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121-562: Shaare Zedek was the first large district general hospital to be located in the Western portion of Jerusalem and is today the city's fastest growing hospital and the only major medical facility in the city's center. After the Ottoman Turks gave permission in the 1890s, and with funding from European donors, the hospital was built on Jaffa Road , two miles (3 km) outside the Old City . The design

242-411: A cell membrane constituent of red and white blood cells . In Gaucher disease, the enzyme is unable to function correctly and glucocerebroside accumulates. The macrophages that clear these cells are unable to eliminate the waste product, which accumulates in fibrils, and turn into 'Gaucher cells', which appear on light microscopy to resemble crumpled-up paper. The exact mechanism of neurotoxicity

363-480: A brownish tint to the skin, anemia , low blood platelet count, and yellow fatty deposits on the white of the eye ( sclera ). Persons seriously affected may also be more susceptible to infection. Some forms of Gaucher's disease may be treated with enzyme replacement therapy. The disease is caused by a recessive mutation in the GBA gene located on chromosome 1 and affects both males and females. About one in 100 people in

484-672: A calamitous end in 1683 when Grand Vizier Kara Mustafa Pasha led a huge army to attempt a second Ottoman siege of Vienna in the Great Turkish War of 1683–1699. The final assault being fatally delayed, the Ottoman forces were swept away by allied Habsburg, German, and Polish forces spearheaded by the Polish king John III Sobieski at the Battle of Vienna . The alliance of the Holy League pressed home

605-574: A constitutional monarchy. However, following the disastrous Balkan Wars , the CUP became increasingly radicalized and nationalistic, leading a coup d'état in 1913 that established a one-party regime. The CUP allied with the German Empire hoping to escape from the diplomatic isolation that had contributed to its recent territorial losses; it thus joined World War I on the side of the Central Powers . While

726-494: A coup, but he did see the need for military mobilization. In 1883, a German military mission under General Baron Colmar von der Goltz arrived to train the Ottoman Army, leading to the so-called "Goltz generation" of German-trained officers, who played a notable role in the politics of the empire's last years. From 1894 to 1896, between 100,000 and 300,000 Armenians living throughout the empire were killed in what became known as

847-491: A fairly modern conscripted army , banking system reforms, the decriminalization of homosexuality, the replacement of religious law with secular law, and guilds with modern factories. The Ottoman Ministry of Post was established in Istanbul in 1840. American inventor Samuel Morse received an Ottoman patent for the telegraph in 1847, issued by Sultan Abdülmecid , who personally tested the invention. The reformist period peaked with

968-545: A figure that vastly exceeded the number of Muslim children in school at the time, who were further hindered by the amount of time spent learning Arabic and Islamic theology. Author Norman Stone suggests that the Arabic alphabet, in which Turkish was written until 1928 , was ill-suited to reflect the sounds of Turkish (which is a Turkic as opposed to Semitic language), which imposed further difficulty on Turkish children. In turn, Christians' higher educational levels allowed them to play

1089-466: A human chitinase, chitotriosidase. This latter enzyme has proved to be very useful for monitoring Gaucher's disease activity in response to treatment, and may reflect the severity of the disease Gaucher's disease (GD) has three common clinical subtypes. These subtypes have come under some criticism for not taking account of the full spectrum of observable symptoms (the phenotypes ). Also, compound heterozygous variations occur which considerably increase

1210-503: A larger role in the economy, with the rise in prominence of groups such as the Sursock family indicative of this. In 1911, of the 654 wholesale companies in Istanbul, 528 were owned by ethnic Greeks. In many cases, Christians and Jews gained protection from European consuls and citizenship, meaning they were protected from Ottoman law and not subject to the same economic regulations as their Muslim counterparts. The Crimean War (1853–1856)

1331-664: A major center for its trade, contributing to its continued prosperity throughout the seventeenth and much of the eighteenth century. Under Ivan IV (1533–1584), the Tsardom of Russia expanded into the Volga and Caspian regions at the expense of the Tatar khanates. In 1571, the Crimean khan Devlet I Giray , commanded by the Ottomans, burned Moscow . The next year, the invasion was repeated but repelled at

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1452-541: A peak in 2001–04, Shaare Zedek treated more victims than any other hospital in Israel. The hospital's trauma unit located within its Weinstock Department of Emergency Medicine on the Fanya Gottesfeld Heller Floor became a model for emergency medicine and handling large-scale mass casualty incidents. The main hospital campus, completed in 1979, consists of ten interconnected buildings with the central structure being

1573-879: A poor ability to suck and swallow. Affected children usually die by age two. GD type III (chronic neuropathic) can begin at any time in childhood or even in adulthood, and occurs in about 1 in 100,000 live births. It is characterized by slowly progressive, but milder neurologic symptoms compared to the acute or type II version. Major symptoms include an enlarged spleen and/or liver, seizures, poor coordination, skeletal irregularities, eye movement disorders, blood disorders including anemia, and respiratory problems. Patients often live into their early teen years and adulthood. For those with type-I and most type-III, enzyme replacement treatment with intravenous recombinant glucocerebrosidase can decrease liver and spleen size, reduce skeletal abnormalities, and reverse other manifestations. This treatment costs about US$ 200,000 annually for

1694-514: A sense of Turkish nationalism. In this period, the Ottoman Empire spent only small amounts of public funds on education; for example, in 1860–1861 only 0.2% of the total budget was invested in education. As the Ottoman state attempted to modernize its infrastructure and army in response to outside threats, it opened itself up to a different kind of threat: that of creditors. As the historian Eugene Rogan has written, "the single greatest threat to

1815-399: A single person and should be continued for life. The rarity of the disease means dose-finding studies have been difficult to conduct, so controversy remains over the optimal dose and dosing frequency. Due to the low incidence, this has become an orphan drug in many countries, meaning a government recognizes and accommodates the financial constraints that limit research into drugs that address

1936-499: A small population. The first drug for Gaucher's was alglucerase (Ceredase), which was a version of glucocerebrosidase that was harvested from human placental tissue and then modified with enzymes. It was approved by the FDA in 1991 and has been withdrawn from the market due to the approval of similar drugs made with recombinant DNA technology instead of being harvested from tissue; drugs made recombinantly are preferable, since there

