title: Eukaryote

text: The presence of eukaryotic-specific biomarkers (steranes) in Australian shales previously indicated that eukaryotes were present in these rocks dated at 2.7 billion years old, which was even 300 million years older than the first geological records of the appreciable amount of molecular oxygen during the Great Oxidation Event. However, these Archaean biomarkers were eventually rebutted as later contaminants. Currently, putatively the oldest biomarker records are only ~800 million years old. In contrast, a molecular clock analysis suggests the emergence of sterol biosynthesis as early as 2.3 billion years ago, and thus there is a huge gap between molecular data and geological data, which hinders a reasonable inference of the eukaryotic evolution through biomarker records before 800 million years ago. The nature of steranes as eukaryotic biomarkers is further complicated by the production of sterols by some bacteria.


title: Eukaryote

text: Whenever their origins, eukaryotes may not have become ecologically dominant until much later; a massive uptick in the zinc composition of marine sediments has been attributed to the rise of substantial populations of eukaryotes, which preferentially consume and incorporate zinc relative to prokaryotes, approximately a billion years after their origin (at the latest).


title: Eukaryote

text: In April 2019, biologists reported that the very large medusavirus, or a relative, may have been responsible, at least in part, for the evolutionary emergence of complex eukaryotic cells from simpler prokaryotic cells.


title: Eukaryote

text: The nuclear DNA and genetic machinery of eukaryotes is more similar to Archaea than Bacteria, leading to a controversial suggestion that eukaryotes should be grouped with Archaea in the clade Neomura. In other respects, such as membrane composition, eukaryotes are similar to Bacteria. Three main explanations for this have been proposed:


title: Eukaryote

text: Assuming no other group is involved, there are three possible phylogenies for the Bacteria, Archaea, and Eukaryota in which each is monophyletic. These are labelled 1 to 3 in the table below, with a modification of hypothesis 2 making the 4th column: The "eocyte hypothesis", in which the Archaea are paraphyletic. (The table and the names for the hypotheses are based on Harish & Kurland, 2017.)


title: Eukaryote

text: In recent years, most researchers have favoured either the three domains (3D) or the eocyte hypothesis. An rRNA analysis supports the eocyte scenario, apparently with the Eukaryote root in Excavata. A cladogram supporting the eocyte hypothesis, positioning eukaryotes within Archaea, based on phylogenomic analyses of the Asgard archaea, is:


title: Eukaryote

text: In this scenario, the Asgard group is seen as a sister taxon of the TACK group, which comprises Thermoproteota (formerly named eocytes or Crenarchaeota), Nitrososphaerota (formerly Thaumarchaeota), and others. This group is reported contain many of the eukaryotic signature proteins and produce vesicles.


title: Eukaryote

text: In 2017, there was significant pushback against this scenario, arguing that the eukaryotes did not emerge within the Archaea. Cunha "et al." produced analyses supporting the three domains (3D) or Woese hypothesis (2 in the table above) and rejecting the eocyte hypothesis (4 above). Harish and Kurland found strong support for the earlier two empires (2D) or Mayr hypothesis (1 in the table above), based on analyses of the coding sequences of protein domains. They rejected the eocyte hypothesis as the least likely. A possible interpretation of their analysis is that the universal common ancestor (UCA) of the current tree of life was a complex organism that survived an evolutionary bottleneck, rather than a simpler organism arising early in the history of life. On the other hand, the researchers who came up with Asgard re-affirmed their hypothesis with additional Asgard samples. Since then, the publication of additional Asgard archaeal genomes and the independent reconstruction of phylogenomic trees by multiple independent laboratories have provided additional support for an Asgard archaeal origin of eukaryotes.


title: Eukaryote

text: Details of the relation of Asgard archaea members and eukaryotes are still under consideration, although, in January 2020, scientists reported that "Candidatus Prometheoarchaeum syntrophicum", a type of cultured Asgard archaea, may be a possible link between simple prokaryotic and complex eukaryotic microorganisms about two billion years ago.


title: Eukaryote

text: The origins of the endomembrane system and mitochondria are also unclear. The phagotrophic hypothesis proposes that eukaryotic-type membranes lacking a cell wall originated first, with the development of endocytosis, whereas mitochondria were acquired by ingestion as endosymbionts. The syntrophic hypothesis proposes that the proto-eukaryote relied on the proto-mitochondrion for food, and so ultimately grew to surround it. Here the membranes originated after the engulfment of the mitochondrion, in part thanks to mitochondrial genes (the hydrogen hypothesis is one particular version).


title: Eukaryote

text: In a study using genomes to construct supertrees, Pisani "et al." (2007) suggest that, along with evidence that there was never a mitochondrion-less eukaryote, eukaryotes evolved from a syntrophy between an archaea closely related to Thermoplasmatales and an alphaproteobacterium, likely a symbiosis driven by sulfur or hydrogen. The mitochondrion and its genome is a remnant of the alphaproteobacterial endosymbiont. The majority of the genes from the symbiont have been transferred to the nucleus. They make up most of the metabolic and energy-related pathways of the eukaryotic cell, while the information system (DNA polymerase, transcription, translation) is retained from archaea.


title: Eukaryote

text: Different hypotheses have been proposed as to how eukaryotic cells came into existence. These hypotheses can be classified into two distinct classes – autogenous models and chimeric models.


title: Eukaryote

text: Autogenous models propose that a proto-eukaryotic cell containing a nucleus existed first, and later acquired mitochondria. According to this model, a large prokaryote developed invaginations in its plasma membrane in order to obtain enough surface area to service its cytoplasmic volume. As the invaginations differentiated in function, some became separate compartments – giving rise to the endomembrane system, including the endoplasmic reticulum, golgi apparatus, nuclear membrane, and single membrane structures such as lysosomes.


title: Eukaryote

text: Mitochondria are proposed to come from the endosymbiosis of an aerobic proteobacterium after an eukaryote with a nucleus has evolved. This theory is less held onto because it requires extra assumptions to explain current conditions. For example, as every known eukaryote has a mitochondrion (or at least show signs of having an ancestor that had), one must assumed that all the eukaryotic lineages that did not acquire mitochondria became extinct. The theory also doesn’t explain why anaerobic variants of mitochondria have evolved.


title: Eukaryote

text: Chimeric models claim that two prokaryotic cells existed initially – an archaeon and a bacterium. The closest living relatives of these appears to be Asgardarchaeota and (distantly related) the alphaproteobacteria called the proto-mitochondrion. These cells underwent a merging process, either by a physical fusion or by endosymbiosis, thereby leading to the formation of a eukaryotic cell. Within these chimeric models, some studies further claim that mitochondria originated from a bacterial ancestor while others emphasize the role of endosymbiotic processes behind the origin of mitochondria.


title: Eukaryote

text: The inside-out hypothesis suggests that the fusion between free-living mitochondria-like bacteria, and an archaeon into a eukaryotic cell happened gradually over a long period of time, instead of in a single phagocytotic event. In this scenario, an archaeon would trap aerobic bacteria with cell protrusions, and then keep them alive to draw energy from them instead of digesting them. During the early stages the bacteria would still be partly in direct contact with the environment, and the archaeon would not have to provide them with all the required nutrients. But eventually the archaeon would engulf the bacteria completely, creating the internal membrane structures and nucleus membrane in the process.


title: Eukaryote

text: It is assumed the archaean group called halophiles went through a similar procedure, where they acquired as much as a thousand genes from a bacterium, way more than through the conventional horizontal gene transfer that often occurs in the microbial world, but that the two microbes separated again before they had fused into a single eukaryote-like cell.


title: Eukaryote

text: An expanded version of the inside-out hypothesis proposes that the eukaryotic cell was created by physical interactions between two prokaryotic organisms and that the last common ancestor of eukaryotes got its genome from a whole population or community of microbes participating in cooperative relationships to thrive and survive in their environment. The genome from the various types of microbes would complement each other, and occasional horizontal gene transfer between them would be largely to their own benefit. This accumulation of beneficial genes gave rise to the genome of the eukaryotic cell, which contained all the genes required for independence.


title: Eukaryote

text: According to serial endosymbiotic theory (championed by Lynn Margulis), a union between a motile anaerobic bacterium (like "Spirochaeta") and a thermoacidophilic crenarchaeon (like "Thermoplasma" which is sulfidogenic in nature) gave rise to the present day eukaryotes. This union established a motile organism capable of living in the already existing acidic and sulfurous waters. Oxygen is known to cause toxicity to organisms that lack the required metabolic machinery. Thus, the archaeon provided the bacterium with a highly beneficial reduced environment (sulfur and sulfate were reduced to sulfide). In microaerophilic conditions, oxygen was reduced to water thereby creating a mutual benefit platform. The bacterium on the other hand, contributed the necessary fermentation products and electron acceptors along with its motility feature to the archaeon thereby gaining a swimming motility for the organism.


title: Eukaryote

text: From a consortium of bacterial and archaeal DNA originated the nuclear genome of eukaryotic cells. Spirochetes gave rise to the motile features of eukaryotic cells. Endosymbiotic unifications of the ancestors of alphaproteobacteria and cyanobacteria, led to the origin of mitochondria and plastids respectively. For example, "Thiodendron" has been known to have originated via an ectosymbiotic process based on a similar syntrophy of sulfur existing between the two types of bacteria – "Desulfobacter" and "Spirochaeta".


title: Eukaryote

text: However, such an association based on motile symbiosis has never been observed practically. Also there is no evidence of archaeans and spirochetes adapting to intense acid-based environments. In addition, the theory posits that mitochondrion-less eukaryotes have existed, tying back to the problem in the autogenous model.


title: Eukaryote

text: In the hydrogen hypothesis, the symbiotic linkage of an anaerobic and autotrophic methanogenic archaeon (host) with an alphaproteobacterium (the symbiont) gave rise to the eukaryotes. The host used hydrogen (H) and carbon dioxide () to produce methane while the symbiont, capable of aerobic respiration, expelled H and as byproducts of anaerobic fermentation process. The host's methanogenic environment worked as a sink for H, which resulted in heightened bacterial fermentation.


title: Eukaryote

text: Endosymbiotic gene transfer acted as a catalyst for the host to acquire the symbionts' carbohydrate metabolism and turn heterotrophic in nature. Subsequently, the host's methane forming capability was lost. Thus, the origins of the heterotrophic organelle (symbiont) are identical to the origins of the eukaryotic lineage. In this hypothesis, the presence of H represents the selective force that forged eukaryotes out of prokaryotes.


