title: Irish elk

text: It has been historically thought that, because both have palmated antlers, the Irish elk and fallow deer ("Dama" spp.) are closely related, this is supported by several other morphological similarities, including the lack of upper canines, proportionally long braincase and nasal bones, and proportionally short front portion of the skull. In 2005, two fragments of mitochondrial DNA (mtDNA) from the cytochrome b gene were extracted and sequenced from 4 antlers and a bone, the mtDNA found that the Irish elk was nested within "Cervus," and were inside the clade containing living red deer ("Cervus elaphus"). Based on this, the authors suggested that the Irish elk and red deer interbred. However, another study from the same year in the journal "Nature" utilising both fragmentary mitochondrial DNA and morphological data found that the Irish elk was indeed most closely related to "Dama". The close relationship with "Dama" was supported by another cytochrome b study in 2006, a 2015 study involving the full mitochondrial genome, and by a 2017 morphological analysis of the bony labyrinth. The 2006 and 2017 studies also directly suggest that the results of the 2005 cytochrome b paper were the result of DNA contamination.


title: Irish elk

text: The Irish elk stood about tall at the shoulders and carried the largest antlers of any known deer, a maximum of from tip to tip and in weight. For body size, at about and up to or more, the Irish elk was the heaviest known cervine ("Old World deer"); and tied with the extant Alaska moose ("Alces alces gigas") as the third largest known deer, after the extinct "Cervalces latifrons" and "Cervalces scotti". Nonetheless, compared to "Alces", Irish elk appear to have had a more robust skeleton, with older and more mature "Alces" skeletons bearing some resemblance to those of prime Irish elk, and younger Irish elk resembling prime "Alces". Likely due to different social structures, the Irish elk exhibits more marked sexual dimorphism than "Alces", with Irish elk bucks being notably larger than does. In total, Irish elk bucks may have ranged from , with an average of , and does may have been relatively large, about 80% of buck size, or on average. The distinguishing characters of "M. giganteus" include concave frontals, proportionally long braincase, proportionally short front section of the skull (orbitofrontal region), alongside the absence of upper canines and the molarisation of the lower fourth premolar (P). The skull and mandible of the Irish elk exhibit substantial thickening (pachyostosis), with the early and complete obliteration of cranial sutures.


title: Irish elk

text: Based on Upper Palaeolithic cave paintings, the Irish elk seems to have had overall light colouration, with a dark stripe running along the back, a stripe on either side from shoulder to haunch, a dark collar on the throat and a chinstrap, and a dark hump on the withers (between the shoulder blades). In 1989, American palaeontologist Dale Guthrie suggested that, like bison, the hump allowed a higher hinging action of the front legs to increase stride length while running. Valerius Geist suggested that the hump may have also been used to store fat. Localising fat rather than evenly distributing it may have prevented overheating while running or in rut during the summer.


title: Irish elk

text: It was not exclusive to Ireland. Rather, it was so named because the most well-known and best-preserved fossil specimens have been found in lake sediments and peat bogs in Ireland. The Irish elk had a far-reaching range, extending from the Atlantic Ocean in the West to Lake Baikal in the East. They do not appear to have extended northward onto the open mammoth steppe, rather keeping to the boreal steppe-woodland environments, which consisted of scattered spruce and pine, as well as low-lying herbs and shrubs including grasses, sedges, "Ephedra, Artemisia" and Chenopodiaceae.


title: Irish elk

text: In 1998, Canadian biologist Valerius Geist hypothesised that the Irish elk was cursorial (adapted for running and stamina). He noted that the Irish elk physically resembled reindeer. The body proportions of the Irish elk are similar to those of the cursorial addax, oryx, and saiga antelope. These include the relatively short legs, the long front legs nearly as long as the hind legs, and a robust cylindrical body. Cursorial saiga, gnus, and reindeer have a top speed of over , and can maintain high speeds for up to 15 minutes.


title: Irish elk

text: At Ballybetagh Bog, over 100 Irish elk individuals were found, all small antlered bucks. This indicates that bucks and does segregated during at least winter and spring. Many modern deer species do this partly because males and females have different nutritional requirements and need to consume different types of plants. Segregation would also imply a polygynous society, with stags fighting for control over harems during rut. Because most of the individuals found were juvenile or geriatric and were likely suffering from malnutrition, they probably died from winterkill. Most Irish elk specimens known may have died from winterkill, and winterkill is the highest source of mortality among many modern deer species. Bucks generally suffer higher mortality rates because they eat little during the autumn rut. For rut, a lean stag normally may have fattened up to , and would burn through the extra fat over the next month.


title: Irish elk

text: Assuming a similar response to starvation as red deer, a large, healthy Irish elk stag with antlers would have had antlers under poor conditions; and an average sized Irish elk stag with antlers would have had antlers under poorer conditions, similar sizes to the moose. A similar change in a typical Irish elk population with prime stags having antlers would result in antler weights of or less in worsening climatic conditions. This is within the range of present-day wapiti/red deer ("Cervus" spp.) antler weights. Irish elk antlers vary widely in form depending upon the habitat, such as a compact, upright shape in closed forest environments. Irish elk likely shed their antlers and re-grew a new pair during mating season. Antlers generally require high amounts of calcium and phosphate, especially those for stags which have larger structures, and the massive antlers of Irish elk may have required much greater quantities. Stags typically meet these requirements in part from their bones, suffering from a condition similar to osteoporosis while the antlers are growing, and replenishing them from food plants after the antlers have grown in or reclaiming nutrients from shed antlers.


title: Irish elk

text: The large antlers have generally been explained as being used for male-male battle during mating season. They may have also been used for display, to attract females and assert dominance against rival males. A finite element analysis of the antlers suggested that during fighting, the antlers were likely to interlock around the middle tine, the high stress when interlocking on the distal tine suggests that the fighting was likely more constrained and predictable than among extant deer, likely involving twisting motions, as is known in extant deer with palmated antlers.


title: Irish elk

text: In deer, gestation time generally increases with body size. A doe may have had a gestation period of about 274 days. Based on this and patterns seen in modern deer, last year's antlers in Irish elk bucks were potentially shed in early March, peak antler growth in early June, completion by mid-July, shedding velvet (a layer of blood vessels on the antlers in-use while growing them) by late July, and the height of rut falling on the second week of August. Geist, believing the Irish elk to have been a cursorial animal, concluded that a doe would have to have produced nutrient-rich milk so that her calf would have enough energy and stamina to keep up with the herd.


title: Irish elk

text: The mesodont (meaning neither high (hypsodont) or low (brachydont) crowned) condition of the teeth suggests that the species was a mixed feeder, being able to both browse and graze. Pollen remains from teeth found in the North Sea around 43,000 years old were found to be dominated by "Artemisia" and other Asteraceae, with minor "Plantago", "Helianthemum", Plumbaginaceae and "Salix". A stable isotope analysis of the terminal Pleistocene Irish population suggests a grass and forb based diet, supplemented by browsing during stressed periods. Dental wear patterns of specimens from the late Middle and Late Pleistocene of Britain suggest a diet tending towards mixed feeding and grazing, but with a wide range including leaf browsing.


title: Irish elk

text: Based on the dietary requirements of red deer, a lean Irish elk stag would have needed to consume of fresh forage daily. Assuming antler growth occurred over a span of 120 days, a stag would have required 1,372 g (3 lb) of protein daily, as well as access to nutrient- and mineral-dense forage starting about a month before antlers began sprouting and continuing until they had fully grown. Such forage is not very common, and stags perhaps sought after aquatic plants in lakes. After antler growing, stags could probably satisfy their nutritional requirements in productive sedge lands bordered by willow and birch forests.


title: Irish elk

text: The Irish elk may have been preyed upon by the large carnivores of the time, including the cave lion, and the cave hyena.


title: Irish elk

text: Outside of the Irish Late Pleistocene, remains of Irish elk are uncommon, suggesting that they were usually rare in the areas that they did occur.


title: Irish elk

text: Historically, its extinction has been attributed to the encumbering size of the antlers, a "maladaptation" making fleeing through forests especially difficult for males while being chased by human hunters, or being too taxing nutritionally when the vegetation makeup shifted. In these scenarios, sexual selection by does for stags with large antlers would have contributed to decline.


title: Irish elk

text: However, antler size decreased through the Late Pleistocene and into the Holocene, and so may not have been the primary cause of extinction. A reduction in forest density in the Late Pleistocene and a lack of sufficient high-quality forage is associated with a decrease in body and antler size. Such resource constriction may have cut female fertility rates in half. Human hunting may have forced Irish elk into suboptimal feeding grounds.


title: Irish elk

text: The range of the taxon appears to have collapsed during the Last Glacial Maximum, with few remains known between 27,500 and 14,600 years ago, and none between 23,300 and 17,500 years ago. The remains of the taxon substantially increase during the latest Pleistocene, where it appears to have re-colonised most of its former range, with abundant remains in the UK, Ireland, and Germany.


title: Irish elk

text: While the range of the taxon was dramatically reduced after the Pleistocene-Holocene transition, it managed to survive into the early Northgrippian in the eastern part of its range within European Russia and Siberia, in a belt extending from Maloarchangelsk in the East to Preobrazhenka in the west. It is suggested that extinction was contributed to by further climatic changes transforming preferred open habitat into uninhabitable dense forest. The final demise may have been caused by several factors both on a continental and regional scale, including climate change and hunting. Lister and Stewart concluded in a study of the extinction of the Irish elk that "it seems clear that environmental factors, cumulatively over thousands of years, reduced giant deer populations to a highly vulnerable state. In this situation, even relatively low-level hunting by small human populations could have contributed to its extinction."


