most likely sources of both MMP12 and MMP8 are inflammatory cells, specifically macrophages and neutrophils. Metabolic syndrome is a chronic proinflammatory state, where the vasculature is characterized by increased infiltration of neutrophils and monocytes, and increased adhesion and extravasation of inflammatory cells into the vascular wall.65,66 The infiltration of inflamatory cells, especially neutrophils and monocytes, is a normal and required component of collateral remodeling,57 which further increases the total number of these cells in and around the forming collaterals in the metabolic syndrome. Our findings are consistent with the idea that these highly elevated numbers of neutrophils, adherent monocytes, and extravasated tissue macrophages in the metabolic syndrome result in the release of high levels of MMP12 and MMP8, which lead to generation of high levels of angiostatin and endostatin, which are sufficient to significantly contribute to collateral growth impairment in the metabolic syndrome. However, endothelial cells50,67 and vascular smooth muscle cells68 have also been shown to be able to secrete MMP12; therefore, other cell types cannot be excluded as possible contributors to the production of these MMPs. Our results showing ≈2-fold higher basal MMP12 activation in the plasma of JCR rats are also intriguing. This may be largely a consequence of adipose tissue macrophage-mediated MMP12 production.69 Although clearly not a consequence of cardiac repetitive ischemia and probably of little predictive value within the context of coronary collateral growth, the contributing value of this factor to impaired CCG in metabolic syndrome is difficult to predict.
Sources of Funding
This work was supported by National Institutes of Health grant R01 HL093052.
The online-only Data Supplement is available with this article at http://atvb.ahajournals.org/lookup/suppl/doi:10.1161/ATVBAHA.113.301533/-/DC1.
- Received May 14, 2012.
- Accepted April 1, 2013.
- © 2013 American Heart Association, Inc.
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This study identifies matrix metalloproteinase (MMP)-12 as a novel positive regulator of angiostatin and endostatin production, which inhibits coronary collateral development in a rat model of metabolic syndrome. Inhibition of MMP12 activation significantly improved coronary collateral development in the metabolic syndrome animals, thus characterizing MMP12 as a potentially important target for revascularization therapy through collateral growth. Furthermore, this study catalogues MMPs that are activated during coronary collateral remodeling in metabolic syndrome versus the normal phenotype, thus identifying targets for future investigation.
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- Impaired Coronary Collateral Growth in the Metabolic Syndrome Is in Part Mediated by Matrix Metalloproteinase 12–Dependent Production of Endostatin and AngiostatinSignificanceTracy Dodd, Luke Wiggins, Rebecca Hutcheson, Erika Smith, Alla Musiyenko, Brenda Hysell, James C. Russell and Petra RocicArteriosclerosis, Thrombosis, and Vascular Biology. 2013;33:1339-1349, originally published May 15, 2013https://doi.org/10.1161/ATVBAHA.113.301533
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- Impaired Coronary Collateral Growth in the Metabolic Syndrome Is in Part Mediated by Matrix Metalloproteinase 12–Dependent Production of Endostatin and AngiostatinSignificanceTracy Dodd, Luke Wiggins, Rebecca Hutcheson, Erika Smith, Alla Musiyenko, Brenda Hysell, James C. Russell and Petra RocicArteriosclerosis, Thrombosis, and Vascular Biology. 2013;33:1339-1349, originally published May 15, 2013https://doi.org/10.1161/ATVBAHA.113.301533


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* Always check the full terms & conditions on the betting website Switch Odds type: percentage / example / decimal
Stats for the AT and EoU as they've appeared on Tipify
A list of recent matches this team has played, green indicates a win and red a loss. Blue is a draw/cancelled
This game is a BO3 in the dingit cup, I think that says it all really. The cup notorious with throws, and dodgy results and I would not at all be surprised if this was another one. I do think AT are the better side, but I think EoU can be strange sometimes, especially z4pper, and I would not trust betting against him or his side. Both teams are honestly not in the best form right now, but with this being the dingit cup, with bad odds, and one side dodgy sometimes, the ONLY thing you should be doing with a game like this, is skipping it and saving your skins for a much more fruitful game. The only thing games like this will do is take your skins unless you are lucky.