2057-524: A ten-story building, which houses the in-patient departments. The bottom three floors are located underground so as to allow the hospital to continue to operate even under the threat of missile strike. The Department of Emergency Medicine, the Wohl Surgical Operating Complex inaugurated in 2010, the Pharmacy and critical supply areas are all located in this underground portion and other areas of

2178-436: A very active academic service as a leading research and teaching institution. Shaare Zedek is classified as a public/private hospital, serving as a non-profit institution and dependent on donor support for capital development, while offering medical care for the wider Jerusalem-area community. Shaare Zedek Medical Center is located across two major campuses. The main campus is located on an 11.5-acre (47,000 m) site between

2299-454: A victory over the Ottoman fleet at the Battle of Lepanto (1571), off southwestern Greece; Catholic forces killed over 30,000 Turks and destroyed 200 of their ships. It was a startling, if mostly symbolic, blow to the image of Ottoman invincibility, an image which the victory of the Knights of Malta over the Ottoman invaders in the 1565 siege of Malta had recently set about eroding. The battle

2420-428: Is a genetic disorder in which glucocerebroside (a sphingolipid , also known as glucosylceramide) accumulates in cells and certain organs. The disorder is characterized by bruising, fatigue , anemia , low blood platelet count and enlargement of the liver and spleen , and is caused by a hereditary deficiency of the enzyme glucocerebrosidase (also known as glucosylceramidase), which acts on glucocerebroside. When

2541-449: Is no concern about diseases being transmitted from the tissue used in harvesting, there are fewer risks of variations in enzyme structure from batch to batch, and they are less expensive to manufacture. Available recombinant glucocerebrosidases are: Miglustat is a small molecule, orally available drug that was first approved for Gaucher's disease in Europe in 2002. It works by preventing

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2662-463: Is not understood, but it is thought to involve a reaction to glucosylsphingosine . Different mutations in the GBA (beta-glucosidase) gene determine the remaining activity of the enzyme. In type I, there is some residual activity of the enzyme, accounting for the lack of neuropathology in this type. Although there is some correlation between genotype and phenotype , neither the amount of stored lipids, nor

2783-486: Is thought to be due to accumulation of glucosylceramide and complex glycosphingolipids. The role of inflammatory processes in Gaucher disease is poorly elucidated. However, sphingolipids are known to participate in inflammation and apoptosis , and markers of macrophage activation are elevated in people with Gaucher disease. These markers include angiotensin-converting enzyme , cathepsin S , chitotriosidase , and CCL18 in

2904-618: The Anatolian Beyliks . One of these, in the region of Bithynia on the frontier of the Byzantine Empire, was led by the Turkish tribal leader Osman I ( d. 1323/4), a figure of obscure origins from whom the name Ottoman is derived. Osman's early followers consisted of Turkish tribal groups and Byzantine renegades, with many but not all converts to Islam. Osman extended control of his principality by conquering Byzantine towns along

3025-564: The Balkans by the mid-14th century, transforming their petty kingdom into a transcontinental empire. The Ottomans ended the Byzantine Empire with the conquest of Constantinople in 1453 by Mehmed II , which marked the Ottomans' emergence as a major regional power. Under Suleiman the Magnificent (1520–1566), the empire reached the peak of its power, prosperity, and political development. By

3146-458: The Battle of Molodi . The Ottoman Empire continued to invade Eastern Europe in a series of slave raids , and remained a significant power in Eastern Europe until the end of the 17th century. The Ottomans decided to conquer Venetian Cyprus and on 22 July 1570, Nicosia was besieged; 50,000 Christians died, and 180,000 were enslaved. On 15 September 1570, the Ottoman cavalry appeared before

3267-702: The Bosporus Strait made it difficult to conquer. In 1402, the Byzantines were temporarily relieved when the Turco-Mongol leader Timur , founder of the Timurid Empire , invaded Ottoman Anatolia from the east. In the Battle of Ankara in 1402, Timur defeated Ottoman forces and took Sultan Bayezid I as prisoner, throwing the empire into disorder. The ensuing civil war lasted from 1402 to 1413 as Bayezid's sons fought over succession. It ended when Mehmed I emerged as

3388-642: The Bulgarian Tsardom of Vidin in 1396, regarded as the last large-scale crusade of the Middle Ages , failed to stop the advance of the victorious Ottomans. As the Turks expanded into the Balkans, the conquest of Constantinople became a crucial objective. The Ottomans had already wrested control of nearly all former Byzantine lands surrounding the city, but the strong defense of Constantinople's strategic position on

3509-583: The Cape of Good Hope in 1488 initiated a series of Ottoman-Portuguese naval wars in the Indian Ocean throughout the 16th century. Despite the growing European presence in the Indian Ocean, Ottoman trade with the east continued to flourish. Cairo, in particular, benefitted from the rise of Yemeni coffee as a popular consumer commodity. As coffeehouses appeared in cities and towns across the empire, Cairo developed into

3630-534: The Constitution of the Ottoman Empire and brought in multi-party politics with a two-stage electoral system ( electoral law ) under the Ottoman parliament . The constitution offered hope by freeing the empire's citizens to modernise the state's institutions, rejuvenate its strength, and enable it to hold its own against outside powers. Its guarantee of liberties promised to dissolve inter-communal tensions and transform

3751-808: The Great Northern War of 1700–1721). Charles XII persuaded the Ottoman Sultan Ahmed III to declare war on Russia, which resulted in an Ottoman victory in the Pruth River Campaign of 1710–1711, in Moldavia. After the Austro-Turkish War , the Treaty of Passarowitz confirmed the loss of the Banat, Serbia, and "Little Walachia" (Oltenia) to Austria. The Treaty also revealed that the Ottoman Empire

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3872-534: The Greek revolt (1821–1829) that ultimately ended with the formal independence of Greece in 1830. It was a costly enterprise for Muhammad Ali, who had lost his fleet at the Battle of Navarino in 1827. Thus began the first Egyptian–Ottoman War (1831–1833) , during which the French-trained army of Muhammad Ali, under the command of his son Ibrahim Pasha , defeated the Ottoman Army as it marched into Anatolia , reaching

