Misplaced Pages

#941058

123-404: Halifax was established as a city in 1749, three years before the newspaper was published, with a population of 4,000 residents. Because of the developing city and the low population, there was a shortage of local news or community news, and advertisements occupied a large portion of the newspaper. It contained news excerpts from the newspapers of Britain, Europe, and New England. The first issue of

246-410: A marker gene . This gene, called GFP , or green fluorescent protein, would cause live samples of the virus to glow green under fluorescent light. The insertion of this gene, which would not influence the virulence of the virus, would be the only allowed modification of the genome. The committee stated the proposed modification would aid in research of treatments by making it easier to assess whether

369-475: A personal union relationship under a shared monarch. Therefore, though today there are legally ten American monarchs, one person occupies each distinct position. In addition to these sovereign states, there are also a number of sub-national ones. In Bolivia , for example, the Afro-Bolivian king claims descent from an African dynasty that was taken from its homeland and sold into slavery. Though largely

492-532: A ceremonial title today, the position of king of the Afro-Bolivians is officially recognized by the government of Bolivia. Polynesian societies were ruled by an ariki from ancient times. The title is variously translated as "supreme chief", "paramount chief" or "king". The Kingdom of Tahiti was founded in 1788. Sovereignty was ceded to France in 1880 although descendants of the Pōmare dynasty claim

615-443: A clinical case was observed, smallpox was confirmed using laboratory tests. Microscopically , poxviruses produce characteristic cytoplasmic inclusion bodies , the most important of which are known as Guarnieri bodies , and are the sites of viral replication . Guarnieri bodies are readily identified in skin biopsies stained with hematoxylin and eosin, and appear as pink blobs. They are found in virtually all poxvirus infections but

738-415: A discrete rash, in which the pustules stood out on the skin separately. The distribution of the rash was most dense on the face, denser on the extremities than on the trunk, and denser on the distal parts of the extremities than on the proximal. The palms of the hands and soles of the feet were involved in most cases. Sometimes, the blisters merged into sheets, forming a confluent rash, which began to detach

861-518: A doctor in Berkeley, Gloucestershire , rural England, discovered that immunity to smallpox could be produced by inoculating a person with material from a cowpox lesion. Cowpox is a poxvirus in the same family as variola. Jenner called the material used for inoculation vaccine from the root word vacca , which is Latin for cow. The procedure was much safer than variolation and did not involve a risk of smallpox transmission. Vaccination to prevent smallpox

984-455: A fatality rate of around 30%, while variola minor’s mortality rate was about 1%. Throughout the 18th century, variola major was responsible for around 400,000 deaths annually in Europe alone. Survivors of the disease often faced lifelong consequences, such as blindness and severe scarring, which were nearly universal among those who recovered. In the first half of the 20th century, variola major

1107-614: A host cell varies across the poxviridae . Recombination of the genome occurs within actively infected cells. Following the onset of viral DNA replication, an intermediate set of genes codes for transcription factors of late gene expression. The products of the later genes include transcription factors necessary for transcribing the early genes for new virions, as well as viral RNA polymerase and other essential enzymes for new viral particles. These proteins are then packaged into new infectious virions capable of infecting other cells. Two live samples of variola major virus remain, one in

1230-474: A king or queen. As of 2022 , in Europe there are twelve monarchies: seven kingdoms ( Belgium , Denmark , Netherlands , Norway , Spain , Sweden and the United Kingdom ), one grand duchy ( Luxembourg ), one papacy ( Vatican City ), and two principalities ( Liechtenstein and Monaco ), as well as one diarchy principality ( Andorra ). In China, before the abolition of the monarchy in 1912,

1353-604: A monarch and is superior to all other titles. Nepal abolished their monarchy in 2008. Sri Lanka had a complex system of monarchies from 543 BC to 1815. Between 47–42 BC, Anula of Sri Lanka became the country's first female head of state as well as Asia's first head of state. In Malaysia 's constitutional monarchy, the Yang di-Pertuan Agong (the Supreme Lord of the Federation) is de facto rotated every five years among

SECTION 10

#1732765337942

1476-601: A potential treatment was effective in killing viral samples. The recommendation could only take effect if approved by the WHA . When the WHA discussed the proposal in 2005, it refrained from taking a formal vote on the proposal, stating that it would review individual research proposals one at a time. Addition of the GFP gene to the Vaccinia genome is routinely performed during research on

1599-423: A region of roughly 100 base pairs necessary for resolving concatomeric DNA (a stretch of DNA containing multiple copies of the same sequence), a few open reading frames , and short tandemly repeating sequences of varying number and length. The ITRs of poxviridae vary in length across strains and species. The coding sequence for most of the viral proteins in variola major virus have at least 90% similarity with

1722-421: A source of infection”; noted that “Current recommendations for control of secondary smallpox infections emphasize transmission ‘by expelled droplets to close contacts (those within 6–7 feet)’”; but warned that the “emphasis on spread via large droplets may reduce the vigilance with which more difficult airborne precautions [i.e. against finer droplets capable of traveling longer distances and penetrating deeply into

1845-492: A usurper who would often install his own family on the throne. A series of pharaohs ruled Ancient Egypt over the course of three millennia ( c.  3150 BC to 31 BC) until it was conquered by the Roman Empire . In the same time period several kingdoms flourished in the nearby Nubia region, with at least one of them, that of the so-called A-Group culture, apparently influencing the customs of Egypt itself. From

1968-425: A variety of titles – king or queen , prince or princess (e.g., Sovereign Prince of Monaco ), emperor or empress (e.g., Emperor of China , Emperor of Ethiopia , Emperor of Japan , Emperor of India ), archduke , duke or grand duke (e.g., Grand Duke of Luxembourg ), emir (e.g., Emir of Qatar ), sultan (e.g., Sultan of Oman ), or pharaoh . Monarchy is political or sociocultural in nature, and

