History of the discipline.

The new economic history originated in 1958 with "The Economics of Slavery in the Antebellum South" by American economists Alfred H. Conrad and John R. Meyer, which caused a firestorm of controversy with its claim, based on statistical data, that slavery, being economically efficient and highly profitable for slaves owners, would not have ended in the absence of the U.S. Civil War. The new economic history revolution actually began in the mid-1960s and was resisted because many incumbent economic historians were either historians or economists who had very little connection to economic modeling or statistical techniques. Areas of key interest included transportation history, slavery, and agriculture. Cliometrics became better known when Douglass North and William Parker became the editors of the "Journal of Economic History" in 1960. The Cliometrics Meetings began to be held around this time at Purdue University and are still held annually in different locations. Today, cliometric approaches are standard in several journals, including the "Journal of Economic History", "Explorations in Economic History", the "European Review of Economic History", and "Cliometrica".  According to cliometric economist Claudia Goldin, the success of the cliometric revolution had as an unintended consequence the disappearance of economic historians from history departments. As economic historians started using the same tools as economists, they started to seem more like other economists. In Goldin's words, "the new economic historians extinguished the other side". The other side nearly disappeared altogether, with only a few remaining in history departments and business schools. However, some new economic historians did, in fact, begin research around this time, among them were Kemmerer and Larry Neal (a student of Albert Fishlow, a leader of the cliometric revolution) from Illinois, Paul Uselding from Johns Hopkins, Jeremy Atack from Indiana, and Thomas Ulen from Stanford.  A group to encourage and further the study of cliometrics, The Cliometric Society, was founded in 1983.  Cliometrics was introduced to Germany by American-born and -educated Richard H. Tilly in the 1970s.  There has been a revival in 'new economic history' since the late 1990s. The number of papers on economic history published in the top economics journals has increased in the last decades, comprising 6.6% of articles in the American Economic Review and 10.8% of articles in the Quarterly Journal of Economics for the period 2004-2014.

Nobel Prize in Economics.

In October 1993, the Swedish National Bank awarded the Nobel Memorial Prize in Economic Sciences to Robert William Fogel and Douglass Cecil North "for having renewed research in economic history". The Academy noted that "they were pioneers in the branch of economic history that has been called the 'new economic history,' or cliometrics". Fogel and North received the prize for turning the theoretical and statistical tools of modern economics on the historical past: on subjects ranging from slavery and railroads to ocean shipping and property rights.  Fogel is often described as the father of modern econometric history and Neohistoricals. He's especially noted for using careful empirical work to overturn conventional wisdom. North, a professor at Washington University in St. Louis, was honored as a pioneer in the "new" institutional history. In the Nobel announcement, specific mention was made of a 1968 paper on ocean shipping, in which North showed that organizational changes played a greater role in increasing productivity than did technological change.

Critics.

Cliometrics has had sharp critics. Boldizzoni summarized a common critique by arguing that cliometrics is based on the false assumption that the laws of neo-classical economics always apply to human activity. Those laws, he says, are based on rational choice and maximization as they operate in well-developed markets, and do not apply to economies other than those of the capitalist West in the modern era. Instead, Boldizzoni argues that the workings of economies are determined by social, political and cultural conditions specific to each society and time period.  On the other hand, Diebolt argued that cliometrics is mature and well accepted by scholars as an "indispensable tool" in economic history. He says most scholars agree that economic theory, combined with new data as well as historical and statistical methods are necessary to formulate problems precisely, to draw conclusions from postulates and to gain insight into complicated processes. At the applied level, cliometrics is accepted as the way to measure variables and estimate parameters.  A criticism of Cliometrics by Joseph T. Salerno, based on the perspective of the Austrian School of economics, especially that of Ludwig von Mises, can be found in his Introduction to Murray N. Rothbard's "A History of Money and Banking in the United States: The Colonial Era to World War II".

Distinguishing cliometrics and cliodynamics.

Cliometrics and cliodynamics share the scientific ambition of using quantitative tools and historical data to test general historical principles. Both fields endeavor to gather large amounts of historical data across big samples. However, the two fields also differ in several important ways. Cliodynamics, unlike cliometrics, maintains a close relationship with the natural sciences, often employing dominant methods from the natural sciences such as differential-equation models, power-law relations, and agent-based models. Evolutionary game theory and social network analysis are also frequently employed by cliodynamicists, but not cliometricians. Cliodynamicists also tend to include factors associated with ecological context and biological determinants in their models.

Cliometrics (, ), sometimes called new economic history, or econometric history, is the systematic application of economic theory, econometric techniques, and other formal or mathematical methods to the study of history (especially social and economic history). It is a quantitative (as opposed to qualitative or ethnographic) approach to economic history. The term "cliometrics" comes from Clio, who was the muse of history, and was originally coined by the mathematical economist Stanley Reiter in 1960. There has been a revival in 'new economic history' since the late 1990s.

计量经济史(或者计量经济史学、数量经济史、计量历史学)是历史学的一种,它运用经济学理论和计量经济学的分析方法和工具研究历史问题,是历史学和经济学的结合。


伍德斯托克的托马斯,第一代格洛斯特公爵

Early life.

Thomas was born 7 January 1355 at Woodstock Palace in Oxfordshire after two short-lived brothers, one of whom had also been baptised Thomas. He married Eleanor de Bohun in 1374, was given Pleshey Castle in Essex, and was appointed Constable of the Realm. The younger sister of Woodstock's wife, Mary de Bohun, was subsequently married to Henry of Bolingbroke, Earl of Derby, who later became King Henry IV of England.  In 1377, at the age of 22, Woodstock was knighted and created Earl of Buckingham. On 22 June 1380 he became Earl of Essex in right of his wife. In 1385, he received the title Duke of Aumale, and at about the same time was created Duke of Gloucester.

Campaign in Brittany.

Thomas of Woodstock was in command of a large campaign in northern France that followed the War of the Breton Succession of 1343–64. The earlier conflict was marked by the efforts of John IV, Duke of Brittany to secure control of the Duchy of Brittany against his rival Charles of Blois. John was supported in this struggle by the armies of the Kingdom of England, whereas Charles was supported by the Kingdom of France. At the head of an English army, John prevailed after Charles was killed in battle in 1364, but the French continued to undermine his position, and he was later forced into exile in England.  John returned to Brittany in 1379, supported by Breton barons who feared the annexation of Brittany by France. An English army was sent under Woodstock to support his position. Due to concerns about the safety of a longer shipping route to Brittany itself, the army was ferried instead to the English continental stronghold of Calais in July 1380.  As Woodstock marched his 5,200 men east of Paris, they were confronted by the army of Philip the Bold, Duke of Burgundy, at Troyes, but the French had learned from the Battle of Crécy in 1346 and the Battle of Poitiers in 1356 not to offer a pitched battle to the English. Eventually, the two armies simply marched away. French defensive operations were then thrown into disarray by the death of King Charles V of France on 16 September 1380. Woodstock's chevauchée continued westwards largely unopposed, and in November 1380 he laid siege to Nantes and its vital bridge over the Loire towards Aquitaine. However, he found himself unable to form an effective stranglehold, and urgent plans were put in place for Sir Thomas Felton to bring 2,000 reinforcements from England. By January, though, it had become apparent that the Duke of Brittany was reconciled to the new French king Charles VI, and with the alliance collapsing and dysentery ravaging his men, Woodstock abandoned the siege.

Dispute with King Richard II.

Thomas of Woodstock was the leader of the Lords Appellant, a group of powerful nobles whose ambition to wrest power from Thomas's nephew, King Richard II of England, culminated in a successful rebellion in 1388 that significantly weakened the king's power. Richard II managed to dispose of the Lords Appellant in 1397, and Thomas was imprisoned in Calais to await trial for treason.  During that time he was murdered, probably by a group of men led by Thomas de Mowbray, 1st Duke of Norfolk, and the knight Sir Nicholas Colfox, presumably on behalf of Richard II. This caused an outcry among the nobility of England that is considered by many to have added to Richard's unpopularity.  Thomas was buried in Westminster Abbey, first in the Chapel of Saint Edmund and Saint Thomas in October 1397, and two years later reburied in the Chapel of Saint Edward the Confessor. His wife was buried next to him.

Marriage and progeny.

Thomas married Eleanor de Bohun (c. 1366–1399), the elder daughter and co-heiress with her sister, Mary de Bohun, of their father Humphrey de Bohun, 7th Earl of Hereford (1341–1373). Thomas of Woodstock and his wife Eleanor had:  As he was attainted as a traitor, his dukedom of Gloucester was forfeit. The title Earl of Buckingham was inherited by his son, who died in 1399 only two years after Thomas' own death. Thomas of Woodstock's eldest daughter, Anne, married into the powerful Stafford family, who were Earls of Stafford. Her son, Humphrey Stafford was created Duke of Buckingham in 1444 and also inherited part of the de Bohun estates.  The other part of these estatesincluding the Earldom of Hereford, which had belonged to Mary de Bohun and had then become incorporated into the holdings of the House of Lancasterbecame a matter of contention in the latter 15th century.

Thomas of Woodstock, 1st Duke of Gloucester (7 January 13558 or 9 September 1397) was the fifth surviving son and youngest child of King Edward III of England and Philippa of Hainault.

格洛斯特公爵伍德斯托克的托马斯(英语:Thomas of Woodstock, 1st Duke of Gloucester,1355年1月7日—1397年9月8日或9日),英格兰国王理查二世(1377年—1399年在位)强有力的对手。爱德华三世的第七子,1385年封格洛斯特公爵。在理查二世年幼的时候,他野心勃勃,企图摄政。理查二世亲政以后对他实行了报复。1397年,他被捕后未及受审就暴死在狱中。他的格洛斯特公爵等爵位被剥夺,其子汉弗莱只继承了白金汉伯爵。


Medical uses.

