document_title: Constantinople

question_text: what is the modern day name for the city of constantinople

question_tokens: what is the modern day name for the city of constantinople

text: Constantinople

text: Names[edit]

text: Before Constantinople[edit]

text: According to Pliny the Elder in his Natural History, the first known name of a settlement on the site of Constantinople was Lygos,[12] a settlement of likely Thracian origin founded between the 13th and 11th century BC.[13] The site, according to the founding myth of the city, was abandoned by the time Greek settlers from the city-state of Megara founded Byzantium (Greek: Βυζάντιον, Byzántion) in around 657 BC,[14] across from the town of Chalcedon on the Asiatic side of the Bosphorus.[citation needed]

text: The origins of the name of Byzantion, more commonly known by the later Latin Byzantium, are not entirely clear, though some suggest it is of Thraco-Illyrian origin.[15][16] The founding myth of the city has it told that the settlement was named after the leader of the Megarian colonists, Byzas. The later Byzantines of Constantinople themselves would maintain that the city was named in honour of two men, Byzas and Antes, though this was more likely just a play on the word Byzantion.[17]

text: The city was briefly renamed Augusta Antonina in the early 3rd century by the Emperor Septimius Severus (193–211), having razed the city to the ground in 196 AD for supporting a rival contender in the civil war and rebuilt, in honour of his son Antoninus, the later Emperor Caracalla.[18][19] The name appears to have been quickly forgotten and abandoned, and the city reverted to Byzantium/Byzantion after either the assassination of Caracalla in 217 or, at the latest, the fall of the Severan dynasty in 235.[citation needed]

text: Names of Constantinople[edit]

text: Byzantium took on the name of Konstantinoupolis ("city of Constantine", Constantinople) after its re-foundation under Roman emperor Constantine I, who transferred the capital of the Roman Empire from Rome to Byzantium in 330 AD and designated his new capital officially as Nova Roma (Νέα Ῥώμη) 'New Rome'. During this time, the city was also called 'Second Rome', 'Eastern Rome', and Roma Constantinopolitana.[20] As the city became the sole remaining capital of the Roman Empire after the fall of the West, and its wealth, population, and influence grew, the city also came to have a multitude of nicknames.[citation needed]

text: As the largest and wealthiest city in Europe during the 4th–13th centuries and a centre of culture and education of the Mediterranean basin, Constantinople came to be known by prestigious titles such as Basileuousa (Queen of Cities) and Megalopolis (the Great City) and was, in colloquial speech, commonly referred to as just Polis (η πόλη) 'the City' by Constantinopolitans and provincial Byzantines alike.[21]

text: In the language of other peoples, Constantinople was referred to just as reverently. The medieval Vikings, who had contacts with the empire through their expansion in eastern Europe (Varangians) used the Old Norse name Miklagarðr (from mikill 'big' and garðr 'city'), and later Miklagard and Miklagarth. In Arabic, the city was sometimes called Rūmiyyat al-kubra (Great City of the Romans) and in Persian as Takht-e Rum (Throne of the Romans).[citation needed]

text: In East and South Slavic languages, including in medieval Russia, Constantinople was referred to as Tsargrad (Царьград) or Carigrad, 'City of the Caesar (Emperor)', from the Slavonic words tsar ('Caesar' or 'King') and grad ('city'). This was presumably a calque on a Greek phrase such as Βασιλέως Πόλις (Vasileos Polis), 'the city of the emperor [king]'.[citation needed]

text: Modern names of the city[edit]

text: The modern Turkish name for the city, İstanbul, derives from the Greek phrase eis tin polin (εἰς τὴν πόλιν), meaning "into the city" or "to the city".[22] This name was used in Turkish alongside Kostantiniyye, the more formal adaptation of the original Constantinople, during the period of Ottoman rule, while western languages mostly continued to refer to the city as Constantinople until the early 20th century. In 1928, the Turkish alphabet was changed from Arabic script to Latin script. After that, as part of the 1920s Turkification movement, Turkey started to urge other countries to use Turkish names for Turkish cities, instead of other transliterations to Latin script that had been used in the Ottoman times.[23][24][25][26] In time the city came to be known as Istanbul and its variations in most world languages.[citation needed]

text: The name "Constantinople" is still used by members of the Eastern Orthodox Church in the title of one of their most important leaders, the Orthodox patriarch based in the city, referred to as "His Most Divine All-Holiness the Archbishop of Constantinople New Rome and Ecumenical Patriarch." In Greece today, the city is still called Konstantinoúpolis/Konstantinoúpoli (Κωνσταντινούπολις/Κωνσταντινούπολη) or simply just "the City" (Η Πόλη / Η Πόλις).[citation needed]

text: History[edit]

text: Byzantium and earlier settlements[edit]

text: Constantinople was founded by the Roman Emperor Constantine I (272–337 AD) in 324[5] on the site of an already-existing city, Byzantium, which was settled in the early days of Greek colonial expansion, in around 657 BC, by colonists of the city-state of Megara. This is the first major settlement that would develop on the site of later Constantinople, but the first known settlements was that of Lygos, referred to in Pliny's Natural Histories,[27] Apart from this, little is known about this initial settlement. The site, according to the founding myth of the city, was abandoned by the time Greek settlers from the city-state of Megara founded Byzantium (Greek: Βυζάντιον, Byzántion) in around 657 BC,[14] across from the town of Chalcedon on the Asiatic side of the Bosphorus.[citation needed]

text: The city maintained independence as a city-state until it was annexed by Darius I in 512 BC into the Persian Empire, who saw the site as the optimal location to construct a pontoon bridge crossing into Europe as Byzantium was situated at the narrowest point in the Bosphorus strait. Persian rule lasted until 478 BC when as part of the Greek counterattack to the Second Persian Invasion of Greece, a Greek army led by the Spartan general Pausanias captured the city which remained an independent, yet subordinate, city under the Athenians, and later to the Spartans after 411 BC.[28] A farsighted treaty with the emergent power of Rome in c.150 BC which stipulated tribute in exchange for independent status allowed it to enter Roman rule unscathed.[29] This treaty would pay dividends retrospectively as Byzantium would maintain this independent status, and prosper under peace and stability in the Pax Romana, for nearly three centuries until the late 2nd century AD.[30]

text: Byzantium was never a major influential city-state like that of Athens, Corinth, and Sparta, but the city enjoyed relative peace and steady growth as a prosperous trading city lent by its remarkable position. The site lay astride the land route from Europe to Asia and the seaway from the Black Sea to the Mediterranean, and had in the Golden Horn an excellent and spacious harbour. Already then, in Greek and early Roman times, Byzantium was famous for its strategic geographic position that made it difficult to besiege and capture, and its position at the crossroads of the Asiatic-European trade route over land and as the gateway between the Mediterranean and Black Seas made it too valuable a settlement to abandon, as Emperor Septimius Severus later realized when he razed the city to the ground for supporting Pescennius Niger's claimancy.[31] It was a move greatly criticized by the contemporary consul and historian Cassius Dio who said that Severus had destroyed "a strong Roman outpost and a base of operations against the barbarians from Pontus and Asia".[32] He would later rebuild Byzantium towards the end of his reign, in which it would be briefly renamed Augusta Antonina, fortifying it with a new city wall in his name, the Severan Wall.[citation needed]

text: 324–337: Foundation of Constantinople[edit]

text: Constantine had altogether more colourful plans. Having restored the unity of the Empire, and, being in the course of major governmental reforms as well as of sponsoring the consolidation of the Christian church, he was well aware that Rome was an unsatisfactory capital. Rome was too far from the frontiers, and hence from the armies and the imperial courts, and it offered an undesirable playground for disaffected politicians. Yet it had been the capital of the state for over a thousand years, and it might have seemed unthinkable to suggest that the capital be moved to a different location. Nevertheless, Constantine identified the site of Byzantium as the right place: a place where an emperor could sit, readily defended, with easy access to the Danube or the Euphrates frontiers, his court supplied from the rich gardens and sophisticated workshops of Roman Asia, his treasuries filled by the wealthiest provinces of the Empire.[citation needed]

text: Constantinople was built over 6 years, and consecrated on 11 May 330.[5][33] Constantine divided the expanded city, like Rome, into 14 regions, and ornamented it with public works worthy of an imperial metropolis.[34] Yet, at first, Constantine's new Rome did not have all the dignities of old Rome. It possessed a proconsul, rather than an urban prefect. It had no praetors, tribunes, or quaestors. Although it did have senators, they held the title clarus, not clarissimus, like those of Rome. It also lacked the panoply of other administrative offices regulating the food supply, police, statues, temples, sewers, aqueducts, or other public works. The new programme of building was carried out in great haste: columns, marbles, doors, and tiles were taken wholesale from the temples of the empire and moved to the new city. In similar fashion, many of the greatest works of Greek and Roman art were soon to be seen in its squares and streets. The emperor stimulated private building by promising householders gifts of land from the imperial estates in Asiana and Pontica and on 18 May 332 he announced that, as in Rome, free distributions of food would be made to the citizens. At the time, the amount is said to have been 80,000 rations a day, doled out from 117 distribution points around the city.[35]

text: Constantine laid out a new square at the centre of old Byzantium, naming it the Augustaeum. The new senate-house (or Curia) was housed in a basilica on the east side. On the south side of the great square was erected the Great Palace of the Emperor with its imposing entrance, the Chalke, and its ceremonial suite known as the Palace of Daphne. Nearby was the vast Hippodrome for chariot-races, seating over 80,000 spectators, and the famed Baths of Zeuxippus. At the western entrance to the Augustaeum was the Milion, a vaulted monument from which distances were measured across the Eastern Roman Empire.[citation needed]

text: From the Augustaeum led a great street, the Mese (Greek: Μέση [Οδός] lit. "Middle [Street]"), lined with colonnades. As it descended the First Hill of the city and climbed the Second Hill, it passed on the left the Praetorium or law-court. Then it passed through the oval Forum of Constantine where there was a second Senate-house and a high column with a statue of Constantine himself in the guise of Helios, crowned with a halo of seven rays and looking toward the rising sun. From there, the Mese passed on and through the Forum Tauri and then the Forum Bovis, and finally up the Seventh Hill (or Xerolophus) and through to the Golden Gate in the Constantinian Wall. After the construction of the Theodosian Walls in the early 5th century, it was extended to the new Golden Gate, reaching a total length of seven Roman miles.[36]

