Kate and John Coleman's marriage is strained after the stillbirth of their third child, Jessica, whose loss is particularly hard on Kate, a recovering alcoholic. She and John decide to adopt a 9-year-old Russian girl, Esther, from St. Mariana's Home for Girls, a local orphanage. Their 5-year-old deaf daughter, Max, embraces Esther, but their 12-year-old son, Daniel, is less welcoming.
One night, Kate and John begin to have sex until Esther interrupts them. Kate becomes suspicious when Esther expresses far more knowledge of sex than expected of a child her age. Esther then exhibits hostile behavior in front of Max and Daniel, such as killing an injured pigeon and badly injuring a classmate who was bullying her. Sister Abigail, the head of the orphanage, visits the household, warning Kate and John that tragic events and incidents occur around Esther, including the house fire that killed her last adoptive family. When Sister Abigail leaves, Esther causes her to crash her car on the road and then bludgeons her to death with a hammer. She forces Max to help her move the body and then hides the evidence in Daniel's treehouse. Daniel sees them at the treehouse, and later that night, she interrogates him about what he saw, threatening to castrate him if he tells Kate and John.
As Kate becomes further convinced about Esther's unusual behavior, John believes she is being paranoid and tells Esther to do something nice for Kate. Esther rips out the flowers from Jessica's grave and gives them to Kate as a bouquet. Kate is horrified and roughly grabs Esther's arm in distress, asserting that she did this on purpose. That night, Esther breaks her own arm and falsely blames Kate, causing further strife in Kate and John's marriage. The next day, Esther releases the brake in the car, causing it to roll into oncoming traffic with Max inside. She also points out the wine she found in the kitchen, causing John and Kate's therapist to suggest Kate return to rehab, with John threatening to leave her and take the children if she refuses. Kate discovers that Esther came from an Estonian mental hospital named the Saarne Institute, and the orphanage she claims she was from has no record of her.
When Daniel learns about Sister Abigail's death from Max and searches the treehouse, Esther sets it on fire and attempts to kill him but is thwarted by Max. Daniel is seriously injured, and while in the hospital in ICU, Esther tries to smother him to death with a pillow, but doctors revive him. Kate, enraged, slaps Esther before she is restrained and sedated. That night, Esther dresses provocatively and attempts to seduce John, who threatens to send Esther back to the orphanage after realizing Kate had been right about Esther's behavior.
Esther of Estonia was inspired by the May 2007 media coverage of 34-year-old Barbora Skrlová, an orphan who abused her first adoptive family and ran away from the police when caught. She eventually was found impersonating Adam, a thirteen-year-old boy who had gone missing.
"The movie Orphan comes directly from this unexamined place in popular culture. Esther's shadowy past includes Eastern Europe; she appears normal and sweet, but quickly turns violent and cruel, especially toward her mother. These are clichés. This is the baggage with which we saddle abandoned, orphaned, or disabled children given a fresh start at family life."
Supporting the development and evaluation of new treatments for rare diseases is a key priority for the FDA. The FDA has authority to grant orphan drug designation to a drug or biological product to prevent, diagnose or treat a rare disease or condition. Orphan drug designation qualifies sponsors for incentives including:
Sponsors seeking orphan drug designation for a drug must submit a request for designation to the agency. Sponsors requesting designation of the same drug for the same rare disease or condition as a previously designated product must submit their own data and information to support their designation request. Orphan drug designation is a separate process from seeking approval or licensing. Drugs for rare diseases go through the same rigorous scientific review process as any other drug for approval or licensing.
In common usage, only a child who has lost both parents due to death is called an orphan. When referring to animals, only the mother's condition is usually relevant (i.e. if the female parent has gone, the offspring is an orphan, regardless of the father's condition).
Various groups use different definitions to identify orphans. One legal definition used in the United States is a minor bereft through "death or disappearance of, abandonment or desertion by, or separation or loss from, both parents".
In the common use, an orphan does not have any surviving parent to care for them. However, the United Nations Children's Fund (UNICEF), Joint United Nations Programme on HIV and AIDS (UNAIDS), and other groups label any child who has lost one parent as an orphan. In this approach, a maternal orphan is a child whose mother has died, a paternal orphan is a child whose father has died, and a double orphan is a child/teen/infant who has lost both parents. This contrasts with the older use of half-orphan to describe children who had lost only one parent.