3993-769: The Greeks declared war on the Sultan. A rebellion that originated in Moldavia as a diversion was followed by the main revolution in the Peloponnese , which, along with the northern part of the Gulf of Corinth , became the first parts of the Ottoman Empire to achieve independence (in 1829). In 1830, the French invaded the Deylik of Algiers . The campaign that took 21 days, resulted in over 5,000 Algerian military casualties, and about 2,600 French ones. Before

4114-566: The Habsburg and Russian empires. The Ottomans consequently suffered severe military defeats in the late 18th and early 19th centuries, culminating in the loss of both territory and global prestige . This prompted a comprehensive process of reform and modernization known as the Tanzimat ; over the course of the 19th century, the Ottoman state became vastly more powerful and organized internally, despite suffering further territorial losses, especially in

4235-497: The Hamidian massacres . In 1897 the population was 19   million, of whom 14   million (74%) were Muslim. An additional 20   million lived in provinces that remained under the sultan's nominal suzerainty but were entirely outside his actual power. One by one the Porte lost nominal authority. They included Egypt, Tunisia, Bulgaria, Cyprus, Bosnia-Herzegovina, and Lebanon. As

4356-646: The Iberian Union . The Ottomans were holders of the Caliph title, meaning they were the leaders of Muslims worldwide. The Iberians were leaders of the Christian crusaders, and so the two fought in a worldwide conflict. There were zones of operations in the Mediterranean and Indian Ocean , where Iberians circumnavigated Africa to reach India and, on their way, wage war upon the Ottomans and their local Muslim allies. Likewise,

4477-690: The Köprülü era (1656–1703), effective control of the Empire was exercised by a sequence of grand viziers from the Köprülü family. The Köprülü Vizierate saw renewed military success with authority restored in Transylvania, the conquest of Crete completed in 1669, and expansion into Polish southern Ukraine , with the strongholds of Khotyn , and Kamianets-Podilskyi and the territory of Podolia ceding to Ottoman control in 1676. This period of renewed assertiveness came to

4598-620: The Oriental Crisis of 1840 . Muhammad Ali had close relations with France , and the prospect of him becoming the Sultan of Egypt was widely viewed as putting the entire Levant into the French sphere of influence. As the Sublime Porte had proved itself incapable of defeating Muhammad Ali, the British Empire and Austrian Empire provided military assistance, and the second Egyptian–Ottoman War (1839–1841) ended with Ottoman victory and

4719-527: The Sakarya River . A Byzantine defeat at the Battle of Bapheus in 1302 contributed to Osman's rise. It is not well understood how the early Ottomans came to dominate their neighbors, due to the lack of sources surviving. The Ghaza thesis popular during the 20th century credited their success to rallying religious warriors to fight for them in the name of Islam , but it is no longer generally accepted. No other hypothesis has attracted broad acceptance. In

4840-671: The Spanish garrison of Castelnuovo on the Adriatic coast ; the successful siege cost the Ottomans 8,000 casualties, but Venice agreed to terms in 1540, surrendering most of its empire in the Aegean and the Morea . France and the Ottoman Empire, united by mutual opposition to Habsburg rule, became allies. The French conquests of Nice (1543) and Corsica (1553) occurred as a joint venture between French king Francis I and Suleiman, and were commanded by

4961-506: The Treaty of Nasuh Pasha , which ceded the entire Caucasus, except westernmost Georgia, back into the possession of Safavid Iran . The treaty ending the Cretan War cost Venice much of Dalmatia , its Aegean island possessions, and Crete . (Losses from the war totalled 30,985 Venetian soldiers and 118,754 Turkish soldiers.) During his brief majority reign, Murad IV (1623–1640) reasserted central authority and recaptured Iraq (1639) from

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5082-603: The Turkish Empire , was an imperial realm that controlled much of Southeast Europe , West Asia , and North Africa from the 14th to early 20th centuries; it also controlled parts of southeastern Central Europe , between the early 16th and early 18th centuries. The empire emerged from a beylik , or principality , founded in northwestern Anatolia in c.  1299 by the Turkoman tribal leader Osman I . His successors conquered much of Anatolia and expanded into

5203-435: The blood plasma ; and tumor necrosis factor alpha in splenic Gaucher cells (engorged macrophages). Gaucher disease is suggested based on the overall clinical picture. Initial laboratory testing may include enzyme testing. As a result, lower than 15% of mean normal activity is considered to be diagnostic. Decreased enzyme levels will often be confirmed by genetic testing. Numerous different mutations occur; sequencing of

5324-406: The Arabic name ʿUthmān ( عثمان ). In Ottoman Turkish , the empire was referred to as Devlet-i ʿAlīye-yi ʿO s mānīye ( دولت عليه عثمانیه ), lit.   ' Sublime Ottoman State ' , or simply Devlet-i ʿO s mānīye ( دولت عثمانيه‎ ), lit.   ' Ottoman State ' . The Turkish word for "Ottoman" ( Osmanlı ) originally referred to the tribal followers of Osman in

5445-463: The Ashkenazi Jewish gene pool in the early Middle Ages (48–55 generations ago). The disease is caused by a defect in the housekeeping gene for lysosomal glucocerebrosidase (also known as beta-glucosidase, EC 3.2.1.45 , PDB : 1OGS ​) on the first chromosome (1q22). The enzyme is a 55.6- kilodalton , 497- amino acid -long protein that catalyses the breakdown of glucocerebroside,

5566-649: The Balkan Peninsula during the Congress of Berlin , and in return, Britain assumed the administration of Cyprus in 1878. Britain later sent troops to Egypt in 1882 to put down the Urabi Revolt (Sultan Abdul Hamid II was too paranoid to mobilize his own army, fearing this would result in a coup d'état), effectively gaining control in both territories. Abdul Hamid II was so fearful of a coup that he did not allow his army to conduct war games, lest this serve as cover for

