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Massive loss of intestinal surface area results in short bowel syndrome, characterized by malabsorption of fluids, electrolytes, and other nutrients. Common causes of short bowel syndrome include resection related to volvulus, thrombosis of the superior mesenteric artery, Crohn's disease, or trauma. While some adaptation of remaining intestinal surface (characterized by elongation and dilation of remnant bowel) can improve nutrient absorption, patients with less than 60 cm of functional jejunum or ileum typically require permanent total parenteral nutrition (TPN). While intestinal transplantation is one alternative, there has been recent interest in methods to increase intestinal adaptation as a non-surgical alternative. Specifically, intestinal adaptation is thought to be related to exposure of the remaining mucosa to luminal nutrients, the presence of enteric hormone and pancreatic-biliary secretion, and the trophic effects of various extrinsic growth factors and growth hormone. For example, the amino acid glutamine administered either enterally or parenterally, is known to induce a nutritive or regenerative effect on the bowel. Growth hormone is also thought to have a nutritive effect on the bowel.
Specialized inpatient programs have been developed to offer intensive counseling and tailored regimens of diet modification, glutamine, and growth hormone therapy to patients with short bowel syndrome. The goal of these programs is to either eliminate or reduce the need for total parenteral nutrition. The Nutritional Restart Center near Boston, Massachusetts (www.nrcenter.com), offers an inpatient program of two to four weeks, during which time the patient undergoes detailed metabolic evaluations to determine the feasibility of an oral diet, intestinal adaptation therapy with dietary modification (diet high in complex carbohydrates and low in fat), glutamine and growth hormone, and a gradual weaning of total parenteral nutrition, if possible. Patients also receive extensive counseling and education, and participate in a physical rehabilitation program. At completion of the program, the patients are discharged on only the restricted diet and the supplemental glutamine. The Nutritional Restart Center also offers outpatient and home-based services to patients requiring continued treatment. The University of Nebraska, in conjunction with the Nutritional Restart Center, maintains an affiliated Inpatient Intestinal Rehabilitation Program in Omaha.
Each benefit plan or contract defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers have the responsibility for consulting the member's benefit plan or contract to determine if there are any exclusions or other benefit limitations applicable to this service or supply. If there is a discrepancy between a Medical Policy and a member's benefit plan or contract, the benefit plan or contract will govern.
Blue Cross and Blue Shield of Montana (BCBSMT) considers an inpatient program of intestinal rehabilitation, consisting of metabolic evaluation, patient counseling and education, nutritional counseling, physical therapy, and treatment with growth hormone and glutamine experimental, investigational and unproven in patients with short bowel syndrome who are dependent on total parenteral nutrition.
The published data are almost exclusively derived from researchers working at the Nutritional Restart Center near Boston. Most reports consist of small case series, many with presumably overlapping patients. One case series consists of 45 patients with short bowel syndrome maintained on long-term parenteral nutrition. These patients were treated with growth hormone, glutamine, and a modified diet for four weeks and then followed up for an average of 1.8 years. After four weeks of therapy, 58% no longer required TPN. At follow-up, the percentage of patients not receiving TPN fell to 40%. A review article published in the same year included 67 adults receiving TPN, and presumably includes overlapping patients. At completion of the four-week program, the TPN requirement for each patient was noted as discontinued (52%), reduced (38%), or no change (10%). Over an unspecified follow-up period, there was some attrition of the treatment effect.
The relative contributions of the pharmacologic, dietary and counseling/education aspects of the overall program cannot be determined. Specifically, some researchers have questioned whether the treatment effect was primarily due to meticulous dietary counseling as opposed to any effect from glutamine or growth hormone. For example, Scolapio conducted a randomized six-week double-blind, placebo-controlled trial of eight patients who alternatively received growth hormone, glutamine supplementation, and a high carbohydrate, low-fat diet which alternated with a placebo treatment. Active treatment was associated with an increased body weight and lean body mass, decreased percent of body fat without increase in fluid, or macronutrient absorption. All patients receiving active treatment developed peripheral edema, suggesting that an increase in extra cellular fluid may have been responsible for the positive findings. In addition, after discontinuation of growth hormone, the weight returned to baseline. In another blinded crossover study of eight patients, Szkudlarek and colleagues examined the effect of growth hormone and glutamine supplementation on intestinal function. Unlike the above study, the patients did not receive a high carbohydrate, low-fat diet. Growth hormone with glutamine was not associated with improved intestinal absorption of energy, carbohydrate, sodium, potassium, calcium, or magnesium.
An additional research question is the contribution of an intensive inpatient program, compared to similar elements of the program offered in an outpatient setting. This issue has not been addressed in the published literature.
An updated search of the medical literature found that there is no consistent definition or components of intestinal rehabilitation nor is there long-term health outcomes measured for intestinal rehabilitation. Studies continued to assess the relative contributions of growth hormone, glutamine, glucagon-like peptide-two, and diet but did not assess the optimal treatment settings or components of intestinal rehabilitation according to patient characteristics.
One study involved twelve adults with short bowel syndrome who were dependent on a home-based, high carbohydrate parenteral nutrition diet. Patients were randomized in a double-blind placebo-controlled crossover study. Patients received daily low-dose growth hormone and placebo for a two- to three-week period, separated by a one-week washout period. Treatment with growth hormone increased intestinal absorption of energy, nitrogen, carbohydrates, and fats. The increased food absorption represented 37% +/- 16% of total parenteral energy delivery. Body weight, lean mass, and D-xylose absorption increased. However, the study did not assess long-term health outcomes beyond the immediate study period.
One study assigned 59 patients with life-threatening complications of intestinal failure to three treatment options. Sixty-eight percent of patients were considered appropriate candidates for intestinal transplants, 10% were managed with rehabilitation, and 17% were maintained on optimized parenteral nutrition. All patients managed with rehabilitation were weaned from parenteral nutrition within six months.
Wu and colleagues assessed bowel rehabilitation combined with nutritional therapy and found that 33 of 38 patients maintained body weight and serum albumin concentrations after an average follow-up of 5.9+/-4.3 years for the 33 survival patients. Nutrient absorption in eight patients treated with growth hormone and glutamine seemed to increase, but the effects occurred only during the treatment period and were not sustained.
The Federal Drug Administration (FDA) label for Zorbtive indicates growth hormone has been shown in human clinical trials to enhance the Tran mucosal transport of water, electrolytes, and nutrients. The FDA approval for Zorbtive was based on the results of a randomized, controlled, Phase III clinical trial in which patients dependent on intravenous parenteral nutrition who received Zorbtive (either with or without glutamine) over a four-week period had significantly greater reductions in the weekly total volume of intravenous parenteral nutrition required for nutritional support. However, the effects beyond four weeks were not evaluated nor were the treatment locations (inpatient vs. outpatient) identified.
The FDA has noted growth hormone for patients with short bowel syndrome should be limited to patients receiving specialized nutritional support in conjunction with optimal management of short bowel syndrome. Specialized nutritional support may consist of a high-carbohydrate, low-fat diet adjusted for individual patient requirements. Optimal management may include dietary adjustments, enteral feedings, parenteral nutrition, fluid and micronutrient supplements. Zorbtive is administered daily at 0.1mg/kg subcutaneously up to eight mg/day. Administration of Zorbtive for longer than four weeks has not been adequately studied per the FDA indications.
Disclaimer for coding information on Medical Policies
Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.
The presence or absence of procedure, service, supply, device or diagnosis codes in a Medical Policy document has no relevance for determination of benefit coverage for members or reimbursement for providers. Only the written coverage position in a medical policy should be used for such determinations.
Benefit coverage determinations based on written Medical Policy coverage positions must include review of the member's benefit contract or Summary Plan Description (SPD) for defined coverage vs. non-coverage, benefit exclusions, and benefit limitations such as dollar or duration caps.


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Andy's Answers: Who makes a good social media analyst?
By Andy Sernovitz on September 18th, 2014 | 54000Comment on this posthttp%3A%2F%2Fsmartblogs.com%2Fsocial-media%2F2014%2F09%2F18%2Fandys-answers-who-makes-a-good-social-media-analyst%2FAndy%27s+Answers%3A+Who+makes+a+good+social+media+analyst%3F2014-09-18+11%3A40%3A55Andy+Sernovitzhttp%3A%2F%2Fsmartblogs.com%2F%3Fp%3D54000
"If you're going to hire an analyst, hire the one that's doing the Sudoku puzzles in the waiting room," says Jim Sterne of eMetrics Summit. But, he says, it's not all about the numbers.
In his presentation at SocialMedia.org's Brands-Only Summit, Jim talks about the human side of social media analytics. He focuses on the role an analyst should play within a company and the qualifications they should have to turn social data into effective business practices.
