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Epinephrine autoinjector

An epinephrine autoinjector (or adrenaline autoinjector, also known by the trademark EpiPen) is a medical device for injecting a measured dose or doses of epinephrine (adrenaline) by means of autoinjector technology. It is most often used for the treatment of anaphylaxis. The first epinephrine autoinjector was brought to market in 1983.

Medical uses
Epinephrine autoinjectors are hand-held devices carried by those who have severe allergies; the epinephrine delivered by the device is an emergency treatment for anaphylaxis.

When anaphylaxis is suspected, epinephrine solution should be given as soon as possible as an intramuscular injection, in the middle of the outer side of the thigh, which corresponds to the location of the vastus lateralis muscle. The injection may be repeated every 5 to 15 minutes if there is insufficient response. A second dose is needed in 16–35% of episodes with more than two doses rarely required; in around 80% of the cases where a second dose is administered, it is by a medical professional. It is not clear which are the people who might need a second injection at the outset. The intramuscular route is preferred over subcutaneous administration because the latter may have delayed absorption. Minor adverse effects from epinephrine include tremors, anxiety, headaches, and palpitations.

The epinephrine in autoinjectors expires after one year. A study in rabbits showed that intramuscular epinephrine has decreased effectiveness after it expires; that study also recommended that if the drug in an expired device has not started to precipitate (if the solution is not cloudy and has no particles in it) using the expired device is better than no injection at all in an emergency situation.

Design
The devices contain a fixed dose of epinephrine and a spring-loaded needle (or, in the case of AuviQ, a CO2-driven needle) that exits the tip or edge of the device and penetrates the recipient's skin, to deliver the medication via intramuscular injection.

People to whom epinephrine autoinjectors are prescribed need to be trained how to use the specific device prescribed. The rate of unintentional injections using these devices is unknown but a 2009 review found that the rate is increasing. Unintentional injections are delivered to a finger or thumb around 90% of the time; they cause intense pain locally but usually completely resolve. The cause of unintentional injections has been attributed to design flaws, where the device is mistaken for a pen or the user mistakes which end of the device contains the needle.

The European Medicines Agency conducted a review of the safety of devices then on the market and found several factors that determine whether the devices successfully deliver drug into muscle, including "needle length, the thickness of fat under the skin, the way the auto-injector works (e.g., if it is spring loaded or not), the angle at which the device is placed on the skin and the force used to activate the device as well as how well the user follows the instructions for injection." It found that how well the user was trained was the most important factor determining successful delivery, and requested companies to develop better training materials for doctors and people to whom the devices are prescribed.

Another design of epinephrine autoinjectors was created by two identical twin brothers (Eric and Evan Edwards) who were also users of epinephrine autoinjectors. They realized the inconveniences of carrying bulky autoinjectors and decided to come up with a new device to address the problems while they were in college. The brothers split to study different fields with a shared goal to create a new device. One brother took an engineering major and the other took a pre-medical track and earned a doctorate degree in pharmaceutical sciences. Eventually, they came up with a design that has the shape and size of a smartphone which can be put into a pocket. The new device also has retractable needle and automated voice instructions to assist the users on how to correctly use the autoinjectors. The Company they created was called Intelliject and was later named kaleo. The product was launched with the brand name "Auvi-Q" in the United States and "Allerject" in Canada.

In 2013, emergency physician Seth C. Hawkins and coauthors published a technique for obtaining multiple additional doses of epinephrine from used, single dose autoinjectors EpiPen and Adrenaclick. It was emphasized this was an emergency adaptation of the intended design for austere environments when no additional epinephrine was available. In 2016, Robinson and Lareau published a similar technique adapted to used AuviQ autoinjectors.

Product introduction
Autoinjectors were originally developed for the rapid administration of nerve gas antidotes in kits like the Mark I NAAK. The first modern epinephrine autoinjector, the EpiPen, was invented in the mid-1970s at Survival Technology in Bethesda, Maryland, US by Sheldon Kaplan and was first approved for marketing by the FDA in 1987.

One of the people who helped in making the EpiPen was Richard B. Toren. He had the idea to use this technology for allergic reactions because his daughter was allergic to bees and had to carry around a complex kit if she was ever stung. He then helped to slightly alter the technology in order to create EpiPen's current design.

