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Why do we need an override?
The problem is Wareham doesn't bring in enough money to pay for its needs and its bills. Our basic expenses exceed our income. The override vote is part of a five-year plan, developed jointly by nearly all of our key elected and appointed officials.
We have already cut $2.5 million from the 2015 budget which begins July 1. Next year we will have to cut more. The year after that even more. Over the next five years, we will have to cut an additional $9.7 million. The 2015 budget already includes severe cuts in our services, and cutting more over the next five years means Wareham will barely be able to function as a town and as a community.
We can reverse this downward spiral and make Wareham financially sound with an override now of $4.5 million. An override will bring our schools, police department, library, and elder services to adequate levels while fixing our crumbling buildings, our outdated computer systems and putting money into our stabilization or savings account so that we can maintain our credit rating and take advantage of low-interest borrowing.
Why can't we live within our budget?
We DO live within our budget. State law requires that every town have a balanced budget. People speak of living within our means, but the problem lies in the fact that our ability to increase our "means" is limited by law (Proposition 2 ½), and our expenses as a town, just like our expenses in our own personal budgets, have increased at a rate greater than 2.5% over a long period of time. In your personal life, if you're not bringing in enough income to support your household, you have a variety of choices. A municipality's options are more limited. The Town has to pay for insurance, loan repayment, retirement benefits, health care for employees and state assessments. We are required to fund our schools at state-set minimum levels. In addition, there are many federal and state regulations that are addressed on a local level that we have no choice but to fund. Over the past years we have cut so much from our budget that we are now at a point that there is no more that we can cut without impacting our education, our safety, and our essential services.
Who will be affected if we don't pass an override?
Everyone will be affected one way or another. Do you have children in the schools? Use the library? Have a neighbor who accesses senior services? Drive on our roads? Might you ever call the police after a car accident or break-in at your home?
Our children will be affected when we can't provide current school books, reasonable class sizes, or bus transportation. Senior citizens will lose the Council on Aging and its elder care services. Library patrons will be affected when the main library will be open only one or two days a week, and there will be very limited service at the Spinney branch in Onset. Public safety will continue to be a concern as our police force is stretched thin. Town-owned property and our roads will continue to deteriorate, our cemeteries will be neglected, and our property values will decline.
How much will the override cost?
For the average homeowner, the override will add $1.43 to the tax rate which is $143 per year for each $100,000 of assessed property value. For the average house in Wareham, that means approximately $27 per month.
How will the override help?
We will be able to fund the contingent budget that was approved at Town Meeting in April.
That budget allows us to fund the library so that it will remain open full time; we can fund the Council on Aging; we can replace the six police officers who are leaving and purchase additional cruisers to replace those in the aging fleet; we can hire additional help for the understaffed municipal maintenance department; the schools can restore some positions lost in the balanced budget and hire reading and math specialists for the primary grades; and both the town and school can address technology issues and provide sorely needed upgrades to equipment and infrastructure. A complete listing of how the funds are being spent is available on this website or on the Town's website at end of the budget under the heading, "Contingent Appropriations."
How do we know how the money will be spent?
The budget was voted and approved at Town Meeting according to a five-year plan. All future budgets will have to be approved by us, the voters, Town Meeting. The plan includes regular reporting and review of benchmarks. The administrators who were instrumental in creating the plan are committed to following it. We must hold our town officials accountable and insist that they follow the five-year plan, and as voters, we can attend subsequent Town Meetings to be sure the plan is followed.
Could we save money by combining the water/fire districts into town government?
No. About a century ago, a number of southeastern and western Massachusetts towns received legislative approval to establish separately governed fire districts, and the town government has no authority over them. Wareham is not unique; Dartmouth has three independent fire districts, and the town of Barnstable has five.
What have other towns done in similar situations?
Other towns use overrides. Surrounding towns have voted favorably on several override questions in past years. Bourne has used overrides to fund operating expenses, schools and police. Sandwich has had seven successful overrides, and, although they were smaller dollar amounts, Marion has had 37, Mattapoisett has had 23, and Rochester has had five successful overrides – all while the town of Wareham has had none.
These overrides have provided financial security to these towns while providing their citizens with efficient services and spending.

subset: commoncrawl


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Invalid's Workshop
A description of what started this particular blog can be found in its first entry --Feb. 9, 2009. It's about healing.
Monday, July 31, 2017
Sunday, July 16, 2017
1970 Poem
[Wendyclip, 1970:]
We stopped on a
Steep little street--
Runs right down to
Dingle Lane.
They intersect
At a drain and
A narrow tunnel.
I believe this town
Began as a funnel.
We stopped on a
Steep little street--
Runs right down to
Dingle Lane.
They intersect
At a drain and
A narrow tunnel.
I believe this town
Began as a funnel.
Posted by Geo. at 7:09 PM 20 comments: Links to this post
Thursday, July 6, 2017
Peace, Please...A 1967 Memory
Seawater, held in
The arms of wind,
Went inland and
Filled night with
Fog, an unlit hill in
Berkeley --clothes
Optional, if not
Theoretical-- as
I recall, lovers kissed.
They wore moonlight
And mist, as youth
Does, and knew only
Where the inside
Of everything was.
Posted by Geo. at 9:43 PM 12 comments: Links to this post
Wednesday, June 14, 2017
The Genie Is You
To feel time
Is to hear the
Genie addressed
In future memory--
The wish and
The wish recalled.
The wish is always
To be the genie
Who makes dreams
Come true --and
That is you.
Posted by Geo. at 5:56 PM 12 comments: Links to this post
Sunday, June 4, 2017
Newyear's bell,
Rung to a world's
Time and tuned
To one brass note,
But each ring is
Followed by a new
And different quiet.
Posted by Geo. at 5:06 PM 16 comments: Links to this post
Friday, May 26, 2017
Beats a thousand times
Each minute -- I ask,
"Isn't that unbearable?"
"Oh yes," she answers.
"But there are moments
When it's merely relentless."
Courage, and encouragement
Come in all sizes.
