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The following policies apply to all formats, including Reviews, Photos, and Videos. Content that does not meet these criteria may be rejected from publication on Google Maps.
Contributions to Google Maps should accurately represent the location in question. Where contributions distort truth, we will remove content. This includes reviews, photos, or videos not related to the location or business where they are tagged. If content is inaccurately placed on the map, or is associated with an incorrect listing, the contribution may be rejected.
Reviews are automatically processed to detect inappropriate content like fake reviews and spam. We may take down reviews that are flagged in order to comply with Google policies or legal obligations.Spam and fake content
Your content should reflect your genuine experience at the location and should not be posted just to manipulate a place's ratings. Don't post fake content, don't post the same content multiple times, and don't post content for the same place from multiple accounts.
Only post content based on your experience or questions about experiences at the specific location. Maps is not meant to be a forum for general political, social commentary, or personal rants. Content that does not meet this standard will be removed.
For some products or services subject to controls and local regulations, you must follow certain guidelines when posting content. The content you upload may not feature calls to action or offers for the sale of products or services that are subject to local legal regulations. This includes, but is not limited to, alcohol, gambling, tobacco, guns, health and medical devices, regulated pharmaceuticals, adult services, and financial services.
The content shouldn't display:
Links to a landing page where it is possible to purchase restricted goods or services.
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About Apple security updates
For our customers' protection, Apple doesn't disclose, discuss, or confirm security issues until an investigation has occurred and patches or releases are available. Recent releases are listed on the Apple security updates page.
For more information about security, see the Apple Product Security page. You can encrypt communications with Apple using the Apple Product Security PGP Key.
Apple security documents reference vulnerabilities by CVE-ID when possible.
Xcode 9.3
Released March 29, 2018
Available for: macOS High Sierra 10.13.2 or later
Impact: Multiple issues in llvm were addressed in this update
Description: Multiple issues were addressed by updating to version the current version of LLVM shipping with Xcode.
CVE-2018-4164: found by OSS-Fuzz

subset: commoncrawl


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Cover image may be preliminary, not including UPC barcode or final edits.
Comic: Faith (2016-) ongoing 8 Cover E 1:20 Incv Coover
Date: Jan 2017
Raw (Average Copy) Guide Value: $20.00
Comments: Previews Note: (NOTE: For every 20 copies of Faith #8 ordered (covers A-C any comb) retailers may order 1 Colleen Coover variant.)
Additional comments: (NOTE: For every 20 copies of Faith #8 ordered (covers A-C any comb) retailers may order 1 Colleen Coover variant.)
Recent comics may be incorrectly identified, and many store exclusives are missing from the database.
Books which sell infrequently may not match guide prices if demand has changed since the last sales.
IMPORTANT NOTE: Automated compiling of sales results may include errors, especially when different books can be described by the same title. For example: X-O Manowar #1 Near Mint could describe a 1992 edition, several different 1997, 2012, 2017, or 2020 editions, a one-shot title, or even a trade paperback. Whenever calculated guide prices seem "impossible" there is a good chance that a data error has occurred, please use the guide with caution.
|Quick link to Valiant items --->


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FASB Issues Guidance to Improve Financial Reporting for SPEs, Off-Balance Sheet Structures and Similar Entities
Norwalk, CT, January 17, 2003—In an effort to expand upon and strengthen existing accounting guidance that addresses when a company should include in its financial statements the assets, liabilities and activities of another entity, the Financial Accounting Standards Board (FASB) has issued Interpretation No. 46, Consolidation of Variable Interest Entities. Many variable interest entities have commonly been referred to as special-purpose entities or off-balance sheet structures, but the guidance applies to a larger population of entities. Printed copies will be available on or about January 22, 2003.
In general, a variable interest entity is a corporation, partnership, trust, or any other legal structure used for business purposes that either (a) does not have equity investors with voting rights or (b) has equity investors that do not provide sufficient financial resources for the entity to support its activities. A variable interest entity often holds financial assets, including loans or receivables, real estate or other property. A variable interest entity may be essentially passive or it may engage in research and development or other activities on behalf of another company.
The objective of Interpretation 46 is not to restrict the use of variable interest entities but to improve financial reporting by companies involved with variable interest entities. Until now, one company generally has included another entity in its consolidated financial statements only if it controlled the entity through voting interests. Interpretation 46 changes that by requiring a variable interest entity to be consolidated by a company if that company is subject to a majority of the risk of loss from the variable interest entity's activities or entitled to receive a majority of the entity's residual returns or both. A company that consolidates a variable interest entity is called the primary beneficiary of that entity.
Consolidation by a primary beneficiary of the assets, liabilities and results of activities of variable interest entities will provide more complete information about the resources, obligations, risks and opportunities of the consolidated company. To further assist financial statement users in assessing a company's risks, the Interpretation also requires disclosures about variable interest entities that the company is not required to consolidate but in which it has a significant variable interest.
The consolidation requirements of Interpretation 46 apply immediately to variable interest entities created after January 31, 2003. The consolidation requirements apply to older entities in the first fiscal year or interim period beginning after June 15, 2003. Certain of the disclosure requirements apply in all financial statements issued after January 31, 2003, regardless of when the variable interest entity was established.
To order a hard copy of Interpretation 46, please contact the FASB's Order Department at 800-748-0659.
About the Financial Accounting Standards Board
Since 1973, the Financial Accounting Standards Board has been the designated organization in the private sector for establishing standards of financial accounting and reporting. Those standards govern the preparation of financial reports and are officially recognized as authoritative by the Securities and Exchange Commission and the American Institute of Certified Public Accountants. Such standards are essential to the efficient functioning of the economy because investors, creditors, auditors and others rely on credible, transparent and comparable financial information. For more information about the FASB, visit our website at www.fasb.org.
The Financial Accounting Standards Board
Serving the investing public through transparent information resulting from high-quality financial reporting standards developed in an independent, private-sector, open due process.


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BMC Racing Team Set For Unique Tour de Pologne
Two challenging stages in the Dolomite mountains in Italy and rosters of only six riders – rather than eight – will provide a unique challenge to this year's Tour de Pologne, said BMC Racing Team's Marco Pinotti.
Race May Be Difficult To Control
Pinotti, who along with teammate Taylor Phinney, is a favorite for the final-day, 37-kilometer individual time trial, said those factors change the complexion of the seven-day race that begins Saturday. "The stages are generally long and surely the last time trial is the key/ goal stage for me," the reigning Italian time trial champion said. "I can see how well I recovered from the early stages and compare myself to other competitors. The race seems open to breaks as with six riders per team it will be difficult to control." BMC Racing Team Performance Manager Allan Peiper, who will be directing the team along with Assistant Director Fabio Baldato, said the team's hopes for the general classification lie with Mathias Frank, who led the Tour de Suisse for five days, and new Italian road champion Ivan Santaromita. "We have a few cards to play in the opening days with the two big mountain stages, plus covering breaks and looking after our leaders," Peiper said. "I think as we get into Poland there will be some stages where Thor Hushovd can build on the success he had in the Tour of Austria and try for some stages."
Download the BMC Racing Team's official race sheet (PDF with roster, statistics, bios, etc.): https://bit.ly/171BgYv.
BMC Racing Team Tour de Pologne Roster (July 27-Aug. 3):
Mathias Frank (SUI), Thor Hushovd (NOR), Dominik Nerz (GER), Taylor Phinney (USA), Marco Pinotti (ITA), Ivan Santaromita (ITA).
Sport Directors:
Allan Peiper (AUS)
Fabio Baldato (ITA)
Scott Major (USA)
Bus Driver: Steven Christiaens (BEL). Chef: Walter Grözinger (GER). Mechanics: Alessandro Gaia (ITA), Kevin Grove (USA), Ronald Ruymen (BEL). Nutritionist: Judith Haudum (AUT). Performance Team: Bobby Julich (USA). Soigneurs: Bernd Coutteau (BEL), Gunther Landrie (BEL), Anthony Pauwels (BEL), Stefano Rubino (ITA).


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Sponsors Needed for our 100 DAY / 100 CHILD Membership Drive
By Manny Lindo On January 1, 2016 · Leave a Comment
Help us make 2016 a Happy New Year for 100 needy Children around the globe. The CFC Family is always seeking to grow in size. Our mission to reach as many Children as possible continues as we seek 100 New Sponsors who are willing to make a difference in transforming the life of […]
Posts by: Manny Lindo


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Werner Herzog (born Werner H. Stipetić; 5 September 1942) is an Academy Award-nominated German film director, screenwriter, actor, and opera director.
He is often associated with the German New Wave movement (also called New German Cinema), along with Rainer Werner Fassbinder, Margarethe von Trotta, Volker Schlöndorff, Hans-Jürgen Syberberg, Wim Wenders and others. His films often feature heroes with impossible dreams, people with unique talents in obscure fields, or individuals who find themselves in conflict with nature.
Herzog was born Werner Stipetić (German pronunciation: ) in Munich. He adopted his father's name Herzog, which means "duke" in German, when his father returned from a prisoner of war camp after World War II. His family moved to the remote Bavarian village of Sachrang (nested in the Chiemgau Alps), after the house next to theirs was destroyed during the bombing at the close of World War II. When he was 12, he and his family moved back to Munich.