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In 1982 I was 19 years old and living in Monaghan Town. I was sexually active but at that time it was illegal for people in the Irish Republic to get the contraceptive pill or even durex. So I became pregnant. I wanted to keep my baby, but my mother who had her 'image' to uphold demanded that I get rid of my child. I had never even heard of abortion back then, but my mother was insistent that I would get rid of my unborn baby.
My mother and father drove to Emyvale in north Monaghan to the home of the lad they thought had got me pregnant and they demanded that he pay for me to travel to England to get rid of my unborn baby. The lad said it was not his baby, which was probably true, and my parents went to his sister and demanded they pay for my abortion.
My mother said she could not afford to pay for me to travel to England as she had her 25th Wedding anniversary that year, and she did not want the neighbours to know that I was pregnant outside of marriage, I would later learn that my Mother had in fact been pregnant when she married my father, still plenty of hypocrites in Ireland.
I continued to insist that I would not kill my unborn baby, however, my mother who continues to hug the altar rails in St Maccartan's Cathedral every Sunday morning insisted that her grandchild would be disposed of or I would be thrown out of the family home where I lived.
Eventually I was put on the boat to England and my Mother had made an appointment for me at one of the abortion clinics over there. I was booked into a seedy bed and breakfast that was full of drunks and drug addicts; this suited my mother, as it was cheap.
When I went to the Clinic I was very scared. I was treated like an animal, I seen young girls coming out crying and their mothers telling them it was for the best. Eventually my name was called and I was taken into a room that had a leatherette bench covered in tissue paper, two stirrups were hanging from the ceiling and an array of surgical tools were laid out on a stainless steel table.
I was told to remove my clothes as two male and one female in white coats moved about the room, I was given a white paper gown to put on. I felt naked, embarrassed and scared.
I was told to get onto the bench, as I did I noticed the large black plastic bucket full of water at the end of the bench, I was so ashamed and scared, but I felt I had no choice, my Church going mother would throw me out if I did not do this terrible thing.
I was given an injection in the top of my leg and my legs placed in the stirrups. I was awake as the doctor placed long stainless steel scissors inside my womb, I could feel cutting motions inside my body, I had no real idea what was happening. The female then placed a vacuum type thing against my virgina and I could hear stuff being sucked from my body. The male doctor them used clamps to remove something from inside my body, I then seen the tiny head and torso of my baby son as they placed his dismembered body into the bucket of water to ensure he would breath no more.
I have never recovered from this horrible ordeal, I can still hear the faint cries, I think that's what I heard. I hate my mother and father for what they forced me to do, I will never recover and I hate those 'feminists' who say it is a woman's choice, it is not a choice for many thousands of young girls who are forced by their hypocrite parents to murder their unborn children each year. It is obvious that these women have never been forced to undergo this murderous procedure or they would have a real understanding that abortion is a tool of oppression and not a tool of liberation for women.
It is worth mentioning that in Ireland in 1982 anyone assisting in the unlawful destruction of an unborn child could face Life in prison under the 1821 Offences Against The Person Act, however, my Mother and Father have never been prosecuted, they are not the only ones to have committed such heinous crimes and I guess they won't be the last.
by Nichol marie2 years ago
Should abortion be illegal?How are your feelings about abortion about legality, I don't.agree but should be a choice,what do you think?
by Peter Leeper5 years ago
What does an unborn baby dream about?
by Tom Cornett7 years ago
Because.....If liberal progressives are for abortion and gay marriage, then it makes sense that mostly progressive liberals will most often enact those rights...far more than conservatives.Which means...there will be...
by theirishobserver.7 years ago
We have been told time and again that unborn babies under 24 weeks have no chance of survival and so the legal limit in the UK for killing an unborn child is 24 weeks - however - we know from the story below that the 24...
by Jackie Lynnley20 months ago
I read this was true and I just have to know if it is, please! Please provide links to prove what you say. Surely we are not going to be aborting babies ready to come into the world fully developed and healthy?
by peter453 years ago
how can i terminate a 6 weeks old pregnancy?
