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STTC Best 1st Pet Scale. Welcome Turtle Lovers! We are frequently asked here at the Turtle Club about which species are the best for beginners to keep. This can be a difficult question to answer; one must consider that turtle ownership is not a short lived hobby but more of a long term commitment. Most turtles live a very long time and many species will definitely outlive their owners. In consideration of this one must not only plan for the long term they often must plan beyond that and consider who will care from them after they're gone. That said turtles are very easy to care for if you provide them with the right stuff. The right stuff depends on which species you have. There are many good sites out there on the internet that provide excellent care sheets once you know which species you have. At this time the Seattle Turtle and Tortoise Club does not provide individual care sheets, but we hope to aid in your identification of your animal by showing some of the more commonly kept (or member kept) species here. Beside each example we will provide a score of 1 to 5 relating to the difficultly of keeping each species. This scale is our own and one we have developed over time from the amount of calls we get asking for assistance.!
Rescue and Adoption - California Turtle & Tortoise Club. Introduction. Each year, California Turtle and Tortoise Club Adoption Committees rescue and place hundreds of abandoned, lost, seized, injured or diseased turtles and tortoises that have been turned in by other humane organizations, members of the public, local and federal government officers and veterinarians. These animals are treated, if sick, and are then placed as quickly as possible into suitable homes. Before you download and submit an adoption application form, please read the following paragraphs carefully: Because adoption applicants are screened, and for other humane and legal reasons, ANIMALS ARE USUALLY PLACED ONLY IN REGIONS WITH CTTC CHAPTERS. CTTC WILL NOT PLACE DESERT TORTOISES IN SITUATIONS WHERE CAPTIVE BREEDING MAY OCCUR. Please contact your local rescue societies, reptile and turtle/tortoise rescues, animal shelters, etc. Please provide your – or the animal's – location, species, gender, age/size and number of animals in your request for assistance. The California Turtle and Tortoise Club's Executive Board compiles Chapter adoption statistics. Quarterly and Annual Adoption Activity Reports are available on this page under the heading . By agreement with California Department of Fish and Wildlife, designated members of California Turtle & Tortoise Club serve as volunteer representatives for the Department for the relocation of desert tortoises (including captive bred hatchlings) within California. This involves Adoption Committee members in each CTTC Chapter responding to requests from State Fish and Game Officers, our own members, the general public, veterinarians and humane organizations such as the ASPCA and local animal shelters, to provide pick- up services, veterinary care and husbandry recommendations for desert tortoises. Every year, CTTC handles hundreds of desert tortoises and works to provide the best homes available. Members of California Turtle & Tortoise Club help to maintain the data base of captive desert tortoises, and process and issue the permits and registration materials for California Department of Fish and Wildlife's . The program was designed to allow the legal possession of a protected species (i. Having a legal mechanism in which to operate is essential in the endeavor to prevent individual members of the public from returning long term captive tortoises to the wild, a once common practice that is widely suspected to have been a major contributing factor in the spread of the Upper Respiratory Tract Disease epidemic that has devastated the wild population. CTTC Adoption Chairpersons require would be desert tortoise adoptees to complete the CDFG Permit Application when they receive a tortoise so that all desert tortoises placed by CTTC are tagged. If you already possess a desert tortoise and need a permit application, please email your closest CTTC Chapter to request a permit form. Permits have been issued for over 3. Limited to residents of Nevada. Under the authority of the US Fish and Wildlife Service and Nevada Department of Wildlife, Tortoise Group has performed adoptions of.Copyright Rio Grande Turtle & Tortoise Club. 