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Chicago.PM Report - Scripting Git With Perl
This month's presentation was on the Git::Repository Perl module, given by me. In both my jobs, I use the Git::Repository module to automate releases.
At Double Cluepon, I use it to create the release packages based on tagged commits, so that releasing our software is exactly: git tag vX.X.X && git push --tags. A Perl script builds every package and then pushes them to our update server, where the game will check for a new release.
At Bank of America, we use it to combine our 20-30 Perl distributions into a single release. Using git submodules, we have a "release repository" that holds references to all the modules for each team's releases (some are team-specific, others are shared between teams). A Perl script manages the submodules, determines when the submodule refs need to be updated, tags and branches for each release, and finally builds and installs our modules using Module::Build and local::lib.
All this Git stuff gave me some ideas for possible useful code I can release, perhaps leading to me finally recovering my CPAN ID.
The slides for my Scripting Git With Perl talk
The code for the script that automatically builds releases tagged like "vX.X.X"


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PESHAWAR, Pakistan – A suicide bomber in an explosives-laden pickup truck leveled a police building in northwest Pakistan Wednesday, killing five officers and wounding 30 other people in the latest attack to rattle the country since the U.S. raid that killed Osama bin Laden.
The Pakistani Taliban claimed responsibility and said the blast was to avenge the death of bin Laden. Already this month, the al-Qaida-allied group has claimed three other revenge attacks, including a bloody 18-hour siege of a naval base.
The target Wednesday in Peshawar appeared to be the police's criminal investigation department, but the building was in an army compound and several military facilities also are nearby, said regional police chief Liaquat Ali Khan. Counterterrorism police officers were stationed at the center, another officer said.
The Pakistani Taliban is violently opposed to the United States, but also is angry at the Pakistani state for cooperating with Washington since the Sept. 11, 2001, attacks. The group has carried out scores of attacks on Pakistan's security establishment over the years.
Police officer Mohammad Zahid was in the basement when the bomb went off.
"I felt like the sky fell on me," Zahid said in hospital, where he was being treated for multiple injuries. "The explosion jammed the door of my room in the basement, but there was a small hole in the wall so I crawled through that."
Five officers died, and at least 30 people were wounded, police said.
Military forces sealed off much of the cantonment as machines were brought in to sift through the piles of rubble left at the site of what was once a multistory building.
Government leaders condemned the bombing.
"Our determination is much higher than before, and we will fight till the defeat of these terrorists," said Bashir Bilour, a senior official with the provincial government. He said at least 660 pounds (300 kilograms) of explosives were used.
Bin Laden was killed on May 2 by a team of U.S. Navy SEALs in the army town of Abbottabad in a house roughly a mile away from Pakistan's premier military academy.
Since the raid, U.S.-Pakistan relations have sunk to new lows. Pakistani leaders insist they had no idea the al-Qaida leader had been living, apparently for five years, in the large, three-story house in Abbottabad. And they are furious that the U.S. raided the house without telling them in advance.
The Taliban have taken responsibility for a twin suicide bombing at a paramilitary police training facility that killed around 90 people and a car bomb that slightly wounded two Americans in northwest Pakistan.
But the siege of the naval base in the southern port city of Karachi was one of the most audacious assaults in years and further rattled a military establishment already humiliated by the unilateral U.S. raid. The militants destroyed two U.S.-supplied surveillance aircraft while killing 10 people on the base. Four militants died in the fighting, officials said.
Associated Press writer Ishtiaq Mahsud in Dera Ismail Khan contributed to this report.


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Fidelity Institutional Wealth Services has published three white papers that use the practice management best practices of a number of successful RIA firms in three key growth-building areas of concern to all advisors: referrals and marketing, how to make strategic hires inside a firm and how to address mergers and acquisitions.
David Canter (left), the executive vice president who heads practice management and consulting at Fidelity IWS, said the series grew from the RIA custodian's benchmarking efforts, in which he and his team kept hearing from advisors, "How do I grow as fast and as cheap as the best firms?" While Canter said, "We have strategies, but wouldn't it be great to capture the special sauce, if you will, of the best firms out there?" Those firms, including Buckingham from St. Louis and Brinton Eaton from New Jersey, were, he said, firms in the top quartile of growth as measured by three-year compound annual growth rate. "Let's focus on bigger firms of $500 million and above—the upper echelon."
While in that "sweet spot" for growth, between $500 million and $1 billion in assets under management, these successful companies implemented strategies to spur further growth. "A number of the strategies" employed by those firms, said Canter, might seem "back to basics—asking for referrals; asking why they don't get referrals" from both end clients and centers of influence, and having a shared knowledge within the firm of how and where they wanted to grow.
According to Canter, "Our mantra is 'We want to make practice management and consulting insightful, strategic and actionable,'" so these white papers, "these profiles in growth" are like a "study group in a box." Canter described his job as making those insights "strategic through our relationship managers and my team." Their approach includes using Fidelity's Referral-Edge database, which allows advisors to "mine for prospects based on publicly available data and interlocking relationships," as well as through business development workshops and direct consulting with firms. On the HR front, Canter said, "we also come into the mix with strategic hires," identifying candidates through his team's networking and an outside human resources search firm.
Canter acknowledged that while "there's no panacea or silver bullet to help a firm grow, there are some strategies that the successful firms are using. If you're serious about taking the time and discipline, you can achieve success." Some of those strategies may sound basic, but "it's all in the execution; that's where we try to help. Strategy is easy but execution is hard."


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Search Results
Toy Truck in Fallout 76 is a Junk that can be Scrapped and turned into Crafting Materials. Scrapping can only be done at a Workbench or Crafting Station, so players will have to return to one in order to do so. Be warned though, players who die before Scrapping their Junk will lose all Junk they have on them.
Where to Find Toy Truck
Locations where you can find Toy Truck are listed below:
- Found in ??
Toy Truck is a Good Source of
- Steel (2)
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The program for the International Conference on Information and Communication Technologies for Development Conference includes a paper session titled "Expanding Participation", which invokes thinking about the clearly rising convergence of many conceptual and practical repertoires of development research, practice and emerging information and communications technologies (ICTs). The sustained interest in participation (as a large and diverse set of methodologies, practices and frameworks) and how it continues to inform the general developmental zeitgeist is paralleled by the steady evolution in technologies and technological practices that have their own embedded manifestations of the participatory ethos. Technically-focused communities such as the open source movement and technologies such as crowdsourcing, with characteristics of openness, social collaboration, and unrestricted information flows mirror the inclusiveness inherent in participatory processes in development work.
With such a similitude in the participative and increasingly democratized cultures characterizing the current evolution in development and technical communities, an important question arises: Are we, as development researchers and practitioners, adequately capitalizing on the potential opportunities created (as a result for such a convergence of shared values) for collaboration with our technical counterparts? Are we able to reimagine development within a context of the accelerating rate of change that the increasingly rapid rate of technological advancement brings about? How are we able to reconceive our 'traditional' ways of thinking about the global developmental priorities in a world characterized by such an accelerating rate of change?
The purpose of this blog post is not to offer any adequate answers to these questions, but to present a call to action on an issue with direct bearing on formulating these answers. How can development practitioners and technology professionals capitalize on shared values, more effectively collaborate on solving complex developmental issues and foster a reciprocal cross-pollination of ideas that is mutually valuable in finding practical and sustainable solutions in an increasingly dynamic global environment? The collaborative spaces already exist, considering the multitude of cross-disciplinary conferences, research programs and development interventions that combine input from and invite partnership between those working in both realms of development practice and technological innovation, as well as local stakeholders and institutions. That is, the attention to inclusiveness and participation as central notions of collaborative efforts across joint undertakings between the development and technology domains is already extant and arguably on the rise. What needs more attention is factors affecting the effectiveness (or lack thereof) of collaboration between those working in development practice and their opposite numbers in the technology and innovation world, and this is what is meant by 'meta-participatory' in the title of this post.
Many of the attributes that both groups have in common have already been discussed. What about divergences? What stands in the way of a more vibrant alliance between development and technology? In many cases, it all about finding the right balance. Here are two key observations:
- Disparate views on the role of technology for development: this is an elementary – even obvious – observation, but remains fundamental to bridging gaps in conception of technological tools and processes for development. Without risking treading into territory mined with multifarious and often polarized debates on the subject, and for the purpose of the main thrust of this post, it would suffice to say that development practitioners need to adopt a little more techno-fetishism, while technologists would probably do well to accept an additional degree of practical conservatism. In other words, we need to balance long-term, futuristic outlooks on the possibilities of what technology can (or cannot) do for development with short-term, pragmatic focuses on specific interventions. An equilibrium of far-sighted vision and effective action cannot exist otherwise.
- Conflicting working 'tempos': technologists often have a 'keyed-up' working pace. Prototypes are built, deployed, tested and improved upon in a cycle that is analogous to but much faster than the slow-paced, deliberative, power-sensitive process that lies at the core of participatory methodologies. In collaborative projects, finding a practical balance of pace is difficult, but achievable.
The late Steve Jobs, one of the technological icons of present times, once said "…innovation comes from people meeting up in the hallways or calling each other at 10:30 at night with a new idea, or because they realized something that shoots holes in how we've been thinking about a problem". Sudden moments of clarity and late night phone calls aside, if we are to truly co-construct knowledge about how find technologically-catalyzed solutions for global development challenges, we need to break out of our respective disciplinary silos and start reciprocally but constructively shooting holes in our preconceived notions about how to find these solutions. We need to open sourcedevelopment by building upon the shared values of participation and inclusiveness and promoting a joint discourse of ideas at the intersection of practical intervention, technological innovation and ethical considerations.