Here are some key points:
- Tell stories instead of reports. Jim advises analysts to skip over the nitty-gritty numbers. Instead, get right to the insight by focusing on customers and business objectives.
- Be careful. Jim acknowledges that humans love to find patterns and make assumptions. Unfortunately, there are a lot of traps the brain can fall into when it comes to processing data. He warns analysts not to confuse correlation with causation or to give in to cognitive bias.
Andy's Answers: Why audiences are assets
By Andy Sernovitz on September 11th, 2014 | 53847Comment on this posthttp%3A%2F%2Fsmartblogs.com%2Fsocial-media%2F2014%2F09%2F11%2Fandys-answers-why-audiences-are-assets%2FAndy%27s+Answers%3A+Why+audiences+are+assets2014-09-11+11%3A07%3A50Andy+Sernovitzhttp%3A%2F%2Fsmartblogs.com%2F%3Fp%3D53847
Some of the best marketing advice author Jeff Rohrs ever received was from legendary rock musician Bruce Springsteen: "Audience is not brought to you or given to you; it's something that you fight for."
Jeff elaborates on this idea in his book, "AUDIENCE." He believes that Facebook fans, Twitter followers and e-mail subscribers are among the most important assets a company can have. Marketing just isn't effective without an engaged customer base.
In his presentation at SocialMedia.org's Brands-Only Summit, Jeff discusses the importance of investing time and resources into audience development.
Here are three key takeaways:
- No audience is owned. In social media, people can unfollow, unlike and unsubscribe any time. Jeff says it's the company's job to keep customers invested.
- Grow the right kind of audience. Everybody likes a big crowd. But marketing is about more than just numbers. While purchasing fake fans and followers makes a brand seem popular, it won't actually create any meaningful engagement.
Andy's Answers: Why Whole Foods looks to its customers for its Pinterest strategy
By Andy Sernovitz on September 4th, 2014 | 53524Comment on this posthttp%3A%2F%2Fsmartblogs.com%2Fsocial-media%2F2014%2F09%2F04%2Fandys-answers-why-whole-foods-looks-to-its-customers-for-its-pinterest-strategy%2FAndy%27s+Answers%3A+Why+Whole+Foods+looks+to+its+customers+for+its+Pinterest+strategy2014-09-04+11%3A05%3A05Andy+Sernovitzhttp%3A%2F%2Fsmartblogs.com%2F%3Fp%3D53524
Natanya Anderson, director of social media and digital marketing at Whole Foods Market, says Pinterest creates a lot of great opportunities for brands. For Whole Foods, it drives a ton of traffic to their website, creates almost 11 times as much as engagement with their followers than Twitter, and it's a great platform for working with influencers.
In her presentation at SocialMedia.org's Brands-Only Summit, Natanya takes us on a tour of Whole Food's "Pinterest Parthenon" and its three tiers:
- Philosophy: Natanya calls Whole Foods' approach to Pinterest "Lifestyle-Centric Curation." It's all about collecting the best and most customer-relevant ideas on the Internet and bringing them together onto one inspirational board.
- Strategy: Whole Foods aims to create images people will share, like a graphic on brining or a recipe card for potato salad. They also reach out to big Pinterest influencers to reach a bigger audience.
- Accountability: Natanya says measurement is essential to a successful Pinterest strategy.
Andy's Answers: Why social media requires "extreme trust"
By Andy Sernovitz on August 21st, 2014 | 53394Comment on this posthttp%3A%2F%2Fsmartblogs.com%2Fsocial-media%2F2014%2F08%2F21%2Fandys-answers-why-social-media-requires-extreme-trust%2FAndy%27s+Answers%3A+Why+social+media+requires+%22extreme+trust%222014-08-21+11%3A15%3A33Andy+Sernovitzhttp%3A%2F%2Fsmartblogs.com%2F%3Fp%3D53394
In today's socially connected world, it isn't enough to just do the right thing. You have to proactively give people a reason to have confidence in your brand. That's why Don Peppers, co-author of "Extreme Trust: Honesty as a Competitive Advantage," says brands have to focus on the quality of their customer experience.
In his presentation at SocialMedia.org's Brands-Only Summit, Peppers talks about making transparency a priority for social media managers. He says with the way word travels through social media, the slightest bit of shadiness can trigger a massive decline in trust.
Here are some other key takeaways from his talk:
- Provide objective advice. While it may seem counterintuitive, Peppers encourages companies to recommend a competitor's product if they know it will be more suitable than their own. This builds a reputation of credibility and authenticity.
- Your employees want to help. People want to work for a trustworthy brand.
Andy's Answers: Why marketing should start with the customers
By Andy Sernovitz on August 14th, 2014 | 53281Comment on this posthttp%3A%2F%2Fsmartblogs.com%2Fsocial-media%2F2014%2F08%2F14%2Fandys-answers-why-marketing-should-start-with-the-customers%2FAndy%27s+Answers%3A+Why+marketing+should+start+with+the+customers2014-08-14+11%3A32%3A56Andy+Sernovitzhttp%3A%2F%2Fsmartblogs.com%2F%3Fp%3D53281
Brains on Fire President Robbin Phillips has some tough news for brands: "People don't want to talk about you." What they want to talk about is their lives. That's why it's so important for brands to understand how to fit into customer passions and interests.
In her presentation at SocialMedia.org's Brands-Only Summit, Robbin talks about the data-driven mentality that dominates social media marketing. She says that brands are so obsessed with getting on the newest social channels and gaining millions of followers, they forget to prioritize people before numbers. Robbin encourages marketers to focus on customers instead to form deeper connections and spark meaningful engagement.
Here are three key takeaways from her presentation:
- Focus on the people, not the product. When scissors manufacturer Fiskars complained to Robbin about the lack of ways to brand their ordinary merchandise, the team at Brains on Fire encouraged them to think beyond the product.

subset: commoncrawl


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Immunogenicity of biotherapeutics is costing the industry huge amounts as a result of loss of efficacy and potential cross-reactivity. Moreover patients are being denied life-saving treatments when given immunogenic products. Leaders in the field are determining what product characteristics and handling can cause immunogenicity, how to predict immunogenicity and how to work out a risk assessment plan. Other experts are focusing on de-immunization approaches and the induction of tolerance. Over 100 participants, including four presenters from the FDA attended in 2014.
Quote from 2014: "Phenomenal presentations of great advances in multiple fronts. The most exciting meeting pertaining to immunogenicity of biotherapeutics."
Who should attend: This conference will bring together individuals from regulatory affairs, bioanalytical development, clinical and non-clinical immunology, PKPD, Pharmacology, toxicology safety and R&D.
I am looking for case studies and practical experience of the following:
Proposed short courses:
Basics of Immunogenicity
Overcoming the Challenges of Immunogenicity Assessment
Immunogenicity Risk Assessment and Regulatory Strategy
Strategic Bioassay Design and Analysis
If you would like to submit a proposal to give a presentation at this meeting, please click here.
Deadline for submission is May 7, 2015.
All proposals are subject to review by the Scientific Advisory Committee to ensure the highest quality of the conference program. Please note that due to limited speaking slots, preference is given to pharmaceutical and biotech companies, regulators and those from academia. Additionally, vendors/consultants who provide products and services to these biopharmaceutical companies are offered opportunities for podium presentation slots based on a variety of Corporate Sponsorships.
For more details on the conference, please contact:
Nicole Lyscom, Ph.D.
Conference Director
Cambridge Healthtech Institute
Tel: +44 7791 866489
Email: email@example.com
For exhibit & sponsorship opportunities, please contact:
Carolyn Benton
Business Development Manager
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Tel: 781-972-5412
Email: firstname.lastname@example.com
Download 2014 Brochure
View All Sponsors
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Reducing and Monitoring Bioassay Variability
2013 Speaker: Janet L. Lathey, Ph.D., Director, Immunology and Assay Development, BioDefenseDivision, Emergent BioSolutions


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Delphi Information Systems Inc. Users Groups Merge.
Delphi Users Association Inc. (DUA) and Delphi Partners International Association Inc. (DPIA) Wednesday announced that they have voted to merge.
The combined organization will adopt the Delphi Users Association name. DUA is a collaborative user advocacy group for users of agency management systems from Delphi Information Systems Inc., including cd.global(TM), cd.one(TM), INfinity(R), INSIGHT(R) and Insurnet(R).
Carolyn Goodnight, the newly elected president of DUA, said: "I'm pleased that the merger of DUA and DPIA puts us just that much closer to a strong, unified Delphi user group. The diversity of our constituents, ranging from the very smallest agencies to the largest in the insurance industry, should lend a new perspective that can further enhance our discussions with Delphi."