2091-602: A year. The final known fatal case occurred in the United Kingdom in 1978 . Inoculation for smallpox appears to have started in China around the 1500s. Europe adopted this practice from Asia in the first half of the 18th century. In 1796, Edward Jenner introduced the modern smallpox vaccine. In 1967, the WHO intensified efforts to eliminate the disease. Smallpox is one of two infectious diseases to have been eradicated,

2214-582: Is a severe form accompanied by extensive bleeding into the skin, mucous membranes, gastrointestinal tract, and viscera . This form develops in approximately 2% of infections and occurs mostly in adults. Pustules do not typically form in hemorrhagic smallpox. Instead, bleeding occurs under the skin, making it look charred and black, hence this form of the disease is also referred to as variola nigra or "black pox". Hemorrhagic smallpox has very rarely been caused by variola minor virus. While bleeding may occur in mild cases and not affect outcomes, hemorrhagic smallpox

2337-420: Is also a later form of hemorrhagic smallpox (referred to late hemorrhagic smallpox, or variolosa pustula hemorrhagica ). The prodrome is severe and similar to that observed in early hemorrhagic smallpox, and the fever persists throughout the course of the disease. Bleeding appears in the early eruptive period (but later than that seen in purpura variolosa ), and the rash is often flat and does not progress beyond

2460-490: Is also under research as a viral vector for vaccines for unrelated diseases. The genome of variola major virus was first sequenced in its entirety in the 1990s. The complete coding sequence is publicly available online. The current reference sequence for variola major virus was sequenced from a strain that circulated in India in 1967. In addition, there are sequences for samples of other strains that were collected during

2583-541: Is believed to have had a mortality rate of less than 1%, as compared to variola major's 30%. Like variola major, variola minor was spread through inhalation of the virus in the air, which could occur through face-to-face contact or through fomites. Infection with variola minor virus conferred immunity against the more dangerous variola major virus. Because variola minor was a less debilitating disease than smallpox, people were more frequently ambulant and thus able to infect others more rapidly. As such, variola minor swept through

SECTION 20

#1732765337942

2706-411: Is caused by infection with variola virus, which belongs to the family Poxviridae , subfamily Chordopoxvirinae , genus Orthopoxvirus . The date of the appearance of smallpox is not settled. It most probably evolved from a terrestrial African rodent virus between 68,000 and 16,000 years ago. The wide range of dates is due to the different records used to calibrate the molecular clock . One clade

2829-488: Is complicated by having multiple infectious forms, with differing mechanisms of cell entry. Poxviruses are unique among human DNA viruses in that they replicate in the cytoplasm of the cell rather than in the nucleus . To replicate, poxviruses produce a variety of specialized proteins not produced by other DNA viruses , the most important of which is a viral-associated DNA-dependent RNA polymerase . Both enveloped and unenveloped virions are infectious. The viral envelope

2952-606: Is considered a monarch despite only holding the position for five years at a time. Hereditary succession within one patrilineal family has been most common (but see the Rain Queen ), with a preference for children over siblings, and sons over daughters. In Europe, some peoples practiced equal division of land and regalian rights among sons or brothers, as in the Germanic states of the Holy Roman Empire, until after

3075-447: Is consistent with the other published estimates, it suggests that the archaeological and historical evidence is very incomplete. Better estimates of mutation rates in these viruses are needed. Examination of a strain that dates from c.  1650 found that this strain was basal to the other presently sequenced strains. The mutation rate of this virus is well modeled by a molecular clock. Diversification of strains only occurred in

3198-441: Is estimated that 400,000 people died from the disease per year, and that one-third of all cases of blindness were due to smallpox. Smallpox is estimated to have killed up to 300 million people in the 20th century and around 500 million people in the last 100 years of its existence. Earlier deaths included six European monarchs , including Louis XV of France in 1774. As recently as 1967, 15 million cases occurred

3321-524: Is generally (but not always) associated with hereditary rule . Most monarchs, both historically and in the present day, have been born and brought up within a royal family (whose rule over a period of time is referred to as a dynasty ) and trained for future duties. Different systems of succession have been used, such as proximity of blood (male preference or absolute), primogeniture , agnatic seniority , Salic law , etc. While traditionally most monarchs have been male, female monarchs have also ruled, and

3444-415: Is made of modified Golgi membranes containing viral-specific polypeptides, including hemagglutinin . Infection with either variola major virus or variola minor virus confers immunity against the other. The more common, infectious form of the disease was caused by the variola major virus strain, known for its significantly higher mortality rate compared to its counterpart, variola minor. Variola major had

3567-493: Is rapidly followed by the development of petechiae and bleeding in the skin, conjunctiva and mucous membranes. Death often occurs suddenly between the fifth and seventh days of illness, when only a few insignificant skin lesions are present. Some people survive a few days longer, during which time the skin detaches and fluid accumulates under it, rupturing at the slightest injury. People are usually conscious until death or shortly before. Autopsy reveals petechiae and bleeding in

3690-453: Is typically fatal. Vaccination does not appear to provide any immunity to either form of hemorrhagic smallpox and some cases even occurred among people that were revaccinated shortly before. It has two forms. The early or fulminant form of hemorrhagic smallpox (referred to as purpura variolosa ) begins with a prodromal phase characterized by a high fever, severe headache, and abdominal pain. The skin becomes dusky and erythematous, and this

3813-592: The Dangun as a collection of nationalistic legends. The monarchs of Goguryeo and some monarchs of Silla used the title Taewang , meaning "Greatest King". The early monarchs of Silla used the titles of Geoseogan , Chachaung , Isageum , and finally Maripgan until 503. The title Gun (prince) can refer to the dethroned rulers of the Joseon dynasty as well. Under the Korean Empire (1897–1910),