text: 337–529: Constantinople during the Barbarian Invasions and the fall of the West[edit]

text: The importance of Constantinople increased, but it was gradual. From the death of Constantine in 337 to the accession of Theodosius I, emperors had been resident only in the years 337-8, 347–51, 358–61, 368–69. Its status as a capital was recognized by the appointment of the first known Urban Prefect of the City Honoratus, who held office from 11 December 359 until 361. The urban prefects had concurrent jurisdiction over three provinces each in the adjacent dioceses of Thrace (in which the city was located), Pontus and Asia comparable to the 100-mile extraordinary jurisdiction of the prefect of Rome. The emperor Valens, who hated the city and spent only one year there, nevertheless built the Palace of Hebdomon on the shore of the Propontis near the Golden Gate, probably for use when reviewing troops. All the emperors up to Zeno and Basiliscus were crowned and acclaimed at the Hebdomon. Theodosius I founded the Church of John the Baptist to house the skull of the saint (today preserved at the Topkapı Palace), put up a memorial pillar to himself in the Forum of Taurus, and turned the ruined temple of Aphrodite into a coach house for the Praetorian Prefect; Arcadius built a new forum named after himself on the Mese, near the walls of Constantine.[citation needed]

text: After the shock of the Battle of Adrianople in 378, in which the emperor Valens with the flower of the Roman armies was destroyed by the Visigoths within a few days' march, the city looked to its defences, and in 413–414 Theodosius II built the 18-metre (60-foot)-tall triple-wall fortifications, which were not to be breached until the coming of gunpowder. Theodosius also founded a University near the Forum of Taurus, on 27 February 425.[citation needed]

text: Uldin, a prince of the Huns, appeared on the Danube about this time and advanced into Thrace, but he was deserted by many of his followers, who joined with the Romans in driving their king back north of the river. Subsequent to this, new walls were built to defend the city and the fleet on the Danube improved.[citation needed]

text: After the barbarians overran the Western Roman Empire, Constantinople became the indisputable capital city of the Roman Empire. Emperors were no longer peripatetic between various court capitals and palaces. They remained in their palace in the Great City and sent generals to command their armies. The wealth of the eastern Mediterranean and western Asia flowed into Constantinople.[citation needed]

text: 527–565: Constantinople in the Age of Justinian[edit]

text: The emperor Justinian I (527–565) was known for his successes in war, for his legal reforms and for his public works. It was from Constantinople that his expedition for the reconquest of the former Diocese of Africa set sail on or about 21 June 533. Before their departure, the ship of the commander Belisarius was anchored in front of the Imperial palace, and the Patriarch offered prayers for the success of the enterprise. After the victory, in 534, the Temple treasure of Jerusalem, looted by the Romans in 70 AD and taken to Carthage by the Vandals after their sack of Rome in 455, was brought to Constantinople and deposited for a time, perhaps in the Church of St. Polyeuctus, before being returned to Jerusalem in either the Church of the Resurrection or the New Church.[38]

text: Chariot-racing had been important in Rome for centuries. In Constantinople, the hippodrome became over time increasingly a place of political significance. It was where (as a shadow of the popular elections of old Rome) the people by acclamation showed their approval of a new emperor, and also where they openly criticized the government, or clamoured for the removal of unpopular ministers. In the time of Justinian, public order in Constantinople became a critical political issue.[citation needed]

text: Throughout the late Roman and early Byzantine periods, Christianity was resolving fundamental questions of identity, and the dispute between the orthodox and the monophysites became the cause of serious disorder, expressed through allegiance to the horse-racing parties of the Blues and the Greens. The partisans of the Blues and the Greens were said[39] to affect untrimmed facial hair, head hair shaved at the front and grown long at the back, and wide-sleeved tunics tight at the wrist; and to form gangs to engage in night-time muggings and street violence. At last these disorders took the form of a major rebellion of 532, known as the "Nika" riots (from the battle-cry of "Victory!" of those involved).[citation needed]

text: Fires started by the Nika rioters consumed Constantine's basilica of Hagia Sophia (Holy Wisdom), the city's principal church, which lay to the north of the Augustaeum. Justinian commissioned Anthemius of Tralles and Isidore of Miletus to replace it with a new and incomparable Hagia Sophia. This was the great cathedral of the Orthodox Church, whose dome was said to be held aloft by God alone, and which was directly connected to the palace so that the imperial family could attend services without passing through the streets.[40] The dedication took place on 26 December 537 in the presence of the emperor, who exclaimed, "O Solomon, I have outdone thee!"[41] Hagia Sophia was served by 600 people including 80 priests, and cost 20,000 pounds of gold to build.[42]

text: Justinian also had Anthemius and Isidore demolish and replace the original Church of the Holy Apostles built by Constantine with a new church under the same dedication. This was designed in the form of an equal-armed cross with five domes, and ornamented with beautiful mosaics. This church was to remain the burial place of the Emperors from Constantine himself until the 11th century. When the city fell to the Turks in 1453, the church was demolished to make room for the tomb of Mehmet II the Conqueror. Justinian was also concerned with other aspects of the city's built environment, legislating against the abuse of laws prohibiting building within 100 feet (30 m) of the sea front, in order to protect the view.[43]

text: During Justinian I's reign, the city's population reached about 500,000 people.[44] However, the social fabric of Constantinople was also damaged by the onset of the Plague of Justinian between 541–542 AD. It killed perhaps 40% of the city's inhabitants.[45]

text: Survival, 565–717: Constantinople during the Byzantine Dark Ages[edit]

text: In the early 7th century, the Avars and later the Bulgars overwhelmed much of the Balkans, threatening Constantinople with attack from the west. Simultaneously, the Persian Sassanids overwhelmed the Prefecture of the East and penetrated deep into Anatolia. Heraclius, son of the exarch of Africa, set sail for the city and assumed the purple. He found the military situation so dire that he is said to have contemplated withdrawing the imperial capital to Carthage, but relented after the people of Constantinople begged him to stay. The citizens lost their right to free grain in 618 when Heraclius realised that the city could no longer be supplied from Egypt as a result of the Persian wars: the population fell substantially as a result.[46]

text: While the city withstood a siege by the Sassanids and Avars in 626, Heraclius campaigned deep into Persian territory and briefly restored the status quo in 628, when the Persians surrendered all their conquests. However, further sieges followed the Arab conquests, first from 674 to 678 and then in 717 to 718. The Theodosian Walls kept the city impregnable from the land, while a newly discovered incendiary substance known as Greek Fire allowed the Byzantine navy to destroy the Arab fleets and keep the city supplied. In the second siege, the second ruler of Bulgaria, Khan Tervel, rendered decisive help. He was called Saviour of Europe.[47]

text: 717–1025: Constantinople during the Macedonian Renaissance[edit]

text: In the 730s Leo III carried out extensive repairs of the Theodosian walls, which had been damaged by frequent and violent attacks; this work was financed by a special tax on all the subjects of the Empire.[48]

text: Theodora, widow of the Emperor Theophilus (died 842), acted as regent during the minority of her son Michael III, who was said to have been introduced to dissolute habits by her brother Bardas. When Michael assumed power in 856, he became known for excessive drunkenness, appeared in the hippodrome as a charioteer and burlesqued the religious processions of the clergy. He removed Theodora from the Great Palace to the Carian Palace and later to the monastery of Gastria, but, after the death of Bardas, she was released to live in the palace of St Mamas; she also had a rural residence at the Anthemian Palace, where Michael was assassinated in 867.[49]

text: In 860, an attack was made on the city by a new principality set up a few years earlier at Kiev by Askold and Dir, two Varangian chiefs: Two hundred small vessels passed through the Bosporus and plundered the monasteries and other properties on the suburban Prince's Islands. Oryphas, the admiral of the Byzantine fleet, alerted the emperor Michael, who promptly put the invaders to flight; but the suddenness and savagery of the onslaught made a deep impression on the citizens.[50]

text: In 980, the emperor Basil II received an unusual gift from Prince Vladimir of Kiev: 6,000 Varangian warriors, which Basil formed into a new bodyguard known as the Varangian Guard. They were known for their ferocity, honour, and loyalty. It is said that, in 1038, they were dispersed in winter quarters in the Thracesian theme when one of their number attempted to violate a countrywoman, but in the struggle she seized his sword and killed him; instead of taking revenge, however, his comrades applauded her conduct, compensated her with all his possessions, and exposed his body without burial as if he had committed suicide.[51] However, following the death of an Emperor, they became known also for plunder in the Imperial palaces.[52] Later in the 11th Century the Varangian Guard became dominated by Anglo-Saxons who preferred this way of life to subjugation by the new Norman kings of England.[53]

text: The Book of the Eparch, which dates to the 10th century, gives a detailed picture of the city's commercial life and its organization at that time. The corporations in which the tradesmen of Constantinople were organised were supervised by the Eparch, who regulated such matters as production, prices, import, and export. Each guild had its own monopoly, and tradesmen might not belong to more than one. It is an impressive testament to the strength of tradition how little these arrangements had changed since the office, then known by the Latin version of its title, had been set up in 330 to mirror the urban prefecture of Rome.[54]

text: In the 9th and 10th centuries, Constantinople had a population of between 500,000 and 800,000.[55]

text: Iconoclast controversy in Constantinople[edit]

text: In the 8th and 9th centuries, the iconoclast movement caused serious political unrest throughout the Empire. The emperor Leo III issued a decree in 726 against images, and ordered the destruction of a statue of Christ over one of the doors of the Chalke, an act that was fiercely resisted by the citizens.[56] Constantine V convoked a church council in 754, which condemned the worship of images, after which many treasures were broken, burned, or painted over with depictions of trees, birds or animals: One source refers to the church of the Holy Virgin at Blachernae as having been transformed into a "fruit store and aviary".[57] Following the death of her son Leo IV in 780, the empress Irene restored the veneration of images through the agency of the Second Council of Nicaea in 787.[citation needed]

