Fossil record.

The earliest sepia-like fossils of cuttlefish are from the Cretaceous period. Whether the earlier "Trachyteuthis" is assigned to this class, or to the Octopodiformes, remains unclear.

Range and habitat.

The family Sepiidae, which contains all cuttlefish, inhabits tropical and temperate ocean waters. They are mostly shallow-water animals, although they are known to go to depths of about. They have an unusual biogeographic pattern: they are present along the coasts of East and South Asia, Western Europe, and the Mediterranean, as well as all coasts of Africa and Australia, but are totally absent from the Americas. By the time the family evolved, ostensibly in the Old World, the North Atlantic possibly had become too cold and deep for these warm-water species to cross. The common cuttlefish ("Sepia officinalis"), is found in the Mediterranean, North and Baltic seas, although populations may occur as far south as South Africa. They are found in sublittoral depths, between the low tide line and the edge of the continental shelf, to about. The cuttlefish is listed under the Red List category of "least concern" by the IUCN Red List of Threatened Species. This means that while some over-exploitation of the marine animal has occurred in some regions due to large-scale commercial fishing, their wide geographic range prevents them from being too threatened. Ocean acidification, however, caused largely by higher levels of carbon dioxide emitted into the atmosphere, is cited as a potential threat.

Anatomy and physiology.

Visual system.

Cuttlefish, like other cephalopods, have sophisticated eyes. The organogenesis and the final structure of the cephalopod eye fundamentally differ from those of vertebrates such as humans. Superficial similarities between cephalopod and vertebrate eyes are thought to be examples of convergent evolution. The cuttlefish pupil is a smoothly curving W-shape. Although cuttlefish cannot see color, they can perceive the polarization of light, which enhances their perception of contrast. They have two spots of concentrated sensor cells on their retinas (known as foveae), one to look more forward, and one to look more backward. The eye changes focus by shifting the position of the entire lens with respect to the retina, instead of reshaping the lens as in mammals. Unlike the vertebrate eye, no blind spot exists, because the optic nerve is positioned behind the retina. They are capable of using stereopsis, enabling them to discern depth/distance because their brain calculates the input from both eyes.  The cuttlefish's eyes are thought to be fully developed before birth, and they start observing their surroundings while still in the egg. In consequence, they may prefer to hunt the prey they saw before hatching.

Circulatory system.

The blood of a cuttlefish is an unusual shade of green-blue, because it uses the copper-containing protein haemocyanin to carry oxygen instead of the red, iron-containing protein haemoglobin found in vertebrates' blood. The blood is pumped by three separate hearts: two branchial hearts pump blood to the cuttlefish's pair of gills (one heart for each), and the third pumps blood around the rest of the body. Cuttlefish blood must flow more rapidly than that of most other animals because haemocyanin carries substantially less oxygen than haemoglobin. Unlike most other mollusks, cephalopods like cuttlefish have a closed circulatory system.

Cuttlebone.

Cuttlefish possess an internal structure called the cuttlebone, which is porous and is made of aragonite. The pores provide it with buoyancy, which the cuttlefish regulates by changing the gas-to-liquid ratio in the chambered cuttlebone via the ventral siphuncle. Each species' cuttlebone has a distinct shape, size, and pattern of ridges or texture. The cuttlebone is unique to cuttlefish, and is one of the features that distinguish them from their squid relatives.

Ink.

Like other marine mollusks, cuttlefish have ink stores that are used for chemical deterrence, phagomimicry, sensory distraction, and evasion when attacked. Its composition results in a dark colored ink, rich in ammonium salts and amino acids that may have a role in phagomimicry defenses. The ink can be ejected to create a "smoke screen" to hide the cuttlefish's escape, or it can be released as a pseudomorph of similar size to the cuttlefish, acting as a decoy while the cuttlefish swims away.  Human use of this substance is wide-ranged. A common use is in cooking with squid ink to darken and flavor rice and pasta. It adds a black tint and a sweet flavor to the food. In addition to food, cuttlefish ink can be used with plastics and staining of materials. The diverse composition of cuttlefish ink, and its deep complexity of colors, allows for dilution and modification of its color. Cuttlefish ink can be used to make noniridescent reds, blues, and greens, subsequently used for biomimetic colors and materials.

Arms and mantle cavity.

Cuttlefish have eight arms and two additional elongated tentacles that are used to grasp prey. The elongated tentacles and mantle cavity serve as defense mechanisms; when approached by a predator, the cuttlefish can suck water into its mantle cavity and spread its arms in order to appear larger than normal. Though the mantle cavity is used for jet propulsion, the main parts of the body that are used for basic mobility are the fins, which can maneuver the cuttlefish in all directions.

Suckers and venom.

The suckers of cuttlefish extend most of the length of their arms and along the distal portion of their tentacles. Like other cephalopods, cuttlefish have "taste-by-touch" sensitivity in their suckers, allowing them to discriminate among objects and water currents that they contact.  Some cuttlefish are venomous. The genes for venom production are thought to be descended from a common ancestor. The muscles of the flamboyant cuttlefish ("Metasepia pfefferi") contain a highly toxic, unidentified compound as lethal as that of a fellow cephalopod, the blue-ringed octopus.

Sleep-like behavior.

Sleep is a state of immobility characterized by being rapidly reversible, homeostatically controlled, and increasing an organism's arousal threshold. To date one cephalopod species, "Octopus vulgaris", has been shown to satisfy these criteria. Another species, "Sepia officinalis", satisfies two of the three criteria but has not yet been tested on the third (arousal threshold). Recent research shows that the sleep-like state in a common species of cuttlefish, "Sepia officinalis", shows predictable periods of rapid eye movement, arm twitching and rapid chromatophore changes.

Life cycle.

The lifespan of cuttlefish is only around one to two years, depending on the species. They hatch from eggs fully developed, around a fourth of an inch long, reaching one inch around the first two months. Before death cuttlefish go through senescence when the cephalopod essentially deteriorates, or rots in place. Their eyesight begins to fail which affects their ability to see, move, and hunt efficiently. Once this process begins, cuttlefish tend to not live long due to predation by other organisms. Captive breeders may euthanize dying cuttlefish by freezing them or using life-ending chemicals that are made by aquarium companies.

Reproduction.

Cuttlefish start to actively mate at around five months of age. Male cuttlefish challenge one another for dominance and the best den during mating season. During this challenge, no direct contact is usually made. The animals threaten each other until one of them backs down and swims away. Eventually, the larger male cuttlefish mate with the females by grabbing them with their tentacles, turning the female so that the two animals are face-to-face, then using a specialized tentacle to insert sperm sacs into an opening near the female's mouth. As males can also use their funnels to flush others' sperm out of the female's pouch, the male then guards the female until she lays the eggs a few hours later. After laying her cluster of eggs, the female cuttlefish secretes ink on them making them look very similar to grapes. The egg case is produced through a complex capsule of the female accessory genital glands and the ink bag.  On occasion, a large competitor arrives to threaten the male cuttlefish. In these instances, the male first attempts to intimidate the other male. If the competitor does not flee, the male eventually attacks it to force it away. The cuttlefish that can paralyze the other first, by forcing near its mouth, wins the fight and the female. Since typically four or five (and sometimes as many as 10) males are available for every female, this behavior is inevitable.  Cuttlefish are indeterminate growers, so smaller cuttlefish always have a chance of finding a mate the next year when they are bigger. Additionally, cuttlefish unable to win in a direct confrontation with a guard male have been observed employing several other tactics to acquire a mate. The most successful of these methods is camouflage; smaller cuttlefish use their camouflage abilities to disguise themselves as a female cuttlefish. Changing their body color, and even pretending to be holding an egg sack, disguised males are able to swim past the larger guard male and mate with the female.

Communication.

Cephalopods are able to communicate visually using a diverse range of signals. To produce these signals, cephalopods can vary four types of communication element: chromatic (skin coloration), skin texture (e.g. rough or smooth), posture, and locomotion. Changes in body appearance such as these are sometimes called polyphenism. The common cuttlefish can display 34 chromatic, six textural, eight postural and six locomotor elements, whereas flamboyant cuttlefish use between 42 and 75 chromatic, 14 postural, and seven textural and locomotor elements. The Caribbean reef squid ("Sepioteuthis sepioidea") is thought to have up to 35 distinct signalling states.

Chromatic.