title: Irish elk

text: A handful of Irish elk depictions are known from the art of the Upper Paleolithic in Europe. However, these are much less abundant than the common red deer and reindeer depictions. The bones of the Irish elk are uncommon in localities where they are found, and only a handful of examples of human interaction are known. A mandible from Ofatinţi, Moldova dating to either the Eemian or the early Late Pleistocene, "is peculiar because it has ancient tool-made notches on its lateral side". Several "M. giganteus" bones from the Chatelperronian levels of the Labeko Koba site in Spain are noted for bearing puncture marks, which have been interpreted as anthropogenic. A terminal Pleistocene (13710-13215 cal BP) skull from Lüdersdorf, Germany is noted to have had the antler and facial part of the skull removed in a way unlikely to be due to natural causes. A calcaneum from an associated lower hind limb from the early Holocene site of Sosnovy Tushamsky in Siberia is noted to have "two short and deep traces of cutting blows", which are interpreted as "clear evidence of butchery". The use of shed antler bases is also known, at the terminal Pleistocene (Allerød) Endingen VI site in Germany, a shed antler base appears to have been used in a way analogous to a lithic core to produce "blanks" for the manufacture of barbed projectile tips. A ring-like mark on a shed antler beam from the similarly aged Paderborn site in Germany has been suggested to be anthropogenic.


title: Irish elk

text: Due to the abundance of Irish elk remains in Ireland, a thriving trade in their bones existed there during the 19th century to supply museums and collectors. Skeletons and skulls with attached antlers were also prized ornaments in aristocratic homes. The remains of Irish elk were of high value: "In 1865, full skeletons might fetch £30, while particularly good heads with antlers could cost £15." with £15 being more than 30 weeks' wages for a low skilled worker at the time. Indeed Leeds Philosophical and Literary Society bought a full skeleton in 1847, from Glennon's in Dublin, for £38. This specimen, discovered at Lough Gur near Limerick, is still on display at Leeds City Museum.


title: Irish elk

text: A folk memory of the Irish elk was once thought to be preserved in the Middle High German word , a large beast mentioned in the 13th-century "Nibelungenlied" along with the then-extant aurochs ( / "After this he straightway slew a Bison and an Elk, Of the strong Wild Oxen four, and a single fierce Schelch.") This opinion is no longer widely held. The Middle Irish word was also suggested as a reference to the Irish elk. Turf cutters of Clooney and Tulla in County Clare, Ireland referred to the Irish elk as the ( meaning Deer, meaning "great", or "large"). However, these interpretations are not conclusive.


title: Step Up (TV series)

text: Step Up (previously titled Step Up: High Water) is an American drama television series, based on the "Step Up" film series. It premiered on January 31, 2018, on YouTube Red. The series was created by Holly Sorensen, who also serves as an executive producer alongside Channing Tatum and Jenna Dewan. After being canceled by YouTube Red after two seasons, Starz picked up the series for a third season, which premiered on October 16, 2022. In December 2022, the series was canceled after three seasons.


title: Step Up (TV series)

text: The series follows the students and faculty of "High Water", Atlanta's most cutthroat performing arts school. When twins Tal and Janelle relocate from Ohio, they find themselves thrust into a world where every move is a test. As they attempt to navigate their new world— on and off the dance floor— they will discover just how deep they are willing to dig to realize their dreams and seize their moment.


title: Step Up (TV series)

text: On June 23, 2016, YouTube announced at the annual VidCon conference in Anaheim, California that they were developing a new drama series based on the "Step Up" film series with Lionsgate Television producing alongside Channing Tatum and Jenna Dewan.


title: Step Up (TV series)

text: On June 23, 2017, YouTube announced that it had officially given "Step Up: High Water" a first season order consisting of ten episodes, each running about 45 minutes in length. The series was described as YouTube Red's first "big-budget, Hollywood-produced television drama" and that its arrival would end up "moving it into more direct competition with players like Netflix and traditional cable networks." In the announcement, it was revealed that each episode of the series would cost several million dollars to produce. A few days later, members of the series' creative team were announced. Original songs for the series were set to be written by singer/songwriter Jason “PooBear” Boyd and “Jingle” Jared Gutstadt. The films series’ choreographer Jamal Sims was expected to choreograph the first episode after which subsequent episodes would be choreographed by Jamaica Craft. The pilot episode was set to be directed by Adam Shankman. It was later reported that Debbie Allen had directed the show's second episode.


title: Step Up (TV series)

text: On May 22, 2018, it was announced that YouTube had renewed the series for a second season. On January 24, 2019, it was reported that the second season would premiere on March 20, 2019. On August 16, 2019, YouTube Premium canceled the series after two seasons. On May 28, 2020, Starz picked up the series for a third season. Following filming restrictions during the COVID-19 pandemic, Blackhall Studios reopened for production on several films and the series, which was being written at the time, on July 13, 2020. Production was immediately paused on the same day when lead actress Naya Rivera was found dead following a boating accident several days prior. Rivera's character had been set to appear; in August 2020 it was announced that a re-worked season would begin filming in January 2021. On September 17, 2022, it was announced that the third season would premiere on October 16, 2022. Days before the season finale, it was announced that Starz had canceled the series.


title: Step Up (TV series)

text: On June 28, 2017, it was announced that Ne-Yo, Naya Rivera, Faizon Love, Lauryn McClain, Petrice Jones, Marcus Mitchell, Jade Chynoweth, Carlito Olivero, Terrence Green, R. Marcos Taylor, Eric Graise, and Kendra Oyesanya had been cast in the series' main roles. On January 19, 2018, it was reported that Savion Glover would make a guest appearance in the series as a teacher at High Water. On August 28, 2018, it was announced that in season two Ashley Greene and Jeremy Copeland were joining the cast, that Rick Ross and Todrick Hall would appear as themselves, and that JaQuel Knight would make a cameo appearance in addition to choreographing episode three. After YouTube canceled the series, Petrice Jones moved on to other projects, leaving him unavailable By the time Starz picked up the show for Season 3, he wasn't available. His role was filled by Keiynan Lonsdale as new character Tal Baker. Because of Naya Rivera's death, Christina Milian was cast as Collette.


title: Step Up (TV series)

text: On July 12, 2017, YouTube released a video introducing the show's main cast. On August 13, 2017, the cast of the series, including Jade Chynoweth and Kendra Oyesanya, performed at the 2017 Teen Choice Awards with a highly choreographed dance routine.


title: Step Up (TV series)

text: On December 19, 2017, YouTube released the first trailer for the series and announced that the show would premiere on January 31, 2018, with all ten episodes released at once. On January 24, 2019, the official trailer for season two was released.


title: Step Up (TV series)

text: On January 30, 2018, YouTube partnered with Fathom Events for special screenings of the first episode of the series at more than 750 movie theaters. The event also included a screening of the original 2006 "Step Up" film that launched the five-film franchise, and a behind-the-scenes look at the making of the television series.


title: Step Up (TV series)

text: In a positive review, Sonia Saraiya of "Variety" offered the series praise saying: "This YouTube Red original has found an intriguing way to blend the mediums of dance, film, and soapy teen television, with an energetic, conscious new installment in the series that is a lot of fun to get sucked into." In another favorable critique, "Decider"s Kayla Cobb described the series as "a genuinely compelling and dramatic story that very well may stand as the best narrative installment of the "Step Up" universe."


title: Hearing range

text: Hearing range describes the range of frequencies that can be heard by humans or other animals, though it can also refer to the range of levels. The human range is commonly given as 20 to 20,000 Hz, although there is considerable variation between individuals, especially at high frequencies, and a gradual loss of sensitivity to higher frequencies with age is considered normal. Sensitivity also varies with frequency, as shown by equal-loudness contours. Routine investigation for hearing loss usually involves an audiogram which shows threshold levels relative to a normal.


title: Hearing range

text: Several animal species are able to hear frequencies well beyond the human hearing range. Some dolphins and bats, for example, can hear frequencies over 100 kHz. Elephants can hear sounds at 14–16 Hz, while some whales can hear infrasonic sounds as low as 7 Hz.


title: Hearing range

text: A basic measure of hearing is afforded by an audiogram, a graph of the absolute threshold of hearing (minimum discernible sound level) at various frequencies throughout an organism's nominal hearing range.


title: Hearing range

text: Behavioural hearing tests or physiological tests can be used to find hearing thresholds of humans and other animals. For humans, the test involves tones being presented at specific frequencies (pitch) and intensities (loudness). When the subject hears the sound, they indicate this by raising a hand or pressing a button. The lowest intensity they can hear is recorded. The test varies for children; their response to the sound can be indicated by a turn of the head or using a toy. The child learns what to do upon hearing the sound, such as placing a toy man in a boat. A similar technique can be used when testing animals, where food is used as a reward for responding to the sound. The information on different mammals hearing was obtained primarily by behavioural hearing tests.


title: Hearing range

text: In humans, sound waves funnel into the ear via the external ear canal and reach the eardrum (tympanic membrane). The compression and rarefaction of these waves set this thin membrane in motion, causing sympathetic vibration through the middle ear bones (the ossicles: malleus, incus, and stapes), the basilar fluid in the cochlea, and the hairs within it, called stereocilia. These hairs line the cochlea from base to apex, and the part stimulated and the intensity of stimulation gives an indication of the nature of the sound. Information gathered from the hair cells is sent via the auditory nerve for processing in the brain.


title: Hearing range

text: The commonly stated range of human hearing is 20 to 20,000 Hz. Under ideal laboratory conditions, humans can hear sound as low as 12 Hz and as high as 28 kHz, though the threshold increases sharply at 15 kHz in adults, corresponding to the last auditory channel of the cochlea. The human auditory system is most sensitive to frequencies between 2,000 and 5,000 Hz. Individual hearing range varies according to the general condition of a human's ears and nervous system. The range shrinks during life, usually beginning at around the age of eight with the upper frequency limit being reduced. Women lose their hearing somewhat less often than men. This is due to a lot of social and external factors. For example, men spend more time in noisy places, and this is associated not only with work but also with hobbies and other activities. Women have a sharper hearing loss after menopause. In women, hearing decrease is worse at low and partially medium frequencies, while men are more likely to suffer from hearing loss at high frequencies.


title: Hearing range

text: Audiograms of human hearing are produced using an audiometer, which presents different frequencies to the subject, usually over calibrated headphones, at specified levels. The levels are weighted with frequency relative to a standard graph known as the minimum audibility curve, which is intended to represent "normal" hearing. The threshold of hearing is set at around 0 phon on the equal-loudness contours (i.e. 20 micropascals, approximately the quietest sound a young healthy human can detect), but is standardised in an ANSI standard to 1 kHz. Standards using different reference levels, give rise to differences in audiograms. The ASA-1951 standard, for example, used a level of 16.5 dB SPL (sound pressure level) at 1 kHz, whereas the later ANSI-1969/ISO-1963 standard uses , with a 10 dB correction applied for older people.