text: The iconoclast controversy returned in the early 9th century, only to be resolved once more in 843 during the regency of Empress Theodora, who restored the icons. These controversies contributed to the deterioration of relations between the Western and the Eastern Churches.[citation needed]

text: 1025–1081: Constantinople after Basil II[edit]

text: In the late 11th century catastrophe struck with the unexpected and calamitous defeat of the imperial armies at the Battle of Manzikert in Armenia in 1071. The Emperor Romanus Diogenes was captured. The peace terms demanded by Alp Arslan, sultan of the Seljuk Turks, were not excessive, and Romanus accepted them. On his release, however, Romanus found that enemies had placed their own candidate on the throne in his absence; he surrendered to them and suffered death by torture, and the new ruler, Michael VII Ducas, refused to honour the treaty. In response, the Turks began to move into Anatolia in 1073. The collapse of the old defensive system meant that they met no opposition, and the empire's resources were distracted and squandered in a series of civil wars. Thousands of Turkoman tribesmen crossed the unguarded frontier and moved into Anatolia. By 1080, a huge area had been lost to the Empire, and the Turks were within striking distance of Constantinople.[citation needed]

text: 1081–1185: Constantinople under the Comneni[edit]

text: Under the Comnenian dynasty (1081–1185), Byzantium staged a remarkable recovery. In 1090–91, the nomadic Pechenegs reached the walls of Constantinople, where Emperor Alexius I with the aid of the Kipchaks annihilated their army.[58] In response to a call for aid from Alexius, the First Crusade assembled at Constantinople in 1096, but declining to put itself under Byzantine command set out for Jerusalem on its own account.[59] John II built the monastery of the Pantocrator (Almighty) with a hospital for the poor of 50 beds.[60]

text: With the restoration of firm central government, the empire became fabulously wealthy. The population was rising (estimates for Constantinople in the 12th century vary from some 100,000 to 500,000), and towns and cities across the realm flourished. Meanwhile, the volume of money in circulation dramatically increased. This was reflected in Constantinople by the construction of the Blachernae palace, the creation of brilliant new works of art, and general prosperity at this time: an increase in trade, made possible by the growth of the Italian city-states, may have helped the growth of the economy. It is certain that the Venetians and others were active traders in Constantinople, making a living out of shipping goods between the Crusader Kingdoms of Outremer and the West, while also trading extensively with Byzantium and Egypt. The Venetians had factories on the north side of the Golden Horn, and large numbers of westerners were present in the city throughout the 12th century. Toward the end of Manuel I Komnenos's reign, the number of foreigners in the city reached about 60,000–80,000 people out of a total population of about 400,000 people.[61] In 1171, Constantinople also contained a small community of 2,500 Jews.[62] In 1182, all Latin (Western European) inhabitants of Constantinople were massacred.[63]

text: In artistic terms, the 12th century was a very productive period. There was a revival in the mosaic art, for example: Mosaics became more realistic and vivid, with an increased emphasis on depicting three-dimensional forms. There was an increased demand for art, with more people having access to the necessary wealth to commission and pay for such work. According to N.H. Baynes (Byzantium, An Introduction to East Roman Civilization):

text: 1185–1261: Constantinople during the Imperial Exile[edit]

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text: On 25 July 1197, Constantinople was struck by a severe fire which burned the Latin Quarter and the area around the Gate of the Droungarios (Turkish: Odun Kapısı) on the Golden Horn.[64][65] Nevertheless, the destruction wrought by the 1197 fire paled in comparison with that brought by the Crusaders. In the course of a plot between Philip of Swabia, Boniface of Montferrat and the Doge of Venice, the Fourth Crusade was, despite papal excommunication, diverted in 1203 against Constantinople, ostensibly promoting the claims of Alexius, son of the deposed emperor Isaac. The reigning emperor Alexius III had made no preparation. The Crusaders occupied Galata, broke the defensive chain protecting the Golden Horn, and entered the harbour, where on 27 July they breached the sea walls: Alexius III fled. But the new Alexius IV found the Treasury inadequate, and was unable to make good the rewards he had promised to his western allies. Tension between the citizens and the Latin soldiers increased. In January 1204, the protovestiarius Alexius Murzuphlus provoked a riot, it is presumed, to intimidate Alexius IV, but whose only result was the destruction of the great statue of Athena, the work of Phidias, which stood in the principal forum facing west.[citation needed]

text: In February 1198, the people rose again: Alexius IV was imprisoned and executed, and Murzuphlus took the purple as Alexius V. He made some attempt to repair the walls and organise the citizenry, but there had been no opportunity to bring in troops from the provinces and the guards were demoralised by the revolution. An attack by the Crusaders on 6 April failed, but a second from the Golden Horn on 12 April succeeded, and the invaders poured in. Alexius V fled. The Senate met in Hagia Sophia and offered the crown to Theodore Lascaris, who had married into the Angelid family, but it was too late. He came out with the Patriarch to the Golden Milestone before the Great Palace and addressed the Varangian Guard. Then the two of them slipped away with many of the nobility and embarked for Asia. By the next day the Doge and the leading Franks were installed in the Great Palace, and the city was given over to pillage for three days.[citation needed]

text: Sir Steven Runciman, historian of the Crusades, wrote that the sack of Constantinople is “unparalleled in history”.

text: “For nine centuries,” he goes on, “the great city had been the capital of Christian civilisation. It was filled with works of art that had survived from ancient Greece and with the masterpieces of its own exquisite craftsmen. The Venetians ... seized treasures and carried them off to adorn ... their town. But the Frenchmen and Flemings were filled with a lust for destruction. They rushed in a howling mob down the streets and through the houses, snatching up everything that glittered and destroying whatever they could not carry, pausing only to murder or to rape, or to break open the wine-cellars ... . Neither monasteries nor churches nor libraries were spared. In Hagia Sophia itself, drunken soldiers could be seen tearing down the silken hangings and pulling the great silver iconostasis to pieces, while sacred books and icons were trampled under foot. While they drank merrily from the altar-vessels a prostitute set herself on the Patriarch’s throne and began to sing a ribald French song. Nuns were ravished in their convents. Palaces and hovels alike were entered and wrecked. Wounded women and children lay dying in the streets. For three days the ghastly scenes ... continued, till the huge and beautiful city was a shambles. ... When ... order was restored, ... citizens were tortured to make them reveal the goods that they had contrived to hide.[66]

text: For the next half-century, Constantinople was the seat of the Latin Empire. Under the rulers of the Latin Empire, the city declined, both in population and the condition of its buildings. Alice-Mary Talbot cites an estimated population for Constantinople of 400,000 inhabitants; after the destruction wrought by the Crusaders on the city, about one third were homeless, and numerous courtiers, nobility, and higher clergy, followed various leading personages into exile. "As a result Constantinople became seriously depopulated," Talbot concludes.[67]

text: The Latins took over at least 20 churches and 13 monasteries, most prominently the Hagia Sophia, which became the cathedral of the Latin Patriarch of Constantinople. It is to these that E.H. Swift attributed the construction of a series of flying buttresses to shore up the walls of the church, which had been weakened over the centuries by earthquake tremors.[68] However, this act of maintenance is an exception: for the most part, the Latin occupiers were too few to maintain all of the buildings, either secular and sacred, and many became targets for vandalism or dismantling. Bronze and lead were removed from the roofs of abandoned buildings and melted down and sold to provide money to the chronically under-funded Empire for defense and to support the court; Deno John Geanokoplos writes that "it may well be that a division is suggested here: Latin laymen stripped secular buildings, ecclesiastics, the churches."[69] Buildings were not the only targets of officials looking to raise funds for the impoverished Latin Empire: the monumental sculptures which adorned the Hippodrome and fora of the city were pulled down and melted for coinage. "Among the masterpieces destroyed, writes Talbot, "were a Herakles attributed to the fourth-century B.C. sculptor Lysippos, and monumental figures of Hera, Paris, and Helen."[70]

text: The Nicaean emperor John III Vatatzes reportedly saved several churches from being dismantled for their valuable building materials; by sending money to the Latins "to buy them off" (exonesamenos), he prevented the destruction of several churches.[71] According to Talbot, these included the churches of Blachernae, Rouphinianai, and St. Michael at Anaplous. He also granted funds for the restoration of the Church of the Holy Apostles, which had been seriously damaged in an earthquake.[70]

text: The Byzantine nobility scattered, many going to Nicaea, where Theodore Lascaris set up an imperial court, or to Epirus, where Theodore Angelus did the same; others fled to Trebizond, where one of the Comneni had already with Georgian support established an independent seat of empire.[72] Nicaea and Epirus both vied for the imperial title, and tried to recover Constantinople. In 1261, Constantinople was captured from its last Latin ruler, Baldwin II, by the forces of the Nicaean emperor Michael VIII Palaiologos.[citation needed]

text: 1261–1453: Palaiologan Era and the Fall of Constantinople[edit]

text: Although Constantinople was retaken by Michael VIII Palaiologos, the Empire had lost many of its key economic resources, and struggled to survive. The palace of Blachernae in the north-west of the city became the main Imperial residence, with the old Great Palace on the shores of the Bosporus going into decline. When Michael VIII captured the city, its population was 35,000 people, but, by the end of his reign, he had succeeded in increasing the population to about 70,000 people.[73] The Emperor achieved this by summoning former residents who had fled the city when the crusaders captured it, and by relocating Greeks from the recently reconquered Peloponnese to the capital.[74] In 1347, the Black Death spread to Constantinople.[75] In 1453, when the Ottoman Turks captured the city, it contained approximately 50,000 people.[76]

text: Constantinople was conquered by the Ottoman Empire on 29 May 1453, due to the use of cannon. The Ottomans were commanded by 22-year-old Ottoman Sultan Mehmed II. The conquest of Constantinople followed a seven-week siege which had begun on 6 April 1453.[citation needed]

text: 1453–1922: Ottoman Kostantiniyye[edit]

text: The Christian Orthodox city of Constantinople was now under Ottoman control. When Mehmed II finally entered Constantinople through what is now known as the Topkapi Gate, he immediately rode his horse to the Hagia Sophia, where he ordered his soldiers to stop hacking at the marbles and 'be satisfied with the booty and captives; as for all the buildings, they belonged to him'.[77] He ordered that an imam meet him there in order to chant the adhan thus transforming the Orthodox cathedral into a Muslim mosque,[77][78] solidifying Islamic rule in Constantinople.[citation needed]