Halifax Gazette - Misplaced Pages Continue

3936-568: The Deji , has to be chosen by an electoral college of nobles from amongst a finite collection of royal princes of the realm upon the death or removal of an incumbent. Within the Holy Roman Empire different titles were used by nobles exercising various degrees of sovereignty within their borders (see below). Such titles were granted or recognized by the emperor or pope. Adoption of a new title to indicate sovereign or semi-sovereign status

4059-592: The 1987 Constitution . Bhutan has been an independent kingdom since 1907. The first Druk Gyalpo ( Dragon King ) was elected and thereafter became a hereditary absolute monarchy. It became a constitutional monarchy in 2008. Tibet was a monarchy since the Tibetan Empire in the 6th century. It was ruled by the Yuan dynasty following the Mongol invasion in the 13th century and became an effective diarchy with

4182-718: The Achaemenid dynasty . Under his rule, the empire embraced all the previous civilized states of the ancient Near East , expanded vastly and eventually conquered most of Southwest Asia and much of Central Asia and the Caucasus. From the Mediterranean Sea and Hellespont in the west to the Indus River in the east, Cyrus the Great created the largest empire the world had yet seen. Thailand and Bhutan are like

4305-585: The Associated Press . This agency worked together to accumulate and spread breaking international news. In this process, Halifax played an integral role; however, it was hardly mentioned. The Gazette published as a newspaper until 1867, three days after Canada was established, when it became the Nova Scotia Royal Gazette , the official publication of laws and legislation for the government of Nova Scotia . In 1977, Part II of

4428-769: The Christianised nobility called the Principalía . After the Spanish–American War , the country was ceded to the United States of America and made into a territory and eventually a Commonwealth , thus ending monarchism. While the Philippines is currently a republic, the Sultan of Sulu and Sultan of Maguindanao retain their titles only for ceremonial purposes but are considered ordinary citizens by

4551-651: The Dalai Lama as co-ruler. It came under the rule of the Chinese Qing dynasty from 1724 until 1912 when it gained de facto independence. The Dalai Lama became an absolute temporal monarch until the annexation of Tibet by the People's Republic of China in 1951. Nepal was a monarchy for most of its history until becoming a federal republic in 2008. The concept of monarchy existed in the Americas long before

4674-698: The East India Company stationed in China and another by Clopton Havers . Lady Mary Wortley Montagu observed smallpox inoculation during her stay in the Ottoman Empire , writing detailed accounts of the practice in her letters, and enthusiastically promoted the procedure in England upon her return in 1718. According to Voltaire (1742), the Turks derived their use of inoculation from neighbouring Circassia . Voltaire does not speculate on where

4797-548: The Halifax Gazette contained an article about the demise of John Goreham, a military officer and businessman who died in London of smallpox . The Halifax Gazette dealt with tough competition from Boston and New York newspapers for breaking news. The publishers plotted and planned in advance to beat each other in printing the headlines first. In the year of 1849, there was a group of six New York publishers who comprised

4920-675: The Library and Archives Canada , and briefly placed on display back in Halifax before being permanently placed in the archives at Ottawa. Smallpox Smallpox was an infectious disease caused by variola virus (often called smallpox virus), which belongs to the genus Orthopoxvirus . The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) certified

5043-643: The Pahlavi dynasty that used the title of "Shahanshah" (or "King of Kings"). The last Iranian Shahanshah was King Mohammad Reza Pahlavi , who was forced to abdicate the throne as a result of a revolution in Iran. In fact the Persian (Iranian) kingdom goes back to about 2,700 BC (see list of Kings of Persia ), but reached its ultimate height and glory when King Cyrus the Great (known as "The Great Kourosh" in Iran) started

Halifax Gazette - Misplaced Pages Continue

5166-793: The Royal Gazette was introduced to publish provincial regulations and was reunited with Part I to form the current Gazette . The Gazette is managed by the Office of the Registrar of Regulations in the Nova Scotia Department of Justice. The only remaining copy of the first issue of Halifax Gazette was long owned by the Massachusetts Historical Society in Boston . It was acquired in 2002 by

5289-422: The common cold : fever of at least 38.3 °C (101 °F), muscle pain , malaise , headache and fatigue. As the digestive tract was commonly involved, nausea, vomiting, and backache often occurred. The early prodromal stage usually lasted 2–4 days. By days 12–15, the first visible lesions – small reddish spots called enanthem – appeared on mucous membranes of the mouth, tongue, palate , and throat, and

5412-582: The emperor of China was traditionally regarded as the ruler of " All under heaven ". "King" is the usual translation for the term wang ( 王 ), the sovereign before the Qin dynasty and during the Ten Kingdoms period. During the early Han dynasty , China had a number of kingdoms, each about the size of a province and subordinate to the Emperor. In Korea, Daewang (great king), or Wang (king),

5535-791: The free election of kings of the Polish–Lithuanian Commonwealth . Modern examples include the Yang di-Pertuan Agong (lit. "He Who is Made Lord') of Malaysia , who is appointed by the Conference of Rulers every five years or after the king's death, and the pope of the Roman Catholic Church , who serves as sovereign of the Vatican City State and is elected to a life term by the College of Cardinals . In recent centuries, many states have abolished

5658-460: The global eradication of the disease in 1980, making smallpox the only human disease to have been eradicated to date. The initial symptoms of the disease included fever and vomiting. This was followed by formation of ulcers in the mouth and a skin rash . Over a number of days, the skin rash turned into the characteristic fluid-filled blisters with a dent in the center. The bumps then scabbed over and fell off, leaving scars. The disease