Zolmitriptan is used for the acute treatment of migraines with or without aura in adults. Zolmitriptan is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine.  Zolmitriptan is available as a swallowable tablet, an oral disintegrating tablet, and a nasal spray, in doses of 2.5 and 5 mg. People who get migraines from aspartame should not use the disintegrating tablet (Zomig ZMT), which contains aspartame.  According to a study of healthy volunteers, food intake seems to have no significant effect on the effectiveness of Zolmitriptan in both men and women.

Contraindications and precautions.

Zolmitriptan should not be given to patients with ischemic heart disease (angina pectoris, history of myocardial infarction, or documented silent ischemia) or to patients who have symptoms or findings consistent with ischemic heart disease, coronary artery vasospasm, including Prinzmetal's angina, or other significant underlying cardiovascular disease.  Zolmitriptan may increase blood pressure, it should not be given to patients with uncontrolled hypertension, should not be used within 24 hours of treatment with another 5-HT1 agonist, or an ergotamine-containing or ergot-type medication like dihydroergotamine or methysergide, and should not be administered to patients with hemiplegic or basilar migraine.  Concurrent administration of MAOI or use of zolmitriptan within 2 weeks of discontinuation of MAO-A inhibitor therapy is contraindicated.

Adverse reactions.

The Zomig ZMT dissolvable pill contains aspartame, and should be avoided by anyone sensitive to that ingredient and by those suffering from phenylketonuria.  Rarely, serious cardiac events, including myocardial infarction (heart attack), have been associated with zolmitriptan.  Reported minor adverse reactions include: hypesthesia, paresthesia (all types), warm and cold sensations, chest pain, throat and jaw tightness, dry mouth, dyspepsia, dysphagia, nausea, somnolence, vertigo, asthenia, myalgia, myasthenia and sweating.  Following administration of cimetidine, the half-life and AUC of zolmitriptan and its active metabolites were approximately doubled (see CLINICAL PHARMACOLOGY in product pamphlet). Cimetidine is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach.

Chemistry.

Zolmitriptan is a synthetic tryptamine derivative and appears as a white powder that is partially soluble in water.

Economics.

Brand names.

Zolmitriptan is marketed by AstraZeneca with the brand names Zomig, Zomigon (Argentina, Canada & Greece), AscoTop (Germany) and Zomigoro (France).

Economics.

In 2008, Zomig generated nearly $154 million in sales.  AstraZeneca's U.S. patent on Zomig tablets expired on November 14, 2012, and its pediatric exclusivity extension expired on May 14, 2013. The patent in certain European countries has already expired too, and generic drug maker Actavis released a generic version in those countries, starting in March 2012.

Legal status.

In Russia versions of zolmitriptan, which are not registered in the National registry of medications, may be regarded as narcotic drugs (derivatives of dimethyltriptamine).

Zolmitriptan, sold under the brand name Zomig among others, is a triptan used in the acute treatment of migraine attacks with or without aura and cluster headaches. It is a selective serotonin receptor agonist of the 1B and 1D subtypes. It was patented in 1990 and approved for medical use in 1997.

佐米曲普坦 (英语:Zolmitriptan)是一种选择性5-HT1激动剂,通过激动颅内血管(包括动静脉吻合处)和三叉神经系统交感神经上的5-HT1B/1D受体,引起颅内血管收缩并抑制前炎症神经肽的释放,从而作为一种治疗偏头痛和丛集性头痛的曲坦类药物。


Location.

The district is bounded by the Chao Phraya River to the west, Khlong Phadung Krung Kasem in the north, and Ratchadamnoen Road and Khlong Ong Ang to the east. The center of Bangkok, marked by the city pillar shrine ("lak mueang"), is in the district. Also surrounding the large open space of the "Sanam Luang" are the Grand Palace and Wat Phra Kaew, the National Museum in the former palace of the Vice King, and the main campus of Thammasat University as well as Silpakorn University.  Other significant landmarks in the district include Wat Pho, the Giant Swing, Wat Suthat, Wat Ratchanadda (with Loha Prasat), and the Democracy Monument. Also the well-known Khaosan Road is in the district. Another significant temple is Wat Bowonniwet, where several Thai kings were ordained as monks.  Of the original 14 forts protecting Bangkok only two survive. Fort Phra Sumen in the northern corner of the district, and Fort Mahakan in the east. Since 2000 a small park named "Santichaiphrakarn" around Fort Phra Sumen was built. In 2005 the riverfront of the Phra Nakhon District, from King Rama I Bridge (Memorial Bridge) in the south to the Wasukri Pier (Dusit District), was submitted to the UNESCO for consideration as a future world heritage site.  Another landmark is Sala Chalermkrung Royal Theatre on Charoen Krung Road. It is Bangkok's oldest cinema and was the first air conditioned theater in Thailand. Built at the order of King Prajadhipok and named by him, it opened on 2 July 1933. It is the only theater from the first "golden age" of Thai cinema still standing. No longer regularly showing movies, the theater has been renovated and is principally used for Thai dance performances. Another point of interest is the Pak Khlong Talat flower market. Tha Phra Chan is a well-known Thai amulets market.  The area around Phahurat Road (พาหุรัด) can be considered Thailand's "Little India". The road was constructed during King Chulalongkorn's reign over a century ago and Indian community started to form after that. Siri Guru Singh Sabha, Thailand's first Sikh temple was built in 1933 near the road. The area is well known for Indian fabric shops and Indian cuisine.

History.

Phra Nakhon was once an amphoe (district) named Chana Songkhram (อําเภอชนะสงคราม). The administration was overhauled on 15 October 1915 when 25 new districts were created for inner Bangkok. On 12 March 1928, six of these districts: Phahurat, Samran Rat, Phra Ratchawang, Chana Songkhram, Sam Yot, and Bang Khun Phrom were merged to form Amphoe Phra Nakhon. It became Khet (district) Phra Nakhon in 1972.

Festivals.

Songkran, the traditional Thai New Year festival, is celebrated throughout the country from 13–15 April of each year. Khaosan Road (or Khao Sarn Road) in Phra Nakhon District is a notable place to celebrate the event where many people, both locals and tourists, splash water.  During another famous festival, Loy Krathong, on the 15th day of the 12th lunar month, the Chao Phraya River bank in the district, with numerous piers and Phra Sumen Fort, is a popular place to float lanterns on the water.  Ratchadamnoen Avenue is often heavily decorated with lights around the king's birthday (28 July), the queen mother's birthday (12 August), National Day (5 December) and other major anniversaries. Sanam Luang and recently created Lan Plabpla Maha Chedsada Bodin (ลานพลับพลามหาเจษฎาบดินทร์) in front of Wat Ratchanadda and its Loha Prasat are open spaces that frequently used to celebrate events.

Administration.

The district is divided into 12 sub-districts ("khwaeng").

Phra Nakhon (, ) is one of the 50 districts ("khet") of Bangkok, Thailand. It is the central district of Bangkok, including Rattanakosin Island. Neighboring districts are, from the north, clockwise: Dusit, Pom Prap Sattru Phai, Samphanthawong, and across the Chao Phraya River, Thon Buri, Bangkok Yai, Bangkok Noi, and Bang Phlat.

拍那空县(,)是泰国曼谷的98个区之一,位于市中心。毗邻的区依顺时针方向从北开始为;律实县、邦巴沙都拍县、三攀他旺县,以及昭披耶河对岸的吞武里县、曼谷艾县、曼谷莲县和挽拍县。


Signs and symptoms.

Lungs.

Symptoms or signs of mesothelioma may not appear until 20 to 50 years (or more) after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural

Abdomen.

The most common symptoms of peritoneal mesothelioma are abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other features may include weight loss, fever, night sweats, poor appetite, vomiting, constipation, and umbilical hernia. If

Heart.

Pericardial mesothelioma is not well characterized, but observed cases have included cardiac symptoms, specifically constrictive pericarditis, heart failure, pulmonary embolism, and cardiac

End stage.

In severe cases of the disease, the following signs and symptoms may

Causes.

Working with asbestos is the most common risk factor for mesothelioma. However, mesothelioma has been reported in some individuals without any known exposure to asbestos. Tentative evidence also raises concern about carbon-fibre nanotubes.

Asbestos.

The incidence of mesothelioma has been found to be higher in populations living near naturally occurring asbestos. People can be exposed to naturally occurring asbestos in areas where mining or road construction is occurring, or when the asbestos-containing rock is naturally weathered. Another common route of exposure is through asbestos-containing soil, which is used to whitewash, plaster, and roof houses in Greece. In central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villages—Tuzköy, Karain, and Sarıhıdır. Initially, this was attributed to erionite. Environmental exposure to asbestos has caused mesothelioma in places other than Turkey, including Corsica, Greece, Cyprus, China, and California. In the northern Greek mountain town of Metsovo, this exposure had resulted in mesothelioma incidence around 300 times more than expected in asbestos-free populations, and was associated with very frequent pleural calcification known as Metsovo lung.  The documented presence of asbestos fibers in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibers.  Exposure to talc is also a risk factor for mesothelioma; exposure can affect those who live near talc mines, work in talc mines, or work in talc mills.  In the United States, asbestos is considered the major cause of malignant mesothelioma and has been considered "indisputably" associated with the development of mesothelioma. Indeed, the relationship between asbestos and mesothelioma is so strong that many consider mesothelioma a “signal” or

Genetic disposition.

In a recent research carried on white American population in 2012, it was found

Erionite.

Erionite is a zeolite mineral with similar properties to asbestos and is known to cause mesothelioma. Detailed epidemiological investigation has shown that erionite causes mesothelioma mostly in families with a genetic predisposition. Erionite is found in

Other.

In rare cases, mesothelioma has also been associated with irradiation of the chest or abdomen, intrapleural thorium dioxide (thorotrast) as a contrast medium, and inhalation of

Pathophysiology.

Systemic.