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Tyronne wins award for hairstyling
A senior stylist at Geiko, one of Leamington's leading hair salons, has won a national hair styling competition.
Tyronne Leon-Fernandez, who has been with Geiko since 2010, was presented with the first ever Shu Uemura 2013 Muse Image Award. His achievement is made all the more commendable, given the incredibly high standard of entries from hairdressers across the UK.
Tyronne's 'Muse' experience started when all entrants were invited to submit photos and a mood board to describe the inspiration behind "their muse". In Tyronne's case, it had been a trip to the Cheltenham Gold Cup amidst a sea of extravagant fur hats that inspired his creation.
Tyronne won the chance to take part in a creative group photo-shoot with top fashion photographer, Jack Eames and mentoring from renowned hair industry figure, India Miller.


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By Balasubramanian Somasundram, Honeywell Technology Solutions Ltd.
In 2009, Gartner had coined a term called 'Emergent Architecture' advocating the need for a re-orientation in Enterprise Architecture practice. According to this paradigm, Gartner suggests Enterprise Architects must adopt a new style of Enterprise Architecture to respond to a growing variety and complexity in markets, economics, nations, networks and companies. Gartner had also listed some of the characteristics of such an Emergent Architecture and the kind of changes that we can foresee in near future.
After two years, I wanted to take a closer look at this observation and correlate some of my personal experiences from Enterprise IT.
To set the context, would like to quote the emergence of situational applications. In simple terms, situational applications solve immediate business challenges by addressing a situation in hand. The key characteristics of situational applications are – unique situation, highly personalized, immediate and time-sensitive nature of business scenario. A "situational application" is a broader term that includes concrete implementations such as Mashups and Composite applications.
So far, Enterprise IT has been busy with ERP/CRM and packaged applications and custom developed web applications. Now, that era of "hand coding" is almost saturated and hit a plateau due to couple of reasons such as – Enterprise roll-outs of ERP/CRM are complete, custom developed applications are rationalized and consolidated with ERP suites and demands for new custom developed applications are challenged for solid business cases.
However, the unique business situations still demand for small/nimble IT solutions that wouldn't wait for long lead times, big business cases. What is the solution?
Situational Applications can help.
The key characteristic of these situational applications is that business doesn't have the details about the requirements or responses. All it has is the outcome that needs to be achieved. Sometimes, business just wants to experiment with multiple options before zeroing on one solution. In some cases, business wants to build just a pilot, scaled-down version of the actual solution and eventually evolve it to an enterprise-class solution. Sound familiar?
I would say this is one of the categories of emergence scenarios that Enterprise Architecture needs to deal with, for both business and IT stakeholders.
In contrast to what Gartner states, the key challenges that EA needs help solving are not just macro issues such as geopolitical risks or outsourcing governance etc., but micro issues that would help executing day-to-day projects much more effectively. This will build the credibility of EA groups at grassroots level and drive some real changes in business/IT. I would like to list some of those challenges to be solved:
- Given the uncertainty in requirements and technologies, what is the best way to cater to these business requests for building situational applications? Certainly, agile methods can help to certain extent. But the scenarios that revolve around situational applications are much more dynamic and need much faster results. Another way to look at this challenge is, how do these unique business situations fit in the overall business architecture?
- How do we engage business users to gather requirements in creative ways, especially when business users themselves may not have all the data upfront?
- If we need to build nimble, simple IT solutions, we need to have a solid architecture foundation. How can EA help both segments? – foundational and situational
- How do we make sure we create an ecosystem where the new architecture 'evolves" as the requirements and solutions themselves evolve over a period of time? How do we make sure architecture not only evolves, but translatable to an enterprise-scale solution?
Thanks to The Open Group, we have robust frameworks and methodologies for building deterministic enterprise architectures. It will be interesting to see how The Open Group addresses the demands and challenges of nondeterministic/emergent enterprise architectures as stated above, in the future.
Enterprise Architecture is a subject that will be discussed in depth during The Open Group Conference, London, May 9-13. Join us for best practices and case studies on Enterprise Architecture, Cloud, Security and more, presented by preeminent thought leaders in the industry.


