Geography.

Marseille is the second-largest metropolitan area in France after Paris. To the east, starting in the small fishing village of Callelongue on the outskirts of Marseille and stretching as far as Cassis, are the Calanques, a rugged coastal area interspersed with small fjord-like inlets. Farther east still are the Sainte-Baume (a mountain ridge rising from a forest of deciduous trees), the city of Toulon and the French Riviera. To the north of Marseille, beyond the low Garlaban and Etoile mountain ranges, is the Mont Sainte Victoire. To the west of Marseille is the former artists' colony of l'Estaque; farther west are the Côte Bleue, the Gulf of Lion and the Camargue region in the Rhône delta. The airport lies to the north west of the city at Marignane on the Étang de Berre.  The city's main thoroughfare (the wide boulevard called the Canebière) stretches eastward from the Old Port to the Réformés quarter. Two large forts flank the entrance to the Old Port—Fort Saint-Nicolas on the south side and Fort Saint-Jean on the north. Farther out in the Bay of Marseille is the Frioul archipelago which comprises four islands, one of which, If, is the location of Château d'If, made famous by the Dumas novel "The Count of Monte Cristo". The main commercial centre of the city intersects with the Canebière at Rue St Ferréol and the Centre Bourse (one of the city's main shopping malls). The centre of Marseille has several pedestrianised zones, most notably Rue St Ferréol, Cours Julien near the Music Conservatory, the Cours Honoré-d'Estienne-d'Orves off the Old Port and the area around the Hôtel de Ville. To the south east of central Marseille in the 6th arrondissement are the Prefecture and the monumental fountain of Place Castellane, an important bus and metro interchange. To the south west are the hills of the 7th and 8th arrondissements, dominated by the basilica of Notre-Dame de la Garde. Marseille's main railway station—Gare de Marseille Saint-Charles—is north of the Centre Bourse in the 1st arrondissement; it is linked by the Boulevard d'Athènes to the Canebière.

Climate.

The city has a hot-summer mediterranean climate (Köppen: "Csa") with cool-mild winters with moderate rainfall and hot, mostly dry summers. December, January, and February are the coldest months, averaging temperatures of around during the day and at night. July and August are the hottest months, averaging temperatures of around during the day and at night in the Marignane airport ( from Marseille) but in the city near the sea the average high temperature is in July.  Marseille is officially the sunniest major city in France with over 2,800 hours of sunshine while the average sunshine in the country is around 1,950 hours. It is also the driest major city with only of precipitation annually, especially thanks to the Mistral, a cold, dry wind originating in the Rhône Valley that occurs mostly in winter and spring and which generally brings clear skies and sunny weather to the region. Less frequent is the Sirocco, a hot, sand-bearing wind, coming from the Sahara Desert. Snowfalls are infrequent; over 50% of years do not experience a single snowfall.  The hottest temperature was on 26 July 1983 during a great heat wave, the lowest temperature was on 13 February 1929 during a strong cold wave.

History.

Marseille was a Gauls port center that became the Greek colony of Massalia circa 600 BC, and was populated by Greeks settlers from Phocaea (modern Foça, Turkey). It became the preeminent Greek "polis" in the Hellenized region of southern Gaul. The city-state sided with the Roman Republic against Carthage during the Second Punic War (218–201 BC), retaining its independence and commercial empire throughout the western Mediterranean even as Rome expanded into Western Europe and North Africa. However, the city lost its independence following the Roman Siege of Massilia in 49 BC, during Caesar's Civil War, in which Massalia sided with the exiled faction at war with Julius Caesar. Afterward the Gallo-Roman culture was initiated.  Marseille continued to prosper as a Gallo-Roman city, becoming an early center of Christianity during the Western Roman Empire. The city maintained its position as a premier maritime trading hub even after its capture by the Visigoths in the 5th century AD, although the city went into decline following the sack of 739 AD by the forces of Charles Martel. It became part of the County of Provence during the 10th century, although its renewed prosperity was curtailed by the Black Death of the 14th century and sack of the city by the Crown of Aragon in 1423. The city's fortunes rebounded with the ambitious building projects of René of Anjou, Count of Provence, who strengthened the city's fortifications during the mid-15th century. During the 16th century the city hosted a naval fleet with the combined forces of the Franco-Ottoman alliance, which threatened the ports and navies of Genoa and the Holy Roman Empire.  Marseille lost a significant portion of its population during the Great Plague of Marseille in 1720, but the population had recovered by mid-century. In 1792 the city became a focal point of the French Revolution and though France's national anthem was born in Strasbourg, it was first sang in Paris by volunteers from Marseille, hence the name the crowd gave it: "La Marseillaise". The Industrial Revolution and establishment of the French Empire during the 19th century allowed for further expansion of the city, although it was occupied by the German Wehrmacht in November 1942 and subsequently heavily damaged during World War II. The city has since become a major center for immigrant communities from former French colonies, such as French Algeria.

Economy.

Marseille is a major French centre for trade and industry, with excellent transportation infrastructure (roads, sea port and airport). Marseille Provence Airport is the fourth largest in France. In May 2005, the French financial magazine "L'Expansion" named Marseille the most dynamic of France's large cities, citing figures showing that 7,200 companies had been created in the city since 2000. Marseille is also France's second largest research centre with 3,000 research scientists within Aix Marseille University., the Marseille metropolitan area had a GDP amounting to $60.3 billion, or $36,127 per capita (purchasing power parity).

Port.

Historically, the economy of Marseille was dominated by its role as a port of the French Empire, linking the North African colonies of Algeria, Morocco and Tunisia with Metropolitan France. The Old Port was replaced as the main port for trade by the Port de la Joliette during the Second Empire and now contains restaurants, offices, bars and hotels and functions mostly as a private marina. The majority of the port and docks, which experienced decline in the 1970s after the oil crisis, have been recently redeveloped with funds from the European Union. Fishing remains important in Marseille and the food economy of Marseille is fed by the local catch; a daily fish market is still held on the Quai des Belges of the Old Port.  The economy of Marseille and its region is still linked to its commercial port, the first French port and the fifth European port by cargo tonnage, which lies north of the Old Port and eastern in Fos-sur-Mer. Some 45,000 jobs are linked to the port activities and it represents 4 billion euros added value to the regional economy. 100 million tons of freight pass annually through the port, 60% of which is petroleum, making it number one in France and the Mediterranean and number three in Europe. However, in the early 2000s, the growth in container traffic was being stifled by the constant strikes and social upheaval. The port is among the 20th firsts in Europe for container traffic with 1,062,408 TEU and new infrastructures have already raised the capacity to 2M TEU. Petroleum refining and shipbuilding are the principal industries, but chemicals, soap, glass, sugar, building materials, plastics, textiles, olive oil, and processed foods are also important products. Marseille is connected with the Rhône via a canal and thus has access to the extensive waterway network of France. Petroleum is shipped northward to the Paris basin by pipeline. The city also serves as France's leading centre of oil refining.

Companies, services and high technologies.

In recent years, the city has also experienced a large growth in service sector employment and a switch from light manufacturing to a cultural, high-tech economy. The Marseille region is home to thousands of companies, 90% of which are small and medium enterprises with less than 500 employees. Among the most famous ones are CMA CGM, container-shipping giant; Compagnie maritime d'expertises (Comex), world leader in sub-sea engineering and hydraulic systems; Airbus Helicopters, an Airbus division; Azur Promotel, an active real estate development company; "La Provence", the local daily newspaper; RTM, Marseille's public transport company; and Société Nationale Maritime Corse Méditerranée (SNCM), a major operator in passenger, vehicle and freight transportation in the Western Mediterranean. The urban operation Euroméditerranée has developed a large offer of offices and thus Marseille hosts one of the main business district in France.  Marseille is the home of three main technopoles: Château-Gombert (technological innovations), Luminy (biotechnology) and La Belle de Mai (17,000 sq.m. of offices dedicated to multimedia activities).

Tourism and attractions.

The port is also an important arrival base for millions of people each year, with 2.4 million including 890,100 from cruise ships. With its beaches, history, architecture and culture (24 museums and 42 theatres), Marseille is one of the most visited cities in France, with 4.1 million visitors in 2012. Marseille is ranked 86th in the world for business tourism and events, advancing from the 150th spot one year before. The number of congress days hosted on its territory increased from 109,000 in 1996 to almost 300,000 in 2011.  They take place in three main sites, the Palais du Pharo, Palais des Congrès et des Expositions (Parc Chanot) and World Trade Center. In 2012 Marseille hosted the World Water Forum. Several urban projects have been developed to make Marseille attractive. Thus new parks, museums, public spaces and real estate projects aim to improve the city's quality of life (Parc du 26e Centenaire, Old Port of Marseille, numerous places in Euroméditerranée) to attract firms and people. Marseille municipality acts to develop Marseille as a regional nexus for entertainment in the south of France with high concentration of museums, cinemas, theatres, clubs, bars, restaurants, fashion shops, hotels, and art galleries.

Employment.

Unemployment in the economy fell from 20% in 1995 to 14% in 2004. However, Marseille unemployment rate remains higher than the national average. In some parts of Marseille, youth unemployment is reported to be as high as 40%.

Administration.

The city of Marseille is divided into 16 municipal arrondissements, which are themselves informally divided into 111 neighbourhoods (French: "quartiers"). The arrondissements are regrouped in pairs, into 8 sectors, each with a mayor and council (like the arrondissements in Paris and Lyon). Municipal elections are held every six years and are carried out by sector. There are 303 councilmembers in total, two-thirds sitting in the sector councils and one third in the city council.  The 9th arrondissement of Marseille is the largest in terms of area because it comprises parts of Calanques National Park. With a population of 89,316 (2007), the 13th arrondissement of Marseille is the most populous one.  From 1950 to the mid-1990s, Marseille was a Socialist (PS) and Communist (PCF) stronghold. Gaston Defferre (PS) was consecutively reelected six times as Mayor of Marseille from 1953 until his death in 1986. He was succeeded by Robert Vigouroux of the European Democratic and Social Rally (RDSE). Jean-Claude Gaudin of the right-wing UMP was elected Mayor of Marseille in 1995. Gaudin was reelected in 2001, 2008 and 2014.  In recent years, the Communist Party has lost most of its strength in the northern boroughs of the city, whereas the National Front has received significant support. At the last municipal election in 2014, Marseille was divided between the northern arrondissements dominated by the left (PS) and far-right (FN) and the southern part of town dominated by the right-wing (UMP). Marseille is also divided in twelve cantons, each of them sending two members to the Departmental Council of the Bouches-du-Rhône department.