The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibers in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fiber can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibers from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibers may be deposited in the gut after ingestion of sputum contaminated with asbestos fibers.  Pleural contamination with asbestos or other mineral fibers has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers). However, there is now evidence that smaller particles may be more dangerous than the larger fibers.

Intracellular.

Analysis of the interactions between asbestos fibers and DNA has shown that phagocytosed fibers are able to make contact with chromosomes, often adhering to the chromatin fibers or becoming entangled within the chromosome. This contact between the asbestos fiber and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.  Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:  Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead

Immune system.

Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic (chromosome-breaking) and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly

Diagnosis.

Diagnosis of mesothelioma can be suspected with imaging but is confirmed with biopsy. It must be clinically and histologically differentiated from other pleural and pulmonary malignancies, including reactive pleural disease, primary lung carcinoma, pleural metastases of other cancers, and other primary pleural cancers.  Primary pericardial mesothelioma is often diagnosed after it has metastasized to lymph nodes or the lungs.

Imaging.

Diagnosing mesothelioma is often difficult because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma. A CT (or CAT) scan or an MRI is usually

Biopsy.

Generally, a biopsy is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a

Immunochemistry.

Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics, such as breast or lung cancer that has metastasized to the pleura. There are numerous tests and panels available, but no

Subtypes.

There are three main histological subtypes of malignant mesothelioma: epithelioid, sarcomatous, and biphasic. Epithelioid and biphasic mesothelioma make up approximately 75-95% of mesotheliomas and have been well characterized histologically, whereas

Staging.

Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group. TNM classification

Prevention.

Mesothelioma can be prevented in most cases by preventing exposure to asbestos. The

Screening.

There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be

Treatment.

Mesothelioma is generally resistant to radiation and chemotherapy treatment. Long-term survival and cures are exceedingly rare. Treatment of malignant mesothelioma at earlier stages has a better prognosis. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease. The histological subtype and the patient's age and health status also help predict prognosis. The epithelioid histology responds better to treatment and has a survival advantage over sarcomatoid histology.  The effectiveness of radiotherapy compared to chemotherapy or surgery for malignant pleural mesothelioma is not known.

Surgery.

Surgery, by itself, has proved disappointing. In one large series, the median survival with surgery (including extrapleural pneumonectomy) was only 11.7 months. However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008), or with one of the latter. A pleurectomy/decortication

Radiation.

For patients with localized disease, and who can tolerate a radical surgery, radiation can be given post-operatively as a consolidative treatment. The entire hemithorax is treated with radiation therapy, often given simultaneously with chemotherapy. Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations. It can also induce severe side-effects, including fatal pneumonitis. As part of a curative approach to

Chemotherapy.

Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery. This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in the combination with pemetrexed and who also received supplementation with folate and vitamin B. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting,

Immunotherapy.

Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Guérin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro

Hyperthermic intrathoracic chemotherapy.

Hyperthermic intrathoracic chemotherapy is used in conjunction with surgery, including in patients with malignant pleural mesothelioma. The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to

Multimodality therapy.

Multimodal therapy, which includes a combined approach of surgery, radiation or photodynamic therapy, and chemotherapy, is not suggested for routine practice for treating malignant pleural mesothelioma. The effectiveness and safety of multimodal therapy is not clear (not enough research has been performed) and one clinical trial has suggested a possible increased risk of adverse effects.  Large series of examining multimodality treatment have only demonstrated modest improvement in survival (median survival 14.5 months and only 29.6% surviving 2 years). Reducing the bulk of the tumor

Prognosis.

Mesothelioma often has a poor prognosis. Typical survival despite surgery is between 12 and 21 months depending on the stage of disease at diagnosis with about 7.5% of people surviving for 5 years.  Women, young people, people with low-stage cancers, and people with epithelioid cancers have better prognoses. Negative prognostic

Epidemiology.

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate varies from one country to another, from a low rate of less than 1 per 1,000,000 in Tunisia and Morocco, to the highest rate in Britain, Australia and Belgium: 30 per 1,000,000 per year. For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades. Worldwide incidence is estimated at 1-6 per 1,000,000. Incidence of mesothelioma lags behind that of asbestosis due to the longer time it takes to develop; due to the cessation of asbestos use in developed countries, mesothelioma incidence is expected to decrease. Incidence is expected to continue increasing in developing countries due to continuing use of asbestos. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal. Less than 5% of mesotheliomas are pericardial. The prevalence of pericardial mesothelioma is less than 0.002%; it is more common in men than women. It typically occurs in a person's 50s-70s.  Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States. Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women. More than 80% of mesotheliomas are caused by asbestos exposure.  The incidence of peritoneal mesothelioma is 0.5–3.0 per million per year in men, and 0.2–2.0 per million per year in women.

UK.

Mesothelioma accounts for less than 1% of all cancers diagnosed in the UK, (around 2,600 people

History.

The connection between asbestos exposure and mesothelioma was discovered in the 1970s. In the United States, asbestos manufacture stopped

Society and culture.

Notable cases.

Mesothelioma, though rare, has had a number of notable patients:  Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould, a

Legal issues.

Some people who were exposed to asbestos have collected damages for an asbestos-related disease, including mesothelioma. Compensation via asbestos funds or class action lawsuits is an important issue in law practices regarding mesothelioma.  The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of

History.

The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. In 1960, an article published by Wagner et al. was seminal in establishing mesothelioma as a disease arising from exposure to asbestos. The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. Before the use of advanced microscopy techniques, malignant mesothelioma was often diagnosed as a variant form of lung cancer. In 1962, McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker. The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.  In the town of Wittenoom, asbestos-containing mine waste was used to

Research.

The WT-1 protein is overexpressed in mesothelioma and is being researched as a potential target for drugs.  There are two high-confidence miRNAs that can potentially serve as biomarkers of asbestos exposure and malignant mesothelioma. Validation studies are needed to assess their relevance.

Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium). The most common area affected is the lining of the lungs and chest wall. Less commonly the lining of the abdomen and rarely the sac surrounding the heart, or the sac surrounding the testis may be affected. Signs and symptoms of mesothelioma may include shortness of breath due to fluid around the lung, a swollen abdomen, chest wall pain, cough, feeling tired, and weight loss. These symptoms typically come on slowly. More than 80% of mesothelioma cases are caused by exposure to asbestos. The greater the exposure the greater the risk. As of 2013, about 125 million people worldwide have been exposed to asbestos at work. High rates of disease occur in people who mine asbestos, produce products from asbestos, work with asbestos products, live with asbestos workers, or work in buildings containing asbestos. Asbestos exposure and the onset of cancer are generally separated by about 40 years. Washing the clothing of someone who worked with asbestos also increases the risk. Other risk factors include genetics and infection with the simian virus 40. The diagnosis may be suspected based on chest X-ray and CT scan findings, and is confirmed by either examining fluid produced by the cancer or by a tissue biopsy of the cancer. Prevention centers around reducing exposure to asbestos. Treatment often includes surgery, radiation therapy, and chemotherapy. A procedure known as pleurodesis, which involves using substances such as talc to scar together the pleura, may be used to prevent more fluid from building up around the lungs. Chemotherapy often includes the medications cisplatin and pemetrexed. The percentage of people that survive five years following diagnosis is on average 8% in the United States. In 2015, about 60,800 people had mesothelioma, and 32,000 died from the disease. Rates of mesothelioma vary in different areas of the world. Rates are higher in Australia, the United Kingdom, and lower in Japan. It occurs in about 3,000 people per year in the United States. It occurs more often in males than females. Rates of disease have increased since the 1950s. Diagnosis typically occurs after the age of 65 and most deaths occur around 70 years old. The disease was rare before the commercial use of asbestos.

间皮瘤(Mesothelioma)是一种源自于覆盖内脏表面的薄层组织(间皮细胞)的癌症。最常患病的部位是胸膜。腹膜也有,但较少见。在罕见的情下会出现在心包膜或睪丸鞘膜。间皮瘤的症状有因肋膜积液造成的呼吸困难、腹部肿胀、胸壁疼痛、咳嗽、疲倦,以及体重减轻。这些症状出现的速度一般而言较为缓慢。 超过80%的间皮瘤是由暴露在含石棉的环境中所导致的。暴露程度越高,风险越大。截至2013年,约有1.25亿人曾在工作环境中接触石棉。患病比例较高的族群有:石棉矿的矿工、将石棉加工制做成产品的人、工作时会接触石棉制品的人、和以上这些人同住的人,以及在含有石棉的建筑物中工作的人。从暴露石棉到癌症出现大约相隔40年。清洗石棉工作者的衣物也会增加清洗者的罹病风险。其他风险因子包含遗传以及被SV40病毒感染。间皮瘤可以用胸部X光及X射线计算机断层成像进行初步诊断,再用细胞生物学或是活体组织切片来确诊。 预防的重点为减少石棉暴露。间皮瘤的治疗通常包括手术、放射线疗法,及化学疗法。有一种称为肋膜黏连术的术式,是用滑石之类的物质使胸膜产生疤痕并沾黏在一起,可用来防止肺部积水增加。化疗一般会用顺铂及培美曲塞。在美国,患者的五年存活率平均而言为8%。 在2015年,约有60800人罹患间皮瘤,其中32000人因此死亡。世界各地的间皮瘤发生率依地区而不同,在澳洲及英国的发生率较高,在日本则较低。在美国,每年约有3000个人得到此病,男性得到此病的比率比女性高。自1950年起,此病的发生率便呈现上升的趋势。被诊断出此病时病患大多年过65,且大多在七十岁左右死亡。在石棉的商业化应用问世以前,这个疾病非常罕见。


History.