text: Mehmed’s main concern with Constantinople had to do with rebuilding the city’s defenses and population. Building projects were commenced immediately after the conquest, which included the repair of the walls, construction of the citadel, and building a new palace.[79] Mehmed issued orders across his empire that Muslims, Christians, and Jews should resettle the city; he demanded that five thousand households needed to be transferred to Constantinople by September.[79] From all over the Islamic empire, prisoners of war and deported people were sent to the city: these people were called "Sürgün" in Turkish (Greek: σουργούνιδες).[10] Two centuries later, Ottoman traveler Evliya Çelebi gave a list of groups introduced into the city with their respective origins. Even today, many quarters of Istanbul, such as Aksaray, Çarşamba, bear the names of the places of origin of their inhabitants.[10] However, many people escaped again from the city, and there were several outbreaks of plague, so that in 1459 Mehmet allowed the deported Greeks to come back to the city.[10]

text: Importance[edit]

text: Culture[edit]

text: Constantinople was the largest and richest urban center in the Eastern Mediterranean Sea during the late Eastern Roman Empire, mostly as a result of its strategic position commanding the trade routes between the Aegean Sea and the Black Sea. It would remain the capital of the eastern, Greek-speaking empire for over a thousand years. At its peak, roughly corresponding to the Middle Ages, it was the richest and largest European city, exerting a powerful cultural pull and dominating economic life in the Mediterranean. Visitors and merchants were especially struck by the beautiful monasteries and churches of the city, in particular, Hagia Sophia, or the Church of Holy Wisdom. According to Russian 14th-century traveler Stephen of Novgorod: "As for Hagia Sophia, the human mind can neither tell it nor make description of it."[citation needed]

text: It was especially important for preserving in its libraries manuscripts of Greek and Latin authors throughout a period when instability and disorder caused their mass-destruction in western Europe and north Africa: On the city's fall, thousands of these were brought by refugees to Italy, and played a key part in stimulating the Renaissance, and the transition to the modern world. The cumulative influence of the city on the west, over the many centuries of its existence, is incalculable. In terms of technology, art and culture, as well as sheer size, Constantinople was without parallel anywhere in Europe for a thousand years.[citation needed]

text: Armenians, Syrians, Slavs, and Georgians were part of the Byzantine social hierarchy.[80]

text: International status[edit]

text: The city provided a defence for the eastern provinces of the old Roman Empire against the barbarian invasions of the 5th century. The 18-meter-tall walls built by Theodosius II were, in essence, impregnable to the barbarians coming from south of the Danube river, who found easier targets to the west rather than the richer provinces to the east in Asia. From the 5th century, the city was also protected by the Anastasian Wall, a 60-kilometer chain of walls across the Thracian peninsula. Many scholars[who?] argue that these sophisticated fortifications allowed the east to develop relatively unmolested while Ancient Rome and the west collapsed.[81]

text: Constantinople's fame was such that it was described even in contemporary Chinese histories, the Old and New Book of Tang, which mentioned its massive walls and gates as well as a purported clepsydra mounted with a golden statue of a man.[82][83][84] The Chinese histories even related how the city had been besieged in the 7th century by Muawiyah I and how he exacted tribute in a peace settlement.[83][85]

text: Architecture[edit]

text: The Byzantine Empire used Roman and Greek architectural models and styles to create its own unique type of architecture. The influence of Byzantine architecture and art can be seen in the copies taken from it throughout Europe. Particular examples include St Mark's Basilica in Venice, the basilicas of Ravenna, and many churches throughout the Slavic East. Also, alone in Europe until the 13th-century Italian florin, the Empire continued to produce sound gold coinage, the solidus of Diocletian becoming the bezant prized throughout the Middle Ages. Its city walls were much imitated (for example, see Caernarfon Castle) and its urban infrastructure was moreover a marvel throughout the Middle Ages, keeping alive the art, skill and technical expertise of the Roman Empire. In the Ottoman period Islamic architecture and symbolism were used.[citation needed]

text: Religion[edit]

text: Constantine's foundation gave prestige to the Bishop of Constantinople, who eventually came to be known as the Ecumenical Patriarch, and made it a prime center of Christianity alongside Rome. This contributed to cultural and theological differences between Eastern and Western Christianity eventually leading to the Great Schism that divided Western Catholicism from Eastern Orthodoxy from 1054 onwards. Constantinople is also of great religious importance to Islam, as the conquest of Constantinople is one of the signs of the End time in Islam.[citation needed]

text: Popular culture[edit]

text:
Constantinople appears as a city of wondrous majesty, beauty, remoteness, and nostalgia in William Butler Yeats' 1928 poem "Sailing to Byzantium."
Constantinople, as seen under the Byzantine emperor Theodosius II, makes several on-screen appearances in the television miniseries "Attila" as the capital of the Eastern Roman Empire.
Finnish author Mika Waltari wrote one of his most-acclaimed historical novels, Johannes Angelos (published in English by name "The Dark Angel") on the fall of Constantinople.
Robert Graves, author of I, Claudius, also wrote Count Belisarius, a historical novel about Belisarius. Graves set much of the novel in the Constantinople of Justinian I.
Constantinople provides the setting of much of the action in Umberto Eco's 2000 novel Baudolino.
The name Constantinople was made easy to spell thanks to a novelty song, "C-O-N-S-T-A-N-T-I-N-O-P-L-E," written by Harry Carlton and performed by Paul Whiteman and his Orchestra, in the 1920s.
Constantinople's change of name was the theme for a song made famous by The Four Lads and later covered by They Might Be Giants and many others, titled "Istanbul (Not Constantinople)."
"Constantinople" was one of the "big words" the Father knows toward the end of Dr. Seuss's book, Hop on Pop. (The other was Timbuktu.)
"Constantinople" was also the title of the opening edit of The Residents' EP Duck Stab!, released in 1978.
Queen's Roger Meddows Taylor included the track "Interlude in Constantinople" on Side 2 of his debut album Fun in Space.
A Montreal-based folk/classical/fusion band calls itself "Constantinople."
Constantinople under Justinian is the scene of the book A Flame in Byzantium (ISBN 0-312-93026-7) by Chelsea Quinn Yarbro, released in 1987.
"Constantinople" is the title of a song by The Decemberists.
Stephen Lawhead's novel Byzantium (1996) is set in 9th-century Constantinople.
Folk Metal band Turisas makes multiple references to Constantinople in their song "Miklagard Overture," referring to it as "Konstantinopolis," "Tsargrad," and "Miklagard."
Constantinople makes an appearance in the MMORPG game Silkroad as a major capital, along with a major Chinese capital.
Constantinople makes an appearance in the "Rome Total War" expansion "Barbarian Invasion" belonging to the Eastern Roman Empire. It would reappear in the same role for the spiritual sequel, Total War: Attila.
Constantinople also makes an appearance in "Medieval Total War." It is a starting province and city of the Byzantines.
Constantinople makes an appearance in the game "Age of Empires II: The Age of Kings" in the fifth scenario of the Barbarossa campaign and again in the third scenario of the Attila the Hun campaign in the expansion pack "Age of Empires II: The Conquerors Expansion."
Constantinople is the main setting of the game "Assassin's Creed: Revelations," the fourth major title in the best-selling "Assassin's Creed" series.[86]
Constantinople is also a setting of the Vampire: The Dark Ages role playing game by White Wolf.[87]
Constantinople is one of the territories featured in the Board Game Diplomacy. It is one of the default territories of Turkey.


document_title: Colon (punctuation)

question_text: while writing time the number after the two dots stands for

question_tokens: while writing time the number after the two dots stands for

root

text: Colon (punctuation)

text: Usage[edit]

text: The most common use of the colon is to inform the reader that what follows the colon proves, explains, defines, describes, or lists elements of what preceded it. In modern American English usage, a complete sentence precedes a colon, while a list, description, explanation, or definition follows it. The elements which follow the colon may or may not be a complete sentence: since the colon is preceded by a sentence, it is a complete sentence whether what follows the colon is another sentence or not. While it is acceptable to capitalize the first letter after the colon in American English, it is not the case in British English, except where a proper noun immediately follows a colon.[2]

tag: p

text: Some writers use fragments (incomplete sentences) before a colon for emphasis or stylistic preferences (to show a character's voice in literature), as in this example:

text: The Bedford Handbook describes several uses of a colon. For example, one can use a colon after an independent clause to direct attention to a list, an appositive or a quotation, and it can be used between independent clauses if the second summarizes or explains the first. In non-literary or non-expository uses, one may use a colon after the salutation in a formal letter, to indicate hours and minutes, to show proportions, between a title and subtitle, and between city and publisher in bibliographic entries.[3]

text: Luca Serianni, an Italian scholar who helped to define and develop the colon as a punctuation mark, identified four punctuational modes for it: syntactical-deductive, syntactical-descriptive, appositive, and segmental.[4] Although Serianni wrote this guide for the Italian language, his definitions apply also to English and many other languages.

text: Syntactical-deductive[edit]

text: The colon introduces the logical consequence, or effect, of a fact stated before.

text: Syntactical-descriptive[edit]

text: In this sense the colon introduces a description; in particular, it makes explicit the elements of a set.

text: Syntactical-descriptive colons may separate the numbers indicating hours, minutes, and seconds in abbreviated measures of time.[5]

text: British English, however, more frequently uses a point for this purpose:

text: Appositive[edit]

text: An appositive colon also separates the subtitle of a work from its principal title. Dillon has noted the impact of colons on scholarly articles,[8][9] but the reliability of colons as a predictor of quality or impact has also been challenged.[10][11] In titles, neither needs to be a complete sentence as titles do not represent expository writing:

text: Segmental[edit]

text: Like a dash or quotation mark, a segmental colon introduces speech. The segmental function was once a common means of indicating an unmarked quotation on the same line. The following example is from the grammar book The King's English:

text: This form is still used in written dialogues, such as in a play. The colon indicates that the words following an individual's name are spoken by that individual.