In 1996, Survival Technology merged with a company called Brunswick Biomedical and the new company was called Meridian Medical Technologies. In 1997, Dey, a subsidiary of Merck KGaA, acquired the exclusive right to market and distribute the EpiPen. In 1998 there was a recall of one million EpiPens, the second such recall in a year.

In 2001 Meridian and Dey introduced a two-pack version of the EpiPen; at that time the device had $23.9 million in annual sales and accounted for 75% of the market in the United States. In 2002 King Pharmaceuticals acquired Meridian for $247.8 million in cash; the deal was completed in January 2003. Kaplan continued to improve his designs over the years, filing for example US Patent 6,767,336 in 2003.

In 2003, Hollister-Stier received approval from the FDA to market an epinephrine autoinjector called Twinject that could deliver two shots of epinephrine, which it had spent ten years developing. In 2005, it sold the product to Verus Pharmaceuticals, which launched the product the same year. In March 2008, Sciele Pharma acquired Twinject from Verus and later that year, Sciele was acquired by Shionogi.

In 2007, Mylan acquired the right to market the EpiPen from Merck KGaA as part of a larger transaction. At that time annual sales were around $200 million and the EpiPen had about 90% of the market.

In 2009, Mylan and King started marketing a new version of EpiPen with the same basic mechanism but a stronger spring, better safety features, and clearer markings and instructions; an expert for NBC News estimated that the cost to redesign the device and packaging may have been "several million dollars" and the cost to retool the manufacturing process may have "run into the double-digit millions."

Market development
In 2009, Teva Pharmaceuticals filed an ANDA to market a generic EpiPen in collaboration with Antares Pharma Inc, a maker of injection systems; Pfizer and King sued them for infringing US Patent 7,449,012 that was due to expire in 2025; Pfizer, Mylan, and Teva settled in April 2012 in a deal that allowed Teva to start selling the device in mid-2015, pending FDA approval.

In 2009, Intelliject, a US startup developing a new epinephrine autoinjector, licensed their product to Sanofi.

King was acquired by Pfizer in 2010 for $3.6 billion in cash.

In 2010, Sciele/Shionogi faced a recall of Twinject devices and launched Adrenaclick, a modified version of the Twinject that could deliver only one dose.

In 2010, European regulators approved Twinject, and also approved a new epinephrine autoinjector made by ALK and sold under the brand name Jext. Jext was launched in the European Union in September 2011.

Also in 2010, Shionogi authorized Greenstone, the authorized generics division of Pfizer, to begin selling an authorized generic of Adrenaclick. The media noted that Pfizer, through Greenstone, was marketing a generic epinephrine autoinjector when Pfizer acquired King later that year. At that time, King and Mylan's EpiPen had 91% of the global market share for epinephrine autoinjectors and 96% of the US market.

In 2010, Pfizer and King sued Novartis' Sandoz generic unit for patent infringement after Sandoz submitted an ANDA to sell a generic EpiPen. In response, Sandoz challenged the validity of the patents, and as of July 2016 this litigation was ongoing.

In 2011, Pfizer and King sued Intelliject and Sanofi after the companies filed a 505(b)(2) New Drug Application for the product, then known as "e-cue"; Pfizer, Mylan and Sanofi settled in 2012 under a deal that allowed the device to enter the market no earlier than November 2012, pending FDA approval. In August 2012, the FDA approved the autoinjector, called "Auvi-Q" after the FDA required a name change from "e-cue". The device is equipped with a sound chip to provide electronic voice instructions to guide the user in the proper use of the device.

In 2012, Mylan launched a program called EpiPen4Schools to sell EpiPens in bulk and with discounts to schools; to participate in the program schools had to agree not to buy epinephrine autoinjectors from any other company for a year.

In December 2012, the National Association of State Boards of Education launched a policy initiative designed to "help state boards of education as they develop student health policies regarding anaphylaxis and epinephrine auto-injector access and use", and advocated for state laws protecting school from legal liability for stocking and using epinephrine autoinjectors. Gayle Conelly Manchin, mother of Mylan's CEO, Heather Bresch, had become president of the association in 2010, and shortly after had discussed donations from her "daughter's company" to the association. Manchin had been appointed to the West Virginia state school board by her husband Joe Manchin, then-governor of the state, in 2012.