Posted by Geo. at 11:32 PM 12 comments: Links to this post
Wednesday, May 10, 2017
We Are Here
Turn up the sound, switch to full screen. This is live feed from orbit. Watch Earth move.
The search for a closed scheme
That provides a complete and
Self-consistent explanation is
Full of flaws --in itself, an
Incomplete statement, consider:
Conscious beings -- universe
Generated self-awareness, no
Minor by-product of mindless
Forces, no trivial detail --no.
We are truly meant to be here.
And yet, it is we who invented
Meaning --good thing too!
Posted by Geo. at 12:20 AM 16 comments: Links to this post
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text: New research from social media agency Immediate Future has revealed that more than half (58%) of B2B marketers don't rate their ability to measure social at all. What's more, more than one in ten marketers don't appear to care, with 13% suggesting that social media measurement is neither important or unimportant. Read More


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For quite a while now, I've been stuck in my ways of using rosewater mist as the balancing agent between cleansing and moisturising. Recently though I decided to try out the Body Shop Aloe Calming Toner, because it seemed like it would be quite gentle and soothing on my recently troubled skin. Thankfully, it worked out to be just as gentle and calming as it sounds. I use this product by soaking a cotton bud in it and applying it to my skin straight after cleansing and it instantly settles down my skin and calms all redness. The toner has no scent to it, is alcohol free and is ideal for those of you like me with sensitive skin. It also doesn't seem to break me out at all, which is a huge bonus. The Body Shop Aloe Calming Toner retails for $17.95 AUD and can be purchased online from The Body Shop Australia's online store.
June 29, 2011
Product Review: The Body Shop Aloe Calming Toner
June 7, 2011
May Favourites
My five favourite and most reached for beauty products during the month of May were: Flourish Almond Milk Perfume Oil, Face of Australia Foxy Roxy Nail Polish, Dermalogica Sheer Tint Redness Relief, Inglot #230 Lipstick & Palmer's Cocoa Butter Moisturizing Body Oil.
June 3, 2011
Product Review: Dermalogica Sheer Tint Redness Relief
Those of you who know me will already know that I am an avid Dermalogica fangirl. For those of you who don't, well now you know. As we move through the colder months of the year here in Australia (as type this it is currently 24 degrees celcius and sunny here in Perth) it's important to work some cold-weather warriors into the skin care regime. At least for me it is, as I suffer from epic red face in the cold and wind. It's not pretty… First up to the bat is Dermalogica's Sheer Tint Redness Relief. I have been using this product every day for a few weeks after receiving it for review and I am loving it. "Neutralize, relieve and defend against inflammation and redness induced by skin sensitivity and rosacea with this three-in-one SPF moisturizer. Natural earth minerals provide a sheer green tint to actively counter telltale redness. Licorice, Green Tea, Sea Buckthorn and Ranunculus calm inflamed, irritated skin while promoting skin recovery from previous environmental assaults." I use this product as a moisturiser, and as I have oily skin this is enough for me but others may wish to layer it under or over their regular moisturiser. I do find that this product has reduced the natural redness of my face and is helping me combat the extra redness that the cold weather seems to inflict on my skin. I also love the fact that it's green, despite being initially disappointed that it blends out and doesn't leave me looking like Elphaba from Wicked. The Dermalogica Sheer Tint Redness Relief retails for $77 and can be purchased online from Australian online beauty retailer Adore Beauty. (note: I was sent this product for consideration for review)
May 22, 2011
Product Review: The Jojoba Company Jojoba Bead & Bamboo Facial Exfoliant
I have a am developing a deep love for The Jojoba Company. Though this is only the second product I have officially reviewed so far, I am loving the entire range of products that was sent to me for review. The Jojoba Company Jojoba Bead & Bamboo Facial Exfoliant is currently my favourite exfoliant that I have on rotation. As I already use Dermalogica Daily Microfoliant quite a bit during the week I try not to overdo it with any other exfoliation products. The Jojoba Bead & Bamboo Exfoliant is a manual exfoliant, which means there are little grainy bits in the product that scrub away to remove dead skin cells. The first time I used this product I used it in the shower and for some reason my face felt like it was reacting negatively to the scrub. I was sure that when I stepped out of the shower my face was going to be beet red, but it wasn't. It was ghost white as always and looked freshly scrubbed and clean. Ever since that first use, I have not experienced the same sensation when using the product so I'm really not sure what that little episode was about. Having said that and despite this product being recommended for sensitive skin, I would recommend those of you with sensitive skin try a sample of this product before investing in the full size tube just to be on the safe side. One of my favourite things about the Jojoba Company products I've tried so far is that my skin doesn't feel "stripped" in any sort of way after using them. Apparently you can also leave the Exfoliant on for 10-15 minutes for a luxury treatment face mask. I am yet to try the product in this way, but it does sound divine. The Jojoba Company Jojoba Bead & Bamboo Facial Exfoliant retails for $34.95 AUD and you can search for a local stockist on the Jojoba Company website. (note: I was sent this product for consideration for review)
May 13, 2011
Random Beauty Haul
The Aussie dollar has been performing like a champion lately, and I know a lot of my fellow beauty bloggers have been taking advantage of the strong exchange rate and doing a bit of online shopping. I am no exception, and have placed a few orders at MAC, Bath + Body Works and Sephora (the elusive Urban Decay Naked Palette shall be mine at last!). Pictured above are my most recent beauty acquisitions: Bath + Body Works Black Raspberry Vanilla Shower Gel & Triple Moisture Body Cream, Dermalogica Concealing Spot Treatment, Barrier Repair and Sheer Tint Redness Relief (all sent for consideration for review), MAC Eyeshadow in Phloof, Eyeshadow in Orb, Softsparkle Eye Pencil in Iris Accents and Mineralize Blush in Buddy Up, Benefit Cha Cha Tint (sent for review), Bobbi Brown Lipgloss in Hot Pink, Co Bigelow Apple Rose Salve, Co Bigelow Blueberry Rose Salve, Liplicious Signature Vanilla Berry Tasty Lipgloss, Liplicious Pineapple Juice Tasty Lipgloss and Co Bigelow Organics Strawberries & Cream Moisturizing Lip Shine.
