Tobacco

Infobox on Tobacco
Example of Tobacco
Facts
Origin	This table shows only a selection of the most important countries of origin and should not be thought of as exhaustive. Europe: Turkey, Italy, Greece, France, Spain, Portugal, Bulgaria, Germany, Russia, Belgium, Croatia, Bosnia, Macedonia, Albania, Poland, Slovakia, Hungary, Ukraine, Moldova, Georgia, Azerbaijan, Uzbekistan, Kyrgyzstan Africa: Nigeria, Kenya, Uganda, Tanzania, Malawi, Zambia, Mozambique, Madagascar, Zimbabwe, South Africa, Cameroon, Ghana Asia: China, Indonesia, Japan, South Korea, India, Sri Lanka, Bangladesh, Thailand, Philippines, Pakistan, Burma, Iran America: USA, Canada, Brazil, Mexico, Dominican Republic, Guatemala, Colombia, Paraguay, Argentina Australia: Queensland, Victoria, New South Wales
Stowage factor (in m3/t)	3.00 m3/t (Asian leaf tobacco from India, bales wrapped in jute fabric, 102 kg) 5.70 m3/t (Oriental tobacco from Greece, bales wrapped in jute fabric, 29.2 kg) 2.8 - 3.4 m3/t (American tobacco, corrugated board cartons, 200 kg) 5.1 - 5.4 m3/t (American tobacco, bales from Havana, 50 kg) 5.1 - 5.7 m3/t (American tobacco, bales from Brazil, 150 kg) 4.0 - 4.8 m3/t (Asian tobacco, bales from China, 75 kg) 2.3 - 3.4 m3/t (Asian tobacco, bales from Sumatra, 70 - 80 kg) 2.8 m3/t (Asian tobacco, bales from Java, 80 kg 4.6 - 5.1 m3/t (Oriental tobacco, bales, 60 kg) 3.1 - 3.6 m3/t (Oriental tobacco, small bales)
Humidity / moisture	Relative humidity: 65 - 70% Water content: 12 - 14%(Oriental tobacco) 10 - 13% (Virginia tobacco) 10 - 12% (Virginia, Burley tobacco) 12 - 14% (Oriental tobacco) 11 - 15% Maximum equilibrium moisture content: 60 - 65% (Oriental tobacco) 50-65% (Virginia tobacco)
Oil content	-
Ventilation	Tobacco requires particular temperature, humidity/moisture and possibly ventilation conditions. Tobacco is generally transported in 40' or 20' standard containers. Ventilated containers are only used for transport from regions with critical climatic conditions, such as Indonesia or the Dominican Republic. If tobacco is loaded as conventional general cargo, ventilation is not normally required, provided that the water content of the tobacco corresponds to set values and there is no risk of sweat formation. If this is not the case, an air exchange rate of 6 changes/hour (airing) or just return air is advisable. Over-vigorous ventilation may dry out the tobacco and cause crumbling or fragmentation damage. For this reason, the system is switched to only vigorous return air.
Risk factors	Under suitable conditions, tobacco has a tendency to postfermentation and self-heating. Tobacco very readily absorbs foreign odors; is extremely sensitive to contamination, moisture damage, mechanical stresses and insect infestation.

Tobacco

Description

Tobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines. It is most commonly used as a drug, and is a valuable cash crop for countries such as Cuba, China and the United States. Tobacco is a name for any plant of the genus Nicotiana of the Solanaceae family (nightshade family) and for the product manufactured from the leaf and used in cigars and cigarettes, snuff, and pipe and chewing tobacco. Tobacco plants are also used in plant bioengineering, and some of the 60 species are grown as ornamentals. The chief commercial species, N. tabacum, is believed native to tropical America, like most nicotiana plants, but has been so long cultivated that it is no longer known in the wild. N. rustica, a mild-flavored, fast-burning species, was the tobacco originally raised in Virginia, but it is now grown chiefly in Turkey, India, and Russia. The alkaloid nicotine is the most characteristic constituent of tobacco and is responsible for its addictive nature. The harmful effects of tobacco derive from the thousands of different compounds generated in the smoke, including polycyclic aromatic hydrocarbons (such as benzpyrene), formaldehyde, cadmium, nickel, arsenic, radioactive polonium-210, tobacco-specific nitrosamines (TSNAs), phenols, and many others.