5781-470: The horsepox virus using publicly available sequence data for horsepox. The researchers argued that their work would be beneficial to creating a safer and more effective vaccine for smallpox, although an effective vaccine is already available. The horsepox virus had previously seemed to have gone extinct, raising concern about potential revival of variola major and causing other scientists to question their motives. Critics found it especially concerning that

5904-496: The medieval era and sometimes (e.g., Ernestine duchies ) into the 19th century. Other European realms practiced one or another form of primogeniture , in which a lord was succeeded by his eldest son or, if he had none, by his brother, his daughters or sons of daughters. The system of tanistry practiced among Celtic tribes was semi-elective and gave weight also to ability and merit. The Salic law , practiced in France and in

6027-468: The replication of viral DNA. The first set of expressed genes are transcribed by pre-existing viral machinery packaged within the infecting virion. These genes encode the factors necessary for viral DNA synthesis and for transcription of the next set of expressed genes. Unlike most DNA viruses, DNA replication in variola virus and other poxviruses takes place within the cytoplasm of the infected cell. The exact timing of DNA replication after infection of

6150-624: The 18th and 19th centuries. Variola virus is large and brick-shaped and is approximately 302 to 350 nanometers by 244 to 270 nm, with a single linear double stranded DNA genome 186 kilobase pairs (kbp) in size and containing a hairpin loop at each end. Four orthopoxviruses cause infection in humans: variola, vaccinia , cowpox , and monkeypox . Variola virus infects only humans in nature, although primates and other animals have been infected in an experimental setting. Vaccinia, cowpox, and monkeypox viruses can infect both humans and other animals in nature. The life cycle of poxviruses

6273-593: The 6th to 19th centuries, Egypt was variously part of the Byzantine Empire , Islamic Empire, Mamluk Sultanate, Ottoman Empire and British Empire with a distant monarch. The Sultanate of Egypt was a short-lived protectorate of the United Kingdom from 1914 until 1922 when it became the Kingdom of Egypt and Sultan Fuad I changed his title to King. After the Egyptian Revolution of 1952 ,

SECTION 50

#1732765337942

6396-727: The Circassians derived their technique from, though he reports that the Chinese have practiced it "these hundred years". In 1721, Cotton Mather and colleagues provoked controversy in Boston by inoculating hundreds. After publishing The present method of inoculating for the small-pox in 1767, Dr Thomas Dimsdale was invited to Russia to variolate the Empress Catherine the Great of Russia and her son, Grand Duke Paul , which he successfully did in 1768. In 1796, Edward Jenner ,

6519-519: The Italian territories of the House of Savoy , stipulated that only men could inherit the crown. In most fiefs , in the event of the demise of all legitimate male members of the patrilineage , a female of the family could succeed (semi-Salic law). In most realms, daughters and sisters were eligible to succeed a ruling kinsman before more distant male relatives (male-preference primogeniture), but sometimes

6642-660: The United Kingdom in that they are constitutional monarchies ruled by a king. Jordan and many other Middle Eastern monarchies are ruled by a Malik and parts of the United Arab Emirates , such as Dubai , are still ruled by monarchs. Saudi Arabia is the largest Arab state in Western Asia by land area and the second-largest in the Arab world (after Algeria). It was founded by Abdul-Aziz bin Saud in 1932, although

6765-770: The United States at the CDC in Atlanta, and one at the Vector Institute in Koltsovo, Russia. Research with the remaining virus samples is tightly controlled, and each research proposal must be approved by the WHO and the World Health Assembly (WHA). Most research on poxviruses is performed using the closely related Vaccinia virus as a model organism. Vaccinia virus, which is used to vaccinate for smallpox,

6888-510: The United States, Great Britain, and South Africa in the early 20th century, becoming the dominant form of the disease in those areas and thus rapidly decreasing mortality rates. Along with variola major, the minor form has now been totally eradicated from the globe. The last case of indigenous variola minor was reported in a Somali cook, Ali Maow Maalin, in October 1977, and smallpox was officially declared eradicated worldwide in May 1980. Variola minor

7011-531: The WHO eradication campaign. A genome browser for a complete database of annotated sequences of variola virus and other poxviruses is publicly available through the Viral Bioinformatics Resource Center . The WHO currently bans genetic engineering of the variola virus. However, in 2004, a committee advisory to the WHO voted in favor of allowing editing of the genome of the two remaining samples of variola major virus to add

7134-507: The absence of Guarnieri bodies could not be used to rule out smallpox. The diagnosis of an orthopoxvirus infection can also be made rapidly by electron microscopic examination of pustular fluid or scabs. All orthopoxviruses exhibit identical brick-shaped virions by electron microscopy. If particles with the characteristic morphology of herpesviruses are seen this will eliminate smallpox and other orthopoxvirus infections. Definitive laboratory identification of variola virus involved growing

7257-525: The arrival of European colonialists. When the Europeans arrived they referred to these tracts of land within territories of different aboriginal groups to be kingdoms, and the leaders of these groups were often referred to by the Europeans as Kings, particularly hereditary leaders. Pre-colonial titles that were used included: The first local monarch to emerge in North America after colonization

7380-448: The bloodstream in large numbers, a condition known as viremia . This resulted in the second wave of multiplication in the spleen , bone marrow , and lymph nodes. The clinical definition of ordinary smallpox is an illness with acute onset of fever equal to or greater than 38.3 °C (101 °F) followed by a rash characterized by firm, deep-seated vesicles or pustules in the same stage of development without other apparent cause. When

7503-477: The central region of the genome is highly consistent across orthopoxviruses , and the arrangement of genes is consistent across chordopoxviruses. The center of the variola virus genome contains the majority of the essential viral genes, including the genes for structural proteins , DNA replication , transcription , and mRNA synthesis. The ends of the genome vary more across strains and species of orthopoxviruses . These regions contain proteins that modulate