May 5, 2011
May Wishlist
01: I am in dire need of a replacement for my Poshe top coat. Mine has gone rather gluggy and gross and has a tendency to drag the top layer of my polish around ruining my meticulously messy manicure efforts. 02: Who could lay eyes on the Chantecaille turtle palette and not want one for their very own? Especially when you know that 5% of proceeds go to widecast to ensure the survival of sea turtles.
03: Lemming, lemming, lemming. I need this in my life after reading Lara's review. 04: Continuing with the lemming trend, after seeing it on Stef's blog, Illamasqua cream blush in lies must be mine. Unfortunately I think this product is discontinued, so anyone who manages to tell me where I can buy it is entitled to my firstborn child with Prince Harry.


text:
Listen to free music by Szarka Tamás
Blip.fm is internet radio made social. It's easy to search for, play, and discover free music recommended by real people. Join today to create your own free station.
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text:
List of Supply Chain Internships
Filed Under Blog
We recently blogged about Supply Chain internships. It's well recognized that many internships offer an important stepping stone into a full-time career providing a combination of experience, training and that all important opportunity to network.
To take some of the grunt work out of finding those roles we're going to look at curating this page as a list of Supply Chain internships that we've come across that might prove interesting
Note#1: If you spot any outdated links or have others you might want to recommend hit us down below and leave some feedback.
Note#2: We'll update this as and when we find new links to share so bookmark us and check back
Note#3: If you're an employer drop us a DM on Twitter if you want your link adding
Johnson Controls
Supply Chain Intern checklist and Q&A
Filed Under Blog
As we discussed on our recent post on Supply Chain internships, they can offer a great route in starting out your supply chain career, providing an opportunity to gain valuable experience and an opportunity for you to showcase your skills and capabilities.
However, internships can seem daunting if you have little work experience. So, to help we've pulled together this helpful checklist/Q&A to help provide an insight on what to expect.
What will the work be like?
1/ Be expected to be asked to complete a variety of Supply Chain related tasks this might vary from speaking to suppliers, data entry, data analysis etc.
Tasks might vary with things like:
• Buying and Expediting
• Market Intelligence
• Spend Analysis
• Rate Competitiveness Studies
• Material Inventory Tracking
Procurement and Business Process Reviews
2/ Be prepared to work several projects simultaneously.
3/ Be prepared to work in a team based environment
4/ Be expected to hit task deadlines (warning these might be tight!)
5/ Expect your assignment to be driven by business need (not necessarily what you want to learn about.
What firms offer Supply Chain internships?
1/ Both large and small firms offer intern roles, there is a huge variety out there.
2/ Many blue chip companies (coca cola etc) have sophisticated recruitment processes and have teams and systems that manage internships – generally this means you should start early – start researching and applying well in advance as the good posts are likely to be taken first.
Who will I work with?
1/ This will vary dependent on which Supply chain function you work within but expect to be team based and have some exposure to people of all levels including management.
2/ Expect a degree of supervision
3/ Don't react badly if people critique your work – after all your new to this and learning.
What are the requirements to get a Supply Chain internship?
1/ Applicant requirements will vary depending on the hirer but expect that you'll need something along the lines of:
• Pursuing a relevant degree i.e. Supply Chain Management, Business or economics. Many interns are in their last year of their degree.
• Strong analytical skills
• Strong communication skills (you'll need to interact with all levels of the organization).
• Good level of IT literacy
• You'll thrive in a team.
What can I expect to get out of a Supply Chain internship?
1/ The goal of internships is to provide value to the organization and for the intern to gain experience
2/ Ideally the assignments should be tied back to classroom learning.
3/ Do not expect to get a job offer. If you do get one consider it a bonus. Do however think of the process as adding significant value to your CV and potential.
Anything else to consider?
1/ Consider the location of the internship and how you will pay for living costs
2/ Look to utilize intern events to meet and connect with other interns and company leadership to learn and build your network.
Finally – an internship is a great idea but should be considered as part of a broader career plan. How do you think it will help you? What do you want to get out of it? Don't just take an internship for the sake of it. Ensure it works for you.
Have some thoughts about Supply Chain internships? We'd love to hear from you in our comments section below.


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like if you haven't kissed or anything. just talked for like a week. and she started calling you babe.
Most Helpful Guy
Yeah it'd be weird. Especially if there's been no discussion on starting a relationship or even of any mutual interest in each other. Calling me 'babe' makes me think of squeaky little pigs anyway.00|00|0


text:
Your marble is a valuable investment and can be damaged by wear, exposure, improper maintenance, using the wrong cleaning chemicals, scratching, staining and etching can reduce the most beautiful stone products to a dull lifeless surface. Almost without exception these surfaces can be restored by us to their original beauty and shine.
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San Diego's Best 2011 Best Stone & Tile Provider
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Web Design and Hosting by iBizwebsite
Cities Serviced


text:
Only for Children
New campaign for the ANAR Foundation and its help line for children suffering any kind of violence. It is a special outdoor with two different messages, one for children, and another for adults.
Outdoor advertisment created by Grey, Spain for Fundación ANAR, within the category: Public Interest, NGO.
Sometimes, child abuse is only visible to the child suffering it. If somebody hurts you, phone us and we'll help you. 116 111.
Chief Creative Officer: Antonio Montero
Executive Creative Directors: Enric Nel·lo, Javier García Monserrat
Creative Directors: Fernando Riveros, Matías López Navajas, María Salomón
Art Directors: Jesús Martínez, Nacho Capelo, Javier Gcía. Maestro
Copywriter: Álvaro Montes, Nuño Martín
Art Buyer: Mayte Carabias, Joquin García-Morato
Account Director: Lucía Gómez Hortigüela
Account Executive: Mar Portela
For numerous reasons, this doesn't seem practical to me. It is very clever and I think this will be a highly celebrated awards wank – but it isn't a real solution to a real problem.