5687-544: The Balkans . Osman's son, Orhan , captured the northwestern Anatolian city of Bursa in 1326, making it the new capital and supplanting Byzantine control in the region. The important port of Thessaloniki was captured from the Venetians in 1387 and sacked. The Ottoman victory in Kosovo in 1389 effectively marked the end of Serbian power in the region, paving the way for Ottoman expansion into Europe. The Battle of Nicopolis for

5808-583: The Balkans, where a number of new states emerged. Beginning in the late 19th century, various Ottoman intellectuals sought to further liberalize society and politics along European lines, culminating in the Young Turk Revolution of 1908 led by the Committee of Union and Progress (CUP), which established the Second Constitutional Era and introduced competitive multi-party elections under

5929-614: The Conqueror , reorganized both state and military, and on 29 May 1453 conquered Constantinople , ending the Byzantine Empire. Mehmed allowed the Eastern Orthodox Church to maintain its autonomy and land in exchange for accepting Ottoman authority. Due to tension between the states of western Europe and the later Byzantine Empire, most of the Orthodox population accepted Ottoman rule, as preferable to Venetian rule. Albanian resistance

6050-444: The Constitution, called the Kanûn-u Esâsî . The empire's First Constitutional era was short-lived. The parliament survived for only two years before the sultan suspended it. The empire's Christian population, owing to their higher educational levels, started to pull ahead of the Muslim majority, leading to much resentment. In 1861, there were 571 primary and 94 secondary schools for Ottoman Christians, with 140,000 pupils in total,

6171-482: The French invasion the total population of Algeria was most likely between 3,000,000 and 5,000,000. By 1873, the population of Algeria (excluding several hundred thousand newly arrived French settlers) had decreased to 2,172,000. In 1831, Muhammad Ali of Egypt revolted against Sultan Mahmud II due to the latter's refusal to grant him the governorships of Greater Syria and Crete , which the Sultan had promised him in exchange for sending military assistance to put down

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6292-507: The French physician Philippe Gaucher , who originally described it in 1882. The three types of Gaucher's disease are autosomal recessive . Both parents must be carriers for a child to be affected. If both parents are carriers, the chance of the disease is one in four, or 25%, with each pregnancy for an affected child. Each type has been linked to particular mutations. In all, about 80 known GBA gene mutations are grouped into three main types: The Gaucher-causing mutations may have entered

6413-405: The Iberians passed through newly-Christianized Latin America and had sent expeditions that traversed the Pacific to Christianize the formerly Muslim Philippines and use it as a base to attack the Muslims in the Far East . In this case, the Ottomans sent armies to aid its easternmost vassal and territory, the Sultanate of Aceh in Southeast Asia. During the 1600s, the world conflict between

6534-664: The Islamic clergy successfully objected under the grounds of theodicy . In 1754 the artillery school was reopened on a semi-secret basis. In 1726, Ibrahim Muteferrika convinced the Grand Vizier Nevşehirli Damat Ibrahim Pasha , the Grand Mufti , and the clergy on the efficiency of the printing press, and Muteferrika was later granted by Sultan Ahmed III permission to publish non-religious books (despite opposition from some calligraphers and religious leaders). Muteferrika's press published its first book in 1729 and, by 1743, issued 17 works in 23 volumes, each having between 500 and 1,000 copies. In North Africa, Spain conquered Oran from

6655-413: The Janissary revolted . Selim's efforts cost him his throne and his life, but were resolved in spectacular and bloody fashion by his successor, the dynamic Mahmud II , who eliminated the Janissary corps in 1826. The Serbian revolution (1804–1815) marked the beginning of an era of national awakening in the Balkans during the Eastern Question . In 1811, the fundamentalist Wahhabis of Arabia, led by

6776-402: The Magnificent (1520–1566) captured Belgrade in 1521, conquered the southern and central parts of the Kingdom of Hungary as part of the Ottoman–Hungarian Wars , and, after his historic victory in the Battle of Mohács in 1526, he established Ottoman rule in the territory of present-day Hungary and other Central European territories. He then laid siege to Vienna in 1529, but failed to take

6897-413: The Ottoman Caliphate and Iberian Union was a stalemate since both were at similar population , technology and economic levels. Nevertheless, the success of the Ottoman political and military establishment was compared to the Roman Empire , despite the difference in size, by the likes of contemporary Italian scholar Francesco Sansovino and French political philosopher Jean Bodin . In the second half of

7018-467: The Ottoman Empire gradually shrank, 7–9   million Muslims from its former territories in the Caucasus, Crimea , Balkans, and the Mediterranean islands migrated to Anatolia and Eastern Thrace . After the Empire lost the First Balkan War (1912–1913), it lost all its Balkan territories except East Thrace (European Turkey). This resulted in around 400,000 Muslims fleeing with the retreating Ottoman armies (with many dying from cholera brought by

7139-406: The Ottoman Empire was once thought to have entered a period of decline after the death of Suleiman the Magnificent, modern academic consensus posits that the empire continued to maintain a flexible and strong economy, society and military into much of the 18th century. However, during a long period of peace from 1740 to 1768, the Ottoman military system fell behind those of its chief European rivals,

7260-403: The Ottoman admirals Hayreddin Barbarossa and Dragut . France supported the Ottomans with an artillery unit during the 1543 Ottoman conquest of Esztergom in northern Hungary. After further advances by the Turks, the Habsburg ruler Ferdinand officially recognized Ottoman ascendancy in Hungary in 1547. Suleiman died of natural causes during the siege of Szigetvár in 1566. Following his death,

7381-432: The Ottoman economy, and used its position to ensure that European capital continued to penetrate the empire, often to the detriment of local Ottoman interests. The Ottoman bashi-bazouks suppressed the Bulgarian uprising of 1876, massacring up to 100,000 people in the process. The Russo-Turkish War (1877–1878) ended with a decisive victory for Russia. As a result, Ottoman holdings in Europe declined sharply: Bulgaria

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7502-488: The Ottomans were said to be declining, although this has been rejected by many scholars. By the end of Suleiman's reign, the Empire spanned approximately 877,888 sq mi (2,273,720 km ), extending over three continents. The Empire became a dominant naval force, controlling much of the Mediterranean Sea . The Empire was now a major part of European politics. The Ottomans became involved in multi-continental religious wars when Spain and Portugal were united under