Cuttlefish are sometimes referred to as the "chameleons of the sea" because of their ability to rapidly alter their skin color – this can occur within one second. Cuttlefish change color and pattern (including the polarization of the reflected light waves), and the shape of the skin to communicate to other cuttlefish, to camouflage themselves, and as a deimatic display to warn off potential predators. Under some circumstances, cuttlefish can be trained to change color in response to stimuli, thereby indicating their color changing is not completely innate.  Cuttlefish can also affect the light's polarization, which can be used to signal to other marine animals, many of which can also sense polarization, as well as being able to influence the color of light as it reflects off their skin. Although cuttlefish (and most other cephalopods) lack color vision, high-resolution polarisation vision may provide an alternative mode of receiving contrast information that is just as defined. The cuttlefish's wide pupil attenuates chromatic aberration, allowing it to perceive color by focusing specific wavelengths onto the retina.  The three broad categories of color patterns are uniform, mottle, and disruptive. Cuttlefish can display as many as 12 to 14 patterns, 13 of which have been categorized as seven "acute" (relatively brief) and six "chronic" (long-lasting) patterns. although other researchers suggest the patterns occur on a continuum. The color-changing ability of cuttlefish is due to multiple types of cells. These are arranged (from the skin's surface going deeper) as pigmented chromatophores above a layer of reflective iridophores and below them, leucophores.

Chromatophores.

The chromatophores are sacs containing hundreds of thousands of pigment granules and a large membrane that is folded when retracted. Hundreds of muscles radiate from the chromatophore. These are under neural control and when they expand, they reveal the hue of the pigment contained in the sac. Cuttlefish have three types of chromatophore: yellow/orange (the uppermost layer), red, and brown/black (the deepest layer). The cuttlefish can control the contraction and relaxation of the muscles around individual chromatophores, thereby opening or closing the elastic sacs and allowing different levels of pigment to be exposed. Furthermore, the chromatophores contain luminescent protein nanostructures in which tethered pigment granules modify light through absorbance, reflection, and fluorescence between 650 and 720 nm.  For cephalopods in general, the hues of the pigment granules are relatively constant within a species, but can vary slightly between species. For example, the common cuttlefish and the opalescent inshore squid ("Loligo opalescens") have yellow, red, and brown, the European common squid ("Alloteuthis subulata") has yellow and red, and the common octopus has yellow, orange, red, brown, and black.  In cuttlefish, activation of a chromatophore can expand its surface area by 500%. Up to 200 chromatophores per mm of skin may occur. In "Loligo plei", an expanded chromatophore may be up to 1.5 mm in diameter, but when retracted, it can measure as little as 0.1 mm.

Iridophores.

Retracting the chromatophores reveals the iridophores and leucophores beneath them, thereby allowing cuttlefish to use another modality of visual signalling brought about by structural coloration. Iridophores are structures that produce iridescent colors with a metallic sheen. They reflect light using plates of crystalline chemochromes made from guanine. When illuminated, they reflect iridescent colors because of the diffraction of light within the stacked plates. Orientation of the schemochrome determines the nature of the color observed. By using biochromes as colored filters, iridophores create an optical effect known as Tyndall or Rayleigh scattering, producing bright blue or blue-green colors. Iridophores vary in size, but are generally smaller than 1 mm. Squid at least are able to change their iridescence. This takes several seconds or minutes, and the mechanism is not understood. However, iridescence can also be altered by expanding and retracting the chromatophores above the iridophores. Because chromatophores are under direct neural control from the brain, this effect can be immediate.  Cephalopod iridophores polarize light. Cephalopods have a rhabdomeric visual system which means they are visually sensitive to polarized light. Cuttlefish use their polarization vision when hunting for silvery fish (their scales polarize light). Female cuttlefish exhibit a greater number of polarized light displays than males and also alter their behavior when responding to polarized patterns. The use of polarized reflective patterns has led some to suggest that cephalopods may communicate intraspecifically in a mode that is "hidden" or "private" because many of their predators are insensitive to polarized light.

Leucophores.

Leucophores, usually located deeper in the skin than iridophores, are also structural reflectors using crystalline purines, often guanine, to reflect light. Unlike iridophores, however, leucophores have more organized crystals that reduce diffraction. Given a source of white light, they produce a white shine, in red they produce red, and in blue they produce blue. Leucophores assist in camouflage by providing light areas during background matching (e.g. by resembling light-colored objects in the environment) and disruptive coloration (by making the body appear to be composed of high-contrasting patches).  The reflectance spectra of cuttlefish patterns and several natural substrates (stipple, mottle, disruptive) can be measured using an optic spectrometer.

Intraspecific communication.

Cuttlefish sometimes use their color patterns to signal future intent to other cuttlefish. For example, during agonistic encounters, male cuttlefish adopt a pattern called the intense zebra pattern, considered to be an honest signal. If a male is intending to attack, it adopts a "dark face" change, otherwise, it remains pale.  In at least one species, female cuttlefish react to their own reflection in a mirror and to other females by displaying a body pattern called "splotch". However, they do not use this display in response to males, inanimate objects, or prey. This indicates they are able to discriminate same-sex conspecifics, even when human observers are unable to discern the sex of a cuttlefish in the absence of sexual dimorphism.  Female cuttlefish signal their receptivity to mating using a display called precopulatory grey. Male cuttlefish sometimes use deception toward guarding males to mate with females. Small males hide their sexually dimorphic fourth arms, change their skin pattern to the mottled appearance of females, and change the shape of their arms to mimic those of nonreceptive, egg-laying females.  Displays on one side of a cuttlefish can be independent of the other side of the body; males can display courtship signals to females on one side while simultaneously showing female-like displays with the other side to stop rival males interfering with their courtship.

Interspecific communication.

The deimatic display (a rapid change to black and white with dark ‘eyespots’ and contour, and spreading of the body and fins) is used to startle small fish that are unlikely to prey on the cuttlefish, but use the flamboyant display towards larger, more dangerous fish, and give no display at all to chemosensory predators such as crabs and dogfish.  One dynamic pattern shown by cuttlefish is dark mottled waves apparently repeatedly moving down the body of the animals. This has been called the passing cloud pattern. In the common cuttlefish, this is primarily observed during hunting, and is thought to communicate to potential prey – “stop and watch me” – which some have interpreted as a type of "hypnosis".

Camouflage.

Cuttlefish are able to rapidly change the color of their skin to match their surroundings and create chromatically complex patterns, despite their inability to perceive color, through some mechanism which is not completely understood. They have been seen to have the ability to assess their surroundings and match the color, contrast and texture of the substrate even in nearly total darkness.  The color variations in the mimicked substrate and animal skin are similar. Depending on the species, the skin of cuttlefish responds to substrate changes in distinctive ways. By changing naturalistic backgrounds, the camouflage responses of different species can be measured. "Sepia officinalis" changes color to match the substrate by disruptive patterning (contrast to break up the outline), whereas "S. pharaonis" matches the substrate by blending in. Although camouflage is achieved in different ways, and in an absence of color vision, both species change their skin colors to match the substrate. Cuttlefish adapt their own camouflage pattern in ways that are specific for a particular habitat. An animal could settle in the sand and appear one way, with another animal a few feet away in a slightly different microhabitat, settled in algae for example, will be camouflaged quite differently.  Cuttlefish are also able to change the texture of their skin. The skin contains bands of circular muscle which as they contract, push fluid up. These can be seen as little spikes, bumps, or flat blades. This can help with camouflage when the cuttlefish becomes texturally as well as chromatically similar to objects in its environment such as kelp or rocks.

Diet.

While the preferred diet of cuttlefish is crabs and fish, they feed on small shrimp shortly after hatching.  Cuttlefish use their camouflage to hunt and sneak up on their prey. They swim at the bottom, where shrimp and crabs are found, and shoot out a jet of water to uncover the prey buried in the sand. Then when the prey tries to escape, the cuttlefish open their eight arms and shoot out two long feeding tentacles to grab them. Each arm has a pad covered in suckers, which grabs and pulls prey toward its beak, paralyzing it with venom before eating it. To achieve a hypnotic effect and stun prey before catching it, cuttlefish are also known to change color rapidly.

Taxonomy.

Over 120 species of cuttlefish are currently recognised, grouped into six families.

Human uses.

As food.