In 2012, Shionogi, the manufacturer of Adrenaclick and Twinject, announced it would stop making them; it had sold the rights to the NDA to a company called Amedra Pharmaceuticals.

In June 2013, Amedra relaunched Adrenaclick. and at the same time, Lineage Therapeutics launched its authorized generic version of Adrenaclick. Lineage was a wholly owned subsidiary of Amedra that had acquired the rights to the Adrenaclick authorized generic from Greenstone/Pfizer.

After successful lobbying from Mylan, in 2013, the "School Access to Emergency Epinephrine Act" became law after passing Congress with broad and bipartisan support; it protected anyone from liability if they administered epinephrine to a child in a school (previously, only trained professionals or the affected person were allowed to administer the drug, and were open to liability), and it provided some financial incentives for schools that didn't already stock epinephrine autoinjector to start stocking them. Joe Manchin, the father of Mylan's CEO, was a senator at that time.

In January 2015 Mylan filed a citizen petition with the FDA raising concerns about TEVA's ANDA application to market a generic EpiPen and filed an additional supplement later in May; the FDA rejected the petition in June.

In March 2015, Impax Laboratories acquired the parent company of Amedra and Lineage, and placed Amedra and the Adrenaclick in its Impax Specialty Pharma division; at the same time it acquired Lineage, which it placed, along with its generic version of Adrenaclick, in its Impax Generics division.

In May 2015, the Emerade epinephrine autoinjector developed by the Swedish company Medeca was approved in Sweden and Germany; it had been approved in the UK in 2013. Also in 2015 Valeant, which had licensed the rights from Medeca, abandoned its efforts to get Emerade approved in the US.

In October 2015, Auvi-Q and Allerject devices were voluntarily recalled by Sanofi in North America. The reason stated by Sanofi was that the products had been found to potentially have inaccurate dosage delivery, which may include failure to deliver drug. In February 2016, Sanofi terminated its license to manufacture and market the Auvi-Q, leaving Kaléo (Intelliject was renamed) to consider how and whether to re-introduce the device.

The EpiPen had 89% of the market for epinephrine autoinjectors in 2015; in the first half of the year it had about 85% share and Auvi-Q had about 10% share.

In March 2016, Teva's ANDA for a generic EpiPen, which had already faced several delays, was rejected by the FDA.

In 2015 Mylan had about $1.5 billion in sales of EpiPens, which accounted for 40% of Mylan's profit. Mylan had maintained about a 90% market share since it had acquired the product, and had continually raised the price of EpiPens starting in 2009: in 2009, the wholesale price of two EpiPens was about $100; by July 2013, the price was about $265; in May 2015, it was around $461; and in May 2016, the price rose again to around $609, around a 500% jump from the price in 2009. The cost of the drug and device to Mylan as of 2016 was about $35. In the summer of 2016, as parents prepared to send their children back to school and went to pharmacies to get new EpiPens, people began to express outrage at the cost of the EpiPen and Mylan was widely and harshly criticized. In September 2016, the New York State Attorney General began an investigation into Mylan's EpiPen4Schools program in New York to determine if the program's contracts violated antitrust law and the West Virginia State Attorney General opened an investigation into whether Mylan had given the state the correct discount under the Medicaid Drug Rebate Program and subpoenaed the company when it refused to provide the documentation the state requested. In October 2016, Mylan announced a $465M settlement with the US Department of Justice over rebates paid by Mylan to states under the Medicaid Drug Rebate Program.

On 5 September 2017, FDA posted a warning letter to the manufacturer, Meridian Medical Technologies. The agency warned Meridian Medical for failing to investigate problems with the devices, recall bad batches, and follow-up on problems found. According to the FDA, the manufacturer of EpiPen devices failed to address known malfunctions in its auto-injectors even as hundreds of customer complaints rolled in and failures were linked to deaths. During an inspection, Meridian employees told inspectors that they weren't allowed to disassemble and investigate complain samples, because they were allowed to do if only it was “approved by management”.

On 16 August 2018 the FDA approved the first generic EpiPen from Teva Pharmaceuticals.

In an effort to address the supply shortage of EpiPens, on August 21, 2018 the FDA approved extending the expiration dates on some products by four months.