The new organization will represent more than 400 user agencies and brokerages varying in agency size and will include some of the largest independent insurance agencies and brokerages in the United States. As a combined organization, DUA will represent the interest of its members with Delphi Information Systems and other software and hardware vendors in the insurance industry.
"The DPIA group is pleased about this merger and sees it as a very positive step in the forward-moving software arena," stated Eric Enis, previous president of DPIA and newly elected vice president of DUA. "The new products that Delphi is presenting are very progressive and we look forward to implementing all platforms on their products as we move into the 21st century!"
The DUA board of directors will be composed of nine members: eight members will provide equal representation from each of the following Delphi platforms: INfinity, INSIGHT, Insurnet and cd.one. The ninth member will represent Delphi's cd.global.
Upcoming activities for the association include active participation in Delphi product development, an Accounting Conference in Orlando, Fla., to be held Sept. 8-10, 1999, and a selection of regional meetings in October 1999.
In collaboration with the Association of Redshaw Insurance Agency Systems (ARIAS) users group, which represents another large group of Delphi users, DUA is in the planning stages for its 2000 annual conference, to be held in Las Vegas, June 20-23, 2000.
About Delphi Information Systems
Founded in 1976, Delphi Information Systems is a leading international supplier of software and Internet solutions to the property and casualty insurance industry. An independent provider, Delphi delivers next-generation and next-step products and services to enhance operations for agencies, brokerages and carriers.
Delphi's cutting-edge agency management products feature fully customizable and scalable software designed to improve the way insurance professionals manage all aspects of insurance distribution, including marketing, sales, service, accounting and management.
About Delphi Users Association
Delphi Users Association is a nonprofit membership organization open to agencies or brokerages that use any products or services of Delphi Information Systems. Its purpose is to promote education, communication, profitability, product development and professionalism for its members.
For more information on the Delphi Users Association, call its West Coast office at 805/529-1165, East Coast office at 407/932-0084 or visit the DUA Web site at www.DUA.org.
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Starring: Mariette Hartley Lou Ferrigno Bill Bixby Kurt Johnson
Learn more about Incredible Hulk Complete Series:
Format: DVD
Manufacturer: Universal Home Video
Sku: 208930800
Category Keywords: 1970s 1980s Action Classic Television Cult Scientists Stress Reduction Superheroes Television/TV Series
Rating: NR
See more in Action/Adventure
Editor's NoteMarvel Comics gave him life, but CBS made the Incredible Hulk an indelible part of the pop culture imagination. Debuting in 1978, the action series strayed from the Marvel mythology: Once physician David Banner (Bill Bixby) loses his wife in a car accident (and is unable to save her), he bombards himself with gamma radiation in an attempt to access the super-human strength he believed all people held within. The experiment, of course, goes famously awry, and instead sticks Banner with a destructive alter-ego--the Hulk (Lou Ferrigno)--that takes over whenever the good doctor gets angry. THE INCREDIBLE HULK's five seasons followed Banner's life in hiding as he sought a cure for his inner-demon, and dodged the dogged pursuit of Jack McGee (Jack Colvin), an investigative reporter always hot on his trail. This complete collector's set includes every episode of the Hulk saga, including the much-lauded original pilot.
Cast & Crew
|Mariette Hartley
|Lou Ferrigno
|Bill Bixby
|Kurt Johnson


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Average employees -- those who do their jobs but give little more -- aren't necessarily a problem, Steve Errey writes. It's worthwhile to figure out what inspires these employees so you can try to give them work they're passionate about. But it's also true that an average employee might be a reliable individual who may stick around for a long time.
View Full Article in:TheDailyMuse.com
Published in Brief:


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Climate finance to Africa has been growing considerably. However, only 45% of approved funding is delivered for adaptation measures.
In this blog series, our experts share their thoughts on key financing for development issues... Read more
The Speakers Corner helps connect think tanks, academia, the media and the public to a diverse group of experts who can speak to UNDP's commitment to "empower lives" and build "resilient nations."


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Timothy 'Tim' Parrilli
Timothy "Tim" Parrilli, passed away early Sunday morning, July 20, 2014, at the age of 63. He died after a short battle with esophageal cancer.
Timothy was born on Jan. 31, 1951, to Joseph and Barbara (Engvalson) Parrilli of Oak Park, Ill. He married Charlotte Fraley on Oct. 8, 1971, in Naperville, Ill.
From stacking Cheerios as a toddler to remodeling and constructing new homes, Tim was a carpenter and builder all his life. Tim owned a successful contracting business with his brother for many years in Maple Park. He was a hard-working husband, father of five and grandfather of five.
Tim had many passions in life, from crafting with wood and enjoying the outdoors, to talking politics and history, inspiring his friends and family with his animated stories—better than a history teacher. Tim could tell even the smallest details about almost any historical event, especially the Civil War and World War II.
Tim was especially passionate about his antique cars. He owned, restored and meticulously cared for his cars, and he loved to drive and show them off at car shows.
Tim left his mark on this world in many ways, but the most important way to him was by his family: his wife, Charlotte; daughters, Julie (Coby), Elizabeth (Ryan) Bobowiec, and Mary; son, Daniel (Tina); as well as grandsons, Chris, Cory and Owen; and granddaughters, Calabria and Olivia. He had an impact on many people and will continue to lead his family through their own lives with his wisdom.
He was preceded in death by his parents; brother, Chris; and daughter, Kathleen Rose.
A memorial will take place from 2 to 6 p.m., with a blessing at 5 p.m., on Saturday, Aug. 9, at Conley Funeral Home, 116 W. Pierce St., Elburn.
In lieu of flowers, send donations in Tim's name to The Esophageal Cancer Action Network. For more information and to make donations, visit ecan.org. For notification recipient address, use 834 County Road Z, Arkdale, Wis. 54613.
Herman-Taylor Funeral Home and Cremation Center is assisting the family. Online condolences may be expressed at www.taylorfuneralhome.net.


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We want to ensure that making a return is as easy and hassle-free as possible! If for any reason you decide that your purchase just isn't for you, simply return the item within 30 days of receipt and we'll cover the cost of return shipping. Learn more about our Return Policy.
Champion Targets "Steady Bags" Gorilla Precision Shooting Bag 40467 is a solid shooting rest made with the serious shooter in mind. The Champion Targets Steady Bags Gorilla Bag can be used in a variety of configurations while range shooting, whether you are shooting prone or from a shooting bench. Reduce recoil impact during rifle shooting with Champion Targets Gorilla Range Bag. The suede bag surface lets you get a secure grip on your rifle without damaging the finish of the rifle barrel. This Champion Targets shooting bag system is pre-filled and comes ready to head to the shooting range or into the field. Your target shooting will be right on the bull's-eye with Champion "Steady Bags" Gorilla Precision Shooting Bag.
Whether you need a gun bag or a shooting stick, a monopod or a rifle bipod, we are your source. We carry a full line of Shooting Accessories to meet your gun shooting needs. Our online store has the best prices on Champion Targets shooting accessories. All of our merchandise is backed by the best customer service to be found online, and comes with a 100% satisfaction guarantee. Our product experts can answer questions about the Champion Targets Gorilla Range Bag and any other product from our store.
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Community rehabilitation interventions for stroke patients have not had a great track record of delivering measurable improvements. But new research from New Zealand focused on Maori and Pacific populations shows how a cheap and simple intervention that puts the patient and families in charge can make a difference to their quality of life. The study can be found in the journal Clinical Rehabilitation, which is published by SAGE.
Two interventions were trialled in this multi-center, randomized study: an inspirational DVD, and a guided 'Take Charge' session. Patients given these interventions shortly after discharge from hospital were followed up a year later, to evaluate their health-related quality of life. The Take Charge session improved patients' physical health scores on a scale of 0-100 by six points, while the DVD upped the result by one point. Those who had received a Take Charge session were also less likely to be rated with more than 'slight disability,' and their carers reported a lower degree of strain.
According to theory, when someone takes charge of their own recovery from an illness or in managing a disability, their perceived quality of life improves. Yet few community rehabilitation interventions have proven effective for those who have suffered a stroke. Most are therapy-led, or involve support workers. However, a third approach in community intervention involves handing back responsibility to the patient, and promoting their self-confidence. This is the approach used in the New Zealand intervention, known as self-directed rehabilitation.