The Kirkendall effect was discovered by Ernest Kirkendall and Alice Smigelskas in 1947, in the course of Kirkendall's ongoing research into diffusion in brass. The paper in which he discovered the famous effect was the third in his series of papers on brass diffusion, the first being his thesis. His second paper revealed that zinc diffused more quickly than copper in alpha-brass, which led to the research producing his revolutionary theory. Until this point, substitutional and ring methods were the dominant ideas for diffusional motion. Kirkendall's experiment produced evidence of a vacancy diffusion mechanism, which is the accepted mechanism to this day. At the time it was submitted, the paper and Kirkendall's ideas were rejected from publication by Robert Franklin Mehl, director of the Metals Research Laboratory at Carnegie Institute of Technology. Mehl refused to accept Kirkendall's evidence of this new diffusion mechanism, and denied publication for over six months, only relenting after a conference was held and several other researchers confirmed Kirkendall's results.

Kirkendall's experiment.

A bar of brass (70% Cu, 30% Zn) was used as a core, with molybdenum wires stretched along its length, and then coated in a layer of pure copper. Molybdenum was chosen as the marker material due to it being very insoluble in brass, eliminating any error due to the markers diffusing themselves. Diffusion was allowed to take place at 785 °C over the course of 56 days, with cross-sections being taken at six times throughout the span of the experiment. Over time, it was observed that the wire markers moved closer together as the zinc diffused out of the brass and into the copper. A difference in location of the interface was visible in cross sections of different times. Compositional change of the material from diffusion was confirmed by x-ray diffraction.

Diffusion mechanism.

Early diffusion models postulated that atomic motion in substitutional alloys occurs via a direct exchange mechanism, in which atoms migrate by switching positions with atoms on adjacent lattice sites. Such a mechanism implies that the atomic fluxes of two different materials across an interface must be equal, as each atom moving across the interface causes another atom to move across in the other direction.  Another possible diffusion mechanism involves lattice vacancies. An atom can move into a vacant lattice site, effectively causing the atom and the vacancy to switch places. If large-scale diffusion takes place in a material, there will be a flux of atoms in one direction and a flux of vacancies in the other.  The Kirkendall effect arises when two distinct materials are placed next to each other and diffusion is allowed to take place between them. In general, the diffusion coefficients of the two materials in each other are not the same. This is only possible if diffusion occurs by a vacancy mechanism; if the atoms instead diffused by an exchange mechanism, they would cross the interface in pairs, so the diffusion rates would be identical, contrary to observation. By Fick's 1st law of diffusion, the flux of atoms from the material with the higher diffusion coefficient will be larger, so there will be a net flux of atoms from the material with the higher diffusion coefficient into the material with the lower diffusion coefficient. To balance this flux of atoms, there will be a flux of vacancies in the opposite direction—from the material with the lower diffusion coefficient into the material with the higher diffusion coefficient—resulting in an overall translation of the lattice relative to the environment in the direction of the material with the lower diffusion constant.  Macroscopic evidence for the Kirkendall effect can be gathered by placing inert markers at the initial interface between the two materials, such as molybdenum markers at an interface between copper and brass. The diffusion coefficient of zinc is higher than the diffusion coefficient of copper in this case. Since zinc atoms leave the brass at a higher rate than copper atoms enter, the size of the brass region decreases as diffusion progresses. Relative to the molybdenum markers, the copper-brass interface moves toward the brass at an experimentally measurable rate.

Darken's equations.

Shortly after the publication of Kirkendall's paper, L.S. Darken published an analysis of diffusion in binary systems much like the one studied by Smigelskas and Kirkendall. By separating the actual diffusive flux of the materials from the movement of the interface relative to the markers, Darken found the marker velocity formula_1 to be formula_2 where formula_3 and formula_4 are the diffusion coefficients of the two materials and formula_5 is an atomic fraction. One consequence of this equation is that the movement of an interface varies linearly with the square root of time, which is exactly the experimental relationship discovered by Smigelskas and Kirkendall.  Darken also developed a second equation that defines a combined chemical diffusion coefficient formula_6 in terms of the diffusion coefficients of the two interfacing materials: formula_7 This chemical diffusion coefficient can be used to mathematically analyze Kirkendall effect diffusion via the Boltzmann-Matano method.

Kirkendall porosity.

One important consideration deriving from Kirkendall's work is the presence of pores formed during diffusion. These voids act as sinks for vacancies, and when enough accumulate they can become substantial and expand in an attempt to restore equilibrium. Porosity occurs due to the difference in diffusion rate of the two species.  Pores in metals have ramifications for mechanical, thermal, and electrical properties, and thus control over their formation is often desired. The equation formula_8 where formula_9 is the distance moved by a marker, formula_10 is a coefficient determined by intrinsic diffusivities of the materials, and formula_11 is a concentration difference between components, has proven to be an effective model for mitigating Kirkendall porosity. Controlling annealing temperature is another method of reducing or eliminating porosity. Kirkendall porosity typically occurs at a set temperature in a system, so annealing can be performed at lower temperatures for longer times to avoid formation of pores.

Nanotechnology applications.

The Catalan Institute of Nanotechnology in Bellaterra, Spain has developed a chemical process creating hollows in nano-particles and forming double-walled boxes and multi-chambered tubes. The results of the study have appeared in the journal Science.  Minute silver cubes were treated with cationic gold which at room temperatures led to a loss of electrons from the silver atoms which were taken up by an electrolytic solution. The gaining of electrons transformed the cationic gold into metallic gold which then attached to the surface of the silver cube. This covering protects the underlying silver, confining the reaction to the uncoated parts. Finally, there remains only a single hole on the surface through which the reaction enters the cube. A secondary effect then takes place when silver atoms from inside the cube begin to migrate through the hole to the gold on the surface, creating a void inside the cube.  The process will have a wide range of applications. Small changes in the chemical environment will allow control of reaction and diffusion at room temperatures, permitting manufacture of diverse polymetallic hollow nanoparticles through galvanic replacement and the Kirkendall effect.  In 1972, C.W. Horsting of the RCA Corporation published a paper which reported test results on the reliability of semiconductor devices in which the connections were made using aluminium wires bonded ultrasonically to gold plated posts. His paper demonstrated the importance of the Kirkendall effect in wire bonding technology, but also showed the significant contribution of any impurities present to the rate at which precipitation occurred at the wire bonds. Two of the important contaminants that have this effect, known as Horsting effect (Horsting voids) are fluorine and chlorine. Both Kirkendall voids and Horsting voids are known causes of wire bond fractures, though historically this cause is often confused with the purple colored appearance of one of the five different gold-aluminium intermetallics, commonly referred to as "purple plague" and less often "white plague".

The Kirkendall effect is the motion of the interface between two metals that occurs as a consequence of the difference in diffusion rates of the metal atoms. The effect can be observed for example by placing insoluble markers at the interface between a pure metal and an alloy containing that metal, and heating to a temperature where atomic diffusion is possible; the boundary will move relative to the markers. This process was named after Ernest Kirkendall (1914–2005), assistant professor of chemical engineering at Wayne State University from 1941 to 1946. The paper describing the discovery of the effect was published in 1947.

科肯德尔效应(英语:Kirkendall effect):二种原子扩散速率不同金属的接口,经扩散后发生移动的现象,称为「科肯德尔效应」。这是欧内斯特·科肯德尔于1947年在韦恩州立大学任化学工程系助理教授时用黄铜(70%铜和30%锌)和铜,接触面用钼丝做记号,在785度摄氏扩散56天后的实验结果发现的。


Etymology.

Italian "solfeggio" and English/French "solfège" derive from the names of two of the syllables used: "sol" and "fa".  The generic term "solmization", referring to any system of denoting pitches of a musical scale by syllables, including those used in India and Japan as well as solfège, comes from French "solmisation", from the Latin solfège syllables "sol" and "mi".  The verb "to sol-fa" means to sing a passage in solfège.

Origin.

In eleventh-century Italy, the music theorist Guido of Arezzo invented a notational system that named the six notes of the hexachord after the first syllable of each line of the Latin hymn "Ut queant laxis", the "Hymn to St. John the Baptist", yielding "ut, re, mi, fa, sol, la". Each successive line of this hymn begins on the next scale degree, so each note's name was the syllable sung at that pitch in this hymn.  <poem> Ut queant laxīs resonāre fībrīs Mīra gestōrum famulī tuōrum, Solve pollūtī labiī reātum, Sancte Iōhannēs. </poem> The words were written by Paulus Diaconus in the 8th century. They translate as: <poem> So that your servants may, with loosened voices, Resound the wonders of your deeds, Clean the guilt from our stained lips, O St. John. </poem> "Ut" was changed in the 1600s in Italy to the open syllable Do, at the suggestion of the musicologue Giovanni Battista Doni (based on the first syllable of his surname), and Si (from the initials for "Sancte Iohannes") was added to complete the diatonic scale. In Anglophone countries, "si" was changed to "ti" by Sarah Glover in the nineteenth century so that every syllable might begin with a different letter. "Ti" is used in tonic sol-fa (and in the famed American show tune "Do-Re-Mi").  An alternative theory argues that the solfège syllables ("do, re, mi, fa, sol, la, ti") derive from the syllables of an Arabic solmization system درر مفصّلات "Durar Mufaṣṣalāt" ("Detailed Pearls") ("dāl, rā', mīm, fā', ṣād, lām, tā"'), mentioned in the works of Francisci a Mesgnien Meninski in 1680 and later discussed by Jean-Benjamin de La Borde in 1780. However, there is no documentary evidence for this theory.

In Elizabethan England.

In the Elizabethan era, England and its related territories used only four of the syllables: mi, fa, sol, and la. "Mi" stood for modern si, "fa" for modern do or ut, "sol" for modern re, and "la" for modern mi. Then, fa, sol and la would be repeated to also stand for their modern counterparts, resulting in the scale being "fa, sol, la, fa, sol, la, mi, fa". The use of "fa", "sol" and "la" for two positions in the scale is a leftover from the Guidonian system of so-called "mutations" (i.e. changes of hexachord on a note, see Guidonian hand). This system was largely eliminated by the 19th century, but is still used in some shape note systems, which give each of the four syllables "fa", "sol", "la", and "mi" a different shape.  An example of this type of solmization occurs in Shakespeare's "King Lear", I, 2 (see ).