title: Hearing range

text: Several primates, especially small ones, can hear frequencies far into the ultrasonic range. Measured with a signal, the hearing range for the Senegal bushbaby is 92 Hz–65 kHz, and 67 Hz–58 kHz for the ring-tailed lemur. Of 19 primates tested, the Japanese macaque had the widest range, 28 Hz–34.5 kHz, compared with 31 Hz–17.6 kHz for humans.


title: Hearing range

text: Cats have excellent hearing and can detect an extremely broad range of frequencies. They can hear higher-pitched sounds than humans or most dogs, detecting frequencies from 55 Hz up to 79 kHz. Cats do not use this ability to hear ultrasound for communication but it is probably important in hunting, since many species of rodents make ultrasonic calls. Cat hearing is also extremely sensitive and is among the best of any mammal, being most acute in the range of 500 Hz to 32 kHz. This sensitivity is further enhanced by the cat's large movable outer ears (their "pinnae"), which both amplify sounds and help a cat sense the direction from which a noise is coming.


title: Hearing range

text: The hearing ability of a dog is dependent on breed and age, though the range of hearing is usually around 67 Hz to 45 kHz. As with humans, some dog breeds' hearing ranges narrow with age, such as the German shepherd and miniature poodle. When dogs hear a sound, they will move their ears towards it in order to maximize reception. In order to achieve this, the ears of a dog are controlled by at least 18 muscles, which allow the ears to tilt and rotate. The ear's shape also allows the sound to be heard more accurately. Many breeds often have upright and curved ears, which direct and amplify sounds.


title: Hearing range

text: As dogs hear higher frequency sounds than humans, they have a different acoustic perception of the world. Sounds that seem loud to humans often emit high-frequency tones that can scare away dogs. Whistles which emit ultrasonic sound, called dog whistles, are used in dog training, as a dog will respond much better to such levels. In the wild, dogs use their hearing capabilities to hunt and locate food. Domestic breeds are often used to guard property due to their increased hearing ability. So-called "Nelson" dog whistles generate sounds at frequencies higher than those audible to humans but well within the range of a dog's hearing.


title: Hearing range

text: Bats have evolved very sensitive hearing to cope with their nocturnal activity. Their hearing range varies by species; at the lowest it can be 1 kHz for some species and for other species the highest reaches up to 200 kHz. Bats that can detect 200 kHz cannot hear very well below 10 kHz. In any case, the most sensitive range of bat hearing is narrower: about 15 kHz to 90 kHz.


title: Hearing range

text: Bats navigate around objects and locate their prey using echolocation. A bat will produce a very loud, short sound and assess the echo when it bounces back. Bats hunt flying insects; these insects return a faint echo of the bat's call. The type of insect, how big it is and distance can be determined by the quality of the echo and time it takes for the echo to rebound. There are two types of call constant frequency (CF), and frequency modulated (FM) that descend in pitch. Each type reveals different information; CF is used to detect an object, and FM is used to assess its distance. The pulses of sound produced by the bat last only a few thousandths of a second; silences between the calls give time to listen for the information coming back in the form of an echo. Evidence suggests that bats use the change in pitch of sound produced via the Doppler effect to assess their flight speed in relation to objects around them. The information regarding size, shape and texture is built up to form a picture of their surroundings and the location of their prey. Using these factors a bat can successfully track change in movements and therefore hunt down their prey.


title: Hearing range

text: Mice have large ears in comparison to their bodies. They hear higher frequencies than humans; their frequency range is 10 kHz to 70 kHz. They do not hear the lower frequencies that humans can; they communicate using high-frequency noises some of which are inaudible by humans. The distress call of a young mouse can be produced at 40 kHz. The mice use their ability to produce sounds out of predators' frequency ranges to alert other mice of danger without exposing themselves, though notably, cats' hearing range encompasses the mouse's entire vocal range. The squeaks that humans can hear are lower in frequency and are used by the mouse to make longer distance calls, as low-frequency sounds can travel farther than high-frequency sounds.


title: Hearing range

text: Hearing is birds' second most important sense and their ears are funnel-shaped to focus sound. The ears are located slightly behind and below the eyes, and they are covered with soft feathers – the auriculars – for protection. The shape of a bird's head can also affect its hearing, such as owls, whose facial discs help direct sound toward their ears.


title: Hearing range

text: The hearing range of birds is most sensitive between 1 kHz and 4 kHz, but their full range is roughly similar to human hearing, with higher or lower limits depending on the bird species. No kind of bird has been observed to react to ultrasonic sounds, but certain kinds of birds can hear infrasonic sounds. "Birds are especially sensitive to pitch, tone and rhythm changes and use those variations to recognize other individual birds, even in a noisy flock. Birds also use different sounds, songs and calls in different situations, and recognizing the different noises is essential to determine if a call is warning of a predator, advertising a territorial claim or offering to share food."


title: Hearing range

text: "Some birds, most notably oilbirds, also use echolocation, just as bats do. These birds live in caves and use their rapid chirps and clicks to navigate through dark caves where even sensitive vision may not be useful enough."


title: Hearing range

text: Pigeons can hear infrasound. With the average pigeon being able to hear sounds as low as 0.5 Hz, they can detect distant storms, earthquakes and even volcanoes. This also helps them to navigate.


title: Hearing range

text: Greater wax moths (Galleria mellonella) have the highest recorded sound frequency range that has been recorded so far. They can hear frequencies up to 300 kHz. This is likely to help them evade bats.


title: Hearing range

text: Fish have a narrow hearing range compared to most mammals. Goldfish and catfish do possess a Weberian apparatus and have a wider hearing range than the tuna.


title: Hearing range

text: As aquatic environments have very different physical properties than land environments, there are differences in how marine mammals hear compared with land mammals. The differences in auditory systems have led to extensive research on aquatic mammals, specifically on dolphins.


title: Hearing range

text: Researchers customarily divide marine mammals into five hearing groups based on their range of best underwater hearing. (Ketten, 1998): Low-frequency baleen whales like blue whales (7 Hz to 35 kHz); Mid-frequency toothed whales like most dolphins and sperm whales (150 Hz to 160 kHz) ; High-frequency toothed whales like some dolphins and porpoises (275 Hz to 160 kHz); Seals (50 Hz to 86 kHz); Fur seals and sea lions (60 Hz to 39 kHz).


title: Hearing range

text: The auditory system of a land mammal typically works via the transfer of sound waves through the ear canals. Ear canals in seals, sea lions, and walruses are similar to those of land mammals and may function the same way. In whales and dolphins, it is not entirely clear how sound is propagated to the ear, but some studies strongly suggest that sound is channelled to the ear by tissues in the area of the lower jaw. One group of whales, the Odontocetes (toothed whales), use echolocation to determine the position of objects such as prey. The toothed whales are also unusual in that the ears are separated from the skull and placed well apart, which assists them with localizing sounds, an important element for echolocation.


title: Hearing range

text: Studies have found there to be two different types of cochlea in the dolphin population. Type I has been found in the Amazon river dolphin and harbour porpoises. These types of dolphin use extremely high frequency signals for echolocation. Harbour porpoises emit sounds at two bands, one at 2 kHz and one above 110 kHz. The cochlea in these dolphins is specialised to accommodate extreme high frequency sounds and is extremely narrow at the base.


title: Hearing range

text: Type II cochlea are found primarily in offshore and open water species of whales, such as the bottlenose dolphin. The sounds produced by bottlenose dolphins are lower in frequency and range typically between 75 and 150,000 Hz. The higher frequencies in this range are also used for echolocation and the lower frequencies are commonly associated with social interaction as the signals travel much farther distances.


title: Hearing range

text: Marine mammals use vocalisations in many different ways. Dolphins communicate via clicks and whistles, and whales use low-frequency moans or pulse signals. Each signal varies in terms of frequency and different signals are used to communicate different aspects. In dolphins, echolocation is used in order to detect and characterize objects and whistles are used in sociable herds as identification and communication devices.


title: Origin (service)

text: Origin is a digital distribution platform developed by Electronic Arts for purchasing and playing video games. In October 2022, Origin ceased operations for its Windows platform, directing players to EA Play. The Mac and mobile versions remain online.


title: Origin (service)

text: Origin contained social features such as profile management, networking with friends with chat and direct game joining along with an in-game overlay, streaming via Twitch and sharing of game library and community integration with networking sites like Facebook, Xbox Live, PlayStation Network, and Nintendo Network. In 2011, Electronic Arts stated that it wanted Origin to match Valve's Steam service, Origin's primary competitor, by adding cloud game saves, auto-patching, achievements, and cross-platform releases. By 2013, Origin had over 50 million registered users.


title: Origin (service)

text: The Origin store allows users to browse and purchase games from Electronic Arts' catalogs. Instead of receiving a box, disc, or even CD key, purchased software is immediately attached to the user's Origin account and is to be downloaded with the corresponding Origin client.


title: Origin (service)

text: Origin guarantees download availability forever after purchase, and there is no limit to the number of times a game can be downloaded.


title: Origin (service)

text: Users may also add certain EA games to their Origin account by using CD keys from retail copies, and digital copies obtained from other digital distribution services. However, the addition of retail keys to Origin is restricted to games from 2009 onwards and older keys will not work even if the game is available on Origin, unless user contacts customer support.


title: Origin (service)

text: The Origin client is self-updating software that allows users to download games, expansion packs, content booster packs and patches from Electronic Arts. It shows the status of components available. The Origin client is designed to be similar to its competitor, Steam. The Origin In Game overlay client can be disabled while playing games. The client also features chat features such as a Friends List and a group chat options (implemented in version 9.3). Client and download performance has been patched and improved in past updates.


title: Origin (service)

text: EA released a subscription service for accessing and playing their games on PC in 2016 originally called EA Access; via the Origin client, this was called Origin Access. Users can choose between paying a monthly or yearly subscription fee to access a large collection of EA titles (known as "The Vault"). Origin Access subscribers also get a 10% discount on all Origin purchases. Starting in March 2018, Origin Access starting offering titles from Warner Bros. Interactive Entertainment and was looking to add other publishers' titles, including those from indie games.