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Finding the Right Medical Education Conference for you
Attending Continuing Medical Education Conferences
When we think of a conference we often associate it with a few hours of travel to sit in a small boardroom or audio-visual theatre and enjoy a 4-8 hour, or even a full day, of lecture from experts in our field. We then either take an exam for evaluation purposes or complete worksheets before it's all over. But nowadays, especially for continuing medical education conferences, physicians and nurses have a lot of choices to choose from in order to acquire their CME credit requirements for the year.
There are a variety of options for medical professionals who are required to attend an annual conference, they can choose to participate in the traditional continuing medical education conference, or they can choose to enjoy a continuing medication education cruise or vacation. They can even attain CME credit-hours in the comfort of their home through interactive online CME conference programs.
Combining a Vacation with your Continuing Education
Just imagine going to Disney land in order to gain CME credits. It's a fun way of learning and maintaining your license right? But continuing medical education conferences of these types usually go on for only half a day in a conference room, and then you can enjoy the location and tour around for the other half of the day. Talk about hitting two birds with one stone right? You can even bring your family and have a nice long vacation together. But, of course you can only be with them in the afternoon as the conferences are typically held in the morning to early afternoon.
Some Great Vacation Style CME Cruises we have Listed are:
- The 16th Annual Renaissance in Primary Care- Alaska Cruise on July 15, 2012
- A French Waterways River Cruise – Healthcare in Southern France on October 18, 2012
- The Galapagos CME Cruise on Oct 12, 2012
- And more…
Finding the Latest Continuing Medical Education conferences around the world is easy, just head to our homepage and browse or search. We list the organization that sponsor the conference, the topic at hand or the title of the conference, the CME credits that will be awarded to you, the registration fee of course and if applicable recreation activities that you can enjoy while on the conference. Most websites of these types are updated daily, others weekly so you can be sure that you are updated on the latest CME conferences not only in your state or in your country, but around the globe. A few of them even publish journals to those who eventually become a member of their group. All you have to do is search for your medical field and the dates you can attend in order to find for more information on conferences and their organizations.
Whatever method of learning you choose to complete your CME requirement for the year, whether you choose live conferences, audio, online, PDA, print, video and other means to learn, what is important is that you understand the topic and know how to apply your learning to your profession. Don't forget to network with other doctors during your continuing medical education conferences too, you never know what you can learn from your peers.
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Each soldier tells a story.
An elegant gravestone in St Mark's Cemetery in Niagara-on-the-Lake marks the final resting place of Earnest J Saunders, 109th Battalion in the Canadian Militia. WW1 personnel records show an Ernest John Saunders served with the non-permanent active militia.
Saunders was born in London, England on 4 January 1879. He worked in the canteen at Niagara Camp, and died of pneumonia in the hospital there on 17 February 1919. Continue reading


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Reto Thüring Curator of Contemporary ArtNalani Dowling Director's Fellow, Summer 2017
Heather Lemonedes Chief Curator
Wadsworth Jarrell (American, b. 1929)
acrylic, metal foil, cotton canvas, Overall: 120.7 x 76.2 cm (47 1/2 x 30 in.). Severance and Greta Millikin Purchase Fund 2016.268
Jarrell became internationally known in the early 1970s as a founder and leading figure of AfriCOBRA (African Commune of Bad Relevant Artists), an artist collective founded in Chicago in the late 1960s that was heavily tied to the Black Arts Movement, the aesthetic branch of the Black Power movement of the 1960s and '70s. This painting shows two jazz musicians exuberantly playing their instruments; their bodies are composed of letters and dots of color with phrases like African Rhythm Our Heritage and Black Funk emerging from the vibrant composition. With vivid colors, the prominent use of language, the integration of collage elements, and the explicit references to the identifying character of jazz music for African American culture, Heritage contains the most crucial aspects of the artist's signature style.
The Cleveland Museum of Art (11/21/2017-02/25/2018): "Heritage: Wadsworth and Jae Jarrell"
To request more information about this object, study images, or bibliography, contact the Ingalls Library Reference Desk.


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Take my heart. Come beam it up. Never let this feeling stop. Drop, your
Love on me. Girl I love you, Can't you see?
You're in my head, you're in my mind. A Love like hers is hard to find.
Girl you're my shining star. Sweet, that's what you are.