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You can export data from Office Access 2007 in a variety of formats, including Microsoft Office Excel 2007, Microsoft Office Word 2007, and Windows SharePoint. This is the security patch for Microsoft Data Access Components as described in the MS04-003 : Security Update for Microsoft Data Access Components. UNI - ENTE ITALIANO DI NORMAZIONE - UNILa Direttiva 2. UE del 2. 5 ottobre 2. Stati membri di conseguire un obiettivo nazionale indicativo globale di risparmio energetico pari al 9% entro il 2. In particolare la direttiva impone, entro il 3. Non solo, l’Unione Europea ha lasciato la possibilit. La norma infatti fornisce i criteri per ripartire la spesa totale di riscaldamento e acqua calda sanitaria e si applica agli edifici di tipo condominiale dotati di impianti termici centralizzati. Se la contabilizzazione permette di “contare” l’energia richiesta per riscaldare la singola unit. Tale sistema mette quindi l’utente nelle condizioni di poter gestire il riscaldamento in maniera completamente autonoma all’interno della propria unit. In altre parole, la termoregolazione e la contabilizzazione del calore premiano il comportamento virtuoso del singolo utente che pu. M&PF Management & Preservation Fuels - Ripartizione del calore in conformit. Sono calcolati e definiti: la quota involontaria, la quota a consumo, i nuovi millesimi di riscaldamento di fabbisogno utile e i millesimi di acqua. Quadro normativo della Contabilizzazione Indiretta del Calore Nuova UNI 10200 «Impianti di riscaldamento centralizzati - Ripartizione delle spese di riscaldamento». Pubblicata sul Catalogo UNI nel mese di marzo 2013. L’aggiornamento della. EVOLUZIONE NORMATIVA IN CORSO Norme Uni 10200 Gratis downloads at Ebookinga.com - Download free pdf files,ebooks and documents. 2 SISTEMA RACCORDI A PRESSARE E TUBO MULTISTRATO PER IMPIANTI GAS Il sistema Comisa Gas Riparto delle spese di riscaldamento e acqua calda sanitaria secondo quanto indicato dalla versione attuale della normativa tecnica UNI 10200 (2013). Il decreto, all’art.16, prevede delle sanzioni per quei condomini che non si adegueranno a quanto stabilito. Nuova UNI 10200 -2013 «Impianti di riscaldamento centralizzati - Ripartizione delle spese di climatizzazione invernale. IL QUADRO LEGISLATIVO NAZIONALE 2. IL QUADRO LEGISLATIVO IN EMILIA-ROMAGNA 3. LA DIRETTIVA 2012/27/UE 4. IL DECRETO LEGISLATIVO n.102/2014 5. LA NORMA TECNICA UNI 10200 7. CONCLUSIONI CONTENUTI EDIFICI. L’energia termica utile prodotta viene quindi suddivisa in base ai: consumi volontari (quota variabile), ovvero quelli dovuti all’azione volontaria dell’utente mediante i dispositivi di termoregolazione (valvola termostatica o termostato), che vanno ripartiti in base alle indicazioni fornite dai dispositivi (letture) atti alla contabilizzazione del calore (contatori, ripartitori e altri sistemi); consumi involontari (quota fissa), ovvero quelli indipendenti dall’azione dell’utente e cio. Nel caso le singole unit. In un contesto di questo tipo, nel caso sia complicato determinare la potenza termica delle singole unit. Di fatto se la rete di distribuzione subisce modifiche o se viene dimostrato che il calcolo precedente . In linea generale, se l’impianto . In entrambi i casi, la UNI 1. Questo approccio ha quindi richiesto ben 7. Nel caso il generatore sia anche adibito alla produzione di acqua calda sanitaria . Nel caso di contabilizzazione diretta (contatori di calore) i consumi involontari, ovvero le dispersioni della rete di distribuzione, sono dati per differenza, sottraendo al consumo totale (energia totale erogata dal generatore) quello delle unit. In presenza invece di contabilizzazione indiretta (ripartitori e altri sistemi), dal momento che non . Normativa Uni 10200 Pdf EditorNormativa Uni 10200 Pdf WriterIn alternativa a tale procedura, la UNI 1. La UNI 1. 02. 00 non prevede la determinazione a priori delle due quote, ma com’. Tale approccio, al contrario del metodo delle percentuali, garantisce quindi una ripartizione della spesa che tiene conto sia delle eventuali variazioni climatiche che si possono registrate da un anno con l’altro, sia del comportamento del singolo utente. Acquista sicuramente rilievo l’introduzione del gi. Tali specifiche, oltre al calcolo dei millesimi di fabbisogno, sono state incluse per la stima del consumo involontario riconducibile alle dispersioni della rete di distribuzione. Inoltre, rimanendo nell’ambito di applicazione delle norme sulle prestazioni energetiche degli edifici, nella prima stagione di attivazione dell’impianto termico il responsabile dell’impianto, secondo la UNI 1. UNI/TS 1. 