title: Eukaryote

text: The syntrophy hypothesis was developed in contrast to the hydrogen hypothesis and proposes the existence of two symbiotic events. According to this model, the origin of eukaryotic cells was based on metabolic symbiosis (syntrophy) between a methanogenic archaeon and a deltaproteobacterium. This syntrophic symbiosis was initially facilitated by H transfer between different species under anaerobic environments. In earlier stages, an alphaproteobacterium became a member of this integration, and later developed into the mitochondrion. Gene transfer from a deltaproteobacterium to an archaeon led to the methanogenic archaeon developing into a nucleus. The archaeon constituted the genetic apparatus, while the deltaproteobacterium contributed towards the cytoplasmic features.


title: Eukaryote

text: A complex scenario of 6+ serial endosymbiotic events of archaea and bacteria has been proposed in which mitochondria and an asgard related archaeota were acquired at a late stage of eukaryogenesis, possibly in combination, as a secondary endosymbiont. The findings have been rebuked as an artifact.


title: Hannibal (2001 film)

text: Hannibal is a 2001 psychological crime thriller film directed by Ridley Scott and based on the 1999 novel by Thomas Harris. A sequel to the 1991 film "The Silence of the Lambs", the plot follows disgraced FBI special agent Clarice Starling as she attempts to apprehend cannibalistic serial killer Hannibal Lecter before his surviving victim, Mason Verger, captures him. Anthony Hopkins reprises his role as Lecter, while Julianne Moore replaces Jodie Foster as Starling and Gary Oldman plays Verger. Ray Liotta, Frankie R. Faison, Giancarlo Giannini, and Francesca Neri also star.


title: Hannibal (2001 film)

text: Following the release of "The Silence of the Lambs", Harris spent several years writing a sequel novel. Foster and "Silence of the Lambs" director Jonathan Demme initially planned to return for the sequel, but they and screenwriter Ted Tally declined because they found it too lurid. Scott became attached while directing "Gladiator" (2000), and signed on after reading the script pitched by Dino De Laurentiis, who had produced "Manhunter" (1986), the first Lecter film. David Mamet and Steven Zaillian wrote the screenplay, and principal photography commenced in May 2000, lasting sixteen weeks.


title: Hannibal (2001 film)

text: "Hannibal" was released on 9 February 2001, ten years after "The Silence of the Lambs". It was highly anticipated and broke box office records in the United States, Australia, Canada and the United Kingdom, and grossed $351.6 million during its theatrical run. It received mixed reviews; critics praised the performances and visuals, but deemed it inferior to "The Silence of the Lambs" and criticized its violence. It was followed by a prequel, "Red Dragon", in 2002, with Hopkins reprising his role as Lecter.


title: Hannibal (2001 film)

text: A decade after tracking down serial killer Jame Gumb, FBI Special Agent Clarice Starling is blamed for a botched drug raid which resulted in the deaths of six people. Starling is contacted by Mason Verger, the only surviving victim of the cannibalistic serial killer Hannibal Lecter, who has been missing since escaping custody during the Gumb investigation. A wealthy child molester, Verger was paralyzed and disfigured by Lecter during a therapy session. He has been pursuing an elaborate scheme to capture, torture, and kill Lecter ever since. Using his wealth and political influence, Verger has Starling reassigned to Lecter's case, hoping her involvement will draw Lecter out.


title: Hannibal (2001 film)

text: After learning of Starling's disgrace, Lecter sends her a letter. A perfume expert identifies a fragrance on the letter: skin cream with ingredients only available to a few shops in the world. She contacts the police departments of the cities where the shops are located, requesting surveillance tapes. In Florence, Chief Inspector Rinaldo Pazzi is investigating the disappearance of a library curator. Pazzi questions Lecter, who is masquerading as Dr. Fell, the assistant curator and caretaker.


title: Hannibal (2001 film)

text: Recognizing Dr. Fell in the surveillance tape, Pazzi accesses the Violent Criminal Apprehension Program database of wanted fugitives. He learns of Verger's US$3 million personal bounty on Lecter. Seeking the bounty, Pazzi ignores Starling's warnings and attempts to capture Lecter alone. He recruits a pickpocket to obtain Lecter's fingerprint to show Verger as proof. The pickpocket manages to get the print and gives it to Pazzi, but is fatally wounded in the process when Lecter severs his femoral artery. Lecter baits Pazzi into an isolated room of the Palazzo Vecchio, ties him up, disembowels him, and hangs him from the balcony.


title: Hannibal (2001 film)

text: Verger bribes Justice Department official Paul Krendler to accuse Starling of withholding a note from Lecter, leading to her suspension. Lecter then gets Starling to come to Union Station while speaking with her through mobile phones. Verger's men, having trailed Starling, capture and bring Lecter to Verger. Verger intends to feed Lecter alive to a herd of wild boars bred for this purpose. After her superiors refuse to act, Starling infiltrates Verger's estate. After neutralizing two guards and freeing Lecter, she is shot by a third guard. Lecter picks up an unconscious Starling just before the boars break through the doors, devouring the two guards but ignoring Lecter. Verger orders his physician Cordell Doemling to shoot Lecter. At Lecter's suggestion, Cordell shoves his hated boss into the pen with Lecter offering to take the blame. Lecter carries Starling away while Verger is eaten alive by his own boars.


title: Hannibal (2001 film)

text: Lecter takes Starling to Krendler's secluded lake house and treats her wound. When Krendler arrives, Lecter subdues and drugs him. Starling, disoriented by morphine and dressed in a cocktail dress, awakens to find Krendler seated at the table set for an elegant dinner. Weakened by the drugs, she watches in horror as Lecter opens Krendler's skull, removes part of his brain, sautés it, and feeds it to him. Starling tries to attack Lecter, but he overpowers her and traps her hair in a refrigerator door. He kisses her; while he is distracted, she handcuffs his wrist to hers. Hearing the police closing in, Lecter raises a cleaver over her hand. Afterwards, Starling surrenders to the FBI with her hands intact.


title: Hannibal (2001 film)

text: On a flight, Lecter prepares to eat a meal he has brought himself while wearing his bandaged arm in a sling. Lecter shares Krendler's cooked brain with a curious boy who was watching him eat, saying it is important "always to try new things".


title: Hannibal (2001 film)

text: "The Silence of the Lambs", based on the 1988 novel by Thomas Harris, was released in 1991 to critical and commercial success, winning five Academy Awards. Harris spent several years writing a sequel novel; "Silence of the Lambs" director Jonathan Demme expressed interest in developing a film adaptation when the novel was complete.


title: Hannibal (2001 film)

text: The film rights to the Lecter character were owned by producer couple Dino De Laurentiis and Martha De Laurentiis. After producing the first Lecter film, "Manhunter," in 1986, they allowed Orion Pictures to produce "The Silence of Lambs" free without their involvement. When "The Silence of the Lambs" became a success, the couple became eager for a new Lecter novel they could adapt. After a lengthy wait, De Laurentiis received a call from Harris telling him he had finished the novel and De Laurentiis purchased the rights for a record $10 million.


title: Hannibal (2001 film)

text: In April 1999, the "Los Angeles Times" reported that the budget for an adaptation of "Hannibal" could cost as much as $100 million. It speculated that both Jodie Foster and Anthony Hopkins would receive $15 million each to reprise their roles and that Demme would receive $5 million to $19 million. Mort Janklow, Harris's agent at the time, told the "Los Angeles Times" that Foster, Hopkins, and Demme would soon receive manuscripts of the novel, claiming it would make an unbelievable film. The novel sold out of its initial 1.6 million print run in the 1999, and went on to sell millions of copies.


title: Hannibal (2001 film)

text: Demme declined the invitation to direct, as he reportedly found the material lurid and too gory. In the 2010 Biography Channel documentary "Inside Story: The Silence of the Lambs", Demme said: "Tom Harris, as unpredictable as ever, took Clarice and Dr. Lecter's relationship in a direction that just didn't compute for me. And Clarice is drugged up, and she's eating brains with him, and I just thought, 'I can't do this.'" De Laurentiis said of Demme's decision to decline: "When the pope dies, we create a new pope. Good luck to Jonathan Demme. Good-bye." He later said that Demme felt he could not make a sequel as good as "The Silence of the Lambs".


title: Hannibal (2001 film)

text: De Laurentiis visited Ridley Scott on the set of "Gladiator" and suggested he direct "Hannibal". Scott, who was conducting principal photography on "Gladiator," thought De Laurentiis was speaking about the Carthaginian general and replied: "Dino, I'm doing a Roman epic right now. I don't wanna do elephants coming over the Alps next, old boy."


title: Hannibal (2001 film)

text: Scott read the manuscript in four sittings within a week, seeing it as a "symphony", and expressed his desire to direct. He said: "I haven't read anything so fast since "The Godfather". It was so rich in all kinds of ways." Scott had reservations with the ending of the novel, in which Lecter and Starling become lovers: "I couldn't take that quantum leap emotionally on behalf of Starling. Certainly, on behalf of Hannibal—I'm sure that's been in the back of his mind for a number of years. But for Starling, no. I think one of the attractions about Starling to Hannibal is what a straight arrow she is." He also did not find the book believable after the opera scene, "which became like a vampire movie". Harris gave Scott permission to change the ending.


title: Hannibal (2001 film)

text: Ted Tally, screenwriter for "The Silence of the Lambs", was another key member of the "Silence of the Lambs" team to decline involvement. Tally, like Demme, had problems with the novel's "excesses". David Mamet was the first screenwriter to produce a draft, which, according to Scott and the producers, needed major revisions. Stacey Snider, co-chairman of Universal Pictures, said: "There's no way David was going to read 15 pages of our notes and then be available to work on the script day-to-day." A script review at ScreenwritersUtopia.com describes the Mamet draft as "stunningly bad" but found Zaillian's rewrite "gripping entertainment". Scott praised Mamet as fast and efficient, but said he passed on his draft because it needed work and he feared Mamet, who was soon directing his own film, would be too busy to redraft it.


title: Hannibal (2001 film)

text: Steven Zaillian, writer of "Schindler's List", initially declined to write "Hannibal", saying he was busy and that "you can almost never win when you do a sequel". He changed his mind, as "it's hard to say no to Dino once and it's almost impossible to say no to him twice". Scott said there were "very few rewrites once I brought in Steve Zaillian ... If you were to ask who were the best three screenwriters in the business, Steve Zaillian would be one of them. We discussed "Hannibal" endlessly." One of Zaillian's key objectives was to revise Mamet's script until it pleased all parties, meaning that the "love story" would be told by suggestion instead of by "assault". Scott worked through the script with Zaillian for 28 days, making him "sweat through it with him and discuss every inch of the way with him". After 25 days, Scott suddenly realized that Zaillian was "exorcising the 600 pages of the book. He was distilling through discussion what he was gonna finally do ... Frankly I could have just made it."