Modern use.

Solfège is still used for sight reading training. In the U.S., traditional American country music was first recorded in the 1920s by solfège-trained singers, often too poor to afford a piano, who used sight reading as a way of making printed music into entertainment. Flanders Bays and "Singing Bob" Leonard were traveling music teachers who trained hundreds of students, among them The Carter Family, who recorded the first nationally distributed recordings of regional "country" music.  There are two main types of solfège: "Movable do" and "Fixed do".

Movable do solfège.

In "Movable do", or "tonic sol-fa", each syllable corresponds to a scale degree. This is analogous to the Guidonian practice of giving each degree of the hexachord a solfège name, and is mostly used in Germanic countries, Commonwealth Countries, and the United States.  One particularly important variant of movable do, but differing in some respects from the system described below, was invented in the nineteenth century by Sarah Ann Glover, and is known as tonic sol-fa.  In Italy, in 1972, Roberto Goitre wrote the famous method "Cantar leggendo", which has come to be used for choruses and for music for young children.  The pedagogical advantage of the movable-Do system is its ability to assist in the theoretical understanding of music; because a tonic is established and then sung in comparison to, the student infers melodic and chordal implications through his or her singing. Thus, while fixed-do is more applicable to instrumentalists, movable-do is more applicable to theorists and, arguably, composers.

Major.

Movable do is frequently employed in Australia, China, Japan (with 5th being so, and 7th being si), Ireland, the United Kingdom, the United States, Hong Kong, and English-speaking Canada. The movable do system is a fundamental element of the Kodály method used primarily in Hungary, but with a dedicated following worldwide. In the movable do system, each solfège syllable corresponds not to a pitch, but to a scale degree: The first degree of a major scale is always sung as "do", the second as "re", etc. (For minor keys, see below.) In movable do, a given tune is therefore always sol-faed on the same syllables, no matter what key it is in.  The solfège syllables used for movable do differ slightly from those used for fixed do, because the English variant of the basic syllables ("ti" instead of "si") is usually used, and chromatically altered syllables are usually included as well.  If, at a certain point, the key of a piece modulates, then it is necessary to change the solfège syllables at that point. For example, if a piece begins in C major, then C is initially sung on "do", D on "re", etc. If, however, the piece then modulates to G major, then G is sung on "do", A on "re", etc., and C is then sung on "fa".

Minor.

Passages in a minor key may be sol-faed in one of two ways in movable do: either starting on do (using "me", "le", and "te" for the lowered third, sixth, and seventh degrees, and "la" and "ti" for the raised sixth and seventh degrees), which is referred to as "do-based minor", or starting on la (using "fi" and "si" for the raised sixth and seventh degrees). The latter (referred to as "la-based minor") is sometimes preferred in choral singing, especially with children.  The choice of which system is used for minor makes a difference as to how you handle modulations. In the first case ("do-based minor"), when the key moves for example from C major to C minor the syllable do keeps pointing to the same note, namely C, (there's no "mutation" of do's note), but when the key shifts from C major to A minor (or A major), the scale is transposed from do = C to do = A. In the second case ("la-based minor"), when the key moves from C major to A minor the syllable do continues to point to the same note, again C, but when the key moves from C major to C minor the scale is transposed from do = C to do = E-flat.

Fixed do solfège.

In "Fixed do", each syllable corresponds to the name of a note. This is analogous to the Romance system naming pitches after the solfège syllables, and is used in Romance and Slavic countries, among others, including Spanish-speaking countries.  In the major Romance and Slavic languages, the syllables Do, Re, Mi, Fa, Sol, La, and Si are used to name notes the same way that the letters C, D, E, F, G, A, and B are used to name notes in English. For native speakers of these languages, solfège is simply "singing the names of the notes", omitting any modifiers such as "sharp" or "flat" in order to preserve the rhythm. This system is called fixed do and is used in Spain, Portugal, France, Italy, Belgium, Romania, Latin American countries and in French-speaking Canada as well as countries such as Bosnia and Herzegovina, Croatia, Russia, Serbia, Ukraine, Georgia, Bulgaria, Greece, Armenia, Albania, North Macedonia, Mongolia, Iran, Israel, the Arab world, Turkey, and Taiwan where non-Romance languages are spoken. In the United States, the fixed-do system is principally taught at The Juilliard School in New York City, the Curtis Institute of Music in Philadelphia, and the Cleveland Institute of Music in Cleveland, Ohio.  In the fixed do system, shown above, accidentals do not affect the syllables used. For example, C, C, and C (as well as and, not shown above) are all sung with the syllable "do".

Chromatic variants.

Several chromatic fixed-do Systems that have also been devised to account for chromatic notes (and even for double-sharp and double-flat variants) are as follows:

Comparison of the two systems.

Movable Do corresponds to our psychological experience of normal tunes. If the song is sung a tone higher it is still perceived to be the same song, and the notes have the same relationship to each other, but in a fixed Do all the note names would be different. A movable Do emphasizes the musicality of the tune as the psychological perception of the notes is always relative to a key for the vast majority of people that do not have absolute pitch.  Sotorrio argues that fixed-do is preferable for serious musicians, as music involving complex modulations and vague tonality is often too ambiguous with regard to key for any movable system. That is, without a prior analysis of the music, any movable-do system would inevitably need to be used like a fixed-do system anyway, thus causing confusion. With fixed-do, the musician learns to regard any syllable as the tonic, which does not force them to make an analysis as to which note is the tonic when ambiguity occurs. Instead, with fixed-do the musician will already be practiced in thinking in multiple/undetermined tonalities using the corresponding syllables.  In comparison to the movable do system, which draws on short-term relative pitch skills involving comparison to a pitch identified as the tonic of the particular piece being performed, fixed do develops long-term relative pitch skills involving comparison to a pitch defined independently of its role in the piece, a practice closer to the definition of each note in absolute terms as found in absolute pitch. The question of which system to use is a controversial subject among music educators in schools in the United States. While movable do is easier to teach and learn, some feel that fixed do leads to stronger sight-reading and better ear training because students learn the relationships between specific pitches as defined independently, rather than only the function of intervals within melodic lines, chords, and chord progressions.  If a performer has been trained using fixed do, particularly in those rare cases in which the performer has absolute pitch or well-developed long-term relative pitch, the performer may have difficulty playing music scored for transposing instruments: Because the "concert pitch" note to be performed differs from the note written in the sheet music, the performer may experience cognitive dissonance when having to read one note and play another. Especially in the early stages of learning a piece, when the performer has yet to gain familiarity with the melodic line of the piece as expressed in relative terms, it may be necessary to mentally re-transpose the sheet music in order to restore the notes to concert pitch.  Those trained in fixed-do will argue that their act is the analogue of reading aloud in a language. Just as one reads this very sentence without parsing it grammatically, so too fixed-do is the direct sounding of the music. Where the movable-do system requires constant real-time analysis of the tonality and modulations in the score, in fixed-do the musician uses knowledge of the changing tonality to understand for example that the pitch class c-natural is the supertonic in B-Flat major or minor, and the dominant when the music modulates to F-major, but the c-note remains the same pitch.  Instrumentalists who begin sight-singing for the first time in college as music majors find movable do to be the system more consistent with the way they learned to read music.  For choirs, sight-singing fixed do using chromatic movable do syllables (see below) is more suitable than sight-singing movable do for reading atonal music, polytonal music, pandiatonic music, music that modulates or changes key often, or music in which the composer simply did not bother to write a key signature. It is not uncommon for this to be the case in modern or contemporary choral works.

Note names.

In the countries with fixed-do, these seven syllables (with Si replacing Ti) – rather than the letters C, D, E, F, G, A, and B – are used to name the notes of the C-Major scale. Here it would be said, for example, that Beethoven's Ninth Symphony (in D minor) is in "Re minor", and that its third movement (in B-flat major) is in "Si-bemol major".  In Germanic countries, on the other hand, it is the letters that are used for this purpose (so that Beethoven's Ninth Symphony is said to be in "d-Moll") and the solfège syllables are encountered only in their use in sight-singing and ear training.

Other possibilities to denote solfège.

Rainbow colors assigned by Isaac Newton.

Isaac Newton had associated the seven solfège syllables with the seven colors of the rainbow and surmised that each color vibrated accordingly (a concept possibly related to the modern view of chromesthesia). Thus, red has the least amount of vibration while violet vibrates the most.

In music, solfège (, ; ) or solfeggio (; ), also called sol-fa, solfa, solfeo, among many names, is a music education method used to teach aural skills, pitch and sight-reading of Western music. Solfège is a form of solmization, and though the two terms are sometimes used interchangeably, this system originated from other "Eastern" music cultures such as "swara", "durar mufaṣṣalāt" and "Jianpu".

唱名(solfège,;solfeggio,)是用来教授音高和视唱的音乐教育方法。有助于演唱者区分音程,并加强对乐理的理解。它是一种阶名唱法,而这两个表达方式实际上常被混用。


Early life.

Natalia, or Natasha to her friends, was the youngest of three daughters of a Moscow lawyer, Sergei Alexandrovich Sheremetevsky. She was born at a rented summer "dacha" at Perovo, on the outskirts of Moscow. Sheremetevsky employed 11 other lawyers, and was a member of the minor nobility, but had no title and was essentially a professional middle-class man. He was a sometime deputy in the Moscow City Duma, and a trustee of the Arbat City School. In the first year of her life, Natalia and her family lived in a rented apartment near the Moscow Kremlin on Ilinka. Their landlord, wealthy industrialist Aleksey Khludov, was also Natalia's godfather. From 1881 to 1893, the family lived at 7 Serebriany Lane, a single-storied wooden house owned by Sheremetevsky. From 1893, the family lived in a succession of rented apartments until Natalia left home on her marriage. She was educated at a private school, and by a French governess employed by her father.

First marriage.