title: Origin (service)

text: At E3 2018 EA announced a premium tier for Origin Access called Origin Access Premier, that allows to play future EA games early, the games will be full version in contrast to the "First Trials" giving to basic Origin Access members. To streamline branding, EA renamed both EA Access and Origin Access both to EA Play, with the Origin Access Premier named to EA Play Pro.


title: Origin (service)

text: In September 2020, EA announced it plans to retire Origin in favor for a new desktop client that will support the new EA Play and EA Play Pro subscriptions. It is expected all Origin content will carry over to the new EA Desktop client once it is fully released. The new client began its beta test in September 2020. The new client, named "EA app" was released on October 7, 2022, for Windows users with a deployed migration to existing users of Origin.


title: Origin (service)

text: EA Downloader was launched in late 2005. It was replaced by EA Link in November 2006, adding trailers, demos and special content to the content delivery service. In September 2007, it was once again replaced by the combination of EA Store and EA Download Manager. Users purchase from the EA Store website and use the downloadable EADM client to download their games. Games bought via EA Link were downloadable using the EA Download Manager. The store and client was reopened under the Origin name on June 3, 2011.


title: Origin (service)

text: The digital distribution software was first used to deliver the "Battlefield 2: Special Forces" expansion pack, and subsequently most EA titles. The biggest product launch on the software is "Spore Creature Creator".


title: Origin (service)

text: EA acquired the trademark "Origin" when it purchased Origin Systems in 1992. Origin Systems was a major game studio in the 1980s and 1990s, best known for its "Ultima", "Wing Commander", and "Crusader" game franchises.


title: Origin (service)

text: Shortly after the launch of Origin, "Crysis 2" was pulled from Steam and appeared on EA's website with an "only on Origin" claim, though it remained available on other distribution services. EA has since stated that Valve removed "Crysis 2" due to imposed "business terms" and that "this was not an EA decision or the result of any action by EA."


title: Origin (service)

text: Since then, "Crysis 2: Maximum Edition" (a re-release of "Crysis 2" with all the DLCs) has been released on Steam, matching EA's story about pulling "Crysis 2" due to DLC restraints. EA has confirmed that "Battlefield 3" would not be available through Steam. The game is currently available for purchase on other non-Origin services such as GameFly, Green Man Gaming or GamersGate, but the Origin client must be used regardless of where the game was purchased. Starting from the release of "Battlefield 3" in 2011 until November 2019, every first-party game EA published on PC was exclusive to the Origin service. In late 2019, EA began releasing their games on Steam again, starting with "", however, the game still uses the Origin client to launch. EA started to release their existing games on Steam in June 2020.


title: Origin (service)

text: There have been several instances of EA enforcing such bans for what critics argue are comparatively minor infractions, such as making rude comments in EA or BioWare's official forums or in chat.


title: Origin (service)

text: During March 2011, a user named "Arno" was banned for allegedly making the comment "Have you sold your souls to the EA devil?" Arno's account was banned for 72 hours which prevented him from playing any of his Origin games. After reporting on the details of the incident, website Rock, Paper, Shotgun received a statement from EA saying that Arno's account ban was a mistake, and that future violations on the forums would not interfere with Origin users' access to their games.


title: Origin (service)

text: Later during October and November 2011, one user was banned for posting about teabagging dead players. Another user received a 72-hour account suspension for posting a link to his own network troubleshooting guide in the EA forums. EA interpreted this as a "commercial" link, even though the same link had been posted elsewhere in the forums, and EA's own corporate support site and FAQ. One user was permanently banned for submitting a forum post containing the portmanteau "e-peen," which is slang for "electronic penis."


title: Origin (service)

text: EA has been criticized for not encrypting Origin's XMPP chat functionality, which is available in Origin and in Origin powered games. Unencrypted data includes account numbers, session tokens, as well as the message contents itself. With this type of data, user accounts might get compromised.


title: Origin (service)

text: Origin's end-user license agreement (EULA) gives EA permission to collect information about users' computers regardless of its relation to the Origin program itself, including "application usage (including but not limited to successful installation and/or removal), software, software usage and peripheral hardware." Initially, the EULA also contained a passage permitting EA to more explicitly monitor activity as well as to edit or remove material at their discretion. A report by the news magazine Der Spiegel covered the allegations. In response to the controversy, EA issued a statement claiming they "do not have access to information such as pictures, documents or personal data, which have nothing to do with the execution of the Origin program on the system of the player, neither will they be collected by us." EA also added a sentence to the EULA stating that they would not "use spyware or install spyware on users' machines," though users must still consent to allowing EA to collect information about their computers.


title: Origin (service)

text: According to reports in German newspapers, the German version of Origin's EULA violates several German laws, mainly laws protecting consumers and users' privacy. According to Thomas Hoeren, a judge and professor for information, telecommunication and media law at the University of Münster, the German version of the EULA is a direct translation of the original without any modifications and its clauses are "null and void".


title: Dangerously in Love

text: Dangerously in Love is the debut solo studio album by American singer Beyoncé. It was released on June 20, 2003, by Columbia Records and Music World Entertainment. During the recording of Destiny's Child's third studio album "Survivor" (2001), the group announced that each member would produce solo albums. Recording sessions for the album took place from March 2002 to March 2003 at various recording studios, during the group's hiatus.


title: Dangerously in Love

text: As the executive producer of "Dangerously in Love", Beyoncé took a wider role in its production, co-writing a majority of the songs, choosing which ones to produce and sharing ideas on mixing and mastering. Although she remained discreet about her interpretation of the songs, their underlying meanings were attributed by music writers as an allusion to her intimate relationship with rapper Jay-Z. Musically, the album's tracks are a mixture of uptempo songs and ballads, all of which are primarily R&B songs, while also incorporating elements of soul, hip hop and Arabic music.


title: Dangerously in Love

text: Upon release, "Dangerously in Love" received generally positive reviews from music critics, many of whom praised Beyoncé's "artistic leap". The album also received numerous accolades, including five Grammy Awards at the 46th Annual Grammy Awards (2004). An international commercial success, the album debuted atop the US "Billboard" 200 chart, selling 317,000 copies in its first week and earning Beyoncé the highest debut sales week among Destiny's Child members' solo albums.


title: Dangerously in Love

text: Beyoncé promoted "Dangerously in Love" via numerous live performances and two concert tours–Dangerously in Love Tour (2003) and Verizon Ladies First Tour (2004), the latter of which was co-headlined with Alicia Keys and Missy Elliott. The album produced two US "Billboard" Hot 100 number-one singles–"Crazy in Love" and "Baby Boy", as well as two top five singles–"Me, Myself and I" and "Naughty Girl". As of 2011, "Dangerously in Love" has sold over 11 million copies worldwide.


title: Dangerously in Love

text: Beyoncé launched her career as the lead singer in the R&B girl group Destiny's Child in the late 1990s. According to Corey Moss of MTV News, "fans are eager to see" how Beyoncé, after years with the group, performs solo. While recording their third album, "Survivor", in late 2000, Beyoncé announced the group would be put on hiatus in order for the members to produce solo albums in the coming years, which they hoped would boost interest in Destiny's Child. The idea of individual releases emanated from the group's manager and Beyoncé's father, Mathew.


title: Dangerously in Love

text: With different types of music for each member to produce, the albums were not intended to compete on the charts. Destiny's Child's management strategically planned to stagger the release of each group member's album to maximize sales. Michelle Williams was the first to release a debut solo album, "Heart to Yours", in April 2002. Meanwhile, Beyoncé debuted on the big screen, starring in the comedy film "Austin Powers in Goldmember", and recorded her debut single, "Work It Out", which is featured on the soundtrack to the film. Rowland collaborated with American rapper Nelly on the song "Dilemma" as a featured artist; it became a hit that year, leading the label to advance the release date of her debut solo album, "Simply Deep", in late 2002. Beyoncé also starred in "The Fighting Temptations" and recorded another solo single. In August 2002, she collaborated with boyfriend Jay-Z as featured vocalist on the song "'03 Bonnie & Clyde". The single earned Beyoncé credibility and paved the way for the release of "Dangerously in Love".


title: Dangerously in Love

text: Before Beyoncé began recording for "Dangerously in Love", she selected the producers with whom she would collaborate. For two days, she held meetings with prospective producers from the West Coast across the East Coast, and had interviews with them. Beyoncé went to Miami to begin sessions with record producer Scott Storch, her first collaborator, and lived in a hotel in the following months. As she wanted to concentrate on the album, Beyoncé took her time to avoid pressure build-up, significantly different from the hasty productions of Destiny's Child. As she did on "Survivor", Beyoncé took a wider role in the production of "Dangerously in Love", co-writing a majority of the songs, choosing which ones to produce and sharing ideas on the mixing and mastering of tracks. Although Beyoncé did not create beats, she came up with melodies and ideas she shared with the producers. With 43 songs completed—15 of which made it to the album—Beyoncé is credited as a co-writer and a co-producer, as well as the album's executive producer alongside Mathew Knowles.


title: Dangerously in Love

text: Beyoncé felt that recording an album without her group mates was "liberating and therapeutic", coming into the studio and freely expressing her ideas with her collaborators. The dependency she developed with Destiny's Child, however, meant it was harder "to be on [her] own creatively". As she wanted to grow as an artist, Beyoncé contacted other artists with a view to forming a collaborative partnership. When the collective finished writing several songs, she printed copies of each and sent them to prospective guest artists. She talked to them by phone for possible collaboration, eventually gaining their approval. Besides Jay-Z, Beyoncé was able to work with Jamaican artist Sean Paul, American rapper Missy Elliott, among others. In contrast, some artists sent copies of songs to Beyoncé, which were eventually produced. Beyoncé also worked with Elliott and Timbaland on a track titled "Wrapped Around Me", but it ultimately failed to appear on the album.


title: Dangerously in Love

text: "Dangerously in Love" was originally a song of the same title which Beyoncé had written for "Survivor". The song was deemed too sophisticated compared to other songs on "Survivor", and the group decided not to release it as a single from the album. After recording several tracks for "Dangerously in Love", Beyoncé decided to add "Dangerously in Love", after realizing that it fit the overriding theme of the album. Since the album's release date was postponed to capitalize on the success of "Dilemma", Beyoncé had been offered the chance to further enhance the album. Although she was disappointed with the move, Beyoncé realized that "everything happens for a reason", agreeing to return to the recording studio to work with other songwriters. This allowed her to record more songs, including the album's lead single "Crazy in Love". In late 2002, Beyoncé paused working on "Dangerously in Love" for a holiday tour with Destiny's Child. With a few weeks left for recording in March 2003, Beyoncé was still collaborating with other guests on the album, including Sean Paul and P. Diddy.