title: Hannibal (2001 film)

text: It was unclear if Jodie Foster (Clarice Starling) and Anthony Hopkins (Hannibal Lecter) would reprise their respective roles for which they won Academy Awards in "The Silence of the Lambs" (Best Actress/Best Actor). Both Hopkins and Foster had expressed interest. It became apparent that the producers and the studio could do without one of the original "stars" and would go on to find a replacement. The withdrawal of both Foster and Hopkins could possibly have been terminal for the project, however. De Laurentiis confirmed this after the film's release: "First and foremost, I knew we had no movie without Anthony Hopkins."


title: Hannibal (2001 film)

text: Foster told Larry King in 1997 that she "would definitely be part of" a sequel to "The Silence of the Lambs". In the same year, she told "Entertainment Weekly:" "Anthony Hopkins always talks about it. I mean, everybody wants to do it. Every time I see him, it's like: 'When is it going to happen? When is it going to happen?'" De Laurentiis thought Foster would decline once she read the book, and believed the final film was better for it. Hopkins also had doubts Foster would be involved, saying he had a "hunch" she would not be.


title: Hannibal (2001 film)

text: Foster confirmed that she had turned down the film in December 1999. This caused problems for Universal and production partner Metro-Goldwyn-Mayer. "The studio is just back from the holiday and is regrouping based on the news, and has no cohesive game plan at the moment," said Kevin Misher, Universal's President of Production. Misher added that, "It was one of those moments when you sit down and think, 'Can Clarice be looked upon as James Bond for instance? A character who is replaceable?' Or was Jodie Foster Clarice Starling, and the audience will not accept anyone else?" Foster said in December 1999 that the characterization of Starling in "Hannibal" had "negative attributes" and "betrayed" the original character.


title: Hannibal (2001 film)

text: Foster's spokeswoman said she declined because Claire Danes had become available for Foster's film "". "Entertainment Weekly" described the "Hannibal" project as having become "a bloody mess, hemorrhaging talent and money" despite Hopkins being on board. In 2005, after the film had been released, Foster told "Total Film": "The official reason I didn't do "Hannibal" is I was doing another movie, "Flora Plum". So I get to say, in a nice dignified way, that I wasn't available when that movie was being shot ... Clarice meant so much to Jonathan and I, she really did, and I know it sounds kind of strange to say but there was no way that either of us could really trample on her."


title: Hannibal (2001 film)

text: When it became clear that Foster would skip "Hannibal", the production team considered several different actresses, including Cate Blanchett, Angelina Jolie, Gillian Anderson, Hilary Swank, Ashley Judd, Helen Hunt and Julianne Moore. Hopkins asked his agent if he had any "power" over casting. He informed De Laurentiis that he knew Moore, with whom he had worked on "Surviving Picasso", and thought her a "terrific actress". Although Hopkins' agent told him he had no contractual influence on casting, Scott thought it correct to discuss who would be Hopkins' "leading lady". Scott said he was "really surprised to find that [he] had five of the top actresses in Hollywood wanting it."


title: Hannibal (2001 film)

text: Scott said his decision was swayed in favor of Moore: "She is a true chameleon. She can be a lunatic in "Magnolia", a vamp in "An Ideal Husband", a porn star in "Boogie Nights" and a romantic in "The End of the Affair"." "Julianne Moore, once Jodie decided to pass, was always top of my list," said Scott on his female lead. Moore talked about stepping into a role made famous by another actress: "The new Clarice would be very different. Of course people are going to compare my interpretation with that of Jodie Foster's ... but this film is going to be very different."


title: Hannibal (2001 film)

text: Hopkins was generally expected to reprise his Academy Award-winning role. Hopkins said in June 1999 that he would only be interested if the script was "really good". Hopkins said he could not make up his mind to commit: "I was kind of surprised by this book, "Hannibal". I thought it was really overreaching and so bizarre. So I couldn't make up my mind about it all. Some of it I found intriguing, some I was a little doubtful about." When the producers confirmed that they were going to film Harris' novel, Hopkins told them yes, but added: "It needs some condensing." "The Hollywood Reporter" confirmed that Hopkins had agreed to reprise his role in late December 1999, saying he had approved the latest draft of the script.


title: Hannibal (2001 film)

text: Hopkins said he had no difficulty moving back into "Lecter's mind". "I just learned the lines and showed up and walked around as Hannibal Lecter. I thought, 'Do I repeat that same performance, or do I vary it?' Ten years had passed so I changed a bit." In the book, Lecter uses bandages to disguise himself as a plastic surgery patient. This was left out of the film because Scott and Hopkins agreed to leave the face alone. Hopkins said: "It's as if he's making a statement—'catch me if you can'. With his big hat, he's so obvious that nobody thinks he's Hannibal Lecter. I've always thought he's a very elegant man, a Renaissance man." In the film, Lecter is first seen in Florence "as the classical Lecter, lecturing and being smooth", according to Hopkins. When the film moves to the U.S., Hopkins changed his appearance by building up muscle and cropping his hair short "to make him like a mercenary, that he would be so fit and so strong that he could just snap somebody in two if they got ... in his way".


title: Hannibal (2001 film)

text: The part of Mason Verger, one of Lecter's two surviving victims, was originally offered to Christopher Reeve based on his work as a police officer who uses a wheelchair in "Above Suspicion" (1995). Not having read the novel, Reeve showed initial interest in the role, but ultimately declined upon realizing that Verger was a quadriplegic, facially-disfigured child rapist. The part was later accepted by secondary choice Gary Oldman. Co-producer Martha De Laurentiis claimed they had a "funny situation" with Oldman wanting a prominent "credit". She said: "Now how can you have a prominent credit with "Hannibal"? The characters are Hannibal and Clarice Starling. So we really couldn't work something out (at first)." Oldman was apparently "out" of the film for a while, but then came back in, asking to go "unbilled". Oldman would become transformed and "unrecognizable as himself" to play the part of Verger. He would have no lips, cheeks or eyelids. Make-up artist Greg Cannom said: "It's really disgusting ... I've been showing people pictures [of Oldman as Verger], and they all just say 'Oh my God,' and walk away, which makes me very happy." Oldman said that having his name completely removed from the billing and credits allowed him to "do it anonymously" under the heavy make-up.


title: Hannibal (2001 film)

text: Other stars subsequently cast included Ray Liotta as U.S. Justice Department official Paul Krendler (the character had appeared in "The Silence of the Lambs", but original actor Ron Vawter had died in the interim) and Italian actor Giancarlo Giannini as Detective Rinaldo Pazzi. Francesca Neri played Pazzi's wife, Allegra. Frankie Faison reprised his role as orderly Barney Matthews, remaining the only actor to play a role in all "Lecter" feature films (until "Hannibal Rising" in 2007), including "Manhunter".


title: Hannibal (2001 film)

text: Scott recruited key production crew whom he had worked with previously. Production designer Norris Spencer had worked on "Thelma & Louise", "Black Rain" and "". Cinematographer John Mathieson, editor Pietro Scalia and composer Hans Zimmer had all worked on Scott's previous film "Gladiator".


title: Hannibal (2001 film)

text: "Hannibal" was filmed in 83 working days over 16 weeks. The film began production on 8 May 2000 in Florence. The film visited key locations in Florence and various locations around the United States. Martha De Laurentiis said the film has almost a hundred locations and that it was a "constant pain of moving and dressing sets. But the locations were beautiful. Who could complain about being allowed to shoot in Palazzo Vecchio in Florence? Or President James Madison's farm in Montpelier or the amazing Biltmore Estate in Asheville?" Eighty million dollars and a year and a half in production were spent before Scott got his first look at "Hannibal" in the editing room.


title: Hannibal (2001 film)

text: Make-up artist Greg Cannom was pleased to be involved in "Hannibal" as it offered him the chance to produce "incredible and original make-ups". For Mason Verger, the make-up team would initially produce 20 different heads which looked like zombies and did not reflect the vision Scott had of the character; Scott wanted Verger to look real with hideous scarring, and not something from the "House of Wax". Scott himself would actually call up the help of expert doctors in an effort to get the look of the character as realistic as possible. Scott showed the make-up team pictures of foetal things, which he thought touching; he wanted to make Mason Verger more touching than monstrous, as he thought of Verger as being someone who hadn't lost his sense of humour ... almost sympathetic. Oldman would spend six hours a day in make-up to prepare for the role.


title: Hannibal (2001 film)

text: For one of the film's final and infamous scenes, an exact duplicate was created of the character Paul Krendler, played by Ray Liotta, a scene which blended make-up, puppet work and CGI in a way which Scott called "seamless".


title: Hannibal (2001 film)

text: The main titles were designed by Nick Livesey, a graduate of the Royal College of Art who worked for one of Scott's production companies in London. The sequence, shot in Florence by Livesey himself was intended as the film's second promotional trailer. The studio thought it not "quite right", but it remained on Scott's mind and would eventually end up as the main title sequence. Livesey would gather footage of pigeons in an empty square in Florence early one morning which, in the final cut, would morph into the face of Hannibal Lecter. Scott believed it a good idea, as it fundamentally asked the question: 'Where is Hannibal Lecter?' Scott explains: "And of course this story tells it, with pigeons in the cobblestones of somewhere, where you wonder where that is ... and there he is... his face appears." The titles are said to have been influenced by the film "Seven".


title: Hannibal (2001 film)

text: Ridley Scott worked very closely with composer Hans Zimmer, during post-production on "Hannibal". Scott believes the music to a film is as important as dialogue—"It is the final adjustment to the screenplay, being able to also adjust the performance of the actors in fact." Zimmer and Scott sat in during the editing process with editor Pietro Scalia to discuss scenes in the film and "not music". Zimmer used a symphony orchestra for the opera sequence, but would mostly use what he described as a "very odd orchestra ... only cellos and basses all playing at the extreme ends of their range." This was done to emphasise the character of Lecter. He explains: "Anthony's character is for me somebody at the extreme range of whatever is humanly imaginable somehow." Zimmer also did not want the score to sound like a "modern day orchestra".