text: Use of capitals[edit]

text: Use of capitalization or lower-case after a colon varies. In British English, the word following the colon is in lower case unless it is normally capitalized for some other reason, as with proper nouns and acronyms. British English also capitalizes a new sentence introduced by colon's segmental use; American English goes further and permits writers to similarly capitalize the first word of any independent clause following a colon. This follows the guidelines of some modern American style guides, including those published by the Associated Press and the Modern Language Association. The Chicago Manual of Style, however, requires capitalization only when the colon introduces a direct quotation, a direct question, or two or more complete sentences.[12]

text: In many European languages, the colon is usually followed by a lower-case letter unless the upper case is required for other reasons, as with British English. German usage requires capitalization of independent clauses following a colon.[13] Dutch further capitalizes the first word of any quotation following a colon, even if it is not a complete sentence on its own.[14]

text: Spacing[edit]

text: In print, a thin space was traditionally placed before a colon and a thick space after it. In modern English-language printing, no space is placed before a colon and a single space is placed after it. In French-language typing and printing, the traditional rules are preserved.

text: One or two spaces may be and have been used after a colon. The older convention (designed to be used by monospaced fonts) was to use two spaces after a colon.[15]

text: History[edit]

text: The English word "colon" is from Latin colon (pl. cola), itself from Ancient Greek κῶλον (kôlon), meaning "limb", "member", or "portion". In Greek rhetoric and prosody, the term did not refer to punctuation but to the expression or passage itself. A "colon" was section of a complete thought or passage. From this usage, in palaeography, a colon is a clause or group of clauses written as a line in a manuscript.[16] In the punctuation system devised by Aristophanes of Byzantium in the 3rd century BC, the end of such a clause was thought to occasion a medium-length breath and was marked by a middot ⟨·⟩. (This was only intermittently used, but eventually revived as the ano teleia, the modern Greek semicolon.[17]) A double dot symbol ⟨⁚⟩, meanwhile, later came to be used as a full stop or to mark a change of speaker. A variant was introduced to English orthography around 1600, marking a pause intermediate between a comma and a period.[18] As late as the 18th century, the appropriateness of a colon was still being related to the length of the pause taken when reading the text aloud, but silent reading eventually replaced this with other considerations.[19]

text: In British English, it was once common for a colon to be followed by a hyphen or dash to indicate a restful pause, in a typographical construction known as the "dog's bollocks", though this usage is now discouraged.[20][21][22]

text: International Phonetic Alphabet[edit]

text: A special triangular colon symbol is used in IPA to indicate that the preceding sound is long. Its form is that of two triangles, each a little larger than a point (dot) of a standard colon, pointing toward each other. It is available in Unicode as modifier letter triangular colon, Unicode U+02D0 (ː). A regular colon is often used as a fallback when this character is not available, and in the practical orthography of some languages which have a phonemic long/short distinction in vowels.

text: If the upper triangle is used without the lower one (modifier letter half triangular colon, Unicode U+02D1: ⟨ˑ⟩), it designates a "half-long" vowel.[23]

text: Other phonetic alphabets also use colons. For example, the Uralic Phonetic Alphabet uses U+02F8 ˸ MODIFIER LETTER RAISED COLON[24]

text: Word-medial separator[edit]

text: In Finnish and Swedish, the colon can appear inside words in a manner similar to the apostrophe in the English possessive case, connecting a grammatical suffix to an abbreviation or initialism, a special symbol, or a digit (e.g., Finnish USA:n and Swedish USA:s for the genitive case of "USA", Finnish %:ssa for the inessive case of "%", or Finnish 20:een for the illative case of "20").

text: Abbreviation[edit]

text: In Swedish, the colon is used in contractions, such as S:t for Sankt (Swedish for "Saint"), e.g. in the Stockholm metro station S:t Eriksplan. This can even occur in people's names, for example Antonia Ax:son Johnson (Ax:son for Axelson). The colon was also used to mark abbreviations in early modern English.[25][26]

text: End of sentence[edit]

text: In Armenian, a colon indicates the end of a sentence, similar to a Latin full stop or period.

text: Letter[edit]

text: The colon is also used as a grammatical tone letter in Budu in the Democratic Republic of the Congo, in Sabaot in Kenya, in some Grebo in Liberia, and in Papua New Guinea: Erima, Gizra, Go꞉bosi, Gwahatike, Kaluli, Kamula, Kasua, Kuni-Boazi, and Zimakani.[27] The Unicode character used for the tone letter U+A789 ꞉ modifier letter colon is different from the punctuation (U+003A), as well from IPA's triangular colon U+02D0.

text: Mathematics and logic[edit]

text: This article needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (January 2018) (Learn how and when to remove this template message)

tag: table

text: This section possibly contains original research. Please improve it by verifying the claims made and adding inline citations. Statements consisting only of original research should be removed. (January 2018) (Learn how and when to remove this template message)

text: The colon is used in mathematics, cartography, model building, and other fields—in this context it denotes a ratio or a scale, as in 3:1 (pronounced "three to one"). When a ratio is reduced to a simpler form, such as 10:15 to 2:3, this may be expressed with a double colon as 10:15::2:3; this would be read "10 is to 15 as 2 is to 3". This form is also used in tests of logic where the question of "Dog is to Puppy as Cat is to _____?" can be expressed as "Dog:Puppy::Cat:_____". Unicode provides a distinct character U+2236 ∶ ratio for mathematical usage. In some languages (e.g. German, Russian and French), the colon is the commonly used sign for division (instead of ÷).

text: The notation |G : H| may also denote the index of a subgroup.

text: The notation ƒ: X → Y indicates that f is a function with domain X and codomain Y.

text: The combination with an equal sign (≔) is used for definitions.

text: In mathematical logic, when using set-builder notation for describing the characterizing property of a set, it is used as an alternative to a vertical bar (which is the ISO 31-11 standard), to mean "such that". Example:

text: In older literature on mathematical logic, it is used to indicate how expressions should be bracketed (see Glossary of Principia Mathematica).

text: In type theory and programming language theory, the colon sign after a term is used to indicate its type, sometimes as a replacement to the "∈" symbol. Example:

text: Some languages like Haskell use a double colon (::) to indicate type instead.

text: A colon is also sometimes used to indicate a tensor contraction involving two indices, and a double colon (::) for a contraction over four indices.

text: Additional colon-related symbols for math are encoding in Unicode:[28]

text:
U+2255 ≕ EQUALS COLON
U+2982 ⦂ Z NOTATION TYPE COLON
U+2A74 ⩴ DOUBLE COLON EQUAL
U+2AF6 ⫶ TRIPLE COLON OPERATOR

tag: ul

text: Computing[edit]

text: This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (November 2011) (Learn how and when to remove this template message)

text: In computing, the colon character is represented by ASCII code 58, (HTML :) and Unicode U+003A : colon. Several compatibility forms for Chinese and Japanese typography are also encoded:

text:
U+FE13 ︓ PRESENTATION FORM FOR VERTICAL COLON is a compatibility character for the Chinese Standard GB 18030.
U+FF1A ： FULLWIDTH COLON
U+FE55 ﹕ SMALL COLON is a compatibility character for the Chinese National Standard CNS 11643.

text: In Hebrew:

text: U+05C3 ׃ SOF PASSUK is used in some writings such as prayer books to signal the end of a verse.

text: Several programming languages use the colon for various purposes.

text: A number of programming languages, most notably Pascal and Ada, use a colon immediately followed by an equality sign (:=), in which case the colon and the equality sign are considering to compose to an independent assignment sign; this can be represented in Unicode as U+2254 ≔ colon equals.

text: Labels—targets for jumps, notably goto, but also some switch statements—are general formed of a label name followed by a colon. These include C and DOS batch files.

text: For the double colon used in computer programming, see the scope resolution operator, and class member access of C++.

text: The colon is also used as part of the ?: conditional operator in C and other[quantify] languages.

text: In a number of languages, including JavaScript and Python, colons are used to define name-value pairs in a dictionary or object.

text: The colon is also used in many operating systems commands. It is often used as a single post-fix delimiter, signifying a token keyword had immediately preceded it or the transition from one mode of character string interpretation to another related mode. Some applications, such as the widely used MediaWiki, utilize the colon as both a pre-fix and post-fix delimiter.

text: In wiki markup, the colon is often used to indent text. Common usage includes separating or marking comments in a discussion as replies (see WP:INDENT), or to distinguish certain parts of a text.

text:
Markup
Renders as

Normal text.
:Dented text by the means of a colon.
::The gap increases with colon number.

Normal text.

Dented text by the means of a colon.

The gap increases with colon number.

text: Addresses[edit]

text: The colon is quite often used as a special control character in URLs,[29] computer programming languages, in the path representation of several file systems (such as FAT, following the drive letter, as in C:\Windows\, and HFS).

text: In an IPv6 address colons (and one optional double colon) separate up to 8 groups of 16 bits in hexadecimal representation.[30] In a URL a colon follows the initial scheme name (such as HTTP and FTP), and separates a port number from the hostname or IP address.[29]

text: Other languages[edit]

text: In BASIC, it is used as a separator between the statements or instructions in a single line, which is represented in other languages via the semicolon.

text: In Forth, a colon precedes definition of a new word.

text: Haskell uses a colon (pronounced as "cons", short for "construct") as an operator to add an element to the front of a list:[31]

text: while a double colon :: is read as "has type of" (confer scope resolution operator):[32]

text: The ML languages (including Standard ML and OCaml) have the above reversed, where the double colon (::) is used to add an element to the front of a list; and the single colon (:) is used for type guards.

text: MATLAB uses the colon as a binary operator that generates vectors, as well as to select particular portions of existing matrices.

text: In Python, which uses indentation to indicate blocks, the colon is used in statements to indicate that the next line is the start of an indented block.

text: APL uses the colon[33]

text:
to introduce a control structure element. In this usage it must be the first non-blank character of the line.
after a label name that will be the target of a :goto or a right-pointing arrow (Note: this style of programming is deprecated and programmers are encouraged to use control structures instead).
to separate a guard (boolean expression) from its expression in a dynamic function. Two colons are used for an Error guard (one or more error numbers).
Colon + space are used in class definitions to indicate inheritance.