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Over 100 Strains Of HPV - No Cure
Some Cause Genital Warts, Some Invade Epithelial Cells
HPV and Cervical Cancer
By Carolyn Vachani, RN, MSN, AOCN
Affiliation: The Abramson Cancer Center of the University of Pennsylvania
The Human Papilloma Virus
The Human Papilloma Virus (HPV) is one of the most common sexually transmitted infections (STI) in the world. It is estimated that 5.5 million people worldwide are infected annually. Sexually active individuals have an 80 to 85% chance of being infected at some time in their life.
The virus invades human epithelial cells (a type of skin cell), including the oral mucosa, esophagus (throat), larynx (voice box), trachea (airway), conjunctiva of the eye, and the anal and genital areas. The time between exposure to the virus and having any symptoms can be 3 to 4 months, yet the virus can be transmitted to someone else during this time (unbeknownst to either person). Although HPV is considered a sexually transmitted infection, this can be misleading. It is transmitted by skin to skin contact, therefore traditional methods of protecting oneself against an STI, such as condoms can reduce, but not eliminate the risk of HPV infection. Infection can occur through skin to skin genital contact without intercourse.
Persons at higher risk for HPV infection include those with numerous lifetime sexual partners (the higher the number, the higher the risk), early age of first intercourse, history of other STIs, alcohol and drug use related to sexual behaviors, and partner's number of sexual partners.
The infection is most prevalent in women in the 20-24 year old age group, with 15-19 year olds being the second largest group. Prevalence decreases with age, dropping significantly after age 30. It is thought that the younger, developing cervix is more likely to be infected, but these infections tend to be short-lived and are usually cleared by the immune system.
Cases of cervical cancer
are extremely rare under age 30.
Researchers have identified 100 different strains of HPV, 40 of which can infect the anal and genital areas. These strains have been further divided into low and high risk strains, which we will address later. Many people think of HPV as the virus that causes genital warts, yet only a few of the 100 strains actually cause warts.
There is no treatment to rid the body of HPV, but 80% of infections are cleared by the body's immune system. For the 20% who develop chronic infection with HPV, the risk of cervical cancer is higher. If the HPV strain is one that causes genital warts, they can be treated by topical methods such as freezing, acid application or imiquimod (a medication used to boost local immune response). Surgical treatments include laser, excision, or CUSA (ultrasound).
Cervical Cancer and the Pap test
Cervical cancer is the second most common cancer in women worldwide. Approximately 500,000 new cases are diagnosed annually worldwide, 83% of which will be in developing countries (estimated 10,370 new cases in the US in 2005). There will be an estimated 273,000 deaths due to the disease annually, three-fourths of these in developing countries. Higher income nations have the Papanicolaou (pap) test to thank for a 75% decrease in cervical cancer cases over the past 50 years. Unfortunately, this test has not been successful in lower income nations due to cost, ability to get the test to women and once available, to get the results back to them. The Pap test has made great strides in catching cervical changes early, but it is not without problems. The traditional Pap test is not very sensitive (55-60% sensitivity), which means that up to 40-45% of the time that the test is read as normal, there is actually cervical dysplasia (abnormality) present. By performing the test annually, along with a manual exam, we increase the chance of detecting a cancer. Newer liquid based cytology tests, called Thin Prep ® and Sure Path ® , reportedly have a sensitivity of 84%, which is better, but still not great.
Cervical cancer is further broken down into 3 types: squamous cell carcinoma (about 75% of cases), adenocarcinoma (15-25% of cases), and rarely, adenosquamous (a combination of the two). It is recommended that women start screening with Pap smears within 3 years of becoming sexually active, but no later than 21 years old. Then annual testing with traditional Pap methods, or every 2 years with the liquid based cytology. Women who have had a hysterectomy should clarify with their surgeon whether or not they still have a cervix and whether they should continue screening.
Pap Test Results
Pap test results in the U.S. are reported in the "2001 Bethesda System". The system is quite detailed, but some of the common results include the following (and common follow-up):
Mild dysplasia (also called CIN 1 or Low grade squamous intraepithelial lesions (LSIL)): most resolve spontaneously, so follow with Pap every 4-6 months, if it lasts more than 2 years an excisional biopsy may be needed.
Moderate or severe dysplasia (also called CIN 2 or CIN 3 or high grade squamous intraepithelial lesions (HSIL)): should be confirmed by colposcopy and treated for the abnormality.
Atypical squamous cells of unknown significance (ASCUS): Repeat Pap in 6 months, if still abnormal, colposcopy to test further. Alternatively, test for high risk HPV strains, if positive, colposcopy to further evaluate, if HPV negative, can repeat Pap in 1 year.
HPV Causing Cervical Cancer
Researchers have determined that HPV is found in almost 100% of cervical cancers worldwide. This is unique to cervical cancer, no other cancer has been found to have one central cause. Even the tie between smoking and lung cancer is not as strong, with only 80 to 85% of cases caused by smoking. Although HPV is necessary to the development of cervical cancer, it alone is not enough. About 80% of HPV infections are transient and resolve without treatment because the immune system is able to fight them off. Some factors that appear to increase the risk of HPV infection not clearing and possibly progressing to cancer include: cigarette smoking, oral contraceptive use for more than 5 years, multiple births, and poor nutrition. Studies have found smokers to be 2-3 times more likely to develop cervical dysplasia or cancer than nonsmokers. Several studies have showed a dose intensity relationship, the more tobacco smoked, the higher the risk. In addition, researchers have found that nicotine is present in the cervical cells of smokers.
There are 40 strains of HPV that can affect the anal and genital tracts and these are further divided into low risk and high risk strains. Thirteen strains are considered high risk, or more likely to progress to high grade lesions (HSIL, CIN 2 or 3) and possibly cancer, if not cleared by the immune system. These strains are: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. Strains 16 and 18 are by far the most common types, and one or both are present in approximately 70% of cervical cancers worldwide. Despite this strong link, only a very small percentage of high risk HPV infections will ever become invasive cancer (estimated at 2%). The time between initial exposure and the development of cancer can vary from months to years, but the average time is thought to be 15 years. Unfortunately, the high risk HPV strains do not usually cause any symptoms to alert someone that they have the infection. The low risk strains are not considered a risk for cervical cancer, but they can cause low grade lesions (CIN 1) and several of these strains can cause genital warts.
Testing for HPV
Several years ago, a test was developed to identify high risk strains of HPV. The test is done on the same cells that are used in a Pap test. Studies have found the Hybrid Capture II test to detect the presence of high risk HPV in 83-100% (depending on the study) of high grade lesions (CIN 2 or 3, HSIL) or invasive cervical cancer.
In women over the age of 30, when both Pap test and high risk HPV tests are negative, the woman should wait 3 years for the next screening.
With a Pap result of atypical squamous cells of undetermined significance (ASCUS), women have the option to repeat the Pap in 6 months and if the result is the same, proceed to colposcopy for further evaluation. Alternatively, the cervical cells can be tested for high risk HPV strains. A Pap result of ASCUS, in conjunction with a negative HPV test, can be followed with a repeat Pap in 6 to 12 months. If either test is positive at that time, colposcopy should be performed. If the initial HPV is positive with an ASCUS Pap, colposcopy is warranted.
The test costs between $50 and $200, depending on the lab used. Many insurance companies cover the cost of the test if it is being used as screening for women over 30 (as this is recommended by several medical organizations). Some companies will cover the cost of HPV testing for women under 30 with an inconclusive or abnormal Pap test result. But many experts agree that abnormalities in young women are a result of transient infections and can be followed by repeat Pap testing in 6 to 12 months.
One thing to keep in mind, almost all women will have an HPV infection at some time in their life. The Hybrid Capture test does not have the ability to tell what HPV strain the person has, just whether or not they have any high risk strain. Multiple positive results over years could be different transient infections and cannot be assumed to be a persistent infection with one strain.
There has been a lot of talk about vaccines for HPV, but they are all still in development or in clinical trials. Merck and Glaxo SmithKline appear to be the first companies ready to apply for FDA approval (applying in early 2006 and 2007 respectively). Their vaccines are targeting the two most common HPV high risk strains, 16 and 18, which are responsible for 70% of cervical cancers worldwide. An important piece of patient education regarding these vaccines, is that they will still need to have Pap tests, as there are still eleven other HPV high risk strains that can lead to cervical dysplasia or cancer. The pharmaceutical companies have found that the vaccine is less effective if they add more strains to it, therefore they feel targeting the 2 most common types is best. Information available from ongoing trials report the vaccine to be about 90% effective in preventing HPV infection. Researchers feel the vaccine would be best given to adolescents ages 9-12, who have not yet been exposed to the virus. Early trials did not include these age groups, but are currently ongoing. In addition, it is not yet known how long the vaccine will protect women from HPV. Regardless of these issues, it is clear that this could be a major step in decreasing cervical cancer mortality in lower income countries.
What About the Men?
Researchers have historically been looking at women and HPV because of the cervical cancer link, but men are getting a closer look. Obviously, men are a large part of the issue of HPV rates, so it makes sense to target them as well. Vaccines are only now being tested in men and adolescent boys.