title: Hannibal (2001 film)

text: The character Mason Verger had his own theme, which become more "perverted" as the film progressed, according to Zimmer. Dante's sonnet was put to music by Zimmer and Patrick Cassidy titled Vide cor Meum for the opera scene in Florence. Tracksounds.com wrote positively of Zimmer's score. "Zimmer truly crafts a score worthy of most fans' full attention ... the classical elements, and yes, even the monologue combine to make this an intense listening experience." In a poll by British Classic FM listeners to find the greatest film soundtrack of all time, "Hannibal" ranked at 59. Strauss's "The Blue Danube" is also played at several points in the film.


title: Hannibal (2001 film)

text: Scott has said he believes the underlying emotion of "Hannibal" is "affection". "In some instances, you might even wonder or certainly from one direction—is it more than affection? It is dark, because the story is of course essentially dark, but it's kind of romantic at the same time." Scott openly admits to a "romantic thematic" running through the film. He told CNN that: ""Hannibal" was quite a different target, essentially a study between two individuals. Funny enough, it's rather romantic and also quite humorous, but also there's some quite bad behaviour as well." During the opera scene in Florence, Lecter attends an operatic adaptation of one of Dante's sonnets, and meets with Detective Pazzi and his wife, Allegra. She asks Lecter, "Do you believe a man could become so obsessed by a woman after a single encounter?" Lecter replies: "Yes, I believe he could ... but would she see through the bars of his plight and ache for "him"?" This scene, in the film, is one which Scott claims most people "missed" the meaning of. It was in reference to Starling—to their encounter in "The Silence of the Lambs". "The New York Times", in its review of the film, said "Hannibal", "toys" with the idea of "love that dare not speak its name".


title: Hannibal (2001 film)

text: Composer Hans Zimmer believed there were messages and subtext in each scene. He said, "I can score this movie truly as a Freudian archetypal beauty and the beast fairy tale, as a horror movie, as the most elegant piece, on corruption in the American police force, as the loneliest woman on earth, the beauty in renaissance ..." Zimmer ultimately believes it to be a dark love story, centering on two people who should never be together—a modern-day "Romeo and Juliet". During post-production, Scott, Zimmer and the editor passionately argued about the meaning of Starling's tear during a confrontation with Lecter. They could not agree if it was a tear of "anguish", "loneliness" or "disgust". Scott told the "New York Post" that, the affair of the heart between Lecter and Starling is metaphorical. "Rolling Stone" magazine said in their review, "Scott offers a sly parody of relationships—think 'When Hannibal met Sally'."


title: Hannibal (2001 film)

text: Scott has said he believed Lecter, in his own way, was "pure", whose motivation is the search for "retribution and punishment". "There is something very moral about Lecter in this film," said Scott in his audio commentary. "The behaviour of Hannibal is never insane—[I] didn't want to use that excuse. Is he insane? No, I think he's as sane as you or I. He just likes it." Scott did say, however, "In our normal terms, he's truly evil." Scott also brings up the notion of absolution in reference to Lecter towards the film's end. Verger has one overriding objective in life: to capture Lecter and subject him to a slow, painful death.


title: Hannibal (2001 film)

text: Part of the story involves the character Rinaldo Pazzi (Giancarlo Giannini), a Florentine policeman who learns "Dr. Fell's" true identity and realizes that this knowledge could make him rich. His escalating abandonment of morality allows him to countenance and facilitate the death of a Romani pickpocket, egged on by the desire to have the best for his much younger wife. There is a moment in the film when Pazzi becomes corrupted, despite being what Scott describes as "very thoughtful".


title: Hannibal (2001 film)

text: The first trailer appeared in theaters and was made available via the official website in early May 2000, over nine months before the film's release. As the film had only just begun production, footage was used from "The Silence of the Lambs". A second trailer, which featured footage from the new film, was released in late November 2000. In marketing the film, Hopkins' portrayal of Hannibal Lecter was chosen as the unique selling point of "Hannibal". "Mr Hopkins is the draw here", said Elvis Mitchell in a 2001 "The New York Times" article. A poster released in the UK to promote "Hannibal", featuring Lecter with a "skin mask" covering the right side of his face, was quickly removed from circulation as it was deemed "too shocking and disturbing for the public."


title: Hannibal (2001 film)

text: Upon its release, "Hannibal" was met with significant media attention, with the film's stars and director making several appearances on television, in newspapers and in magazines. In an article for CBS News, Jill Serjeant stated that "the long-awaited sequel to the grisly 1991 thriller "Silence of the Lambs" is cooking up the hottest Internet and media buzz since the 1999 ." Stars Anthony Hopkins and Julianne Moore made the covers of a number of magazines, including "Vanity Fair", "Entertainment Weekly", "Premiere" and "Empire".


title: Hannibal (2001 film)

text: "Hannibal" is available on VHS, as well as a one-disc and two-disc DVD. The two-disc DVD contains an array of special features including: commentary by director Ridley Scott, deleted and alternate scenes, five production featurettes and a "marketing gallery" which contains trailers, production stills and unused poster concepts. While the VHS version features the deleted scenes.


title: Hannibal (2001 film)

text: A special "steel-book" edition of "Hannibal" was released in 2007. There are no significant changes made to the DVD itself; only the package artwork was changed.


title: Hannibal (2001 film)

text: The film was originally released as part of "The Hannibal Lecter Collection" on Blu-ray in 2009. It was re-released as a stand-alone in 2011.


title: Hannibal (2001 film)

text: On February 6, 2019, it was announced that the film would be released on Ultra HD Blu-ray in April. The release includes a new 4K restoration supervised by cinematographer John Mathieson, as well as all special features on the previous two-disc DVD release.


title: Hannibal (2001 film)

text: "Hannibal" grossed $58 million (U.S.) in its opening weekend (from 3,230 screens). At the time (February 2001), this was the third-biggest debut ever behind 1997's "" and 1999's "". It went on to surpass "Scream 3" to have the highest debut in February. That record was surpassed by "The Passion of the Christ" in 2004. The film also had the largest opening weekend for an R-rated film, beating "Scary Movie". "Hannibal" would hold this record until it was taken by "The Matrix Reloaded" in 2003. In October 2012, it was ranked 90th all time. Final domestic box office gross (U.S.) reached $165,092,268, with a worldwide gross of $351,692,268. The film spent three weeks at number one in the U.S. box office chart, and four weeks at number one in the UK, and was the year's third highest-grossing film in that country behind "" and "Harry Potter and the Philosopher's Stone". In Italy, it grossed $4.6 million in its opening weekend, setting a record for a US release, beating "The Blair Witch Project". It also set a record opening week in the Netherlands with $1.3 million in six days, beating "Independence Day". It also had the second biggest opening in Spain with $4.1 million in 6 days. "Hannibal" was the tenth highest-grossing film of the year worldwide, in a year which also saw the blockbuster releases (a year which also had already established franchises such as "The Mummy Returns", "Planet of the Apes", "American Pie 2" and "Jurassic Park III", or would later become big franchises like "The Fast and the Furious", "Shrek", "Monsters, Inc.", "Harry Potter and the Philosopher's Stone", and "". "Hannibal" also made over $87,000,000 in U.S. video rentals following release in August 2001.


title: Hannibal (2001 film)

text: The reviews for "Hannibal" were mixed. On Rotten Tomatoes, the film holds an approval rating of 40% based on 171 reviews, with an average rating of 5.1/10. The website's critical consensus reads, "While superbly acted and stylishly filmed, "Hannibal" lacks the character interaction between the two leads which made the first movie so engrossing." On Metacritic, the film has a rating of 57 out of 100 from 36 reviews. Audiences surveyed by CinemaScore gave the film a grade "C+" on scale of A to F.


title: Hannibal (2001 film)

text: "Time" magazine wrote: "A banquet of creepy, gory or grotesque incidents is on display in "Hannibal". But this superior sequel has romance in its dark heart." "Empire" magazine gave it two out of five stars, calling it "laughable to just plain boring, "Hannibal" is toothless to the end." David Thomson, writing in the British Film Institute magazine "Sight & Sound", praised the film. "It works. It's smart, good-looking, sexy, fun ... dirty, naughty and knowing." Thomson does make clear he is a great fan of director Ridley Scott's work. He adds: "It is, literally, that Hannibal Lecter has become such a household joke that he can't be dreadful again. It seems clear that Anthony Hopkins and Scott saw that, and planned accordingly. That's how the movie was saved." "Variety" magazine in its review said ""Hannibal" is not as good as "Lambs" ... ultimately more shallow and crass at its heart than its predecessor, "Hannibal" is nevertheless tantalizing, engrossing and occasionally startling."


title: Hannibal (2001 film)

text: A negative review in "The Guardian" claimed that what was wrong with the film was carried over from the book: "The result is an inflated, good-looking bore of a movie. "The Silence of the Lambs" was a marvelous thing. This, by contrast, is barely okey-dokey." Roger Ebert gave the film 2.5 stars out of 4, and described "Hannibal" as "a carnival geek show elevated in the direction of art. It never quite gets there, but it tries with every fiber of its craft to redeem its pulp origins, and we must give it credit for the courage of its depravity", and although he was "left with admiration for Scott's craft in pulling [it] off at all, and making it watchable", and praised the Mason Verger character as "a superb joining of skill and diabolical imagination," as well as Hopkins' performance as Lecter, which he described as "fascinating every second he is on the screen", he concluded, "I cannot approve of the movie, not because of its violence, which belongs to the Grand Guignol tradition, but because the underlying story lacks the fascination of "Silence of the Lambs"."


title: Hannibal (2001 film)

text: According to "Variety" magazine, the script for "Hannibal" was: "quite faithful to the Harris blueprint; fans of the tome may regret the perhaps necessary excision of some characters, most notably Mason Verger's muscle-bound macho sister Margot, as well as the considerable fascinating academic detail, but will basically feel the book has been respected (yes, even the climactic dinner party is served up almost intact, with the only surprise twists saved for its wake)." "Time Out" noted: "The weight-watchers script sensibly dispenses with several characters to serve a brew that's enjoyably spicy but low on substance. So much story is squeezed into 131 minutes that little time's left for analysis or characterization." Producer Dino De Laurentiis was asked why some characters, notably Jack Crawford, were left out of the film: "I think if you get a book which is 600 pages, you have to reduce it to a script of 100 pages. In two hours of film, you cannot possibly include all the characters. We set ourselves a limit, and cut characters which weren't so vital."


title: Hannibal (2001 film)

text: In the book, Mason Verger runs an orphanage, from which he calls children to verbally abuse as a substitute for his no longer being able to molest them. He also has a sister, Margot, whom he had raped when they were children and who is a lesbian. When she disclosed her sexual orientation to her family, their father disowned her. As she is sterile due to steroid abuse, Verger exerts some control over her by promising her a semen sample with which to impregnate her lover, who could then inherit the Verger fortune. At the book's end, Margot and Starling both help Lecter escape during a shootout between Starling and Verger's guards. Margot, at Lecter's advice, stimulates her brother to ejaculate with a rectally inserted cattle prod, and then kills him by ramming his pet moray eel down his throat.