text: U+2360 ⍠ APL FUNCTIONAL SYMBOL QUAD COLON is used by APL for its variant operator.[33]

text: In the esoteric programming language INTERCAL, the colon is called "two-spot" and is used to identify a 32-bit variable—distinct from a spot (.) which identifies a 16-bit variable.

text: Internet usage[edit]

text: This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (January 2018) (Learn how and when to remove this template message)

text: On the Internet, a colon, or multiple colons, is sometimes used to denote an action (similar to how asterisks are used)[original research?] or to emote (for example, in vBulletin). In the action denotation usage it has the inverse function of quotation marks, denoting actions where unmarked text is assumed to be dialogue. For example:

text: Colons may also be used for sounds, e.g., ::click::, though sounds can also be denoted by asterisks or other punctuation marks.

text: Colons can also be used to represent eyes in emoticons.


document_title: Middle Way

question_text: eightfold path of buddhism is known as the middle path because

text: Middle Way

text: Theravada Buddhism and the Pali canon[edit]

text: Dhammacakkappavattana Sutta[edit]

text: In the Pāli Canon of Theravada Buddhism, the term "Middle Way" was used in the Dhammacakkappavattana Sutta, which the Buddhist tradition regards to be the first teaching that the Buddha delivered after his awakening.[b] In this sutta, the Buddha describes the Noble Eightfold Path as the middle way of moderation, between the extremes of sensual indulgence and self-mortification:[2]

text: Monks, these two extremes ought not to be practiced by one who has gone forth from the household life. (What are the two?) There is addiction to indulgence of sense-pleasures, which is low, coarse, the way of ordinary people, unworthy, and unprofitable; and there is addiction to self-mortification, which is painful, unworthy, and unprofitable.

text: Avoiding both these extremes, the Tathagata (the Perfect One) has realized the Middle Path; it gives vision, gives knowledge, and leads to calm, to insight, to enlightenment and to Nibbana. And what is that Middle Path realized by the Tathagata...? It is the Noble Eightfold path, and nothing else, namely: right understanding, right thought, right speech, right action, right livelihood, right effort, right mindfulness and right concentration.[3]

text: According to the scriptural account, when the Buddha delivered the Dhammacakkappavattana Sutta, he was addressing five ascetics with whom he had previously practiced severe austerities.[c] Thus, it is this personal context as well as the broader context of Indian shramanic practices that gives particular relevancy to the caveat against the extreme (Pali: antā) of self-mortification (Pali attakilamatha).

text: Later Pali literature has also used the phrase Middle Way to refer to the Buddha's teaching of dependent origination as a view between the extremes[2] of eternalism and annihilationism.

text: Dependent Origination[edit]

text: Pratītyasamutpāda, or "dependent origination", describes the existence of objects and phenomena as the result of causes. When one of these causes changes or disappears, the resulting object or phenomena will also change or disappear, as will the objects or phenomena depending on the changing object or phenomena. Thus, there is nothing with an eternal self or atman, only mutually dependent origination and existence. However, the absence of an eternal atman does not mean there is nothing at all. Early Buddhism adheres to a realistic approach which does not deny existence as such, but denies the existence of eternal and independent substances. This view is the Middle Way between eternalism and annihilationism:

text: The understanding that sees a "person" as subsisting in the causal connectedness of dependent arising is often presented in Buddhist thought as "the middle" (madhyama/majjhima) between the views of "eternalism" (śaśvata-/sassata-vāda) and "annihilationism" (uccheda-vāda).[4][d]

text: Anatta[edit]

text: Dependent origination views human persons too as devoid of a personal essence or atman. In Theravadin literature, this usage of the term "Middle Way" can be found in 5th century CE Pali commentaries:

text: The Tathāgata teaches the Dhamma by the middle without veering to either of these extremes – eternalism or annihilationism – having abandoned them without reservation. He teaches while being established in the middle way. What is that Dhamma? By the formula of dependent origination, the effect is shown to occur through the cause and to cease with the cessation of the cause, but no agent or experiencer [...] is described.[5]

text: In the Visuddhimagga, the following is found :

text: "Dependent origination" (paticca-samuppada) represents the middle way, which rejects the doctrines, 'He who acts is he who reaps' and 'One acts while another reaps' (S.ii.20) ..."[6]

text: In the Pali Canon itself, this view is not explicitly called the "Middle Way" but is literally referred to as "teaching by the middle" (majjhena dhamma).

text: Rebirth[edit]

text: Paticcasamuppāda "dependent origination" also gives a rationale for rebirth:

text: Conditioned Arising is [...] a 'Middle Way' which avoids the extremes of 'eternalism' and 'annihilationism': the survival of an eternal self, or the total annihilation of a person at death.[7]

text: In Theravadin soteriology, the principle of anattā means there is neither a permanent self nor complete annihilation of the person at death; there is only the arising and ceasing of causally related phenomena.[e] Paticcasamuppāda also describes the Twelve Nidānas of dukkha "suffering" that lead to rebirth, from avijjā "ignorance" to jarāmaraṇa "aging and death", and the parallel reverse-order interdependent cessation of these factors.

text: In Theravada Buddhism, only nibbana is unconditioned; nonetheless, even the arahant or tathāgata, upon passing, neither exists nor non-exists according to the Pāli Canon.

text: Mahayana[edit]

text: In Mahayana Buddhism, the Middle Way refers to the insight into śūnyatā "emptiness" that transcends the extremes of existence and non-existence, the two truths doctrine. According to Kalupahana,

text: Two aspects of the Buddha's teachings, the philosophical and the practical, which are mutually dependent, are clearly enunciated in two discourses, the Kaccāyanagotta-sutta and the Dhammacakkappavattana-sutta, both of which are held in high esteem by almost all schools of Buddhism in spite of their sectarian rivalries. The Kaccāyanagotta-sutta, quoted by almost all the major schools of Buddhism, deals with the philosophical "middle path", placed against the backdrop of two absolutistic theories in Indian philosophy, namely, permanent existence (atthitaa) propounded in the early Upanishads and nihilistic non-existence (natthitā) suggested by the Materialists.[8]

text: Madhyamaka[edit]

text: In Mahayana Buddhism, the Madhyamaka ("Middle Way") school portrays a "middle way" position between metaphysical claims that things ultimately either exist or do not exist.[9] Nagarjuna's influential Mūlamadhyamakakārikā deconstructs the usage of terms describing reality, leading to the insight into śūnyatā "emptiness". It contains only one reference to a sutta, the Kaccāyanagotta Sutta from the Samyutta Nikaya:

text:
"Everything exists": That is one extreme.
"Everything doesn't exist": That is a second extreme.
Avoiding these two extremes,
The Tathagata teaches the Dhamma via the middle.[10]

text: East Asian conceptions[edit]

text: Tendai[edit]

text: In the Tendai school, the Middle Way refers to the synthesis of the thesis that all things are śūnyatā and the antithesis that all things have phenomenal existence.[11]

text: Chan Buddhism[edit]

text: In Chan Buddhism, the Middle Way describes the realization of being free of the one-sidedness of perspective that takes the extremes of any polarity as objective reality. In chapter ten of the Platform Sutra, Huineng gives instructions for the teaching of the Dharma. Huineng enumerates 36 basic oppositions of consciousness and explains how the Way is free from both extremes:

text: If one asks about the worldly, use the paired opposite of the saintly; if asking about the saintly use the paired opposite of the worldly. The mutual causation of the Way of dualities, gives birth to the meaning of the Middle Way. So, for a single question, a single pair of opposites, and for other questions the single [pair] that accords with this fashion, then you do not lose the principle.[12][f]


document_title: Newborn screening

question_text: when did they start screening newborns for cystic fibrosis

text: Newborn screening

text: Targeted disorders[edit]

text: Newborn screening is intended as a public health program to identify infants with treatable conditions before they present clinically, or suffer irreversible damage. Phenylketonuria (PKU) was the first disorder targeted for newborn screening, being implemented in a small number of hospitals and quickly expanding across the United States and the rest of the world.[1] After the success of newborn screening for PKU (39 infants were identified and treated in the first two years of screening, with no false negative results), Guthrie and others looked for other disorders that could be identified and treated in infants, eventually developing bacterial inhibition assays to identify classic galactosemia and maple syrup urine disease.[1][2]

text: Newborn screening has expanded since the introduction of PKU testing in the 1960s, but can vary greatly between countries. In 2011, the United States screened for 54 conditions, Germany for 12, the United Kingdom for 2 (PKU and medium chain acyl-CoA dehydrogenase deficiency (MCADD)), while France and Hong Kong only screened for one condition (PKU and congenital hypothyroidism, respectively).[3] The conditions included in newborn screening programs around the world vary greatly, based on the legal requirements for screening programs, prevalence of certain diseases within a population, political pressure, and the availability of resources for both testing and follow-up of identified patients.