title: Dangerously in Love

text: The creative output of the sessions for "Dangerously in Love" left several tracks ready for another album pressing. In late 2003, Beyoncé planned to release a follow-up album that would comprise leftover songs from "Dangerously in Love". The move was prompted when "Summertime", a leftover track featuring P. Diddy, was sent to radio stations and received favorable response.


title: Dangerously in Love

text: Beyoncé's father-manager Mathew Knowles said that "Dangerously in Love" showcases her musical roots. While Williams and Rowland were on gospel and alternative pop, respectively, Beyoncé focused on recording R&B songs. Songs in the album are varied: from mid-tempo and club-oriented tracks in the first half, and ballads in the second half. Beyoncé commented: "My album is a good balance of ... ballads and ... mid-tempos with just ridin'-in-your-car feels, to a lot of ... up-tempo club songs, to really sexy songs, to songs that make you feel emotional. It's a nice mixture of different types of tracks." Although the album contains high-energy songs like "Crazy in Love" and "Naughty Girl", the album's focal mode, however, is slow and moody. Beyoncé said she had written many ballads for the album. According to Beyoncé, she wanted to be understood as an artist and showcase her range, and by doing so, she blended various genres and musical influences in the album. The album incorporates R&B, hip hop, soul and reggae influences. The album took hip hop influences from Jay-Z, Outkast, and Lil' Kim; the reggae is from Sean Paul; and courtesy of Storch, the album explores Arabic music. His personal study of that kind of music gave the album a Middle Eastern vibe. Beyoncé and the producers also used a wide array of instrumentations.


title: Dangerously in Love

text: When "'03 Bonnie & Clyde" was released as a single in late 2002, critics and the public had speculated that Beyoncé and Jay-Z were having a mutual affair. Despite widespread rumors, they remained silent about their relationship. According to critics, the title itself of the album sounded "more intriguing" with Beyoncé singing personal songs. Though love is the theme Beyoncé had incorporated in the album, "most the material is vague enough to be about any relationship"; however, there are songs that suggested affirmation of their relationship. In the song "Signs", Beyoncé sings about being in love with a Sagittarius, which coincidentally is Jay-Z's zodiac sign. In response to the persistent rumors about them, Beyoncé stated, "People can come to whatever conclusion they like... That's the beauty of music... I'm a singer, I'll talk about writing songs all you want. But when it comes to certain personal things any normal person wouldn't tell people they don't know, I just feel like I don't have to [talk about it]."


title: Dangerously in Love

text: Beyoncé said that "Dangerously in Love" is lyrically similar to Destiny's Child's albums. But because she only had to write for herself, Beyoncé had the chance to compose personally deeper songs than her previous records with the group. With a theme that is based upon different stages of a romantic relationship, "Dangerously in Love" contains songs that speak of love and honesty. In addition, Beyoncé admitted that there are songs about love-making. The personal content of the album, however, was not generally attributed to Beyoncé's own experiences—although some were based from hers—instead, the theme kept recurring in her mind. Beyoncé later explained: "I wanted to have an album that everyone could relate to and would listen to as long as I'm alive and even after... Love is something that never goes out of style. It's something everybody experiences, and if they are not in love, people usually want to feel that..." While some songs merely focus on the "beauty of love", the album also explores another side of love, with songs that "celebrate breakup" and songs that narrate a woman's desire to have a degree of control in a relationship. The album's hidden track, "Daddy", is a tribute to Beyoncé's father, Mathew Knowles, who fronted Destiny's Child as their manager. The song is an account of Beyoncé wanting her future husband and child to possess qualities similar to her father's. Originally, Beyoncé did not intend to include the track in the album, having thought its lyrics would make her appear immature. However, considering it one of the songs that reflected her life at that transitional moment, she instead relegated "Daddy" as the closing track.


title: Dangerously in Love

text: Beyoncé said that she had trouble convincing executives at Columbia Records to release "Dangerously in Love". She recounted that it was almost not released: "In 2003, I had my first solo album. But when I played it through for my record label, they told me I didn't have one hit on my album. I guess they were kinda right, I had five. "Dangerously in Love", "Naughty Girl", "Me, Myself and I", "Baby Boy" and "Crazy in Love"." Since Kelly Rowland's "Dilemma" was concurrently charting atop the "Billboard" Hot 100, Beyoncé's management released "Work It Out", one of the songs on the soundtrack to "Austin Powers in Goldmember", instead of a single from "Dangerously in Love" to preclude it from possibly competing with "Dilemma".


title: Dangerously in Love

text: "Dangerously in Love" was pushed back from its original October 2002 release date to December, and then to May 2003. Beyoncé recorded a version of 50 Cent's "In Da Club", which served its way to mixtapes before its original release date. The single failed to dominate as a "dancefloor favorite"; Mathew Knowles, however, confirmed that it was just a "buzz cut" and was not included on the album. Nonetheless, it earned enough airplay to chart on the US Hot R&B/Hip-Hop Songs. While Beyoncé was wrapping up the album, several of its songs had leaked online. In efforts to prevent more tracks in the album from being spread illegally, as well as being a victim of bootlegging, Columbia Records, with high commercial expectations from the album, pulled the release of "Dangerously in Love" to June 24, two weeks ahead of the planned July 8 release.


title: Dangerously in Love

text: Buyers who pre-ordered "Dangerously in Love" online received links where they could download a song titled "I Can't Take No More"; the offer lasted until the album's release. On June 14, Beyoncé premiered songs from the album during her first solo concert and the pay-per-view television special titled "Ford Presents Beyoncé Knowles, Friends & Family, Live From Ford's 100th Anniversary Celebration in Dearborn, Michigan". By the night of the album's release, Beyoncé's concert was broadcast in over 20 theaters across the United States. Rowland, Michelle Williams, Tyrese and Beyoncé's younger sister Solange also performed during the show. Beyoncé also promoted the album by performing on television shows such as "Saturday Night Live", "Late Show with David Letterman", "Today", "The Early Show", and "The View".


title: Dangerously in Love

text: Beyoncé further promoted "Dangerously in Love" with her Dangerously in Love Tour in November 2003, performing in the United Kingdom, Ireland and the Netherlands. Her concert at Wembley Arena in London on November 10, was filmed for her live album "Live at Wembley", released on April 26, 2004. Additionally, Beyoncé co-headlined the Verizon Ladies First Tour with Alicia Keys and Missy Elliott across the US from March to April.


title: Dangerously in Love

text: In April 2003, Columbia Records was choosing the lead single from "Dangerously in Love" between two songs. Sent to clubs, the song that would receive better reception would be selected as the lead single. Finally, "Crazy in Love" was released as the lead single on May 14, 2003. It was lauded by critics who described it as "deliriously catchy". The single topped the US "Billboard" Hot 100, based on heavy rotation alone. The same week the song reached number one, "Dangerously in Love" topped the "Billboard" 200 as well. The substantial airplay and later retail sales of "Crazy in Love" facilitated it to dominate the chart, subsequently spending eight straight weeks atop the "Billboard" Hot 100, making it Beyoncé's first number-one single in her solo career. According to Nielsen SoundScan, "Crazy in Love" was the most downloaded song in the United States for four consecutive weeks in July 2003. It also became a success internationally, reaching the top of the charts in Croatia, Ireland and the United Kingdom.


title: Dangerously in Love

text: "Baby Boy" was released as the second single on August 3, 2003. It was well received by critics, who declared it a "high-profile collaboration" that "bridges the gap between the genres of R&B and dancehall." It ultimately topped the "Billboard" Hot 100 eight weeks after its debut, and stayed there for nine consecutive weeks, surpassing the eight-week run atop the chart of "Crazy in Love". It peaked at number two on the UK Singles Chart.


title: Dangerously in Love

text: "Me, Myself and I" was released as the album's third single on October 19, 2003. It received generally positive critical response, being considered a typical sounding R&B ballad with a familiar theme, in which Beyoncé sings with passion. It peaked at number four on the US "Billboard" Hot 100, and reached the top ten in Canada.


title: Dangerously in Love

text: "Naughty Girl" was released as the fourth and final single from the album on March 14, 2004. The song was lauded by critics, who cited its sensual vibe and writing: "Beyoncé borrowed a portion of Donna Summer's naughty classic "Love to Love You Baby" to create this celebration of sensual naughtiness." It peaked at number three on the US "Billboard" Hot 100, continuing Beyoncé's string of top-five singles on the chart. Internationally, it became a top ten hit in Australia, Canada, the Netherlands, New Zealand and the United Kingdom. Despite "Me, Myself and I" and "Naughty Girl" not peaking atop the "Billboard" Hot 100, they still achieved high commercial success and helped "Dangerously in Love" reach a multi-platinum status.


title: Dangerously in Love

text: "Dangerously in Love" received generally positive reviews from music critics. At Metacritic, which assigns a normalized rating out of 100 to reviews from mainstream critics, the album received an average score of 63, based on 17 reviews. Anthony DeCurtis of "Rolling Stone" viewed that it presents Beyoncé in two styles, one "far more flattering" than the other, and found the ballad-oriented songs on the album least flattering, commenting that Beyoncé has "plenty of time" to develop the style maturely that would "[make] sense for her". "Entertainment Weekly"s Neil Drumming commented that the album validates Beyoncé's "taste in innovation". He also viewed that Beyoncé's collaboration with various record producers explores new directions in contemporary music, doing more reinventing than revisiting. Like DeCurtis' review, however, Drumming pointed out that "most of the disc's missteps" are in its latter part. "Slant Magazine"s Sal Cinquemani wrote that "[Beyoncé] is allowed more room to experiment vocally as a solo artist, exploring softer registers and lathering on the coquettish persona that was only hinted at on Destiny's Child tracks like 'Bootylicious.'". Steve Jones of "USA Today" stated, "Beyoncé succeeds by showing greater depth as a songwriter and broader range as a singer". "Blender"s Ben Ratliff complimented Beyoncé's performance and stated, "She's playing the cool-hunter but covering the bases with seraphic arrangements of multiple voices. Her reach is remarkable". Mark Anthony Neal of "PopMatters" called it an "artistic leap" and wrote that it "finds Ms. B in the midst of a fully flowering womanhood and doing the best singing of her career".