Population.

Immigration.

Because of its pre-eminence as a Mediterranean port, Marseille has always been one of the main gateways into France. This has attracted many immigrants and made Marseille a cosmopolitan melting pot. By the end of the 18th century about half the population originated from elsewhere in Provence mostly and also from southern France.  Economic conditions and political unrest in Europe and the rest of the world brought several other waves of immigrants during the 20th century: Greeks and Italians started arriving at the end of the 19th century and in the first half of the 20th century, up to 40% of the city's population was of Italian origin; Russians in 1917; Armenians in 1915 and 1923; Vietnamese in the 1920s, 1954 and after 1975; Corsicans during the 1920s and 1930s; Spanish after 1936; Maghrebis (both Arab and Berber) in the inter-war period; Sub-Saharan Africans after 1945; Maghrebi Jews in the 1950s and 1960s; the Pieds-Noirs from the former French Algeria in 1962; and then from Comoros. In 2006, it was reported that 70,000 city residents were considered to be of Maghrebi origin, mostly from Algeria. The second largest group in Marseille in terms of single nationalities were from the Comoros, amounting to some 45,000 people.  Currently, over one third of the population of Marseille can trace their roots back to Italy. Marseille also has the second-largest Corsican and Armenian populations of France. Other significant communities include Maghrebis, Turks, Comorians, Chinese, and Vietnamese.  In 1999, in several arrondissements, about 40% of the young people under 18 were of Maghrebi origin (at least one immigrant parent).  Since 2013 a significant number of Eastern European immigrants have settled in Marseille, attracted by better job opportunities and the good climate of this Mediterranean city. The main nationalities of the immigrants are Romanians and Poles.

Religion.

According to data from 2010, major religious communities in Marseille include:

Culture.

Marseille is a city that has its own unique culture and is proud of its differences from the rest of France. Today it is a regional centre for culture and entertainment with an important opera house, historical and maritime museums, five art galleries and numerous cinemas, clubs, bars and restaurants.  Marseille has a large number of theatres, including La Criée, Le Gymnase and the Théâtre Toursky. There is also an extensive arts centre in La Friche, a former match factory behind the Saint-Charles station. The Alcazar, until the 1960s a well known music hall and variety theatre, has recently been completely remodelled behind its original façade and now houses the central municipal library. Other music venues in Marseille include Le Silo (also a theatre) and GRIM.  Marseille has also been important in the arts. It has been the birthplace and home of many French writers and poets, including,, Pierre Bertas, Edmond Rostand and André Roussin. The small port of l'Estaque on the far end of the Bay of Marseille became a favourite haunt for artists, including Auguste Renoir, Paul Cézanne (who frequently visited from his home in Aix), Georges Braque and Raoul Dufy.

Multi-cultural influences.

Rich and poor neighborhoods exist side-by-side. Although the city is not without crime, Marseille has a larger degree of multicultural tolerance. Urban geographers say the city's geography, being surrounded by mountains, helps explain why Marseille does not have the same problems as Paris. In Paris, ethnic areas are segregated and concentrated in the periphery of the city. Residents of Marseille are of diverse origins, yet appear to share a similar particular identity. An example of shared identity is seen at the public beaches, where ethnic groups sit on the sand together. Another example is how Marseille responded in 2005, when ethnic populations living in other French cities' suburbs rioted, but Marseille remained relatively calm.  Marseille served as the European Capital of Culture for 2013 along with Košice. It was chosen to give a 'human face' to the European Union to celebrate cultural diversity and to increase understanding between Europeans. One of the intentions of highlighting culture is to help reposition Marseille internationally, stimulate the economy, and help to build better interconnection between groups. Marseille-Provence 2013 (MP2013) featured more than 900 cultural events held throughout Marseille and the surrounding communities. These cultural events generated more than 11 million visits. The European Capital of Culture was also the occasion to unveil more than 600 million euros in new cultural infrastructure in Marseille and its environs, including the MuCEM designed by Rudy Ricciotti.  Early on, immigrants came to Marseille locally from the surrounding Provence region. By the 1890s immigrants came from other regions of France as well as Italy. Marseille became one of Europe’s busiest port by 1900. Marseille has served as a major port where immigrants from around the Mediterranean arrive. Marseille continued to be multicultural. Armenians from the Ottoman empire began arriving in 1913. In the 1930s, Italians settled in Marseille. After World War II, a wave of Jewish immigrants from North Africa arrived. In 1962, a number of French colonies gained their independence, and the French citizens from Algeria, Morocco, and Tunisia arrived in Marseille. The city had an economic downturn and lost many jobs. Those who could afford to move left and the poorest remained. For a while, the mafia appeared to run the city, and for a period of time the communist party was prominent.  Multi-cultural Marseille can be observed by a visitor at the market at Noailles, also called Marché des Capucins, in old town near the Old Port. There, Lebanese bakeries, an African spice market, Chinese and Vietnamese groceries, fresh vegetables and fruit, shops selling couscous, shops selling Caribbean food are side by side with stalls selling shoes and clothing from around the Mediterranean. Nearby, people sell fresh fish and men from Tunisia drink tea.

Tarot de Marseille.

The most commonly used tarot deck takes its name from the city; it has been called the "Tarot de Marseille" since the 1930s—a name coined for commercial use by the French cardmaker and cartomancer Paul Marteau, owner of B–P Grimaud. Previously this deck was called "Tarot italien" (Italian Tarot) and even earlier it was simply called Tarot. Before being "de Marseille", it was used to play the local variant of tarocchi before it became used in cartomancy at the end of the 18th century, following the trend set by Antoine Court de Gébelin. The name "Tarot de Marseille" (Marteau used the name "ancien Tarot de Marseille") was used by contrast to other types of Tarots such as "Tarot de Besançon"; those names were simply associated with cities where there were many cardmakers in the 18th century (previously several cities in France were involved in cardmaking).  Another local tradition is the making of santons, small hand-crafted figurines for the traditional Provençal Christmas creche. Since 1803, starting on the last Sunday of November, there has been a Santon Fair in Marseille; it is currently held in the Cours d'Estienne d'Orves, a large square off the Vieux-Port.

Opera.

Marseille's main cultural attraction was, since its creation at the end of the 18th century and until the late 1970s, the Opéra. Located near the Old Port and the Canebière, at the very heart of the city, its architectural style was comparable to the classical trend found in other opera houses built at the same time in Lyon and Bordeaux. In 1919, a fire almost completely destroyed the house, leaving only the stone colonnade and peristyle from the original façade. The classical façade was restored and the opera house reconstructed in a predominantly Art Deco style, as the result of a major competition. Currently the Opéra de Marseille stages six or seven operas each year.  Since 1972, the Ballet national de Marseille has performed at the opera house; its director from its foundation to 1998 was Roland Petit.

Popular events and festivals.

There are several popular festivals in different neighborhoods, with concerts, animations, and outdoor bars, like the Fête du Panier in June. On 21 June, there are dozens of free concerts in the city as part of France's Fête de la Musique, featuring music from all over the world. Being free events, many Marseille residents attend.  Marseille hosts a Gay Pride event in early July. In 2013, Marseille hosted Europride, an international LGBT event, 10 July20. At the beginning of July, there is the International Documentary Festival. At the end of September, the electronic music festival Marsatac takes place. In October, the "Fiesta des Suds" offers many concerts of world music.

Hip hop music.

Marseille is also well known in France for its hip hop music. Bands like IAM originated from Marseille and initiated the rap phenomenon in France. Other known groups include Fonky Family, Psy 4 de la Rime (including rappers Soprano and Alonzo), and Keny Arkana. In a slightly different way, ragga music is represented by Massilia Sound System.

Films set in Marseille.

Marseille has been the setting for many films.

Marseille in television.

The French television series "Plus belle la vie" is set in an imaginary quarter, "Le Mistral", of Marseille; it was in fact filmed in the Panier quarter. Very few characters in the series speak with the accent of Marseille: most speak with the accent of Paris or Tours.  The Netflix series "Marseille" is set in the city in the 2010s.

Main sights.

Marseille is listed as a major centre of art and history. The city has many museums and galleries and there are many ancient buildings and churches of historical interest.

Central Marseille.

Most of the attractions of Marseille (including shopping areas) are located in the 1st, 2nd, 6th and 7th arrondissements. These include:

Museums.

In addition to the two in the Centre de la Vieille Charité, described above, the main museums are:

Outside central Marseille.

The main attractions outside the city centre include:

Education.

A number of the faculties of the three universities that comprise Aix-Marseille University are located in Marseille:  In addition Marseille has four "grandes écoles":  The main French research bodies including the CNRS, INSERM and INRA are all well represented in Marseille. Scientific research is concentrated at several sites across the city, including Luminy, where there are institutes in developmental biology (the IBDML), immunology (CIML), marine sciences and neurobiology (INMED), at the CNRS Joseph Aiguier campus (a world-renowned institute of molecular and environmental microbiology) and at the Timone hospital site (known for work in medical microbiology). Marseille is also home to the headquarters of the IRD, which promotes research into questions affecting developing countries.

Transport.

International and regional transport.

The city is served by an international airport, Marseille Provence Airport, located in Marignane. The airport is the fifth busiest French airport, and known the 4th most important European traffic growth in 2012. An extensive network of motorways connects Marseille to the north and west (A7), Aix-en-Provence in the north (A51), Toulon (A50) and the French Riviera (A8) to the east.  Gare de Marseille Saint-Charles is Marseille's main railway station. It operates direct regional services to Aix-en-Provence, Briançon, Toulon, Avignon, Nice, Montpellier, Toulouse, Bordeaux, Nantes, etc. Gare Saint-Charles is also one of the main terminal stations for the TGV in the south of France making Marseille reachable in three hours from Paris (a distance of over 750 km) and just over one and a half hours from Lyon. There are also direct TGV lines to Lille, Brussels, Nantes, Geneva, Strasbourg and Frankfurt as well as Eurostar services to London (just in the summer) and Thello services to Milan (just one a day), via Nice and Genoa. In addition, the night train (Intercités de Nuit) from Luxembourg and Strasbourg stops here on its way to Nice, whereas the night train from Paris to Nice serves the Gare de Marseille-Blancarde.  There is a new long distance bus station adjacent to new modern extension to the Gare Saint-Charles with destinations mostly to other Bouches-du-Rhône towns, including buses to Aix-en-Provence, Cassis, La Ciotat and Aubagne. The city is also served with 11 other regional trains stations in the east and the north of the city.  Marseille has a large ferry terminal, the "Gare Maritime", with services to Corsica, Sardinia, Algeria and Tunisia.