text: Amino acid disorders[edit]

text: Newborn screening originated with an amino acid disorder, phenylketonuria (PKU), which can be easily treated by dietary modifications, but causes severe mental retardation if not identified and treated early. Robert Guthrie introduced the newborn screening test for PKU in the early 1960s.[4] With the knowledge that PKU could be detected before symptoms were evident, and treatment initiated, screening was quickly adopted around the world. Austria started screening for PKU in 1966[5] and England in 1968.[6]

text: Fatty acid oxidation disorders[edit]

text: With the advent of tandem mass spectrometry as a screening tool, several fatty acid oxidation disorders were targeted for inclusion in newborn screening programs. Medium chain acyl-CoA dehydrogenase deficiency (MCADD), which had been implicated in several cases of sudden infant death syndrome[7][8][9] was one of the first conditions targeted for inclusion. MCADD was the first condition added when the United Kingdom expanded their screening program from PKU only.[3] Population based studies in Germany, the United States and Australia put the combined incidence of fatty acid oxidation disorders at 1:9300 among Caucasians. The United States screens for all known fatty acid oxidation disorders, either as primary or secondary targets, while other countries screen for a subset of these.[10]

text: The introduction of screening for fatty acid oxidation disorders has been shown to have reduced morbidity and mortality associated with the conditions, particularly MCADD. An Australian study found a 74% reduction in episodes of severe metabolic decompensation or death among individuals identified by newborn screening as having MCADD versus those who presented clinically prior to screening. Studies in the Netherlands and United Kingdom found improvements in outcome at a reduced cost when infants were identified before presenting clinically.[10]

text: Newborn screening programs have also expanded the information base available about some rare conditions. Prior to its inclusion in newborn screening, short-chain acyl-CoA dehydrogenase deficiency (SCADD) was thought to be life-threatening. Most patients identified via newborn screening as having this enzyme deficiency were asymptomatic, to the extent that SCADD was removed from screening panels in a number of regions. Without the cohort of patients identified by newborn screening, this clinical phenotype would likely not have been identified.[10]

text: Endocrinopathies[edit]

text: The most commonly included disorders of the endocrine system are congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH).[11] Testing for both disorders can be done using blood samples collected on the standard newborn screening card. Screening for CH is done by measuring thyroxin (T4), thyrotropin (TSH) or a combination of both analytes. Elevated 17α-hydroxyprogesterone (17α-OHP) is the primary marker used when screening for CAH, most commonly done using enzyme-linked immunosorbant assays, with many programs using a second tier tandem mass spectrometry test to reduce the number of false positive results.[11] Careful analysis of screening results for CAH may also identify cases of congenital adrenal hypoplasia, which presents with extremely low levels of 17α-OHP.[11]

text: CH was added to many newborn screening programs in the 1970s, often as the second condition included after PKU. The most common cause of CH is dysgenesis of the thyroid gland After many years of newborn screening, the incidence of CH worldwide had been estimated at 1:3600 births, with no obvious increases in specific ethnic groups. Recent data from certain regions have showed an increase, with New York reporting an incidence of 1:1700. Reasons for the apparent increase in incidence have been studied, but no explanation has been found.[11]

text: Classic CAH, the disorder targeted by newborn screening programs, is caused by a deficiency of the enzyme steroid 21-hydroxylase, and comes in two forms - simple virilizing and a salt-wasting form. Incidence of CAH can vary greatly between populations. The highest reported incidence rates are among the Yupic Eskimos of Alaska (1:280) and on the French island of Réunion (1:2100).[11]

text: Hemoglobinopathies[edit]

text: Any condition that results in the production of abnormal hemoglobin is included under the broad category of hemoglobinopathies. Worldwide, it is estimated that 7% of the population may carry a hemoglobinopathy with clinical significance.[12] The most well known condition in this group is sickle cell disease.[12] Newborn screening for a large number of hemoglobinopathies is done by detecting abnormal patterns using isoelectric focusing, which can detect many different types of abnormal hemoglobins.[12] In the United States, newborn screening for sickle cell disease was recommended for all infants in 1987, however it was not implemented in all 50 states until 2006.[12]

text: Early identification of individuals with sickle cell disease and other hemoglobinopathies allows treatment to be initiated in a timely fashion. Penicillin has been used in children with sickle cell disease, and blood transfusions are used for patients identified with severe thalassemia.[12]

text: Organic acidemias[edit]

text: Most jurisdictions did not start screening for any of the organic acidemias before tandem mass spectrometry significantly expanded the list of disorders detectable by newborn screening. Quebec has run a voluntary second-tier screening program since 1971 using urine samples collected at three weeks of age to screen for an expanded list of organic acidemias using a thin layer chromatography method.[13] Newborn screening using tandem mass spectrometry can detect several organic acidemias, including propionic acidemia, methylmalonic acidemia and isovaleric acidemia.

text: Cystic fibrosis[edit]

text: Cystic fibrosis (CF) was first added to newborn screening programs in New Zealand and regions of Australia in 1981, by measuring immunoreactive trypsinogen (IRT) in dried blood spots.[14] After the CFTR gene was identified, Australia introduced a two tier testing program to reduce the number of false positives. Samples with an elevated IRT value were then analyzed with molecular methods to identify the presence of disease causing mutations before being reported back to parents and health care providers.[15] CF is included in the core panel of conditions recommended for inclusion in all 50 states, Texas was the last state to implement their screening program for CF in 2010.[16] Alberta was the first Canadian province to implement CF screening in 2007.[17] Quebec, New Brunswick, Nova Scotia, Newfoundland and Prince Edward Island do not include CF in their screening programs.[18] The United Kingdom as well as many European Union countries screen for CF as well.[18] Switzerland is one of the latest countries to add CF to their newborn screening menu, doing so in January 2011.[14]

text: Urea cycle disorders[edit]

text: Disorders of the distal urea cycle, such as citrullinemia, argininosuccinic aciduria and argininemia are included in newborn screening programs in many jurisdictions that using tandem mass spectrometry to identify key amino acids. Proximal urea cycle defects, such as ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase deficiency are not included in newborn screening panels because they are not reliably detected using current technology, and also because severely affected infants will present with clinical symptoms before newborn screening results are available. Some regions claim to screen for HHH syndrome (hyperammonemia, hyperornithinemia, homocitrullinuria) based on the detection of elevated ornithine levels in the newborn screening dried blood spot, but other sources have shown that affected individuals do not have elevated ornithine at birth.[19]

text: Lysosomal storage disorders[edit]

text: Lysosomal storage disorders are not included in newborn screening programs with high frequency. As a group, they are heterogenous, with screening only being feasible for a small fraction of the approximately 40 identified disorders. The arguments for their inclusion in newborn screening programs center around the advantage of early treatment (when treatment is available), avoiding a diagnostic odyssey for families and providing information for family planning to couples who have an affected child.[20] The arguments against including these disorders, as a group or individually center around the difficulties with reliably identifying individuals who will be affected with a severe form of the disorder, the relatively unproven nature of the treatment methods, and the high cost / high risk associated with some treatment options.[20]

text: New York State started a pilot study to screen for Krabbe disease in 2006, largely due to the efforts of Jim Kelly, whose son, Hunter, was affected with the disease.[21] A pilot screening program for four lysosomal storage diseases (Gaucher disease, Pompe disease, Fabry disease and Niemann-Pick disease was undertaken using anonymised dried blood spots was completed in Austria in 2010. Their data showed an increased incidence from what was expected in the population, and also a number of late onset forms of disease, which are not typically the target for newborn screening programs.[22]

text: Hearing loss[edit]

text: Undiagnosed hearing loss in a child can have serious effects on many developmental areas, including language, social interactions, emotions, cognitive ability, academic performance and vocational skills, any combination of which can have negative impacts on the quality of life.[23] The serious impacts of a late diagnosis, combined with the high incidence (estimated at 1 - 3 per 1000 live births, and as high as 4% for neonatal intensive care unit patients) have been the driving forces behind screening programs designed to identify infants with hearing loss as early as possible. Early identification allows these patients and their families to access needed resources to help them develop.[23]

text: Newborn hearing testing is done at the bedside using transiently evoked otoacoustic emissions, automated auditory brainstem responses or a combination of both techniques. Hearing screening programs have found the initial testing to cost between $10.20 and $23.37 per baby, depending on the technology used.[23] As these are screening tests only, false positive results will occur. A review of hearing screening programs found varied initial referral rates (screen positive results) from 0.6% to 16.7%. The highest overall incidence of hearing loss detection was 0.517%.[23] A significant proportion of screen positive infants were lost to follow-up, before a diagnosis could be confirmed or ruled out in all screening programs.[23]

text: Congenital heart defects[edit]

text: Pulse oximetry has been recently added as a bedside screening test for critical congenital heart defects.[24]

text: Severe combined immunodeficiency[edit]

text: Severe combined immunodeficiency (SCID) caused by T-cell deficiency is a disorder that was recently added to newborn screening programs in some regions of the United States. Wisconsin was the first state to add SCID to their mandatory screening panel in 2008, and it was recommended for inclusion in all states' panels in 2010. Identification of infants with SCID is done by detecting T-cell receptor excision circles (TRECs) using real-time polymerase chain reaction (qPCR). TRECs are decreased in infants affected with SCID.[25]

text: SCID has not been added to newborn screening in a wide scale for several reasons. It requires technology that is not currently used in most newborn screening labs, as PCR is not used for any other assays included in screening programs. Follow-up and treatment of affected infants also requires skilled immunologists, which may not be available in all regions. Treatment for SCID is a stem cell transplant, which cannot be done in all centers.[25]

text: Other conditions[edit]

text: Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by defective production of dystrophin. Many jurisdictions around the world have screened for, or attempted to screen for DMD using elevated levels of creatine kinase measured in dried blood spots. Because universal newborn screening for DMD has not been undertaken, affected individuals often have a significant delay in diagnosis. As treatment options for DMD become more and more effective, interest in adding a newborn screening test increases. At various times since 1978, DMD has been included (often as a pilot study on a small subset of the population) in newborn screening programs in Edinburgh, Germany, Canada, France, Wales, Cyprus, Belgium and the United States. In 2012, Belgium was the only country that continued to screen for DMD using creatine kinase levels.[26]

text: As treatments improve, newborn screening becomes a possibility for disorders that could benefit from early intervention, but none was previously available. Adrenoleukodystrophy (ALD), a peroxisomal disease that has a variable clinical presentation is one of the disorders that has become a target for those seeking to identify patients early. ALD can present in several different forms, some of which do not present until adulthood, making it a difficult choice for countries to add to screening programs. The most successful treatment option is a stem cell transplant, a procedure that carries a significant risk.[27]

text: Eye and vision screening that can be performed within the few months of life include: strabismus screening using the Hirschberg test (or more recently using binocular retinal birefringence screening for higher precision), and retinoblastoma screening using the red reflex. Further eye examination may be called for in some cases.