title: Dangerously in Love

text: In a mixed review, "Vibe" magazine's Jason King said that the album occasionally "sounds desperate to reach every demographic". Kelefa Sanneh, writing in "The New York Times", felt that it missed the harmonies Beyoncé had in Destiny's Child records and that she is more effective "when she's got a posse behind her". Rob Fitzpatrick of "NME" called it "a cruel glimpse of a talent that occasionally blazes but is frustratingly inconsistent". "Uncut" called its ballads "self-pitying/self-mythologising", while "Q" stated, "She has good songs, but no great songs". "Los Angeles Times" writer Natalie Nichols expressed that it "demonstrates vocal finesse [...] But, especially on the ballads, [Beyoncé] often drags things out with diva acrobatics". "The Guardian"s Adam Sweeting wrote that "the desperate urge to cover every musical base from dancefloor to soul-ballad means that there is barely a track here with any distinctive identity or even a tune". In his consumer guide for "The Village Voice", Robert Christgau cited "Yes" and "Baby Boy" as the album's highlights and quipped that the artist was ""Dangerously in Love" ... with her daddy, the bonus cut reveals—as if we didn't know." He gave the album a one-star honorable mention, indicating "a worthy effort consumers attuned to its overriding aesthetic or individual vision may well like." In a retrospective review, AllMusic editor Stephen Thomas Erlewine commented that "the first half is good enough to make "Dangerously in Love" one of the best mainstream urban R&B records released in 2003, and makes a strong case that Beyoncé might be better off fulfilling this destiny instead of reuniting with Destiny".


title: Dangerously in Love

text: "Dangerously in Love" debuted at number one on the US "Billboard" 200 chart, with first-week sales of 317,000 copies according to Nielsen SoundScan. In its second week the album slid to number two with 183,000 sold, behind Ashanti's "Chapter II". Although the album's first-week sales failed to match that of "Survivor", which sold 663,000 copies in its debut in 2001, Beyoncé earned the highest among Destiny's Child members' solo albums by best weeks: Rowland sold 77,000 copies for "Simply Deep" while Williams earned 17,000 copies for "Heart to Yours" in its strongest week. The album has been certified sextuple platinum by the Recording Industry Association of America (RIAA). "Dangerously in Love" remains Beyoncé's best-selling album to date, with cumulative sales of five million copies in the United States as of June 2016.


title: Dangerously in Love

text: Internationally, "Dangerously in Love" had similar commercial reception. On July 12, 2003, Beyoncé became the first female artist (and the fifth artist ever) to top both the singles—with "Crazy in Love"— and albums chart simultaneously in the United States and the United Kingdom, following the Beatles, Simon & Garfunkel, Rod Stewart and Men at Work. As of June 2011, the album had sold over 1,150,000 copies in the United Kingdom, and the British Phonographic Industry (BPI) has since certified the album quadruple platinum for sales of over 1.2 million units. "Dangerously in Love" was the fifteenth best-selling album of 2003 in the United Kingdom, and is Beyoncé's second best-selling album in the country, behind "I Am... Sasha Fierce". In Australia, it reached number two; the album has been certified triple platinum by the Australian Recording Industry Association (ARIA) for sales of 210,000 copies. In 2003, "Dangerously in Love" was the fifty-first best-selling album in Australia, and the seventy-fourth the following year. As of 2011, the album has sold over 11 million copies worldwide.


title: Dangerously in Love

text: With the release of "Dangerously in Love" and the combined commercial success of its singles, Beyoncé had established herself as a viable solo artist. Rebecca Louie of the "New York Daily News" wrote that the success of "Dangerously in Love" brought Beyoncé into a "sultry solo star" who "blossomed from a girly group", referring to Destiny's Child. The album also facilitated her to become one of the most marketable artists in the industry. She appeared on the cover of numerous magazines, guested television shows for promotions, and signed lucrative commercial deals. In 2003, she signed a contract with the conglomerate beverage manufacturer PepsiCo, and appeared on several television commercials for its products within the next ten years.


title: Dangerously in Love

text: The success of "Dangerously in Love" also incited the public to infer that it signalled the disbandment of Destiny's Child, as pop singer Justin Timberlake "could not go back to 'N Sync after tasting solo success". However, Beyoncé said that their side projects were only "a brief diversion in the juggernaut that has become Destiny's Child". As time did not permit, Beyoncé's musical aspirations were put on hiatus for her to concentrate on her Super Bowl XXXVIII performance, wherein she was slated to sing the US national anthem, and the recording of Destiny's Child's fourth studio album "Destiny Fulfilled" (2004). The group ultimately disbanded in 2006.


title: Dangerously in Love

text: After the group's formal disbandment, Beyoncé recorded and released her second studio album "B'Day" on her 25th birthday on September 4, 2006. The album became her second number-one in the United States, and its debut-week sales exceeded that of "Dangerously in Love", the former having sold 541,000 units. Despite the album's first two singles' average commercial performance—neither of which reached the peak of the "Billboard" Hot 100—its "handsome debut" was noted by Keith Caulfield of "Billboard" as having been generated "by goodwill earned from the performance of [Beyoncé's] smash first album "Dangerously in Love"."


title: Acute lymphoblastic leukemia

text: Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated.


title: Acute lymphoblastic leukemia

text: In most cases, the cause is unknown. Genetic risk factors may include Down syndrome, Li-Fraumeni syndrome, or neurofibromatosis type 1. Environmental risk factors may include significant radiation exposure or prior chemotherapy. Evidence regarding electromagnetic fields or pesticides is unclear. Some hypothesize that an abnormal immune response to a common infection may be a trigger. The underlying mechanism involves multiple genetic mutations that results in rapid cell division. The excessive immature lymphocytes in the bone marrow interfere with the production of new red blood cells, white blood cells, and platelets. Diagnosis is typically based on blood tests and bone marrow examination.


title: Acute lymphoblastic leukemia

text: ALL is typically treated initially with chemotherapy aimed at bringing about remission. This is then followed by further chemotherapy typically over a number of years. Treatment usually also includes intrathecal chemotherapy since systemic chemotherapy can have limited penetration into the central nervous system and the central nervous system is a common site for relapse of acute lymphoblastic leukemia.


title: Acute lymphoblastic leukemia

text: Treatment can also include radiation therapy if spread to the brain has occurred. Stem cell transplantation may be used if the disease recurs following standard treatment. Additional treatments such as Chimeric antigen receptor T cell immunotherapy are being used and further studied.


title: Acute lymphoblastic leukemia

text: ALL affected about 876,000 people globally in 2015 and resulted in about 111,000 deaths. It occurs most commonly in children, particularly those between the ages of two and five. In the United States it is the most common cause of cancer and death from cancer among children. ALL is notable for being the first disseminated cancer to be cured. Survival for children increased from under 10% in the 1960s to 90% in 2015. Survival rates remain lower for babies (50%) and adults (35%).


title: Acute lymphoblastic leukemia

text: Initial symptoms can be nonspecific, particularly in children. Over 50% of children with leukemia had one or more of five features: a liver one can feel (64%), a spleen one can feel (61%), pale complexion (54%), fever (53%), and bruising (52%). Additionally, recurrent infections, feeling tired, arm or leg pain, and enlarged lymph nodes can be prominent features. The B symptoms, such as fever, night sweats, and weight loss, are often present as well.


title: Acute lymphoblastic leukemia

text: Central nervous system (CNS) symptoms such as cranial neuropathies due to meningeal infiltration are identified in less than 10% of adults and less than 5% of children, particularly mature B-cell ALL (Burkitt leukemia) at presentation.


title: Acute lymphoblastic leukemia

text: The cancerous cell in ALL is the lymphoblast. Normal lymphoblasts develop into mature, infection-fighting B-cells or T-cells, also called lymphocytes. Signals in the body control the number of lymphocytes so neither too few nor too many are made. In ALL, both the normal development of some lymphocytes and the control over the number of lymphoid cells become defective.


title: Acute lymphoblastic leukemia

text: ALL emerges when a single lymphoblast gains many mutations to genes that affect blood cell development and proliferation. In childhood ALL, this process begins at conception with the inheritance of some of these genes. These genes, in turn, increase the risk that more mutations will occur in developing lymphoid cells. Certain genetic syndromes, like Down Syndrome, have the same effect. Environmental risk factors are also needed to help create enough genetic mutations to cause disease. Evidence for the role of the environment is seen in childhood ALL among twins, where only 10–15% of both genetically identical twins get ALL. Since they have the same genes, different environmental exposures explain why one twin gets ALL and the other does not.


title: Acute lymphoblastic leukemia

text: Infant ALL is a rare variant that occurs in babies less than one-year-old. "KMT2A" (formerly "MLL") gene rearrangements are most common and occur in the embryo or fetus before birth. These rearrangements result in increased expression of blood cell development genes by promoting gene transcription and through epigenetic changes. In contrast to childhood ALL, environmental factors are not thought to play a significant role. Aside from the "KMT2A" rearrangement, only one extra mutation is typically found. Environmental exposures are not needed to help create more mutations.


title: Acute lymphoblastic leukemia

text: Common inherited risk factors include mutations in "ARID5B", "CDKN2A/2B", "CEBPE", "IKZF1", "GATA3", "PIP4K2A" and, more rarely, "TP53". These genes play important roles in cellular development, proliferation, and differentiation. Individually, most of these mutations are low risk for ALL. Significant risk of disease occurs when a person inherits several of these mutations together.


title: Acute lymphoblastic leukemia

text: The uneven distribution of genetic risk factors may help explain differences in disease rates among ethnic groups. For instance, the "ARID5B" mutation is less common in ethnic African populations.


title: Acute lymphoblastic leukemia

text: Several genetic syndrome also carry increased risk of ALL. These include: Down syndrome, Fanconi anemia, Bloom syndrome, X-linked agammaglobulinemia, severe combined immunodeficiency, Shwachman-Diamond syndrome, Kostmann syndrome, neurofibromatosis type 1, ataxia-telangiectasia, paroxysmal nocturnal hemoglobinuria, and Li-Fraumeni syndrome. Fewer than 5% of cases are associated with a known genetic syndrome.