Public transport.

Marseille is connected by the Marseille Métro train system operated by the "Régie des transports de Marseille" (RTM). It consists of two lines: Line 1 (blue) between Castellane and La Rose opened in 1977 and Line 2 (red) between Sainte-Marguerite-Dromel and Bougainville opened between 1984 and 1987. An extension of the Line 1 from Castellane to La Timone was completed in 1992, another extension from La Timone to La Fourragère ( and 4 new stations) was opened in May 2010. The Métro system operates on a turnstile system, with tickets purchased at the nearby adjacent automated booths. Both lines of the Métro intersect at Gare Saint-Charles and Castellane. Three bus rapid transit lines are under construction to better connect the Métro to farther places (Castellane -> Luminy; Capitaine Gèze – La Cabucelle -> Vallon des Tuves; La Rose -> Château Gombert – Saint Jérome).  An extensive bus network serves the city and suburbs of Marseille, with 104 lines and 633 buses. The three lines of the tramway, opened in 2007, go from the CMA CGM Tower towards Les Caillols.  As in many other French cities, a bike-sharing service nicknamed "Le vélo", free for trips of less than half an hour, was introduced by the city council in 2007.  A free ferry service operates between the two opposite quays of the Old Port. From 2011 ferry shuttle services operate between the Old Port and Pointe Rouge; in spring 2013 it will also run to l'Estaque. There are also ferry services and boat trips available from the Old Port to Frioul, the Calanques and Cassis.

Sport.

The city boasts a wide variety of sports facilities and teams. The most popular team is the city's football club, Olympique de Marseille, which was the finalist of the UEFA Champions League in 1991, before winning the competition in 1993. The club also became finalists of the UEFA Europa League in 1999, 2004 and 2018. The club had a history of success under then-owner Bernard Tapie. The club's home, the Stade Vélodrome, which can seat around 67,000 people, also functions for other local sports, as well as the national rugby team. Stade Velodrome hosted a number of games during the 1998 FIFA World Cup, 2007 Rugby World Cup, and UEFA Euro 2016. The local rugby teams are Marseille XIII and Marseille Vitrolles Rugby. Marseille is famous for its important pétanque activity, it is even renowned as the "pétanque capitale". In 2012 Marseille hosted the Pétanque World Championship and the city hosts every year the Mondial la Marseillaise de pétanque, the main pétanque competition. Sailing is a major sport in Marseille. The wind conditions allow regattas in the warm waters of the Mediterranean. Throughout most seasons of the year it can be windy while the sea remains smooth enough to allow sailing. Marseille has been the host of 8 (2010) Match Race France events which are part of the World Match Racing Tour. The event draws the world's best sailing teams to Marseille. The identical supplied boats (J Boats J-80 racing yachts) are raced two at a time in an on the water dogfight which tests the sailors and skippers to the limits of their physical abilities. Points accrued count towards the World Match Racing Tour and a place in the final event, with the overall winner taking the title ISAF World Match Racing Tour Champion. Match racing is an ideal sport for spectators in Marseille, as racing in close proximity to the shore provides excellent views. The city was also considered as a possible venue for 2007 America's Cup.  Marseille is also a place for other water sports such as windsurfing and powerboating. Marseille has three golf courses. The city has dozens of gyms and several public swimming pools. Running is also popular in many of Marseille's parks such as Le Pharo and Le Jardin Pierre Puget. An annual footrace is held between the city and neighbouring Cassis: the Marseille-Cassis Classique Internationale.

Notable people.

Marseille was the birthplace of:

International relations.

Twin towns – sister cities.

Marseille is twinned with 14 cities, all of them being a port city, with the exception of Marrakech.

Partner cities.

In addition, Marseille has signed various types of formal agreements of cooperation with 27 cities all over the world:

Marseille (, also spelled in English as Marseilles;, ; ) is the prefecture of the department of Bouches-du-Rhône and region of Provence-Alpes-Côte d'Azur in France. It is located on the Mediterranean coast near the mouth of the Rhône. The city covers an area of and had a population of 870,018 in 2016. Its metropolitan area, which extends over is the third-largest in France after those of Paris and Lyon, with a population of 1,831,500 as of 2010.

<mapframe text="Carte occitane de Marseille (provençal)-(Geoccitania:IEO-BdTopoc)."latitude="43.299197" longitude="5.369225" zoom="10" lang="oc" width="285" height="206" align="right" />Marseille (en provençal : "Marselha" [maʁˈsɛ.jɔ], prononcé localement [maʁˈsi.jɔ]) est une commune du Sud-Est de la France, chef-lieu du département des Bouches-du-Rhône et préfecture de la région Provence-Alpes-Côte d'Azur.


Definition.

In Europe, the term is "medicinal product", and it is defined by EU law as:  In the US, a "drug" is:

Usage.

Drug use among elderly Americans has been studied; in a group of 2377 people with average age of 71 surveyed between 2005 and 2006, 84% took at least one prescription drug, 44% took at least one over-the-counter (OTC) drug, and 52% took at least one dietary supplement; in a group of 2245 elderly Americans (average age of 71) surveyed over the period 2010 – 2011, those percentages were 88%, 38%, and 64%.

Classification.

One of the key classifications is between traditional small molecule drugs; usually derived from chemical synthesis, and biologic medical products; which include recombinant proteins, vaccines, blood products used therapeutically (such as IVIG), gene therapy, and cell therapy (for instance, stem cell therapies).  Pharmaceuticals or drugs or medicines are classified in various other groups besides their origin on the basis of pharmacological properties like mode of action and their pharmacological action or activity, such as by chemical properties, mode or route of administration, biological system affected, or therapeutic effects. An elaborate and widely used classification system is the Anatomical Therapeutic Chemical Classification System (ATC system). The World Health Organization keeps a list of essential medicines.  A sampling of classes of medicine includes: Pharmaceuticals may also be described as "specialty", independent of other classifications, which is an ill-defined class of drugs that might be difficult to administer, require special handling during administration, require patient monitoring during and immediately after administration, have particular regulatory requirements restricting their use, and are generally expensive relative to other drugs.

Types of medicines.

For the central nervous system.

Drugs affecting the central nervous system include: Psychedelics, hypnotics, anaesthetics, antipsychotics, eugeroics, antidepressants (including tricyclic antidepressants, monoamine oxidase inhibitors, lithium salts, and selective serotonin reuptake inhibitors (SSRIs)), antiemetics, Anticonvulsants/antiepileptics, anxiolytics, barbiturates, movement disorder (e.g., Parkinson's disease) drugs, stimulants (including amphetamines), benzodiazepines, cyclopyrrolones, dopamine antagonists, antihistamines, cholinergics, anticholinergics, emetics, cannabinoids, and 5-HT (serotonin) antagonists.

For pain.

The main classes of painkillers are NSAIDs, opioids and Local anesthetics.  For consciousness (anesthetic drugs)  Some anesthetics include Benzodiazepines and Barbiturates.

For musculo-skeletal disorders.

The main categories of drugs for musculoskeletal disorders are: NSAIDs (including COX-2 selective inhibitors), muscle relaxants, neuromuscular drugs, and anticholinesterases.

For the ear, nose and oropharynx.

Antibiotics, sympathomimetics, antihistamines, anticholinergics, NSAIDs, corticosteroids, antiseptics, local anesthetics, antifungals, cerumenolytic

For the respiratory system.

bronchodilators, antitussives, mucolytics, decongestantsinhaled and systemic corticosteroids, Beta2-adrenergic agonists, anticholinergics, Mast cell stabilizers. Leukotriene antagonists

For endocrine problems.

androgens, antiandrogens, estrogens, gonadotropin, corticosteroids, human growth hormone, insulin, antidiabetics (sulfonylureas, biguanides/metformin, thiazolidinediones, insulin), thyroid hormones, antithyroid drugs, calcitonin, diphosphonate, vasopressin analogues

For the reproductive system or urinary system.

antifungal, alkalinizing agents, quinolones, antibiotics, cholinergics, anticholinergics, antispasmodics, 5-alpha reductase inhibitor, selective alpha-1 blockers, sildenafils, fertility medications

For obstetrics and gynecology.

NSAIDs, anticholinergics, haemostatic drugs, antifibrinolytics, Hormone Replacement Therapy (HRT), bone regulators, beta-receptor agonists, follicle stimulating hormone, luteinising hormone, LHRH gamolenic acid, gonadotropin release inhibitor, progestogen, dopamine agonists, oestrogen, prostaglandins, gonadorelin, clomiphene, tamoxifen, Diethylstilbestrol

For the skin.

emollients, anti-pruritics, antifungals, antiseptics, scabicides, pediculicides, tar products, vitamin A derivatives, vitamin D analogues, keratolytics, abrasives, systemic antibiotics, topical antibiotics, hormones, desloughing agents, exudate absorbents, fibrinolytics, proteolytics, sunscreens, antiperspirants, corticosteroids, immune modulators

For infections and infestations.

antibiotics, antifungals, antileprotics, antituberculous drugs, antimalarials, anthelmintics, amoebicides, antivirals, antiprotozoals, probiotics, prebiotics, antitoxins and antivenoms.

For the immune system.

vaccines, immunoglobulins, immunosuppressants, interferons, monoclonal antibodies

For allergic disorders.

anti-allergics, antihistamines, NSAIDs, Corticosteroids

For nutrition.

Tonics, electrolytes and mineral preparations (including iron preparations and magnesium preparations), parenteral nutritions, vitamins, anti-obesity drugs, anabolic drugs, haematopoietic drugs, food product drugs

For neoplastic disorders.

cytotoxic drugs, therapeutic antibodies, sex hormones, aromatase inhibitors, somatostatin inhibitors, recombinant interleukins, G-CSF, erythropoietin

For diagnostics.

contrast media

For euthanasia.