According to the authors of this report, stroke patients of Maori and Pacific ethnicity have some of the worst outcomes, despite similar levels of activity and independence to New Zealanders of European heritage on leaving hospital. So these two groups were targeted in this study. However, the authors say that emphasis on self-directed rehabilitation has the potential to improve
|Contact: Jayne Fairley
SAGE Publications


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Series of Erotica
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For the first five years of his life Tim has never seen his fraternal twin sister, Traci, nor his mother. Now he only sees them as beautiful, sexual women, not as his mother and sister.
One day, while secretly observing Mom sun bathing nude–and masturbating–his sister walks in. Much to his surprise, rather than running screaming from the room, Sis performs oral sex on him. The action gets hotter until all three – Mom, Son, and Daughter, end up in bed together.
The Pilgrims' Progress
By E.R.O. Scott
[INCEST EROTICA: Father Daughter Incest, Mother Daughter Incest, Brother Sister Incest, Incest Threesome, Incest Orgy, IR, Anal Sex, Fisting, Golden Showers, Scat, Pregnancy]
The final book in the Lauren's Desires Trilogy where a chance encounter makes Lauren disclose her desire for her hugely endowed father. Lauren shares her father's sexual appetite for anal sex. This opens up reams of tempestuous sex spanning across all human kinks and sexual proclivities.
Strong adult content. Repeated incestuous sex. Strong sexual fetishes. If you enjoy milder erotica please use caution.
My Little Girl
Lauren's Desire Trilogy III By Allison Heather
[Incest Erotica: Mother Daughter Incest, Sister Sister Lovers, Lesbian Sex & Fisting, Family Ménage à Trois, The UPS Man]
Carrie was excited. It will really happen! My daughter wants to go down on me; to lick and suck and "eat" my pussy! she realized. Carrie was almost in a state of shock over what she and her daughter intended to do. So taboo! So condemned by regular society! But, yes, she wanted it to happen, wrong or not. She was so excited that she felt lightheaded. Oh yes! She was so ready to feel Caitlin's mouth on her pussy and all the pleasure that would follow. And, later to do the same for her daughter.
Remembered Desires
By E.R.O. Scott
Daughter Incest: also with Father- Daughter Incest, Older Man/Young Girl Sex,
Ménage à trois]
Why did her boyfriend stop, Carolyn wonders.Is there something wrong with her? If you thought something was wrong with you, would you not turn to your mother for help? What's a mother to do? Right, but Carolyn seduces her mother's boyfriend first!
A young girls coming of age incest novel, in a split home with no father. Mom understands. Find out how understanding ... READ MORE>>>
More Than Her Mother
By Honey Bliss
Sophie's Decision
By Allison Heather
[INCEST EROTICA: Mother Daughter Incest, Uncle Niece sex, Brother Sister Sex, watersports,
lesbian futanari, hermaphrodite dickgirl, monster cock, females with cocks, Futuristic
A futuristic story involving hermaphrodite sexuality (Futanari) for adults. Sophie invents the ultimate molecular modifying gene, and decides to complete the work her father could not finish. She chooses herself as the subject: if she succeeds, she wishes to express her love towards her mother. All is at stake. An intense incestuous love story between a mom and her daughter who possesses a monster cock with plenty of uncle niece sex included.
[Incest Erotica & BDSM Erotica: Mother Daughter Incest, Father Daughter Incest, Uncle Niece Sex, Domination & Submission, Spanking]
Jasmine grows up in a strict family with one major rule. She must never enter one
particular room in the house. Mother has watched her little girl grow up and long
planned for the day her daughter turns eighteen. Now that her daughter is a young
woman, she must follow in her mother's footsteps by entering the forbidden room.
Since Mother has always had a close relationship with her daughter, now it's time
for the Mother to teach her daughter all about the ways of sex. Little does Mother
realize her daughter is a natural submissive, and that she will rise quickly within
the ranks of her family. When her father gives her to an uncle she's never met, Jasmine
gets a taste of the kinky lifestyle her parents grew up in -
A Family Confessed Tradition
By Lily Weidner
Family Traditions
[Father Daughter Incest, Mother Daughter Incest, Brother Sister Incest, Spanking, BDSM, M/F/F]
Virginia is tired of bad dates and boring young guys. She wants the experience only an older man can provide and she has her eyes set on Father. But when things start to heat up, they get hotter than she ever expected. Now he has her tied down naked on his bed, her legs spread wide, just as Mother walks in…
By Stephani Wilder
[INCEST EROTICA & BDSM: Father and Daughter Incest, Mother and Daughter Incest, Sister and Sister Incest, Grandmother and Granddaughter Incest, Humiliation, Spanking, Tickling, Force]
The continuing story of Sarah Jane who discovers her dominant side. She assists Daddy first in abducting Mother, then plots her own sweet revenge on Grandmother, not to mention sister. Tricking the family into a soundproof dungeon built in daddy's basement, she subjects Mother and the rest of the family females into forced incest, bondage and orgiastic sexuality, dealing out both pleasure and pain in exacting revenge. Warning: Not for faint of heart.
Sarah Jane's Revenge
By Phaedrus T. Wolfe
Book #2
The Sarah Jane Trilogy
Pussycat Smile
Edited By Phaedrus T. Wolfe
A Controlling Interest
By Honey Bliss
[INCEST EROTICA: Father Daughter Incest, Mother Daughter Incest, Mother's Consent and Assistance, Family Exotica Threesome, Menage mff]
Nancy finds herself fantasizing about, and even doing things that would have previously been unthinkable. Is it simply uncontrollable lust? There's only person in the world Nancy will give her virginity to. But Daddy is not comfortable and she is powerless to do anything about seducing him without help. Is Nancy deviant? She turns to Mom, the one person who possesses the controlling interest.
Give And Take
By Forrest Young
[INCEST EROTICA: Mother daughter Sex, Daddy Daughter Taboo, Father Daughter Incest, Exhibitionism & Voyeurism, Spanking and Interracial Sex]
Paige steers Natalie in the direction of having her ultimate incestuous fantasies and desires fulfilled. In the meantime, Paige gains an unexpected ally in her attempts at fulfilling her own incestuous cravings: Her mother!
Book #3
Angel Falls Library Files
Blackmail On The Prairie
By Baron LeSade
[Mother Son Incest, Mother Daughter Incest, Menage, Anal & Oral Sex, Blackmailed into Sex, Multiple Partners, Cowboy Western Incest Novel]
Catching Mom with panties at her ankles being blackmailed by a local bad guy, cowboy Jake risks everything to save Mom's honor and restore her dignity while avoiding jail for revenge murder. Mom has an extra secret to share with Jake when Pa is not around—a ploy concocted by Mom to secure her son's perpetual silence in a small Texas town, the key to leaving her troubled past behind… and making a worthy gamble with her heart.
The Truth
By Phaedrus T. Wolfe
[Father Daughter Incest, Mother Daughter Sex, Dubious Consent, Submissive Girl, Light Dominance & Submission BDSM, Family Exotica, Grandparent Incest]
Vivian sets out on a weeklong camping trip alone with Daddy to learn the ugly truth about her childhood. Daddy seems surprisingly willing to assist her in discovering forgotten memories. Will he take advantage of her? In the process, Vivian learns she has a natural submissive personality. Only then is she ready to learn 'why' from Mother. Based on the true story of a father and daughters relationship.
WARNING: Explicit Photos Inside
Adult Toy Store
Daughter Models
By Lydia Gray
[Mother Daughter Incest, Lesbian Sex, Barely Legal Seduction, MILF, XXX X-
When professional photographer Scott shows up, Sandra and Kathy discover a simple but revolutionary idea. Lonely divorced mothers and young daughters can band together, beat the odds and thrive through adolescence. By facing the challenges of finding a man together, a mother and daughter can love staying close and having fun while taking on the hottest sexual issues girls and women face.
Maria & Her Mom
By Dinkleberry
[Mother Daughter Incest, Lesbian Intimacy, Cougar MILF, Older Woman Sex, Gay Romance, Family Exotica, Mom Girl Lovers]
Being a girl is awesome! As women, we're allowed to display our emotions. We can express our feelings by joyously hugging our girlfriends. Spontaneously, we can kiss our best friend to show our happiness of being with them. When a daughter loves her mother completely, she can hug, kiss and physically bond with her. Mother and daughter can display their love many ways. Yes, being a girl is awesome!