title: Hannibal (2001 film)

text: The book's controversial ending has Lecter presenting Starling with the exhumed bones of her father, which he "brings to life" by hypnotizing Starling, allowing her to say goodbye. This forges an odd alliance between Starling and Lecter, culminating in their becoming lovers and escaping to Argentina. At the novel's end, Barney sees them at the Teatro Colón of Buenos Aires.


title: Hannibal (2001 film)

text: Also gone from the film are the flashbacks to Lecter's childhood, in which he sees his younger sister, Mischa, eaten by German deserters in 1944. These flashbacks formed the basis for the 2007 film "Hannibal Rising" (written concurrently with the 2006 novel of the same name) which portrays Lecter as a young man.


title: Hannibal (2001 film)

text: Hopkins was asked in an interview on the subject of whether or not he believed the idea of Starling and Lecter heading off into the sunset as lovers (as happens in the book). "Yes, I did. Other people found that preposterous. I suppose there's a moral issue there. I think it would have been a very interesting thing though. I think it would have been very interesting had she gone off, because I suspected that there was that romance, attachment there, that obsession with her. I guessed that a long time ago, at the last phone call to Clarice, at the end of "SotL", she said, 'Dr. Lecter, Dr. Lecter ... '."


title: Hannibal (2001 film)

text: The film was followed by two films which are prequels based on novels by Thomas Harris (although the novel of "Red Dragon" isn't itself a prequel as it was written before Hannibal).


title: Hannibal (2001 film)

text: In 2013, there was a news story from Italy where a gangster fed his rival alive to pigs. Many media stories compared this to a similar scene in "Hannibal".


title: Typhoid fever

text: Typhoid fever, also known as typhoid, is a disease caused by "Salmonella" serotype Typhi bacteria. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several days. This is commonly accompanied by weakness, abdominal pain, constipation, headaches, and mild vomiting. Some people develop a skin rash with rose colored spots. In severe cases, people may experience confusion. Without treatment, symptoms may last weeks or months. Diarrhea may be severe, but is uncommon. Other people may carry the bacterium without being affected, but they are still able to spread the disease. Typhoid fever is a type of enteric fever, along with paratyphoid fever. "S. enterica" Typhi is believed to infect and replicate only within humans.


title: Typhoid fever

text: Typhoid is caused by the bacterium "Salmonella enterica" subsp. "enterica" serovar Typhi growing in the intestines, peyers patches, mesenteric lymph nodes, spleen, liver, gallbladder, bone marrow and blood. Typhoid is spread by eating or drinking food or water contaminated with the feces of an infected person. Risk factors include limited access to clean drinking water and poor sanitation. Those who have not yet been exposed to the pathogen and ingest contaminated drinking water or food are most at risk for developing symptoms. Only humans can be infected; there are no known animal reservoirs.


title: Typhoid fever

text: Diagnosis is by culturing and identifying "S. enterica Typhi" from patient samples or detecting an immune response to the pathogen from blood samples. Recently, new advances in large-scale data collection and analysis have allowed researchers to develop better diagnostics, such as detecting changing abundances of small molecules in the blood that may specifically indicate typhoid fever. Diagnostic tools in regions where typhoid is most prevalent are quite limited in their accuracy and specificity, and the time required for a proper diagnosis, the increasing spread of antibiotic resistance, and the cost of testing are also hardships for under-resourced healthcare systems.


title: Typhoid fever

text: A typhoid vaccine can prevent about 40% to 90% of cases during the first two years. The vaccine may have some effect for up to seven years. For those at high risk or people traveling to areas where the disease is common, vaccination is recommended. Other efforts to prevent the disease include providing clean drinking water, good sanitation, and handwashing. Until an infection is confirmed as cleared, the infected person should not prepare food for others. Typhoid is treated with antibiotics such as azithromycin, fluoroquinolones, or third-generation cephalosporins. Resistance to these antibiotics has been developing, which has made treatment more difficult.


title: Typhoid fever

text: In 2015, 12.5 million new typhoid cases were reported. The disease is most common in India. Children are most commonly affected. Typhoid decreased in the developed world in the 1940s as a result of improved sanitation and the use of antibiotics. Every year about 400 cases are reported in the U.S. and an estimated 6,000 people have typhoid. In 2015, it resulted in about 149,000 deaths worldwide – down from 181,000 in 1990. Without treatment, the risk of death may be as high as 20%. With treatment, it is between 1% and 4%.


title: Typhoid fever

text: Typhus is a different disease. Owing to their similar symptoms, they were not recognized as distinct diseases until the 1800s. "Typhoid" means "resembling typhus".


title: Typhoid fever

text: Classically, the progression of untreated typhoid fever has three distinct stages, each lasting about a week. Over the course of these stages, the patient becomes exhausted and emaciated.


title: Typhoid fever

text: The Gram-negative bacterium that causes typhoid fever is "Salmonella enterica" subsp. enterica serovar Typhi. Based on MLST subtyping scheme, the two main sequence types of the "S." Typhi are ST1 and ST2, which are widespread globally. Global phylogeographical analysis showed dominance of a haplotype 58 (H58), which probably originated in India during the late 1980s and is now spreading through the world with multi-drug resistance. A more detailed genotyping scheme was reported in 2016 and is now being used widely. This scheme reclassified the nomenclature of H58 to genotype 4.3.1.


title: Typhoid fever

text: Unlike other strains of "Salmonella", no animal carriers of typhoid are known. Humans are the only known carriers of the bacterium. "S. enterica" subsp. enterica serovar Typhi is spread by the fecal-oral route from people who are infected and from asymptomatic carriers of the bacterium. An asymptomatic human carrier is someone who is still excreting typhoid bacteria in their stool a year after the acute stage of the infection.


title: Typhoid fever

text: Diagnosis is made by any blood, bone marrow, or stool cultures and with the Widal test (demonstration of antibodies against "Salmonella" antigens O-somatic and H-flagellar). In epidemics and less wealthy countries, after excluding malaria, dysentery, or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of the Widal test and blood and stool cultures.


title: Typhoid fever

text: The Widal test is used to identify specific antibodies in the serum of people with typhoid by using antigen-antibody interactions.


title: Typhoid fever

text: In this test, the serum is mixed with a dead bacterial suspension of salmonella with specific antigens. If the patient's serum contains antibodies against those antigens, they get attached to them, forming clumps. If clumping does not occur, the test is negative. The Widal test is time-consuming and prone to significant false positives. It may also be falsely negative in recently infected people. But unlike the Typhidot test, the Widal test quantifies the specimen with titres.


title: Typhoid fever

text: Typhidot is based on the presence of specific IgM and IgG antibodies to a specific 50Kd OMP antigen. This test is carried out on a cellulose nitrate membrane where a specific "S. typhi" outer membrane protein is attached as fixed test lines. It separately identifies IgM and IgG antibodies. IgM shows recent infection; IgG signifies remote infection.


title: Typhoid fever

text: The sample pad of this kit contains colloidal gold-anti-human IgG or gold-anti-human IgM. If the sample contains IgG and IgM antibodies against those antigens, they will react and turn red. The typhidot test becomes positive within 2–3 days of infection.


title: Typhoid fever

text: Two colored bands indicate a positive test. A single control band indicates a negative test. A single first fixed line or no band at all indicates an invalid test. Typhidot's biggest limitation is that it is not quantitative, just positive or negative.


title: Typhoid fever

text: The Tubex test contains two types of particles: brown magnetic particles coated with antigen and blue indicator particles coated with O9 antibody. During the test, if antibodies are present in the serum, they will attach to the brown magnetic particles and settle at the base, while the blue indicator particles remain in the solution, producing a blue color, which means the test is positive.


title: Typhoid fever

text: If the serum does not have an antibody in it, the blue particles attach to the brown particles and settle at the bottom, producing a colorless solution, which means the test is negative.


title: Typhoid fever

text: Sanitation and hygiene are important to prevent typhoid. It can spread only in environments where human feces can come into contact with food or drinking water. Careful food preparation and washing of hands are crucial to prevent typhoid. Industrialization contributed greatly to the elimination of typhoid fever, as it eliminated the public-health hazards associated with having horse manure in public streets, which led to a large number of flies, which are vectors of many pathogens, including "Salmonella" spp. According to statistics from the U.S. Centers for Disease Control and Prevention, the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever.


title: Typhoid fever

text: Two typhoid vaccines are licensed for use for the prevention of typhoid: the live, oral Ty21a vaccine (sold as Vivotif by Crucell Switzerland AG) and the injectable typhoid polysaccharide vaccine (sold as Typhim Vi by Sanofi Pasteur and Typherix by GlaxoSmithKline). Both are efficacious and recommended for travelers to areas where typhoid is endemic. Boosters are recommended every five years for the oral vaccine and every two years for the injectable form. An older, killed whole-cell vaccine is still used in countries where the newer preparations are not available, but this vaccine is no longer recommended for use because it has more side effects (mainly pain and inflammation at the site of the injection).


title: Typhoid fever

text: To help decrease rates of typhoid fever in developing nations, the World Health Organization (WHO) endorsed the use of a vaccination program starting in 1999. Vaccination has proven effective at controlling outbreaks in high-incidence areas and is also very cost-effective: prices are normally less than US$1 per dose. Because the price is low, poverty-stricken communities are more willing to take advantage of the vaccinations. Although vaccination programs for typhoid have proven effective, they alone cannot eliminate typhoid fever. Combining vaccines with public-health efforts is the only proven way to control this disease.


title: Typhoid fever

text: Since the 1990s, the WHO has recommended two typhoid fever vaccines. The ViPS vaccine is given by injection, and the Ty21a by capsules. Only people over age two are recommended to be vaccinated with the ViPS vaccine, and it requires a revaccination after 2–3 years, with a 55%–72% efficacy. The Ty21a vaccine is recommended for people five and older, lasting 5–7 years with 51%–67% efficacy. The two vaccines have proved safe and effective for epidemic disease control in multiple regions.


title: Typhoid fever

text: Results of a phase 3 trial of typhoid conjugate vaccine (TCV) in December 2019 reported 81% fewer cases among children.


title: Typhoid fever

text: The rediscovery of oral rehydration therapy in the 1960s provided a simple way to prevent many of the deaths of diarrheal diseases in general.