SECTION 60

#1732765337942

7626-503: The closely related Vaccinia virus . The public availability of the variola virus complete sequence has raised concerns about the possibility of illicit synthesis of infectious virus. Vaccinia , a cousin of the variola virus, was artificially synthesized in 2002 by NIH scientists. They used a previously established method that involved using a recombinant viral genome to create a self-replicating bacterial plasmid that produced viral particles. In 2016, another group synthesized

7749-464: The conquests which eventually led to the creation of the Kingdom began in 1902 when he captured Riyadh , the ancestral home of his family, the House of Saud ; succession to the throne was limited to sons of Ibn Saud until 2015, when a grandson was elevated to Crown Prince. The Saudi Arabian government has been an absolute monarchy since its inception, and designates itself as Islamic . The King bears

7872-535: The continent. Places like St. Helena , Ceuta , Melilla and the Canary Islands are ruled by the king of the United Kingdom of Great Britain and Northern Ireland or the king of Spain . So-called "sub-national monarchies" of varying sizes can be found all over the rest of the continent, e.g., the Yoruba city-state of Akure in south-western Nigeria is something of an elective monarchy: its reigning Oba ,

7995-485: The country, such as the Xhosa and the Tswana , have also had and continue to have a series of kings and chiefs (namely the Inkosis and the Kgosis ) whose local precedence is recognised, but who exercise no legal authority. As part of the Scramble for Africa , seven European countries invaded and colonized most of the African continent. Currently, the African nations of Morocco , Lesotho , and Eswatini are sovereign monarchies under dynasties that are native to

8118-621: The course of the illness, but this happened most frequently during the first week of the rash when most of the skin lesions were intact. Infectivity waned in 7 to 10 days when scabs formed over the lesions, but the infected person was contagious until the last smallpox scab fell off. Concern about possible use of smallpox for biological warfare led in 2002 to Donald K. Milton's detailed review of existing research on its transmission and of then-current recommendations for controlling its spread. He agreed, citing Rao, Fenner and others, that “careful epidemiologic investigation rarely implicated fomites as

8241-403: The diagnosis of infection. Chickenpox was commonly confused with smallpox in the immediate post-eradication era. Chickenpox and smallpox could be distinguished by several methods. Unlike smallpox, chickenpox does not usually affect the palms and soles. Additionally, chickenpox pustules are of varying size due to variations in the timing of pustule eruption: smallpox pustules are all very nearly

8364-408: The genome of vaccinia , a related virus used for vaccination against smallpox. Gene expression of variola virus occurs entirely within the cytoplasm of the host cell , and follows a distinct progression during infection. After entry of an infectious virion into a host cell, synthesis of viral mRNA can be detected within 20 minutes. About half of the viral genome is transcribed prior to

8487-429: The group was able to recreate viable virus in a short time frame with relatively little cost or effort. Although the WHO bans individual laboratories from synthesizing more than 20% of the genome at a time, and purchases of smallpox genome fragments are monitored and regulated, a group with malicious intentions could compile, from multiple sources, the full synthetic genome necessary to produce viable virus. Smallpox

8610-409: The head of state of a monarchy . A monarch may exercise the highest authority and power in the state , or others may wield that power on behalf of the monarch. Usually a monarch either personally inherits the lawful right to exercise the state's sovereign rights (often referred to as the throne or the crown ) or is selected by an established process from a family or cohort eligible to provide

8733-449: The hosts' immune systems, and are primarily responsible for the variability in virulence across the orthopoxvirus family. These terminal regions in poxviruses are inverted terminal repetitions (ITR) sequences. These sequences are identical but oppositely oriented on either end of the genome, leading to the genome being a continuous loop of DNA. Components of the ITR sequences include an incompletely base paired A/T rich hairpin loop ,

8856-399: The husband of the heiress became the ruler, and most often also received the title, jure uxoris . Spain today continues this model of succession law, in the form of cognatic primogeniture . In more complex medieval cases, the sometimes conflicting principles of proximity and primogeniture battled, and outcomes were often idiosyncratic. As the average life span increased, the eldest son

8979-616: The king as a largely symbolic figurehead. In the Philippines , the pre-Colonial Filipino nobility, variously titled the harì (today meaning "king"), Lakan , Raja and Datu belonged to the caste called Uring Maharlika (Noble Class). When the islands were annexed to the Spanish Empire in the late 16th century, the Spanish monarch became the sovereign while local rulers often retained their prestige as part of

9102-595: The last Emperor of Ethiopia, was deposed in a communist coup . Various Somali Sultanates also existed, including the Adal Sultanate (led by the Walashma dynasty of the Ifat Sultanate ), Sultanate of Mogadishu , Ajuran Sultanate , Warsangali Sultanate, Geledi Sultanate , Majeerteen Sultanate and Sultanate of Hobyo . Central and Southern Africa were largely isolated from other regions until

9225-436: The lesions remained almost flush with the skin at the time when raised vesicles would have formed in the ordinary type. It is unknown why some people developed this type. Historically, it accounted for 5–10% of cases, and most (72%) were children. Malignant smallpox was accompanied by a severe prodromal phase that lasted 3–4 days, prolonged high fever, and severe symptoms of viremia . The prodromal symptoms continued even after

9348-406: The lower respiratory tract] are maintained”. Once inhaled, the variola virus invaded the mucous membranes of the mouth, throat, and respiratory tract. From there, it migrated to regional lymph nodes and began to multiply. In the initial growth phase, the virus seemed to move from cell to cell, but by around the 12th day, widespread lysis of infected cells occurred and the virus could be found in

9471-408: The malignant and hemorrhagic forms were usually fatal. The modified form was almost never fatal. In early hemorrhagic cases, hemorrhages occurred before any skin lesions developed. The incubation period between contraction and the first obvious symptoms of the disease was 7–14 days. At least 90% of smallpox cases among unvaccinated persons were of the ordinary type. In this form of the disease, by