Finally! The only definitive mother/daughter story of true lesbian love. Written
by a woman, to be enjoyed by all, this girl-


text:
Dan's Papers June 8, 2012
Dan's Papers June 8, 2012 Issue
DAN'S PAPERS danshamptons.comPage12June8,2012 VOLUME LII NUMBER 12 This issue is dedicated to Laurie Anderson. 35 200th Anniversary by Dan Rattiner Most celebrations of the War of 1812 (the 200th anniversary is this year) involve defeats. The encounter in Sag Harbor at Long Wharf involved a victory. The enemy came, landed briefly on Long Wharf and was driven off, never to return. 29 South O' the Highway All the latest Hamptons celebrity news. 31 Hamptons Subway by Dan Rattiner 32 Police Blotter by David Lion Rattiner All the news that's not fit to print on the East End. Featuring Shelter Island. 33 PAGE 27 Your route to where the beautiful people play. 41 Empire State Building, Jealous, Strikes Back by Dan Rattiner Is it possible for the legendary 102 story Empire State Building to be jealous of competitors? 43 PotatoHampton Diary by Dan Rattiner My day watching the run for the potatoes in Bridgehampton 43 All About the Bulova Watchcase Factory by Evan Reeves Getting closer to completion... 45 Jesus, or Someone Like him, Carries a Cross Here by Evan Reeves "Jesus" "crosses" the Forks? 47 Let's Get Together in Quogue by Mr. Sniev My scientific endeavors 49 My Brilliant Divorce by Dan Koontz Review of Bay Street Theatre 50 Johnny Winter by Debbie Slevin Performing at Riverhead Blues and Music Festival 52 A Bay Street Comedy Preview by Katey McCutcheon Coming to Sag Harbor in June guest essay 55 Diving Under the Influence by Raymond Conklin An idyllic East End summer 58 Graduation and Beyond by Robert Sforza What happens after graduation? Who's here 59 Polly Draper by Debbie Slevin Actress 20something 61 Life: Love it, Hate it by David Lion Rattiner Go to the gym in the morning honoring the artist 62 Dinah Maxwell Smith by Marion Wolberg Weiss sheltered islander 62 Cricket Anyone? by Sally Flynn The Brits' plan for the Island hamptons epicure 63 No Hallmark Card by Stacy Dermont It's hard to put a name to this 10 minute golf 65 Tom Watson Honored by Darren deMaille The Memorial Tournament 66 News Briefs Dan's weekly update from around the East End 37 The Hot Mercedes-Benz by Dan Rattiner In an astonishing parallel to the movie Ferris Bueller's Day Off, some kids in their early 20s "borrow" one of their parent's hot red Mercedes convertible without permission and plan to have it back before the parents find out, but then something goes horribly, horribly wrong. 37 East Hampton's Main Beach Ranked 3rd by Evan Reeves Dr. Beach has come out with this year's Top 10 Beaches in America. Main Beach in East Hampton continues to rise, mak- ing it to the No. 3 spot. All other beaches in the Hamptons are not nearly as good... 41 Problem by Dan Rattiner The author sees a black cable loose, halfway down on the side of his house and figures out it is a TV cable. He has an interesting conversation with the people who put it up on the building. 36 June 8, 2012


text:
The Washington think tank, The Center of Foreign Affairs and Geographical Shifts has identified a unique trend in American's knowledge of international affairs and world geography. During an exhaustive 24-year study, they have released a 1200 page report. The most significant conclusion is that most Americans exclusively gain 90 percent of their information about world affairs and geographical shifts from Bob Costas, every four years during the Olympics. The majority of this information is obtained during the opening ceremonies, after which most of the study's participants lose interest, unless a really cute teen with a heartwarming story wins a medal.
The other significant spikes in interest in geographical shifts coincide with events where the US bombs foreign countries, displaying the latest high tech weapons.
Apparently, Bob Costas' commentary on geography and world events relating to Olympic teams often creates more questions than it answers. Certain trends have emerged during the London Games, including these questions that consistently were raised by study participants during a focus group:
"Who is Stan, and why are so many countries named after him? Oh, and what happened to the USSR? If I remember, they used to be pretty good. "
"How is there an Arab Spring, when it's the Summer Olympics?"
"I've never even heard of that country!"
"When does Apolo Ohno come on? I saw him on a Subway commercial."
"I've never heard of that sport! Why isn't there real football in the Olympics?"
"What does Abraham Lincoln have to do with England?"
"Look at those funny hats!"
"I thought we bombed that country out of existence?
"Why are we paying these NBA players millions, if they're going to be traitors and play for some third-rate country we rescued them from?"
"What's a Euro? Oh, I think, it's the piss-ant green hippy car my neighbor drives. I told my wife that thing was going to be nothing but trouble."
"Why aren't the sand volleyball women wearing those sexy outfits this year?"
The study also identified a sharp division among Americans over who is smarter: Bob Costas or Alex Trebek? However, 94 percent of Americans said they would vote for a Costas / Trebek presidential ticket (or vice versa).


text:
Cole Haan Accessories
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Material: Woven Leather
Brand: Cole Haan Accessories


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text:
Calcium sparks are ryanodine receptor mediated transient calcium signals that have been shown to hyperpolarize the membrane potential by activating large conductance calcium activated potassium (BK) channels in vascular smooth muscle cells. Along with voltage-dependent calcium channels, they form a signaling unit that has a vasodilatory influence on vascular diameter and regulation of myogenic tone. The existence and role of calcium sparks has hitherto been unexplored in the spiral modiolar artery, the end artery that controls blood flow to the cochlea. The goal of the present study was to determine the presence and properties of calcium sparks in the intact gerbil spiral modiolar artery.
Calcium sparks were recorded from smooth muscle cells of intact arteries loaded with fluo-4 AM. Calcium sparks occurred with a frequency of 2.6 Hz, a rise time of 17 ms and a time to half-decay of 20 ms. Ryanodine reduced spark frequency within 3 min from 2.6 to 0.6 Hz. Caffeine (1 mM) increased spark frequency from 2.3 to 3.3 Hz and prolonged rise and half-decay times from 17 to 19 ms and from 20 to 23 ms, respectively. Elevation of potassium (3.6 to 37.5 mM), presumably via depolarization, increased spark frequency from 2.4 to 3.2 Hz. Neither ryanodine nor depolarization changed rise or decay times.
This is the first characterization of calcium sparks in smooth muscle cells of the spiral modiolar artery. The results suggest that calcium sparks may regulate the diameter of the spiral modiolar artery and cochlear blood flow.
The gerbil spiral modiolar artery (SMA) originates via the anterior inferior cerebellar artery from the basilar artery and provides the blood supply to the cochlea. It has an outer diameter of ~60 μm and follows the eighth cranial nerve from the brain stem to the modiolus of the cochlea [1]. The SMA is an end-artery that feeds the capillary networks of the spiral ligament and the stria vascularis, which maintains the endocochlear potential essential for hearing [2]. This energy-intensive mechanism renders the cochlea vulnerable to ischemia, which is thought to be involved in the pathogenesis of hearing loss and tinnitus. Consequently, the mechanisms that regulate the diameter of the SMA and thereby cochlear blood flow are of great interest.
Vascular tone is determined by the contractility of the smooth muscle cell, which is regulated by membrane-potential and Ca2+-dependent as well as independent mechanisms [3]. An important regulator of smooth muscle contractility is the ryanodine receptor (RyR) mediated "Ca2+ spark". Ca2+ sparks are the physical manifestation of coordinated openings of clustered RyRs causing a highly localized and transient increase in the Ca2+ concentration in the subsarcolemmal space [4]. Ca2+ sparks have been demonstrated in all muscle cells - cardiac, skeletal as well as smooth muscle cells. In cardiac and skeletal muscle cells, tight coupling between sarcolemmal voltage-dependent Ca2+ channels (VDCCs) in the T-tubules and RyRs in the terminal cisternae generates a depolarization-induced Ca2+-induced-Ca2+-release (CICR) process that causes contraction [4]. On the other hand, in smooth muscle cells, particularly in vascular smooth muscle cells, RyRs, large-conductance calcium- and voltage-activated K+ (BK) channels and VDCCs have been shown to form a functional triad that maintains or mediates vasodilation by limiting Ca2+ influx via VDCCs [5-8]. Increases in the Ca2+ concentration in the subsarcolemmal space caused by Ca2+ sparks, which engulf the cytosolic face of BK channels, cause activation of these channels and hyperpolarization of the membrane potential, closure of VDCCs and vasodilation via a decrease in the cytosolic Ca2+ concentration in the vicinity of the contractile myofilaments. Thus, Ca2+ sparks form a negative feedback mechanism that regulates vascular tone and hence blood flow. This mechanism has not yet been identified in the regulation of cochlear blood flow. Previous studies from our lab have indicated the presence of a ryanodine-sensitive Ca2+ sensing receptor in vascular smooth muscle cells that regulates the contractility of the gerbil SMA [9]. A role for RyR-mediated Ca2+ release in hyperpolarization of smooth muscle cells, mediated by activation of BK channels, has been previously suggested in guinea-pig SMA [10].