title: Typhoid fever

text: Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin. Otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice. Cefixime is a suitable oral alternative.


title: Typhoid fever

text: Properly treated, typhoid fever is not fatal in most cases. Antibiotics such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, amoxicillin, and ciprofloxacin have been commonly used to treat it. Treatment with antibiotics reduces the case-fatality rate to about 1%.


title: Typhoid fever

text: Without treatment, some patients develop sustained fever, bradycardia, hepatosplenomegaly, abdominal symptoms, and occasionally pneumonia. In white-skinned patients, pink spots, which fade on pressure, appear on the skin of the trunk in up to 20% of cases. In the third week, untreated cases may develop gastrointestinal and cerebral complications, which may prove fatal in 10%–20% of cases. The highest case fatality rates are reported in children under 4. Around 2%–5% of those who contract typhoid fever become chronic carriers, as bacteria persist in the biliary tract after symptoms have resolved.


title: Typhoid fever

text: Surgery is usually indicated if intestinal perforation occurs. One study found a 30-day mortality rate of 9% (8/88), and surgical site infections at 67% (59/88), with the disease burden borne predominantly by low-resource countries.


title: Typhoid fever

text: For surgical treatment, most surgeons prefer simple closure of the perforation with drainage of the peritoneum. Small-bowel resection is indicated for patients with multiple perforations. If antibiotic treatment fails to eradicate the hepatobiliary carriage, the gallbladder should be resected. Cholecystectomy is sometimes successful, especially in patients with gallstones, but is not always successful in eradicating the carrier state because of persisting hepatic infection.


title: Typhoid fever

text: As resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, and streptomycin is now common, these agents are no longer used as first–line treatment of typhoid fever. Typhoid resistant to these agents is known as multidrug-resistant typhoid.


title: Typhoid fever

text: Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent and Southeast Asia. Many centres are shifting from ciprofloxacin to ceftriaxone as the first line for treating suspected typhoid originating in South America, India, Pakistan, Bangladesh, Thailand, or Vietnam. Also, it has been suggested that azithromycin is better at treating resistant typhoid than both fluoroquinolone drugs and ceftriaxone. Azithromycin can be taken by mouth and is less expensive than ceftriaxone, which is given by injection.


title: Typhoid fever

text: A separate problem exists with laboratory testing for reduced susceptibility to ciprofloxacin; current recommendations are that isolates should be tested simultaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), that isolates sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin", and that isolates sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". But an analysis of 271 isolates found that around 18% of isolates with a reduced susceptibility to fluoroquinolones, the class which CIP belongs (MIC 0.125–1.0 mg/L), would not be detected by this method.


title: Typhoid fever

text: In 2000, typhoid fever caused an estimated 21.7 million illnesses and 217,000 deaths. It occurs most often in children and young adults between 5 and 19 years old. In 2013, it resulted in about 161,000 deaths – down from 181,000 in 1990. Infants, children, and adolescents in south-central and Southeast Asia have the highest rates of typhoid. Outbreaks are also often reported in sub-Saharan Africa and Southeast Asia. In 2000, more than 90% of morbidity and mortality due to typhoid fever occurred in Asia. In the U.S., about 400 cases occur each year, 75% of which are acquired while traveling internationally.


title: Typhoid fever

text: Before the antibiotic era, the case fatality rate of typhoid fever was 10%–20%. Today, with prompt treatment, it is less than 1%, but 3%–5% of people who are infected develop a chronic infection in the gall bladder. Since "S. enterica" subsp. enterica serovar Typhi is human-restricted, these chronic carriers become the crucial reservoir, which can persist for decades for further spread of the disease, further complicating its identification and treatment. Lately, the study of "S. enterica" subsp. enterica serovar Typhi associated with a large outbreak and a carrier at the genome level provides new insight into the pathogenesis of the pathogen.


title: Typhoid fever

text: In industrialized nations, water sanitation and food handling improvements have reduced the number of typhoid cases. Developing nations, such as those in parts of Asia and Africa, have the highest rates. These areas lack access to clean water, proper sanitation systems, and proper health-care facilities. In these areas, such access to basic public-health needs is not expected in the near future.


title: Typhoid fever

text: In 2004–2005 an outbreak in the Democratic Republic of Congo resulted in more than 42,000 cases and 214 deaths. Since November 2016, Pakistan has had an outbreak of extensively drug-resistant (XDR) typhoid fever.


title: Typhoid fever

text: In Europe, a report based on data for 2017 retrieved from The European Surveillance System (TESSy) on the distribution of confirmed typhoid and paratyphoid fever cases found that 22 EU/EEA countries reported a total of 1,098 cases, 90.9% of which were travel-related, mainly acquired during travel to South Asia.


title: Typhoid fever

text: The plague of Athens, during the Peloponnesian War, was most likely an outbreak of typhoid fever. During the war, Athenians retreated into a walled-in city to escape attack from the Spartans. This massive influx of humans into a concentrated space overwhelmed the water supply and waste infrastructure, likely leading to unsanitary conditions as fresh water became harder to obtain and waste became more difficult to collect and remove beyond the city walls. In 2006, examining the remains for a mass burial site from Athens from around the time of the plague (~430 B.C.) revealed that fragments of DNA similar to modern day "S." Typhi DNA were detected, whereas "Yersinia pestis" (plague), "Rickettsia prowazekii" (typhus), "Mycobacterium tuberculosis", cowpox virus, and "Bartonella henselae" were not detected in any of the remains tested.


title: Typhoid fever

text: It is possible that the Roman emperor Augustus Caesar had either a liver abscess or typhoid fever, and survived by using ice baths and cold compresses as a means of treatment for his fever. There is a statue of the Greek physician, Antonius Musa, who treated his fever.


title: Typhoid fever

text: The French doctors Pierre-Fidele Bretonneau and Pierre-Charles-Alexandre Louis are credited with describing typhoid fever as a specific disease, unique from typhus. Both doctors performed autopsies on individuals who died in Paris due to fever – and indicated that many had lesions on the Peyer's patches which correlated with distinct symptoms before death. British medics were skeptical of the differentiation between typhoid and typhus because both were endemic to Britain at that time. However, in France only typhoid was present circulating in the population. Pierre-Charlles-Alexandre Louis also performed case studies and statistical analysis to demonstrate that typhoid was contagious - and that persons who already had the disease seemed to be protected. Afterward, several American doctors confirmed these findings, and then Sir William Jenner convinced any remaining skeptics that typhoid is a specific disease recognizable by lesions in the Peyer's patches by examining sixty six autopsies from fever patients and concluding that the symptoms of headaches, diarrhea, rash spots, and abdominal pain were only present in patients which then had intestinal lesions after death; which solidified the association of the disease with the intestinal tract and gave the first clue to the route of transmission.


title: Typhoid fever

text: In 1847 William Budd learned of an epidemic of typhoid fever in Clifton, and identified that all 13 of 34 residents who had contracted the disease drew their drinking water from the same well. Notably, this observation was two years prior to John Snow discovering the route of contaminated water as the cause for a cholera outbreak. Budd later became health officer of Bristol and ensured a clean water supply, and documented further evidence of typhoid as a water-borne illness throughout his career.


title: Typhoid fever

text: Polish scientist Tadeusz Browicz described a short bacillus in the organs and feces of typhoid victims in 1874. Browicz was able to isolate and grow the bacilli but did not go as far as to insinuate or prove that they caused the disease.


title: Typhoid fever

text: In April 1880, three months prior to Eberth's publication, Edwin Klebs described short and filamentous bacilli in the Peyer's patches in typhoid victims. The bacterium's role in disease was speculated but not confirmed.


title: Typhoid fever

text: In 1880, Karl Joseph Eberth described a bacillus that he suspected was the cause of typhoid. Eberth is given credit for discovering the bacterium definitively by successfully isolating the same bacterium from 18 of 40 typhoid victims and failing to discover the bacterium present in any "control" victims of other diseases. In 1884, pathologist Georg Theodor August Gaffky (1850–1918) confirmed Eberth's findings. Gaffky isolated the same bacterium as Eberth from the spleen of a typhoid victim, and was able to grow the bacterium on solid media. The organism was given names such as Eberth's bacillus, "Eberthella" Typhi, and Gaffky-Eberth bacillus. Today, the bacillus that causes typhoid fever goes by the scientific name "Salmonella enterica" serovar Typhi.


title: Typhoid fever

text: Most developed countries had declining rates of typhoid fever throughout the first half of the 20th century due to vaccinations and advances in public sanitation and hygiene. In 1893 attempts were made to chlorinate the water supply in Hamburg, Germany and in 1897 Maidstone, England, was the first town to have its entire water supply chlorinated. In 1905, following an outbreak of typhoid fever, the City of Lincoln, England, instituted permanent water chlorination. The first permanent disinfection of drinking water in the US was made in 1908 to the Jersey City, New Jersey, water supply. Credit for the decision to build the chlorination system has been given to John L. Leal. The chlorination facility was designed by George W. Fuller.


title: Typhoid fever

text: Outbreaks in traveling military groups led to the creation of the Lyster bag in 1915; a bag with a faucet which can be hung from a tree or pole, filled with water, and comes with a chlorination tablet to drop into the water. The Lyster bag was essential for the survival of American soldiers in the Vietnam War.


title: Typhoid fever

text: There were several occurrences of milk delivery men spreading typhoid fever throughout the communities they served. Although typhoid is not spread through milk itself, there were several examples of milk distributors in many locations watering their milk down with contaminated water, or cleaning the glass bottles the milk was placed in with contaminated water. Boston had two such cases around the turn of the 20th century. In 1899 there were 24 cases of typhoid traced to a single milkman, whose wife had died of typhoid fever a week before the outbreak. In 1908, J.J. Fallon, who was also a milkman, died of typhoid fever. Following his death and confirmation of the typhoid fever diagnosis, the city conducted an investigation of typhoid symptoms and cases along his route and found evidence of a significant outbreak. A month after the outbreak was first reported, the "Boston Globe" published a short statement declaring the outbreak over, stating "[a]t Jamaica Plain there is a slight increase, the total being 272 cases. Throughout the city there is a total of 348 cases." There was at least one death reported during this outbreak: Mrs. Sophia S. Engstrom, aged 46. Typhoid continued to ravage the Jamaica Plain neighborhood in particular throughout 1908, and several more people were reported dead due to typhoid fever, although these cases were not explicitly linked to the outbreak. The Jamaica Plain neighborhood at that time was home to many working-class and poor immigrants, mostly from Ireland.