A euthanaticum is used for euthanasia and physician-assisted suicide. Euthanasia is not permitted by law in many countries, and consequently, medicines will not be licensed for this use in those countries.

Administration.

Administration is the process by which a patient takes a medicine. There are three major categories of drug administration; enteral (via the human gastrointestinal tract), injection, and other (dermal, nasal, ophthalmic, otologic, and urogenital).  Oral administration, the most common form of enteral administration, can be performed in various dosage forms including pills, tablets, or capsules, and other routes likewise have various forms.  The drug may contain a single or multiple active ingredients.  They can be administered all at once as a bolus, at frequent intervals or continuously. Frequencies are often abbreviated from Latin, such as "every 8 hours" reading Q8H from "Quaque VIII Hora".

Drug discovery.

In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new drugs are discovered.  Historically, drugs were discovered through identifying the active ingredient from traditional remedies or by serendipitous discovery. Later chemical libraries of synthetic small molecules, natural products or extracts were screened in intact cells or whole organisms to identify substances that have a desirable therapeutic effect in a process known as classical pharmacology. Since sequencing of the human genome which allowed rapid cloning and synthesis of large quantities of purified proteins, it has become common practice to use high throughput screening of large compounds libraries against isolated biological targets which are hypothesized to be disease-modifying in a process known as reverse pharmacology. Hits from these screens are then tested in cells and then in animals for efficacy. Even more recently, scientists have been able to understand the shape of biological molecules at the atomic level, and to use that knowledge to design (see drug design) drug candidates.  Modern drug discovery involves the identification of screening hits, medicinal chemistry and optimization of those hits to increase the affinity, selectivity (to reduce the potential of side effects), efficacy/potency, metabolic stability (to increase the half-life), and oral bioavailability. Once a compound that fulfills all of these requirements has been identified, it will begin the process of drug development prior to clinical trials. One or more of these steps may, but not necessarily, involve computer-aided drug design.  Despite advances in technology and understanding of biological systems, drug discovery is still a lengthy, "expensive, difficult, and inefficient process" with low rate of new therapeutic discovery. In 2010, the research and development cost of each new molecular entity (NME) was approximately US$1.8 billion. Drug discovery is done by pharmaceutical companies, sometimes with research assistance from universities. The "final product" of drug discovery is a patent on the potential drug. The drug requires very expensive Phase I, II and III clinical trials, and most of them fail. Small companies have a critical role, often then selling the rights to larger companies that have the resources to run the clinical trials.

Development.

Drug development is the process of bringing a new drug to the market once a lead compound has been identified through the process of drug discovery. It includes pre-clinical research (microorganisms/animals) and clinical trials (on humans) and may include the step of obtaining regulatory approval to market the drug.

Regulation.

The regulation of drugs varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions, they are regulated at the state level, or at both state and national levels by various bodies, as is the case in Australia. The role of therapeutic goods regulation is designed mainly to protect the health and safety of the population. Regulation is aimed at ensuring the safety, quality, and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered before they are allowed to be marketed. There is usually some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers.  Depending upon the jurisdiction, drugs may be divided into over-the-counter drugs (OTC) which may be available without special restrictions, and prescription drugs, which must be prescribed by a licensed medical practitioner in accordance with medical guidelines due to the risk of adverse effects and contraindications. The precise distinction between OTC and prescription depends on the legal jurisdiction. A third category, "behind-the-counter" drugs, is implemented in some jurisdictions. These do not require a prescription, but must be kept in the dispensary, not visible to the public, and only be sold by a pharmacist or pharmacy technician. Doctors may also prescribe prescription drugs for off-label use – purposes which the drugs were not originally approved for by the regulatory agency. The Classification of Pharmaco-Therapeutic Referrals helps guide the referral process between pharmacists and doctors.  The International Narcotics Control Board of the United Nations imposes a world law of prohibition of certain drugs. They publish a lengthy list of chemicals and plants whose trade and consumption (where applicable) is forbidden. OTC drugs are sold without restriction as they are considered safe enough that most people will not hurt themselves accidentally by taking it as instructed. Many countries, such as the United Kingdom have a third category of "pharmacy medicines", which can only be sold in registered pharmacies by or under the supervision of a pharmacist.  Medical errors include overprescription and polypharmacy, misprescription, contraindication and lack of detail in dosage and administrations instructions. In 2000 the definition of a prescription error was studied using a Delphi method conference; the conference was motivated by ambiguity in the what a prescription error and a need to use a uniform definition in studies.

Drug pricing.

In many jurisdictions drug prices are regulated.

United Kingdom.

In the UK, the Pharmaceutical Price Regulation Scheme is intended to ensure that the National Health Service is able to purchase drugs at reasonable prices. The prices are negotiated between the Department of Health, acting with the authority of Northern Ireland and the UK Government, and the representatives of the Pharmaceutical industry brands, the Association of the British Pharmaceutical Industry (ABPI). For 2017 this payment percentage set by the PPRS will be 4,75%.

Canada.

In Canada, the Patented Medicine Prices Review Board examines drug pricing and determines if a price is excessive or not. In these circumstances, drug manufacturers must submit a proposed price to the appropriate regulatory agency. Furthermore, "the International Therapeutic Class Comparison Test is responsible for comparing the National Average Transaction Price of the patented drug product under review" different countries that the prices are being compared to are the following: France, Germany, Italy, Sweden, Switzerland, the United Kingdom, and the United States

Brazil.

In Brazil, the prices are regulated through a legislation under the name of "Medicamento Genérico" (generic drugs) since 1999.

India.

In India, drug prices are regulated by the National Pharmaceutical Pricing Authority.

United States.

In the United States, drug costs are unregulated, but instead are the result of negotiations between drug companies and insurance companies.  High prices have been attributed to monopolies given to manufacturers by the government and a lack of ability for organizations to negotiate prices. New drug development costs continue to rise as well. Despite the enormous advances in science and technology, the number of new blockbuster drugs approved per billion dollars spent has halved every 9 years since 1950.

Blockbuster drug.

A blockbuster drug is a drug that generates more than $1 billion in revenue for a pharmaceutical company in a single year. Cimetidine was the first drug ever to reach more than $1 billion a year in sales, thus making it the first blockbuster drug.

History.

Prescription drug history.

Antibiotics first arrived on the medical scene in 1932 thanks to Gerhard Domagk; and were coined the "wonder drugs". The introduction of the sulfa drugs led to the mortality rate from pneumonia in the U.S. to drop from 0.2% each year to 0.05% by 1939. Antibiotics inhibit the growth or the metabolic activities of bacteria and other microorganisms by a chemical substance of microbial origin. Penicillin, introduced a few years later, provided a broader spectrum of activity compared to sulfa drugs and reduced side effects. Streptomycin, found in 1942, proved to be the first drug effective against the cause of tuberculosis and also came to be the best known of a long series of important antibiotics. A second generation of antibiotics was introduced in the 1940s: aureomycin and chloramphenicol. Aureomycin was the best known of the second generation.  Lithium was discovered in the 19th century for nervous disorders and its possible mood-stabilizing or prophylactic effect; it was cheap and easily produced. As lithium fell out of favor in France, valpromide came into play. This antibiotic was the origin of the drug that eventually created the mood stabilizer category. Valpromide had distinct psychotrophic effects that were of benefit in both the treatment of acute manic states and in the maintenance treatment of manic depression illness. Psychotropics can either be sedative or stimulant; sedatives aim at damping down the extremes of behavior. Stimulants aim at restoring normality by increasing tone. Soon arose the notion of a tranquilizer which was quite different from any sedative or stimulant. The term tranquilizer took over the notions of sedatives and became the dominant term in the West through the 1980s. In Japan, during this time, the term tranquilizer produced the notion of a psyche-stabilizer and the term mood stabilizer vanished.  Premarin (conjugated estrogens, introduced in 1942) and Prempro (a combination estrogen-progestin pill, introduced in 1995) dominated the hormone replacement therapy (HRT) during the 1990s. HRT is not a life-saving drug, nor does it cure any disease. HRT has been prescribed to improve one's quality of life. Doctors prescribe estrogen for their older female patients both to treat short-term menopausal symptoms and to prevent long-term diseases. In the 1960s and early 1970s, more and more physicians began to prescribe estrogen for their female patients. between 1991 and 1999, Premarin was listed as the most popular prescription and best-selling drug in America.  The first oral contraceptive, Enovid, was approved by FDA in 1960. Oral contraceptives inhibit ovulation and so prevent conception. Enovid was known to be much more effective than alternatives including the condom and the diaphragm. As early as 1960, oral contraceptives were available in several different strengths by every manufacturer. In the 1980s and 1990s, an increasing number of options arose including, most recently, a new delivery system for the oral contraceptive via a transdermal patch. In 1982, a new version of the Pill was introduced, known as the "biphasic" pill. By 1985, a new triphasic pill was approved. Physicians began to think of the Pill as an excellent means of birth control for young women.  Stimulants such as Ritalin (methylphenidate) came to be pervasive tools for behavior management and modification in young children. Ritalin was first marketed in 1955 for narcolepsy; its potential users were middle-aged and the elderly. It wasn't until some time in the 1980s along with hyperactivity in children that Ritalin came onto the market. Medical use of methlyphenidate is predominantly for symptoms of attention deficit/hyperactivity disorder (ADHD). Consumption of methylphenidate in the U.S. out-paced all other countries between 1991 and 1999. Significant growth in consumption was also evident in Canada, New Zealand, Australia, and Norway. Currently, 85% of the world's methylphanidate is consumed in America.  The first minor tranquilizer was Meprobamate. Only fourteen months after it was made available, meprobamate had become the country's largest-selling prescription drug. By 1957, meprobamate had become the fastest-growing drug in history. The popularity of meprobamate paved the way for Librium and Valium, two minor tranquilizers that belonged to a new chemical class of drugs called the benzodiazepines. These were drugs that worked chiefly as anti-anxiety agents and muscle relaxants. The first benzodiazepine was Librium. Three months after it was approved, Librium had become the most prescribed tranquilizer in the nation. Three years later, Valium hit the shelves and was ten times more effective as a muscle relaxant and anti-convulsant. Valium was the most versatile of the minor tranquilizers. Later came the widespread adoption of major tranquilizers such as chlorpromazine and the drug reserpine. In 1970, sales began to decline for Valium and Librium, but sales of new and improved tranquilizers, such as Xanax, introduced in 1981 for the newly created diagnosis of panic disorder, soared.  Mevacor (lovastatin) is the first and most influential statin in the American market. The 1991 launch of Pravachol (pravastatin), the second available in the United States, and the release of Zocor (simvastatin) made Mevacor no longer the only statin on the market. In 1998, Viagra was released as a treatment for erectile dysfunction.