First of all, it isn't even made crystal clear to the kid that only they can see the line. The agency tried to make the line clever instead of clear. It could say something more like, "Hey kid, only you can read this. Call this number if you need help."
And what difference would it make if an abusive adult can see the line? Are they going to cover the kid's eyes?
Meredith Singh : you took the words out of my mouth. So funny I was just ranting about those exact points to a buddy of mine this morning.
The idea is emotional so it will work.
But it has more Whys than Wows for me.
Advertising in funnier than making weapons.
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text:
The Diagnostics Shop at HighTideHealth.com
To view the product and ordering page, click on the image.
Flents Medi-Scope Combo Nose Speculum & Ear Otoscope
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text:
12 of 19, Instructional Strategies for VI Stude...
12 of 19, Instructional Strategies for VI Students Under the Developmental Age of 3 - TETN 20440
TETN 20440 - 12 of 19. Strategy 8: Develop the tactile sense. In this training Kate Hurst focuses on strategies for learning and instruction when the child or student with visual impairment or deafblindness is under the developmental age of 3 years. Assessment and programming that is effective for students who are primarily in the sensory-motor stage of development may seem hard to come by, but there are many tried and true approaches to use for individuals at this stage, no matter their chronological age. A discussion of specific strategies suggested by Dr. van Dijk, Lilli Nielsen, and Barbara Miles, as well as resources are shared.
Original contributor Kate Hurst
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text:
We gots ourselves a new bot on Discord. Because it is so much easier to read this info in a table (which unfortunately we don't have support for on here yet), I have attached a PDF with all of the commands which you can download here: http://pawncraft.co.uk/xf/attachments/alfred-commands-pdf.2273/
we are running version 1.12Dismiss Notice
| Join us at IP: pawncraft.co.uk |
There is trouble with our mail service and we are looking into it. For a backup solution mail will come from firstname.lastname@example.com and email@example.com //StarScoreDismiss Notice
Discussion in 'Announcements' started by Pawned, 2 May 2016.
Discussion in 'Announcements' started by Pawned, 2 May 2016.


text:
Ending a marriage can be a tough, emotional process. The issues of dividing assets, debts, property, and child custody issues can be complicated and difficult to deal with alone. Janese Caruthers Law Firm and provide legal assistance by explaining your options for divorce, explaining your legal rights under the law in Florida, and help you understand each step of the process. We charge competitive rates that include flat fees for common services and payment plan options.
The laws in Florida for divorce may be different than the laws of other states. It is important to consult with an attorney licensed in Florida if the divorce will be filed in Florida. We're available for consultations Monday-Friday during normal business hours and on weekends by request. Give our office in Fort Myers, FL a call to schedule a free consultation.
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text:
JRC Healthcare Quality Team
JRC coordinates the technical and scientific aspects of the work ensuring synchronisation of all the initiative's objectives. JRC also provides the outsourced supports, the collaborating tools and logistics for the ECIBC working groups and other involved stakeholders. JRC also ensures appropriate communication with other EC services or working/expert groups in areas relevant for the project.
Contact us at email@example.com
Contact "Health in Society" Unit secretariat at firstname.lastname@example.com
Donata Lerda
Healthcare Quality Group leader
Born in 1962, graduated in Chemistry in 1987. Worked in the Public Health Administration in Italy for more than 20 years and started working in the EC-JRC in 2007 and for the ECIBC in 2012.
She's expert in quality assurance, accreditation, auditing and management of networks; she also has a deep knowledge of the European Commission working rules.She coordinates the European Commission Initiative on Breast Cancer.
Last update: 2016


text:
Hotel was clean large rooms and clean fitness center . Restaurant in front "Bistro". Was marvelous lady running the show for restaurant was top notch. All staff very friendly. Great location if in Dallas again will stay here again
Getting you more information on this room
Getting you more information on this room
"An inside room has sliding doors to the courtyard/pool. Very pleasant vista!"
"We picked it for the location, so don't think there are any attractions near the hotel."


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|Home | About | Journals | Submit | Contact Us | Français
Based on remarkable success of PTH as an anabolic drug for osteoporosis, case reports of off-label use of teriparatide (1-34 PTH) in patients with complicated fractures and non-unions are emerging. We investigated the mechanisms underlying PTH accelerated fracture repair. Bone marrow cells from 7 days 40cg/kg of teriparatide treated or saline control mice were cultured and Osx and osteoblast phenotypic gene expression assessed by real time RT-PCR in these cells. Fractured animals injected daily with either saline or 40cg/kg of teriparatide for up to 21 days were X-rayed and histological assessment performed, as well as immunohistochemical analyses of the Osx expression in the fracture callus. Osx, Runx2 and osteoblast or chondrocyte phenotypic gene expression was also assessed in fracture calluses. Our data shows that Osx and Runx2 are up-regulated in marrow-derived MSCs isolated from mice systemically treated with teriparatide. Furthermore, these MSCs undergo accelerated osteoblast maturation compared to saline injected controls. Systemic teriparatide treatments also accelerated fracture healing in these mice concomitantly with increased Osx expression in the PTH treated fracture calluses compared to controls. Collectively, these data suggest a mechanism for teriparatide mediated fracture healing possibly via Osx induction in MSCs.
Osteoporosis affecting more than 20 million Americans accounts for approximately 1.5 million fragility fractures every year [Finkelstein J.S., 2000], including more than 700, 000 vertebral fractures and over 300, 000 hip fractures [Riggs et al., 1995]. The probability of death following a hip fracture in osteoporotic patients is estimated to be 10 to 20% within the first year, and less than 50% of survivors regain their pre-fracture level of mobility and independence [Finkelstein J.S., 2000]. Furthermore, mortality within 90 days of an osteoporotic fracture in individuals who are older than 65 years is substantially higher than predicted; and for a subset of these fractures the risk for early lethality increases by approximately seven fold [Heaney, 2003]. During the past decade, the prevention of osteoporotic fractures has been limited to the use of anti-resorptive drugs [Cranney et al., 2002], which have proven to be insufficient for decreasing the mortality and morbidity in this patient population.