Anal cancer rates have increased 160% in men from 1973 to 2000, which is very concerning to researchers (rates in women have increased 78%). One study found 88% of anal tumors studied contained HPV, suggesting it may be a causative factor. Several other factors also increased the risk: >14 lifetime sexual partners, receptive anal intercourse, and smokers were almost 4 times as likely to develop anal cancer. HPV has also been linked to penile cancer in men and head and neck cancers in both sexes.
Most men, like women, have no symptoms, unless they develop genital warts. Currently, aside from treating genital warts, there is no treatment for HPV in men. It is known that anal warts can be a precursor to anal cancer and these warts can be tested for high risk HPV strains. This can allow for surgical intervention for the patients at highest risk for developing anal cancer.
Knowledge about Human Papilloma Virus has grown tremendously in the last 10 years and is certain to continue. Healthcare providers and consumers will need to keep abreast with changes in practice in order to achieve improved health outcomes for women. Look to OncoLink for periodic updates!
Abeloff, M., Armitage, J., Niederhuber, J., Kastan, M. & McKenna, G. (Eds.): Clinical Oncology (2004). Elsevier, Philadelphia , PA.
The American Cancer Society. Facts and Figures 2005 . <http://www.cancer.org/>www.cancer.org
Arbyn, Mark et al. Virologic Versus Cytologic Triage of Women With Equivocal Pap Smears: A Meta-analysis of the Accuracy To Detect High-Grade Intraepithelial Neoplasia. Journal of the National Cancer Institute , 2004; 96(4):280-293.
Castellsague X, Bosch FX, Munoz N. Environmental co-factors in HPV carcinogenesis. Virus Res 2002;89:191-9.
Daling JR, Madeleine MM, Johnson LG et al. Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer 2004;101:270-80.
Damasus-Awatai G, Freeman-Wang T. Human papilloma virus and cervical screening. Curr Opin Obstet Gynecol 2003;15:473-7.
Fey MC, Beal MW. Role of human papilloma virus testing in cervical cancer prevention. J Midwifery Womens Health 2004;49:4-13.
Franco EL, Harper DM. Vaccination against human papillomavirus infection: a new paradigm in cervical cancer control. Vaccine 2005;23:2388-94.
Goldie SJ, Kohli M, Grima D et al. Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine. J Natl Cancer Inst 2004;96:604-15.
Munoz N, Bosch FX, de Sanjose S et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518-27.
Papaconstantinou HT, Lee AJ, Simmang CL et al. Screening methods for high-grade dysplasia in patients with anal condyloma. J Surg Res 2005;127:8-13.
Raley JC, Followwill KA, Zimet GD, Ault KA. Gynecologists' attitudes regarding human papilloma virus vaccination: a survey of Fellows of the American College of Obstetricians and Gynecologists. Infect Dis Obstet Gynecol 2004;12:127-33.
Sankaranarayanan R, Chatterji R, Shastri SS et al. Accuracy of human papillomavirus testing in primary screening of cervical neoplasia: results from a multicenter study in India . Int J Cancer 2004;112:341-7.
Washam C. Targeting teens and adolescents for HPV vaccine could draw fire. J Natl Cancer Inst 2005;97:1030-1.
Washam C. Two HPV vaccines yielding similar success. J Natl Cancer Inst 2005;97:1030.
Wright TC, Jr., Schiffman M, Solomon D et al. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gynecol 2004;103:304-9.
Last Modified: November 11, 2005
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text:
Title: Escape from
Director: John Carpenter
Cast: Kurt Russell, Steve Buscemi, Peter Fonda, Valeria Golino, Pamela Grier, Bruce Campbell, A.J. Langer
Escape from
is a strange kind of film. When I first heard the news that a sequel to John Carpenter's Escape from New York (1981) was being
made I was excited to see the resulting film because not only was John
Carpenter back behind the directors chair, but Kurt Russell was still going to
play Snake Plissken! That's really all I needed to know. Sadly, when I went to
the theater to see it, I came out being disappointed. Where was all the
darkness? Where was that terrifying post- apocalyptic world that I loved from
the first film? Why were characters trying to be funny? Why was everything so
silly? Why? Why? Why? Well, many years have passed since my initial disappointment
with Escape from L.A.
I've grown some, matured some. I had a chance to recently re-watch Escape from L.A. How do I see this
film now?
Carpenter and Russell on the set of Escape from L.A.
Well, I honestly can't bring myself to hate it. I see why I didn't like it when it was first released, but I've grown to accept this film for what it is. It's pure unadulterated campy fun. Funny thing is that a script was written for this film way back in 1985, by a guy called Coleman Luck, but Carpenter thought the script was too light and campy. What? X-squeeze me? Baking Powder? That's exactly what Escape from
turned out to be anyways! Ultra campy and ultra light; at least when compared to
the first film which was so dark and brooding. Escape from New York was a film that took itself very
seriously. Yeah it's a science fiction film, but it was a decidedly serious one.
Not many laughs or jokes in sight. In
contrast Escape from L.A.
is colorful, filled with one joke after the another, and very, very campy. This
movie is obviously making fun of itself. And to tell you the truth, I like that
about it because it's obviously what Carpenter and Russell were going for. So you'll
be better of just erasing your expectations for this film. If you haven't seen
this one yet, you have to go in expecting a different film than Escape from New York.
What makes Escape from
so different? It's all about the tone of the film, the look of it. While
Escape from New York felt like a horror movie at times with it's darkness and
freaky looking characters, Escape from L.A. is actually well lit and colorful, filled with comic book heroes, villains and
one liners galore. Take for example the character called 'The Surgeon General
of Beverly Hills' the one played by Bruce Campbell. This character feels like a
comic book villain, like something out of an episode of the old Batman
television show. He's a surgeon general who has
performed so much surgery on himself and on his patients, that they have
disfigured their faces! He likes chopping up good looking people to use for his
surgeries. This is a prime example of the kind of totally over the top
characters you will find on this film. They aren't particularly scary or
intimidating like the villains on the first film, but they are entertaining none
the less. And the comic book characters don't stop there my friends! Pamela Grier plays a transvestite who used to be Snake Plissken's
partner in crime! Steve Buscemi plays a double crossing tourist guide! Peter
Fonda plays a surfer who likes to ride Tsunami tidal waves! And so on. But even though this film is filled with funny, entertaining characters such as the ones I've
mentioned, this doesn't make Escape from L.A.
a bad film in book, just a different kind of film than its predecessor.
Bruce Campbell's 'Surgeon General of Beverly Hills'
Both Escape from
New York
and Escape from L.A.
are decidedly anti-establishment films. They both have this cynical view of the
government; in these films, the government is not to be trusted. There are terrorist
attacks aimed at the government on both films. On the first one they hijack and crash Air Force One;
forcing The President of the United States
to fall into the hands of the freaks inside Manhattan. On this second one, the president's
own daughter is the one that rebels against the government and decides to live
with the leader of the criminals; a guy called 'Cuervo Jones'. And here's what
I liked about this movie. While it does criticize fascist forms of government,
it also criticizes rebellious leaders who instigate their followers towards committing
violent acts. So it doesn't side with anyone. On this film, both sides are
wrong. The film pleads for a new beginning, it's asking governments to forget
their old grudges and start from scratch. Snake himself says it in one scene: "I
shut down the third world, you win, they loose. I shut down America, they
win, you loose. The more things change, the more they stay the same" This is
one of the ideas presented in the film that I truly liked. The idea that both
sides should just call it quits and bring on the peace, bring on the freedom. Again,
this last bit demonstrates how much of Kurt Russell's Libertarian views are on
this film. After all, he wrote a lot of it himself along with John Carpenter
and Debra Hill. These are three life long buddies writing a movie they would
find amusing, which makes this film a labor of love. This is probably why the
film has a more laid back, 'were having fun here' vibe to it.
That being said, the film does have some faults going for it. The visual effects for example are freaking horrendous, I mean this was a 50 million dollar movie, one would think that better effects could have been afforded. There's this painfully bad effects sequence in which Snake drives this mini-submarine through the underwater ruins of L.A….wow, there's some bad CGI for you. I mean, granted this was early CGI, but even for 1996, these effects where half assed in my book. The scene where Snake Plissken rides a tsunami wave on a surfboard with Peter Fonda, while campy and kind of cool in a way (it's all about that Hippy attitude!) the scene just comes off as one bad special effect. The scenes with Snake and crew flying these gliders, wow, you could just tell those things weren't really flying; the list just goes on and on. So expect lots of cheesy effects on this show.
But don't get me wrong, I don't hate this movie. I quite enjoyed it actually. I mean yeah, I loved the first one a whole lot more. It's just darker and scarier; it's got more of an edge to it. This second one is tongue in cheek every step of the way. Watching Escape from
L.A. feels like watching a cheap Italian Rip
Off like 2019: After the Fall of New York (1983), but with a bigger budget. Actually, Escape from L.A. has a lot of similarities with 2019: After the Fall of New York, so in a way, this is Carpenter's pay back for all those cheap Escape from New York rip offs that the Italians made. Ultimately, I love both Escape from New York and Escape from L.A. for different reasons. And for
all the tonal differences between both films, they still have many similarities.
No matter where, Snake Plissken will always be Snake Plissken, you can tell
Russell has lots of love for this character. Plissken is what kept me watching.
The opening and closing segments of the films are extremely similar as well. And
here's where we get to the best part of the film, the ending. Not gonna spoil
it don't worry, but I will tell you that it is the best thing about the movie.
Russell himself came up with it and I applaud him for it, it encapsulates
everything Snake Plissken is in terms of attitude. That idea that maybe the world
would be better off if we simply started again, from scratch, screw the way things are, let's
try something new! Welcome to the human race my friends, welcome to the human
Rating 3 ½ out of 5