title: Acute lymphoblastic leukemia

text: Rare mutations in "ETV6" and "PAX5" are associated with a familial form of ALL with autosomal dominant patterns of inheritance.


title: Acute lymphoblastic leukemia

text: The environmental exposures that contribute to emergence of ALL is contentious and a subject of ongoing debate.


title: Acute lymphoblastic leukemia

text: High levels of radiation exposure from nuclear fallout is a known risk factor for developing leukemia. Evidence whether lesser radiation, as from x-ray imaging during pregnancy, increases risk of disease remains inconclusive. Studies that have identified an association between x-ray imaging during pregnancy and ALL found only a slightly increased risk. Exposure to strong electromagnetic radiation from power lines has also been associated with a slightly increased risk of ALL. This result is questioned as no causal mechanism linking electromagnetic radiation with cancer is known.


title: Acute lymphoblastic leukemia

text: High birth weight (greater than 4000g or 8.8lbs) is also associated with a small increased risk. The mechanism connecting high birth weight to ALL is also not known.


title: Acute lymphoblastic leukemia

text: Evidence suggests that secondary leukemia can develop in individuals treated with certain types of chemotherapy, such as epipodophyllotoxins and cyclophosphamide.


title: Acute lymphoblastic leukemia

text: There is some evidence that a common infection, such as influenza, may indirectly promote the emergence of ALL. The delayed-infection hypothesis states that ALL results from an abnormal immune response to infection in a person with genetic risk factors. Delayed development of the immune system due to limited disease exposure may result in excessive production of lymphocytes and increased mutation rate during an illness. Several studies have identified lower rates of ALL among children with greater exposure to illness early in life. Very young children who attend daycare have lower rates of ALL. Evidence from many other studies looking at disease exposure and ALL is inconclusive. Some researchers have linked the hygiene hypothesis.


title: Acute lymphoblastic leukemia

text: Several characteristic genetic changes lead to the creation of a leukemic lymphoblast. These changes include chromosomal translocations, intrachromosomal rearrangements, changes in the number of chromosomes in leukemic cells, and additional mutations in individual genes. Chromosomal translocations involve moving a large region of DNA from one chromosome to another. This move can result in placing a gene from one chromosome that promotes cell division to a more actively transcribed area on another chromosome. The result is a cell that divides more often. An example of this includes the translocation of "C-MYC", a gene that encodes a transcription factor that leads to increased cell division, next to the immunoglobulin heavy- or light-chain gene enhancers, leading to increased "C-MYC" expression and increased cell division. Other large changes in chromosomal structure can result in the placement of two genes directly next to each other. The result is the combination of two usually separate proteins into a new fusion protein. This protein can have a new function that promotes the development of cancer. Examples of this include the "ETV6"–"RUNX1" fusion gene that combines two factors that promote blood cell development and the "BCR"-"ABL1" fusion gene of the Philadelphia chromosome. "BCR"–"ABL1" encodes an always-activated tyrosine kinase that causes frequent cell division. These mutations produce a cell that divides more often, even in the absence of growth factors.


title: Acute lymphoblastic leukemia

text: Other genetic changes in B-cell ALL include changes to the number of chromosomes within the leukemic cells. Gaining at least five additional chromosomes, called high hyperdiploidy, occurs more commonly. Less often, chromosomes are lost, called hypodiploidy, which is associated with a poorer prognosis. Additional common genetic changes in B-cell ALL involve non-inherited mutations to "PAX5" and "IKZF1". In T-cell ALL, "LYL1", "TAL1", "TLX1", and "TLX3" rearrangements can occur.


title: Acute lymphoblastic leukemia

text: ALL results when enough of these genetic changes are present in a single lymphoblast. In childhood ALL, for example, one fusion gene translocation is often found along with six to eight other ALL-related genetic changes. The initial leukemic lymphoblast copies itself into an excessive number of new lymphoblasts, none of which can develop into functioning lymphocytes. These lymphoblasts build up in the bone marrow and may spread to other sites in the body, such as lymph nodes, the mediastinum, the spleen, the testicles, and the brain, leading to the common symptoms of the disease.


title: Acute lymphoblastic leukemia

text: Diagnosing ALL begins with a thorough medical history, physical examination, complete blood count, and blood smears. While many symptoms of ALL can be found in common illnesses, persistent or unexplained symptoms raise suspicion of cancer. Because many features on the medical history and exam are not specific to ALL, further testing is often needed. A large number of white blood cells and lymphoblasts in the circulating blood can be suspicious for ALL because they indicate a rapid production of lymphoid cells in the marrow. The higher these numbers typically point to a worse prognosis. While white blood cell counts at initial presentation can vary significantly, circulating lymphoblast cells are seen on peripheral blood smears in the majority of cases.


title: Acute lymphoblastic leukemia

text: A bone marrow biopsy provides conclusive proof of ALL, typically with >20% of all cells being leukemic lymphoblasts. A lumbar puncture (also known as a spinal tap) can determine whether the spinal column and brain have been invaded. Brain and spinal column involvement can be diagnosed either through confirmation of leukemic cells in the lumbar puncture or through clinical signs of CNS leukemia as described above. Laboratory tests that might show abnormalities include blood count, kidney function, electrolyte, and liver enzyme tests.


title: Acute lymphoblastic leukemia

text: Pathological examination, cytogenetics (in particular the presence of Philadelphia chromosome), and immunophenotyping establish whether the leukemic cells are myeloblastic (neutrophils, eosinophils, or basophils) or lymphoblastic (B lymphocytes or T lymphocytes). Cytogenetic testing on the marrow samples can help classify disease and predict how aggressive the disease course will be. Different mutations have been associated with shorter or longer survival. Immunohistochemical testing may reveal TdT or CALLA antigens on the surface of leukemic cells. TdT is a protein expressed early in the development of pre-T and pre-B cells, whereas CALLA is an antigen found in 80% of ALL cases and also in the "blast crisis" of CML.


title: Acute lymphoblastic leukemia

text: Medical imaging (such as ultrasound or CT scanning) can find invasion of other organs commonly the lung, liver, spleen, lymph nodes, brain, kidneys, and reproductive organs.


title: Acute lymphoblastic leukemia

text: In addition to cell morphology and cytogenetics, immunophenotyping, a laboratory technique used to identify proteins that are expressed on their cell surface, is a key component in the diagnosis of ALL. The preferred method of immunophenotyping is through flow cytometry. In the malignant lymphoblasts of ALL, expression of terminal deoxynucleotidyl transferase (TdT) on the cell surface can help differentiate malignant lymphocyte cells from reactive lymphocytes, white blood cells that are reacting normally to an infection in the body. On the other hand, myeloperoxidase (MPO), a marker for the myeloid lineage, is typically not expressed. Because precursor B cell and precursor T cells look the same, immunophenotyping can help differentiate the subtype of ALL and the level of maturity of the malignant white blood cells. The subtypes of ALL as determined by immunophenotype and according to the stages of maturation.


title: Acute lymphoblastic leukemia

text: An extensive panel of monoclonal antibodies to cell surface markers, particularly CD or cluster of differentiation markers, are used to classify cells by lineage. Below are immunological markers associated with B cell and T cell ALL.


title: Acute lymphoblastic leukemia

text: Cytogenetic analysis has shown different proportions and frequencies of genetic abnormalities in cases of ALL from different age groups. This information is particularly valuable for classification and can in part explain the different prognoses of these groups. In regards to genetic analysis, cases can be stratified according to ploidy, a number of sets of chromosomes in the cell, and specific genetic abnormalities, such as translocations. Hyperdiploid cells are defined as cells with more than 50 chromosomes, while hypodiploid are defined as cells with less than 44 chromosomes. Hyperdiploid cases tend to carry a good prognosis while hypodiploid cases do not. For example, the most common specific abnormality in childhood B-ALL is the t(12;21) "ETV6"–"RUNX1" translocation, in which the "RUNX1" gene, encoding a protein involved in transcriptional control of hemopoiesis, has been translocated and repressed by the "ETV6"–"RUNX1" fusion protein.


title: Acute lymphoblastic leukemia

text: Below is a table with the frequencies of some cytogenetic translocations and molecular genetic abnormalities in ALL.


title: Acute lymphoblastic leukemia

text: Historically, prior to 2008, ALL was classified morphologically using the French-American-British (FAB) system that heavily relied on morphological assessment. The FAB system takes into account information on size, cytoplasm, nucleoli, basophilia (color of cytoplasm), and vacuolation (bubble-like properties).


title: Acute lymphoblastic leukemia

text: While some clinicians still use the FAB scheme to describe tumor cell appearance, much of this classification has been abandoned because of its limited impact on treatment choice and prognostic value.


title: Acute lymphoblastic leukemia

text: In 2008, the World Health Organization classification of acute lymphoblastic leukemia was developed in an attempt to create a classification system that was more clinically relevant and could produce meaningful prognostic and treatment decisions. This system recognized differences in genetic, immunophenotype, molecular, and morphological features found through cytogenetic and molecular diagnostics tests. This subtyping helps determine the prognosis and the most appropriate treatment for each specific case of ALL.


title: Acute lymphoblastic leukemia

text: The aim of treatment is to induce a lasting remission, defined as the absence of detectable cancer cells in the body (usually less than 5% blast cells in the bone marrow).


title: Acute lymphoblastic leukemia

text: Over the past several decades, there have been strides to increase the efficacy of treatment regimens, resulting in increased survival rates. Possible treatments for acute leukemia include chemotherapy, steroids, radiation therapy, intensive combined treatments (including bone marrow or stem cell transplants), targeted therapy, and/or growth factors.


title: Acute lymphoblastic leukemia

text: Chemotherapy is the initial treatment of choice, and most people with ALL receive a combination of medications. There are no surgical options because of the body-wide distribution of the malignant cells. In general, cytotoxic chemotherapy for ALL combines multiple antileukemic drugs tailored to each person. Chemotherapy for ALL consists of three phases: remission induction, intensification, and maintenance therapy.