In consumption it most commonly appears in the forms of smoking, chewing, snuffing, or dipping tobacco. Tobacco had long been in use as an entheogen in the Americas, but upon the arrival of Europeans in North America, it quickly became popularized as a trade item and a widely-abused drug. This popularization led to the development of the southern economy of the United States until it gave way to cotton. Following the American Civil War, a change in demand and a change in labor force allowed for the development of the cigarette. This new product quickly led to the growth of tobacco companies. There are more than 70 species of tobacco in the plant genus Nicotiana.

Tobacco is cultivated similarly to other agricultural products. Seeds are sown in cold frames or hotbeds to prevent attacks from insects, and then transplanted into the fields. Tobacco is an annual crop, which is usually harvested mechanically or by hand. After harvest, tobacco is stored for curing, which allows for the slow oxidation and degradation of carotenoids. This allows for the agricultural product to take on properties that are usually attributed to the "smoothness" of the smoke. Following this, tobacco is packed into its various forms of consumption, which include smoking, chewing, snuffing, and so on. Most cigarettes incorporate flue-cured tobacco, which produces a milder, more inhalable smoke. Use of low pH, inhalable, flue cured tobacco is one of the principal reasons smoking causes lung cancer and other diseases association with smoke inhalation.

Types of tobacco
There are a number of types of tobacco including, but are not limited to:

• Aromatic fire-cured is cured by smoke from open fires. In the United States, it is grown in northern middle Tennessee, central Kentucky and in Virginia. Fire-cured tobacco grown in Kentucky and Tennessee are used in some chewing tobaccos, moist snuff, some cigarettes, and as a condiment in pipe tobacco blends. Another fire-cured tobacco is Latakia, which is produced from oriental varieties of N. tabacum. The leaves are cured and smoked over smoldering fires of local hardwoods and aromatic shrubs in Cyprus and Syria.
• Brightleaf tobacco, Brightleaf is commonly known as "Virginia tobacco", often regardless of the state where they are planted. Prior to the American Civil War, most tobacco grown in the US was fire-cured dark-leaf. This type of tobacco was planted in fertile lowlands, used a robust variety of leaf, and was either fire cured or air cured. Most Canadian cigarettes are made from 100% pure Virginia tobacco.
• Burley tobacco, is an air-cured tobacco used primarily for cigarette production. In the U.S., burley tobacco plants are started from palletized seeds placed in polystyrene trays floated on a bed of fertilized water in March or April.
• Cavendish is more a process of curing and a method of cutting tobacco than a type. The processing and the cut are used to bring out the natural sweet taste in the tobacco. Cavendish can be produced from any tobacco type, but is usually one of, or a blend of Kentucky, Virginia, and burley, and is most commonly used for pipe tobacco and cigars.
• Criollo tobacco is a type of tobacco, primarily used in the making of cigars. It was, by most accounts, one of the original Cuban tobaccos that emerged around the time of Columbus.
• Dokha, is a tobacco originally grown in Iran, mixed with leaves, bark, and herbs for smoking in a midwakh.
• Turkish tobacco, is a sun-cured, highly aromatic, small-leafed variety (Nicotiana tabacum) that is grown in Turkey, Greece, Bulgaria, and Macedonia. Originally grown in regions historically part of the Ottoman Empire, it is also known as "oriental". Many of the early brands of cigarettes were made mostly or entirely of Turkish tobacco; today, its main use is in blends of pipe and especially cigarette tobacco (a typical American cigarette is a blend of bright Virginia, burley and Turkish).
• Perique, a farmer called Pierre Chenet is credited with first turning this local tobacco into the Perique in 1824 through the technique of pressure-fermentation. Considered the truffle of pipe tobaccos, it is used as a component in many blended pipe tobaccos, but is too strong to be smoked pure. At one time, the freshly moist Perique was also chewed, but none is now sold for this purpose. It is typically blended with pure Virginia to lend spice, strength, and coolness to the blend.
• Shade tobacco, is cultivated in Connecticut and Massachusetts. Early Connecticut colonists acquired from the Native Americans the habit of smoking tobacco in pipes, and began cultivating the plant commercially, even though the Puritans referred to it as the "evil weed". The industry has weathered some major catastrophes, including a devastating hailstorm in 1929, and an epidemic of brown spot fungus in 2000, but is now in danger of disappearing altogether, given the value of the land to real estate speculators.
• White burley, in 1865, George Webb of Brown County, Ohio planted red burley seeds he had purchased, and found that a few of the seedlings had a whitish, sickly look. The air-cured leaf was found to be more mild than other types of tobacco.
• Wild tobacco, is native to the southwestern United States, Mexico, and parts of South America. Its botanical name is Nicotiana rustica.
• Y1 is a strain of tobacco cross-bred by Brown & Williamson in the 1970s to obtain an unusually high nicotine content. In the 1990's, the United States Food and Drug.
  