Ancient pharmacology.

Using plants and plant substances to treat all kinds of diseases and medical conditions is believed to date back to prehistoric medicine.  The Kahun Gynaecological Papyrus, the oldest known medical text of any kind, dates to about 1800 BC and represents the first documented use of any kind of drug. It and other medical papyri describe Ancient Egyptian medical practices, such as using honey to treat infections and the legs of bee-eaters to treat neck pains.  Ancient Babylonian medicine demonstrate the use of prescriptions in the first half of the 2nd millennium BC. Medicinal creams and pills were employed as treatments.  On the Indian subcontinent, the Atharvaveda, a sacred text of Hinduism whose core dates from the 2nd millennium BC, although the hymns recorded in it are believed to be older, is the first Indic text dealing with medicine. It describes plant-based drugs to counter diseases. The earliest foundations of ayurveda were built on a synthesis of selected ancient herbal practices, together with a massive addition of theoretical conceptualizations, new nosologies and new therapies dating from about 400 BC onwards. The student of Āyurveda was expected to know ten arts that were indispensable in the preparation and application of his medicines: distillation, operative skills, cooking, horticulture, metallurgy, sugar manufacture, pharmacy, analysis and separation of minerals, compounding of metals, and preparation of alkalis.  The Hippocratic Oath for physicians, attributed to 5th century BC Greece, refers to the existence of "deadly drugs", and ancient Greek physicians imported drugs from Egypt and elsewhere.

Medieval pharmacology.

Al-Kindi's 9th century AD book, "De Gradibus" and Ibn Sina (Avicenna)'s "The Canon of Medicine" cover a range of drugs known to Medicine in the medieval Islamic world.  Medieval medicine saw advances in surgery, but few truly effective drugs existed, beyond opium (found in such extremely popular drugs as the "Great Rest" of the Antidotarium Nicolai at the time) and quinine. Folklore cures and potentially poisonous metal-based compounds were popular treatments. Theodoric Borgognoni, (1205–1296), one of the most significant surgeons of the medieval period, responsible for introducing and promoting important surgical advances including basic antiseptic practice and the use of anaesthetics. Garcia de Orta described some herbal treatments that were used.

Modern pharmacology.

For most of the 19th century, drugs were not highly effective, leading Oliver Wendell Holmes, Sr. to famously comment in 1842 that "if all medicines in the world were thrown into the sea, it would be all the better for mankind and all the worse for the fishes".  During the First World War, Alexis Carrel and Henry Dakin developed the Carrel-Dakin method of treating wounds with an irrigation, Dakin's solution, a germicide which helped prevent gangrene.  In the inter-war period, the first anti-bacterial agents such as the sulpha antibiotics were developed. The Second World War saw the introduction of widespread and effective antimicrobial therapy with the development and mass production of penicillin antibiotics, made possible by the pressures of the war and the collaboration of British scientists with the American pharmaceutical industry.  Medicines commonly used by the late 1920s included aspirin, codeine, and morphine for pain; digitalis, nitroglycerin, and quinine for heart disorders, and insulin for diabetes. Other drugs included antitoxins, a few biological vaccines, and a few synthetic drugs. In the 1930s, antibiotics emerged: first sulfa drugs, then penicillin and other antibiotics. Drugs increasingly became "the center of medical practice". In the 1950s, other drugs emerged including corticosteroids for inflammation, rauvolfia alkaloids as tranqulizers and antihypertensives, antihistamines for nasal allergies, xanthines for asthma, and typical antipsychotics for psychosis. As of 2007, thousands of approved drugs have been developed. Increasingly, biotechnology is used to discover biopharmaceuticals. Recently, multi-disciplinary approaches have yielded a wealth of new data on the development of novel antibiotics and antibacterials and on the use of biological agents for antibacterial therapy.  In the 1950s, new psychiatric drugs, notably the antipsychotic chlorpromazine, were designed in laboratories and slowly came into preferred use. Although often accepted as an advance in some ways, there was some opposition, due to serious adverse effects such as tardive dyskinesia. Patients often opposed psychiatry and refused or stopped taking the drugs when not subject to psychiatric control.  Governments have been heavily involved in the regulation of drug development and drug sales. In the U.S., the Elixir Sulfanilamide disaster led to the establishment of the Food and Drug Administration, and the 1938 Federal Food, Drug, and Cosmetic Act required manufacturers to file new drugs with the FDA. The 1951 Humphrey-Durham Amendment required certain drugs to be sold by prescription. In 1962, a subsequent amendment required new drugs to be tested for efficacy and safety in clinical trials.  Until the 1970s, drug prices were not a major concern for doctors and patients. As more drugs became prescribed for chronic illnesses, however, costs became burdensome, and by the 1970s nearly every U.S. state required or encouraged the substitution of generic drugs for higher-priced brand names. This also led to the 2006 U.S. law, Medicare Part D, which offers Medicare coverage for drugs.  As of 2008, the United States is the leader in medical research, including pharmaceutical development. U.S. drug prices are among the highest in the world, and drug innovation is correspondingly high. In 2000, U.S.-based firms developed 29 of the 75 top-selling drugs; firms from the second-largest market, Japan, developed eight, and the United Kingdom contributed 10. France, which imposes price controls, developed three. Throughout the 1990s, outcomes were similar.

Controversies.

Controversies concerning pharmaceutical drugs include patient access to drugs under development and not yet approved, pricing, and environmental issues.

Access to unapproved drugs.

Governments worldwide have created provisions for granting access to drugs prior to approval for patients who have exhausted all alternative treatment options and do not match clinical trial entry criteria. Often grouped under the labels of compassionate use, expanded access, or named patient supply, these programs are governed by rules which vary by country defining access criteria, data collection, promotion, and control of drug distribution.  Within the United States, pre-approval demand is generally met through treatment IND (investigational new drug) applications (INDs), or single-patient INDs. These mechanisms, which fall under the label of expanded access programs, provide access to drugs for groups of patients or individuals residing in the US. Outside the US, Named Patient Programs provide controlled, pre-approval access to drugs in response to requests by physicians on behalf of specific, or "named", patients before those medicines are licensed in the patient's home country. Through these programs, patients are able to access drugs in late-stage clinical trials or approved in other countries for a genuine, unmet medical need, before those drugs have been licensed in the patient's home country.  Patients who have not been able to get access to drugs in development have organized and advocated for greater access. In the United States, ACT UP formed in the 1980s, and eventually formed its Treatment Action Group in part to pressure the US government to put more resources into discovering treatments for AIDS and then to speed release of drugs that were under development.  The Abigail Alliance was established in November 2001 by Frank Burroughs in memory of his daughter, Abigail. The Alliance seeks broader availability of investigational drugs on behalf of terminally ill patients.  In 2013, BioMarin Pharmaceutical was at the center of a high-profile debate regarding expanded access of cancer patients to experimental drugs.

Access to medicines and drug pricing.

Essential medicines as defined by the World Health Organization (WHO) are "those drugs that satisfy the health care needs of the majority of the population; they should therefore be available at all times in adequate amounts and in appropriate dosage forms, at a price the community can afford." Recent studies have found that most of the medicines on the WHO essential medicines list, outside of the field of HIV drugs, are not patented in the developing world, and that lack of widespread access to these medicines arise from issues fundamental to economic development – lack of infrastructure and poverty. Médecins Sans Frontières also runs a Campaign for Access to Essential Medicines campaign, which includes advocacy for greater resources to be devoted to currently untreatable diseases that primarily occur in the developing world. The Access to Medicine Index tracks how well pharmaceutical companies make their products available in the developing world.  World Trade Organization negotiations in the 1990s, including the TRIPS Agreement and the Doha Declaration, have centered on issues at the intersection of international trade in pharmaceuticals and intellectual property rights, with developed world nations seeking strong intellectual property rights to protect investments made to develop new drugs, and developing world nations seeking to promote their generic pharmaceuticals industries and their ability to make medicine available to their people via compulsory licenses.  Some have raised ethical objections specifically with respect to pharmaceutical patents and the high prices for drugs that they enable their proprietors to charge, which poor people in the developed world, and developing world, cannot afford. Critics also question the rationale that exclusive patent rights and the resulting high prices are required for pharmaceutical companies to recoup the large investments needed for research and development. One study concluded that marketing expenditures for new drugs often doubled the amount that was allocated for research and development. Other critics claim that patent settlements would be costly for consumers, the health care system, and state and federal governments because it would result in delaying access to lower cost generic medicines.  Novartis fought a protracted battle with the government of India over the patenting of its drug, Gleevec, in India, which ended up in India's Supreme Court in a case known as Novartis v. Union of India & Others. The Supreme Court ruled narrowly against Novartis, but opponents of patenting drugs claimed it as a major victory.

Environmental issues.

The environmental impact of pharmaceuticals and personal care products is controversial. PPCPs are substances used by individuals for personal health or cosmetic reasons and the products used by agribusiness to boost growth or health of livestock. PPCPs comprise a diverse collection of thousands of chemical substances, including prescription and over-the-counter therapeutic drugs, veterinary drugs, fragrances, and cosmetics. PPCPs have been detected in water bodies throughout the world and ones that persist in the environment are called Environmental Persistent Pharmaceutical Pollutants. The effects of these chemicals on humans and the environment are not yet known, but to date there is no scientific evidence that they affect human health.

A medication (also referred to as medicine, pharmaceutical drug, or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and relies on the science of pharmacology for continual advancement and on pharmacy for appropriate management.