Help me make it through the night. Be my lover, be my life. Stay with me,
And feel the heat, Girl, you're all I need.
Fear no fighting, fear no force, never let us get divorced Ooh, I feel so
Fine. Yeah, Gonna make you mine.
Gonna make you mine. Do it right in time . Let me take you anyway forever.
(2x) Gonna make you mine. Do it right in time.(2x)
Anyway forever.
I dream of you. Oh yes, it's true. Without your love I'm feeling blue.
This is our night. Tonight's the night.
Celebrating yours with candle lights I can't be holding back for love You
Must be sent from high above
And if you think that dissipates. No you break. I'm hungry for the words
You say Can't wait in vain for another day
Call anytime and I'll be there. I'll always love you yes I swear. The
Rhythm of my heart beats fast. Forever, Our love will last.
I'm feeling fine Yeah, gonna make you mine.


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Awards Honor Navy Petty Officer Third Class Chiarini for his life saving actions
WALLINGFORD, Conn.--(BUSINESS WIRE)--Apr 2, 2012-- Z-Medica(R) Corporation, a medical device company which develops and distributes innovative hemostatic agents, announced today that the office of U.S.
Senator Jack Reed (D-RI) presented Navy Petty Officer Third Class Joshua Chiarini with Z-Medica's Thomas "Doc" Eagles and Francis X.
Hursey awards. The awards were given in recognition for Chiarini's heroic and life-saving actions as a medic with the 1st Platoon, 2nd Marine Division in Iraq and his current role as an EMT/firefighter in West Greenwich, RI.
The Thomas "Doc" Eagles award is named for a highly decorated Navy Corpsman who served in Vietnam and is responsible for the development of the new Marine Corps Individual First Aid Kit (IFAK), carried by every warfighter deployed by the U.S. Military, which includes QuikClot Combat Gauze(R). The Award is given annually to "the warfighter who puts the care of others above all consideration of self." The Francis X. Hursey Award is named for Z-Medica's founder and the inventor of QuikClot(R) and is given to the civilian first responder who best exemplifies Z-Medica's creed: "The Greatest Privilege is to Make a Difference(R)." As a medic on his third tour of duty in Iraq, Chiarini rescued numerous injured Marines during a convoy ambush where he placed himself in the line of fire while simultaneously providing medical aid. After a roadside explosive hit the first vehicle in his unit's convoy and another explosion went off near a group of Marines and their interpreter, Chiarini stepped in to bring the injured to safety, applying QuikClot to treat bleeding wounds and stabilize the injured, all the while returning fire and continuing to defend his comrades until reinforcements arrived. Chiarini's actions helped lead each Marine to safety that day.
This was not the only mission that placed Chiarini in harm's way. His team was repeatedly fired on by snipers while thirty (30) of the convoys he rode in were struck by roadside bombs and three suicide bombers. The constant danger makes it all the more impressive that due to his bravery and battlefield medical expertise that of the 100 Marines he treated in theater, none lost their lives. For "Gallantry in Action," Joshua was awarded The Silver Star, the U.S. Military's third highest combat decoration, in October of 2007.
Currently a fire arms instructor in Middletown, RI, Chiarini includes QuikClot as part of the tactical trauma and rescue medical training he provides to law enforcement and military service members.
"As a Navy Hospital Corpsman, Petty Officer Third Class Joshua Chiarini is part of a rare breed of individuals who consistently risk their lives to save others. In wartime and peacetime, at home or abroad, Petty Officer Chiarini has answered the call. His uncommon courage and dedication to duty on the battlefield earned him a Silver Star, and his service as an EMT/firefighter in West Greenwich has earned him the gratitude of his fellow citizens. On behalf of Rhode Islanders, I salute Petty Officer Chiarini and his fellow Hospital Corpsmen," said Senator Reed.