In 1902, she married Sergei Mamontov (1 October 1877, Moscow – 30 December 1939, Tallinn), a nephew of Savva Mamontov. Sergei was a rehearsal accompanist for Savva Mamontov's Opera Company, which was renamed Association of Russian Opera after Savva's bankruptcy in 1899, and later at the Bolshoi Theatre. Through her first husband's connections, Natalia became friendly with noted musicians such as Sergei Rachmaninoff and Feodor Chaliapin. The couple moved into 13 Mansurovsky Lane, a new apartment building near the fashionable Prechistenka street, and had a daughter, Natalia or "Tata" to the family, on 2 June 1903. Sergei had a stammer and was of a retiring disposition, but Natalia was keen to socialise. Finding him socially dull, she began to go out unaccompanied by her husband. Russian divorce law followed the teachings of the Orthodox Church, and in practice divorce was only possible in cases of adultery where the husband was the guilty party. In 1905, Sergei agreed to a divorce and to act in the proceedings as if he was the unfaithful partner. Now free from her first husband, Natalia married her lover, cavalry officer Vladimir Vladimirovich Wulfert ().

Second marriage.

Natalia and Wulfert had known each other as children, but only fell in love after re-meeting in Moscow when Wulfert was on leave. He was an army officer serving in The Dowager Empress's Life Guard Cuirassier Regiment, known as the Blue Cuirassiers from the colour of their uniforms, stationed at Gatchina near Saint Petersburg. Natalia and Wulfert set up home at 7 Baggout Street, Gatchina.  In early December 1907, Natalia was introduced to one of her husband's fellow officers in the Blue Cuirassiers: Grand Duke Michael Alexandrovich of Russia, the brother of Tsar Nicholas II. The following month, they met again at the Regimental Winter Ball. From then on, they began to see each other regularly, though Michael was always careful to include Wulfert in his letters and invitations, at least until October 1908, and use the formal form of "you" ("vy") rather than the familiar one ("ty"). Rumours of their affair spread through the regiment, and Wulfert grew resentful. Michael began sending her secret letters to a separate postal address, now writing to her in familiar terms, and Wulfert grew physically violent, as Natalia refused to share his bed. In July 1909, privately in a letter, she accused her husband of rape. She packed luggage, and with their daughter, an elderly female cousin, and two maids, she left Wulfert for a break abroad in Switzerland. Both Michael and Wulfert turned up at the train station to see her off, and Wulfert created a scene by loudly accusing her of ruining him.  Through Baron Frederiks, the court minister, Michael tried to buy off Wulfert by offering him a post in Moscow as aide-de-camp to Prince Odoevsky-Maslov at the Kremlin. Wulfert threatened to commit suicide if Natalia did not return to him, and then challenged Michael to a duel. Nicholas II intervened, and transferred Michael from the Blue Cuirassiers to the Chernigov Hussars at Orel, from Saint Petersburg. In August 1909, Michael went to Denmark with his mother, and arranged for Natalia to meet him there. They were reunited in a hotel in Copenhagen, unbeknownst to his mother, and consummated their relationship for the first time.

Royal mistress.

Wulfert accepted the Kremlin post, at an enlarged salary, and as Natalia's residence permit was tied to her husband's she also returned to Moscow to live temporarily at a hotel opposite the Kremlin. By November, she was living in an 8-room apartment at 36 Petersburg Road, paid for by Michael, where he visited her about 3 times a month from Orel. Wulfert was still demanding that Natalia return to him, as well as threatening to shoot her. Against the wishes of Michael and Natalia, Nicholas II insisted that she remain in Moscow, and refused to vary the conditions of her residence permit.  By December 1909, Natalia was pregnant. Fearful that her husband would try to claim the child and take it away from her, her desire for a divorce grew stronger. Eventually, after prolonged negotiations and a hefty pay-off, Wulfert agreed to a divorce on the pretence that he had been unfaithful. Natalia's divorce petition was submitted to the Moscow Ecclesiastical Consistory Court on 19 February 1910, but by July 1910 it had not been granted. When she gave birth to a son on 24 July 1910, the child was legally Wulfert's. The boy was named George in honour of Michael's late brother. It was said that Wulfert was bought off with a bribe of 200,000 roubles, and the date of their divorce was back-dated, so that George was recognised as Natalia's illegitimate son, though inheriting her noble status, rather than the legitimate child of Wulfert's.  In May 1911, Nicholas II granted Natalia the surname "Brasova" and the right to live at Michael's estate at Brasovo, from his posting at Orel. Michael, Natalia and her two children moved there immediately. By the end of the year, Michael was posted to a command in Saint Petersburg, and they moved to the capital. He officially lived in regimental quarters while paying for a 28-room apartment at 16 Liteyny Prospekt for her. She felt trapped in the apartment, feared that her letters were opened, and was ostracised by society. After a few months, Michael moved her to a villa at 24 Nikolaevskaya, Gatchina, nearer to his base at the Gatchina Palace.

Third marriage.

Just as they had done for the previous two years, in summer 1912, Michael and Natalia holidayed in Western Europe. After shaking off agents of Nicholas II's secret police, the Okhrana, Michael and Natalia married in Vienna on 16 October 1912 in a Serbian Orthodox Church. They had successfully planned the wedding without either Nicholas II's or the Okhrana's knowledge. On their eventual arrival in Cannes, after a few days travelling through Venice and Milan, Natalia's two children joined them from Russia. The Grand Duke wrote to his brother, the Tsar, to inform him of the marriage, but because Natalia was divorced and not of royal blood the Tsar refused to approve it. Michael was perceived by the court as being "under the hypnotic influence of a malicious vamp". Nicholas II said Natalia was "such a cunning, wicked beast that it's disgusting even to talk about her". Michael was removed from the imperial succession, and exiled from Russia in disgrace. Though members of society felt some sympathy for Michael, thinking his punishment severe, there was little sympathy for Natalia. Despite marrying a Grand Duke, she was not entitled to be known as "Grand Duchess", and instead used the style "Madame or Countess Brasova".  Until September 1913, they stayed in hotels throughout Europe, without any decrease in their standard of living. They met Michael's sister Grand Duchess Xenia and cousin Grand Duke Andrew, and in July 1913, they saw Michael's mother in London who told Natalia "a few home truths" according to Xenia's diary. From September 1913, they leased an English country house, Knebworth, north of London. Natalia acted as hostess for any of their guests, which included her friend Chaliapin, the Ballets Russes, and the artist Serge Sudeikin. As a divorcée, however, Natalia was often excluded from invitations to social events elsewhere; the divorced were not received at court and could not enter the Royal Enclosure at Ascot.

War.

Upon the outbreak of World War I, Michael requested Nicholas II's permission to return home and to the army, with the understanding his wife and children could accompany him. Nicholas agreed and the family returned to the house on Nikolaevskaya street; Natalia was still not permitted to live in any of the imperial palaces. Michael was appointed to the rank of major-general, and given command of the "Savage Division" (Дикая Дивизия) formed from Chechens and Daghestani. The post was perceived as a relatively low position in the Army, and was believed to be Nicholas II's punishment for Michael's marriage.  As was expected of women in the imperial family, Natalia founded two hospitals, one at Gatchina and one at Saint Petersburg, in properties owned by Michael. In January 1915, her sister Olga died in Moscow, and she went there for the funeral. At her hotel in Moscow, she was visited by Michael's cousin, Grand Duke Dmitri Pavlovich of Russia, who professed himself in love with her. Dmitri had a reputation as a rake, and Natalia, though flattered, turned him down and told her husband of the encounter. Just eight weeks later, her eldest sister Vera also died.  In March 1915, Nicholas II agreed to legitimise George, and grant him the style of Count Brasov, although George still held no claim to the throne. Natalia's social circle expanded as more people began to accept her. As the war began to go badly for the Russians, Natalia was dismayed by the change in Michael's appearance as he abandoned his smart uniforms and decorations and wore a plain uniform with his muddy boots. Michael was "deeply upset" by Natalia's criticisms of his decision to be in the frontline of the war. He wrote to her, "the present time is so hard for Russia that my conscience could not allow me "not" to join the frontline service – and I am convinced that having done that, I also brought you some good in terms of public opinion, which, unfortunately, we can't totally ignore."  Natalia's social circle widened to include deputies in the Duma, and she was perceived as a liberal who supported a constitutional monarchy rather than the Tsar's autocracy. The Tsarina, Alexandra, even feared that Natalia was conspiring to make Michael Emperor. The Tsarina and Dowager Empress still would not accept Natalia. A portrait of her in a Kiev hospital she had funded with her own money was hidden by hospital staff for a visit by the Dowager Empress, and Alexandra had an exhibition of photographs of Michael and Natalia cleared by the imperial police. Natalia was depressed by the snubs, and by her separation from Michael, who was still at the front. In September 1916, they reunited at Mogilev, and spent time at Brasovo and Gatchina for the next six weeks, until Michael fell ill with stomach ulcers. They moved to the Crimea for Michael's recuperation. Christmas 1916 was spent at Brasovo as a family, where Natalia's daughter was "thrilled to the core" to hear that Dimitri had helped murder Rasputin, Tsarina Alexandra's self-styled spiritual mentor.

Revolution.