Un médicament est toute substance ou composition présentée comme possédant des propriétés curatives ou préventives à l'égard des maladies humaines ou animales. Par extension, un médicament comprend toute substance ou composition pouvant être utilisée chez l'être humain ou l'animal ou pouvant leur être administrée, en vue d'établir un diagnostic médical ou de restaurer, corriger ou modifier leurs fonctions physiologiques en exerçant une action pharmacologique, immunologique ou métabolique.


History.

Christian Nagasaki.

Nagasaki was a small fishing village set in a secluded harbor and had little historical significance until contact with Portuguese explorers in 1543. An early visitor was Fernão Mendes Pinto, who came from Sagres on a Portuguese ship which landed nearby in Tanegashima.  Soon after, Portuguese ships started sailing to Japan as regular trade freighters, thus increasing the contact and trade relations between Japan and the rest of the world, and particularly with mainland China, with whom Japan had previously severed its commercial and political ties, mainly due to a number of incidents involving Wokou piracy in the South China Sea, with the Portuguese now serving as intermediaries between the two Asian countries.  Despite the mutual advantages derived from these trading contacts, which would soon be acknowledged by all parties involved, the lack of a proper seaport in Kyūshū for the purpose of harboring foreign ships posed a major problem for both merchants and the Kyushu "daimyōs" (feudal lords) who expected to collect great advantages from the trade with the Portuguese.  In the meantime, Spanish Jesuit missionary St. Francis Xavier arrived in Kagoshima, South Kyūshū, in 1549, and soon initiated a thorough campaign of evangelization throughout Japan, and left for China in 1552 and died soon afterwards. His followers who remained behind converted a number of "daimyōs". The most notable among them was Ōmura Sumitada. In 1569, Ōmura granted a permit for the establishment of a port with the purpose of harboring Portuguese ships in Nagasaki, which was finally set up in 1571, under the supervision of the Jesuit missionary Gaspar Vilela and Portuguese Captain-Major Tristão Vaz de Veiga, with Ōmura's personal assistance.  The little harbor village quickly grew into a diverse port city, and Portuguese products imported through Nagasaki (such as tobacco, bread, textiles and a Portuguese sponge-cake called "castellas") were assimilated into popular Japanese culture. Tempura derived from a popular Portuguese recipe originally known as "peixinho-da-horta", and takes its name from the Portuguese word, 'tempero,' seasoning, and refers to the tempora quadragesima, forty days of Lent during which eating meat was forbidden, another example of the enduring effects of this cultural exchange. The Portuguese also brought with them many goods from other Asian countries such as China. The value of Portuguese exports from Nagasaki during the 16th century were estimated to ascend to over 1,000,000 "cruzados", reaching as many as 3,000,000 in 1637.  Due to the instability during the Sengoku period, Sumitada and Jesuit leader Alexandro Valignano conceived a plan to pass administrative control over to the Society of Jesus rather than see the Catholic city taken over by a non-Catholic "daimyō". Thus, for a brief period after 1580, the city of Nagasaki was a Jesuit colony, under their administrative and military control. It became a refuge for Christians escaping maltreatment in other regions of Japan. In 1587, however, Toyotomi Hideyoshi's campaign to unify the country arrived in Kyūshū. Concerned with the large Christian influence in southern Japan, as well as the active and what was perceived as the arrogant role the Jesuits were playing in the Japanese political arena, Hideyoshi ordered the expulsion of all missionaries, and placed the city under his direct control. However, the expulsion order went largely unenforced, and the fact remained that most of Nagasaki's population remained openly practicing Catholic.  In 1596, the Spanish ship "San Felipe" was wrecked off the coast of Shikoku, and Hideyoshi learned from its pilot that the Spanish Franciscans were the vanguard of an Iberian invasion of Japan. In response, Hideyoshi ordered the crucifixions of twenty-six Catholics in Nagasaki on February 5 of the next year (i.e. the "Twenty-six Martyrs of Japan"). Portuguese traders were not ostracized, however, and so the city continued to thrive.  In 1602, Augustinian missionaries also arrived in Japan, and when Tokugawa Ieyasu took power in 1603, Catholicism was still tolerated. Many Catholic "daimyōs" had been critical allies at the Battle of Sekigahara, and the Tokugawa position was not strong enough to move against them. Once Osaka Castle had been taken and Toyotomi Hideyoshi's offspring killed, though, the Tokugawa dominance was assured. In addition, the Dutch and English presence allowed trade without religious strings attached. Thus, in 1614, Catholicism was officially banned and all missionaries ordered to leave. Most Catholic daimyo apostatized, and forced their subjects to do so, although a few would not renounce the religion and left the country for Macau, Luzon and Japantowns in Southeast Asia. A brutal campaign of persecution followed, with thousands of converts across Kyūshū and other parts of Japan killed, tortured, or forced to renounce their religion (see Martyrs of Japan).  Catholicism's last gasp as an open religion and the last major military action in Japan until the Meiji Restoration was the Shimabara Rebellion of 1637. While there is no evidence that Europeans directly incited the rebellion, Shimabara Domain had been a Christian "han" for several decades, and the rebels adopted many Portuguese motifs and Christian icons. Consequently, in Tokugawa society the word "Shimabara" solidified the connection between Christianity and disloyalty, constantly used again and again in Tokugawa propaganda. The Shimabara Rebellion also convinced many policy-makers that foreign influences were more trouble than they were worth, leading to the national isolation policy. The Portuguese, who had been previously living on a specially constructed island-prison in Nagasaki harbour called Dejima, were expelled from the archipelago altogether, and the Dutch were moved from their base at Hirado into the trading island.

Seclusion era.

The Great Fire of Nagasaki destroyed much of the city in 1663, including the Mazu shrine at the Kofuku Temple patronized by the Chinese sailors and merchants visiting the port.  In 1720 the ban on Dutch books was lifted, causing hundreds of scholars to flood into Nagasaki to study European science and art. Consequently, Nagasaki became a major center of what was called "rangaku", or "Dutch Learning". During the Edo period, the Tokugawa shogunate governed the city, appointing a "hatamoto", the "Nagasaki bugyō", as its chief administrator. During this period, Nagasaki was designated a "shogunal city". The number of such cities rose from three to eleven under Tokugawa administration.  Consensus among historians was once that Nagasaki was Japan's only window on the world during its time as a closed country in the Tokugawa era. However, nowadays it is generally accepted that this was not the case, since Japan interacted and traded with the Ryūkyū Kingdom, Korea and Russia through Satsuma, Tsushima and Matsumae respectively. Nevertheless, Nagasaki was depicted in contemporary art and literature as a cosmopolitan port brimming with exotic curiosities from the Western World.  In 1808, during the Napoleonic Wars, the Royal Navy frigate HMS "Phaeton" entered Nagasaki Harbor in search of Dutch trading ships. The local magistrate was unable to resist the crews demand for food, fuel, and water, later committing "seppuku" as a result. Laws were passed in the wake of this incident strengthening coastal defenses, threatening death to intruding foreigners, and prompting the training of English and Russian translators.  The "Tōjinyashiki" (唐人屋敷) or Chinese Factory in Nagasaki was also an important conduit for Chinese goods and information for the Japanese market. Various colourful Chinese merchants and artists sailed between the Chinese mainland and Nagasaki. Some actually combined the roles of merchant and artist such as 18th century Yi Hai. It is believed that as much as one-third of the population of Nagasaki at this time may have been Chinese. The Chinese traders at Nagasaki were confined to a walled compound () which was located in the same vicinity as Dejima island; and the activities of the Chinese, though less strictly controlled than the Dutch, were closely monitored by the Nagasaki bugyō.

Meiji Japan.

With the Meiji Restoration, Japan opened its doors once again to foreign trade and diplomatic relations. Nagasaki became a treaty port in 1859 and modernization began in earnest in 1868. Nagasaki was officially proclaimed a city on April 1, 1889. With Christianity legalized and the Kakure Kirishitan coming out of hiding, Nagasaki regained its earlier role as a center for Roman Catholicism in Japan.  During the Meiji period, Nagasaki became a center of heavy industry. Its main industry was ship-building, with the dockyards under control of Mitsubishi Heavy Industries becoming one of the prime contractors for the Imperial Japanese Navy, and with Nagasaki harbor used as an anchorage under the control of nearby Sasebo Naval District. During World War II, at the time of the nuclear attack, Nagasaki was an important industrial city, containing both plants of the Mitsubishi Steel and Arms Works, the Akunoura Engine Works, Mitsubishi Arms Plant, Mitsubishi Electric Shipyards, Mitsubishi Steel and Arms Works, Mitsubishi-Urakami Ordnance Works, several other small factories, and most of the ports storage and trans-shipment facilities, which employed about 90% of the city's labor force, and accounted for 90% of the city's industry. These connections with the Japanese war effort made Nagasaki a major target for strategic bombing by the Allies during the war.

Atomic bombing of Nagasaki during World War II.