13. 00. Per quanto concerne invece la contabilizzazione del calore diretta, i contatori di calore vengono descritti dalle sei parti della UNI EN 1. Le attivit. A livello europeo, il CT 8. Contabilizzazione del calore” segue i lavori del CEN/TC 1. Contatori di calore” e congiuntamente funge da comitato specchio del CEN/TC 1. Ripartitori”. Inoltre, con riferimento all’attivit. Il CTI informa”, del mese di maggio 2. La norma UNI 10200 'ripartizione delle spese di climatizzazione invernale ed acqua calda sanitaria' . Download free Effective Reading Programs For The Elementary Grades A Best-Evidence Synthesis10/25/2016 Effective Reading Programs for the Elementary Grades: A Best-Evidence Synthesis. Effective Reading Programs for the Elementary Grades. Effective Reading Programs for the Elementary Grades. Effective Programs for Elementary. Effective Reading Programs for Middle and High Schools: A Best Evidence Synthesis By. Uses a cooperative learning structure that groups students for reading instruction according to their reading level across grades and. Effective Programs in Elementary Science: A Best Evidence Synthesis. Robert Slavin: SOE Faculty. Program Affiliations. Evidence- Based Education, Cooperative Learning, Comprehensive School Reform. Complete CVRobert Edward Slavin. Center for Research and Reform in Education. Johns Hopkins University. E. Joppa Road, Suite 5. Baltimore, MD 2. 12. Institute for Effective Education. Reading Programs for Middle and High Schools: a Best-evidence synthesis (2008) Cached. Effective reading programs for English language learners. Research in Brief: Effective Reading Programs for All. Effective Reading Programs for all Students in the. Effective Reading Programs for the Elementary Grades. It is useful, for example, to know that effective beginning reading programs emphasize phonemic awareness. Best-Evidence Synthesis.University of York. Robert. Slavin@york. Education. B. A. History), Aloha High School, Aloha, ORAwards and Scholarships. Honorary Doctorate, University of Groningen, The Netherlands, 2. AERA Fellow, 2. 01. AERA Review of Research Award, 2. Member, National Academy of Education, 2. Palmer O. Johnson Award (best article in an AERA journal in 2. American Educational. Research Association, 2. Honorary Doctorate, University of Ghent, Belgium, 2. Dana Award, 1. 99. Parents Magazine “As They Grow” award in education, 1. Award for Distinguished Scientific Contributions to Psychology, Maryland Psychological Association, 1. Distinguished Achievement Award for Excellence in Educational Journalism, Educational Press Association of America, 1. Palmer 0. Johnson Award (best article in an AERA journal in 1. American. Educational Research Association, 1. Distinguished Scholar, AERA Committee on the Role and Status of Minorities in. Educational Research, 1. Raymond B. Cattell Early Career Award for Programmatic Research, American Educational. Research Association, 1. NIMH Training Grant, Johns Hopkins University, 1. Commendation for Excellence in Scholarship, Reed College, 1. Professional Associations. National Academy of Education, 2. North American Editor, Educational Research and Evaluation, 1. International Association for the Study of Cooperation in Education. President, 1. 98. Vice President, 1. Association for Supervision and Curriculum Development. American Educational Research Association. Member- at- Large, AERA Council, 1. Chair, Publications Committee, 1. Slavin, R. E. Proven programs in education: Science, technology, and mathematics (STEM). Thousand Oaks, CA: Corwin. Proven programs in education: Classroom management and assessment. Thousand Oaks, CA: Corwin. Educational psychology: Theory into practice (1. Ed.). Two million children: Success for All. Thousand Oaks, CA: Corwin. Boston: Allyn & Bacon. Effective programs for Latino students. Show me the evidence: Proven and promising programs for America’s schools. Lisse, The Netherlands: Swets & Zeitlinger. Cooperative learning: Theory, research, and practice (2nd Ed.). Boston: Allyn & Bacon. Preventing early school failure: Research, policy, and practice. Boston: Allyn & Bacon. Using Student Team Learning (4th Ed). Baltimore, MD: Johns Hopkins Team Learning Project. Success for All: A relentless approach to prevention and early intervention in elementary schools. Arlington, VA: Educational Research Service. Effective programs for students at risk. Boston, MA: Allyn and Bacon. School and classroom organization. Hillsdale, NJ: Erlbaum. Team Accelerated Instruction - Mathematics. Watertown, MA: Charlesbridge. E., Sharan, S., Kagan, S., Hertz- Lazarowitz, R., Webb, C., & Schmuck, R. Learning to cooperate, cooperating to learn. Research methods in education: A practical guide (2nd Ed.). Englewood Cliffs, NJ: Prentice- Hall. Student Team Learning: An overview and practical guide (2nd Ed.). Washington, D. C.: National Education Association. Cooperative learning in student teams: What research says to the teacher. Washington, D. C.: National Education Association. J., & Lombardo, M. Teams- Games- Tournament: Theteam learning approach. Englewood Cliffs, NJ: Educational Technology Publications. Journal Articles. Slavin, R. Five essential strategies to make cooperative learning effective. Educational Leadership. E., Lake, C., Hanley, P., & Thurston, A. Experimental evaluations of elementary science programs: A best- evidence synthesis. Journal of Research in Science Teaching, 5. SAGE Open,4( 3), 1- 1. DOI: 1. 0. 1. 17. Cooperative learning and academic achievement: Why does groupwork work? Anales de Psicologia (Spain), 3. Success for All at 2. New developments in whole- school reform. Journal of Education for Students Placed at Risk, 1. Effective programmes in reading and mathematics: Lessons from the Best Evidence Encyclopaedia. School Effectiveness and School Improvement, 2. Taking Success for All to scale. Phi Delta Kappan, 9. Effects of educational technology applications on reading outcomes for struggling readers: A best- evidence synthesis. Reading Research Quarterly, 4. Overcoming the four barriers to evidence- based education. Education Week, 3. The effectiveness of educational technology applications for enhancing mathematics achievement in K- 1. A meta- analysis. Educational Research Review, 9, 8. E., Holmes, G., Madden, N. A., Chamberlain, A., & Cheung, A. Effects of a data- driven district reform model on state assessment outcomes. American Educational Research Journal, 5. Effective reading programs for Spanish- dominant English language learners (ELLs) in the elementary grades. Review of Educational Research, 8. How features of educational technology programs affect student reading outcomes: A meta- analysis. Educational Research Review, 7 (3), 1. Doi: 1. 0. 1. 01. JRN>. Ross, S., Sheard, M. K., Cheung, A., Elliott, L., & Slavin, R. E. Promoting primary pupils’ social- emotional learning and pro- social behavior: Longitudinal evaluation of the Together 4 All programme in Northern Ireland. Effective Education, 3 (2), 6. Effects of cooperative writing with embedded multimedia: A randomized experiment. Effective Education, 3 (1), 1- 9. A three- tier model of reading instruction supported by technology. International Journal of Innovation and Learning, 9 (3), 2. C., Karanzalis, M., & Gifford, R. Small- group computer- assisted tutoring to improve reading outcomes for struggling first and second graders. Elementary School Journal, 1. E., Lake, C., Davis, S., & Madden, N. Effective programs for struggling readers: A best- evidence synthesis. Educational Research Review, 6, 1- 2. E., Chamberlain, A., & Hennessy, M. Reading and language outcomes of a five- year randomized evaluation of transitional bilingual education. Educational Evaluation and Policy Analysis, 3. Job one for Title I: Use what works. Measures inherent to treatments in program effectiveness reviews. Journal of Research on Educational Effectiveness, 4 (4), 3. Effects of co- operative learning on the mathematics achievement of Years 4 and 5 pupils in Britain: A randomised control trial. Effective Education, 2 (1), 8. Evidence- based reform in education. Revista Ibero Americana de Educaci. Can financial incentives enhance educational outcomes? Evidence from international experiments. Educational Research Review, 5(1), 6. Letter to the editors: Response to Greenleaf and Petrosino. Reading Research Quarterly, 4. Effective programs in middle and high school mathematics: A best- evidence synthesis. Review of Educational Research, 7. E., Lake, C., Chambers, B., Cheung, A., & Davis, S. Effective reading programs for the elementary grades: A best- evidence synthesis. Review of Educational Research, 7. Issues in synthesizing educational program evaluations. Educational Researcher, 3. Computer assisted tutoring in Success for All: Reading outcomes for first grade. Journal of Research on Effective Education, 1 (2), 1. Effective programs in elementary mathematics: A best- evidence synthesis. Review of Educational Research, 7. Winner of the 2. 