  

Cultivation of tobacco
Tobacco is cultivated annually, and can be harvested in several ways. In the oldest method still used today, the entire plant is harvested at once by cutting off the stalk at the ground with a tobacco knife. It is then speared onto sticks, four to six plants a stick and hung in a curing barn. In the 19th century, bright tobacco began to be harvested by pulling individual leaves off the stalk as they ripened. The leaves ripen from the ground upwards, so a field of tobacco may go through several so-called "pullings," more commonly known as cropping. Before this the crop needs to be topped when the pink flowers develop. Topping always refers to the removal of the tobacco flower before the leaves are systematically removed and, eventually, entirely harvested. As the industrial revolution took hold, harvesting wagons used to transport leaves were equipped with man-powered stringers, an apparatus that used twine to attach leaves to a pole. In modern times, large fields are harvested mechanically, although topping the flower and in some cases the plucking of immature leaves is still done by hand.

Curing of tobacco
Curing and subsequent aging allow for the slow oxidation and degradation of carotenoids in tobacco leaf. This produces certain compounds in the tobacco leaves, and gives a sweet hay, tea, rose oil, or fruity aromatic flavor that contributes to the "smoothness" of the smoke. Starch is converted to sugar, which glycates protein, and is oxidized into advanced glycation endproducts (AGEs), a caramelization process that also adds flavor. Inhalation of these AGEs in tobacco smoke contributes to atherosclerosis and cancer. Levels of AGE's is dependent on the curing method used.

Tobacco can be cured through several methods, including:

• Air cured tobacco is hung in well-ventilated barns and allowed to dry over a period of four to eight weeks. Air-cured tobacco is low in sugar, which gives the tobacco smoke a light, mild flavor, and high in nicotine. Cigar and burley tobaccos are air cured.
• Fire cured tobacco is hung in large barns where fires of hardwoods are kept on continuous or intermittent low smoulder and takes between three days and ten weeks, depending on the process and the tobacco. Fire curing produces a tobacco low in sugar and high in nicotine. Pipe tobacco, chewing tobacco, and snuff are fire cured.
• Flue cured tobacco was originally strung onto tobacco sticks, which were hung from tier-poles in curing barns (Aus: kilns, also traditionally called Oasts). These barns have flues run from externally-fed fire boxes, heat-curing the tobacco without exposing it to smoke, slowly raising the temperature over the course of the curing. The process generally takes about a week. This method produces cigarette tobacco that is high in sugar and has medium to high levels of nicotine.
• Sun-cured tobacco dries uncovered in the sun. This method is used in Turkey, Greece and other Mediterranean countries to produce oriental tobacco. Sun-cured tobacco is low in sugar and nicotine and is used in cigarettes.
  
  

Applications

Tobacco is consumed in many forms and through a number of different methods. Below are examples including, but not limited to, such forms and usage.