Cuttlefish are caught for food in the Mediterranean, East Asia, the English Channel, and elsewhere.  In East Asia, dried, shredded cuttlefish is a popular snack food. In the Qing Dynasty manual of Chinese gastronomy, the "Suiyuan shidan", the roe of the cuttlefish is considered a difficult-to-prepare, but sought-after delicacy.  Cuttlefish are quite popular in Europe. For example, in northeast Italy, they are used in "risotto al nero di seppia" (risotto with cuttlefish ink), also found in Croatia and Montenegro as "crni rižot" (black risotto). Catalan cuisine, especially that of the coastal regions, uses cuttlefish and squid ink in a variety of "tapas" and dishes such as "arròs negre". Breaded and deep-fried cuttlefish is a popular dish in Andalusia. In Portugal, cuttlefish is present in many popular dishes. "Chocos com tinta" (cuttlefish in black ink), for example, is grilled cuttlefish in a sauce of its own ink. Cuttlefish is also popular in the region of Setúbal, where it is served as deep-fried strips or in a variant of "feijoada", with white beans. Black pasta is often made using cuttlefish ink.

Sepia.

Cuttlefish ink was formerly an important dye, called sepia. To extract the sepia pigment from a cuttlefish (or squid), the inc sac is removed and dried then dissolved in a dilute alkali. The resulting solution is filtered to isolate the pigment, which is then precipitated with dilute hydrochloric acid. The isolated precipitate is the sepia pigment. It is relatively chemically inert, which contributes to its longevity. Today, artificial dyes have mostly replaced natural sepia.

Metal casting.

Cuttlebone has been used since antiquity to make casts for metal. A model is pushed into the cuttlebone and removed, leaving an impression. Molten gold, silver or pewter can then be poured into the cast.

Smart clothing.

Research into replicating biological color-changing has led to engineering artificial chromatophores out of small devices known as dielectric elastomer actuators. Engineers at the University of Bristol have engineered soft materials that mimic the color-changing skin of animals like cuttlefish, paving the way for "smart clothing" and camouflage applications.

Pets.

Though cuttlefish are rarely kept as pets, due in part to their fairly short lifetimes, the most common to be kept are "Sepia officinalis" and "Sepia bandensis". Cuttlefish may fight or even eat each other if there is inadequate tank space for multiple individuals.  Cuttlebone is given to parakeets and other cagebirds as a source of dietary calcium.

Cuttlefish or cuttles are marine molluscs of the order Sepiida. They belong to the class Cephalopoda, which also includes squid, octopuses, and nautiluses. Cuttlefish have a unique internal shell, the cuttlebone.

Les seiches ou sépiides (Sepiida) forment un ordre de petits céphalopodes décapodes, dont la plupart sont appelées « seiches », sépioles, supions, chipirons ou encore casserons (ces derniers termes notamment en cuisine).


Description.

Some squid may grow to in mantle length and weigh up to. Generally, the mantle (or body) constitutes about 40% of the animal's mass, the fins (or wings) about 12%, the arms and tentacles about 14%, the outer skin about 3%, the head (including eyes and beak) about 5%, with the balance (26%) made up of the inner organs.

Behavior.

Humboldt squid are carnivorous marine invertebrates that move in shoals of up to 1,200 individuals. They swim at speeds up to propelled by water ejected through a hyponome (siphon) and by two triangular fins. Their tentacles bear 100–200 suckers, each lined with razor-sharp teeth, with which they grasp prey and drag it towards a large, sharp beak.  Although Humboldt squid have a reputation of being aggressive towards humans, some disagreement exists on this subject. Research suggests these squid are only aggressive while feeding; at other times, they are quite passive. Their behavior while feeding often extends to cannibalism and they have been seen to readily attack injured or vulnerable squid of their own shoal. A quarter of squid stomachs analyzed contained remains of other squid. This behavior may account for a large proportion of their rapid growth. Some scientists claim the only reports of aggression towards humans have occurred when reflective diving gear or flashing lights have been present as a provocation. Roger Uzun, a veteran scuba diver and amateur underwater videographer who swam with a swarm of the animals for about 20 minutes, said they seemed to be more curious than aggressive. In circumstances where these animals are not feeding or being hunted, they exhibit curious and intelligent behavior..  Electronic tagging has shown Humboldt squid undergo diel vertical migrations, which bring them closer to the surface from dusk to dawn. Humboldt squid are thought to have a lifespan of only about a year, although larger individuals may survive up to 2 years.  A crittercam attached to two Humboldt squid revealed that they "flash talk" with each other by changing color in certain ways, and that they can disguise themselves by shifting the color patterns in other ways. What they are communicating to each other is unknown.  Recent footage of shoals of these animals demonstrates a tendency to meet unfamiliar objects aggressively. Having risen to depths of below the surface to feed (up from their typical diving depth, beyond the range of human diving), they have attacked deep-sea cameras and rendered them inoperable. Humboldt squid have also been observed engaging in swarm behavior when met by the lights of submersibles, suggesting that they may follow or are attracted to light. Reports of recreational scuba divers being attacked by Humboldt squid have been confirmed. One particular diver, Scott Cassell, who has spent much of his career videotaping this species, has created body armor to protect against attacks.

Distribution.

The Humboldt squid lives at depths of in the eastern Pacific (Chile, Peru), ranging from Tierra del Fuego north to California. It gets its name from the Humboldt Current, in which it lives, off the coast of South America. Recently, the squid have been appearing farther north, as far as British Columbia. They have also ventured into Puget Sound.  Though they usually prefer deep water, between 1,000 and 1,500 squid washed up on the Long Beach Peninsula in southwest Washington in late 2004 and red algae were a speculated cause for the late 2012 beaching of an unspecified number of juvenile squid (average length ) at Monterey Bay over a 2-month period.

Ecology.

The Humboldt squid's diet consists mainly of small fish, crustaceans, cephalopods, and copepods. The squid uses its barbed tentacle suckers to grab its prey and slices and tears the victim's flesh with its beak and radula. They often approach prey quickly with all 10 appendages extended forward in a cone-like shape. Upon reaching striking distance, they open their eight swimming and grasping arms, and extend two long tentacles covered in sharp 'teeth', grabbing their prey and pulling it back towards a parrot-like beak, which can easily cause serious lacerations to human flesh. These two longer tentacles can reach full length, grab prey, and retract so fast that almost the entire event happens in one frame of a normal-speed video camera. Each of the squid's suckers is ringed with sharp teeth, and the beak can tear flesh, although they are believed to lack the jaw strength to crack heavy bone.  Another method of hunting is pulling the prey to great depths until it faints. The Humboldt squid is also known to quickly devour larger prey when hunting in groups. Until recently, claims of cooperative or coordinated hunting in "D. gigas" were considered unconfirmed and without scientific merit. However, research conducted between 2007 and 2011, published in June 2012, indicates this species does engage in cooperative hunting.  Scientists suspect the recent expansion of the squid's range north along the West Coast of the U.S. is the result of overfishing of longer-lived apex predators.

Fishing.

Commercially, this species has been caught to serve the European community market (mainly Spain, Italy, France, and Ireland), Russia, China, Japan, Southeast Asia, and increasingly North and South American markets.  Fishermen catch squid at night. Lights from the fishing boats reflect brightly on the plankton, which lure the squid to the surface to feed. Since the 1990s, the most important areas for landings of Humboldt squid are Chile, Mexico, and Peru (122–297, 53–66, and 291–435 thousand tonnes, respectively, in the period 2005–2007).  Humboldt squid are known for their speed in feasting on hooked fish, sharks, and squid, even from their own species and shoal. Numerous accounts have the squid attacking fishermen and divers in the area. Their coloring and aggressive reputation have earned them the nickname "diablos rojos" (red devils) from fishermen off the coast of Mexico, as they flash red and white when struggling with the fishermen.

Changes in migration patterns.

Humboldt squid are generally found in the warm Pacific waters off the Mexican coast; studies published in the early 2000s indicated an increase in northern migration. The large 1997–98 El Niño event triggered the first sightings of Humboldt squid in Monterey Bay. Then, during the minor El Niño event of 2002, they returned to Monterey Bay in higher numbers and have been seen there year-round since then. Similar trends have been shown off the coasts of Washington, Oregon, and even Alaska, although no year-round Humboldt squid populations are in these locations. This change in migration is suggested to be due to warming waters during El Niño events, but other factors, such as a decrease in upper trophic level predators that would compete with the squid for food, could be impacting the migration shift, as well.

Humboldt squid and ocean acidification.

A 2008 study published in the "Proceedings of the National Academy of Sciences of the United States of America" predicts that by the end of the 21st century, ocean acidification will lower the Humboldt squid's metabolic rate by 31% and activity levels by 45%. This will lead the squid to have to retreat to shallower waters, where they can take up oxygen at higher rates.