The goal of the present study was to detail the presence and properties of Ca2+ sparks in smooth muscle cells of the intact gerbil spiral modiolar artery. To that end, a protocol for the measurement of Ca2+ sparks in the gerbil SMA was established and software for the analysis of Ca2+ sparks was developed. We demonstrate for the first time, a detailed analysis of the kinetics and properties of Ca2+ sparks in smooth muscle cells of the intact gerbil SMA and their regulation by pharmacological activators and inhibitors of RyRs as well as changes in smooth muscle membrane potential. The data suggest that Ca2+ sparks are important for regulating the contractility of the smooth muscles of the SMA and thereby vascular tone and cochlear blood flow.
Localization of ryanodine receptors
In the first series of experiments, ryanodine receptors were visualized using a green fluorescent derivative of ryanodine. A punctuate staining pattern was expected if ryanodine receptors were limited to or concentrated at distinct spark sites. Staining with 1 μM Bodipy® FL-X ryanodine produced a pattern that was consistent with RyRs being uniformly expressed in the sarcoplasmic reticulum (Figure 1). Specificity of staining was verified by competition with unlabeled ryanodine. Nearly no staining was observed with 1 μM Bodipy® FL-X ryanodine in the presence of 250 μM unlabelled ryanodine. No evidence for a concentration of ryanodine receptors to distinct spark sites was obtained. The staining pattern is consistent with the theory of loose coupling between plasmalemmal L-type Ca2+ channels and sarcoplasmic RyRs in smooth muscle as against the direct spatial and physical coupling observed in cardiac and skeletal muscle respectively [11].
Figure 1. Staining for ryanodine receptors in the spiral modiolar artery. (A) Ryanodine receptors were labeled with 1 μM Bodipy®-ryanodine. Specificity was evaluated by staining with 1 μM Bodipy®-ryanodine in the absence (B) or presence (C) of 250 μM unlabelled ryanodine.
Detection of Ca2+ sparks
In a typical recording of Ca2+ sparks from a smooth muscle cell of the intact SMA loaded with the Ca2+ indicator fluo-4, Ca2+ sparks occurred spontaneously (Figure 2). Representative image frames recorded at 41.5 ms intervals show a Ca2+ spark occurring at 124.5 ms after the start of recording (frame 3 of Figure 2A), that rapidly decayed within a single frame interval of 41.5 ms (frame 4). Ca2+ sparks occupied a mean spatial width of 2.4 ± 0.1 μm (n = 25 spark sites). For further analysis of sparks, nine consecutive line-scans, each lasting 5s with a 20s interval between scans, were recorded at selected spark sites. There was no loss of fidelity in the observed Ca2+ sparks under control conditions for the duration of the nine line-scans. Figure 2B shows a typical 5s line scan recording of a chosen spark site where robust Ca2+ sparks occurred with high frequency. Custom written software described in methods proved very effective in detecting and analyzing Ca2+ sparks and spark kinetics from line scans (Figure 2C and 2D). Spark parameters were averaged over the entire recording period. In this preparation under control conditions, Ca2+ sparks occurred with a frequency of 2.6 ± 0.1 Hz/spark site (n = 105 spark sites), with a rise time of 17 ± 0.3 ms and a time to half decay of 21 ± 0.7 ms (averaged from 4,103 sparks recorded from 105 spark sites).
Figure 2. Imaging and recording of Ca2+ sparks. (A) Series of confocal images obtained at a temporal resolution of 41.5 ms. Ca2+ sparks were identified as highly localized elevations in the cytosolic Ca2+ concentration of the smooth muscle cell (outlined in the left-most image).(B) Image and fluorescent trace obtained from a typical 5s scan at a temporal resolution of 1.92 ms shows spontaneous Ca2+ sparks occurring with high frequency. Numbers beside transients indicate sparks. Sparks were identified and frequency was calculated using custom-designed software. The sparks marked 'x' and 'y' are shown in (C) and (D) with an expanded resolution. Amplitude (Peak - Base intensity), rise time (Peak - Base time) and time to half decay (Half decay - Peak time) were obtained from individual Ca2+ sparks. (C) An example showing identification of sparks and calculation of spark parameters by the software for a Ca2+ spark rising from the baseline. (D) An example showing identification of sparks and calculation of spark parameters by the software for a Ca2+ spark "pair", where the second spark rises before the first returns to baseline. Spark amplitude, rise time and decay time are calculated only from the first and not the second spark.
Effect of ryanodine and caffeine on Ca2+ sparks
Ryanodine is a plant alkaloid that specifically binds to RyRs and inhibits them at micromolar concentration, leading to the cessation of Ca2+ sparks. A typical line-scan experiment for the application of ryanodine is depicted in Figure 3A. 1 μM ryanodine caused a significant decrease in Ca2+ spark frequency and amplitude by scan 9 (Figure 3B). In five experiments, there was complete cessation of sparks before the end of the experiment. Ca2+ spark frequency in the presence of ryanodine, averaged from 11 experiments, was 0.6 ± 0.3 Hz/spark site, which is a ~4-fold decrease to that observed without ryanodine (Figure 3C). Interestingly, ryanodine did not have a significant effect on the rise-time or decay time of sparks. Rise time and decay time were 17 ± 1 ms and 14 ± 2 ms respectively in the presence of ryanodine (averaged from 104 sparks recorded from 8 spark sites) and 18 ± 0.6 ms and 21 ± 3 ms respectively in time-matched controls.
Figure 3. Ryanodine reduces the frequency of Ca2+ sparks. (A) A typical experiment for the effects of ryanodine on sparks. Ryanodine decreased spark frequency by the 9th scan. (B) Expanded line scans from (A) shows a trace in control (scan 1) and in ryanodine (scan 9). Numbers beside transients indicate sparks. (C) Ryanodine reduced the frequency of Ca2+ sparks but had no major effect on Ca2+ spark rise time or time to half-decay. Recordings in the presence of ryanodine were made at 10, 40, 70, 100, 130 and 160s after application of ryanodine. Time control experiments revealed that Ca2+ spark frequency, amplitude, rise time and time to half-decay were reasonably stable for nine 5 s line scans spread over 225s.
Caffeine is an activator of RyRs, which at very low concentrations (μM - 1 mM) causes an increase in spark frequency whereas when used in high concentrations (> 5 mM) induces a robust Ca2+ release that depletes the Ca2+ stores [4]. Consistent with previous reports of the effects of low concentrations of caffeine, 1 mM caffeine induced significant reversible increases in Ca2+ spark frequency, rise time and time to half-decay in the smooth muscle cells of the SMA (Figure 4). Spark frequency was 3.3 ± 0.4 Hz/spark site in caffeine vs. 2.3 ± 0.2 Hz/spark site in time-matched controls without caffeine (n = 25). Rise time was 19 ± 0.5 ms (1186 sparks from n = 25 sites) in caffeine vs. 17 ± 0.3 ms (1618 sparks from n = 25 sites) in time-matched controls. Time to half-decay was 23 ± 1 ms (1186 sparks from n = 25 sites) in caffeine vs. 20 ± 1 ms (1618 sparks from n = 25 sites) in time-matched controls. In addition to measured spark attributes, spark morphology was altered significantly (Figure 4A). In the presence of caffeine, many sparks exhibited a slower, more rounded rise that lingered at the peak longer than normal sparks, suggesting altered kinetics of RyRs due to activation by caffeine.
Figure 4. Caffeine altered frequency, rise and decay times of Ca2+ sparks. (A) Original recordings of Ca2+ sparks in the absence (top trace), presence (middle trace) and washout (bottom trace) of 1 mM caffeine. Numbers beside transients indicate sparks. (B) Caffeine increased the frequency, rise and decay time of Ca2+ sparks but had no effect on Ca2+ spark amplitude. Recordings in the presence of caffeine were made at 10, 40 and 70s after drug application and recordings during washout were made at 10, 40 and 70s after termination of drug application. Time control experiments revealed that Ca2+ spark frequency, amplitude, rise time and time to half-decay were reasonably stable for nine 5 s line scans spread over 225 s.
Effect of membrane potential depolarization on Ca2+ sparks
Membrane potential depolarization increases intracellular Ca2+ which in turn increases Ca2+ spark frequency in vascular smooth muscle cells [11-13]. Intact SMA segments were depolarized with a 37.5 mM [K+] superfusing solution. Consistent with observations in other vascular smooth muscle cells, high K+ significantly increased Ca2+ spark frequency in smooth muscle cells of the SMA that returned to control levels upon re-perfusion with PSS (Figure 5A). Spark frequency in high K+ was 3.2 ± 0.3 Hz/spark site (n = 21 experiments), a 1.4 - fold increase in frequency, with no significant change in spark amplitude, rise time or time to half-decay (Figure 5B).