The known anabolic effects of parathyroid hormone (PTH) on bone formation has led to the development of a human recombinant peptide, teriparatide (1-34 human parathyroid hormone), corresponding to the first 34 amino acids of PTH. This drug was initially developed to treat postmenopausal osteoporotic women to enhance bone mineral density [Neer et al., 2001], and cortical thickness and trabecular bone volume [Jiang et al., 2005; Kurland et al., 2000] compared to placebo controls. In addition to its anabolic effects on bone turnover [Dempster et al., 2001; Neer et al., 2001; Rodan et al., 2000] teriparatide used in clinical trials was shown to significantly reduce the risk of vertebral and non-vertebral fractures in osteoporotic women [Black et al., 2003; Neer et al., 2001]. Using various animal models, several groups have shown that intermittent exposure to PTH stimulates osteoblast differentiation and function [Hock et al., 1992; Kulkarni et al., 2007] in vivo. In addition, this intermittent PTH treatment was also shown to enhance fracture callus formation [Nakazawa et al., 2005] and increase mechanical strength in adult rat fractures [Andreassen et al., 1999; Andreassen et al., 2004] in vivo. This PTH mediated anabolic effect was sustained throughout the remodeling phase of fracture healing [Alkhiary et al., 2005].
We hypothesized that PTH may enhance Osx expression in mesenchymal stem cells thereby inducing their differentiation into mature osteoblasts to achieve bony union. Our data show that daily teriparatide exposure induces Osx expression in mouse fracture callus compared to saline controls and promotes the differentiation of bone marrow derived MSCs to the osteoblastic lineage. We further show that intermittent PTH treatment up-regulates Osx in osteoprogenitor cells as well as markers of osteoblast differentiation in vitro.
7–9 week old C57BL/6 mice (Jackson Labs, Bar Harbor, ME) were used for fracture experiments. Mice were housed at the University of Rochester animal facilities according to state and federal law requirements. The animal studies were conducted in accordance with the principles and procedures approved by the University of Rochester IACUC. Mice were randomly selected to control or teriparatide (a generous gift from Eli Lilly) treated groups. Immediately following fracture experiments as described below, mice received daily subcutaneous teriparatide 40cg/kg or saline as control for 21 days.
Groups of 6 mice were anesthetized with ketamine (60 mg/kg) and xylazine (4 mg/kg) in normal saline via intraperitoneal injection. The femur fracture were performed using a 3-point bending system adapted from Bonnarens and Einhorn [Bonnarens et al., 1984] and as we have previously described [Kaback et al., 2008]. Fractures were radiographed by the Faxitron x-ray system (Faxitron, X-ray, Wheeling, IL) under anesthesia on Days 7, 10, 14, and 21 to monitor initial pin fixation as well as ongoing callus formation. Mice were sacrificed 7, 10, 14, and 21 days following fracture by induction of CO2 narcosis followed by cervical dislocation. For each experiment legs from 6 saline control mice and 6 teriparatide treated mice were harvested, and whole calluses (Including vessels, cartilage and bone) isolated for RNA extraction prior to gene expression analyses. Another set of control and treated mice (6 each) were used for histologic study as described below.
Fractured femurs were harvested as described above, fixed in 10% formalin, decalcified in an EDTA solution, embedded in paraffin and cut into 3 micron thick serial sections. These sections were stained in Alcian blue/hematoxylin solution as described previously [Zhang et al., 2002; Kaback et al., 2008]. Histomorphometric analyses were performed using the Osteometrics software (Decatur, GA). Briefly, bone and cartilage formation was quantified on H&E-stained sections by outlining the perimeter of the fracture callus under the 2x objective. Areas of new woven bone and cartilage were then traced. This procedure was repeated until the entire fracture callus has been evaluated. The areas of woven bone, cartilage, and total fracture callus are represented in square millimeters. Data is representative of three separate samples per group and the average total fracture callus size determined in each group. Immunohistochemical staining for Osx was performed using a rabbit polyclonal antibody (a generous gift from AbCam, UK) as previously described [Kaback et al., 2008].
For in vitro experiments, we used primary bone marrow derived cells harvested from tibias and femurs of mice treated daily for 7 days, via intraperitoneal injections, with 40cg/kg with teriparatide or saline control. A 25G5/8 needle (BD biosciences, Franklin Lakes, NJ) was used to flush the marrow with α-MEM (Gibco BRL, Grand Island, NY) containing 20% fetal bovine serum. Marrow was filtered using a swinnex syringe filter (Millipore, Billerica, MA) as previously described [Drissi et al., 1999]. Cells were plated in 6 well plates at the desired density of 2 × 106 cells per well, allowed to adhere for 4 days, and then cultured in complete media containing ascorbic acid (50cg/ml) and beta-glycerophosphate (10mM) for 7, 14 and 28 days prior to either staining or RNA harvesting.
For our in vitro experiments, total RNA was isolated using the RNeasy Kit (Qiagen, Valencia, CA) following the manufacturer's recommendations. Trizol (Invitrogen, Carlsbad, CA) was used to extract RNAs from fracture calluses according to the manufacturer protocol for tissue extraction using a Tissue Lyser (Qiagen, Valencia, CA). For our gene expression experiments, cDNA was synthesized using the advantage Superscript II RT-PCR kit (Invitrogen, Carlsbad, CA), following the manufacturer recommendation. Real time RT-PCR with specific primers for murine (Table 1) were performed using the fluorescent dye SYBR Green I (SYBR Green PCR Master Mix, Applied Biosystems, Foster City, CA) as previously described [Soung et al., 2007].
Statistical analyses were performed using the student t-test. Mean and standard error (SE) were calculated using GradphPad InStat (Version 4.03, San Diego, CA). The t-test was performed to determine which means were significantly different (p < 0.05).