00. AERA Review of Research Award. C., Tucker, B., J., Cheung, A., & Gifford, R. Technology infusion in Success for All: Reading outcomes for first graders. Elementary School Journal, 1. Raising the bar at Furness High. Educational Leadership, 6. Retrieved January 2. A randomized evaluation of the Success for All Middle School reading program. Middle Grades Reading Journal, 2 (1), 1- 2. Preventing reading failure. Educational Leadership, 6. Final reading outcomes of the national randomized field trial of Success for All. American Educational Research Journal, 4. Research and effectiveness: A . Reducing the gap: Success for All and the achievement of African American students. The Journal of Negro Education, 7. Achievement effects of embedded multimedia in a Success for All reading program. Educational Evaluation and Policy Analysis, 2. Middle School Journal, 3. Bilingual Research Journal, 2. Review of Educational Research, 7. E., Cheung, A., Chamberlain, A., Madden, N. A., & Chambers, B. The national randomized field trial of Success for All: Second- year outcomes. American Educational Research Journal, 4. Educational Leadership, 6. How the two approaches can work together. American School Board Journal, 1. Reauthorizing Title I: A comprehensive vision. Effects of Success for All on TAAS Reading: A Texas statewide evaluation. The facts about comprehensive school reform. Putting the school back in school reform. Research on achievement outcomes of Success for All: A summary and response to critics. Roots & Wings: Effects of whole school reform on student achievement. American School Board Journal, 1. Comprehensive approaches to cooperative learning. Effects of bilingual and English as a second language adaptations of Success for All on the reading achievement of students acquiring English. Improving intergroup relations: Lessons learned from cooperative learning programs. Educational research in the 2. Century: Lessons from the 2. Schoolwide reform models: What works? Effects of Bilingual Cooperative Integrated Reading and Composition on students transitioning from Spanish to English reading. Elementary School Journal, 9. Effective dropout prevention and college attendance programs for students placed at risk. Journal of Education for Students Placed at Risk, 3 (2), 1. Reading by nine: What will it take? Peabody Journal of Education, 7. Far and wide: Developing and disseminating research- based programs. American Educator, 2. Can education reduce social inequity? Promising programs for elementary and middle schools: Evidence of effectiveness and replicability. What is malicious code and can I download it accidentally using Skype? Malicious code is a computer program put on your computer either without your knowledge (such as when you browse an infected website) or which you are tricked into installing. Such code is called “malicious” because its creators want to use it to annoy, scam, or harm you or others, either through: Damaging your computer’s inner systems, such as wiping its data or interfering with effectiveness. Using your computer to relay spam emails and viruses to your friends and contacts over the internet without your knowledge (a network of such infected computers is called a “botnet”). Spying on your activities to steal personal information to be used in identity theft (such programs are called “spyware”. Malicious code can take many forms, such as: Type Description. Scripts These attempt to run on your computer when you visit an infected website. Most modern browsers will give you a warning that a website wants to run a script when it happens. There are in fact many legitimate reasons a website may try to run a script on your computer – for instance, some websites will try to put a little file on your computer that remembers your details for your next visit (such a file is called a “cookie”) so you do not have to enter them again, so it can be hard to tell when a script is malicious. Worms These are a kind of virus, sent through emails and increasingly also through instant messaging. They are often hidden in an instant message or email in the form of an attachment, and the email will try to persuade you to open it. Some worms can mimic the email address of a friend in your contact list, to make you more likely to open it. Viruses These programs are spread through network links between computers. They work by installing themselves on the infected computer and giving it instructions, usually to interfere with the computer’s effectiveness or damage it, and also to distribute itself to as many other computers as possible. How to Record Phone Calls on