Figure 5. K+ induced depolarization increased the frequency of Ca2+ sparks. (A) Original recordings of Ca2+ sparks in the absence (top trace), presence (middle trace) and washout (bottom trace) of 37.5 mM K+. Numbers beside transients indicate sparks. (B) Elevation of extracellular K+ from 3.6 to 37.5 mM increased the frequency of Ca2+ sparks but had no effect on amplitude, rise and half decay times of Ca2+ sparks. Recordings in the presence of 37.5 mM K+ were made at 10, 40 and 70s after K+ application and recordings during washout were made at 10, 40 and 70s after termination of K+ application. Time control experiments are replotted from Figure 3.
Discussion and Conclusion
The SMA, a coiled artery inside the cochlea, is a branch of the anterior inferior cerebellar artery, which in turn branches off from the basilar artery located on the surface of the brain stem [1]. The SMA is a small-caliber vessel (diameter ~ 60 μm) and has a single layer of smooth muscle cells that lacks tightly attached connective tissue [14]. This architecture makes the SMA exquisitely suitable for investigating smooth muscle cell calcium regulation in small vessels (< 70 μm) using intact arteries, as opposed to isolated cells, which are devoid of their natural milieu. The major findings of this study using an intact vessel preparation of the SMA are as follows: (1) The SMA contains ryanodine receptors (RyRs) in the smooth muscle cells. (2) Smooth muscle cells of the SMA exhibit Ca2+ sparks, which are inhibited by ryanodine, an inhibitor of RyR. (3) Elevation of K+ and caffeine increased the frequency of Ca2+ sparks. The kinetics (rise time, decay time and amplitude) were not affected by K+ but were altered by caffeine. These results suggest that RyR-mediated Ca2+ sparks regulate smooth muscle contractility and play a role in the regulation of cochlear blood flow.
Ca2+ sparks, along with BK channel and Ca2+ channel currents play a prominent role in regulating myogenic tone of extra-cerebral arteries on the surface of the brain [5,8]. Ca2+ sparks have been identified in many smooth muscle cells including smooth muscle cells from arteries [8,15,16], portal vein [17], urinary bladder [11,18], airways [19,20] and retinal arterioles [21]. Interestingly, ryanodine-dependent Ca2+ sparks were detected in smooth muscle cells of cremaster feed arteries but not in cremaster arterioles [22]. In this context, the observation of robust ryanodine-sensitive Ca2+ sparks in the smooth muscle cells of the intact SMA, a small-caliber third order branch of the basilar artery, is an important observation (Figure 2).
The gerbil SMA was found to generate well-defined sparks at robust frequencies. Ca2+ sparks occurred at individual spark sites with an average frequency of 2.6 ± 0.1 Hz (Figure 2). This frequency is higher than what has been reported for isolated smooth muscle cells [8,11,15,17,18,20,23] as well as intact cerebral arteries [13] and pressurized mesenteric arteries [16]. Rise time was ~ 17 ms, which is roughly similar to the rise time of 20 ms reported for rat cerebral vessels [8,24]. Time to half decay was ~ 21 ms, which is slightly faster than the 27 ms reported for rat portal vein [17,19] and much faster than 48 - 65 ms reported in cerebral vessels [8,24,25]. In fact, time to half decay of Ca2+ sparks in the gerbil SMA was more similar to the 23 - 37 ms reported for rat heart [26,27]. Reasons for these differences may be due to species differences, due to individuality among blood vessels and differences in experimental conditions.
Ca2+ sparks are regulated by intracellular Ca2+ [4]. In smooth muscle cells, intracellular Ca2+ is strictly regulated by membrane potential. Membrane depolarization by electrical or chemical means or graded increases in intraluminal pressure increases intracellular Ca2+ via Ca2+ influx and Ca2+ release [13,28,29]. Membrane depolarization induced by elevation of K+ has been previously shown to induce vasoconstriction of the SMA, which is sensitive to block of L-type VDCCs [30]. The observation that elevation of K+ increased Ca2+ spark frequency (Figure 5) suggests that Ca2+ sparks play a role in the regulation of smooth muscle excitability and contractility.
In summary, the data presented here establish the intact spiral modiolar artery as an excellent model for the study of RyR-mediated Ca2+ signaling in smooth muscle cells of small arteries (< 70 μm) since it generates high amplitude Ca2+ sparks at robust frequencies. The data suggest a role for Ca2+ sparks in regulating vascular tone of the SMA and cochlear blood flow.
Animal use
Female gerbils (2 - 3 months old) were anesthetized with sodium pentobarbital (100 mg/kg i.p.) and sacrificed by decapitation. All procedures concerning animals were performed under a protocol approved by the Institutional Animal Care and Use Committee at Kansas State University. Temporal bones housing the cochleae were removed, opened, and placed in a chilled (at 4°C) physiological salt solution. The spiral modiolar artery (SMA) is a long vessel (about 7-9 mm in the gerbil) that surrounds and remains loosely coiled against the eighth cranial nerve in the modiolus of the cochlea. The SMA was gently separated from the surrounding nerve and uncoiled taking care not to stretch the artery. Vessels segments were obtained from the center portion of the vessel, avoiding edges that may have been damaged during isolation.
Bodipy staining
Isolated vessel segments were incubated for 1 hr at RT in PSS containing 0.2% Triton-X and 1 μM Bodipy®-ryanodine (Molecular Probes, Eugene OR) with or without 250 μM unlabelled ryanodine. Vessels segments were washed, mounted on slides and observed by confocal microscopy (LSM-510Meta, Carl Zeiss, Germany).
Vascular superfusion
Isolated vessel segments were mounted on a custom-built superfusion chamber and held with two blunt glass needles operated by joy-stick micromanipulators (MN-151, Narashige, Japan). The bath chamber was installed on the stage of an inverted microscope. Superfusion was set to a rate of 2.5 bath chamber volumes per second. Water jacketing of perfusion lines ensured a constant temperature of 37°C and minimized the formation of air bubbles, which pose a threat to the vessel segment. Vessels were superfused either with a physiological saline solution (PSS) containing (in mM) 150 NaCl, 3.6 KCl, 1 MgCl2, 1 CaCl2, 5 HEPES, and 5 glucose, pH 7.4 or with a 37.5 mM K+ solution containing 115 NaCl, 37.5 KCl, 1 MgCl2, 1 CaCl2, 5 HEPES and 5 glucose, pH 7.4. Caffeine was directly dissolved in PSS and ryanodine was solubilized in DMSO before introduction into PSS. The final DMSO concentration was 0.1%. Drugs were purchased from Sigma-Aldrich (St. Louis, MO).
Measurement of Ca2+ Sparks
Isolated vessel segments were loaded with the Ca2+ indicator dye fluo-4 AM (5 μM, Molecular Probes, Eugene, OR) for 40 minutes at 37°C and mounted in a superfusion chamber fixed on the motorized stage of an inverted microscope (Axiovert 200, Carl Zeiss, Göttingen, Germany). The Ca2+ indicator dye fluo-4 is an analog of the commonly used fluo-3 that provides higher signal levels in response to excitation with the 488 nm line of the argon laser (Molecular Probes Product Information Sheet). Superfusion was carried out as described above. Fluo-4 was excited by the argon laser (488 nm) operated at 9 mW (30% of the maximum power of 30 mW) that was attenuated by an acousto-optical tunable filter to 1% for the measurement of Ca2+ sparks (LSM-Meta, Carl Zeiss, Göttingen, Germany). The beam path consisted of a notch filter (488 nm) followed by two long-pass filters (490 and 505 nm) and an oil immersion objective (Plan-Neofluar 40x, 1.3 NA, Carl Zeiss). Ca2+ sparks were imaged in confocal xy scans (76.8 × 5.2 μm corresponding to 512 × 35 pixels) with a spatial (x,y,z) resolution of 0.15 × 0.15 μm spatial resolution, an optical depth <0.9 μm and a temporal resolution of 41.5 ms (Figure 2A). For detailed analysis of spark kinetics, Ca2+ sparks were recorded in 5s non-confocal (open pinhole) line scans. Line scans, defined as repeated sweeps of the scanner along a single line (76.8 μm corresponding to 512 pixels), were performed at a chosen spark site with a spatial (x,z) resolution of 0.15 × <12.4 μm and a temporal resolution of 1.92 ms. Nine consecutive line scans, each lasting 5s, were taken. The time interval between line scans was ~40 s between the first and the second scan and ~25 s between all further scans.