• Beedi are thin, often flavored, south Asian cigarettes made of tobacco wrapped in a tendu leaf, and secured with colored thread at one end.
• Chewing tobacco is the oldest way of consuming tobacco leaves. It is consumed orally, in two forms: through sweetened strands, or in a shredded form. When consuming the long sweetened strands, the tobacco is lightly chewed and compacted into a ball. When consuming the shredded tobacco, small amounts are placed at the bottom lip, between the gum and the teeth, where it is gently compacted, thus it can often be called dipping tobacco. Both methods stimulate the saliva glands, which led to the development of the spittoon.
• Cigars are tightly rolled bundles of dried and fermented tobacco, which is ignited so its smoke may be drawn into the smoker's mouth.
• Cigarettes are a product consumed through inhalation of smoke and manufactured from cured and finely cut tobacco leaves and reconstituted tobacco, often combined with other additives, then rolled or stuffed into a paper cylinder.
• Creamy snuffs are tobacco paste, consisting of tobacco, clove oil, glycerin, spearmint, menthol, and camphor, and sold in a toothpaste tube. It is marketed mainly to women in India, and is known by the brand names Ipco (made by Asha Industries), Denobac, Tona, Ganesh. It is locally known as "mishri" in some parts of Maharashtra.
• Dipping tobaccos are a form of smokeless tobacco. Dip is occasionally referred to as "chew", and because of this, it is commonly confused with chewing tobacco, which encompasses a wider range of products. A small clump of dip is 'pinched' out of the tin and placed between the lower or upper lip and gums.
• Gutka is a preparation of crushed betel nut, tobacco, and sweet or savory flavorings. It is manufactured in India and exported to a few other countries. A mild stimulant, it is sold across India in small, individual-size packets.
• Hookah is a single or multi-stemmed (often glass-based) water pipe for smoking. Originally from India, the hookah has gained immense popularity, especially in the Middle East. A hookah operates by water filtration and indirect heat. It can be used for smoking herbal fruits or moassel, a mixture of tobacco, flavouring and honey or glycerin.
• Kreteks are cigarettes made with a complex blend of tobacco, cloves and a flavoring "sauce". It was first introduced in the 1880s in Kudus, Java, to deliver the medicinal eugenol of cloves to the lungs.
• Roll-Your-Own, often called rollies or roll ups, are very popular, particularly in European countries. These are prepared from loose tobacco, cigarette papers and filters all bought separately. They are usually much cheaper to make.
• Pipe smoking typically consists of a small chamber (the bowl) for the combustion of the tobacco to be smoked and a thin stem (shank) that ends in a mouthpiece (the bit). Shredded pieces of tobacco are placed into the chamber and ignited.
• Snuff is a generic term for fine-ground smokeless tobacco products. Originally the term referred only to dry snuff, a fine tan dust popular mainly in the 18th century. Snuff powder originated in the UK town of Great Harwood, and was famously ground in the town's monument prior to local distribution and transport further up north to Scotland. There are two major varieties: European (dry) and American (moist)—though American snuff is often called dipping tobacco.
• Snus is a steam-cured moist powder tobacco product that is not fermented, and does not induce salivation. It is consumed by placing it in the mouth against the gums for an extended period of time. It is a form of snuff used in a manner similar to American dipping tobacco, but does not require regular spitting.
• Topical tobacco paste is sometimes recommended as a treatment for wasp, hornet, fire ant, scorpion, and bee stings.[37] An amount equivalent to the contents of a cigarette is mashed in a cup with about a 0.5 to 1 teaspoon of water to make a paste that is then applied to the affected area.
• Tobacco water is a traditional organic insecticide used in domestic gardening. Tobacco dust can be used similarly. It is produced by boiling strong tobacco in water, or by steeping the tobacco in water for a longer period. When cooled, the mixture can be applied as a spray, or 'painted' on to the leaves of garden plants, where it kills insects. Tobacco is however banned from use as pesticide in certified organic production.
  
  

Shipment / storage

Packaging
Virginia, Burley, Maryland, Kentucky and the like are packaged almost solely in cartons. The cartons are of internationally standard dimensions and weigh between 180 and 200 kg net. Since the leaf is deribbed where it is grown, leaf and ribs are packaged separately. Oriental tobacco and dark air-cured tobacco are generally packaged in jute bales, different weights being specific to different countries. Oriental tobaccos are generally Tonga manipulated, i.e. the tobacco leaves are compressed into bales in a random arrangement. Bales from Turkey, Greece and Albania are Sira-Pastal manipulated, i.e. the tobacco leaves are arranged in a single direction.

The dimensions are approximately standardized. Some countries (e.g. China, India) also package lower quality Virginia tobaccos in bales. Bales are generally wrapped in jute fabric. However, linen, palm leaves, banana leaves (Cuba), reed matting or best are also used.