an iPhone. Can I record phone conversation on my kid phone that was under my name?Trojan horses These malicious downloads include code hidden in other programs which the user actually wants to download. For instance: Music or movies downloaded illegally from the internet can frequently host malicious code. A user may encounter a pop- up message warning the user that their computer has failed a security check and needs to upgrade. A company the user trusts may seem to contact them with instructions to download a “patch” or upgrade, such as a chat message from someone purporting to work for Skype. This way the user will be tricked into downloading the program. Once installed, it is under the control of another person and your computer is then vulnerable to them if you have insufficient security. The best way to avoid malicious code of all kinds when using Skype is to ALWAYS have up- to- date security software. There are many different kinds on the market, some of them free. They can include the following features: Anti- virus software – this checks your computer for signs of viral activity and scans it against a database run by the anti- virus company. If a match is found, the program discovered will be disabled or deleted. Browsing security – this scans websites you browse to and checks whether they are legitimate. If not, you will be advised of any problems. Additionally, scripts such as cookies cannot be run or downloaded without your express permission. Firewall – this feature protects your computer from intrusion from the network. Only trusted connections will be made between your computer and the network. Skype for computer and Xbox. All Forum Topics; Previous Topic; Next Topic; Top tags. Other Microsoft sites. Windows; Office; Surface; Windows Phone; Mobile Devices; XBOX; MSN. Computer Help; Computer Newbies; Laptops; Phones; TVs. You don’t need any specialized hardware to record a phone call, Skype conversation. How to Record a Phone Call or Voice Chat From Your Computer or. We’ve previously covered how to record a phone call on. Correct and troubleshoot voip phone problems with echo, buzzing, dropped. Astra has a patch to correct this and it can be found at Aastra's site under v2. 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Melanoma, also known as malignant melanoma, is a type of cancer that develops from the pigment- containing cells known as melanocytes. About 2. 5% develop from moles. In those with slightly larger cancers, nearby lymph nodes may be tested for spread. Pregnant diabetic diet diabetes symptoms dry tongue Read More; treatment diabetic foot infection treatment diabetic foot infection Read More; reversing diabetes with diet reversing diabetes with diet Read More; diabetes.Most people are cured if spread has not occurred. For those in whom melanoma has spread, immunotherapy, biologic therapy, radiation therapy, or chemotherapy may improve survival. Globally, in 2. 01. Australia and New Zealand have the highest rates of melanoma in the world. There are also high rates in Europe and North America while it is less common in Asia, Africa, and Latin America. At later stages, the mole may itch, ulcerate or bleed. Metastasis of early melanoma is possible, but relatively rare: less than a fifth of melanomas diagnosed early become metastatic. Brain metastases are particularly common in patients with metastatic melanoma. Genetics also play a role. Having trouble identifying your pills? Melanoma is divided into the following types: Lentigo maligna; Lentigo maligna melanoma; Superficial spreading melanoma; Acral lentiginous melanoma; Mucosal melanoma; Nodular melanoma; Polypoid melanoma; Desmoplastic melanoma. Recipes and diet notes on them. During my holiday to Bombay this time, I visited this Spanish dessert joint with friends and tried out their speciality called Churros for the first time. UV radiation. Thymine- thymine, cytosine- cytosine or cytosine- thymine dimers are formed by the joining of two adjacent pyrimidine bases within a DNA strand. Somewhat similarly to UVB, UVA light (longer wavelengths between 4. Occasional extreme sun exposure (resulting in . The risk appears to be strongly influenced by socio- economic conditions rather than indoor versus outdoor occupations; it is more common in professional and administrative workers than unskilled workers. Use of sunbeds (with deeply penetrating UVA rays) has been linked to the development of skin cancers, including melanoma. Melanoma rates tend to be highest in countries settled by migrants from northern Europe