For 12 months prior to the nuclear attack, Nagasaki had experienced five small-scale air attacks by an aggregate of 136 U.S. planes which dropped a total of 270 tons of high explosive, 53 tons of incendiary, and 20 tons of fragmentation bombs. Of these, a raid of August 1, 1945, was most effective, with a few of the bombs hitting the shipyards and dock areas in the southwest portion of the city, several hitting the Mitsubishi Steel and Arms Works, and six bombs landing at the Nagasaki Medical School and Hospital, with three direct hits on buildings there. While the damage from these few bombs was relatively small, it created considerable concern in Nagasaki and a number of people, principally school children, were evacuated to rural areas for safety, thus reducing the population in the city at the time of the atomic attack.  On the day of the nuclear strike (August 9, 1945) the population in Nagasaki was estimated to be 263,000, which consisted of 240,000 Japanese residents, 10,000 Korean residents, 2,500 conscripted Korean workers, 9,000 Japanese soldiers, 600 conscripted Chinese workers, and 400 Allied POWs. That day, the Boeing B-29 Superfortress "Bockscar", commanded by Major Charles Sweeney, departed from Tinian's North Field just before dawn, this time carrying a plutonium bomb, code named "Fat Man". The primary target for the bomb was Kokura, with the secondary target being Nagasaki, if the primary target was too cloudy to make a visual sighting. When the plane reached Kokura at 9:44 a.m. (10:44 am. Tinian Time), the city was obscured by clouds and smoke, as the nearby city of Yahata had been firebombed on the previous day – the steel plant in Yahata also had their workforce intentionally set fire to containers of coal tar, to produce target-obscuring black smoke. Unable to make a bombing attack on visual due to the clouds and smoke and with limited fuel, the plane left the city at 10:30 a.m. for the secondary target. After 20 minutes, the plane arrived at 10:50 a.m. over Nagasaki, but the city was also concealed by clouds. Desperately short of fuel and after making a couple of bombing runs without obtaining any visual target, the crew was forced to use radar to drop the bomb. At the last minute, the opening of the clouds allowed them to make visual contact with a racetrack in Nagasaki, and they dropped the bomb on the city's Urakami Valley midway between the Mitsubishi Steel and Arms Works in the south, and the Mitsubishi-Urakami Ordnance Works in the north. 53 seconds after its release, the bomb exploded at 11:02 a.m. at an approximate altitude of 1,800 feet.  Less than a second after the detonation, the north of the city was destroyed and 35,000 people were killed. Among the deaths were 6,200 out of the 7,500 employees of the Mitsubishi Munitions plant, and 24,000 others (including 2,000 Koreans) who worked in other war plants and factories in the city, as well as 150 Japanese soldiers. The industrial damage in Nagasaki was high, leaving 68–80% of the non-dock industrial production destroyed. It was the second and, to date, the last use of a nuclear weapon in combat, and also the second detonation of a plutonium bomb. The first combat use of a nuclear weapon was the "Little Boy" bomb, which was dropped on the Japanese city of Hiroshima on August 6, 1945. The first plutonium bomb was tested in central New Mexico, United States, on July 16, 1945. The Fat Man bomb was somewhat more powerful than the one dropped over Hiroshima, but because of Nagasaki's more uneven terrain, there was less damage.

Contemporary era.

The city was rebuilt after the war, albeit dramatically changed. The pace of reconstruction was slow. The first simple emergency dwellings were not provided until 1946. The focus of redevelopment was the replacement of war industries with foreign trade, shipbuilding and fishing. This was formally declared when the Nagasaki International Culture City Reconstruction Law was passed in May 1949. New temples were built, as well as new churches, owing to an increase in the presence of Christianity. Some of the rubble was left as a memorial, such as a one-legged "torii" at Sannō Shrine and an arch near ground zero. New structures were also raised as memorials, such as the Atomic Bomb Museum. Nagasaki remains primarily a port city, supporting a rich shipbuilding industry.  On January 4, 2005, the towns of Iōjima, Kōyagi, Nomozaki, Sanwa, Sotome and Takashima (all from Nishisonogi District) were officially merged into Nagasaki.

Geography.

Nagasaki and Nishisonogi Peninsulas are located within the city limits. The city is surrounded by the cities of Isahaya and Saikai, and the towns of Togitsu and Nagayo in Nishisonogi District.  Nagasaki lies at the head of a long bay that forms the best natural harbor on the island of Kyūshū. The main commercial and residential area of the city lies on a small plain near the end of the bay. Two rivers divided by a mountain spur form the two main valleys in which the city lies. The heavily built-up area of the city is confined by the terrain to less than.

Climate.

Nagasaki has the typical humid subtropical climate of Kyūshū and Honshū, characterized by mild winters and long, hot, and humid summers. Apart from Kanazawa and Shizuoka it is the wettest sizeable city in Japan. In the summer, the combination of persistent heat and high humidity results in unpleasant conditions, with wet-bulb temperatures sometimes reaching. In the winter, however, Nagasaki is drier and sunnier than Gotō to the west, and temperatures are slightly milder than further inland in Kyūshū. Since records began in 1878, the wettest month has been July 1982, with including in a single day, whilst the driest month has been September 1967, with. Precipitation occurs year-round, though winter is the driest season; rainfall peaks sharply in June and July. August is the warmest month of the year. On January 24, 2016, a snowfall of was recorded.

Transportation.

The nearest airport is Nagasaki Airport in the nearby city of Ōmura. The Kyushu Railway Company (JR Kyushu) provides rail transportation on the Nagasaki Main Line, whose terminal is at Nagasaki Station. In addition, the Nagasaki Electric Tramway operates five routes in the city. The Nagasaki Expressway serves vehicular traffic with interchanges at Nagasaki and Susukizuka. In addition, six national highways crisscross the city: Route 34, 202, 206, 251, 324, and 499.

Demographics.

On August 9, 1945 the population was estimated to be 263,000. As of March 1, 2017, the city had population of 505,723 and a population density of 1,000 persons per km.

Sports.

Nagasaki is represented in the J. League of football with its local club, V-Varen Nagasaki.

Events.

The Prince Takamatsu Cup Nishinippon Round-Kyūshū Ekiden, the world's longest relay race, begins in Nagasaki each November.  Kunchi, the most famous festival in Nagasaki, is held from October 7–9.  The Nagasaki Lantern Festival, celebrating the Chinese New Year, is celebrated from February 18 to March 4.

Twin towns.

The city of Nagasaki maintains sister cities or friendship relations with other cities worldwide.

During World War II, the American atomic bombings of Hiroshima and Nagasaki made Nagasaki the second and, to date, last city in the world to experience a nuclear attack (at 11:02 am, August 9, 1945 'Japan Standard Time (UTC+9)').

L'histoire de Nagasaki a presque entièrement été construite par des étrangers ; en effet, ce sont les Portugais qui en font une ville portuaire prospère au. Sous la période Tokugawa, la persécution des chrétiens y fut particulièrement vive, avant que la ville ne soit ouverte après la restauration Meiji. Nagasaki a été, le, la cible du deuxième bombardement atomique de l'histoire par les États-Unis durant la Seconde Guerre mondiale après celui d'Hiroshima trois jours plus tôt. C'est donc à ce jour la dernière ville à avoir subi le feu nucléaire.


Etymology.

Through French "nome", the word comes from Ancient Greek νομός, "nomós", meaning "district"; the Ancient Egyptian term was "sepat" or "spAt".  Today's use of the Ancient Greek rather than the Ancient Egyptian term came about during the Ptolemaic period, when the use of Greek was widespread in Egypt. The availability of Greek records on Egypt influenced the adoption of Greek terms by later historians.

History.

Dynastic Egypt.

The division of ancient Egypt into nomes can be traced back to prehistoric Egypt (before 3100 BC). These nomes originally existed as autonomous city-states, but later began to unify. According to ancient tradition, the ruler Menes completed the final unification.  Not only did the division into nomes remain in place for more than three millennia, the areas of the individual nomes and their ordering remained remarkably stable. Some, like Xois in the Nile Delta or Khent in Upper Egypt, were first mentioned on the Palermo Stone, which was inscribed in the Fifth Dynasty. The names of a few, like the nome of Bubastis, appeared no earlier than the New Kingdom. Under the system that prevailed for most of pharaonic Egypt's history, the country was divided into 42 nomes.

Lower Egypt nomes.

Lower Egypt (Egyptian "Ā-meḥty"), from the Old Kingdom capital Memphis to the Mediterranean Sea, comprised 20 nomes. The first was based around Memphis, Saqqara, and Giza, in the area occupied by modern-day Cairo. The nomes were numbered in a more or less orderly fashion south to north through the Nile Delta, first covering the territory on the west before continuing with the higher numbers to the east. Thus, Alexandria was in the Third Nome; Bubastis was in the Eighteenth.

Upper Egypt nomes.

Upper Egypt was divided into 22 nomes. The first of these was centered on Elephantine close to Egypt's border with Nubia at the First Cataract – the area of modern-day Aswan. From there the numbering progressed downriver in an orderly fashion along the narrow fertile strip of land that was the Nile valley. Waset (ancient Thebes or contemporary Luxor) was in the Fourth Nome, Amarna in the Fourteenth, and Meidum in the Twenty-first.

Ptolemaic Egypt.

Some nomes were added or renamed during the Graeco-Roman occupation of Egypt. For example, the Ptolemies renamed the Crocodilopolitan nome to Arsinoe. Hadrian created a new nome, Antinoopolites, for which Antinoöpolis was the capital.

Roman Egypt.

The nomes survived into Roman times. Under Roman rule, individual nomes minted their own coinage, the so-called "nome coins," which still reflect individual local associations and traditions. The nomes of Egypt retained their primary importance as administrative units until the fundamental rearrangement of the bureaucracy during the reigns of Diocletian and Constantine the Great.  From AD 307/8, their place was taken by smaller units called "pagi". Eventually powerful local officials arose who were called pagarchs, through whom all patronage flowed. The pagarch's essential role was as an organizer of tax-collection. Later the pagarch assumed some military functions as well. The pagarchs were often wealthy landowners who reigned over the "pagi" from which they originated.

Nomarch.

For most of the history, each nome was headed by a nomarch. The position of the nomarch was at times hereditary, while at others they were appointed by the pharaoh. Generally, when the national government was stronger, nomarchs were the king's appointed governors. When the central government was weaker, however—such as during foreign invasions or civil wars—individual nomes would assert themselves and establish hereditary lines of succession. Conflicts among these different hereditary nomarchies were common, most notably during the First Intermediate Period, a time that saw a breakdown in central authority lasting from the 7th–11th Dynasties which ended when one of the local rulers became strong enough to again assert control over the entire country as pharaoh.

List of nomes (ancient Egyptian: "Sepat-Isti").

The nomes (Ancient Egyptian: sepat) are listed in separate tables for "Isti" - "the two Egypts" (Upper and Lower Egypt).  Note:

A nome (, from, "nomós", “district”) was a territorial division in ancient Egypt. Each nome was ruled by a nomarch (Ancient Egyptian: "heri-tep a'a"). The number of nomes changed through the various periods of the history of ancient Egypt.

Les nomes, au nombre de trente-huit pendant l'Ancien Empire et le Moyen Empire et quarante-deux à l’époque ptolémaïque, sont les circonscriptions administratives de l’Ancienne Égypte.


History.

Numerals.

Numbers should be distinguished from numerals, the symbols used to represent numbers. The Egyptians invented the first ciphered numeral system, and the Greeks followed by mapping their counting numbers onto Ionian and Doric alphabets. Roman numerals, a system that used combinations of

First use of numbers.

Bones and other artifacts have been discovered with marks cut into them that many believe are tally marks. These tally marks may have been used for counting elapsed time, such as numbers of days, lunar cycles or keeping records of quantities, such as of

Zero.