Container transport
These days, tobacco is generally transported in 40' or 20' standard containers. Ventilated containers are only used for transport from regions with critical climatic conditions (e.g. Indonesia, Dominican Republic), subject to compliance with lower limits for water content of goods, packaging and flooring. Containers intended for loading have to be watertight and must not be contaminated in any way. Containers whose floors release a foreign odor, are contaminated by any substances or are too damp should be rejected. Below deck stowage is required, to rule out the possibility of exposure to rain or seawater or of overheating by day and cooling at night. Tobacco containers must not be stowed near heat sources.

Cargo handling
Containers are often stuffed with cartons via locks (comparable to refrigeration locks), which provide protection against rain and snowfall. If the cartons are handled in the open air, the cargo must be protected from rain and snow and the like, since losses are otherwise inevitable. When transporting leaf tobacco, the bales must be prevented from bumping against the hatch coaming, the ship's sides, container walls or the like during packing, as the leaves of excessively dry tobacco may break under the slightest mechanical stress and thereby lose value. Hooks or cargo nets must not be used; instead, the tobacco must be loaded on pallets. Point loads must not occur at the corners and edges of the bales.

Unmanufactured Tobacco
The main source of damage to tobacco leaf, strip or stem in transit is moisture either by contact with water or through being packed with an exceptionally high percentage of moisture. When packed containing excess moisture the tobacco will turn mouldy, ferment and become ‘off’ in flavour; these conditions will be more noticeable and severe towards the centre of the pack, whereas signs of mould and discolouration on the outer edges of the pack will rather indicate contact with water or excess moisture from external causes. Another source of damage to tobacco in transit is contamination by substances or liquids which give off pungent or penetrating odours. Damage by all oils can be very serious.

Tobacco which has been tainted due to close contact with substances such as creosote or phenol is not necessarily remedied by exposure to the open air. Tobacco can remain tainted if exposed to such substances, with subsequent loss of value. All damaged tobacco should be separated from the sound in order to prevent penetration of the damage. If wetted by fresh water tobacco should be opened up and allowed to dry thoroughly to prevent mildew or mould. Snuff may be extracted from tobacco damaged by fresh water. If wet by salt water the damaged portion must be quickly separated from the sound in order to prevent penetration. It may be possible for the wet tobacco to be reconditioned and sold as an inferior grade. Tainted tobacco may not lose the taint even when removed from the cause.

Immediate survey is desirable. The weight of tobacco damaged by moisture should be subject to proper allowance for water, which can be ascertained by comparison of the weights of sound and damaged tobacco. Depreciation can arise:

• Where a proportion of the bale is damaged by water, the sound tobacco absorbing extra moisture.
• When garbling it is found necessary to cut the leaves to remove the damaged portion, leaving mutilated leaves in the bale.
  
  

Cigars, Cigarettes and Pipe Tobacco:

The main causes of damage to these are the same as for unmanufactured tobacco. Heat and/or moisture may adversely affect the retail packaging and could have an effect on the contents. In order to identify content damage the retail pack must be destroyed by opening in order to examine the contents, should the survey proceed in that direction. In dealing with matters such as suggested, rejection of contents by damage, the surveyor must not overlook the value aspect which attaches to any local customs duty arrangements.

Additional information on tobacco
Tobacco is shipped in a variety of categories, leaf, strip and stem with leaf tobacco including the highest grades. The main issues for the carriage of tobacco are its susceptibility to damage from:

• Excess moisture within the tobacco causing mould, fermentation and “off flavour”
• Condensation within the cargo hold/container
• Tainting from other cargoes such as timer, creosote and phenol
• Infestation from the Lasioderma beetle
  
  

The main problems in transporting tobacco result from its hygroscopicity: conditioning of the tobaccos with respect to their water content (10 - 12% Virginia, Burley, 12 - 14% Oriental) is tightly specified. If the relative humidity is excessive, the tobacco absorbs so much water vapor that it becomes a nutrient medium for molds. Mold, mustiness, mildew stains and a musty odor reduce the quality of the tobacco. Oriental tobaccos are the most sensitive of all tobaccos to the effects of moisture. If the water content is higher than the recommended values (14%) or ventilation is inadequate (dead air zones), mustiness and decay may arise within just three days due to the mold Oespora tabaci. Depending on the type of mold, white, gray, green or black spots are visible in the tobacco bales.