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Angelman Syndrome
OverviewAngelman syndrome (AS) is a genetic disorder that causes severe developmental delay, intellectual disability, and a distinctive and recognizable pattern of behaviors including frequent smiling, laughing, and hyperactivity. Although children with AS are typically social, delays in language and other features, such as decreased eye contact, are reminiscent of autism. Seizures, acquired microcephaly, gait ataxia, tremor, scoliosis, sleep and eating problems, and speech impairment are common. Children with AS appear normal at birth, then show progressive developmental delays. It is not until 2 years of age or later that the typical syndrome phenotype becomes obvious, though feeding problems and hypotonia may be present at birth and developmental delay is often apparent by 6 months of age. The diagnosis of AS is based on clinical features and genetic testing, which confirms the diagnosis in approximately 90% of individuals with the typical phenotype.
Other Names & Coding
Q93.5, Other deletions of part of a chromosome
Q93.51, Angelman syndrome (usable after October 1, 2018)
See ICD-10 Other Deletions of Part of a Chromosome (icd10data.com) for further coding details.
PrevalenceAngelman syndrome affects an estimated 1:12,000 to 1:20,000 people. [Genetic: 2018]
GeneticsAS and Prader-Willi syndrome are examples of a genetic phenomenon called imprinting, where the clinical phenotype of a gene abnormality depends on the parent of origin of the gene defect. Individuals with AS are missing a functional copy of the UBE3A gene from their mother.
Genetic abnormalities leading to AS may result from:
- Deletions in the 15q11.2-q13 region of the maternally inherited chromosome 15
- Paternal uniparental disomy, where both copies of the gene derive from the father
- Mutations in the maternally inherited UBE3A gene
- An imprinting defect of the maternally inherited 15q11.2-q13 locus
PrognosisMost children with AS will have seizures and will need antiepileptic therapy. Children with AS do not show developmental regression and, with good proactive care, should have normal life expectancies. They are, however, at risk for early death due to seizures, aspiration pneumonia, and chronic and restrictive lung diseases.
Practice Guidelines
Roles of the Medical HomeIn addition to well-child and acute-care visits, the medical home may want to schedule periodic chronic-care visits to help with ongoing issues including behavior and educational progress. Needs will change over the life of the child; an infant may require only early intervention, whereas an adolescent with seizures, difficulty sleeping, hyperactivity, and self-injurious behavior may need many more interventions.
Clinical Assessment
Pearls & Alerts for AssessmentPain may be the cause of prolonged irritability
The happy affect seen in children with AS is so persistent that medical causes for pain, such as severe gastroesophageal reflux, should be considered when patients appear irritable or "miserable" for prolonged periods.Response to negative genetic testing
If genetic testing comes back negative for AS, consider differential diagnoses.Considerations when diagnosing seizures
The majority of children with AS will require treatment for seizures; however, diagnosis can be challenging since movement abnormalities can be mistaken for seizures and EEG abnormalities can exist despite absence of seizures.
Of Family MembersNo specific screening is indicated for family members of the child with AS. However, because point mutations in UBE3A and some imprinting deletions can be inherited from the mother, maternal genetic testing should be performed when these are identified in the child
For ComplicationsBecause scoliosis occurs in about 50% of individuals with AS and is diagnosed at a mean age of 12 years, early and routine scoliosis screening may be useful. [Larson: 2015]
Diagnostic CriteriaInitial diagnosis is based on clinical features and confirmatory molecular genetic testing or UBE3A sequence analysis. Approximately 10% of children with AS have negative genetic testing and are diagnosed based on clinical features alone. Few children with AS are diagnosed before their second birthday due to non-specific presentation in infancy. Consensus criteria for the clinical diagnosis of AS, published in 2006, are summarized below. [Williams: 2006]
A. Consistent features (found in 100% of children with AS):
- Developmental delay, functionally severe
- Movement or balance disorder, usually ataxia of gait and/or tremulous movement of limbs. Movement disorder can be mild. May not appear as frank ataxia but can be forward lurching, unsteadiness, clumsiness, or quick, jerky motion.
- Behavioral uniqueness: any combination of frequent laughter/smiling; apparent happy demeanor; easily excitable personality, often with uplifted hand-flapping or waving movements; hyper-motoric behavior
- Speech impairment, none or minimal use of words; receptive and non-verbal communication skills higher than verbal ones
- Delayed, disproportionate growth in head circumference, usually resulting in microcephaly (≤2 S.D. of normal OFC) by age 2 years. Microcephaly is more pronounced in those with 15q11.2-q13 deletions.
- Seizures, onset usually <3 years of age. Seizure severity usually decreases with age, but the seizure disorder lasts throughout adulthood.
- Abnormal EEG, with a characteristic pattern. The EEG abnormalities can occur in the first 2 years of life and can precede clinical features; they are often not correlated with clinical seizure events.
- Flat occiput
- Occipital groove
- Protruding tongue
- Tongue thrusting; suck/swallowing disorders
- Feeding problems and/or truncal hypotonia during infancy
- Prognathia
- Wide mouth, wide-spaced teeth
- Frequent drooling
- Excessive chewing/mouthing behaviors
- Strabismus
- Hypopigmented skin, light hair, and eye color (compared to family), seen only in deletion cases
- Hyperactive lower extremity deep tendon reflexes
- Uplifted, flexed arm position especially during ambulation
- Wide-based gait with pronated or valgus-positioned ankles
- Increased sensitivity to heat
- Abnormal sleep-wake cycles and diminished need for sleep
- Attraction to/fascination with water; fascination with crinkly items such as certain papers and plastics
- Abnormal food-related behaviors
- Obesity (in the older child)
- Scoliosis
- Constipation
Differential DiagnosisCerebral palsy, static encephalopathy, idiopathic seizures, and other non-specific entities may be diagnosed during the time when infants with AS present with non-specific developmental delay and then develop seizures and more-typical facial features. More specific diagnoses of inborn errors of metabolism or mitochondrial disorders, which will be ruled out based on negative testing for these disorders, may also be considered.
Rett syndrome (in girls) and other MECP2-associated persistent developmental delays can be difficult to distinguish from AS, particularly in girls who do not demonstrate the typical regressive development and hand-wringing noted in Rett syndrome. [Jedele: 2007] The smiling, happy effect of children with AS is not seen in girls with Rett syndrome. Diagnosis can be made by MECP2 gene testing in Rett syndrome and UBE3A gene testing in AS. See the Portal's Rett Syndrome for diagnosis and management information.
Mowat/Mowat-Wilson syndrome can also be associated with a happy affect, microcephaly, seizures, constipation, and developmental delay. Mowat syndrome is caused by mutations in the ZEB2 gene. AS and Mowat syndrome can be differentiated by genetic testing. See Mowat-Wilson Syndrome (MedlinePlus) for more information.
Phelan-McDermid syndrome (deletion 22q13) may also have some clinical overlap with AS. Other non-specific chromosome imbalances are also possible.
Christianson syndrome presents only in males and has been attributed to mutations of SLC9A6. This is very rare and does not account for the 10% of individuals with negative genetic testing.
Pitt-Hopkins Syndrome (GeneReviews) is characterized by intellectual disability, wide mouth and distinctive facial features, and intermittent hyperventilation followed by apnea. Features that may overlap with AS include microcephaly, seizures, ataxic gait, and happy personality.
Other chromosome anomalies, some inborn errors of metabolism, and brain anomalies that result in speech and balance impairments should also be considered. [Tan: 2014]
Comorbid & Secondary ConditionsConditions or problems commonly found in children with AS include:
- Seizures
- Sleep disturbance
- Strabismus
- Aspiration pneumonia
- Chronic lung disease
- Scoliosis
- Gastroesophageal reflux
- Constipation
- Contractures
History & Examination
Family HistoryAsk about a family history of AS, autistic features, intellectual disability, and neurologic problems.
Pregnancy/Perinatal HistoryPregnancy and birth history is usually normal. Newborns may have difficulty learning to drink by breast and/or bottle. There may be a history of mild hypotonia.
Developmental & Educational ProgressEvaluate for achievement of developmental milestones. Gross motor and language delay are common. Ask about hyper-motoric activity, frequent mouthing of objects, and short attention span. Language delay and impairment are usually severe. Receptive language may be better than expressive language, but still quite delayed for age. [Dan: 2003]
Physical Exam
GeneralLook for a happy, smiling demeanor with frequent laughing and decreased eye contact. See Photographs of Individuals with AS (Angelman Syndrome Foundation).
Growth ParametersHt | Wt | OFC - 50% of children with AS will have acquired microcephaly with head circumferences below the 2nd percentile by 1 year of age. Monitor for weight loss due to eating difficulties.
HEENT/OralEvaluate for strabismus. Sometimes children with AS will have hypopigmented irises, skin, and hair due to deletion of a contiguous gene that is associated with albinism, OCA2. Dental hygiene may be challenging. Check teeth for orthodontic issues and caries.
Extremities/MusculoskeletalLook for hypotonia and tremulousness. Check deep tendon reflexes that may be hyperreflexic. Walking typically occurs after the age of 2 years; the gait of children with AS is often stilted with a robot-like character. Arms are often held up, bent at the elbows, palms facing outward. Scoliosis is common in adolescents. Tight ankles and knees may also be noted, particularly in adolescents and adults.
Genetic TestingDNA methylation analysis identifies approximately 80% of individuals with AS, including microdeletions of the AS/Prader-Willi syndrome critical region in 68%, UBE3A mutations in 11%, paternal uniparental disomy of chromosome 15 in 7%, imprinting defects in 3%, unbalanced chromosome translocation in <1%, and unknown (11%). If this test is negative, yet AS is still highly suspected, UBE3A sequence analysis may be ordered by genetics.
See Diagnostic Testing for Angelman Syndrome (Angelman.org) for a diagram with a suggested order for testing of AS, Lab Testing for AS (Genetic Testing Registry) for testing sites, and Practice Guidelines for the Molecular Analysis of Prader-Willi and Angelman Syndrome [Ramsden: 2010] for more details.
Other TestingRecommended baseline assessments for diagnosis and preventive care: [Dagli: 2017]
- Brain MRI - baseline. Does not usually need to be repeated unless clinical picture changes. May show atrophy and delayed myelination, but no structural lesions.
- EEG - Baseline and as clinically indicated for management of seizures. Many seizure types are associated with AS, including grand mal, absence, and others; infantile spasms are rare. The typical abnormalities involve generalized changes with areas of high-amplitude delta activity alternating with spike and slow-wave activity.
- Orthopedic assessment if scoliosis, gait impairment, tight Achilles tendons, and/or moderate to severe hypotonia are present. Children with AS tend to walk late, between 2 1/2 and 6 years of age. The gait may appear jerky and stiff. Scoliosis tends to appear later in childhood or in adolescence.
- Ophthalmology examination to look for strabismus, ocular albinism (seen in a subgroup of children with AS), and to evaluate visual acuity
- Speech/language evaluation as needed, though verbal expression is rare in this disorder
- Physical therapy evaluation as needed
- Assess for Gastroesophageal Reflux Disease in infants and toddlers; maximize diet and avoid under/over nutrition in children of all ages.
Specialty Collaborations & Other Services
Developmental - Behavioral Pediatrics (see NV providers [2])
Refer for developmental evaluation, which can help guide care and planning.
Pediatric Physical Medicine & Rehabilitation (see NV providers [3])
Refer for developmental evaluation and care planning.
Pediatric Gastroenterology (see NV providers [6])
Gastroesophageal reflux and constipation are common; referral may help with evaluation and management.
Pediatric Orthopedics (see NV providers [8])
Consider baseline referral and periodic follow-up for gross motor delay, hypotonia, tight Achilles tendons, and/or scoliosis. Frequency of evaluations will depend on degree of scoliosis.
Pediatric Ophthalmology (see NV providers [6])
Refer for problems with eye muscle coordination, acuity, and evaluation of ocular albinism.
Speech - Language Pathologists (see NV providers [13])
Evaluation and treatment are helpful for enhancing verbal and nonverbal communication skills.
Electroencephalography (EEG) (see NV providers [1])
Recommend to establish baseline and if there is a significant change in seizure pattern.
Medical Genetics (see NV providers [5])
Periodic visits can help establish an appropriate referral base and can help explore differential diagnoses.
Pediatric Neurology (see NV providers [5])
Seizures may be difficult to control, and periodic evaluations or concurrent care with a pediatric neurologist may be helpful.
Sleep Studies/Polysomnography (see NV providers [0])
Polysomnography can help diagnose sleep difficulties.
Pediatric Dentistry (see NV providers [31])
Refer for management of orthodontic issues, caries, and basic care, which can be challenging to manage in children with AS.
Treatment & Management
OverviewNo treatments are available for the underlying cause of Angelman syndrome, though researchers are currently exploring gene therapy to "unsilence" the paternal UBE3A gene to allow it to express, mitigating the impact of the defective maternal gene. [Beaudet: 2016] [Meng: 2015]
Pearls & Alerts for Treatment & ManagementSeizure medications may make seizures worse
Use of vigabatrin, carbamazepine, and tiagabine in children with AS may lead to an increase in absence and myoclonic seizures. This paradoxical seizure development is not limited to individuals with AS.Communication
Speech therapy should focus on nonverbal methods of communication. Augmentative communication aids such as picture cards or communication boards should be used at the earliest appropriate time. Attempts to teach signing should begin as soon as the child is sufficiently attentive.
How should common problems be managed differently in children with Angelman Syndrome?