The Sandoz division of Novartis announced on 9 July 2019 the availability of Symjepi, a manual epinephrine injection as an alternative to autoinjectors, in 0.3 mg and 0.15 mg versions.

Brands
As of 2015, the following epinephrine autoinjectors were available in various parts of Europe: Adrenalina WZF, Adrenaline (epinephrine) 1 in 1000 solution for injection BP auto-injector, Altellus, Anapen, Emerade, EpiPen, Fastjekt, FastPen, and Jext. As of 2018, three branded products were available in the United States: Adrenaclick, Auvi-Q, and EpiPen.

As of 2020, three brands of autoinjectors are available in Canada: Allerject, Emerade, and EpiPen. One generic autoinjector has been approved by Health Canada but is not marketed. From 2015 to 2020 the only autoinjector marketed in Canada was EpiPen and production issues led to supply shortages during that period. During a 2018 shortage of EpiPens, Health Canada temporarily permitted the importation of Auvi-Q autoinjectors from the United States.

As of 2005, epinephrine autoinjectors were not available in most of the developing world.

Canada
, in Canada the wholesale cost of a single EpiPen is approximately CA$95.00.

Europe
, two EpiPens cost around $100 in France and at maximum 10€ for members of the statutory health insurance in Germany.

, two Jext autoinjectors cost users about £8.50 (US$) in Britain, and the National Health Service pays around £48 (US$) in order to make them available; that price was about 17 percent less than 2013.

Supplies of 150 microgram adrenaline auto-injectors were said to be “critical” in the United Kingdom in October 2018. Community pharmacists were told to prioritise supplies for children weighing 25 kg or less. Mylan identified shortages because of manufacturing problems in May 2018.

United States
In October 2016 the CEO of Mylan testified to Congress that Pfizer/King charged Mylan about $34.50 for one EpiPen. The devices deliver about $1 worth of drug. In September 2016, a Silicon Valley engineering consultancy performed a teardown analysis of the EpiPen and estimated the manufacturing and packaging costs at about $10 for a two-pack.

The EpiPen, manufactured by Meridian Medical Technologies, and marketed by Mylan, has dominated the market. In 2007 when Mylan acquired the rights to market the product, annual sales of all epinephrine autoinjectors were about $200 million and EpiPen had around 90% of the market; in 2015 the market size was around $1.5 billion and Mylan still had about 90% of the market. Mylan raised the price from around $100 for a package of two EpiPens in 2007 to around $600 in 2016. In the United Kingdom, an EpiPen costs £26.45 as of 2015. In Canada they are about 120 CAD each.

Mylan acquired the right to market the EpiPen line of epinephrine autoinjector devices from Merck KGaA as part of their 2007 deal. Heather Bresch, Mylan's CEO, saw an opportunity to increase sales in the US through marketing and advocacy, and the company launched a marketing campaign to increase awareness of the dangers of anaphylaxis for people with severe allergies that made the EpiPen brand as identified with epinephrine autoinjectors as Kleenex is for facial tissue; the company also successfully lobbied the FDA to broaden the label to include risk of anaphylaxis and in parallel, successfully lobbied Congress to generate legislation making EpiPens available in public places like defibrillators are, and hired the same people that Medtronic had worked with on defibrillator legislation to do so.

Mylan's efforts to maintain its market dominance were aided when Sanofi's competing product was recalled in November 2015 and further when Teva's generic competitor was rejected by the FDA in March 2016. By the first half of 2015, sales of EpiPen accounted for 40% of Mylan's profit. Those profits were also due in part to Mylan's continually raising the price of EpiPens starting in 2009: in 2007, the wholesale price of two EpiPens was about $100; the price was about the same in 2009; by July 2013, the price was about $265; in May 2015, it was around $461; and in May 2016, the price rose again to around $609, around a 500% jump from the price in 2009. The last price increase sparked widespread outrage in the late summer as parents prepared to send their children back to school and went to pharmacies to get new EpiPens. Some Americans responded to the high price by buying EpiPens online from pharmacies outside the US, forgoing new EpiPens and relying on their expired EpiPen, or forgoing an autoinjector altogether and having their children carry pre-loaded syringes.