7623-463: The Russian Empire (2 November 1914) and its allies France (5 November 1914) and the British Empire (5 November 1914) declared war on the Ottoman Empire. Also on 5 November 1914, the British government changed the status of the Khedivate of Egypt and Cyprus , which were de jure Ottoman territories prior to the war, to British protectorates . Gaucher%27s disease Gaucher's disease or Gaucher disease ( / ɡ oʊ ˈ ʃ eɪ / ) ( GD )

7744-483: The Russian intervention, Sultan Mahmud II could have faced the risk of being overthrown and Muhammad Ali could have even become the new Sultan. These events marked the beginning of a recurring pattern where the Sublime Porte needed the help of foreign powers to protect itself. In 1839, the Sublime Porte attempted to take back what it lost to the de facto autonomous, but de jure still Ottoman Eyalet of Egypt , but its forces were initially defeated, which led to

7865-424: The Russians. After this treaty the Ottoman Empire was able to enjoy a generation of peace in Europe, as Austria and Russia were forced to deal with the rise of Prussia . Educational and technological reforms came about, including the establishment of higher education institutions such as the Istanbul Technical University . In 1734 an artillery school was established to impart Western-style artillery methods, but

7986-518: The Safavids. The resulting Treaty of Zuhab of that same year decisively divided the Caucasus and adjacent regions between the two neighbouring empires as it had already been defined in the 1555 Peace of Amasya. The Sultanate of Women (1533–1656) was a period in which the mothers of young sultans exercised power on behalf of their sons. The most prominent women of this period were Kösem Sultan and her daughter-in-law Turhan Hatice , whose political rivalry culminated in Kösem's murder in 1651. During

8107-400: The Turks, but was again defeated at the Second Battle of Kosovo in 1448. According to modern historiography, there is a direct connection between the rapid Ottoman military advance and the consequences of the Black Death from the mid-fourteenth century onwards. Byzantine territories, where the initial Ottoman conquests were carried out, were exhausted demographically and militarily due to

8228-412: The United States are carriers of the most common type of Gaucher disease. The carrier rate among Ashkenazi Jews is 8.9% while the birth incidence is 1 in 450. Gaucher's disease is the most common of the lysosomal storage diseases . It is a form of sphingolipidosis (a subgroup of lysosomal storage diseases), as it involves dysfunctional metabolism of sphingolipids . The disease is named after

8349-412: The advantage of the defeat at Vienna, culminating in the Treaty of Karlowitz (26 January 1699), which ended the Great Turkish War. The Ottomans surrendered control of significant territories, many permanently. Mustafa II (1695–1703) led the counterattack of 1695–1696 against the Habsburgs in Hungary, but was undone at the disastrous defeat at Zenta (in modern Serbia), 11 September 1697. Aside from

8470-417: The al-Saud family, revolted against the Ottomans. Unable to defeat the Wahhabi rebels, the Sublime Porte had Muhammad Ali Pasha of Kavala , the vali (governor) of the Eyalet of Egypt , tasked with retaking Arabia, which ended with the destruction of the Emirate of Diriyah in 1818. The suzerainty of Serbia as a hereditary monarchy under its own dynasty was acknowledged de jure in 1830. In 1821,

8591-436: The autonomous Deylik of Algiers . The Bey of Oran received an army from Algiers, but it failed to recapture Oran ; the siege caused the deaths of 1,500 Spaniards, and even more Algerians. The Spanish also massacred many Muslim soldiers. In 1792, Spain abandoned Oran, selling it to the Deylik of Algiers. In 1768 Russian-backed Ukrainian Haidamakas , pursuing Polish confederates, entered Balta , an Ottoman-controlled town on

8712-526: The beta-glucosidase gene is sometimes necessary to confirm the diagnosis. Prenatal diagnosis is available and is useful when a known genetic risk factor is present. A diagnosis can also be implied by biochemical abnormalities such as high alkaline phosphatase , angiotensin-converting enzyme , and immunoglobulin levels, or by cell analysis showing "crinkled paper" cytoplasm and glycolipid-laden macrophages. Some lysosomal enzymes are elevated, including tartrate-resistant acid phosphatase , hexosaminidase, and

8833-579: The border of Bessarabia in Ukraine, massacred its citizens, and burned the town to the ground. This action provoked the Ottoman Empire into the Russo-Turkish War of 1768–1774 . The Treaty of Küçük Kaynarca of 1774 ended the war and provided freedom of worship for the Christian citizens of the Ottoman-controlled provinces of Wallachia and Moldavia. By the late 18th century, after a number of defeats in

8954-637: The century after Osman I, Ottoman rule had begun to extend over Anatolia and the Balkans . The earliest conflicts began during the Byzantine–Ottoman wars , waged in Anatolia in the late 13th century before entering Europe in the mid-14th century, followed by the Bulgarian–Ottoman wars and the Serbian–Ottoman wars in the mid-14th century. Much of this period was characterised by Ottoman expansion into

9075-499: The city of Kütahya within 320 km (200 mi) of the capital, Constantinople. In desperation, Sultan Mahmud II appealed to the empire's traditional arch-rival Russia for help, asking Emperor Nicholas I to send an expeditionary force to assist him. In return for signing the Treaty of Hünkâr İskelesi , the Russians sent the expeditionary force which deterred Ibrahim Pasha from marching any further towards Constantinople. Under

9196-611: The city. In 1532, he made another attack on Vienna, but was repulsed in the siege of Güns . Transylvania , Wallachia and, intermittently, Moldavia , became tributary principalities of the Empire. In the east, the Ottoman Turks took Baghdad from the Persians in 1535, gaining control of Mesopotamia and naval access to the Persian Gulf . In 1555, the Caucasus became partitioned for

9317-660: The civil strife, Austria-Hungary officially annexed Bosnia and Herzegovina in 1908. The last of the Ottoman censuses was performed in 1914 . Despite military reforms which reconstituted the Ottoman Modern Army , the Empire lost its North African territories and the Dodecanese in the Italo-Turkish War (1911) and almost all of its European territories in the Balkan Wars (1912–1913). The Empire faced continuous unrest in