Humidity, temperatures above 25°C and stack pressure promote postfermentation on extended storage. Stack pressure causes the lowest layers of tobacco to deform, if excessively damp. The bales become compacted and completely worthless. Distortion may also arise in tobacco which has been improperly set down ashore (uneven ground). Not only if storage conditions are excessively dry, but also if the optimum water content is exceeded, the tobacco loses aroma due to water vapor release. The tobacco then becomes less enjoyable, taking on a hay-like, bitter, sharp flavor. It may also become hard and brittle, so meaning that the leaves break under the slightest mechanical stress and eventually end up as powder. Before the cargo is accepted, a certificate stating water content should be demanded from the consignor. If the tobacco is accepted at a later time (e.g. in the case of intermediate storage), the water content may have changed due to external influences and retesting is necessary.

Packaging of tobacco includes hogsheads, bales, cases and cartons. Containerised stowage is normally either in:

• 20 High Vent : Moisture content over 27%. Includes black tobacco from Venezuela, Dominican Republic, Cuba and cover leaf from Indonesia.
• 20 Integral Reefer : New business for quality leaf tobacco from Indonesia and Sri Lanka at minus 20 degrees Celsius. Bobbin reels for this carriage are often returned under refrigeration when empty.
• 20/40 GP : Various grades with moisture below 25%. Container is prepared as for carriage of coffee/cocoa. A moisture absorbing strip stretched over the inner roof is an alternative to the use of "Dry- Bags".
  
  

Container Cleanliness
Containers selected for stuffing with tobacco must be thoroughly cleaned and treated with an insecticide. A surveyor will normally inspect the container and issue a cleanliness certificate prior to stuffing.

General Stowage Precautions

• Away from heat tank tops and any sources of heat including radiant heat on deck
• Stowage with tea is not allowed and timber can also taint tobacco if strong smelling
• No Dockers hooks to be used for handling and bales must be kept clear of the steelwork of the container.
• Care must be taken not to contaminate the bales with dust or infestation from other cargoes
• Bales of tobacco shall never be stowed on their sides and not be stuffed/unstuffed during rain, snow or damp fog
• Only bales of equal size to be stowed on top of each other to avoid deformation
• Moist and distorted bales must not be loaded
  
  

Maximum stack heights:

Type	Stack height
Oriental tobacco	2.50 m. (Greece, Black sea)
	3.60 m. (Smyrna tobacco)
Sumatra/Bornea tobacco (only wrapping leaves)	7 bales high
Brazilian tobacco (no wrapping leaves)	7 -9 bales high

Ventilation
Tobacco requires particular temperature, humidity/moisture and possibly ventilation conditions. Conventional general cargo transport is becoming ever more unusual, having been largely replaced by container transport.

Tobacco is generally transported in 40' or 20' standard containers. Ventilated containers are only used for transport from regions with critical climatic conditions, such as Indonesia or the Dominican Republic. If tobacco is loaded as conventional general cargo, ventilation is not normally required, provided that the water content of the tobacco corresponds to set values and there is no risk of sweat formation. If this is not the case, advises an air exchange rate of 6 changes/hour (airing) or just return air. Over-vigorous ventilation may dry out the tobacco and cause crumbling or fragmentation damage. For this reason, the system is switched to only vigorous return air.

Infestation
As a rule shippers will fumigate tobacco to kill all harmful insects and larvae before shipment and specifically the Lasioderma beetle. Not all eggs present inside the tobacco will be destroyed during the fumigation and larvae can hatch after about 2 weeks (in temperature above 20°C ) and damage the tobacco. In order to minimise the chances of tobacco contracting insects from other cargoes liable to be infested (cereals, groundnuts), cargoes to be loaded in the same container with tobacco should be vetted. However, It is recommended that normally tobacco will be stowed by itself.

The aerosol “Rentofume” can be used for fumigation being a legally permitted insecticide. Vapours released are extremely toxic (MAC-value 10 PPM). No persons are allowed in the vicinity of containers undergoing fumigation unless equipped with breathing apparatus. Ventilation must be closed for the duration of the gassing period (about 24 hours) thereafter the containers must be thoroughly ventilated for a couple of hours.

Risk factors

• Self-heating / Spontaneous combustion
• Moisture
• Odor
• Contamination
• Mechanical influences
• Storage height
• Toxicity / Hazards to health
• Shrinkage / Shortage
• Insect infestation / Diseases