In response to criticism, Mylan increased financial assistance available for some patients to purchase EpiPens, a gesture that was called a "classic public relations move" by Harvard Medical School professor Aaron Kesselheim. The up to $300 saving cards can be used only by a small number of people who need the drug, and no one on Medicaid. They do nothing about the high price which is still being paid by insurers, who ultimately pass the cost on to consumers. In October 2016, Mylan announced a settlement with the US Department of Justice over rebates paid by Mylan to states under the Medicaid Drug Rebate Program. Questions had been raised by Congress and others about why EpiPen had been classified as a generic rather a proprietary product in the program since 1997; generic drugs have lower rebates (13%) than proprietary drugs (23%), and price hikes for generic drugs cannot be passed onto states, and a common form of pharmaceutical fraud involves misclassifying proprietary drugs as generic under the program. Under the agreement, Mylan agreed to pay a $465 million payment and to a sign a corporate integrity agreement requiring it to perform better in the future; the settlement also resolved cases brought by states related to the rebates.

, the authorized generic of Adrenaclick cost $142 at retail stores.

In September 2016, a group of hackers called the Four Thieves Vinegar published a video and documents describing what they call an EpiPencil, an autoinjector which can be built using off-the-shelf parts, for a claimed price tag of about $30. At its core is a repurposed insulin autoinjector. This device has not been subject to any validation by regulatory agencies.

title: Epinephrine autoinjector


text:
Séance

A séance or seance is an attempt to communicate with spirits. The word séance comes from the French word for "session", from the Old French seoir, "to sit". In French, the word's meaning is quite general and mundane: one may, for example, speak of "une séance de cinéma" (lit. 'a movie session'). In English, however, the word came to be used specifically for a meeting of people who are gathered to receive messages from ghosts or to listen to a spirit medium discourse with or relay messages from spirits. In modern English usage, participants need not be seated while engaged in a séance.

Fictionalised conversations between the deceased appeared in Dialogues of the Dead by George, First Baron Lyttelton, published in England in 1760. Among the notable spirits quoted in this volume are Peter the Great, Pericles, a "North-American Savage", William Penn, and Christina, Queen of Sweden. The popularity of séances grew dramatically with the founding of the religion of Spiritualism in the mid-nineteenth century. Perhaps the best-known series of séances conducted at that time were those of Mary Todd Lincoln who, grieving the loss of her son, organized Spiritualist séances in the White House, which were attended by her husband, President Abraham Lincoln, and other prominent members of society. The 1887 Seybert Commission report marred the credibility of Spiritualism at the height of its popularity by publishing exposures of fraud and showmanship among secular séance leaders. Modern séances continue to be a part of the religious services of Spiritualist, Spiritist, and Espiritismo churches today, where a greater emphasis is placed on spiritual values versus showmanship.

Varieties of séance
The term séance is used in a few different ways, and can refer to any of four different activities, each with its own social norms and conventions, its own favoured tools, and its own range of expected outcomes.

Religious séances
In the religion of Spiritualism, and the religion of Divine Metaphysics (a federally recognized religious branch out of Spiritualism in the United States), it is generally a part of services to communicate with living personalities in the spirit world. Usually, this is only called "séance" by outsiders; the preferred term for Spiritualists is "receiving messages". In these sessions, which generally take place in well-lit Spiritualist churches or outdoors at Spiritualist camps (such as Lily Dale in upstate New York or Camp Cassadaga in Florida), an ordained minister or gifted contact medium will relate messages from spirit personalities to those here in the physical form. Generally Spiritualist "message services" or "demonstrations of the continuity of life" are open to the public. Sometimes the medium stands to receive messages and only the sitter is seated; in some churches, the message service is preceded by a "healing service" involving some form of faith healing.

In addition to communicating with the spirits of people who have a personal relationship to congregants, some Spiritual Churches also deal with spirits who may have a specific relationship to the medium or a historic relationship to the body of the church. An example of the latter is the spirit of Black Hawk, a Native American warrior of the Fox tribe who lived during the 19th century. Black Hawk was a spirit who was often contacted by the Spiritualist medium Leafy Anderson and he remains the central focus of special services in the African American Spiritual Churches that she founded.

In the Latin American religion of Espiritismo, which somewhat resembles Spiritualism, séance sessions in which congregants attempt to communicate with spirits are called misas (literally "masses"). The spirits addressed in Espiritismo are often those of ancestors or Catholic saints.