Common ComplaintsConstipation is a common problem for individuals with AS and may be difficult to manage. See the Portal's Constipation for assistance in managing and minimizing constipation.
Development (general)
Language: Speech therapy should be initiated as soon as the diagnosis is confirmed. Most children will use only nonverbal methods of communication; begin early with signing, picture cards, and communication boards. See Augmentative Communication (AAC).
Specialty Collaborations & Other Services
Developmental - Behavioral Pediatrics (see NV providers [2])
May be helpful for an evaluation of strengths and weaknesses and the development of a specific plan for developmental services.
Early Intervention for Children with Disabilities/Delays (see NV providers [32])
Free or low cost for most families; provides developmental assessment and interventions, generally in the home.
Physical Therapy (see NV providers [11])
Often helpful, particularly for non-ambulatory patients
Occupational Therapy (see NV providers [27])
Helpful for those with feeding and fine motor problems
Speech - Language Pathologists (see NV providers [13])
May be effective for enhancing communication
Specialty Collaborations & Other Services
Pediatric Neurology (see NV providers [5])
Helpful for management of seizures
If associated medical causes are ruled out and the child is still not sleeping well, medications may be helpful. The medical home may consider using short-term medications such as chloral hydrate or diphenhydramine for transient sleep problems, but often medications such as trazodone, clonidine, or amitryptiline may be necessary. Melatonin is sometimes successful. [Braam: 2008] Some families have had to confine the child to a safe bedroom so the family can get rest. See the Portal's Sleep Medications and Sleep Issues for more information.
Specialty Collaborations & Other Services
Sleep Disorders (see NV providers [0])
Consider referral for evaluation and/or help in management, especially when apnea, restless legs, or seizures are suspected.
Specialty Collaborations & Other Services
Pediatric Orthopedics (see NV providers [8])
A baseline visit and periodic evaluations may be helpful.
Gastro-Intestinal & Bowel Function
Constipation is also a common problem; see the Portal's Constipation for more information.
Specialty Collaborations & Other Services
Pediatric Gastroenterology (see NV providers [6])
Consider referral for challenging feeding problems and poor weight gain, gastroesophageal reflux, and severe constipation.
Specialty Collaborations & Other Services
Pediatric Ophthalmology (see NV providers [6])
Initial and periodic evaluation may identify problems early and limit consequences of poor vision.
Mental Health/Behavior
Specialty Collaborations & Other Services
General Counseling Services (see NV providers [209])
Behavior evaluation and management may be helpful for families
Psychiatry/Medication Management (see NV providers [49])
If medications are necessary, consider a consult with a child psychiatrist.
CSHCN Clinics (see NV providers [4])
A clinic or program that focuses on AS or individuals with dual diagnosis may be very helpful.
Pharmacy & Medications
A pivotal Phase 3 trial of gaboxadol will enroll approximately 50-60 pediatric Angelman patients ages 4 to 12 years, who will either receive the treatment candidate or placebo, with recruitment anticipated to begin in the second half of 2019. Families interested in participating should see An Open-Label Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of OV101 in Individuals With Angelman Syndrome (ELARA). See Phase 3 Trial of Gaboxadol In Children with Angelman Syndrome (ASN) for more information.
Females with AS may have difficulty with personal hygiene; families may benefit from help with menstrual management of individuals with disabilities.
Specialty Collaborations & Other Services
Developmental - Behavioral Pediatrics (see NV providers [2])
May be helpful in issues of sexuality and menstruation management
Gynecology: Pediatric/Adolescent; Special Needs (see NV providers [0])
Consider referral for problems associated with menses and concern about fertility
- Medical care - Families should discuss the transition of medical care from their pediatric medical home to an adult care provider. All necessary screening evaluations, e.g., scoliosis evaluation, should be performed before transition.
- Financial considerations - If appropriate, once the individual turns 18 years of age, caregivers can apply for guardianship and supplemental security income. (See Guardianship/Estate Planning for more information for families.) In many states, supplemental security income will automatically qualify the individual for Medicaid benefits.
- Life planning - The public education system covers individuals with AS until they turn 22. Transition planning, covering topics such as where the individual will live and how they will support themselves, should begin in the early teens so that appropriate skills can be taught in school.
Issues Related to Angelman Syndrome
Ask the Specialist
If I suspect Angelman syndrome, what testing should I send?
Consider beginning with methylation studies (detects approximately 78% of individuals with AS, including those with a deletion, uniparental disomy (UPD), or an imprinting defect). If methylation studies are normal, proceed with UBE3A sequence analysis (detects an additional 11% of individuals with AS).
What type of screening studies and/or subspecialty care does this patient need?
Screen for feeding difficulties, constipation, gastroesophageal reflux, strabismus, scoliosis, seizures, and sleep dysregulation. Refer to GI, neurology, ortho, or sleep if needed.
What is the risk of seizure in Angelman syndrome?
Eighty percent of children with Angelman syndrome have seizures, usually presenting prior to 3 years of age.
What therapies are most beneficial for patients with Angelman syndrome?
Physical therapy, occupational therapy, and speech therapy with an emphasis on nonverbal methods of communication, including augmentative communication aids (e.g., picture cards or communication boards) and signing are beneficial.
Resources for Clinicians
On the Web
Angelman Syndrome (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.
Angelman Syndrome (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
Helpful Articles
PubMed search for Angelman syndrome in children, last 5 years.
Bird LM.
Angelman syndrome: review of clinical and molecular aspects.
Appl Clin Genet. 2014;7:93-104. PubMed abstract / Full Text
Kyllerman M.
Angelman syndrome.
Handb Clin Neurol. 2013;111:287-90. PubMed abstract
Larson AM, Shinnick JE, Shaaya EA, Thiele EA, Thibert RL.
Angelman syndrome in adulthood.
Am J Med Genet A. 2015;167A(2):331-44. PubMed abstract / Full Text
Tan WH, Bird LM, Thibert RL, Williams CA.
If not Angelman, what is it? A review of Angelman-like syndromes.
Am J Med Genet A. 2014;164A(4):975-92. PubMed abstract
Williams CA, Dagli A.
Management of Genetic Syndromes (Chapter 6-Angelman Syndrome).
3rd ed. Wiley-Blackwell; 2010. 978-0-470-19141-5 http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470191414.html
Textbook with information about the medical management of common genetic syndromes; chapter 6 has information about Angelman syndrome.
Clinical Tools
Letters of Medical Necessity
Sample Letter of Medical Necessity, Angelman/Rett (GeneDx.com) ( 24 KB)
A customizable letter in Word format to provide support for testing for Angelman and Rett syndromes; from GeneDx, a commercial company that provides genomic testing and related services.
Angelman & Rett / CGH Microarray - Letter of Medical Necessity / Preauthorization.docx ( 18 KB)
Angelman, Smith-Magenis, and Underlying Syndromes / High-Resolution Chromosomes, FISH, Methylation - Letter of Medical Necessity / Preauthorization ( 18 KB)
Resources for Patients & Families
This page, in the Portal's For Parents & Families section, answers several common questions about Angelman syndrome and includes links to the Information on the Web resources listed here.
Information on the Web
Angelman Syndrome Foundation
Information, resources, and discussion forums for individuals with AS and their families. This organization also raises money for research on AS.
Angelman Syndrome (Orphanet)
Information and links about AS.
Angelman Syndrome (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.
American Epilepsy Society
Information and resources to understand epilepsy, especially for those who are not familiar with the condition.
Prescription Assistance Programs (Epilepsy Foundation)
Information and links to various prescription assistance programs, which may help reduce the cost of medications significantly.
National & Local Support
Foundation for Angelman Syndrome Therapeutics (FAST)
Established in 2008, FAST aims to assist individuals living with Angelman syndrome to realize their full potential and quality of life and to bring practical treatment into current medical practice as quickly as possible. The website offers educational material, ways to connect with the founder (a parent of a child with Angelman syndrome) and with other parents, and other resources.
Support Resources (Angelman Syndrome Foundation)
Educational and community resources by topic for those caring for children with Angelman syndrome.
Foundation for Angelman Syndrome Therapeutics (FAST)
Established in 2008, FAST aims to assist individuals living with Angelman syndrome to realize their full potential and quality of life and to bring practical treatment into current medical practice as quickly as possible. The website offers educational material, ways to connect with the founder (a parent of a child with Angelman syndrome) and with other parents, and other resources.
Epilepsy Foundation
A national organization that provides information about epilepsy; programs to improve epilepsy treatment; materials to assist in helping people with epilepsy find jobs; activities in schools to educate the public; activities to educate policymakers; funds for research; links to find local and state resources; and news about conferences and other items of interest.
Angelman Syndrome Studies (clinicaltrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.
Angelman Syndrome Foundation Contact Registry
Sponsored by the Angelman Syndrome Foundation, the registry asks for contact and demographic data for individuals with Angelman syndrome and their families so they can: notify potential participants about Angelman research trials and alert families about recent events and research findings.
Global Angelman Syndrome Registry
The Registry aims to collect data on individuals with Angelman syndrome (AS) through a series of online surveys to build the largest and most comprehensive global collection of information on AS to date; supported by AS foundations in over 20 countries.
Angelman Collaborative Research Partnership
Newsletter from the Angelman Syndrome Foundation notes two studies, one related to identifying biomarkers that could be used to assess the effects of drugs on AS and the other evaluating measures and technologies related to problems areas such as sleep, communication, and brain activity.
Services for Patients & Families in Nevada (NV)
|Service Categories
|# of providers* in:
|Other states (4) (show)
|CSHCN Clinics
|Developmental - Behavioral Pediatrics
|Early Intervention for Children with Disabilities/Delays
|Electroencephalography (EEG)
|General Counseling Services
|Gynecology: Pediatric/Adolescent; Special Needs
|Medical Genetics
|Occupational Therapy
|Pediatric Dentistry
|Pediatric Gastroenterology
|Pediatric Neurology
|Pediatric Ophthalmology
|Pediatric Orthopedics
|Pediatric Physical Medicine & Rehabilitation
|Physical Therapy
|Psychiatry/Medication Management
|School Districts
|Sleep Disorders
|Sleep Studies/Polysomnography
|Speech - Language Pathologists
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
Beaudet AL, Meng L.
Gene-targeting pharmaceuticals for single-gene disorders.
Hum Mol Genet. 2016;25(R1):R18-26. PubMed abstract / Full Text
Bird LM.
Angelman syndrome: review of clinical and molecular aspects.
Appl Clin Genet. 2014;7:93-104. PubMed abstract / Full Text
Braam W, Didden R, Smits MG, Curfs LM.
Melatonin for chronic insomnia in Angelman syndrome: a randomized placebo-controlled trial.
J Child Neurol. 2008;23(6):649-54. / Full Text
Conant KD, Thibert RL, Thiele EA.
Epilepsy and the sleep-wake patterns found in Angelman syndrome.
Epilepsia. 2009;50(11):2497-500. PubMed abstract
Dagli AI, Williams CA.
Angelman Syndrome.
GeneReviews. 2017. PubMed abstract / Full Text
Dan B, Boyd SG.
Angelman syndrome reviewed from a neurophysiological perspective. The UBE3A-GABRB3 hypothesis.
Neuropediatrics. 2003;34(4):169-76. PubMed abstract
Forrest KM, Young H, Dale RC, Gill DS.
Benefit of corticosteroid therapy in Angelman syndrome.
J Child Neurol. 2009;24(8):952-8. PubMed abstract
Genetic Home Reference.
Angelman syndrome.
U.S. Library of Medicine; (2018) http://ghr.nlm.nih.gov/condition/angelman-syndrome. Accessed on 8/2018.
Jedele KB.
The overlapping spectrum of rett and angelman syndromes: a clinical review.
Semin Pediatr Neurol. 2007;14(3):108-17. PubMed abstract
Kyllerman M.
Angelman syndrome.
Handb Clin Neurol. 2013;111:287-90. PubMed abstract
Larson AM, Shinnick JE, Shaaya EA, Thiele EA, Thibert RL.
Angelman syndrome in adulthood.
Am J Med Genet A. 2015;167A(2):331-44. PubMed abstract / Full Text
U.S. National Library of Medicine; (2017) http://www.nlm.nih.gov/medlineplus/druginfo/meds/a603012.html. Accessed on 8/2018.
Meng L, Ward AJ, Chun S, Bennett CF, Beaudet AL, Rigo F.
Towards a therapy for Angelman syndrome by targeting a long non-coding RNA.
Nature. 2015;518(7539):409-12. PubMed abstract / Full Text
Pelc K, Cheron G, Dan B.
Behavior and neuropsychiatric manifestations in Angelman syndrome.
Neuropsychiatr Dis Treat. 2008;4(3):577-84. PubMed abstract / Full Text
Ramsden SC, Clayton-Smith J, Birch R, Buiting K.
Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes.
BMC Med Genet. 2010;11:70. PubMed abstract / Full Text
Summers JA, Allison DB, Lynch PS, Sandler L.
Behaviour problems in Angelman syndrome.
J Intellect Disabil Res. 1995;39 ( Pt 2):97-106. PubMed abstract
Tan WH, Bird LM, Thibert RL, Williams CA.
If not Angelman, what is it? A review of Angelman-like syndromes.
Am J Med Genet A. 2014;164A(4):975-92. PubMed abstract
Thibert RL, Pfeifer HH, Larson AM, Raby AR, Reynolds AA, Morgan AK, Thiele EA.
Low glycemic index treatment for seizures in Angelman syndrome.
Epilepsia. 2012;53(9):1498-502. PubMed abstract / Full Text
Williams CA, Beaudet AL, Clayton-Smith J, Knoll JH, Kyllerman M, Laan LA, Magenis RE, Moncla A, Schinzel AA, Summers JA, Wagstaff
Angelman syndrome 2005: updated consensus for diagnostic criteria.
Am J Med Genet. 2006;140(5):413-8. PubMed abstract
Williams CA, Dagli A.
Management of Genetic Syndromes (Chapter 6-Angelman Syndrome).
3rd ed. Wiley-Blackwell; 2010. 978-0-470-19141-5 http://www.wiley.com/WileyCDA/WileyTitle/productCd-0470191414.html
Textbook with information about the medical management of common genetic syndromes; chapter 6 has information about Angelman syndrome.