In popular media.

In 2009, the Humboldt squid was featured in the final episode of the BBC's "Last Chance to See", with Stephen Fry and Mark Carwardine. The episode was about blue whales, but the presenters interviewed fishermen who talked about the exploding "diablo rojo" population in the Sea of Cortez and human attacks, and showed a squid trying to take a bite of a protectively clad forearm.  In 2016, the Humboldt squid featured in three television shows. The first, "Man Eating Super Squid: A Monster Invasion," premiered on the National Geographic Wild channel and explored various attacks by Humboldt squid in Mexico. In the show, the Humboldt squid is referred to as a real-life kraken and as "a global threat".  The second show to feature the Humboldt squid recently is "River Monsters: Devil of the Deep," where angler and TV show host Jeremy Wade sets off to the Sea of Cortez to investigate strange attacks on fishermen. Jeremy discovers that the fishermen were in fact attacked by Humboldt squid and that the Humboldt squid have now moved on from the Sea of Cortez south towards the coast of Peru. After joining a local fishing crew, Jeremy Wade catches multiple Humboldt squid off the coast of Peru.  In "Fishing Impossible" shown on British TV in 2016, the team travel 10 hours out into the Pacific Ocean and put on diving suits reinforced with chain mail to protect themselves, as they plan to capture a Humboldt squid by hand. However, bad weather prevents them from diving for the squid.  In 2016, Humboldt squid were featured on BBC Earth's "Blue Planet II" where the Humboldt's cannibalistic pack hunting was captured on film for the first time.  A Humboldt Squid is a minor antagonist in the 2016 film "Finding Dory" where it chases and attempts to eat the main characters. This squid is presented as much larger than its real-life counterparts, easily destroying a shipping container which it seems to barely fit inside.  In another film, fishermen report, among other things, that a fisherman was caught in the abyss by a squid. And another fisherman was bitten by the squid on his skull, breaking his skull.

The Humboldt squid ("Dosidicus gigas"), also known as jumbo squid, jumbo flying squid, pota, or "diablo rojo" (red devil), is a large, predatory squid living in the waters of the Humboldt Current in the eastern Pacific Ocean. It is the only species of the genus "Dosidicus" of the subfamily Ommastrephinae, family Ommastrephidae.

L'Encornet géant ("Dosidicus gigas") est une espèce de calmar, la seule connue du genre Dosidicus. Il est parfois appelé diable des profondeurs ou calmar de Humboldt. C'est la plus grande espèce connue d'ommastrephidé mais non le plus grand calmar (il est dépassé par ceux du genre Architeuthis qui sont rares, mais qu'on a trouvés dans tous les océans terrestres, sauf peut être sous les glaces polaires).


Life.

Little is known of Marpurg's early life. According to various sources, he studied "philosophy" and music. It is clear that he enjoyed a strong education and was friendly with various leading figures of the Enlightenment, including Winckelmann and Lessing. In 1746, he travelled to Paris as the secretary for a General named either Rothenberg or Bodenberg. There, he became acquainted with important intellectual luminaries, such as the writer and philosopher Voltaire, the mathematician d'Alembert and the composer Jean-Philippe Rameau.  After 1746, he returned to Berlin where he was more or less independent. Marpurg's offer to write exclusively for Breitkopf & Härtel was declined by the firm in 1757. In 1760, he received an appointment to the Royal Prussian Lotteries, whose director he became in 1763, receiving the title of War Councillor. His son, Johann Friedrich Marpurg, who later became a celebrated violinist, was born in 1766.  Marpurg's quarrelsome disposition and his enthusiasm for public polemics made him many enemies. Contemporaries also described him, however, as courteous and open-hearted.  Marpurg is most likely at the source of a two-centuries misunderstanding that J. S. Bach would have been using the equal temperament for the performance of "Das Wohltemperirte Clavier", because of his publication "Versuch über die musikalische Temperatur", 1776, This misunderstanding was only much later first challenged by Robert Holford Bosanquet in "An Elementary Treatise on Musical Intervals and Temperament" 1876, pp. 29–30, but this position did not acquire fame. The above position of Bosanquet, that a distinction should be made between "well temperament" and "equal temperament" was rediscovered by H. Kelletat, and thoroughly defended and analysed historically in "Zur musikalischen Temperatur", 1960, especially p. 32. Thanks to this publication by H. Kelletat, almost all musicologists subscribe to this distinction nowadays.

Works.

Marpurg published the bulk of his writings on music between 1750 and 1763. After he had attained his lottery position in 1763, he penned two works on this topic but continued to write on wider areas of music.  One of the first (and most influential) works of Marpurg was his tract on the Fugue (1753) which is considered one of the oldest sources for the performance practice of J.S. Bach's "Art of the Fugue". His "Handbuch bey dem Generalbasse und der Composition" and the translation of d'Alembert's "Elémens de musique" stand at the beginning of Rameau reception in German harmonic theory. Other works treat questions of instrumental performance, vocal music, music history and mathematical music theory. His journal projects continued to promote the institution of German music criticism in the wake of Mattheson and Scheibe; his "Kritische Briefe über die Tonkunst" contains significant contributions to the theory of meter, the esthetics of the ode and other topics of current interest. His manuscript work on the ancient water organ remained unfinished. The scope and unprecedented clarity of Marpurg's writings on music made him the leading German music theorist of the late eighteenth century; he and his rivals Kirnberger and Schulz made up a distinct "Berlin School" of music criticism and -theory.

Friedrich Wilhelm Marpurg (21 November 1718 – 22 May 1795) was a German music critic, music theorist and composer. He was friendly and active with many figures of the Enlightenment of the 18th century.

Friedrich Wilhelm Marpurg (Altmärkische Wische, – Berlin, ), est un théoricien et compositeur, également, musicographe, chroniqueur, critique et éditeur allemand, membre de l'École de Berlin du lied.


Youth, education and World War I service.

Lewis Wendell Willkie was born in Elwood, Indiana, on February 18, 1892, the son of Henrietta (Trisch) and Herman Francis Willkie. Both of his parents were lawyers, his mother being one of the first women admitted to the Indiana bar. His father was born in Germany and his mother was born in Indiana, to German parents; his grandparents were involved in the unsuccessful 1848 revolutions in Germany. The Trisches initially settled in Kansas Territory but, as they were abolitionists, moved to Indiana after the territory was opened to slavery in the mid-1850s. Willkie was the fourth of six children, all intelligent, and learned skills during the nightly debates around the dinner table that would later serve him well.  Although given the first name Lewis, Willkie was known from childhood by his middle name. Herman Willkie, who had come from Prussia with his parents at age four, was intensely involved in progressive politics, and in 1896 took his sons to a torchlight procession for Democratic presidential candidate William Jennings Bryan, who had come to Elwood during his campaign. The Willkie boys had a sidewalk fight with Republican youths, and though the Willkies won their battle, Bryan did not, defeated by former Ohio governor William McKinley. When Bryan ran again in 1900, he stayed overnight at the Willkie home, and the Democratic candidate for president became the first political hero for the boy who would later seek that office.  By the time Willkie reached age 14 and enrolled in Elwood High School, his parents were concerned about a lack of discipline and a slight stoop, and they sent him to Culver Military Academy for a summer in an attempt to correct both. Willkie began to shine as a student in high school, inspired by his English teacher; one classmate said that Philip "Pat" Bing "fixed that boy up. He started preaching to Wendell to get to work and that kid went to town." Faced with a set of athletic brothers—Edward became an Olympic wrestler—Willkie joined the football team

Lawyer and executive (1919–39).

Akron attorney and activist.

Discharged from the army, Willkie returned to Elwood. He considered a run for Congress as a Democrat, but was advised that the district was so Republican he would be unlikely to keep the seat even if he could win it, and his chances might be better in a more urban area. Herman Willkie wanted Wendell and Robert to rejoin the family law firm, but Henrietta was opposed, feeling that opportunities in Elwood were too limited for her sons. She got her way, and in May 1919 Wendell Willkie successfully applied for a job with the Firestone Tire and Rubber Company in Akron, Ohio as head of the legal office that advised workers on wills and other personal matters. He was soon bored there, and on the advice of his wife, left for a law firm despite an offer from Harvey Firestone to double his salary. Firestone told the departing lawyer that he would never amount to anything because he was a Democrat.  Willkie became active in the Akron Democratic Party, becoming prominent enough while still with

Commonwealth & Southern executive.