Stage mediumship séances
Mediums who give performances on stage of contacting spirits, with audience members seated before them, are not literally holding a séance, because they themselves are not seated; however, this is still called "séance". One of the foremost early practitioners of this type of contact with the dead was Paschal Beverly Randolph, who worked with the spirits of the relatives of audience members, but was also famed for his ability to contact and deliver messages from ancient seers and philosophers, such as Plato.

Leader-assisted séances
Leader-assisted séances are generally conducted by small groups of people, with participants seated around a table in a dark or semi-dark room. The leader is typically asserted to be a medium and he or she may go into a trance that theoretically allows the spirits to communicate through his or her body, conveying messages to the other participants. Other modes of communication may also be attempted, including psychography or automatic writing, numbered raps, levitation of the table or of spirit trumpets, apports, or even smell. It was thought spirits of the dead resided within the realm of dark and shadow, making the absence of light a necessity to invoke them. Skeptics were unwilling to accept this required condition. Saying,"You would not buy an automobile if it was only presented in the dark."

This is the type of séance that is most often the subject of shock and scandal when it turns out that the leader is practicing some form of stage magic illusion or using mentalism tricks to defraud clients.

Informal social séances
Among those with an interest in the occult, a tradition has grown up of conducting séances outside of any religious context and without a leader. Sometimes only two or three people are involved, and, if they are young, they may be using the séance as a way to test their understanding of the boundaries between reality and the paranormal. It is in such small séances that the planchette and ouija board are most often utilized.

Spiritualist Seance
Here spiritualists and practitioners (psychic and mediums) hold a seance so that all participants speak with various personalities in the spirit world. This held in a seating manner in a circle.

Mediumship, trance, and channeling

Mediumship involves an act where the practitioner attempts to receive messages from spirits of the dead and from other spirits that the practitioner believes exist. Some self-ordained mediums are fully conscious and awake while functioning as contacts; others may slip into a partial or full trance or into an altered state of consciousness. These self-called "trance-mediums" often state that, when they emerge from the trance state, they have no recollection of the messages they conveyed; it is customary for such practitioners to work with an assistant who writes down or otherwise records their words.

Spirit boards, talking boards, and ouija boards
Spirit boards, also known as talking boards, or ouija boards (after a well-known brand name) are flat tablets, typically made of wood, Masonite, chipboard, or plastic. On the board are a number of symbols, pictures, letters, numbers and/or words. The board is accompanied by a planchette (French for "little board"), which can take the form of a pointer on three legs or magnifying glass on legs; homemade boards may employ a shot glass as a planchette. A most basic Ouija board would contain simply the alphabet of whatever country the board is being used in, although it is not uncommon for whole words to be added.

The board is used as follows: One or more of the participants in the séance place one or two fingers on the planchette which is in the middle of the board. The appointed medium asks questions of the spirit(s) with whom they are attempting to communicate.

Trumpets, slates, tables, and cabinets
During the latter half of the 19th century, a number of Spiritualist mediums began to advocate the use of specialized tools for conducting séances, particularly in leader-assisted sessions conducted in darkened rooms. "Spirit trumpets" were horn-shaped speaking tubes that were said to magnify the whispered voices of spirits to audible range. "Spirit slates" consisted of two chalkboards bound together that, when opened, were said to reveal messages written by spirits. "Séance tables" were special light-weight tables which were said to rotate, float, or levitate when spirits were present. "Spirit cabinets" were portable closets into which mediums were placed, often bound with ropes, in order to prevent them from manipulating the various aforementioned tools.

Critical objections
Scientific skeptics and atheists generally consider both religious and secular séances to be scams, or at least a form of pious fraud, citing a lack of empirical evidence. The exposure of supposed mediums whose use of séance tools derived from the techniques of stage magic has been disturbing to many believers in spirit communication. In particular, the 1870s exposures of the Davenport Brothers as illusionists and the 1887 report of the Seybert Commission brought an end to the first historic phase of Spiritualism. Stage magicians like John Nevil Maskelyne and Harry Houdini made a side-line of exposing fraudulent mediums during the late 19th and early 20th centuries. In 1976, M. Lamar Keene described deceptive techniques that he himself had used in séances; however, in the same book, Keene also stated that he still had a firm belief in God, life after death, ESP, and other psychic phenomena. In his 2004 television special Seance, magician Derren Brown held a séance and afterwards described some of the tricks used by him (and 19th-century mediums) to create the illusion of paranormal events.