text:
Welcome back.
Tuesday, January 20, 2009
And Hoopinion's Back
Recap of the MLK Day matinee and other relevant news to follow this morning.
3 comments:
- bonitis said...
whats up over at peachtree hoops?
and i dont despise mario nearly as much as you do, but mike woodson has officially lost his mind.
player min
acie law 2
thomas gardner 6
mario west 3
- 1:12 AM, January 20, 2009
- Jason Walker said...
Gratz on the ESPN Affiliate Status!
Well deserved!
PS---If this was old news, I hang my head in shame---
- 9:49 AM, January 20, 2009
- Bret LaGree said...
I'll let Peachtree Hoops make its own announcement at the appropriate time but I intend to read it every day.
- 10:00 AM, January 20, 2009
Subscribe to: Post Comments (Atom)


text:
Lufthansa is streamlining connections to Ethiopia. Starting from the winter timetable, Addis Ababa will be served non-stop from Frankfurt. The connection will be operated five times a week with an Airbus A340-300. In addition to more comfort and seats in Business Class and Economy Class, the modern long-haul aircraft also offers seats in Premium Economy Class. With the change to the winter timetable, flight times on this route will be shortened and transfer options optimised.
New from Frankfurt: Addis Ababa non-stop with Lufthansa


text:
Follow the instructions on this page to contact Johnnie Walker. It may save you time to check that the answer you're looking for isn't already in our Frequently Asked Questions
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CFP – JLDCS Special Issue: "Disability and Blood: Blood and the Crips"
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Journal of Literary and Cultural Disability Studies – Call for Papers
Special Issue: "Disability and Blood: Blood and the Crips"
Guest Editors: Michael Davidson (UCSD) and Sören Fröhlich (UCSD)
Since the HIV/AIDS blood feuds of the 1990s, scholarship into social and cultural definitions of blood has provided much-needed insights into statistical (Tukufu Zuberi), economical (Catherine Waldby and Robert Mitchell), and medical constructions of what blood was, is and how it can function (Keith Wailoo). This special issue of the Journal of Literary and Cultural Disability Studies (JLCDS) aims to close a gap in considerations of disability and blood. What does blood mean in cultural constructions of disability? How are disability and the body's fluid tissue related in literary and cultural productions? Blood seems omnipresent in cultural representations, ranging from mass-murderers and pure-blooded wizards, vampires, and the undead, to ritual uncleanness, illegitimate Presidential offspring, and pre-natal diagnostics. Be it in the blood work chart and diagnostics, in statistics of pathology, or in other definitions of individuals through blood, 'abnormalities' in the blood constitute disability just as disability qualifies blood itself. Yet blood always transgresses boundaries and destabilizes categories; it simultaneously defines and defies constructions of disabled and disability. We invite submissions from scholars who consider how blood functions in the construction of disability. Is it stable or fluid, definable or contagious, visible or hidden? How does blood make the crip, and how does the crip change the blood? How is either or are both abjected from the 'normal' to create what Lennard J. Davis calls a "diverse sameness?"
Possible topics include (but are not limited to):
– The female body as disabled, menarche, menstruation, birth,
– Race as disability, disability as race, the "one-drop rule,"
– Scientific racism, racial historiography and disability,
– Eugenics in cultural productions,
– Gendered disability, gendered blood,
– Medical discourses,
– Blood in treatments, procedures, and as medical commodity,
– Contagion and infection, conversely, immunization and vaccination,
– Purity and pollution as disabling discourses,
– Disability and blood in religious discourses,
– Containment and rupture as definitions of disability,
– Pathology and normalization of blood,
– Migration, exile, asylum and definitions of blood,
– Indigeneity, inheritance, lineage and disabilities,
– Representations of bleeding and blood.
Please email a one-page proposal firstname.lastname@example.com by June 1, 2014. Contributors can expect to be selected and notified by August 1, 2014. (Full drafts of the selected articles will be due on February 1, 2015). Please direct any questions to Sören Fröhlich.
For further information about JLCDS please contact Dr. David Bolt (firstname.lastname@example.com).