Orphans are relatively rare in developed countries, because most children can expect both of their parents to survive their childhood. Much higher numbers of orphans exist in war-torn nations such as Afghanistan.
Famous orphans include world leaders such as Aaron Burr, Andrew Jackson, and Pedro II of Brazil; writers such as Edgar Allan Poe and Leo Tolstoy; and athletes such as Aaron Hernandez. The American orphan Henry Darger portrayed the horrible conditions of his orphanage in his art work. Other notable orphans include entertainment greats such as Louis Armstrong, Marilyn Monroe, Babe Ruth, Ray Charles and Frances McDormand, and innumerable fictional characters in literature and comics.
Orphaned characters are extremely common as literary protagonists, especially in children's and fantasy literature. The lack of parents leaves the characters to pursue more interesting and adventurous lives, by freeing them from familial obligations and controls, and depriving them of more prosaic lives. It creates characters that are self-contained and introspective and who strive for affection. Orphans can metaphorically search for self-understanding through attempting to know their roots. Parents can also be allies and sources of aid for children, and removing the parents makes the character's difficulties more severe. Parents, furthermore, can be irrelevant to the theme a writer is trying to develop, and orphaning the character frees the writer from the necessity to depict such an irrelevant relationship; if one parent-child relationship is important, removing the other parent prevents complicating the necessary relationship. All these characteristics make orphans attractive characters for authors.
A number of well-known authors have written books featuring orphans. Examples from classic literature include Charlotte Brontë's Jane Eyre, Charles Dickens's Oliver Twist, Mark Twain's Tom Sawyer and Huckleberry Finn , L. M. Montgomery's Anne of Green Gables, Thomas Hardy's Jude the Obscure, and J. R. R. Tolkien's The Lord of the Rings. Among more recent authors, A. J. Cronin, Lemony Snicket, A. F. Coniglio, Roald Dahl and J. K. Rowling, as well as some less well-known authors of famous orphans like Little Orphan Annie have used orphans as major characters. One recurring storyline has been the relationship that the orphan can have with an adult from outside their immediate family as seen in Lyle Kessler's play Orphans.
Orphans are especially common as characters in comic books. Almost all the most popular heroes are orphans: Superman, Batman, Spider-Man, Robin, The Flash, Captain Marvel, Captain America, and Green Arrow were all orphaned. Orphans are also very common among villains: Bane, Catwoman, and Magneto are examples. Lex Luthor, Deadpool, and Carnage can also be included on this list, though they killed one or both of their parents. Supporting characters befriended by the heroes are also often orphans, including the Newsboy Legion and Rick Jones.
Many religious texts, including the Bible and the Quran, contain the idea that helping and defending orphans is a very important and God-pleasing matter. The religious leaders Moses and Muhammad were orphaned as children. Several scriptural citations describe how orphans should be treated:
About 26 million people living in the European Union (EU) suffer from a rare disease. The European Medicines Agency (EMA) plays a central role in facilitating the development and authorisation of medicines for rare diseases, which are termed 'orphan medicines' in the medical world.
Applications for orphan designation are examined by the EMA's Committee for Orphan Medicinal Products (COMP), using the network of experts that the Committee has built up. The evaluation process takes a maximum of 90 days from validation.
The Agency sends the COMP opinion to the European Commission, which is responsible for granting the orphan designation. The full list of orphan designations is available in the Community register of orphan medicinal products for human use.
Developing medicines intended for small numbers of patients has little commercial incentive under normal market conditions. Therefore, the EU offers a range of incentives to encourage the development of designated orphan medicines.
Sponsors who obtain orphan designation benefit from protocol assistance, a type of scientific advice specific for designated orphan medicines, and market exclusivity once the medicine is on the market. Fee reductions are also available depending on the status of the sponsor and the type of service required.
Applicants from the academic sector are eligible to receive free protocol assistance for developing orphan medicines, as of 19 June 2020. For more information seeAcademia andFees payable to the European Medicines Agency. 041b061a72