PTH was previously shown to promote MSC differentiation into mature osteoblasts in vivo [Nishida et al., 1994]. However, the molecular events underlying this PTH anabolic effect on murine bone marrow derived MSCs are still unclear. We harvested bone marrow mesenchymal progenitors from mice previously treated or not with daily teriparatide via intra-peritoneal injections for 7 days. Flushed marrow mesenchymal cells from both groups were then maintained in osteogenic media for up to four weeks. Alkaline phosphatase staining was increased upon systemic teriparatide treatment in these cells in comparison to cells harvested from saline injected controls (data not shown). Using RNA extracted from these cultures, we assessed mRNA levels of Osx and other osteoblast phenotypic genes. Figure 1A shows that Osx expression is significantly and time dependently up-regulated after 14 and 28 days of culture (2.5 and 4 fold respectively) in MSCs from mice treated with teriparatide compared to saline controls. Similarly, Runx2 transcripts were also induced by teriparatide treatment at 14 and 28 days in culture by approximately 2.5 fold (Figure 1B). Figure 1D shows that while teriparatide did not induce alkaline phosphatase mRNA levels at 7 days, it strongly and significantly enhanced its transcript levels at days 14 and 28 by 15 and 8 fold respectively. Finally, transcripts of type I collagen (Figure 1C) and osteocalcin (Figure 1E) were likewise up-regulated by 2 to 3 fold after 14 and 28 days in culture. These results show that systemic teriparatide treatment can induce mesenchymal stem cell differentiation into osteoblasts possibly through induction of Osx and Runx2 expression.
Intermittent 1-34 PTH was previously shown to increase callus size and bone mineral density in rats [Alkhiary et al., 2005; Andreassen et al., 1999]. Here we investigated the effects of human recombinant PTH (teriparatide) on bone repair in a mouse femoral fracture model. We first examined the effects of teriparatide on fracture healing by radiographic and histological analyses. Saline injected animals were also used as controls. Figure 2 shows that while at day 7 post-fracture no differences are radiographically apparent between teriparatide and saline treated controls, the size of the radiolucent soft callus at 10 days post-fracture in the teriparatide treated mice was increased compared to saline controls. By day 14 this difference in callus size persists in the teriparatide treated mice compared to controls as shown by X-ray analysis (Figure 2A). Histological assessments of these fractures (Figure 2B) show that 10 days following teriparatide treatment, enhanced cartilage formation, as evidenced by Alcian blue staining, was observed in these calluses compared to the controls. By day 14 of treatment, increased bone formation was observed in the teriparatide treated mice compared to the saline injected animals. Our histomorphometric measurements of callus sizes in teriparatide treated compared to saline injected controls show that teriparatide induced a significant increase in callus formation at 7, 10, and 14 days post fracture by 35%, 264%, and 75%, respectively (Figure 2C). These results suggest that PTH enhances fracture healing possibly through enhanced differentiation of mesenchymal progenitor cells into mature osteoblasts at the fracture site.
The effects of teriparatide on fracture healing suggest the recruitment of mesenchymal progenitor cells into the fracture site and their differentiation into mature osteoblasts. In addition, systemic treatment of mice with teriparatide enhanced Osx expression in marrow derived osteogenic cells (shown above in Figure 1). In order to determine the cellular representation of Osx during fracture repair in response to teriparatide, we performed immunohistochemical assays using an Osx specific antibody [Kaback et al., 2008]. Figure 3A shows that Osx protein is expressed in periosteal cells and confined in the immature chondrocyte cell population while it is absent from fibrous tissue and chondrocytes undergoing hypertrophy in the saline injected controls at day 7 post-fracture. After 10 days of treatment, while both the saline controls and the teriparatide injected mice exhibit onset of trabecular bone formation in the fracture calluses, the number of Osx expressing osteoblasts and the volume of de novo trabecular bone is increased in the treated fractures compared to controls. The expression of Osx in the fracture calluses was also evaluated after cartilage remodeling and at the onset of bony union and trabecular bone remodeling at days 14 and 21. Fourteen days following teriparatide treatment, massive bone formation is observed and Osx expression is seen in the osteoblast lining cells as well as in osteocytes embedded in the woven bone. This expression is also observed in the saline injected controls. This same effect is seen after 21 days of treatment with an enhanced representation of trabecular bone compared to day 14. This accelerated trabecular bone formation is also concomitant with the absence of marrow cavities in the calluses of teriparatide treated animals compared to saline controls. Negative controls using secondary antibody alone did not show any reactivity at all time points (data not shown). Together, these results suggest that PTH accelerates fracture healing through enhanced commitment of progenitor cells towards an osteoblastic phenotype possibly through induction of Osx expression.
Intermittent PTH systemic injection was previously shown to increase fracture callus size, bone mineral density, and mechanical strength in rat femur fractures [Alkhiary et al., 2005]. However, the effects of daily teriparatide treatment on gene expression in fracture callus have yet to be defined. To further investigate the molecular targets of PTH in fracture calluses during bone repair, we performed gene expression analyses using RNAs extracted from fracture calluses of teriparatide treated mice and saline controls at 7, 10, 14 and 21 days post-fracture. Figure 4A shows that Osx transcripts are significantly up-regulated (3 fold) in calluses isolated 10 days post-fracture in the teriparatide treated groups compared to saline injected controls. Transcript levels continue to be elevated at 14 days post fracture in the teriparatide treated group (1.5 fold) in comparison to the saline injected animals. However, no difference was observed in Osx expression at 7 and 21 days post-fracture. We also assessed the expression of the bone and cartilage related gene Runx2. Runx2 transcripts are significantly induced at 7 days (2 fold) and 10 days following teriparatide treatment in these fracture calluses (2.5 fold) compared to untreated controls. However, Runx2 transcript levels are similar to saline controls 14 and 21 days post fracture (Figure 4B). Cartilage and bone phenotypic marker gene expression was also evaluated in these calluses. Thus, while teriparatide treatment only induces Sox9 expression in the early time point at 7 days compared to controls (Figure 4C), type II collagen expression is first enhanced at day 7 then inhibited at day 10 upon teriparatide treatment (Figure 4D). As expected, both control and treated levels of the chondrocyte phenotypic genes are reduced 14 and 21 days post-fracture when the cartilage matrix is remodeled in the fracture callus. On the other hand, type I collagen mRNA levels were initially slightly but significantly inhibited at day 7 post-fracture, then up-regulated between 10 and 14 days of teriparatide treatment (2 and 3 fold, respectively), while they were thereafter down-regulated 21 days post-fracture in the teriparatide treated groups compared to controls (by 2 fold) (Figure 4E). The marker for matrix mineralization, osteocalcin was progressively up-regulated by 4 fold following 10 and 14 days of teriparatide treatment compared to saline controls in these fracture calluses. After 21 days of teriparatide exposure, osteocalcin levels were enhanced 2 fold compared to saline treated animals (Figure 4F). Together, these results indicate that daily systemic teriparatide therapy post-fracture is not only able to up-regulate Osx transcripts in fracture callus but also induce mesenchymal stem cell commitment towards osteogenesis in the fracture site.