After the February Revolution in 1917, Nicholas abdicated in Michael's favour, but Michael refused to accept the throne until ratified by the will of the people. By naming Michael as his successor, Nicholas effectively reversed the long-standing law that morganatically married dynasts forfeited rights of succession, but his actions were ultimately irrelevant. Power lay with the revolutionaries, not with the Tsar, whether it was Nicholas or Michael. Michael and his family were placed under house arrest in Gatchina.  In September 1917, the house arrest was lifted. At the end of the following month the Prime Minister, Alexander Kerensky, was deposed in the October Revolution and the Bolsheviks seized power. With a permit to travel issued by Peter Polotsov, a former army colleague of Michael's who held a command in Saint Petersburg, the family planned to move to the greater safety of Finland. Valuables were packed and the children were moved to an estate south of Gatchina owned by Vladimir Dmitrievich Nabokov, the brother of one of Natalia's closest friends (Nadine Vonlyarlarskaya) and the father of the famous writer, Vladimir Vladimirovich Nabokov. The Bolsheviks discovered their plan, however, and their escape was blocked. The children returned to Gatchina, and they were once again under house arrest. Natalia managed to gain access to her safety deposit box, by claiming that she needed to examine some papers at the bank, and thus retrieved as much of her jewellery as she could conceal without arousing suspicion. The house arrest was lifted in November, but on 7 March 1918 Michael and Nicholas Johnson—who had been his secretary since December 1912—were re-arrested on the orders of Moisei Uritsky, the Head of the Petrograd secret police. They were imprisoned at Bolshevik headquarters in the Smolny Institute.  Natalia visited Michael the next two days, 8 and 9 March 1918, with their friend Princess Putyatina. On 9 March, she barged her way into Lenin's office, which was in the same building, to remonstrate with him. In the evening, the Council of the People's Commissars decided to send Michael and Johnson into internal exile. On 11 March, they were sent a thousand miles eastwards to the remote city of Perm.  Concerned for her entire family's safety, Natalia made plans for the children to be taken abroad. With the help of the Danish embassy, which was next-door to Princess Puyatina's apartment, George was smuggled out of the country to Denmark by his nanny, Miss Neame. The Danes extended diplomatic protection to the villa in Gatchina by pretending to rent it and flying the Danish flag over the house. Natalia wanted to join Michael in Perm, and after repeated pleading received a travel permit to join him. They spent about a week together, until an army of disgruntled Czechs advanced on Perm. The Bolsheviks had attempted to ship prisoners-of-war from Austria–Hungary out of Russia, ethnic Czech troops amongst them. The Czechs, however, were not going home to fight once more for the Austrian empire, but to fight for a separate independent homeland. The Germans demanded that the Bolsheviks disarm the Czechs, with the result that the Czech forces joined with the White Army, fighting against the Bolsheviks. With the approach of the Czechs, Michael and Natalia feared that she would become trapped in Perm, possibly in a dangerous situation, and so on 18 May she left for Moscow.  In Moscow, Natalia continued to badger Bolshevik Commissars, including Lenin, Trotsky and Sverdlov, for Michael's release, but to no avail. In June 1918, her husband and Johnson were shot by their captors on the outskirts of Perm. To cover their tracks, the Perm authorities distributed a concocted story that Michael was abducted by unidentified men and had disappeared. Natalia went to Uritsky in a quest for an explanation, but Uritsky ordered her arrest and incarceration. The Soviet disinformation about Michael's disappearance led to unfounded rumours that he had escaped and was leading a successful counter-revolution. Natalia heard the rumours in prison, and chose to believe them. Ten weeks after her imprisonment, in early September, Natalia pretended that she had developed tuberculosis, and was moved to a nursing home. Once there, she escaped and took refuge in the apartment above her brother-in-law's with family friend Princess Vyazemskaya. Uritsky had been murdered in late August, and the Bolsheviks were terrorising Petrograd in what was later called the Red Terror. Natalia's daughter, "Tata", was arrested and imprisoned, but released after a few days when it became apparent she had no knowledge of her mother's whereabouts. With no money or food, "Tata" made her way to her uncle's apartment, and so was fortuitously re-united with her mother.

Exile.

The Germans believed the widespread rumours that Michael was still alive, and plotted to rescue Natalia from Russia in an attempt to gain influence with Michael. Through the German-controlled Ukrainian consulate, Natalia and her daughter were provided with false passports. Natalia's daughter used her own name, while Natalia's passport was in the name of a nun called Frau Tania Klenow. They travelled separately to Kiev, with Natalia disguised as a nun. They were still in Kiev when the war ended with Germany's defeat on 11 November 1918. German authority began to collapse. Natalia and her daughter, along with Princess Vyazemskaya and Natalia's widowed brother-in-law Aleksei Matveev, who had both made it to Kiev as well, fled to Odessa in the hope they could escape by sea. Two British naval vessels at the port, HMS "Nereide" and HMS "Skirmisher", provided them with sanctuary. Aboard HMS "Nereide" they were evacuated to Constantinople.  By way of HMS "Agamemnon" to Malta, merchant ship to Marseilles, and rail to Paris, Natalia arrived in England. Johnson's widowed mother had leased a house, Snape in Wadhurst, Sussex, for Michael's family, and all the furniture and furnishings stored at Paddockhurst were moved in. George arrived from Copenhagen with his nanny in spring 1919, and was sent to an English boarding school. Natalia's daughter, Natalia Mamontova, was enrolled at a convent school in France. For funds, Natalia used money in Michael's bank accounts in Paris and Copenhagen, and started selling her jewellery. She met Michael's mother, the Dowager Empress Marie, who had also escaped Russia, in London, and their meeting this time was courteous. Conflicting rumours about Michael's fate and whereabouts continued without any solid news. In 1920, "Tata" was sent to Cheltenham Ladies' College and George was enrolled at Harrow School. Natalia moved out of Snape as the lease ended, and moved to Percy Lodge near Richmond, Surrey.  On 12 August 1921, 18-year-old Natalia Mamontova married future BBC broadcaster Val Gielgud, against her mother's wishes and without her foreknowledge. Natalia Mamontova was on school break and returned home as if nothing had happened. When Natalia found out, she ordered her daughter out of her house. Natalia left Percy Lodge and moved into an apartment in Kensington. The Gielguds divorced in 1923, and Natalia Mamontova married composer and music critic Cecil Gray.  By 1924, there was still no sign of Michael, and Natalia had him declared legally dead on 5 July 1924. She inherited his estate in Britain, which was valued at a mere £95. The following month, Michael's cousin, Grand Duke Cyril Vladimirovich, declared himself Emperor on the basis that he had inherited the throne at the moment of the previous Emperor's death, despite the abolition of the Russian monarchy by the communists. In 1928, he gave Natalia the title of Princess, followed in 1935 by the style "Her Serene Highness Princess Romanovskaya-Brasova". He made George a Prince. Cyril's claim to the throne was met with opposition from within the Romanov family because at his birth his mother was a Lutheran and not a member of the Russian Orthodox Church. Furthermore, Cyril had married Princess Victoria Melita of Saxe-Coburg and Gotha, who was a divorcée and his first cousin, without the Emperor's consent. The House law that determined the Russian line of succession excluded princes born to non-Orthodox mothers, and princes who married without the Tsar's consent. The Russian Orthodox Church did not recognise Victoria's divorce from her first husband as valid, and did not permit marriage between first cousins. Cyril's title, and by extension Natalia's and George's, were only recognised by Cyril's supporters.

Decline.

To save money, in 1927 Natalia moved to Paris where living costs were less than in London. George joined her in France, but he was killed after a car accident in 1931. She was at his bedside when he died, though he had not regained consciousness after the crash. She was emotionally devastated. Natalia's granddaughter, Pauline Gray, was born in 1929, but the Grays' marriage also ended in divorce. Natalia Mamontova's third and last marriage was to naval officer Michael Majolier, with whom she had a second daughter, Alexandra, born in 1934.  Natalia continued attempts to recover Michael's assets. The Polish government had seized Michael's Polish estate, and Natalia sued them for its return or compensation. By the Peace of Riga, the Poles were entitled to any imperial property in the former Russian Poland, but Natalia pointed out that Michael was already dead before the Peace, and so any of Michael's property in Poland was legally hers, as a commoner. In 1937, the court ruled against her. In 1938, she did receive a pay-out from the German courts, when the Tsar's estate in Germany was shared between all his heirs, but hyper-inflation had reduced its value. She continued to sell anything she could in a desperate attempt to raise cash.  During World War II, Natalia and her daughter were separated as Natalia lived in Paris, and her daughter was in Britain. They were unable to communicate with each other until after the war, by which time Natalia was penniless and lived as a refugee in an attic box-room. On 23 January 1952, she died of cancer at the Laënnec charity hospital in Paris in complete poverty, and was buried in Passy Cemetery (Section 9, near the intersection with the outer wall and Section 8) in Paris beside her son George, Count Brasov.

Natalia Brasova, Countess Brasova (; born Natalia Sergeyevna Sheremetyevskaya, ; 27 June 1880 – 26 January 1952) was a Russian noblewoman who married, as her third husband, Grand Duke Michael Alexandrovich of Russia.

娜塔莉娅·布拉索娃(1880年-6月27日-1952年-1月23日),俄罗斯帝国米哈伊尔大公之妻。


Underpinning theory.

Applied ethics is distinguished from normative ethics, which concerns standards for right and wrong behavior, and from meta-ethics, which concerns the nature of ethical properties, statements, attitudes, and judgments.  Whilst these three areas of ethics appear to be distinct they are also interrelated. The use of an applied ethics approach often draws upon certain normative ethical theories like the following:  Sometimes, these normative ethical theories clash which poses challenges when trying to resolve real-world ethical dilemmas. One approach which attempts to overcome the seemingly impossible divide between deontology and utilitarianism (of which the divide is caused by the opposite takings of an absolute and relativist moral view) is case-based reasoning, also known as casuistry. Casuistry does not begin with theory, rather it starts with the immediate facts of a real and concrete case. While casuistry makes use of ethical theory, it does not view ethical theory as the most important feature of moral reasoning. Casuists, like Albert Jonsen and Stephen Toulmin ("The Abuse of Casuistry" 1988), challenge the traditional paradigm of applied ethics. Instead of starting from theory and applying theory to a particular case, casuists start with the particular case itself and then ask what morally significant features (including both theory and practical considerations) ought to be considered for that particular case. In their observations of medical ethics committees, Jonsen and Toulmin note that a consensus on particularly problematic moral cases often emerges when participants focus on the facts of the case, rather than on ideology or theory. Thus, a Rabbi, a Catholic priest, and an agnostic might agree that, in this particular case, the best approach is to withhold extraordinary medical care, while disagreeing on the reasons that support their individual positions. By focusing on cases and not on theory, those engaged in moral debate increase the possibility of agreement.