Wendell and Edith Willkie moved to New York in October 1929, only weeks before the Wall Street Crash of 1929, and found an apartment overlooking Central Park. Initially intimidated by the size and anonymity of the big city, Wendell Willkie soon learned to love it. He attended the Broadway theatre, and read through ten newspapers each day. Willkie and his wife had little in common, and grew apart through the 1930s. He acquired a social life, and met Irita Van Doren, the book review editor of the "New York Herald Tribune" who became a friend, and later his lover. Cultured, brilliant and well connected, Van Doren introduced him to new books, new ideas, and new circles of friends. Unlike Van Doren, Willkie was indiscreet about their relationship, and their affair was well known to the reporters covering him during his 1940 presidential campaign. None of them printed a word.  At C&S, Willkie rose rapidly under the eye of Cobb, impressing his

TVA battle.

Soon after taking office, President Roosevelt proposed legislation creating the Tennessee Valley Authority (TVA), a government agency with far-reaching influence that promised to bring flood control and cheap electricity to the impoverished Tennessee Valley. However, the TVA would compete with existing private power companies in the area, including C&S subsidiaries. Willkie appeared before the House Military Affairs Committee on April 14, 1933. He approved of the ideas for development of the Tennessee Valley, but felt that the government role should be limited to selling power generated by dams. Although the House of Representatives passed a bill limiting the TVA's powers, the Senate took the opposite stance, and the latter position prevailed. Negotiations took place through the remainder of 1933 for C&S to sell assets, including a transmission line, to allow the TVA to distribute energy to retail customers, leading to an agreement

1940 presidential election.

Dark horse candidate.

The 1940 presidential campaign was conducted against the backdrop of World War II. Although the United States remained neutral, the nation—and especially the Republican Party—was deeply divided between isolationists, who felt the nation should avoid any steps that could lead America into the war, and interventionists, who felt that America's survival depended upon helping the Allies defeat Nazi Germany. The three leading candidates for the 1940 Republican nomination were all isolationists to varying degrees: Senators Robert A. Taft of Ohio and Arthur Vandenberg of Michigan, and Thomas E. Dewey, the young (only 38 years old), "gangbusting" Manhattan District Attorney. Roosevelt's popularity had declined since the 1936 landslide, but many still hoped he would run for an unprecedented third term. He had long contemplated one, but made no announcement. Roosevelt's decision-making on this point is uncertain: as late as April 1940, he may have been thinking of retirement. If he stepped aside, possible candidates included Vice President Garner, Secretary of State

Convention.

The 1940 Republican National Convention opened at the Philadelphia Civic Center on June 24, 1940. As the delegates assembled, they discussed the war, the candidates, and Roosevelt's appointment of two Republican interventionists to his cabinet four days before the convention. Henry L. Stimson, Secretary of War under President Taft and Secretary of State under Hoover, was restored to the War position, and Landon's 1936 running mate, Frank Knox, was appointed Navy Secretary. The cabinet appointments divided the Republicans, who accused Roosevelt of dirty politics. Willkie arrived by train in Philadelphia on June 22, two days before the convention, and immediately attracted attention by walking from 30th Street Station to his hotel, answering questions from reporters and anyone else who could get close enough to be heard. Dewey, Vandenberg and Taft had large public headquarters, but Willkie's campaign was run from clandestine rooms at the Benjamin Franklin Hotel. Root's Willkie Clubs and other supporters bombarded the delegates with telegrams urging support for their candidate, to the annoyance of some.

General election campaign.

After the convention, Willkie returned to New York. When he went to the movies, he received a standing ovation, as he did when he went to see the play "Life With Father". He resigned from C&S on July 8, 1940, confident that even if he lost his presidential bid, he would not lack for work. He had Republican National Committee (RNC) chairman John Hamilton dismissed on the advice of some of his advisors, who felt Hamilton was too conservative and isolationist, though the former chairman was given the post of executive director with partial responsibility for the Willkie campaign. Congressman Martin became RNC chair. At a time when little campaigning was done until after Labor Day, Willkie left on a five-week working vacation to The Broadmoor, a resort in Colorado Springs, but found neither peace nor privacy.  Roosevelt had been surprised by the outcome of the Republican convention, having expected to oppose a conservative isolationist. The polls showed Willkie behind by only six points, and the president expected this to be a more difficult race than he had faced in his defeats of Hoover and Landon. Roosevelt felt that Willkie's nomination would remove the war issue from

Activist and statesman (1940–43).

Visit to the United Kingdom.

Although defeated in the election, Willkie had become a major figure on the public scene, and at age 48, was deemed likely to remain one for years to come. Landon had received some 6,000 letters commiserating with him in his defeat; Willkie received over 100,000. Financially independent, he was in no hurry to decide among the many offers of employment from top law firms and major corporations. He resumed his affair with Van Doren.  While on vacation, Willkie decided his next cause should be military aid to embattled Britain, and announced support of the president's Lend-Lease program on January 13, 1941. Lend-Lease was highly unpopular in the Republican Party, and Willkie's announcement created a firestorm, with Landon and Taft decrying his actions. Former RNC chairman Hamilton wrote that of the almost 200 Republican members of the House and Senate, "Willkie couldn't

Wartime advocate.

After the Japanese attack on Pearl Harbor, Willkie offered his full support to Roosevelt. Willkie was interested in the post of war production czar, but that position went to Donald M. Nelson. Labor Secretary Perkins offered to have Willkie arbitrate between management and labor in war industries, but Willkie declined after White House officials informed the press. In early 1942, Willkie considered a run for Governor of New York. He later stated that Roosevelt had been willing to endorse him, but Willkie ultimately concluded that the Dewey forces were too

Civil rights activism.

During his 1940 campaign, Willkie had pledged to integrate the civil service and armed forces, and proudly pointed to what he deemed the strongest civil rights plank in history in the Republican platform. He also promised to end racial segregation in Washington, D.C. He gained the endorsements of the two largest African American newspapers, the "Pittsburgh Courier" and the "Baltimore Afro-American". With Willkie running to the left of Roosevelt on civil rights, Roosevelt feared that blacks would return to their traditional home in the

1944 presidential campaign.

Willkie spent much of 1943 preparing for a second presidential run, addressing Republican and nonpartisan groups. He did not meet with Roosevelt; with the presidential election approaching and with both men likely to run in it as candidates, their continued association would have been awkward. Although they differed with him on many issues, Republican leaders recognized Willkie's appeal and they had wanted him to campaign for the party in the 1942 midterm elections, but he went around the world instead. The huge publicity received by the titular head of the Republican Party as an emissary for a Democratic president frustrated leading Republicans. In spite of this, the Republicans gained seats in both the House and the Senate, though they still remained in the minority. Few Republican members of Congress were by then willing to support Willkie, and he dropped to second place behind General Douglas MacArthur in polls of likely voters in the party's 1944 presidential primaries. By 1943, even liberal Democrats did not doubt Willkie's progressive credentials. He spoke of appointing an African American to either the cabinet or the Supreme Court, and he warned California's Republican committee that the New Deal was irreversible and he stated that all they would get by opposing it was oblivion.  Willkie made his candidacy clear in an interview with "Look" magazine in early October 1943, arguing that a return to isolationism would lead the party to disaster. He decided to enter several presidential primaries in order to demonstrate his public support of the party, and he

Final months and death.

Defeated in his second bid for the White House, Willkie announced that he was returning to the practice of law, but his friends doubted that he would be content there. Roosevelt was anxious to dump Vice President Wallace from the ticket in his bid for a fourth term, and he had an intermediary sound out Willkie about running in Wallace's place. Willkie was reluctant even to respond, knowing that Roosevelt had made promises to potential running mates which he did not follow through on. There were further discussions between Willkie and the White House, of which third parties were aware though the details are not known; the vice presidential nomination went to Harry S Truman. Willkie got Roosevelt interested in a new liberal party which would be formed once peace came that would combine the left of the two existing major parties, but Willkie broke off contact with the White House after there were leaks of this to the press, because he felt that Roosevelt had used him for political gain. Roosevelt sent a letter expressing his regret for the leak, but that too was printed in the papers, and Willkie stated, "I've been lied to for the last time."  In spite of their breach, Roosevelt continued to try to conciliate Willkie. Roosevelt's son Elliott later stated that his father hoped to have Willkie be the first Secretary General of the United Nations, and the two men agreed to meet later in the year. Willkie had not been invited to speak at the 1944 Republican National Convention in Chicago that nominated Dewey for president, and he declined a pass as an "honored guest". Dewey hoped to get Willkie's endorsement, and he sent his foreign policy advisor, John Foster Dulles, to see Willkie. The former candidate refused to be drawn, and he made no endorsement before he died. Willkie wrote two articles for Collier's, one urging an internationalist foreign policy, and the other demanding advances in civil rights for

Legacy and remembrance.