9438-1259: The complexity of predicting disease course. GD type I (non-neuropathic) is the most common and least severe form of the disease. Symptoms may begin early in life or in adulthood and mainly affect the liver, spleen, and bone. Enlarged liver and grossly enlarged spleen (together hepatosplenomegaly ) are common; the spleen can rupture and cause additional complications. Skeletal weakness and bone disease may be extensive. Spleen enlargement and bone marrow replacement cause anemia, thrombocytopenia, and leukopenia . The brain and nervous system are not affected pathologically, but lung and, rarely, kidney impairment may occur. Patients in this group usually bruise easily (due to low levels of platelets) and experience fatigue due to low numbers of red blood cells. Depending on disease onset and severity, type I patients may live well into adulthood. The range and severity of symptoms can vary dramatically between patients. GD type II (acute infantile neuropathic) typically begins within six months of birth and has an incidence rate around 1 in 100,000 live births. Symptoms include an enlarged liver and spleen, extensive and progressive brain damage, eye movement disorders, spasticity , seizures , limb rigidity, and

9559-991: The core of the unit, which receives patients from around the country. Shaare Zedek was the first hospital in Israel to develop fully integrated oncology and palliative medicine services in 1994. The model of care developed at Shaare Zedek formed the basis for the 13 criteria for designation of a cancer center as a center of integrated oncology and palliative care that was developed by the European Society of Medical Oncology (ESMO). The hospital has specialized units for Gaucher's disease and cystic fibrosis . In addition, neurosurgery department headed by Dr. Nevo Margalit opened in 2017, offering skull base surgery, neurooncoloy, pediatric neurosurgery , orthopedic surgery and trauma services. 31°46′23″N 35°11′06″E  /  31.77306°N 35.18500°E  / 31.77306; 35.18500 Ottoman Empire The Ottoman Empire ( / ˈ ɒ t ə m ə n / ), also called

9680-630: The eastern and southern frontiers by defeating Shah Ismail of Safavid Iran , in the Battle of Chaldiran . Selim I established Ottoman rule in Egypt by defeating and annexing the Mamluk Sultanate of Egypt and created a naval presence on the Red Sea . After this Ottoman expansion, competition began between the Portuguese Empire and the Ottomans to become the dominant power in the region. Suleiman

9801-514: The empire into a more harmonious place. Instead, this period became the story of the twilight struggle of the Empire. Members of Young Turks movement who had once gone underground now established their parties. Among them " Committee of Union and Progress ", and " Freedom and Accord Party " were major parties. On the other end of the spectrum were ethnic parties, which included Poale Zion , Al-Fatat , and Armenian national movement organised under Armenian Revolutionary Federation . Profiting from

9922-624: The empire was able to largely hold its own during the conflict, it struggled with internal dissent, especially the Arab Revolt . During this period, the Ottoman government engaged in genocide against Armenians , Assyrians , and Greeks . In the aftermath of World War I , the victorious Allied Powers occupied and partitioned the Ottoman Empire, which lost its southern territories to the United Kingdom and France . The successful Turkish War of Independence , led by Mustafa Kemal Atatürk against

10043-582: The end of the Caucasian Wars , 90% of the Circassians were ethnically cleansed and exiled from their homelands in the Caucasus, fleeing to the Ottoman Empire, resulting in the settlement of 500,000 to 700,000 Circassians in the Ottoman Empire. Crimean Tatar refugees in the late 19th century played an especially notable role in seeking to modernise Ottoman education and in first promoting both Pan-Turkism and

10164-515: The end of the seventeenth century, and instead the word increasingly became associated with the Greek population of the empire, a meaning that it still bears in Turkey today. In Western Europe, the names Ottoman Empire, Turkish Empire and Turkey were often used interchangeably, with Turkey being increasingly favoured both in formal and informal situations. This dichotomy was officially ended in 1920–1923, when

10285-557: The enzyme is defective, glucocerebroside accumulates, particularly in white blood cells and especially in macrophages ( mononuclear leukocytes , which is often a target for intracellular parasites ). Glucocerebroside can collect in the spleen , liver , kidneys , lungs , brain , and bone marrow . Manifestations may include enlarged spleen and liver, liver malfunction, skeletal disorders or bone lesions that may be painful, severe neurological complications, swelling of lymph nodes and (occasionally) adjacent joints, distended abdomen,

10406-750: The fall of 2010. In early 2014, Shaare Zedek opened the first phase of The Next Generation Building, a comprehensive response to medical care for children from infancy through adolescence. The ten-story building houses the Wilf Children's Hospital and the Glaubach Department of Pediatric Emergency Medicine. It also includes a pediatric intensive care unit (PICU), as well as departments for pediatric neurology, cardiology, urology, nephrology, rheumatology, pulmonology, hematology, gastroenterology, infectious disease, and neonatology. The hospital's maternity facilities were also expanded. A third maternity department

10527-531: The first time between the Safavids and the Ottomans, a status quo that remained until the end of the Russo-Turkish War (1768–1774) . By this partitioning as signed in the Peace of Amasya , Western Armenia , western Kurdistan , and Western Georgia fell into Ottoman hands, while southern Dagestan , Eastern Armenia , Eastern Georgia , and Azerbaijan remained Persian. In 1539, a 60,000-strong Ottoman army besieged

10648-460: The formation of glucocerebroside, the substance that builds up and causes harm in Gaucher's. This approach is called substrate reduction therapy . Eliglustat (Cerdelga) (approved in 2014) is also a small molecule. The compound is believed to work by inhibition of glucosylceramide synthase . The National Gaucher Foundation (United States) states the incidence of Gaucher's disease is about one in 20,000 live births. Around one in 100 people in

10769-456: The fourteenth century. The word subsequently came to be used to refer to the empire's military-administrative elite. In contrast, the term "Turk" ( Türk ) was used to refer to the Anatolian peasant and tribal population and was seen as a disparaging term when applied to urban, educated individuals. In the early modern period , an educated, urban-dwelling Turkish speaker who was not a member of