text: Disease qualification[edit]

text: Newborn screening programs initially used screening criteria based largely on criteria established by JMG Wilson and F. Jungner in 1968.[28] Although not specifically about newborn population screening programs, their publication, Principles and practice of screening for disease proposed ten criteria that screening programs should meet before being used as a public health measure. Newborn screening programs are administered in each jurisdiction, with additions and removals from the panel typically reviewed by a panel of experts. The four criteria from the publication that were relied upon when making decisions for early newborn screening programs were:

text:
having an acceptable treatment protocol in place that changes the outcome for patients diagnosed early with the disease
an understanding of the condition's natural history
an understanding about who will be treated as a patient
a NBS screening test that is reliable for both affected and unaffected patients and is acceptable to the public[29]

tag: ol

text: As diagnostic techniques have progressed, debates have arisen as to how screening programs should adapt. Tandem mass spectrometry has greatly expanded the potential number of diseases that can be detected, even without satisfying all of the other criteria used for making screening decisions.[29][30] Duchenne muscular dystrophy is a disease that has been added to screening programs in several jurisdictions around the world, despite the lack of evidence as to whether early detection improves the clinical outcome for a patient.[29]

text: Techniques[edit]

text: Sample collection[edit]

text: Newborn screening tests are most commonly done from whole blood samples collected on specially designed filter paper. The filter paper is often attached to a form containing required information about the infant and parents. This includes date and time of birth, date and time of sample collection, the infant's weight and gestational age. The form will also have information about whether the baby has had a blood transfusion and any additional nutrition the baby may have received (total parenteral nutrition). Most newborn screening cards also include contact information for the infant's physician in cases where follow up screening or treatment is needed. The Canadian province of Quebec performs newborn screening on whole blood samples collected as in most other jurisdictions, and also runs a voluntary urine screening program where parents collect a sample at 21 days of age and submit it to a provincial laboratory for an additional panel of conditions.[31][13]

text: Newborn screening samples are collected from the infant between 24 hours and 7 days after birth, with the requirement that the baby has fed at least once. Samples can be collected at the hospital, or by midwives. If a sample is collected from an infant who is less than 24 hours old, the laboratory will often request a repeat specimen be taken after 24 hours. Samples are mailed daily to the laboratory responsible for testing. In the United States and Canada, newborn screening is mandatory, with an option for parents to opt out of the screening in writing if they desire.[32][33] In most of Europe, newborn screening is done with the consent of the parents. Proponents of mandatory screening claim that the test is for the benefit of the child, and that parents should not be able to opt out on their behalf. In regions that favour informed consent for the procedure, they report no increase in costs, no decrease in the number of children screened and no cases of included diseases in children who did not undergo screening.[34]

text: Laboratory testing[edit]

text: Because newborn screening programs test for a number of different conditions, a number of different laboratorial methodologies are used, as well as bedside testing for hearing loss using evoked auditory potentials[23] and congenital heart defects using pulse oximetry.[24] Newborn screening started out using simple bacterial inhibition assays to screen for a single disorder, starting with phenylketonuria in the early 1960s.[4] With this testing methodology, newborn screening required one test to detect one condition. As mass spectrometry became more widely available, the technology allowed rapid determination of a number of acylcarnitines and amino acids from a single dried blood spot. This increased the number of conditions that could be detected by newborn screening. Enzyme assays are used to screen for galactosemia and biotinidase deficiency. Immunoassays measure thyroid hormones for the diagnosis of congenital hypothyroidism and 17α-hydroxyprogesterone for the diagnosis of congenital adrenal hyperplasia. Molecular techniques are used for the diagnosis of cystic fibrosis and severe combined immunodeficiency.

text: Reporting results[edit]

text: The goal is to report the results within a short period of time. If screens are normal, a paper report is sent to the submitting hospital and parents rarely hear about it. If an abnormality is detected, employees of the agency, usually nurses, begin to try to reach the physician, hospital, and/or nursery by telephone. They are persistent until they can arrange an evaluation of the infant by an appropriate specialist physician (depending on the disease). The specialist will attempt to confirm the diagnosis by repeating the tests by a different method or laboratory, or by performing other corroboratory or disproving tests. The confirmatory test varies depending on the positive results on the initial screen. Confirmatory testing can include analyte specific assays to confirm any elevations detected, functional studies to determine enzyme activity, and genetic testing to identify disease-causing mutations. In some cases, a positive newborn screen can also trigger testing on other family members, such as siblings who did not undergo newborn screening for the same condition or the baby's mother, as some maternal conditions can be identified through results on the baby's newborn screen. Depending on the likelihood of the diagnosis and the risk of delay, the specialist will initiate treatment and provide information to the family. Performance of the program is reviewed regularly and strenuous efforts are made to maintain a system that catches every infant with these diagnoses. Guidelines for newborn screening and follow up have been published by the American Academy of Pediatrics[35] and the American College of Medical Genetics.[36]

text: Laboratory performance[edit]

text: Newborn screening programs participate in quality control programs as in any other laboratory, with some notable exceptions. Much of the success of newborn screening programs is dependent on the filter paper used for the collection of the samples. Initial studies using Robert Guthrie's test for PKU reported high false positive rates that were attributed to a poorly selected type of filter paper.[37] This source of variation has been eliminated in most newborn screening programs through standardization of approved sources of filter paper for use in newborn screening programs. In most regions, the newborn screening card (which contains demographic information as well as attached filter paper for blood collection) is supplied by the organization carrying out the testing, to remove variations from this source.[37]

text: History[edit]

text: Robert Guthrie is given much of the credit for pioneering the earliest screening for phenylketonuria in the late 1960s using blood samples obtained by pricking a newborn baby's heel on the second day of life on filter paper.[38] Congenital hypothyroidism was the second disease widely added in the 1970s.[39] Guthrie and colleagues also developed bacterial inhibition assays for the detection of maple syrup urine disease and classic galactosemia.[40] The development of tandem mass spectrometry screening in the early 1990s led to a large expansion of potentially detectable congenital metabolic diseases that can be identified by characteristic patterns of amino acids and acylcarnitines.[41]

text: In the United States, the American College of Medical Genetics recommended a uniform panel of diseases that all infants born in every state should be screened for. They also developed an evidence-based review process for the addition of conditions in the future. The implementation of this panel across the United States meant all babies born would be screened for the same number of conditions. Prior to this, babies born in different states had received different levels of screening. On April 24, 2008, President George W. Bush signed into law the Newborn Screening Saves Lives Act of 2007. This act was enacted to increase awareness among parents, health professionals, and the public on testing newborns to identify certain disorders. It also sought to improve, expand, and enhance current newborn screening programs at the state level.

text: Society and culture[edit]

text: Controversies[edit]

text: Newborn screening tests have become a subject of political controversy in the last decade. In 2003, two California babies, Zachary Wyvill and Zachary Black, were both born with Glutaric acidemia type I. Wyvill's birth hospital only tested for the four diseases mandated by state law, while Black was born at a hospital that was participating in an expanded testing pilot program. Black's disease was treated with diet and vitamins; Wyvill's disease went undetected for over six months, and during that time the damage from the enzyme deficiency became irreversible.[42] Birth-defects lobbyists pushing for broader and more universal standards for newborn testing cite this as an example of how much of an impact testing can have.[citation needed]

text: Instituting MS/MS screening often requires a sizable up front expenditure. When states choose to run their own programs the initial costs for equipment, training and new staff can be significant. Moreover, MS/MS gives only the screening result and not the confirmatory result. The same has to be further done by higher technologies or procedure like GC/MS, Enzyme Assays or DNA Tests. This in effect adds more cost burden and makes physicians lose precious time. To avoid at least a portion of the up front costs, some states such as Mississippi have chosen to contract with private labs for expanded screening. Others have chosen to form Regional Partnerships sharing both costs and resources.

text: But for many states, screening is an integrated part of the department of health which can not or will not be easily replaced. Thus the initial expenditures can be difficult for states with tight budgets to justify. Screening fees have also increased in recent years as health care costs rise and as more states add MS/MS screening to their programs. (See Report of Summation of Fees Charged for Newborn Screening, 2001–2005) Dollars spent for these programs may reduce resources available to other potentially lifesaving programs. It has been recommended that one disorder, Short Chain Acyl-coenzyme A Dehydrogenase Deficiency, or SCAD, be eliminated from screening programs, due to a "spurious association between SCAD and symptoms.[43] However, recent studies suggest that expanded screening is cost effective (see ACMG report page 94-95 and articles published in Pediatrics[44]'.[45] Advocates are quick to point out studies such as these when trying to convince state legislatures to mandate expanded screening.

text: Expanded newborn screening is also opposed by among some health care providers, who are concerned that effective follow-up and treatment may not be available, that false positive screening tests may cause harm, and issues of informed consent.[46] A recent study by Genetic Alliance and partners suggests that communication between health care providers and parents may be key in minimizing the potential harm when a false positive test occurs. The results from this study also reveal that parents found newborn screening to be a beneficial and necessary tool to prevent treatable diseases.[47] To address the false positive issue, researchers from the University of Maryland, Baltimore and Genetic Alliance established a check-list to assist health care providers communicate with parents about a screen-positive result.[48]

text: Controversy has also erupted in some countries over collection and storage of blood or DNA samples by government agencies during the routine newborn blood screen. It was revealed that in Texas the state had collected and stored blood and DNA samples on millions of newborns without the parents' knowledge or consent. These samples were then used by the state for genetic experiments and to set up a database to catalog all of the samples/newborns. Samples obtained without parents' consent were destroyed.[49]

text: Bioethics[edit]

text: As additional tests are discussed for addition to the panels, issues arise. Many question if the expanded testing still falls under the requirements necessary to justify the additional tests.[50] Many of the new diseases being tested for are rare and have no known treatment, while some of the diseases need not be treated until later in life.[50] This raises more issues, such as: if there is no available treatment for the disease should we test for it at all? And if we do, what do we tell the families of those with children bearing one of the untreatable diseases?[51] Studies show that the more rare the disease is and the more diseases being tested for, the more likely the tests are to produce false-positives.[52] This is an issue because the newborn period is a crucial time for the parents to bond with the child, and it has been noted that ten percent of parents whose children were diagnosed with a false-positive still worried that their child was fragile and/or sickly even though they were not, potentially preventing the parent-child bond forming as it would have otherwise.[51] As a result, some parents may begin to opt out of having their newborns screened. Many parents are also concerned about what happens with their infant's blood samples after screening. The samples were originally taken to test for preventable diseases, but with the advance in genomic sequencing technologies many samples are being kept for DNA identification and research,[50][51] increasing the possibility that more children will be opted out of newborn screening from parents who see the kept samples as a form of research done on their child.[50]