Darbepoetin alfa is a re-engineered form of erythropoietin containing 5 amino acid changes resulting in the creation of 2 new sites for N-linked carbohydrate addition. It has a 3-fold longer serum half-life compared to epoetin alpha and epoetin beta, it stimulates erythropoiesis by the same mechanism as rHuEpo and is used to treat anemia associated with chronic kidney failure and cancer chemotherapy. Darbepoetin is marketed by Amgen under the trade name Aranesp; the medication was approved in September 2001 by the Food and Drug Administration for treatment of anemia in patients with chronic kidney failure by intravenous or subcutaneous injection. In June 2001, it had been approved by the European Medicines Agency for this indication as well as the treatment of anemia in cancer patients undergoing chemotherapy. Dr. Reddy's Laboratories launched darbepoetin alfa in India under the brand name ‘Cresp’ in August 2010; this is the world’s first follow-on biologic of darbepoetin alfa. Darbepoetin is produced by recombinant DNA technology in modified Chinese hamster ovary cells.

It differs from endogenous erythropoietin by containing two more N-linked oligosaccharide chains. It is an erythropoiesis-stimulating 165-amino acid protein. Use of darbepoetin alfa is contraindicated in patients with hypersensitivity to the drug, pre-existing uncontrolled hypertension, pure red cell aplasia. Darbepoetin alfa has black box warnings in the United States for increased risk of death, myocardial infarction, venous thromboembolism, thrombosis of vascular access, tumor progression or recurrence. To avoid side effects, it is recommended for patients with chronic kidney failure or cancer to use the lowest possible dose needed to avoid red blood cell transfusions. In addition to those listed in the black box warning, use of darbepoetin alfa increases the risk of cardiovascular problems, including cardiac arrest, arrhythmia and congestive heart failure, edema. A recent study has extended these findings to treatment of patients exhibiting cancer-related anemia. Other reported adverse reactions include increased risk of seizure and chest pain.

Darbepoetin alfa is a Pregnancy Category C drug in the United States. Pregnant women who are taking darbepoetin alfa may enroll in Amgen’s Pregnancy Surveillance Program, it is not known. Mothers who choose to breast-feed are advised to use caution. Darbepoetin alfa binds to the erythropoietin receptor on erythroid progenitor cells, stimulating RBC production and differentiation. Amgen sent a "dear doctor" letter in January, 2007, that highlighted results from a recent anemia of cancer trial, warned doctors to consider use in that off-label indication with caution. Amgen advised the U. S. Food and Drug Administration as to the results of the DAHANCA 10 clinical trial; the DAHANCA 10 data monitoring committee found that 3-year loco-regional control in subjects treated with Aranesp was worse than for those not receiving Aranesp. In response to these advisories, the FDA released a Public Health Advisory on March 9, 2007, a clinical alert for doctors on February 16, 2007, about the use of erythropoeisis-stimulating agents such as epoetin alfa and darbepoetin alfa.

The advisory recommended caution in using these agents in cancer patients receiving chemotherapy or off chemotherapy, indicated a lack of clinical evidence to support improvements in quality of life or transfusion requirements in these settings. According to the 2010 update to clinical practice guidelines from the American Society of Clinical Oncology and the American Society of Hematology, use of ESAs such as darbepoetin alfa in cancer patients is appropriate when following stipulations outlined in FDA-approved labeling. Like EPO, darbepoetin alfa has the potential to be abused by athletes seeking a competitive advantage, its use during the 2002 Winter Olympic Games to improve performance led to the disqualification of cross-country skiers Larisa Lazutina and Olga Danilova of Russia and Johann Mühlegg of Spain from their final races. Epogen and Aranesp had more than $6 billion in combined sales in 2006. Procrit sales were about $3.2 billion in 2006

The environmental impact of recreational diving is the effects of diving tourism on the marine environment. These are considered to be adverse effects, include damage to reef organisms by incompetent and ignorant divers, but there may be positive effects as the environment is recognised by the local communities to be worth more in good condition than degraded by inappropriate use, which encourages conservation efforts. During the 20th century recreational scuba diving was considered to have low environmental impact, was one of the activities permitted in most marine protected areas. Since the 1970s diving has changed from an elite activity to a more accessible recreation, marketed to a wide demographic. To some extent better equipment has been substituted for more rigorous training, the reduction in perceived risk has shortened minimum training requirements by several training agencies. Training has concentrated on an acceptable risk to the diver, paid less attention to the environment; the increase in the popularity of diving and in tourist access to sensitive ecological systems has led to the recognition that the activity can have significant environmental consequences.