Soon after the 1940 convention, Roosevelt described Willkie's nomination as a "Godsend to our country", because it ensured that the presidential race would not turn on the issue of aid to Britain. Walter Lippmann believed Willkie's nomination to have been crucial to Britain's survival, "second only to the Battle of Britain, the sudden rise and nomination of Willkie was the decisive event, perhaps providential, which made it possible to rally the free world when [Britain] was almost conquered. Under any other leadership but his the Republican party in 1940 would have turned its back on Great Britain, causing all who resisted Hitler to feel abandoned". Charles Peters wrote that "it is arguable that [Willkie's] impact on [the United States] and the world was greater than that of most men who actually held the office [of president]. At a crucial moment in history, he stood for the right things at the right time." When Georgia Senator Zell Miller, a Democrat, gave the keynote address at the 2004 Republican National Convention, he urged unity instead of partisan strife in the War on Terror, and recalled Willkie's actions, "He gave Roosevelt the critical support he needed for a peacetime draft, an unpopular idea at the time. And he made it clear that he would rather lose the election than make national security a partisan campaign issue."  Historian Hugh Ross argued that in gaining the nomination, Willkie "gave exceptional promise of being a winner. There were ample precedents from American political history in which a minority party, queasy over prospects for survival, bypassed professional leadership in order to entrust its political fortunes to a man without political experience. In most of the previous instances, the nomination had gone to a military

Notes.

Explanatory notes

Wendell Lewis Willkie (born Lewis Wendell Willkie; February 18, 1892 – October 8, 1944) was an American lawyer, corporate executive, and the 1940 Republican nominee for President of the United States. Willkie appealed to many convention delegates as the Republican field's only interventionist: although the U.S. remained neutral prior to Pearl Harbor, he favored greater U.S. involvement in World War II to support Britain and other Allies. His Democratic opponent, incumbent President Franklin D. Roosevelt, won the 1940 election with about 55% of the popular vote and took the electoral college vote by a wide margin.

Wendell Lewis Willkie, né à Elwood (Indiana) le et mort à New York le, est un avocat et homme politique américain, membre du Parti démocrate puis du Parti républicain. Il est le candidat républicain à la présidence des États-Unis en 1940.


Plot.

Frank Martin (Jason Statham) is a highly skilled driver/ mercenary whose callsign is "The Transporter." He will transport anything, no questions asked, always on time, and is the best in the business. He strictly follows three rigid rules when transporting:  In Nice, Frank is hired to transport three bank robbers with his black BMW 735i, but they hoist a fourth man into his car after the robbery. Explaining the extra weight will affect his precisely planned getaway, he refuses to drive until, in desperation, the leader kills one of his men who is pushed out of the car. Later they offer more money for Frank to drive them to Avignon. He refuses the deal. The robbers escape in another car but are foiled by their amateur driving.  At Frank's villa on the Mediterranean, local Police Inspector Tarconi (François Berléand) questions Frank about the black BMW that fled the scene of the robbery. However, lacking any real proof, Tarconi leaves. Frank is then hired to deliver a package of to an American, Darren "Wall Street" Bettencourt (Matt Schulze), that is loaded into Frank's trunk. While changing a flat tire, Frank notices the package moving. Realizing a person is inside, he violates Rule No. 3 in order to give the person something to drink. He discovers a woman, who is tied up and also gagged with tape on her mouth (Shu Qi). She attempts to escape but Frank recaptures her and returns her to the trunk along with two policemen who spot them.  Frank delivers the package to Bettencourt as promised and agrees to transport a briefcase for him. He stops to buy Pepsi Cola for the cops in his trunk, but they are killed by the bomb hidden in the briefcase. Out for vengeance, Frank returns to Bettencourt's villa, where he kills and wounds several of Bettencourt's henchmen. Frank then steals a car (a Mercedes-Benz S-Klasse) to get away, only to find "the package" bound and tapegagged in the back seat. He brings the young woman, who is named Lai, back to his house.  Bettencourt visits one of his surviving men in hospital in order to determine who attacked his residence, before killing the man after discovering that Frank is alive. The next day, Tarconi arrives and asks about Frank's car, which Frank claims was stolen. Lai says she is Frank's new cook and, afterwards, girlfriend, supporting Frank's alibi. Tarconi again leaves with no concrete evidence. Shortly after, Bettencourt's henchmen rain missiles down on the house. Frank and Lai barely escape, using scuba gear, to a nearby safe house Frank has prepared for such contingencies. Frank is irritated by all the chaos, but Lai makes it up to him by seducing him.  While being questioned at the police station, Lai accesses Tarconi's computer to find information on Bettencourt. Lai tells Frank that Bettencourt is a human trafficker with 400 Chinese (including her family) trapped in shipping containers. Lai and Frank go to Bettencourt's office, where Bettencourt reveals that Lai's father, Kwai (Ric Young), is also a human trafficker and Bettencourt's partner in crime. Kwai arrives and his henchmen subdue Frank. When Tarconi arrives, Kwai and Bettencourt accuse Frank of kidnapping Lai. Tarconi has Frank arrested and locked up in the station.  Realizing Frank would not be constrained by search warrants, Tarconi agrees to aid Frank's escape as his faux hostage. Frank then tracks the criminals to the docks, where they load the containers onto trucks. However, Frank is spotted and is forced to fight his way through the guards, and fails to stop the trucks. He then steals a small airplane and parachutes onto one of the trucks. After a lengthy fight, Frank manages to kill Bettencourt and some of his henchmen, only to be ambushed by Kwai once he gets out of the truck. However, Frank is saved when Lai reluctantly shoots her father. Afterwards, Tarconi arrives with the police, and they rescue the people trapped inside the two containers.

Releases.

Theatrical release.

"The Transporter" premiered in 2,573 theaters. With a production budget of $20.5 million, it grossed $25,296,447 in the United States and a total of $43,928,932 worldwide.

Cut and uncut releases.

The film was cut to receive a PG-13 rating in the United States, and this version was also released in the United Kingdom and several other countries. Japan and France received the uncut versions. Certain sequences of violence were either cut or toned down for the PG-13 cut. These include: The uncut fight on the bus can be seen in the "Extended Fight Sequences" on the North American DVD, but with no sound.  The Japanese region-free Blu-ray cut of this film has the original uncut French version of the film. It also has several special features and deleted scenes. However, it does not include the North American special feature of the uncut fight scenes (with no sound). The uncut version of "Transporter 2" is also included in this special boxed set.  † indicates that the song did not appear in the film

Home media.

The DVD version was released on 23 October 2003. It included fifteen minutes of extended fight scene footage and a feature-length commentary. On 23 August 2005, the film was released again in a "Special Delivery Edition". This version included all the features of the original release plus a new behind-the-scenes documentary, a making-of featurette, and a storyboard-to-film comparison. The film was also released as a part of "The Transporter Collection", which featured the first two films in the series. A Blu-ray format was released on 14 November 2006.

Reception.

Review aggregation website Rotten Tomatoes gives the film a score of 54% based on reviews from 127 critics and an average rating of 5.6 out of 10. The site's consensus reads: ""The Transporter" delivers the action at the expense of coherent storytelling." At Metacritic, which assigns a weighted average score out of 100 to reviews from mainstream critics, the film received an average score of 51 based on 27 reviews, indicating "mixed or average reviews".  Manohla Dargis, of the "Los Angeles Times", complimented the action, saying, "[Statham] certainly seems equipped to develop into a mid-weight alternative to Vin Diesel. That's particularly true if he keeps working with director Corey Yuen, a Hong Kong action veteran whose talent for hand-to-hand mayhem is truly something to see."  Roger Ebert wrote, "Too much action brings the movie to a dead standstill." Eric Harrison, of the "Houston Chronicle", said, "It's junk with a capital J. The sooner you realize that, the more quickly you can settle down to enjoying it."

The Transporter (French: Le Transporteur) is a 2002 English-language French action-thriller film directed by Corey Yuen and Louis Leterrier (who is credited as artistic director on the film), and written by Luc Besson, who was inspired by BMW Films' "The Hire" series. The film stars Jason Statham as Frank Martin, a driver for hire—a mercenary "transporter" who will deliver anything, anywhere, no questions asked—for the right price. It also stars Shu Qi as Lai Kwai.