Applied ethics refers to the practical application of moral considerations. It is ethics with respect to real-world actions and their moral considerations in the areas of private and public life, the professions, health, technology, law, and leadership. For example, the bioethics community is concerned with identifying the correct approach to moral issues in the life sciences, such as euthanasia, the allocation of scarce health resources, or the use of human embryos in research. Environmental ethics is concerned with ecological issues such as the responsibility of government and corporations to clean up pollution. Business ethics includes questions regarding the duties or duty of 'whistleblowers' to the general public or their loyalty to their employers.

应用伦理学属于哲学的学科,旨在应用伦理学的理论解决日常生活的困境,相关理论包括功利主义、社会契约理论和义务伦理等。被视为属于应用伦理学范畴的题目包括商业伦理、生物伦理学、环境伦理、人权问题、企业社会责任等。


Business structure.

ACE provides insurance and reinsurance products and services through several operating units.

North American.

ACE USA provides commercial property insurance and casualty (P&C), risk management and accident and health (A&H) coverages through retail brokers. ACE Agriculture offers crop, farm and agribusiness P&C coverages through agents and brokers. ACE Westchester offers commercial P&C excess and surplus lines through wholesale brokers.  ACE Bermuda provides liability, property, political risk coverages and captive programs through large international brokers.  ACE Private Risk Services offers high-value personal lines coverages through independent agents and brokers. ACE Commercial Risk Services provides specialty small business coverage through agents and brokers.

International.

ACE International provides commercial P&C, A&H, and traditional and specialty personal lines through retail brokers, agents and other channels in 51 countries outside North America. ACE Global Markets offers commercial P&C excess and surplus lines and A&H sold by wholesale brokers and through Lloyd’s. In North America, Combined Insurance, acquired by ACE in 2008, provides personal accident and supplemental health insurance through captive agents.

Reinsurance.

ACE Tempest Re, based in Stamford, Connecticut, offers P&C and life reinsurance sold worldwide by reinsurance brokers.

Life.

ACE Life provides protection and savings products through agents, bancassurance and other channels in Asia, Latin America, and the Middle East. Combined Insurance offers personal accident and supplemental health coverage sold by captive agents in North America.

History.

Chubb.

In 1882, Thomas Caldecot Chubb and his son Percy started a marine underwriting business in New York City. They collected $1,000 from 100 prominent merchants and focused on insuring ships and cargoes.  The Chubb Corporation was incorporated in 1967 and was listed on the New York Stock Exchange in 1984.  Beginning in 1970, the corporation owned The Chubb Institute, a chain of commercial technical schools which grew out of the company's employee training program, but the schools were sold for $1 to a partnership of private equity firms Great Hill Partners and the High-Tech Institute in 2004.  In 2007, Chubb was named the Readers' Choice winner as "Best Admitted Property/Casualty Insurance Company" by "Business Insurance". In 2010 Chubb was number five on Chicago Business "Best Places to Work" list.

ACE Limited.

1985–1999.

ACE Limited was established in 1985, funded by a group of 34 U.S. companies seeking difficult-to-obtain Excess Liability and Directors and Officers (D&O) insurance coverage. That year, ACE and its Bermuda subsidiary, incorporated in the Cayman Islands and headquartered in Hamilton, Bermuda, wrote its first insurance policy with John Cox as its President and CEO. In 1987 the company assumed management of Corporate Officers & Directors Assurance Limited (CODA), expanding ACE Bermuda's product line.  Walter Scott became Chairman, President, and CEO of ACE in 1990 and saw the company listed on the New York Stock Exchange in 1993. Brian Duperreault succeeded Scott in 1994 as Chairman, President & CEO and worked for the next ten years as ACE went through a series of acquisitions and a diversification process that brought the ACE Group of Companies global status. One of the multiple acquisitions made during this time was the global property and casualty business of Cigna Corporation (most significantly the Insurance Company of North America, known as INA), which was purchased for $3.45 billion in 1999.

2000–2014.

In 2004, Evan G. Greenberg became President and CEO of ACE Ltd. In 2004 ACE was also investigated by NY Attorney General Eliot Spitzer for participating in a bid rigging and price fixing scheme with insurance broker Marsh & McLennan.  In 2008, ACE purchased the accident and health insurance provider Combined Insurance Company of America (founded by W. Clement Stone in 1919) from Aon Corporation for $2.56 billion and the high-net-worth personal lines business of the Atlantic Companies.  Also in 2008, ACE relocated from the Cayman Islands to Zurich, Switzerland. Evan Greenberg described the move as a "natural progression" that would provide ACE with a "better strategic flexibility...and a solid legal and regulatory environment..." The re-domestication was completed in July that year.  In 2010, the ACE company ESIS Inc. was hired by BP to process claims made by the victims of the Deepwater Horizon oil spill.  In 2010, ACE Limited purchased Rain and Hail, LLC for $1.1 billion. Rain and Hail Insurance Service, headquartered in Johnston, Iowa, is an industry leader in crop insurance in the United States. ACE Limited also acquired the Hong Kong and Korea life insurance operations of New York Life.  In 2011, ACE Limited purchased agribusiness insurer Penn Millers. In 2012, they purchased Indonesian insurer Asuransi Jaya Proteksi. In 2013, they purchased Mexican Surety Lines Company Fianzas Monterrey and Mexican Personal Lines Insurer ABA Seguros.  In April 2014, ACE Limited acquired a majority stake in Siam Commercial Samaggi Insurance PCL from Siam Commercial Bank. Following a subsequent tender offer in June 2014, ACE and its local partner owned 93.03% of the Samaggi.  In October 2014, ACE Limited acquired the large commercial property and casualty business of Itaú Unibanco Holding SA. The transaction made ACE the largest property and casualty insurer in Brazil. In April 2015, ACE Limited acquired the Fireman’s Fund high net worth personal lines insurance business in the U.S. from Allianz for $365 million. ACE Private Risk Services is one of the largest high net worth insurers in the U.S.

ACE acquires Chubb.

In July 1, 2015, ACE announced that it would acquire Chubb Corporation for $28.3 billion in cash and ACE stock. Upon completion, ACE shareholders held 70% while Chubb shareholders got 30% of the new combined company. The new company was to be based in Zurich, where ACE Limited's headquarters were. Evan Greenberg of ACE became the Chairman and CEO of the new company, while Chubb Chairman and CEO John Finnegan became Executive Vice Chairman for North America External Affairs. The company's board was expanded to 18, with 4 of them coming from Chubb. The new combined company then decided to adopt the Chubb name. The deal received ACE and Chubb shareholder approval and all required regulatory approval, and closed on January 14, 2016.

Controversies.

2004 Eliot Spitzer investigation.

In 2004 New York Attorney General Eliot Spitzer conducted an investigation in the insurance industry. ACE, American International Group (AIG), Marsh & McLennan, and other large insurers and brokerages were named in Spitzer's investigation for possibly participating in questionable insurance practices including the payment of contingent commissions, bid-rigging, price-fixing, and improper accounting. Spitzer asserted that contingent commissions contributed to a widespread practice of "bid-rigging" where brokers solicited fake bids with deliberately less favorable terms for the consumer than the bid offered by the insurance company paying the highest commissions.  As part of an $80 million settlement that abated further inquiry, ACE signed an Assurance of Discontinuance in which they acknowledged their prior conduct and agreed to alter their business practices. Evan Greenberg himself admitted no fault in Spitzer's allegations although a junior executive did plead guilty to criminal charges.  Spitzer's insurance industry probe additionally looked in early 2005 into ACE Ltd's subsidiary ACE Tempest Re's reporting to the SEC of a series of reinsurance transactions, together with the SEC reporting of a further 16 unaffiliated re-insurers. Evan Greenberg said that his company's investigation should be completed within a month. According to Greenberg, contracts appeared "generally structured in a way to provide for appropriate risk transfer and accounted for properly."  The Spitzer investigations also triggered civil litigation by policyholders who claim they were victimized by the bid rigging and commission schemes.

Iran Held Liable for 9/11.

On March 9, 2016, U.S. District Judge George B. Daniels issued a default judgement against Iran, ordering it to pay $7.5 billion in damages to families of victims who died in the September 11, 2001 attacks, as well as $3 billion to Chubb Limited & other unnamed insurers that paid out claims resulting from the event. The plaintiffs in the case argued that Iran "provided material support" and training to al-Qaeda members, including 9/11 hijackers, through Hezbollah prior to the attacks and was therefore liable.

Chubb Group Classic.

The Chubb Classic is a Champions Tour golf tournament located at The Classics Country Club at Lely Resort in Naples, FL. The Chubb Classic has raised more than $3 million for charity.

Chubb Limited, incorporated in Zurich, Switzerland, is the parent company of Chubb, a global provider of insurance products covering property and casualty, accident and health, reinsurance, and life insurance and the largest publicly traded property and casualty company in the world. Chubb operates in 54 countries and territories and in the Lloyd's insurance market in London. Clients of Chubb consist of multinational corporations and local businesses, individuals, and insurers seeking reinsurance coverage. Chubb provides commercial and personal property and casualty insurance, personal accident and supplemental health insurance, reinsurance and life insurance. The current corporate branding was established when ACE Limited acquired Chubb in 2016, then adopted the Chubb name.

安达保险集团(英语:Chubb Limited)是一家总部位于瑞士苏黎世的保险公司,在全球54个国家和地区开展业务,是全球最大的上市产物保险公司集团。客户包括寻求再保险的跨国公司和本地企业、个人以及其他保险公司。安达保险提供商业和个人财产及意外伤害保险、人身意外和补充健康保险、再保险和人寿保险。安达保险在2016年被ACE Limited收购后成立安达保险集团,新集团名称继续沿用安达保险旧名。