Scuba diving has grown in popularity during the 21st century, as is shown by the number of certifications issued worldwide, which has increased to about 23 million by 2016 at about one million per year. Scuba diving tourism is a growth industry, it is necessary to consider environmental sustainability, as the expanding impact of divers can adversely affect the marine environment in several ways, the impact depends on the specific environment. Tropical coral reefs are more damaged by poor diving skills than some temperate reefs, where the environment is more robust due to rougher sea conditions and fewer fragile, slow-growing organisms; the same pleasant sea conditions that allow development of delicate and diverse ecologies attract the greatest number of tourists, including divers who dive infrequently on vacation and never develop the skills to dive in an environmentally friendly way. Low impact diving training has been shown to be effective in reducing diver contact. Research on the effects of divers on tropical coral reefs has shown reduced coral cover on dived sites and a change in coral structure, with more resilient corals becoming dominant and a loss of species diversity over time.

These reefs may be less resilient to other stressors like disease outbreaks and severe weather damage. There is persuasive evidence that reefs can be damaged and the amenity value of dive sites compromised by badly planned or over-intensive tourist use. Marine tourism affects reef communities directly through disturbance such as structural damage to corals, boats grounding on reefs and damage by anchors, indirectly through alteration of water quality by nutrient enrichment and pollution by toxic substances, waste water and increased turbidity; the level of degradation depends on the intensity, frequency and type of use and the specific environment. Diver impact damage to corals includes skeletal breakage of branching species, tissue abrasion leading to infection by coral diseases, an overall reduction of hard coral coverage on reefs. Diving related activities may reduce the reef's resilience to reef stressors like climate change and bleaching events. In some dived tropical coral reef sites recreational divers have caused negative ecological impacts by inadvertent impacts with live corals causing physical damage at a rate faster than compensated for by natural recovery.

The long term result is reef degradation. One of the common challenges for local policy and management is maximising tourism benefits while reducing environmental degradation to long-term sustainable levels. In the soft sediment bottomed "muck diving" environment, it was observed that photography causes greater environmental disturbances than effects caused by diving experience, certification level, gender or age. Divers came into contact with the substrate more on soft sediment than on coral reefs, but environmental damage was not greater. Divers tend to touch animals more when observing or photographing cryptobenthic fauna, spent up to five times linger in interactions when using dSLR-cameras. Long-term impacts of this behaviour on cryptobenthic fauna and soft sediment habitats are unknown; the impacts of photographer behaviour and photographic flashes on a small sample of benthic fish species was investigated. The study showed negligible effects beyond those caused by human presence alone.

Flash photography caused no discernible ocular changes in seahorses and feeding success was not affected. Physical handling of animals produced strong stress responses. Diver impact on subtropical, temperate reefs is less researched than tropical reefs; the perception is that these reefs are less vulnerable than tropical reefs and the sessile species are less exposed to diver impact. Research in the Mediterranean in Spain indicates that sessile organisms with fragile and brittle calcareous or corneous skeletons are not resilient to frequent disturbances by divers. Diver contact with the bottom is prevalent on temperate reefs. One of the main forms mentioned is fin contact with the bottom sediment, raising particulate material into the water column and degrading visibility. Repetitive contact by divers and their equipment on the benthos is the general mechanism of reef degradation by recreational divers. Factors correlating with frequency of reef contact were found to be: Interval since the previous dive Experience in terms of number of dives to date Location of certification training Awareness of marine park zoning Use of photographic equipment - photographers are more likely

Íþróttabandalag Ísafjarðar known as ÍBÍ, was a sports union in Ísafjörður, best known for its football teams. In 2000, ÍBÍ merged with Héraðssamband Vestur-Ísfirðinga to form Héraðssamband Vestfirðinga. ÍBÍ's men's football team was founded in 1955 and participated in the Icelandic top-tier league in 1962, 1982 and 1983. It folded prior to the 1988 season due to financial difficulties and most of the players transferred over to Boltafélag Ísafjarðar. 1. Deild karla: Winners: 19611 Runner-up:: 198111 Then known as 2. Deild karla 2. Deild karla: Winners: 19731 Runner-up:: 196911 Then known as 3. Deild karla Gísli Magnússon 1973 Gísli Magnússon 1978 Martin Wilkinson 1983 Gísli Magnússon 1984–1985 Jón Oddsson 1986 Helgi Ragnarsson 1987 ÍBÍ's women´s team was founded in 1981 and participated in the Football Cup that year, it competed in the Icelandic top-tier league in 1984, 1985 and 1988. After being religated in 1988, the team folded and most of the players moved to Boltafélag Ísafjarðar. 1. Deild kvenna: Winners: 19871 Runner-up: 198311 Then known as 2.