10890-401: The general US population is a carrier for type I Gaucher's disease, giving a prevalence of one in 40,000. Among Ashkenazi Jews, the rate of carriers is considerably higher, at roughly one in 15. Type II Gaucher's disease shows no particular preference for any ethnic group. Type III Gaucher's disease is especially common in the population of the northern Swedish region of Norrbotten , where

11011-550: The hospital can be evacuated to this portion when necessary. Shaare Zedek is the on-call facility in the event of chemical warfare attacks in the Jerusalem area. Shaare Zedek's decontamination facilities served as an inspiration for New York's largest similar facility at the New York Downtown Hospital . Shaare Zedek is a private hospital that relies on fundraising for capital development projects. The director general of

11132-735: The hospital is Prof. Ofer Merin . Professor Jonathan Halevy who served as the Director General of the hospital from 1988 until 2019 was appointed as the Medical Center's president. The hospital maintains public relations offices in ten countries, among them are England and the United States . An interesting fact is that a high percentage of the hospital's physicians and other staff are immigrants, especially from English-speaking countries. In June 2007, Shaare Zedek renovated its surgical facilities. The Wohl Surgical Operating Complex opened in

11253-399: The incidence of the disease is one in 50,000. The disease was first recognized by the French doctor Philippe Gaucher , who originally described it in 1882 and lent his name to the condition. In 1902, its mode of inheritance was discovered by Nathan Brill. The neuronal damage associated with the disease was discovered in the 1920s, and the biochemical basis for the disease was elucidated in

11374-622: The independence of the Middle East" in the 19th century "was not the armies of Europe but its banks". The Ottoman state, which had begun taking on debt with the Crimean War, was forced to declare bankruptcy in 1875. By 1881, the Ottoman Empire agreed to have its debt controlled by the Ottoman Public Debt Administration , a council of European men with presidency alternating between France and Britain. The body controlled swaths of

11495-507: The last Venetian stronghold in Cyprus, Famagusta. The Venetian defenders held out for 11 months against a force that at its peak numbered 200,000 men with 145 cannons; 163,000 cannonballs struck the walls of Famagusta before it fell to the Ottomans in August 1571. The Siege of Famagusta claimed 50,000 Ottoman casualties. Meanwhile, the Holy League consisting of mostly Spanish and Venetian fleets won

11616-540: The late 16th and early 17th centuries. With the Empire's population reaching 30 million people by 1600, the shortage of land placed further pressure on the government. In spite of these problems, the Ottoman state remained strong, and its army did not collapse or suffer crushing defeats. The only exceptions were campaigns against the Safavid dynasty of Persia, where many of the Ottoman eastern provinces were lost, some permanently. This 1603–1618 war eventually resulted in

11737-518: The loss of the Banat and the temporary loss of Belgrade (1717–1739), the Ottoman border on the Danube and Sava remained stable during the eighteenth century. Russian expansion , however, presented a large and growing threat. Accordingly, King Charles XII of Sweden was welcomed as an ally in the Ottoman Empire following his defeat by the Russians at the Battle of Poltava of 1709 in central Ukraine (part of

11858-459: The military-administrative class typically referred to themselves neither as an Osmanlı nor as a Türk , but rather as a Rūmī ( رومى ), or "Roman", meaning an inhabitant of the territory of the former Byzantine Empire in the Balkans and Anatolia. The term Rūmī was also used to refer to Turkish speakers by the other Muslim peoples of the empire and beyond. As applied to Ottoman Turkish speakers, this term began to fall out of use at

11979-537: The need for greater numbers of Ottoman infantry equipped with firearms, resulting in a relaxation of recruitment policy. This contributed to problems of indiscipline and outright rebelliousness within the corps, which were never fully solved. Irregular sharpshooters ( Sekban ) were also recruited, and on demobilisation turned to brigandage in the Celali rebellions (1590–1610), which engendered widespread anarchy in Anatolia in

12100-418: The neighborhoods of Bayit VeGan in the south and Ramat Beit HaKerem in the north, east of Mount Herzl in southwest Jerusalem. The downtown campus, formerly known as Bikur Cholim Hospital, is located in the heart of Jerusalem's downtown commercial zone. The hospital has 1000 beds and treats over 500,000 patients a year in its in-patient and out-patient facilities. As terrorist attacks in Jerusalem reached

12221-421: The new conditions of the seventeenth century and remain powerful, both militarily and economically. Historians of the mid-twentieth century once characterised this period as one of stagnation and decline, but this view is now rejected by the majority of academics. The discovery of new maritime trade routes by Western European states allowed them to avoid the Ottoman trade monopoly. The Portuguese discovery of

12342-459: The newly established Ankara -based Turkish government chose Turkey as the sole official name. At present, most scholarly historians avoid the terms "Turkey", "Turks", and "Turkish" when referring to the Ottomans, due to the empire's multinational character. As the Rum Sultanate declined in the 13th century, Anatolia was divided into a patchwork of independent Turkish principalities known as

12463-458: The occupying Allies, led to the emergence of the Republic of Turkey in the Anatolian heartland and the abolition of the Ottoman monarchy in 1922, formally ending the Ottoman Empire. The word Ottoman is a historical anglicisation of the name of Osman I , the founder of the Empire and of the ruling House of Osman (also known as the Ottoman dynasty). Osman's name in turn was the Turkish form of

12584-406: The plague, which facilitated Ottoman expansion. In addition, slave hunting was the main economic driving force behind Ottoman conquest. Some 21st-century authors re-periodize conquest of the Balkans into the akıncı phase , which spanned 8 to 13 decades, characterized by continuous slave hunting and destruction, followed by administrative integration into the Empire. The son of Murad II, Mehmed

12705-436: The residual enzyme activity correlates well with disease symptoms. This circumstance has called for alternative explanations accounting for disease symptoms including Heterozygotes for particular acid beta-glucosidase mutations carry about a five-fold risk of developing Parkinson's disease , making this the most common known genetic risk factor for Parkinson's. Cancer risk may be increased, particularly myeloma . This

12826-563: The restoration of Ottoman suzerainty over Egypt Eyalet and the Levant . By the mid-19th century, the Ottoman Empire was called the " sick man of Europe ". Three suzerain states – the Principality of Serbia , Wallachia and Moldavia – moved towards de jure independence during the 1860s and 1870s. During the Tanzimat period (1839–1876), the government's series of constitutional reforms led to