Although the main function of PTH remains to regulate bone metabolism and maintain calcium homeostasis [Arnaud et al., 1970], several studies have investigated its anabolic effects in osteoporotic patients [Bilezikian et al., 2005; Black et al., 2003; Neer et al., 2001]. As fragility fractures continue to pose a unique dilemma to clinicians in terms of understanding fracture biology as well as establishing practical pharmacological agents that will reduce the relative risk of future fractures, the anabolic effects of PTH were also investigated during bone repair both in clinical trials and using animal models [Alkhiary et al., 2005; Jiang et al., 2005; Neer et al., 2001]. Previously, a fracture prevention trial established the role of teriparatide as an anabolic agent capable of reducing the risk of fragility fractures in postmenopausal women [Black et al., 2003; Neer et al., 2001]. However, a possible role for teriparatide in enhancing bony union of post-traumatic fractures should be postulated. Here we report the effects of teriparatide on bone repair in a mouse fracture model. We examined the cellular and molecular pathways underlying PTH enhancement of fracture healing. We believe that one possible mechanism by which PTH mediates fracture repair is through up-regulation of the zinc finger transcription factor Osx in mesenchymal stem cells, which in turn stimulates their recruitment and differentiation into mature osteoblasts.
Previous studies have described antagonistic effects of PTH on bone formation upon its mode of administration in vitro and in vivo [Alkhiary et al., 2005; Andreassen et al., 1999; Andreassen et al., 2004; Black et al., 2003; Jiang et al., 2005; Nakazawa et al., 2005; Neer et al., 2001; Thomas, 2006]. While continuous exposure to PTH leads to massive bone loss in vivo through increased osteoclast mediated bone resorption following enhanced osteoclast density and activity [Hadjidakis et al., 2006; Potts, 2005], Ishizuya and colleagues demonstrated the ability of PTH treatment administered under an intermittent regimen to induce bone formation through enhanced alkaline phosphatase activity, calcium content and the number of mineralized bone nodules deposited by rat calvaria-derived osteoprogenitor cells in vitro [Ishizuya et al., 1997]. Here we show that intermittent exposure of osteoprogenitor cells to PTH enhances Osx expression and promotes osteoblast differentiation.
The cellular events required for proper fracture healing of long bones through endochondral ossification are well documented [Ferguson et al., 1999; Gerstenfeld et al., 2003; Vortkamp et al., 1998]. Systemic and growth factors are produced in response to skeletal injury leading to the recruitment of progenitor cells from both the bone marrow as well as the periosteum to the site of injury [Hiltunen et al., 1993]. Several investigations reported the requirement for factors including the TGF-β superfamily, the PDGF, FGF, Ihh, prostaglandins, Wnt and VEGF during fracture repair [Gerstenfeld et al., 2003] yet very limited information is available about the mechanisms of action of their downstream targets in fracture calluses. Therefore, we addressed the molecular aspects of mesenchymal stem cell recruitment and differentiation that mediate fracture healing in response to PTH using an animal mouse model. We found that teriparatide increases cartilage and bone formation in the fracture callus at 7 and 10 days post-fracture.
Our assessment of gene expression in the fracture calluses in response to teriparatide shows that Osx expression was up-regulated in the fracture callus following treatment compared to saline injected controls. These results clearly suggest a correlation between PTH enhanced fracture repair and the known Osx mediated commitment of MSCs to the osteoblastic phenotype. We found that while markers of chondrocyte maturation are decreased as the fracture calluses ossify, osteoblast differentiation markers be induced. However, the inductive effects of teriparatide on Sox9 and type II collagen gene expression 7 days post-facture suggest a positive effect on chondrogenesis. Although, chondrocytes exhibit receptors for PTHrP, the effects of PTH on chondrogenesis are not known. These effects may also be indirect. Finally, although the effects of teriparatide on type I collagen gene expression were inductive in the fracture callus between 10 and 14 days post-fracture, PTH treatment inhibited type I collagen expression three weeks following treatment. This could be attributed to enhanced osteoblast maturation in the fracture callus as evidenced by the significant increase in osteocalcin expression at day 21. However, at day 7 post-fracture, teriparatide also inhibited type I collagen expression which in combination with its effects on Sox9 and type II collagen further suggests an effect of PTH on chondrogenesis during fracture healing.
In addition to its role in mediating bi-potent mesenchymal progenitor cell commitment toward osteogenesis [Nakashima et al., 2002], we have recently reported that Osx not only mediates MSC differentiation into mature osteoblasts but also strongly inhibits chondrocyte maturation [Kaback et al., 2008]. Our present study demonstrates that systemic treatment of these mice with teriparatide not only enhanced mesenchymal progenitor cell differentiation into mature osteoblasts, but also increased Osx expression in these marrow derived cells isolated from teriparatide treated mice in vivo. This increase in Osx expression along with osteoblastic phenotypic markers was concomitant with Runx2 expression. Our results demonstrate that systemic teriparatide treatment was able to induce Runx2 levels in the callus in the early time points following fracture healing. It is however noteworthy that Runx2 levels were not induced after day 10 when cartilage is replaced with bone in the callus, while Osx levels were still upregulated. While this shift is Osx versus Runx2 expression during callus formation and remodeling may be in support of the dogma of Osx being downstream of Runx2, it is not clear why PTH did not continue to induce Runx2 expression when cartilage is replaced with bone.