9594-456: The modern era, but they did later feature kingdoms like the Kingdom of Kongo (1400–1914). The Zulu people formed a powerful Zulu Kingdom in 1816, one that was subsequently absorbed into the Colony of Natal in 1897. The Zulu king continues to hold a hereditary title and an influential cultural position in contemporary South Africa, although he has no direct political power. Other tribes in

9717-489: The monarch. A form of government may, in fact, be hereditary without being considered a monarchy, such as a family dictatorship. Monarchies take a wide variety of forms, such as the two co-princes of Andorra , positions held simultaneously by the Roman Catholic bishop of Urgel (Spain) and the elected president of France (although strictly Andorra is a diarchy ). Similarly, the Yang di-Pertuan Agong of Malaysia

9840-487: The monarchy and become republics . Advocacy of government by a republic is called republicanism , while advocacy of monarchy is called monarchism . A principal advantage of hereditary monarchy is the immediate continuity of national leadership, as illustrated in the classic phrase " The [old] King is dead. Long live the [new] King! ". In cases where the monarch serves mostly as a ceremonial figure (e.g., most modern constitutional monarchies), real leadership does not depend on

9963-636: The monarchy was dissolved and Egypt became a republic. West Africa hosted the Kanem Empire (700–1376) and its successor, the Bornu principality which survives to the present day as one of the traditional states of Nigeria . In the Horn of Africa , the Kingdom of Aksum and later the Zagwe dynasty , Ethiopian Empire (1270–1974), and Aussa Sultanate were ruled by a series of monarchs. Haile Selassie ,

10086-515: The nation's monarch. Alternatively, an individual may proclaim oneself monarch, which may be backed and legitimated through acclamation , right of conquest or a combination of means. If a young child is crowned the monarch, then a regent is often appointed to govern until the monarch reaches the requisite adult age to rule. Monarchs' actual powers vary from one monarchy to another and in different eras; on one extreme, they may be autocrats ( absolute monarchy ) wielding genuine sovereignty ; on

10209-507: The nine Rulers of the Malay states of Malaysia (those nine of the thirteen states of Malaysia that have hereditary royal rulers), elected by Majlis Raja-Raja ( Conference of Rulers ). Under Brunei 's 1959 constitution, the Sultan of Brunei is the head of state with full executive authority, including emergency powers, since 1962. The Prime Minister of Brunei is a title held by the Sultan. As

10332-404: The onset of the rash. The rash on the mucous membranes ( enanthem ) was extensive. Skin lesions matured slowly, were typically confluent or semi-confluent, and by the seventh or eighth day, they were flat and appeared to be buried in the skin. Unlike ordinary-type smallpox, the vesicles contained little fluid, were soft and velvety to the touch, and may have contained hemorrhages. Malignant smallpox

10455-429: The oral, nasal, or pharyngeal mucosa of an infected person. It was transmitted from one person to another primarily through prolonged face-to-face contact with an infected person. Some infections of laundry workers with smallpox after handling contaminated bedding suggested that smallpox could be spread through direct contact with contaminated objects ( fomites ), but this was found to be rare. Also rarely, smallpox

10578-464: The other being rinderpest (a disease of even-toed ungulates ) in 2011. The term "smallpox" was first used in England in the 16th century to distinguish the disease from syphilis , which was then known as the "great pox". Other historical names for the disease include pox, speckled monster, and red plague. The United States and Russia retain samples of variola virus in laboratories, which has sparked debates over safety . There are two forms of

10701-429: The other they may be ceremonial heads of state who exercise little or no direct power or only reserve powers , with actual authority vested in a parliament or other body ( constitutional monarchy ). A monarch can reign in multiple monarchies simultaneously. For example, the 15 Commonwealth realms are all separate sovereign states, but share the same monarch through personal union . Monarchs, as such, bear

10824-523: The outer layers of skin from the underlying flesh. Patients with confluent smallpox often remained ill even after scabs had formed over all the lesions. In one case series, the case-fatality rate in confluent smallpox was 62%. Referring to the character of the eruption and the rapidity of its development, modified smallpox occurred mostly in previously vaccinated people. It was rare in unvaccinated people, with one case study showing 1–2% of modified cases compared to around 25% in vaccinated people. In this form,

10947-535: The person was infected with variola virus, a severe infection could result, and the person could transmit smallpox to others. Variolation had a 0.5–2 percent mortality rate, considerably less than the 20–30 percent mortality rate of smallpox. Two reports on the Chinese practice of inoculation were received by the Royal Society in London in 1700; one by Dr. Martin Lister who received a report by an employee of

11070-497: The practice arrived in Europe. The idea that inoculation originated in India has been challenged, as few of the ancient Sanskrit medical texts described the process of inoculation. Accounts of inoculation against smallpox in China can be found as early as the late 10th century, and the procedure was widely practiced by the 16th century, during the Ming dynasty . If successful, inoculation produced lasting immunity to smallpox. Because

11193-480: The prime minister, the Sultan presides over the cabinet. Cambodia has been a kingdom since the 1st century. The power of the absolute monarchy was reduced when it became the French Protectorate of Cambodia from 1863 to 1953. It returned to an absolute monarchy from 1953 until the establishment of a republic following the 1970 coup . The monarchy was restored as a constitutional monarchy in 1993 with

11316-442: The prime ministers of the sixteen Commonwealth Realms at the 22nd Commonwealth Heads of Government Meeting. In some monarchies, such as Saudi Arabia , succession to the throne usually first passes to the monarch's next eldest brother and so on through his other brothers, and only after them to the monarch's children ( agnatic seniority ). In some other monarchies (e.g., Jordan ), the monarch chooses who will be his successor within