"We have never awarded both awards to the same individual before, but when we learned of Joshua's amazing courage and all of the lives he has saved using QuikClot both on the battlefield and at home, we realized that he was the perfect candidate to receive both," said Bart Gullong, Founder and Chief Executive Officer of Z-Medica. "At Z-Medica we are focused on helping to ensure that heroes like Joshua have access to QuikClot, a life-saving innovation designed to stop hemorrhagic bleeding no matter where it occurs, on the battlefield, by first responders and in the hospital environment." About Z-Medica(R) Z-Medica Corporation is a medical device company developing innovative hemostatic agents. Their mission is to develop fast acting, easy to use, hemostasis products that stop bleeding wherever it occurs, enabling their customers to save lives and improve patient outcomes.
The company manufactures and markets its QuikClot family of hemostasis products for use by healthcare professionals, first responders, law enforcement officers and the military. QuikClot products rapidly enhance the body's natural coagulation process, helping to achieve hemostasis rapidly.
Based on tests conducted by the Naval Medical Research Center and the U.S. Army Institute for Surgical Research, the Committee on Tactical Combat Casualty Care (CoTCCC) recommended QuikClot Combat Gauze as the hemostatic agent for the Department of Defense, used by all U.S.
Military Forces as the first line treatment of hemorrhage. QuikClot products are also widely used by first responders, in hospital emergency rooms, interventional cardiology and radiology laboratories and other healthcare environments where bleeding requires fast and effective control. Z-Medica is a privately-held company based in Wallingford, CT. More information about Z-Medica Corporation is available at www.z-medica.com.
CONTACT: For Z-Medica Corporation Matthew Lindberg, 203-682-8214 email@example.com KEYWORD: UNITED STATES NORTH AMERICA CONNECTICUT INDUSTRY KEYWORD: HEALTH MEDICAL DEVICES GENERAL HEALTH SOURCE: Z-Medica Corporation Copyright Business Wire 2012 PUB: 04/02/2012 09:30 AM/DISC: 04/02/2012 09:30 AM http://www.businesswire.com/news/home/20120402006007/


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The newest edition to the Cosmos line! Lunee is a crater shaped ball perfect for smaller dogs looking for an engaging and textured ball with out of this world durability.
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Available in 2.25" in Translucent Red. Like all Orbee-Tuff® toys, Lunee is made in the USA, non-toxic, durable, bouncy, chewy, buoyant and always 100% guaranteed.


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This section assumes you either know something about stylesheets or can learn about them incredibly fast. Put your thinking helmet on.
Many people are starting to build their Web pages using stylesheets and to position elements by placing them in layers. Generally, this is a great way to build a Web site, and it's decreased the amount of time it takes me to build one. Unfortunately, it can throw a wrench into any mouseovers you have.


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Hi all Tess here sorry havent posted for a while thanks again for all the messages, really enjoy your comments. Anyway just a few pics taken before we went out for a few on saturday night more were taken when we got back may podst them soon!! Tess xx
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One of the greatest skills you can teach your children is to communicate effectively. Most children learn how to speak during their toddler years; however, it usually takes a few years for them to speak easy enough to where they can be fully understood. As your children grow, they will continue to develop their vocabulary and language skills, enabling them to converse with you and express their wants and needs.
Why is Good Communication Important?
Verbal communication is the most common method of sharing information, thoughts, ideas and opinions with others. Whether you are a parent, child or teen, one of the best ways to express yourself is through talking. Talking is an essential element in bonding with members of your family and establishing a close relationship with others.
Listening also plays an important role in effective communications. By learning how to talk and listen to one another, parents and children can establish an open line of communication that can help draw them closer together as the years go by.
Communications skills are used in every aspect of a person's life. This makes it an important area for parents to focus on when raising their children. Although children will hone these skills at school, they will learn the basics of communicating from parents and other relatives at home. Children will also learn to articulate their needs, express their thoughts and convey emotions through the experiences they go through in their home environment.
Children who develop good communication skills will reap the benefits for years to come. Their ability to communicate effectively will help them perform better at school, establish stronger friendships, strengthen family ties and aid them in establishing a career once they are grown.
Teaching Kids to Communicate Effectively
While it's true that some children learn to speak easy on most any topic without having to be pushed or prodded, many kids find it difficult to express what's on their mind or heart at any given time. As a parent, there are various ways you can help your children overcome any doubts or fears they may have about communicating with others so they can learn to speak openly and honestly from their hearts.