title: Typhoid fever

text: The most notorious carrier of typhoid fever, but by no means the most destructive, was Mary Mallon, known as Typhoid Mary. Although other cases of human-to-human spread of typhoid were known at the time, the concept of an asymptomatic carrier, who was able to transmit disease, had only been hypothesized and not yet identified or proven. Mary Mallon became the first known example of an asymptomatic carrier of an infectious disease, making typhoid fever the first known disease being transmissible through asymptomatic hosts. The cases and deaths caused by Mallon were mainly upper-class families in New York City. At the time of Mallon's tenure as a personal cook for upper-class families, New York City reported 3,000 to 4,500 cases of typhoid fever annually. In the summer of 1906 two daughters of a wealthy family and maids working in their home became ill with typhoid fever. After investigating their home water sources and ruling out water contamination, the family hired civil engineer George Soper to conduct an investigation of the possible source of typhoid fever in the home. Soper described himself as an "epidemic fighter". His investigation ruled out many sources of food, and led him to question if the cook the family hired just prior to their household outbreak, Mallon, was the source. Since she had already left and begun employment elsewhere, he proceeded to track her down in order to obtain a stool sample. When he was able to finally meet Mallon in person he described her by saying "Mary had a good figure and might have been called athletic had she not been a little too heavy." In recounts of Soper's pursuit of Mallon, his only remorse appears to be that he was not given enough credit for his relentless pursuit and publication of her personal identifying information, stating that the media "rob[s] me of whatever credit belongs to the discovery of the first typhoid fever carrier to be found in America." Ultimately, 51 cases and 3 deaths were suspected to be caused by Mallon.


title: Typhoid fever

text: In 1924 the city of Portland, Oregon, experienced an outbreak of typhoid fever, consisting of 26 cases and 5 deaths, all deaths due to intestinal hemorrhage. All cases were concluded to be due to a single milk farm worker, who was shedding large amounts of the typhoid pathogen in his urine. Misidentification of the disease, due to inaccurate Widal test results, delayed identification of the carrier and proper treatment. Ultimately, it took four samplings of different secretions from all of the dairy workers in order to successfully identify the carrier. Upon discovery, the dairy worker was forcibly quarantined for seven weeks, and regular samples were taken, most of the time the stool samples yielding no typhoid and often the urine yielding the pathogen. The carrier was reported as being 72 years old and appearing in excellent health with no symptoms. Pharmaceutical treatment decreased the amount of bacteria secreted, however, the infection was never fully cleared from the urine, and the carrier was released "under orders never again to engage in the handling of foods for human consumption." At the time of release, the authors noted "for more than fifty years he has earned his living chiefly by milking cows and knows little of other forms of labor, it must be expected that the closest surveillance will be necessary to make certain that he does not again engage in this occupation."


title: Typhoid fever

text: Overall, in the early 20th century the medical profession began to identify carriers of the disease, and evidence of transmission independent of water contamination. In a 1933 American Medical Association publication, physicians' treatment of asymptomatic carriers is best summarized by the opening line "Carriers of typhoid bacilli are a menace". Within the same publication, the first official estimate of typhoid carriers is given: 2 to 5% of all typhoid patients, and distinguished between temporary carriers and chronic carriers. The authors further estimate that there are four to five chronic female carriers to every one male carrier, although offered no data to explain this assertion of a gender difference in the rate of typhoid carriers. As far as treatment, the authors suggest: "When recognized, carriers must be instructed as to the disposal of excreta as well as to the importance of personal cleanliness. They should be forbidden to handle food or drink intended for others, and their movements and whereabouts must be reported to the public health officers".


title: Typhoid fever

text: Today, typhoid carriers exist all over the world, but the highest incidence of asymptomatic infection is likely to occur in South/Southeast Asian and Sub-Saharan countries. The Los Angeles County department of public health tracks typhoid carriers and reports the number of carriers identified within the county yearly; between 2006 and 2016 0-4 new cases of typhoid carriers were identified per year. Cases of typhoid fever must be reported within one working day from identification. As of 2018, chronic typhoid carriers must sign a "Carrier Agreement" and are required to test for typhoid shedding twice yearly, ideally every 6 months. Carriers may be released from their agreements upon fulfilling "release" requirements, based on completion of a personalized treatment plan designed with medical professionals. Fecal or gallbladder carrier release requirements: 6 consecutive negative feces and urine specimens submitted at 1-month or greater intervals beginning at least 7 days after completion of therapy. Urinary or kidney carrier release requirements: 6 consecutive negative urine specimens submitted at 1-month or greater intervals beginning at least 7 days after completion of therapy. As of 2016 the male:female ratio of carriers in Los Angeles county was 3:1.


title: Typhoid fever

text: Due to the nature of asymptomatic cases, many questions remain about how individuals are able to tolerate infection for long periods of time, how to identify such cases, and efficient options for treatment. Researchers are currently working to understand asymptomatic infection with "Salmonella" species by studying infections in laboratory animals, which will ultimately lead to improved prevention and treatment options for typhoid carriers. In 2002, Dr. John Gunn described the ability of "Salmonella" sp. to form biofilms on gallstones in mice, providing a model for studying carriage in the gallbladder. Dr. Denise Monack and Dr. Stanley Falkow described a mouse model of asymptomatic intestinal and systemic infection in 2004, and Dr. Monack went on to demonstrate that a sub-population of superspreaders are responsible for the majority of transmission to new hosts, following the 80/20 rule of disease transmission, and that the intestinal microbiota likely plays a role in transmission. Dr. Monack's mouse model allows long-term carriage of salmonella in mesenteric lymph nodes, spleen and liver.


title: Typhoid fever

text: British bacteriologist Almroth Edward Wright first developed an effective typhoid vaccine at the Army Medical School in Netley, Hampshire. It was introduced in 1896 and used successfully by the British during the Second Boer War in South Africa. At that time, typhoid often killed more soldiers at war than were lost due to enemy combat. Wright further developed his vaccine at a newly opened research department at St Mary's Hospital Medical School in London from 1902, where he established a method for measuring protective substances (opsonin) in human blood. Wright's version of the typhoid vaccine was produced by growing the bacterium at body temperature in broth, then heating the bacteria to 60 °C to "heat inactivate" the pathogen, killing it, while keeping the surface antigens intact. The heat-killed bacteria was then injected into a patient. To show evidence of the vaccine's efficacy, Wright then collected serum samples from patients several weeks post-vaccination, and tested their serum's ability to agglutinate live typhoid bacteria. A "positive" result was represented by clumping of bacteria, indicating that the body was producing anti-serum (now called antibodies) against the pathogen.


title: Typhoid fever

text: Citing the example of the Second Boer War, during which many soldiers died from easily preventable diseases, Wright convinced the British Army that 10 million vaccine doses should be produced for the troops being sent to the Western Front, thereby saving up to half a million lives during World War I. The British Army was the only combatant at the outbreak of the war to have its troops fully immunized against the bacterium. For the first time, their casualties due to combat exceeded those from disease.


title: Typhoid fever

text: In 1909, Frederick F. Russell, a U.S. Army physician, adopted Wright's typhoid vaccine for use with the Army, and two years later, his vaccination program became the first in which an entire army was immunized. It eliminated typhoid as a significant cause of morbidity and mortality in the U.S. military. Typhoid vaccination for members of the American military became mandatory in 1911. Before the vaccine, the rate of typhoid fever in the military was 14,000 or greater per 100,000 soldiers. By World War I, the rate of typhoid in American soldiers was 37 per 100,000.


title: Typhoid fever

text: During the second world war, the United States army authorized the use of a trivalent vaccine – containing heat-inactivated Typhoid, Paratyphi A and Paratyphi B pathogens.


title: Typhoid fever

text: In 1934, discovery of the Vi capsular antigen by Arthur Felix and Miss S. R. Margaret Pitt enabled development of the safer Vi Antigen vaccine – which is widely in use today. Arthur Felix and Margaret Pitt also isolated the strain Ty2, which became the parent strain of Ty21a, the strain used as a live-attenuated vaccine for typhoid fever today.


title: Typhoid fever

text: Chloramphenicol was isolated from "Streptomyces" by Dr. David Gotlieb during the 1940s. In 1948 American army doctors tested its efficacy in treating typhoid patients in Kuala Lumpur, Malaysia. Individuals who received a full course of treatment cleared the infection, whereas patients given a lower dose had a relapse. Asymptomatic carriers continued to shed bacilli despite chloramphenicol treatment - only ill patients were improved with chloramphenicol. Resistance to chloramphenicol became frequent in Southeast Asia by the 1950s, and today chloramphenicol is only used as a last resort due to the high prevalence of resistance.


title: Typhoid fever

text: The disease has been referred to by various names, often associated with symptoms, such as gastric fever, enteric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever, pythogenic fever, drain fever and low fever.


title: Troian Bellisario

text: Troian Avery Bellisario (born October 28, 1985) is an American actress. A graduate of the University of Southern California, in 2010, she received her breakthrough role as Spencer Hastings in the Freeform drama series "Pretty Little Liars" (20102017), for which she received worldwide recognition and multiple awards and nominations.


title: Troian Bellisario

text: Bellisario was born and raised in Los Angeles. Her parents are producers Deborah Pratt and Donald P. Bellisario, her father having created "Magnum, P.I.", "Quantum Leap", and "NCIS", among other TV series. She has a younger brother, three half-sisters, two half-brothers, and two stepbrothers, actor Sean Murray and producer Chad W. Murray. Her father is of Italian and Serbian descent, and her mother is of African American and Creole descent.


title: Troian Bellisario

text: Attending Campbell Hall School in Studio City, California, from kindergarten through twelfth grade, Bellisario was the valedictorian of her class. After high school, she attended Vassar College for several months before taking a break for the sake of her mental health, feeling that the institution only enhanced her perfectionist tendencies. She graduated with a Bachelor of Fine Arts degree from the University of Southern California in 2009.


title: Troian Bellisario

text: Bellisario made her acting debut in the 1988 film "Last Rites" at the age of three, which was directed, written and produced by her father, Donald P. Bellisario. In 1990, she guest-starred in an episode of her father's series "Quantum Leap". In 1998, she co-starred with Mary-Kate and Ashley Olsen in the film "Billboard Dad". Beginning in 2006, Bellisario began appearing in a number of independent short films namely, "Unspoken", "Archer House" and "Intersect".


title: Troian Bellisario

text: In November 2009, Bellisario was cast as Spencer Hastings in the TV series "Pretty Little Liars" based on the book series of the same name by Sara Shepard. In October 2011, Bellisario announced she was in the process of writing and creating her own film, which was successfully funded through Kickstarter on November 16, 2011. Filming ended in December 2011 and the film was officially completed by August 2012.