Previous evidence attributed the anabolic effects of PTH on bone formation to the induction of Runx2 [Krishnan et al., 2003]. The anabolic effects of PTH on bone formation were previously attributed to the increased expression of Runx2 through the PKA pathway [Krishnan et al., 2003]. The genetic evidence provided by the loss of Osx or Runx2 function suggested that Osx may be downstream of Runx2. We have previously shown that Osx may be a direct downstream target of Runx2 in various cell lines [Nishio et al., 2006]. However, emerging evidence in recent studies also advocate a Runx2 independent activation of Osx gene expression [Lee et al., 2003; Nakashima et al., 2003; Tu et al., 2006; van der et al., 2005]. It is possible that while PTH targets both Runx2 and Osx, its effects may be directly mediated through Osx and independently from Runx2. Further studies will delineate the precise role of Osx in mesenchymal stem cell recruitment to the fracture site in response to PTH treatment. Together, our findings bring novel insight into the cellular and molecular pathways underlying PTH mediated fracture repair thereby supporting its use not only as an anabolic agent for postmenopausal/osteoporotic bone loss but also for skeletal tissue repair and bone regeneration.
Contract grant sponsor: National Institutes of Health (NIH) RO1 grant No. AR052674-01 to HD; Contract grant sponsor: NIH CORT P50 grant No. AR05404 to RNR.
The authors would like to thank the National Institutes of Health (NIH RO1 grant No. AR052674-01 to HD and NIH CORT P50 grant No. AR05404 to RNR) for financial support and Krista Scorsone for her technical assistance.
PubMed Central Canada is a service of the Canadian Institutes of Health Research (CIHR) working in partnership with the National Research Council's national science library in cooperation with the National Center for Biotechnology Information at the U.S. National Library of Medicine(NCBI/NLM). It includes content provided to the PubMed Central International archive by participating publishers.


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I "rescued" a bird bath from the curb that had a hole in it. I thought "no problem, I'll mosaic over it and the hole will be covered and it will be prettier."
|Seems small enough to cover
Lesson 1: in mosaic-ing-or any other any craft project. Have the right materials.
|You should not try breaking pieces with a rolling pin...you'll just dent your rolling pin
|Quick-drying is not what you want for a mosaic-art takes time!
Lesson 2: Have a plan.
Mosaics are not usually abstract and if you want it to have some sort of design you need to know and have the pieces ready for that design because your medium is drying while you're thinking, it doesn't stop working just because you do.
|Have the pieces you need ready
Lesson 3: Sometimes you have to let go.
|From memespp.com
This was my second (yes second) attempt at doing a mosaic to rescue this bird bath (yes I know my second attempt looks like my nieces did it thank you for your moral support). That's two times that I failed and I have discovered that I was not enjoying it, and it wasn't worth it. I literally was spending more money and time into something than I spent on it (it was free remember!). So this project, we're going to accept defeat...and let it go.
So the moral of this story is yes, even my amazing self fails sometimes (its actually my specialty). So now go forth and FAIL!


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Instructor's Manual to accompany Madden Exploring Literature Second Edition Frank Madden SUNY Westchester Community College New York Boston San Francisco. Lyberty.com's weekly/monthly splash page. (Yes, a splash page is old fashioned, but it's been a tradition here since 1999..
CHAPTER 1 : CAPITULO I : Loomings: Espejismos: Call me Ishmael. Some years ago — never mind how long precisely — having little or no money in my purse, and.
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Action mature.com efuckt cortoon sex vedio red tube the hun.com the hun lesbiaj videos free praise and worship sheet music crosdresing in uk i`, m a student from. FIFTY YEARS AGO, when I was a boy of fifteen and helping to inhabit a Missourian village on the banks of the Mississippi, I had a friend whose society was very dear.


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|This Month
Candor: 06/02/17
Candor by Pam Bachorz is about the perfect self sufficient suburb in Florida. Once swampland, it's now the place that every self respecting family wants to live. It's the place where trouble teens become model citizens, where the addicted can finally kick the habit. Oscar Banks, though, knows the truth behind the miracles. He knows about the brainwashing — the 24/7 messages. He's the mayor's son.
Candor is utopia — a "no place" — completely cut off from the rest of the world. It is totalitarian, hiding away from the rest of the United States, away from unhealthy influences. It is Pleasantville.
As Oscar narrates he lets us know that the messages are inescapable, even if he thinks he has found a way to keep his mind clear of them. He believes his own counterculture of bootleg messages, which he sells to other teens for a hefty price, will allow him the freedom to be himself.
Like any hero in a dystopian novel, he's mistaken. He is as much a cog in the works as anyone else. How long he can last is all dependent on how much of a fanatic his father is.
In terms of the road narrative project, Candor is a road not taken. People who arrive have one of three options. First they shunned and moved out of the town as quickly as possible (as the undesirable who aren't even showed a model home when they come to visit Candor). Second, they are assimilated. Third, the free thinkers are destroyed.
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Intensive Supports
A small percentage of students generally does not respond to either schoolwide or targeted prevention and intervention efforts. These are usually children who experience severe or chronic problem behavior that regularly affects the ability to learn in a school environment, both their own learning and that of their peers. Children at the intensive level generally require a great deal of time and energy, and teachers and administrators are more likely to have the time to devote to these children if many of the minor and moderate behaviors are prevented and managed appropriately at the schoolwide and targeted levels.
Systems Features at the Intensive level include:
- Intensive supports coordinator
- Staff training in intensive supports
- School-based referral processes
- Deescalation response team
- Emergency preparedness team
Practices at the Intensive level include:
- Conflict Cycle
- Escalating Behavior Cycle
- Intensive level FBA and BSP
- Life Space Crisis Intervention
- Engaging Families
- Community-based referral processes
- Person-Centered Planning
- Wraparound