title: Acute lymphoblastic leukemia

text: Adult chemotherapy regimens mimic those of childhood ALL; however, are linked with a higher risk of disease relapse with chemotherapy alone. It should be known that 2 subtypes of ALL (B-cell ALL and T-cell ALL) require special considerations when it comes to selecting an appropriate treatment regimen in adults with ALL. B-cell ALL is often associated with cytogenetic abnormalities (specifically, t(8;14), t (2;8), and t(8;22)), which require aggressive therapy consisting of brief, high-intensity regimens. T-cell ALL responds to cyclophosphamide-containing agents the most.


title: Acute lymphoblastic leukemia

text: Radiation therapy (or radiotherapy) is used on painful bony areas, in high disease burdens, or as part of the preparations for a bone marrow transplant (total body irradiation). In the past, physicians commonly utilized radiation in the form of whole-brain radiation for central nervous system prophylaxis, to prevent the occurrence and/or recurrence of leukemia in the brain. Recent studies showed that CNS chemotherapy provided results as favorable but with fewer developmental side effects. As a result, the use of whole-brain radiation has been more limited. Most specialists in adult leukemia have abandoned the use of radiation therapy for CNS prophylaxis, instead using intrathecal chemotherapy.


title: Acute lymphoblastic leukemia

text: Selection of biological targets on the basis of their combinatorial effects on the leukemic lymphoblasts can lead to clinical trials for improvement in the effects of ALL treatment. Tyrosine-kinase inhibitors (TKIs), such as imatinib, are often incorporated into the treatment plan for people with "Bcr-Abl1+ (Ph+)" ALL. However, this subtype of ALL is frequently resistant to the combination of chemotherapy and TKIs and allogeneic stem cell transplantation is often recommended upon relapse.


title: Acute lymphoblastic leukemia

text: Chimeric antigen receptors (CARs) have been developed as a promising immunotherapy for ALL. This technology uses a single chain variable fragment (scFv) designed to recognize the cell surface marker CD19 as a method of treating ALL.


title: Acute lymphoblastic leukemia

text: CD19 is a molecule found on all B-cells and can be used as a means of distinguishing the potentially malignant B-cell population. In this therapy, mice are immunized with the CD19 antigen and produce anti-CD19 antibodies. Hybridomas developed from mouse spleen cells fused to a myeloma cell line can be developed as a source for the cDNA encoding the CD19 specific antibody. The cDNA is sequenced and the sequence encoding the variable heavy and variable light chains of these antibodies are cloned together using a small peptide linker. This resulting sequence encodes the scFv. This can be cloned into a transgene, encoding what will become the endodomain of the CAR. Varying arrangements of subunits serve as the endodomain, but they generally consist of the hinge region that attaches to the scFv, a transmembrane region, the intracellular region of a costimulatory molecule such as CD28, and the intracellular domain of CD3-zeta containing ITAM repeats. Other sequences frequently included are: 4-1bb and OX40. The final transgene sequence, containing the scFv and endodomain sequences is then inserted into immune effector cells that are obtained from the person and expanded "in vitro". In trials these have been a type of T-cell capable of cytotoxicity.


title: Acute lymphoblastic leukemia

text: Inserting the DNA into the effector cell can be accomplished by several methods. Most commonly, this is done using a lentivirus that encodes the transgene. Pseudotyped, self-inactivating lentiviruses are an effective method for the stable insertion of a desired transgene into the target cell. Other methods include electroporation and transfection, but these are limited in their efficacy as transgene expression diminishes over time.


title: Acute lymphoblastic leukemia

text: The gene-modified effector cells are then transplanted back into the person. Typically this process is done in conjunction with a conditioning regimen such as cyclophosphamide, which has been shown to potentiate the effects of infused T-cells. This effect has been attributed to making an immunologic space within which the cells populate. The process as a whole result in an effector cell, typically a T-cell, that can recognize a tumor cell antigen in a manner that is independent of the major histocompatibility complex and which can initiate a cytotoxic response.


title: Acute lymphoblastic leukemia

text: In 2017, tisagenlecleucel was approved by the FDA as a CAR-T therapy for people with acute B-cell lymphoblastic leukaemia who did not respond adequately to other treatments or have relapsed. In a 22-day process, the "drug" is customized for each person. T cells purified from each person are modified by a virus that inserts genes that encode a chimaeric antigen receptor into their DNA, one that recognizes leukemia cells.


title: Acute lymphoblastic leukemia

text: Typically, people who experience a relapse in their ALL after initial treatment have a poorer prognosis than those who remain in complete remission after induction therapy. It is unlikely that recurrent leukemia will respond favorably to the standard chemotherapy regimen that was initially implemented, and instead, these people should be trialed on reinduction chemotherapy followed by allogeneic bone marrow transplantation. These people in relapse may also receive blinatumomab, as it has shown to increase remission rates and overall survival rates, without increased toxic effects.


title: Acute lymphoblastic leukemia

text: Low dose palliative radiation may also help reduce the burden of tumor inside or outside the central nervous system and alleviate some symptoms.


title: Acute lymphoblastic leukemia

text: Recently, there has also been evidence and approval of use for dasatinib, a tyrosine kinase inhibitor. It has shown efficacy in cases of people with Ph1-positive and imatinib-resistant ALL, but more research needs to be done on long-term survival and time to relapse.


title: Acute lymphoblastic leukemia

text: Chemotherapies or stem cell transplantations may require a platelet transfusion to prevent bleeding. Moreover, patients undergoing a stem cell transplantation can develop a graft-versus-host disease (GvHD). It was evaluated whether mesenchymal stromal cells can be used to prevent a GvHD. The evidence is very uncertain about the therapeutic effect of mesenchymal stromal cells to treat graft-versus-host diseases after a stem cell transplantation on the all-cause mortality and complete disappear of chronic acute graft-versus-host diseases. Mesenchymal stromal cells may results in little to no difference in the all-cause mortality, relapse of malignant disease and incidence of acute and chronic graft-versus-host diseases if they are used for prophylactic reason.


title: Acute lymphoblastic leukemia

text: Adding physical exercises to the standard treatment for adult patients with haematological malignancies like ALL may result in little to no difference in mortality, the quality of life, and physical functioning. These exercises may result in a slight reduction in depression. Furthermore, aerobic physical exercises probably reduce fatigue. The evidence is very uncertain about the effect on anxiety and serious adverse events.


title: Acute lymphoblastic leukemia

text: Brexucabtagene autoleucel (Tecartus) was approved for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia in October 2021.


title: Acute lymphoblastic leukemia

text: Each dose of brexucabtagene autoleucel is a customized treatment created using the recipient's own immune system to help fight the lymphoma. The recipient's T cells, a type of white blood cell, are collected and genetically modified to include a new gene that facilitates the targeting and killing of the lymphoma cells. These modified T cells are then infused back into the recipient.


title: Acute lymphoblastic leukemia

text: Prior to the development of chemotherapy regimens and hematopoietic stem cell transplant, children were surviving a median length of 3 months, largely due to either infection or bleeding. Since the advent of chemotherapy, the prognosis for childhood leukemia has improved greatly and children with ALL are estimated to have a 95% probability of achieving a successful remission after 4 weeks of initiating treatment. People in pediatric care with ALL in developed countries have a greater than 80% five-year survival rate. It is estimated that 60–80% of adults undergoing induction chemotherapy achieve complete remission after 4 weeks, and those over the age of 70 have a cure rate of 5%.


title: Acute lymphoblastic leukemia

text: Cytogenetics, the study of characteristic large changes in the chromosomes of cancer cells, is an important predictor of outcome. Some cytogenetic subtypes have a worse prognosis than others. These include:


title: Acute lymphoblastic leukemia

text: Unclassified ALL is considered to have an intermediate prognosis risk, somewhere in-between the good and poor risk categories.


title: Acute lymphoblastic leukemia

text: ALL affected about 876,000 people and resulted in 111,000 deaths globally in 2015. It occurs in both children and adults with highest rates seen between the ages three and seven years. Around 75% of cases occur before the age of 6 with a secondary rise after the age of 40. It is estimated to affect 1 in 1500 children.


title: Acute lymphoblastic leukemia

text: Accounting for the broad age profiles of those affected, ALL newly occurs in about 1.7 per 100,000 people per year. ALL represents approximately 20% of adults and 80% of childhood leukemias, making it the most common childhood cancer. Although 80 to 90% of children will have a long term complete response with treatment, it remains the leading cause of cancer-related deaths among children. 85% of cases are of B-cell lineage and have an equal number of cases in both males and females. The remaining 15% of T-cell lineage have a male predominance.


title: Acute lymphoblastic leukemia

text: Globally, ALL typically occurs more often in Caucasians, Hispanics, and Latin Americans than in Africans. In the US, ALL is more common in children from Caucasian (36 cases/million) and Hispanic (41 cases/million) descent when compared to those from African (15 cases/million) descent.


title: Acute lymphoblastic leukemia

text: Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women. The management of leukemia in a pregnant woman depends primarily on the type of leukemia. Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester.


title: Gracy Singh

text: Gracy Singh (born 20 July 1980) is an Indian actress who primarily works in Hindi films. She is best known for her role in the films "Lagaan" and "Munna Bhai M.B.B.S." "Singh" is also a trained Bharatnatyam and Odissi dancer.


title: Gracy Singh

text: Born in Delhi, India, Singh began her career touring with the dance group "The Planets". Her first acting role was in the 1997 television soap, "Amanat". In 1999 she was seen in Bengali Film "Sundori Bou. She" then went on to star opposite Aamir Khan in Ashutosh Gowariker's epic sports-drama "Lagaan", where she played a village belle. She was nominated in this role for the Filmfare Award for Best Female Debut, and won the Screen Award for Most Promising Newcomer – Female.


title: Gracy Singh

text: Post "Lagaan", Singh appeared in a few successful films in Hindi and Telugu including "Munna Bhai M.B.B.S." and "Santosham". She has also starred in Punjabi films such as "Lakh Pardesi Hoye" and a Malayalam film "Loudspeaker" directed by Jayaraj.


title: Stephanie Beacham

text: Stephanie Beacham (born 28 February 1947) is an English television, film, radio and theatre actress. Although she has a wide number of credits to her name, Beacham is best known for for playing Sable Colby in the ABC soap operas "The Colbys" (1985–1987) and "Dynasty" (1985, 1988–1989) and Dr. Kristin Westphalen in Steven Spielberg's NBC science fiction series "seaQuest DSV" (1993–1994).