Here's some valuable advice from educational psychologist Michele Borba on how to accomplish this goal:
- Encourage your children to talk about what's happening in their lives and listen attentively to what they have to say. Your genuine interest will boost your kids' confidence to share matters of the heart.
- Convey feelings of support and encouragement when your kids face difficulties or challenges without lecturing or interjecting your opinion, unless asked.
- Take time daily to talk "with" your children – not "at" them. Look for opportunities to start interesting conversations that draw you closer together as a family.
- Ask your children questions that require more than a simple yes/no response.
- Get involved in activities your kids enjoy so you'll have something in common to talk about.
- Use positive body language when listening to your children, i.e. smile, nod your head, maintain eye contact, etc., to show them you are all there. Your kids can tell from your facial expression and body language whether or not you care.
- As reading can help stimulate a child's mind and imagination, encourage your kids to read and talk about the stories they enjoy most.
Another good way to teach your kids good communication skills is to model them yourself. If you put these skills into practice at home with your family, your kids will learn from your example. The earlier you model these skills for your children, the better, as it gives them the opportunity to grow in this area from the time they are small. As your kids grow older, the good habits they have developed in communicating effectively will stay with them through adolescence and adulthood, enhancing their lives.
The Importance of Self-Expression
The ability to express your feelings as an individual is a valuable asset in life. Unfortunately, many school age children today don't learn this skill due to peer pressure from their friends to speak, think and be a certain way in order to be accepted. Many children and teens are all too willing to sacrifice who they really are for the sake of popularity. This doesn't leave too much room for individuality or self-expression. Children who just go with the flow never learn how to express themselves as an individual. As a result, they often grow into adulthood lacking confidence and self-esteem.
It's important for children and teens to learn how to express their thoughts, feelings and ideas and stand up for what they believe, especially on matters of importance. As an adult, you recognize the importance of individuality; you know how to communicate with others and express yourself in terms that others will understand. This same knowledge needs to be imparted to your children so they can grow into who and what they were meant to be.
Children and teens who are not afraid of expressing their ideas, opinions and beliefs are more confident, creative and capable of accomplishing their goals. Here are a few ways in which parents can encourage their children grow in this area:
Artistic expression
Provide opportunities for your kids to express themselves through the arts such as painting, drawing, sculpting, dance, music, theater, etc.
Let your children experiment with different forms of dress, hairstyles, room décor, etc. This helps them grow in developing their personal taste and style.
Encourage your kids to pursue their personal interests and goals, even if they're different from your own.
As much as possible, let your children make their own choices. Growing up provides ample opportunities for you to teach your children how to make good choices. As a parent, you can help them grow into mature teens and adults by leading and guiding their decision making and letting them learn by their mistakes.
The Quick and Easy Way to Speak Easy
The Quick and Easy Way to Effective Speaking written by Dorothy and Dale Carnegie provides readers with a step by step guide on how to enhance public speaking and communication skills. In this book, Carnegie emphasizes the importance of having confidence in yourself and speaking from personal experience in order to help you connect with your audience. Speaking about topics you know enables you to speak from the heart rather than from a prepared script.
Similarly, children and teens need to learn to speak from their heart. They need to be able to express their thoughts and feelings in their own words and in the right way. Your children will experience a myriad of emotions in their lifetime, ranging from joy and contentment to sadness, frustration, anger and fear. As they transition from toddlers and preschoolers to older children and teens, it's essential they learn to understand and manage their feelings, particularly negative emotions, in ways that don't hurt themselves or others. Here are some ways in which you can help your kids better understand and cope with negative feelings that may arise:
- Allow your children to express themselves, even if you don't agree with why they feel the way they do.
- Help your kids recognize the emotions they are feeling by identifying what they are, i.e. anger, disgust, fear, etc.
- Teach your kids how to express anger and frustration in a calm and collective manner, without yelling, breaking things or throwing a fit.
- Praise your kids for being open and honest about how they feel.
- Model the example you want your children to follow by expressing your own feelings in a constructive and positive way.
The ability to speak easy, openly and naturally is a gift your children will treasure for many years to come. According to life coach Anthony Robbins, "the way we communicate with others and with ourselves ultimately determines the quality of our lives."