The first known documented use of zero dates to AD 628, and appeared in the "Brāhmasphuṭasiddhānta", the main work of the Indian mathematician Brahmagupta. He treated 0 as a number and discussed operations involving it, including division. By this time (the 7th century) the concept had clearly reached Cambodia as Khmer numerals, and documentation shows the idea later spreading to China and the Islamic world.  Brahmagupta's "Brāhmasphuṭasiddhānta" is the first book that mentions zero as a number, hence Brahmagupta is usually considered the first to formulate the concept of zero. He gave rules of

Negative numbers.

The abstract concept of negative numbers was recognized as early as 100–50 BC in China. "The Nine Chapters on the Mathematical Art" contains methods for finding the areas of figures; red rods were used to denote positive coefficients, black for negative. The first reference in a Western work was in the 3rd century AD in Greece. Diophantus referred to the equation equivalent to (the solution is negative) in "Arithmetica", saying that the equation gave an absurd result.  During the 600s, negative numbers were in use in India to represent debts. Diophantus' previous reference was discussed more explicitly by Indian mathematician Brahmagupta, in "Brāhmasphuṭasiddhānta" in 628, who used negative numbers to produce the general form quadratic formula that remains in

Rational numbers.

It is likely that the concept of fractional numbers dates to prehistoric times. The Ancient Egyptians used their Egyptian fraction notation for rational numbers in mathematical texts such as the Rhind Mathematical Papyrus and the Kahun Papyrus. Classical Greek and Indian mathematicians made studies of the theory of rational numbers, as part of the general study of number theory. The best

Irrational numbers.

The earliest known use of irrational numbers was in the Indian Sulba Sutras composed between 800 and 500 BC. The first existence proofs of irrational numbers is usually attributed to Pythagoras, more specifically to the Pythagorean Hippasus of Metapontum, who produced a (most likely geometrical) proof of the irrationality of the square root of 2. The story goes that Hippasus discovered irrational numbers when trying to represent the square root of 2 as a fraction. However, Pythagoras believed in the absoluteness of numbers, and could not accept the existence of irrational numbers. He could not disprove their existence through logic, but he could not accept irrational numbers, and so, allegedly and frequently reported, he sentenced Hippasus to death by drowning, to impede spreading of this disconcerting news.  The 16th century brought final European acceptance of negative integral and fractional numbers. By the 17th century, mathematicians generally used decimal fractions with modern notation. It was not, however, until the 19th century that mathematicians separated irrationals into algebraic and transcendental parts, and once more undertook the scientific study of irrationals. It had remained almost dormant since Euclid. In 1872,

Transcendental numbers and reals.

The existence of transcendental numbers was first established by Liouville (1844, 1851). Hermite proved in 1873 that "e" is transcendental and Lindemann proved in 1882

Infinity and infinitesimals.

The earliest known conception of mathematical infinity appears in the Yajur Veda, an ancient Indian script, which at one point states, "If you remove a part from infinity or add a part to infinity, still what remains is infinity." Infinity was a popular topic of philosophical study among the Jain mathematicians c. 400 BC. They distinguished between five types of infinity: infinite in one and two directions, infinite in area, infinite everywhere, and infinite perpetually.  Aristotle defined the traditional Western notion of mathematical infinity. He distinguished between actual infinity and potential infinity—the general consensus being that only the latter had true value. Galileo Galilei's "Two New Sciences"

Complex numbers.

The earliest fleeting reference to square roots of negative numbers occurred in the work of the mathematician and inventor Heron of Alexandria in the, when he considered the volume of an impossible frustum of a pyramid. They became more prominent when in the 16th century closed formulas for the roots of third and fourth degree polynomials were discovered by Italian mathematicians such as Niccolò Fontana Tartaglia and Gerolamo Cardano. It was soon realized that these formulas, even if one was only interested in

Prime numbers.

Prime numbers have been studied throughout recorded history. Euclid devoted one book of the "Elements" to the theory of primes; in it he proved the infinitude of the primes and the fundamental theorem of arithmetic, and presented the Euclidean algorithm for finding the greatest common divisor of two numbers.  In 240 BC, Eratosthenes used the Sieve of Eratosthenes to quickly isolate prime numbers. But most further development of the theory of primes

Main classification.

Numbers can be classified into sets, called number systems, such as the natural numbers and the real numbers. The major categories of numbers are as follows: There is generally no problem in identifying each number system with a proper subset of the next one (by abuse of notation), because each of these number systems is canonically isomorphic to a proper subset of the next one. The resulting hierarchy allows, for example, to talk, formally correctly, about real numbers that are rational numbers, and is expressed symbolically by writing

Natural numbers.

The most familiar numbers are the natural numbers (sometimes called whole numbers or counting numbers): 1, 2, 3, and so on. Traditionally, the sequence of natural numbers started with 1 (0 was not even considered a number for the Ancient Greeks.) However, in the 19th century, set theorists and other mathematicians started including 0 (cardinality of the empty set, i.e. 0 elements, where 0 is thus the smallest cardinal number) in the set of natural numbers. Today, different mathematicians use the term to describe both sets, including 0 or not. The mathematical symbol for the set of all natural numbers is N, also written formula_8, and sometimes formula_9 or formula_10 when it is necessary to indicate whether the set should start with 0 or 1, respectively.  In the base

Integers.

The negative of a positive integer is defined as a number that produces 0 when it is added to the corresponding positive integer. Negative numbers are usually written with a negative sign (a minus sign). As an example, the negative of 7 is written −7, and. When the set of negative numbers is combined with the set

Rational numbers.

A rational number is a number that can be expressed as a fraction with an integer numerator and a positive integer denominator. Negative denominators are allowed, but are commonly avoided, as every rational number is equal to a fraction with positive denominator. Fractions are written as two integers, the numerator and the denominator, with a dividing bar between them. The fraction represents "m" parts of a whole divided into "n" equal

Real numbers.

The symbol for the real numbers is R, also written as formula_16 They include all the measuring numbers. Every real number corresponds to a point on the number line. The following paragraph will focus primarily on positive real numbers. The treatment of negative real numbers is according to the general rules of arithmetic and their denotation is simply prefixing the corresponding positive numeral by a minus sign, e.g. −123.456.  Most real numbers can only be "approximated" by decimal numerals, in which a decimal point is placed to the right of the digit with place value 1. Each digit to the right of the decimal point has a place value one-tenth of the place value of the digit to its left. For example, 123.456 represents, or, in words, one hundred, two tens, three ones, four tenths, five hundredths, and six thousandths. A real number can be expressed by a finite number of decimal digits only

Complex numbers.

Moving to a greater level of abstraction, the real numbers can be extended to the complex numbers. This set of numbers arose historically from trying to find closed formulas for the roots of cubic and quadratic polynomials. This led to expressions involving the square roots of negative numbers, and eventually to the definition of a new number: a square root of −1, denoted by "i", a symbol assigned by Leonhard Euler, and called the imaginary unit. The complex numbers consist of all numbers of the form where "a" and "b" are real numbers. Because of this, complex numbers correspond to points on the complex plane, a vector space of two real dimensions. In the expression, the real number "a" is called the real

Subclasses of the integers.

Even and odd numbers.

An even number is an integer that is "evenly divisible" by two, that is divisible by two without remainder; an odd number is an integer that is not even. (The old-fashioned term "evenly divisible" is now almost always

Prime numbers.

A prime number is an integer greater than 1 that is not the product of two smaller positive integers. The first few prime numbers are 2, 3, 5, 7, and 11. There is no such simple formula as for odd and even numbers to generate the prime numbers. The primes have been widely studied for more than 2000 years and

Other classes of integers.

Many subsets of the natural numbers have been the subject of specific studies and have been named, often

Subclasses of the complex numbers.

Algebraic, irrational and transcendental numbers.

Algebraic numbers are those that are a solution to a polynomial equation with integer coefficients. Real numbers that are not rational numbers

Constructible numbers.

Motivated by the classical problems of constructions with straightedge and compass, the constructible numbers are those complex numbers

Computable numbers.

A computable number, also known as "recursive number", is a real number such that there exists an algorithm which, given a positive number "n" as input, produces the first "n" digits of the computable number's decimal representation. Equivalent definitions can be given using μ-recursive functions, Turing machines or λ-calculus. The computable numbers are stable for all usual arithmetic operations, including the computation of the roots of a polynomial, and thus form a real closed field that contains the real algebraic numbers.  The

Extensions of the concept.

"p"-adic numbers.

The "p"-adic numbers may have infinitely long expansions to the left of the decimal point, in the same way that real numbers may have infinitely long expansions to the right. The number system that results depends on what base is used for the digits: any base is possible,

Hypercomplex numbers.

Some number systems that are not included in the complex numbers may be constructed from the real numbers in a way that generalize the construction of the complex numbers. They are sometimes

Transfinite numbers.

For dealing with infinite sets, the natural numbers have been generalized to the ordinal numbers and to the cardinal numbers. The former gives the

Nonstandard numbers.

Hyperreal numbers are used in non-standard analysis. The hyperreals, or nonstandard reals (usually denoted as *R), denote an ordered field that is a proper extension of the ordered field of

A number is a mathematical object used to count, measure, and label. The original examples are the natural numbers 1, 2, 3, 4, and so forth. For being manipulated, individual numbers need to be represented by symbols, called "numerals"; for example, "5" is a numeral that represents the number five. As only a small number of symbols can be memorized, basic numerals are commonly organized in a numeral system, which is an organized way to represent any number. The most common numeral system is the Hindu–Arabic numeral system, which allows representing any number by a combination of ten basic numerals called digits. In addition to their use in counting and measuring, numerals are often used for labels (as with telephone numbers), for ordering (as with serial numbers), and for codes (as with ISBNs). In common usage, a "numeral" is not clearly distinguished from the "number" that it represents.

Un nombre est un concept permettant d’évaluer et de comparer des quantités ou des rapports de grandeurs, mais aussi d’ordonner des éléments par une numérotation. Souvent écrits à l’aide d’un ou plusieurs chiffres, les nombres interagissent par le biais d’opérations qui sont résumées par des règles de calcul. Les propriétés de ces relations entre les nombres sont l’objet d’étude de l’arithmétique, qui se prolonge avec la théorie des nombres.