11439-491: The prodromal illness still occurred but may have been less severe than in the ordinary type. There was usually no fever during the evolution of the rash. The skin lesions tended to be fewer and evolved more quickly, were more superficial, and may not have shown the uniform characteristic of more typical smallpox. Modified smallpox was rarely, if ever, fatal. This form of variola major was more easily confused with chickenpox . In malignant-type smallpox (also called flat smallpox)

11562-409: The royal family, who need not necessarily be his eldest son. Lastly, some monarchies are elective ( UAE , Malaysia , Holy See and Cambodia ), meaning that the monarch is elected instead of assuming office due to direct inheritance. Rules and laws regarding election vary country to country. Whatever the rules of succession, there have been many cases of a monarch being overthrown and replaced by

11685-474: The rulers of Korea were given the title of Hwangje , meaning the "Emperor". Today, Members of the Korean Imperial family continue to participate in numerous traditional ceremonies, and groups exist to preserve Korea's imperial heritage. The Japanese monarchy is now the only monarchy to still use the title of emperor. In modern history, between 1925 and 1979, Iran was ruled by two emperors from

11808-454: The same size since the viral effect progresses more uniformly. A variety of laboratory methods were available for detecting chickenpox in the evaluation of suspected smallpox cases. The earliest procedure used to prevent smallpox was inoculation with variola minor virus (a method later known as variolation after the introduction of smallpox vaccine to avoid possible confusion), which likely occurred in India, Africa, and China well before

11931-479: The second day of the rash the macules had become raised papules . By the third or fourth day, the papules had filled with an opalescent fluid to become vesicles . This fluid became opaque and turbid within 24–48 hours, resulting in pustules . By the sixth or seventh day, all the skin lesions had become pustules. Between seven and ten days the pustules had matured and reached their maximum size. The pustules were sharply raised, typically round, tense, and firm to

12054-491: The separation of variola virus from Taterapox (an Orthopoxvirus of some African rodents including gerbils ) at 3,000 to 4,000 years ago. This is consistent with archaeological and historical evidence regarding the appearance of smallpox as a human disease which suggests a relatively recent origin. If the mutation rate is assumed to be similar to that of the herpesviruses , the divergence date of variola virus from Taterapox has been estimated to be 50,000 years ago. While this

12177-427: The smallpox. Variola major is the severe and most common form, with a more extensive rash and higher fever. Variola minor is a less common presentation, causing less severe disease, typically discrete smallpox, with historical death rates of 1% or less. Subclinical ( asymptomatic ) infections with variola virus were noted but were not common. In addition, a form called variola sine eruptione (smallpox without rash)

12300-520: The spleen, kidney, serous membranes , skeletal muscles, pericardium , liver, gonads and bladder. Historically, this condition was frequently misdiagnosed, with the correct diagnosis made only at autopsy. This form is more likely to occur in pregnant women than in the general population (approximately 16% of cases in unvaccinated pregnant women were early hemorrhagic smallpox, versus roughly 1% in nonpregnant women and adult males). The case fatality rate of early hemorrhagic smallpox approaches 100%. There

12423-425: The temperature fell to near-normal. These lesions rapidly enlarged and ruptured, releasing large amounts of virus into the saliva. Variola virus tended to attack skin cells, causing the characteristic pimples, or macules , associated with the disease. A rash developed on the skin 24 to 48 hours after lesions on the mucous membranes appeared. Typically the macules first appeared on the forehead, then rapidly spread to

12546-470: The term queen regnant refers to a ruling monarch, as distinct from a queen consort , the wife of a reigning king. Some monarchies are non-hereditary. In an elective monarchy , the monarch is elected but otherwise serves as any other monarch. Historical examples of elective monarchy include the Holy Roman Emperors (chosen by prince-electors , but often coming from the same dynasty) and

12669-762: The title "Custodian of the Two Holy Mosques" in reference to the two holiest places in Islam: Masjid al-Haram in Mecca , and Masjid al-Nabawi in Medina . Oman is led by Sultan Haitham bin Tariq Al Said . The Kingdom of Jordan is one of the Middle East 's more modern monarchies is also ruled by a Malik . In Arab and Arabized countries, Malik (absolute King) is the absolute word to render

12792-411: The touch. The pustules were deeply embedded in the dermis, giving them the feel of a small bead in the skin. Fluid slowly leaked from the pustules, and by the end of the second week, the pustules had deflated and began to dry up, forming crusts or scabs. By day 16–20 scabs had formed over all of the lesions, which had started to flake off, leaving depigmented scars. Ordinary smallpox generally produced

12915-475: The vesicular stage. Hemorrhages in the mucous membranes appear to occur less often than in the early hemorrhagic form. Sometimes the rash forms pustules which bleed at the base and then undergo the same process as in ordinary smallpox. This form of the disease is characterized by a decrease in all of the elements of the coagulation cascade and an increase in circulating antithrombin . This form of smallpox occurs anywhere from 3% to 25% of fatal cases, depending on

13038-439: The virulence of the smallpox strain. Most people with the late-stage form die within eight to 10 days of illness. Among the few who recover, the hemorrhagic lesions gradually disappear after a long period of convalescence. The case fatality rate for late hemorrhagic smallpox is around 90–95%. Pregnant women are slightly more likely to experience this form of the disease, though not as much as early hemorrhagic smallpox. Smallpox

13161-442: The virus on chorioallantoic membrane (part of a chicken embryo ) and examining the resulting pock lesions under defined temperature conditions. Strains were characterized by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Serologic tests and enzyme linked immunosorbent assays (ELISA), which measured variola virus-specific immunoglobulin and antigen were also developed to assist in

13284-554: The whole face, proximal portions of extremities, the trunk, and lastly to distal portions of extremities. The process took no more than 24 to 36 hours, after which no new lesions appeared. At this point, variola major disease could take several very different courses, which resulted in four types of smallpox disease based on the Rao classification: ordinary, modified, malignant (or flat), and hemorrhagic smallpox. Historically, ordinary smallpox had an overall fatality rate of about 30%, and