Le Transporteur ("" en anglais) est un film français réalisé par Louis Leterrier et Corey Yuen, sorti en 2002. Le film met en vedette Jason Statham dans le rôle de Frank Martin, un qui livre n'importe quoi et n'importe où et sans poser de questions pour le bon prix.


Medical uses.

Warfarin is used to decrease the tendency for thrombosis or as secondary prophylaxis (prevention of further episodes) in those individuals who have already formed a blood clot (thrombus). Warfarin treatment can help prevent formation of future blood clots and help reduce the risk of embolism (migration of a thrombus to a spot where it blocks blood supply to a vital organ).  Warfarin is best suited for anticoagulation (clot formation inhibition) in areas of slowly running blood (such as in veins and the pooled blood behind artificial and natural valves) and in blood pooled in dysfunctional cardiac atria. Thus, common clinical indications for warfarin use are atrial fibrillation, the presence of artificial heart valves, deep venous thrombosis, and pulmonary embolism (where the embolized clots first form in veins). Warfarin is also used in antiphospholipid syndrome. It has been used occasionally after heart attacks (myocardial infarctions), but is far less effective at preventing new thromboses in coronary arteries. Prevention of clotting in arteries is usually undertaken with antiplatelet drugs, which act by a different mechanism from warfarin (which normally has no effect on platelet function). It can be used to treat people following an ischemic strokes due to atrial fibrillation, though direct oral anticoagulants (DOAC) may offer increased benefits.

Dosing.

Dosing of warfarin is complicated because it is known to interact with many commonly used medications and certain foods. These interactions may enhance or reduce warfarin's anticoagulation effect. To optimize the therapeutic effect without risking dangerous side effects such as bleeding, close monitoring of the degree of anticoagulation is required by a blood test measuring an INR. During the initial stage of treatment, INR is checked daily; intervals between tests can be lengthened if the patient manages stable therapeutic INR levels on an unchanged warfarin dose. Newer point-of-care testing is

Maintenance dose.

Recommendations by many national bodies, including the American College of Chest Physicians, have been distilled to help manage dose adjustments.  The maintenance dose of warfarin can fluctuate significantly depending on the amount of vitamin K in the diet. Keeping vitamin K intake at a stable level can prevent these fluctuations. Leafy green vegetables tend to contain higher amounts of vitamin K. Green parts of members

Self-testing.

Patients are making increasing use of self-testing and home monitoring of oral anticoagulation. International guidelines on home testing were published in 2005. The guidelines stated: "The consensus agrees that patient self-testing and patient self-management are effective methods of monitoring oral anticoagulation therapy, providing outcomes at least as good as, and possibly better than, those achieved with an anticoagulation clinic. All patients must be appropriately selected and trained. Currently available self-testing/self-management devices give INR results that are comparable with those obtained in laboratory testing." A 2006 systematic review and meta-analysis of 14 randomized trials showed home testing led to a reduced incidence of complications (thrombosis and major bleeding) and improved the time in the therapeutic range.

Alternative anticoagulants.

In some countries, other coumarins are used instead of warfarin, such as acenocoumarol and phenprocoumon. These have a shorter (acenocoumarol) or longer (phenprocoumon) half-life, and are not completely interchangeable with warfarin. Several

Contraindications.

All anticoagulants are generally contraindicated in situations where the reduction in clotting that they cause might lead to serious and potentially life-threatening bleeds. This includes people with active bleeding conditions (such as gastrointestinal ulcers), or disease states with increased risk of bleeding e.g. low platelets, severe liver disease, uncontrolled hypertension. For patients undergoing surgery, treatment with anticoagulants is generally suspended. Similarly, spinal or lumbar puncture (e.g. spinal injections, epidurals, etc.) carry increased risk so treatment is suspended prior to these procedures.  Warfarin should not be given to people with heparin-induced thrombocytopenia until platelet count has improved or normalised. Warfarin is usually best avoided in people with protein C or protein S deficiency as these thrombophilic conditions increase the risk of skin necrosis, which is a rare but serious side effect associated with warfarin.

Pregnancy.

Warfarin is contraindicated in pregnancy, as it passes through the placental barrier and may cause bleeding in the fetus; warfarin use during pregnancy is commonly associated with spontaneous abortion, stillbirth, neonatal death, and preterm birth. Coumarins (such as warfarin) are also teratogens, that is, they cause birth defects; the incidence of birth defects in infants exposed to warfarin "in utero" appears to be around 5%, although higher figures (up to 30%) have been reported in some studies. Depending on when exposure occurs during pregnancy, two distinct combinations of congenital abnormalities can arise.

First trimester of pregnancy.

Usually, warfarin is avoided in the first trimester, and a low molecular weight heparin such as enoxaparin is substituted. With heparin, risk of maternal haemorrhage and other complications are still increased, but heparins do not cross the placental barrier, so do not cause birth defects. Various solutions exist for the time around delivery.  When warfarin (or another 4-hydroxycoumarin derivative) is given

Second trimester and later.

Warfarin administration in the second and third trimesters is much less commonly associated with birth defects, and when they do occur, are considerably different from fetal warfarin syndrome. The most common congenital abnormalities associated with warfarin use in late pregnancy are central nervous system disorders, including spasticity and seizures, and eye defects. Because of such later pregnancy birth defects, anticoagulation with warfarin poses a problem in pregnant women requiring warfarin for vital indications, such as stroke prevention in those with artificial heart valves.  According to the American College of Chest Physicians (ACCP), warfarin may be used in lactating women who wish to breast-feed their infants. Available data does not suggest that warfarin crosses into the breast milk. Similarly, INR levels should be checked to avoid adverse effects.

Adverse effects.

Bleeding.

The only common side effect of warfarin is bleeding. The risk of severe bleeding is small but definite (a typically yearly rate of 1–3% has been reported) and any benefit needs to outweigh this risk when warfarin is considered. All types of bleeding occur more commonly, but the most severe ones are those involving the brain (intracerebral hemorrhage/hemorrhagic stroke) and the spinal cord. Risk of bleeding is increased if the INR is out of range (due to accidental or deliberate overdose or due to interactions). This risk increases greatly once the INR exceeds 4.5.  A number of risk scores exist to

Warfarin necrosis.

A rare but serious complication resulting from treatment with warfarin is warfarin necrosis, which occurs more frequently shortly after commencing treatment in patients with a deficiency of protein C. Protein C is an innate anticoagulant that, like the procoagulant factors that warfarin inhibits, requires vitamin K-dependent carboxylation

Osteoporosis.

After initial reports that warfarin could reduce bone mineral density, several studies have demonstrated a link between warfarin use and osteoporosis-related fracture. A 1999 study in 572 women taking warfarin for deep venous thrombosis, risk of vertebral fracture and rib fracture was increased; other fracture types did not occur more commonly. A 2002 study looking at a randomly selected selection of 1523 patients with

Purple toe syndrome.

Another rare complication that may occur early during warfarin treatment (usually within 3 to 8 weeks of commencement) is "purple toe syndrome". This condition is thought to result from small deposits of cholesterol breaking loose and causing embolisms

Calcification.

Several studies have also implicated warfarin use in valvular

Overdose.

The major side effect of warfarin use is bleeding. Risk of bleeding is increased if the INR is out of range (due to accidental or deliberate overdose or due to interactions). Many drug interactions can increase the effect of warfarin, also causing an overdose.  For people who need rapid reversal of warfarin – such as due to serious bleeding – or who need emergency surgery, the effects of warfarin can be reversed with vitamin K, prothrombin complex concentrate (PCC), or fresh frozen plasma (FFP). Generally, 4-factor PCC can be given more quickly than FFP, the amount needed is a smaller volume of fluid than FFP, and does

Interactions.

Warfarin interacts with many commonly used drugs, and the metabolism of warfarin varies greatly between patients. Some foods have also been reported to interact with warfarin. Apart from the metabolic interactions, highly protein bound drugs can displace warfarin from serum albumin and cause an increase in the INR. This makes finding the correct dosage difficult, and accentuates the need of monitoring; when initiating a medication that is known to interact with warfarin (e.g. simvastatin), INR checks are increased or dosages adjusted until a new ideal dosage is found.  When taken with nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin increases the risk for gastrointestinal bleeding. This increased risk is due to the anti-platelet effect of NSAIDs as well as the possible damage to the gastrointestinal mucosa.  Many commonly used antibiotics, such as metronidazole or the macrolides, will greatly increase the effect of warfarin by reducing the metabolism of warfarin in the body. Other broad-spectrum antibiotics can reduce the amount of the normal bacterial flora in the bowel, which make significant quantities of vitamin K, thus potentiating the effect of warfarin. In addition, food

Chemistry.