that have a large amount of direct, intense sunlight that the skin of the settlers is not adapted to, most notably Australia. Exposure during childhood is a more important risk factor than exposure in adulthood. This is seen in migration studies in Australia. Several genes increase risks. Shop online for vitamins, skin care, makeup, supplements, beauty, hair care, health products and much more! Save up to 60% at drugstore.com. Prepare for Your Procedure. Get the facts on what to expect during your procedure as well as your recovery. First of all let me say I am not a doctor or a dentist. Nothing on this page should be considered advice. You should not assume I am an expert on Geographic Tongue nor that any information presented on this page is from an. Montana's longest running web based business news portal, promoting Montana Business & Montana Lifestyle since 2005. Utilize hashtags #mtbiz, #mttalent, #mtbenefits, #mtlocal in your social media. Rx treatment for fibromyalgia, painful DPN, pain after shingles & partial onset seizure in adults with epilepsy. Risks & benefits of LYRICA Some rare genes have a relatively high risk of causing melanoma; some more common genes, such as a gene called MC1. R that causes red hair, have a relatively lower elevated risk. Genetic testing can be used to search for the mutations. One class of mutations affects the gene CDKN2. A. An alternative reading frame mutation in this gene leads to the destabilization of p. Another mutation in the same gene results in a nonfunctional inhibitor of CDK4, a cyclin- dependent kinase that promotes cell division. Mutations that cause the skin condition xeroderma pigmentosum (XP) also increase melanoma susceptibility. Scattered throughout the genome, these mutations reduce a cell's ability to repair DNA. Both CDKN2. A and XP mutations are highly penetrant (the chances of a carrier to express the phenotype is high). Familial melanoma is genetically heterogeneous. Multiple genetic events have been related to melanoma's pathogenesis (disease development). People with mutations in the MC1. R gene, for example, are two to four times more likely to develop melanoma than those with two wild- type (typical unaffected type) copies. MC1. R mutations are very common; in fact, all red- haired people have a mutated copy. Mutation of the MDM2 SNP3. Melanocytes are found between the outer layer of the skin (the epidermis) and the next layer (the dermis). This early stage of the disease is called the radial growth phase, when the tumor is less than 1 mm thick. Because the cancer cells have not yet reached the blood vessels deeper in the skin, it is very unlikely that this early- stage melanoma will spread to other parts of the body. If the melanoma is detected at this stage, then it can usually be completely removed with surgery. When the tumor cells start to move in a different direction . From this point on the melanoma is capable of spreading. The Breslow's depth of the lesion is usually less than 1 mm (0. Clark level is usually 2. The vertical growth phase (VGP) following is the invasive melanoma. The tumor becomes able to grow into the surrounding tissue and can spread around the body through blood or lymph vessels. The tumor thickness is usually more than 1 mm (0. The host elicits an immunological reaction against the tumor during the VGP. These cells sometimes completely destroy the primary tumor; this is called regression, which is the latest stage of development. In certain cases, the primary tumor is completely destroyed and only the metastatic tumor is discovered. About 4. 0% of human melanomas contain activating mutations affecting the structure of the B- Raf protein, resulting in constitutive signaling through the Raf to MAP kinase pathway. The most frequent mutations due to inaccurate synthesis past CPDs are cytosine to thymine (C> T) or CC> TT transition mutations. These are commonly referred to as UV fingerprint mutations, as they are the most specific mutation caused by UV, being frequently found in sun- exposed skin but rarely found in internal organs. This is much higher than the approximately 7. When the cell divides, these mutations are propagated to new generations of cells. If the mutations occur in protooncogenes or tumor suppressor genes, the rate of mitosis in the mutation- bearing cells can become uncontrolled, leading to the formation of a tumor. Data from patients suggest that aberrant levels of activating transcription factor in the nucleus of melanoma cells are associated with increased metastatic activity