Ca2+ spark detection and analysis
Line scan images (512 × 2605 pixels), covering 76.8 μm for 5 s, were visually inspected for sparks. Intensity values covering the width of a spark site were averaged and exported to a text file ('raw data') for analysis using an algorithm written in Labtalk (Origin 6.0, OriginLab). Frequency, amplitude, rise time (0 - 100%) and time to half-decay were determined for individual spark sites (Figure 2).
The analysis algorithm used the 'raw' data as well as a 'subtracted' data set that was generated by subtraction of a 'baseline' dataset generated by a 601-point sliding window average from a 'smoothed' dataset generated by a 5-point sliding window average of the 'raw' data. The 'subtracted' data were used for the identification of Ca2+ sparks. Sparks were identified by a user-defined number of consecutive intensity increases that spanned a user-defined minimum amplitude. 'Subtracted' data were further used to evaluate whether a spark is suitable for determining amplitude, rise and decay times. Suitable sparks are sparks that arise near or below the baseline (Figure 2C). Sparks that follow a previous spark too closely arise from a higher value which could lead to an underestimate of their amplitude (Figure 2D). Amplitude was determined as difference between the raw data peak and the base of the spark. The base was determined as the average of 10 raw data points immediately prior to the first of the consecutive increases. The rise time was the time from the end of the base to the peak and the time to half decay was the time between the peak and the time when the 'averaged' data decayed by half of the amplitude. The 'raw' data were graphed and annotated for visual inspection (Figure 2). Each identified spark was marked by a number and by a vertical indicator line transecting the peak of the spark. Measurable sparks received additional annotation including a horizontal line segment marking the base of the spark and a vertical line transecting the time of half decay. Measurements of amplitude, rise time and time to half-decay were averages of data that passed visual inspection.
Frequency, amplitude, rise and half-decay times of Ca2+ sparks were graphed as averages of values during each of the nine sequential measurements. Ca2+ spark data reported in the text are averages of three sequential measurements. Error bars are SEM. Significance was assumed at p < 0.05 and determined by either paired or unpaired t-test, as appropriate.
Authors' contributions
GK, KR, EQS and PW wrote the manuscript. KR collected and analyzed Ca2+ sparks data, developed the software code for sparks analysis. SB performed the Bodipy-ryanodine staining. PW conceived of the study and participated in the design of experiments and development of the analysis software. All authors have read and agreed to the final version of the manuscript.
The support by NIH R01 DC04280 is gratefully acknowledged. A major portion of this study has been submitted by Keil Regehr in partial fulfillment of the requirements for the degree of Master of Science in Electrical Engineering and Computer Science at Kansas State University.
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Community Based Services
- You Can Cook! Cook Book (Link will open on Information Page. Click the back button to return here.)
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- Infant Development Program
- Special Services to Children
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- Adult Life Skills
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Infant Development Program (IDP)
The Infant Development Program provides home based early intervention services to families with children from birth to three years of age who are experiencing delays in their development, or who are at risk for developmental delay.
Home visits are made on a regular basis by professional staff to assist the family in planning learning activities and to utilize appropriate community resources. Opportunities for parents to meet and support each other are provided through regular drop-in groups and classes organized on topics of interest to families.
Resource library materials of books and toys are also available for loan to families. Referrals can be made directly to the IDP.
Contact:Donna Colodey, Manager of the Infant Development Program at 604.986.1358
Special Services to Children
This program is for individuals between the ages of 5 and 18. Each person along with their family or support network develops a plan in order to be successful in reaching specific goals in community settings.Participants enjoy fun, skill-building activities with their one to one support worker who is suitably matched with the individual for the best possible outcome.Average hours of service are 5hrs per week.
Referrals are required from the Ministry of Children and Families (MCFD). MCFD is responsible for the order of acceptance and can be reached at 604.904.4300.
Contact the Director of Community Based Services at 604.904.4090 for more information.
View the Community Based Services Handbook (pdf).
Teen and Pre-Teen Social Program
This weekend program is for individuals between the ages of 9 and 18. Participants enjoy recreational activities and community outings with their peers while building social and life skills.They are actively involved in planning activities and meet as a group at the beginning of every month to create a recreation plan.This program runs on Saturday afternoons and is only closed on statutory holiday weekends.
Referrals are required from the Ministry of Children and Families (MCFD). MCFD is responsible for the order of acceptance and can be reached at 604.904.4300.
Contact the Director of Community Based Services at 604.904.4090 for more information.
View the Community Based Services Handbook (pdf).
Transition and Employment Services
A service to help young people and their families move through the transition process and to provide supports toward employment.
How we can help…
- Assist youth with disabilities to transition into the government services system
- Develop a transition plan for your future
- Provide information regarding transition and employment
- Facilitate workshops and information sessions
- Link you to services and resources in the community
- Attend school transition IEP meetings by request
- Job Club and employment workshops for job seekers
- Job development supports
- Individual appointments are available
To speak to the Transition and Employment Facilitator call:
604 904-4075 or 604 985-5371 email: email@example.com
Adult Life Skills
This service is for adults aged 19 and over who have disabilities and are interested in continuing to learn life skills. Participants choose a variety of life skills to learn at home or in community settings, assisted by a worker selected by the participant and their family or support network.
Referrals are required from Community Living BC (CLBC) www.communitylivingbc.ca. CLBC is responsible for the order of acceptance and can be reached at 604.981.0321. On average, CLBC allocates program participants with 4 hours of service per week and reviews their progress bi-annually.
Contact the Director of Community Based Services at 604.904.4090 for more information.
View the Community Based Services Handbook (pdf).
STAGE (Supportive Transition Adult Group Education)
STAGE is a transition service for young adults that facilitates growth and independence in educational, vocational and social skills after completing high school.
This program is designed for individuals with disabilities who want to improve academic, work and life skills and will transition out of the service within 1-4 years to access other educational or employment related services and opportunities. This service is best suited to those who wish to further their independence through community-based activities and do not require one to one assistance.
STAGE offers a varied schedule based on the goals of the participants:
- Functional academics (Smart Readers, Math 2 Go, Money Skills )
- Skill development (bus skills, office skills, basic computer skills)
- Work skill training through community volunteering
- Employment exploration through Informational interviews and tours with local businesses and services
To apply to the STAGE Program you must first call Community Living British Columbia (CLBC) at 604.981.0321 and speak to a Facilitator. The Facilitator will assist you with developing a plan and if appropriate will make a referral to the program on your behalf
View the STAGE Schedule-Fall 2014.
View the STAGE Handbook (PDF).
Summer Bursary Program
Individuals who have applied for a 2015 bursary will be notified by email as to the amount of bursary by June 12, 2015.
The maximum bursary available per child is $350.00. You may or may not receive the maximum depending on the number of applications received.
Funding allocations are made in conjunction with representatives of MCFD and other service providers on the North Shore. As refund policies are usually good and as programs often fill up quickly, we suggest you register your child/youth for a program before you receive confirmation.
Families/guardians are expected to pay for the program/camp first. Reimbursements for costs occur once the NSDRC has received all receipts required.
Families/guardians are responsible for hiring their own support worker and paying those wages that are mutually agreed upon. Receipt forms for support work will be issued as required.
The NSDRC Summer Bursary Program provides financial support to North Shore families/guardians of children and youth who have a special need, disability or are in the process of receiving a diagnosis and may require additional support to attend summer recreation programs, camps or community-based activities. Bursaries can be used towards program or camp fees or to assist with payment of a support worker.
Funding for bursaries is made possible from a contract from the Ministry of Children and Family Development (MCFD), CKNW Orphans' Fund, Variety the Children's Charity, United Way, CIBC Wood Gundy, North Vancouver Kiwanis Foundation, Deep Cove Lions Club, Lynn Valley Legion, D. Mowafaghian Foundation, North Shore Optimist Club, Other Service Clubs and private donations. We gratefully acknowledge the support of the District of West Vancouver, District of North Vancouver and City of North Vancouver through their Community Grants programs.
For more information please contact Kathleen Jessop email@example.com or 604-985-5371


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I am developing a website that contains a number of "forms" for entering data, etc, and I plan on using Silverlight and RIA Services for managing the data within these forms. The rest of the site will be normal HTML/CSS/JavaScript.
The plan was to create a single Silverlight control with many pages and each page would represent a single form. A HTML page would display this control, but would display a specific page within the Silverlight control.
So, my questions are:
When embedding a Silverlight control within a HTML page how would have the control automatically navigate to a specific page?
After loading a HTML page, and display the Silverlight control, would it be possible to have some JavaScript tell the Silverlight control to navigate to another page?