X-ray crystallographic studies of warfarin show that it exists in tautomeric form, as the cyclic hemiketal, which is formed from the 4-hydroxycoumarin and the ketone in the 3-position substituent. However, the existence of many 4-hydroxycoumadin anticoagulants (for example phenprocoumon) that possess no ketone group in the 3-substituent to form such a structure, suggests that the hemiketal must tautomerise to the 4-hydroxy form in order for warfarin to be active.

Stereochemistry.

Warfarin contains a stereocenter and consists of two enantiomers. This is a

Pharmacology.

Pharmacokinetics.

Warfarin consists of a racemic mixture of two active enantiomers—"R"- and "S"- forms—each of which is cleared by different pathways. S-warfarin is 2–5 times more potent than the R-isomer in producing an anticoagulant response. Both the enantiomers of warfarin undergo CYP-mediated metabolism by many different CYPs to form 3',4',6,7,8 and 10-hydroxy warfarin metabolites, major being 7-OH warfarin formed from S-warfarin by CYP2C9 and 10-OH warfarin from R-warfarin by CYP3A4.  Warfarin is slower acting than the common anticoagulant heparin, though it has a number of advantages. Heparin

Mechanism of action.

While warfarin is one of several drugs popularly referred to as a "blood thinner", this is a misnomer since it does not affect the viscosity of blood.  Warfarin inhibits the vitamin K-dependent synthesis of biologically active forms of the clotting factors II, VII, IX and X, as well as the regulatory factors protein C, protein S, and protein Z. Other proteins not involved in blood clotting, such as osteocalcin, or matrix Gla protein, may also be affected. The precursors of these factors require gamma carboxylation of their glutamic acid residues to allow the coagulation factors to bind to phospholipid surfaces inside blood vessels, on the vascular endothelium. The enzyme that carries out the carboxylation of glutamic acid is gamma-glutamyl carboxylase. The carboxylation reaction will proceed only if the carboxylase enzyme is able to convert a reduced form of vitamin K (vitamin K hydroquinone) to vitamin K epoxide at the same time. The vitamin K epoxide is in turn recycled back to vitamin K and vitamin K hydroquinone by another enzyme, the vitamin K epoxide reductase (VKOR). Warfarin inhibits epoxide reductase (specifically the VKORC1 subunit), thereby diminishing available vitamin K and vitamin K hydroquinone in the tissues, which

Pharmacogenomics.

Warfarin activity is determined partially by genetic factors. Polymorphisms in two genes ("VKORC1" and "CYP2C9") play a particularly large role in response to warfarin.  VKORC1 polymorphisms explain 30% of the dose variation between patients: particular mutations make VKORC1 less susceptible to suppression by warfarin. There are two main haplotypes that explain 25% of variation: low-dose haplotype group (A) and a high-dose haplotype group (B). "VKORC1" polymorphisms explain why African Americans are on average relatively resistant to warfarin (higher proportion of group B haplotypes), while Asian Americans are generally more sensitive (higher proportion of group A haplotypes). Group A "VKORC1" polymorphisms lead to a more rapid

History.

In the early 1920s, there was an outbreak of a previously unrecognized cattle disease in the northern United States and Canada. Cattle were haemorrhaging after minor procedures and on some occasions, spontaneously. For example, 21 out of 22 cows died after dehorning and 12 out of 25 bulls died after castration. All of these animals had bled to death.  In 1921, Frank Schofield, a Canadian veterinary pathologist, determined that the cattle were ingesting moldy silage made from sweet clover, and that this was functioning as a potent anticoagulant. Only spoiled hay made from sweet clover (grown in northern states of the US and in Canada since the turn of the century) produced the disease. Schofield separated good clover stalks and damaged clover stalks from the same hay mow, and fed each to a different rabbit. The rabbit that had ingested the good stalks remained well, but the rabbit that had ingested the damaged stalks died from a haemorrhagic illness. A duplicate experiment with a different sample of clover hay produced the same result. In 1929, North Dakota veterinarian Lee M. Roderick demonstrated that the condition was due to a lack of functioning prothrombin.  The identity of the anticoagulant substance in spoiled sweet clover remained a mystery until 1940. In 1933 Karl Paul Link and his lab of chemists working at the University of Wisconsin set out to isolate and characterize the haemorrhagic agent from the spoiled hay. It took five years before Link's student Harold A. Campbell recovered 6 mg of crystalline anticoagulant. Next, Link's student Mark A. Stahmann took over the project and initiated a large-scale extraction, isolating 1.8 g of recrystallized anticoagulant in about 4 months. This was enough material for Stahmann and Charles F. Huebner to check their results against Campbell's and to thoroughly characterize the compound. Through degradation experiments they established that the anticoagulant was 3,3'-methylenebis-(4-hydroxycoumarin), which they later named dicoumarol.

Pest control.

Rodents.

Coumarins (4-hydroxycoumarin derivatives) are used as rodenticides for controlling rats and mice in residential, industrial, and agricultural areas. Warfarin is both odorless and tasteless, and is effective when mixed with food bait, because the rodents will return to the bait and continue to feed over a period of days until a lethal dose is accumulated (considered to be 1 mg/kg/day over about six days). It may also be mixed with talc and used as a "tracking powder", which accumulates on the animal's skin

Vampire bats.

Warfarin is used to cull vampire bat populations in areas where human–wildlife conflict is a concern. Vampire bats are captured with mist nets and coated with a combination of petroleum jelly and warfarin. The bat returns to its roost and other members of the roost become

Occupational safety.

People can be exposed to warfarin in the workplace by breathing it in, swallowing it, skin absorption, and eye contact. The Occupational Safety and Health Administration (OSHA) has set the legal limit (permissible exposure limit) for warfarin exposure in the workplace as 0.1 mg/m over an 8-hour workday. The National Institute for Occupational

Names.

Warfarin is a derivative of dicoumarol, an anticoagulant originally discovered in spoiled sweet clover. Dicoumarol, in turn, is from coumarin, a sweet-smelling but coagulation-inactive chemical found in "sweet" clover and tonka beans (also known as "cumaru" from which coumarin's name derives). The name "warfarin" stems from its discovery at the University of Wisconsin, incorporating the

External links.

Bleeding risk calculators

Warfarin, sold under the brand name Coumadin among others, is a medication that is used as an anticoagulant (blood thinner). It is commonly used to treat blood clots such as deep vein thrombosis and pulmonary embolism and to prevent stroke in people who have atrial fibrillation, valvular heart disease or artificial heart valves. Less commonly it is used following ST-segment elevation myocardial infarction (STEMI) and orthopedic surgery. It is generally taken by mouth but may also be used by injection into a vein. The common side effect is bleeding. Less common side effects may include areas of tissue damage and purple toes syndrome. Use is not recommended during pregnancy. It is recommended that the effects of warfarin typically be monitored by checking prothrombin time (INR) every one to four weeks. Many other medications and dietary factors can interact with warfarin, either increasing or decreasing its effectiveness. The effects of warfarin may be reversed with phytomenadione (vitamin K), fresh frozen plasma, or prothrombin complex concentrate. Warfarin decreases blood clotting by blocking an enzyme called vitamin K epoxide reductase that reactivates vitamin K. Without sufficient active vitamin K, clotting factors II, VII, IX, and X have decreased clotting ability. The anticlotting protein C and protein S are also inhibited but to a lesser degree. A few days are required for full effect to occur and these effects can last for up to five days. Warfarin first came into commercial use in 1948 as a rat poison. In 1954 it was approved for medical use in the United States. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system. Warfarin is available as a generic medication. The wholesale cost in the developing world is about US$1.12 to 7.20 for a typical month of treatment. In the United States it usually costs less than $25 a month. In 2017, it was the 51st most commonly prescribed medication in the United States, with more than 15 million prescriptions.

Le coumaphène ou warfarine () est un composé organique de la famille des coumarines. C'est une substance active de produit phytosanitaire (ou produit phytopharmaceutique, ou pesticide), qui présente un effet rodenticide, avec toutefois de possibles phénomènes de résistance aux rodenticides.