Deild kvenna Jóhann Torfason 1981 Þór Albertsson 1982 Bjarni Jóhannsson 1983 Rósa Áslaug Valdimarsdóttir 1984 Jóhann Torfason 1985 Jón E. Haraldsson 1986–1987 Örnólfur Oddsson 1988

Cannabis in Bulgaria is classified as a class A drug, together with heroin, amphetamines and MDMA. Until 2004, a loosely defined. Since 2006, after the last amendment of the Penal Code, the penalty for possession is 1 to 6 years in prison and a fine between 1,000 and 5,000 euros. Many offenders have been prosecuted and put in jail for possession of a single joint. For possession with an aim of distribution, the sentence can range from 2 to 8 years for small amounts, to 3 to 12 years for large amounts, up to 5 to 15 years when executed by an organized criminal group. In these cases, the maximum fine to be determined together with the prison time is 50,000 euros. Growing is punishable by a fine up to 5,000 euros; the organizer of a growers' group can receive a jail sentence of 10 to 20 years and has to pay a fine of up to 100,000 euros, a participant 3 to 10 years in prison and a fine of 2,500 to 5,000 euros

Kevin Corke is an American journalist and is presently a White House Correspondent for Fox News Channel in Washington D. C. Corke was a national news correspondent based in Washington D. C. for NBC News from 2004-2008. Most of his work there involved coverage of the Bush Administration as a member of the White House Press Corps. Additionally, Corke reported from The Pentagon, U. S. Supreme Court and other locations in Washington D. C. Corke figured prominently in NBC's coverage of the Virginia Tech shooting. Corke was a news anchor at WTVJ-TV NBC in Miami. Corke has been seen as a play-by-play sports broadcaster for ESPN. Corke was an anchor and coordinating producer at ESPN in Bristol, CT. While there, he could be seen anchoring the network's flagship program. Corke was a sportscaster at 9News KUSA in Denver. Corke covered the Olympic Games in the latter while a correspondent at NBC News. Corke is a graduate of Harvard University where he earned a Master's degree and received the Littauer Fellow citation for academic excellence and commitment to work in the public interest.

He graduated from the University of Colorado Boulder where he earned Master's and Bachelor's degrees in Journalism. Kevin Corke has won numerous journalism awards, among them regional Emmys. Corke is a Life Member of Kappa Alpha Psi fraternity

A great comet is a comet that becomes exceptionally bright. There is no official definition. Great comets are rare. Although comets are named after their discoverers, great comets are sometimes referred to by the year in which they appeared great, using the formulation "The Great Comet of...", followed by the year. The vast majority of comets are never bright enough to be seen by the naked eye, pass through the inner Solar System unseen by anyone except astronomers; however a comet may brighten to naked eye visibility, more it may become as bright as or brighter than the brightest stars. The requirements for this to occur are: a large and active nucleus, a close approach to the Sun, a close approach to the Earth. A comet fulfilling all three of these criteria will be spectacular. Sometimes, a comet failing on one criterion will still be impressive. For example, Comet Hale–Bopp had an exceptionally large and active nucleus, but did not approach the Sun closely at all, yet it still became an famous and well observed comet.

Comet Hyakutake was a small comet, but appeared bright because it passed close to the Earth. Cometary nuclei vary in size from a few hundreds of metres across or less to many kilometres across; when they approach the Sun, large amounts of gas and dust are ejected by cometary nuclei, due to solar heating. A crucial factor in how bright a comet becomes is how large. After many returns to the inner Solar System, cometary nuclei become depleted in volatile materials and thus are much less bright than comets which are making their first passage through the Solar System; the sudden brightening of comet 17P/Holmes in 2007 showed the importance of the activity of the nucleus in the comet's brightness. On October 23–24, 2007, the comet suffered a sudden outburst which caused it to brighten by factor of about half a million, it unexpectedly brightened from an apparent magnitude of about 17 to about 2.8 in a period of only 42 hours, making it visible to the naked eye. All these temporarily made comet 17P the largest object in the Solar System although its nucleus is estimated to be only about 3.4 km in diameter.

The brightness of a simple reflective body varies with the inverse square of its distance from the Sun. That is, if an object's distance from the Sun is halved, its brightness is quadrupled. However, comets behave differently, due to their ejection of large amounts of volatile gas which also reflect sunlight and may fluoresce, their brightness varies as the inverse cube of their distance from the Sun, meaning that if a comet's distance from the Sun is halved, it will become eight times as bright. This means that the peak brightness of a comet depends on its distance from the Sun. For most comets, the perihelion of their orbit lies outside the Earth's orbit. Any comet approaching the Sun to within 0.5 AU or less may have a chance of becoming a great comet. For a comet to become spectacular, it needs to pass close to the Earth if it is to be seen. Halley's Comet, for example, is very bright when it passes through the inner Solar System every seventy-six years, but during its 1986 apparition, its closest approach to Earth was the most distant possible.

The comet was unspectacular. On the other hand, the intrinsically small and faint Comet Hyakutake appeared bright and spectacular due to its close approach to Earth at its nearest during March 1996, its passage near the Earth was one of the closest cometary approaches on record. Great comets of the past two millennia include the following: The bright-comet chronicles. John E. Bortle Memorable Comets of the Past Gary W. Kronk. Brightest comets seen since 1935