title: Troian Bellisario

text: In 2014, she starred in the music video for The Head and the Heart's song "Another Story". Bellisario also starred in "Immediately Afterlife", a short film about two cult members who are the only survivors of their group's mass suicide, playing Bennett, alongside her "Pretty Little Liars" co-stars Shay Mitchell (Emily), Ian Harding (Ezra Fitz) and Nolan North (Peter Hastings). In 2015, she was cast in a leading role in the American remake of the French-Canadian film "Martyrs". In 2015, Bellisario and fiancée Patrick J. Adams filmed short film "We Are Here in Haida Gwaii", which Bellisario wrote and starred in. In 2017, Bellisario starred in her feature film, "Feed", which she also wrote and produced. The film was written based on Bellisario's own experiences with an eating disorder.


title: Troian Bellisario

text: On April 7, 2016, it was announced that Bellisario would be directing season 7, episode 15 of "Pretty Little Liars". This made her one of the first in the cast, alongside Chad Lowe, to direct an episode on the series. In 2020, Bellisario appeared as the bride character Jenna Marshall from the episode "Til Dex Do Us Part" in "Stumptown".


title: Troian Bellisario

text: Further in television, she costarred with Australian actress Jacki Weaver in the television drama film "Sister Cities" (2016), and opposite Bradley Whitford in the Me Too drama "Lauren" (20122013). In film, Bellisario has received recognition for her performances in "C.O.G." (2013), "Feed" (2017), "Clara" (2018) and "Where'd You Go, Bernadette" (2019).


title: Troian Bellisario

text: In March 2020, Bellisario played the lead role of Claire in the CBS political drama pilot "Ways & Means", written by Ed Redlich. The pilot, which also starred Patrick Dempsey, focused on a secret alliance between a disillusioned career politician and an idealist up-and-comer in the gridlocked American system. The show was not picked up.


title: Troian Bellisario

text: In 2022, she appeared in the comedy "Doula" alongside Arron Shiver (who also wrote the film) and Will Greenberg. The film, produced by Chris Pine and directed by Cheryl Nichols, deals with Bellisario's character hiring her midwife's son as the latter's replacement when she passes away.


title: Troian Bellisario

text: Bellisario started dating "Suits" star Patrick J. Adams after they met on the set of the play "Equivocation" in 2009. The couple briefly split, but after Adams' guest appearance as Hardy in "Pretty Little Liars", 2010, the two got back together. Since working on "Equivocation" and "Pretty Little Liars", the couple also worked together on the 2012 short film "The Come Up", "Suits", and the short film "We Are Here". Bellisario and Adams were married on December 10, 2016, in Santa Barbara, California. In May of 2018, they attended the royal wedding of Prince Harry and Meghan Markle. The couple has two daughters, born in 2018 and 2021.


title: Troian Bellisario

text: In an episode of actress Katie Lowes's podcast, "Katie's Crib", Bellisario and Adams said their second child was born in the backseat of their car at the hospital parking lot due to an accelerated labour, with Adams delivering the baby. Hospital staff assisted within minutes of the delivery, and Bellisario and the baby were found healthy.


title: Troian Bellisario

text: Bellisario said in January 2014 that she endured personal problems during high school, resulting in self-harm and an eating disorder. "I was the youngest daughter, the perfect little girl. My school was a very intense college prep school. So it was about wanting to please my father and mother and wanting to be perfect to everybody."


title: Troian Bellisario

text: In 2014, Bellisario returned to her alma mater, USC School of Dramatic Arts, delivering the commencement speech.


title: John Paul Jones (musician)

text: John Richard Baldwin (born 3 January 1946), better known by his stage name John Paul Jones, is an English musician, composer and record producer who was the bassist and keyboardist for the rock band Led Zeppelin. Prior to forming the band with Jimmy Page in 1968, he was a session musician and arranger. After the death of drummer John Bonham in 1980, Led Zeppelin disbanded, and Jones developed a solo career. He has collaborated with musicians across a variety of genres, including the supergroup Them Crooked Vultures with Dave Grohl and Josh Homme. He was inducted into the Rock and Roll Hall of Fame in 1995 as a member of Led Zeppelin.


title: John Paul Jones (musician)

text: John Richard Baldwin was born in Sidcup, Kent, England, on 3 January 1946. He started playing piano at age six, learning from his father, Joe Baldwin, a pianist and arranger for big bands in the 1940s and 1950s, notably with Ambrose and his Orchestra. His mother was also in the music business which allowed the family to often perform together touring around England as a vaudeville comedy act. His influences ranged from the blues of Big Bill Broonzy, the jazz of Charles Mingus, to the classical piano of Sergei Rachmaninoff.


title: John Paul Jones (musician)

text: Because his parents often toured, Baldwin was sent to boarding school at a young age. He was a student at Christ's College, Blackheath, London where he studied music formally. At the age of 14, Baldwin became choirmaster and organist at a local church and during that year, he also bought his first bass guitar, a Dallas Tuxedo solid body electric followed by multiple basses which he part exchanged until he finally bought his 1962 Fender Jazz Bass which he used until 1976. The fluid playing of Chicago musician Phil Upchurch on his "You Can't Sit Down" LP, which includes a memorable bass solo, is cited by Jones as being his inspiration to take up the instrument.


title: John Paul Jones (musician)

text: Baldwin joined his first band, The Deltas, at the age of 15. He then played bass for jazz-rock London group, Jett Blacks, a collective that included guitarist John McLaughlin. His big break came in 1962, when he was hired by Jet Harris and Tony Meehan of the successful British group the Shadows for a two-year stint. Shortly before hiring Baldwin, Harris and Meehan had just had a number 1 hit with "Diamonds" (a track on which Jones' bandmate-to-be Jimmy Page had played). Baldwin's collaboration with the Shadows nearly prevented the future formation of Led Zeppelin, when the parties engaged in talks about the possibility of Baldwin replacing their bassist Brian Locking, who left the band in October 1963, but John Rostill was ultimately chosen to fill the position.


title: John Paul Jones (musician)

text: In 1964, on the recommendation of Meehan, Baldwin began studio session work with Decca Records. From then until 1968, he played on hundreds of recording sessions. He soon expanded his studio work by playing keyboards, arranging and undertaking general studio direction, resulting in his services coming under much demand. He worked with numerous artists including the Rolling Stones on "Their Satanic Majesties Request" (Jones' string arrangement is heard on "She's a Rainbow"); Herman's Hermits; Donovan (on "Sunshine Superman", "Hurdy Gurdy Man", and "Mellow Yellow"); Jeff Beck; Françoise Hardy; Cat Stevens; Rod Stewart; Shirley Bassey; Lulu; and numerous others. As well as recording sessions with Dusty Springfield, Jones also played bass for her "Talk of the Town" series of performances. His arranging and playing on Donovan's "Sunshine Superman" resulted in producer Mickie Most using his services as choice arranger for many of his own projects, with Tom Jones, Nico, Wayne Fontana, the Walker Brothers, and many others. In 1967, Most, as music supervisor, also tabbed Jones to arrange the music for Herman's Hermits' theatrical film "Mrs. Brown, You've Got a Lovely Daughter", released in January 1968. Such was the extent of Jones' studio work – amounting to hundreds of sessions – that he said years later that "I can't remember three-quarters of the sessions I was on."


title: John Paul Jones (musician)

text: It was during his time as a session player that Baldwin adopted the stage name John Paul Jones. This name was suggested to him by a friend, Andrew Loog Oldham, who had seen a poster for the 1959 film "John Paul Jones" in France. He released his first solo recording as John Paul Jones, "Baja" (written by Lee Hazlewood and produced by Oldham) / "A Foggy Day in Vietnam", as a single on Pye Records in April 1964.


title: John Paul Jones (musician)

text: Jones has stated that, as a session musician, he was completing two and three sessions a day, six and seven days a week. However, by 1968 he was feeling burned out by the heavy workload: "I was arranging 50 or 60 things a month and it was starting to kill me."


title: John Paul Jones (musician)

text: During his time as a session player, Jones often crossed paths with guitarist Jimmy Page, a fellow session veteran. In June 1966, Page joined The Yardbirds, and in 1967 Jones contributed to that band's "Little Games" album. The following winter, during the sessions for Donovan's "The Hurdy Gurdy Man", Jones expressed to Page a desire to be part of any projects the guitarist might be planning. Later that year, The Yardbirds disbanded, leaving Page and bassist Chris Dreja to complete previously booked Yardbirds dates in Scandinavia. Before a new band could be assembled, Dreja left to take up photography. Jones, at the suggestion of his wife, asked Page about the vacant position, and the guitarist eagerly invited Jones to collaborate. Page later explained:


title: John Paul Jones (musician)

text: Vocalist Robert Plant and drummer John Bonham joined the two to form a quartet. Initially dubbed the "New Yardbirds" for the Scandinavian dates, the band soon became known as Led Zeppelin.


title: John Paul Jones (musician)

text: Jones was responsible for the classic bass lines of the group, notably those in "Ramble On" and "The Lemon Song" ("Led Zeppelin II"), and shifting time signatures, such as those in "Black Dog" ("Led Zeppelin IV"). As half of Led Zeppelin's rhythm section with drummer John Bonham, Jones shared an appreciation for funk and soul rhythmic grooves which strengthened and enhanced their musical affinity. In an interview he gave to "Global Bass" magazine, Jones remarked on this common musical interest:


title: John Paul Jones (musician)

text: After retiring his Fender Jazz Bass (which he had been using since his days with The Shadows in the early 1960s) from touring in 1975, Jones switched to using custom-designed Alembic basses for touring.


title: John Paul Jones (musician)

text: However, he still preferred to use the Jazz Bass in the studio and in a 2010 interview mentioned that he still had that bass at the time.


title: John Paul Jones (musician)

text: Jones' keyboard skills added an eclectic dimension that realised Led Zeppelin as more than just a hard rock band. Keyboard highlights include the delicate "The Rain Song" ("Houses of the Holy") played on a Mellotron; the funky "Trampled Under Foot", played on a Clavinet ("Physical Graffiti"); and the eastern scales of "Kashmir", also played on a Mellotron (also on "Physical Graffiti"). In live performances, Jones' keyboard showpiece was "No Quarter", often lasting for up to half-an-hour and sometimes including snatches of "Amazing Grace", Joaquín Rodrigo's "Concierto de Aranjuez", which had inspired Miles Davis' "Sketches of Spain", and variations of classical pieces by composers such as Rachmaninoff.