13407-406: Was Jean-Jacques Dessalines , who declared himself Emperor of Haiti on September 22, 1804. Haiti again had an emperor, Faustin I from 1849 to 1859. In South America, Brazil had a royal house ruling as emperor between 1822 and 1889, under emperors Pedro I and Pedro II . Between 1931 and 1983, nine other previous British colonies attained independence as kingdoms. All, including Canada, are in

13530-441: Was a Chinese royal style used in many states rising from the dissolution of Gojoseon , Buyeo , Goguryeo , Baekje , Silla , Balhae , Goryeo , and Joseon . The legendary Dangun Wanggeom founded the first kingdom, Gojoseon. Some scholars maintain that the term Dangun also refers to a title used by all rulers of Gojoseon and that Wanggeom is the proper name of the founder. Gyuwon Sahwa (1675) describes The Annals of

13653-621: Was about 30%, with higher rates among babies. Often, those who survived had extensive scarring of their skin, and some were left blind. The earliest evidence of the disease dates to around 1500 BC in Egyptian mummies . The disease historically occurred in outbreaks . It was one of several diseases introduced by the Columbian exchange to the New World , resulting in large swathes of Native Americans dying . In 18th-century Europe, it

13776-431: Was also called white pox, kaffir pox, Cuban itch, West Indian pox, milk pox, and pseudovariola. The genome of variola major virus is about 186,000 base pairs in length. It is made from linear double stranded DNA and contains the coding sequence for about 200 genes . The genes are usually not overlapping and typically occur in blocks that point towards the closer terminal region of the genome. The coding sequence of

13899-428: Was highly contagious, but generally spread more slowly and less widely than some other viral diseases, perhaps because transmission required close contact and occurred after the onset of the rash. The overall rate of infection was also affected by the short duration of the infectious stage. In temperate areas, the number of smallpox infections was highest during the winter and spring. In tropical areas, seasonal variation

14022-442: Was less evident and the disease was present throughout the year. Age distribution of smallpox infections depended on acquired immunity . Vaccination immunity declined over time and was probably lost within thirty years. Smallpox was not known to be transmitted by insects or animals and there was no asymptomatic carrier state. Transmission occurred through inhalation of airborne variola virus, usually droplets expressed from

14145-657: Was more likely to reach majority age before the death of his father, and primogeniture became increasingly favored over proximity, tanistry, seniority, and election. In 1980, Sweden became the first monarchy to declare equal primogeniture , absolute primogeniture or full cognatic primogeniture , meaning that the eldest child of the monarch, whether female or male, ascends to the throne. Other nations have since adopted this practice: Netherlands in 1983, Norway in 1990, Belgium in 1991, Denmark in 2009, and Luxembourg in 2011. The United Kingdom adopted absolute (equal) primogeniture on April 25, 2013, following agreement by

14268-421: Was nearly always fatal and death usually occurred between the 8th and 12th day of illness. Often, a day or two before death, the lesions turned ashen gray, which, along with abdominal distension, was a bad prognostic sign. This form is thought to be caused by deficient cell-mediated immunity to smallpox. If the person recovered, the lesions gradually faded and did not form scars or scabs. Hemorrhagic smallpox

14391-412: Was not always recognized by other governments or nations, sometimes causing diplomatic problems. During the nineteenth century, many small monarchies in Europe merged with other territories to form larger entities, and following World War I and World War II , many monarchies were abolished , but of those remaining, all except Luxembourg, Liechtenstein, Andorra, Vatican City, and Monaco were headed by

14514-456: Was seen generally in vaccinated persons. This form was marked by a fever that occurred after the usual incubation period and could be confirmed only by antibody studies or, rarely, by viral culture . In addition, there were two very rare and fulminating types of smallpox, the malignant (flat) and hemorrhagic forms, which were usually fatal. The initial symptoms were similar to other viral diseases that are still extant, such as influenza and

14637-459: Was soon practiced all over the world. During the 19th century, the cowpox virus used for smallpox vaccination was replaced by the vaccinia virus. Vaccinia is in the same family as cowpox and variola virus but is genetically distinct from both. The origin of the vaccinia virus and how it came to be in the vaccine are not known. Monarch Philosophers Works A monarch is a head of state for life or until abdication , and therefore

14760-440: Was spread by virus carried in the air in enclosed settings such as buildings, buses, and trains. The virus can cross the placenta , but the incidence of congenital smallpox was relatively low. Smallpox was not notably infectious in the prodromal period and viral shedding was usually delayed until the appearance of the rash, which was often accompanied by lesions in the mouth and pharynx. The virus can be transmitted throughout

14883-404: Was the primary cause of smallpox outbreaks across Asia and most of Africa. Meanwhile, variola minor was more commonly found in regions of Europe, North America, South America, and certain parts of Africa. Variola minor virus, also called alastrim, was a less common form of the virus, and much less deadly. Although variola minor had the same incubation period and pathogenetic stages as smallpox, it

15006-516: Was the variola major strains (the more clinically severe form of smallpox) which spread from Asia between 400 and 1,600 years ago. A second clade included both alastrim (a phenotypically mild smallpox) described from the American continents and isolates from West Africa which diverged from an ancestral strain between 1,400 and 6,300 years before present. This clade further diverged into two subclades at least 800 years ago. A second estimate has placed

15129-420: Was transmitted from one person to another primarily through prolonged face-to-face contact with an infected person or rarely via contaminated objects . Prevention was achieved mainly through the smallpox vaccine . Once the disease had developed, certain antiviral medications could potentially have helped, but such medications did not become available until after the disease was eradicated. The risk of death

#941058