12947-467: The sixteenth century, the Ottoman Empire came under increasing strain from inflation and the rapidly rising costs of warfare that were impacting both Europe and the Middle East. These pressures led to a series of crises around the year 1600, placing great strain upon the Ottoman system of government. The empire underwent a series of transformations of its political and military institutions in response to these challenges, enabling it to successfully adapt to

13068-478: The soldiers), and 400,000 non-Muslims fled territory still under Ottoman rule. Justin McCarthy estimates that from 1821 to 1922, 5.5   million Muslims died in southeastern Europe, with the expulsion of 5   million. The defeat and dissolution of the Ottoman Empire (1908—1922) began with the Second Constitutional Era , a moment of hope and promise established with the Young Turk Revolution . It restored

13189-557: The start of the 17th century, the Ottomans presided over 32 provinces and numerous vassal states , which over time were either absorbed into the Empire or granted various degrees of autonomy. With its capital at Constantinople (modern-day Istanbul ) and control over a significant portion of the Mediterranean Basin , the Ottoman Empire was at the centre of interactions between the Middle East and Europe for six centuries. While

13310-663: The sultan and restored Ottoman power. The Balkan territories lost by the Ottomans after 1402, including Thessaloniki, Macedonia, and Kosovo, were later recovered by Murad II between the 1430s and 1450s. On 10 November 1444, Murad repelled the Crusade of Varna by defeating the Hungarian, Polish, and Wallachian armies under Władysław III of Poland and John Hunyadi at the Battle of Varna , although Albanians under Skanderbeg continued to resist. Four years later, John Hunyadi prepared another army of Hungarian and Wallachian forces to attack

13431-502: The terms of the Convention of Kütahya , signed on 5 May 1833, Muhammad Ali agreed to abandon his campaign against the Sultan, in exchange for which he was made the vali (governor) of the vilayets (provinces) of Crete , Aleppo , Tripoli , Damascus and Sidon (the latter four comprising modern Syria and Lebanon ), and given the right to collect taxes in Adana . Had it not been for

13552-565: The wars with Russia, some people in the Ottoman Empire began to conclude that the reforms of Peter the Great had given the Russians an edge, and the Ottomans would have to keep up with Western technology in order to avoid further defeats. Selim III (1789–1807) made the first major attempts to modernise the army , but his reforms were hampered by the religious leadership and the Janissary corps. Jealous of their privileges and firmly opposed to change,

13673-517: The years leading up to World War I , including the 31 March Incident and two further coups in 1912 and 1913 . The Ottoman Empire entered World War I on the side of the Central Powers and was ultimately defeated. The Ottoman participation in the war began with the combined German-Ottoman surprise attack on the Black Sea coast of the Russian Empire on 29 October 1914. Following the attack,

13794-450: Was a major obstacle to Ottoman expansion on the Italian peninsula. In the 15th and 16th centuries, the Ottoman Empire entered a period of expansion . The Empire prospered under the rule of a line of committed and effective Sultans . It flourished economically due to its control of the major overland trade routes between Europe and Asia. Sultan Selim I (1512–1520) dramatically expanded

13915-605: Was by German architect Theodor Sandel [ German ] . Its opening ceremony took place on January 27, 1902. Dr. Moshe Wallach was the director from then until 1947. Schwester Selma lived in the hospital and cared for abandoned children. The building in Bayit Vegan was inaugurated in 1980. In December 2012, Shaare Zedek assumed operational control over Bikur Cholim Hospital and merged many of its activities. The hospital treats over 600,000 patients per year in more than 30 inpatient departments and over 70 outpatient units and maintains

14036-465: Was established as an independent principality inside the Ottoman Empire; Romania achieved full independence; and Serbia and Montenegro finally gained complete independence, but with smaller territories. In 1878, Austria-Hungary unilaterally occupied the Ottoman provinces of Bosnia-Herzegovina and Novi Pazar . British Prime Minister Benjamin Disraeli advocated restoring the Ottoman territories on

14157-590: Was far more damaging to the Ottoman navy in sapping experienced manpower than the loss of ships, which were rapidly replaced. The Ottoman navy recovered quickly, persuading Venice to sign a peace treaty in 1573, allowing the Ottomans to expand and consolidate their position in North Africa. By contrast, the Habsburg frontier had settled somewhat, a stalemate caused by a stiffening of the Habsburg defenses. The Long Turkish War against Habsburg Austria (1593–1606) created

14278-469: Was on the defensive and unlikely to present any further aggression in Europe. The Austro-Russian–Turkish War (1735–1739), which was ended by the Treaty of Belgrade in 1739, resulted in the Ottoman recovery of northern Bosnia , Habsburg Serbia (including Belgrade), Oltenia and the southern parts of the Banat of Temeswar ; but the Empire lost the port of Azov , north of the Crimean Peninsula, to

14399-591: Was opened in March 2009. Well over 1200 children are born in the hospital each month, on average; this figure is higher than that of all other Jerusalem hospitals combined. After the merger with Bikur Cholim Hospital in December 2012, the number of births grew to over 20,000 a year. The tenth floor of the hospital is occupied by the Jesselson Heart Center, which combines cardiology and cardiothoracic surgery. In 2008, it

14520-479: Was part of a long-running contest between the major European powers for influence over territories of the declining Ottoman Empire. The financial burden of the war led the Ottoman state to issue foreign loans amounting to 5   million pounds sterling on 4 August 1854. The war caused an exodus of the Crimean Tatars , about 200,000 of whom moved to the Ottoman Empire in continuing waves of emigration. Toward

14641-456: Was the first hospital in Israel to replace heart valves via cardiac catheterization. Shaare Zedek's emergency department includes a 14-bed observation and short stay unit, as well as a 5-bed chest pain unit. The department, opened in the early 2000s, served 112,000 patients in 2012. The department includes separate units for the spine, arthroscopy, hand surgery, joint reconstruction, and foot and ankle care. A total of 14 orthopedic surgeons form

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