of melanoma cells. The normal moles on the right side do not have abnormal characteristics (no asymmetry, even border, even color, no change in diameter). The brown pigment is focal deposition of melanin. Visual inspection is the most common diagnostic technique. To detect melanomas (and increase survival rates), it is recommended to learn to recognize them (see . Physicians typically examine all moles, including those less than 6 mm in diameter. Seborrheic keratosis may meet some or all of the ABCD criteria, and can lead to false alarms. Doctors can generally distinguish seborrheic keratosis from melanoma upon examination, or with dermatoscopy. Some advocate replacing enlarging with evolution. Certainly moles that change and evolve will be a concern. Alternatively, some practitioners prefer elevation. Elevation can help identify a melanoma, but lack of elevation does not mean that the lesion is not a melanoma. Most melanomas in the US are detected before they become elevated. By the time elevation is visible, they may have progressed to the more dangerous invasive stage. Nodular melanomas do not fulfill these criteria, having their own mnemonic, . Correlation of common lesion characteristics is made. Lesions that greatly deviate from the common characteristics are labeled an . Extra care is required when examining such individuals, as they might have multiple melanomas and severely dysplasticnevi. A dermatoscope must be used to detect . Their borders are often indistinct, complicating visual identification without a dermatoscope. Amelanotic melanomas and melanomas arising in fair- skinned individuals are very difficult to detect, as they fail to show many of the characteristics in the ABCD rule, break the . A skin biopsy performed under local anesthesia is often required to assist in making or confirming the diagnosis and in defining severity. Elliptical excisional biopsies may remove the tumor, followed by histological analysis and Breslow scoring. Punch biopsies are contraindicated in suspected melanomas, for fear of seeding tumor cells and hastening the spread of malignant cells. Total body photography, which involves photographic documentation of as much body surface as possible, is often used during follow- up for high- risk patients. The technique has been reported to enable early detection and provides a cost- effective approach (with any digital camera), but its efficacy has been questioned due to its inability to detect macroscopic changes. Although controversial, sentinel lymph node biopsies and examination of the lymph nodes are also performed in patients to assess spread to the lymph nodes. A diagnosis of melanoma is supported by the presence of the S- 1. HMB- 4. 5 is a monoclonal antibody that reacts against an antigen present in melanocytic tumors such as melanomas. It is used in anatomic pathology as a marker for such tumors. The antibody was generated to an extract of melanoma. It reacts positively against melanocytic tumors but not other tumors, thus demonstrating specificity and sensitivity. The antibody also reacts positively against junctional nevus cells but not intradermal nevi, and against fetal melanocytes but not normal adult melanocytes. HMB- 4. 5 is nonreactive with almost all non- melanoma human malignancies, with the exception of rare tumors showing evidence of melanogenesis (e. Staging. Sunscreen also protects against squamous cell carcinoma, another skin cancer. This is usually followed up with a wider excision of the scar or tumor. Depending on the stage, a sentinel lymph node biopsy is done, as well, although controversy exists around trial evidence for this procedure. Complete surgical excision with adequate surgical margins and assessment for the presence of detectable metastatic disease along with short- and long- term followup is standard. Often this is done by a wide local excision (WLE) with 1 to 2 cm margins. Melanoma- in- situ and lentigo malignas are treated with narrower surgical margins, usually 0. Many surgeons consider 0. The wide excision aims to reduce the rate of tumor recurrence at the site of the original lesion. This is a common pattern of treatment failure in melanoma. Considerable research has aimed to elucidate appropriate margins for excision with a general trend toward less aggressive treatment during the last decades. Attempts to improve survival by removing lymph nodes surgically (lymphadenectomy) were associated with many complications, but no overall survival benefit. |
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