Critics of channeling—including both skeptics and believers—state that since the most commonly reported physical manifestations of channeling are an unusual vocal pattern or abnormal overt behaviors of the medium, it can be quite easily faked by anyone with theatrical talent. Critics of spirit board communication techniques—again including both skeptics and believers—state that the premise that a spirit will move the planchette and spell out messages using the symbols on the board is undermined by the fact that several people have their hands on the planchette, which allows any of them to spell out anything they want without the others knowing. They say that this is a common trick, used on occasions such as teenage sleepover parties, to scare the people present.

Another criticism of spirit board communication involves what is called the ideomotor effect which has been suggested as an automatism, or subconscious mechanism, by which a Ouija-user's mind unknowingly guides his hand upon the planchette, hence he will honestly believe he is not moving it, when, in fact, he is. This theory rests on the embedded premise that human beings actually have a "subconscious mind," a belief not held by all.

The exposures of fraud by tool-using mediums have had two divergent results: skeptics have used historic exposures as a frame through which to view all spirit mediumship as inherently fraudulent, while believers have tended to eliminate the use of tools but continued to practice mediumship in full confidence of its spiritual value to them.

Jews and Christians are taught that it is sinful to attempt to conjure or control spirits in accordance with Deuteronomy 18:9–12.

Psychology
Research in anomalistic psychology has revealed the role of suggestion in seances. In a series of fake seance experiments (Wiseman et al.. 2003) paranormal believers and disbelievers were suggested by an actor that a table was levitating when, in fact, it remained stationary. After the seance, approximately one third of the participants incorrectly reported that the table had moved. The results showed a greater percentage of believers reporting that the table had moved. In another experiment the believers had also reported that a handbell had moved when it had remained stationary and expressed their belief that the fake seances contained genuine paranormal phenomena. The experiments strongly supported the notion that in the seance room, believers are more suggestible than disbelievers for suggestions that are consistent with their belief in paranormal phenomena.

Mediums

Popular 19th-century trance medium lecturers include Cora Scott Hatch, Achsa W. Sprague, Emma Hardinge Britten (1823–1899), and Paschal Beverly Randolph (1825–1875).

Among the notable people who conducted small leader-assisted séances during the 19th century were the Fox sisters, whose activities included table-rapping, and the Davenport Brothers, who were famous for the spirit cabinet work. Both the Foxes and the Davenports were eventually exposed as frauds.

In the 20th century, notable trance mediums also include Edgar Cayce, Arthur Ford and David Marius Guardino.

Attendees
Notable people who have attended séances and professed a belief in Spiritualism include the social reformer Robert Owen; the journalist and pacifist William T. Stead; William Lyon Mackenzie King, the Prime Minister of Canada for 22 years, who sought spiritual contact and political guidance from his deceased mother, his pet dogs, and the late US President Franklin D. Roosevelt; the journalist and author Lloyd Kenyon Jones; and the physician and author Arthur Conan Doyle.

A number of artists, including abstractionists Hilma af Klint, the Regina Five, and Paulina Peavy have given partial or complete credit for some of their work to spirits that they contacted during seances. Paulina said that "when she painted, she did not have control over her brush, that it moved on its own, and that it was Lacamo (the spirit) who was directing it."

Scientists who have conducted a search for real séances and believed that contact with the dead is a reality include chemist William Crookes, evolutionary biologist Alfred Russel Wallace, inventor of radio Guglielmo Marconi, inventor of the telephone Alexander Graham Bell, experimental physicist Oliver Lodge, and inventor of television technology John Logie Baird, who said he had contacted the spirit of inventor Thomas Edison.

Debunkers
Among the best-known exposers of fraudulent mediumship acts have been the researchers Frank Podmore of the Society for Psychical Research, Harry Price of the National Laboratory of Psychical Research, the professional stage magicians John Nevil Maskelyne (who exposed the Davenport Brothers) and Harry Houdini, who clearly stated that he did not oppose the religion of Spiritualism itself, but only the trickery by phony mediums that was being practiced in the name of the religion.

The psychical researcher Hereward Carrington exposed the tricks of fraudulent mediums such as those used in slate-writing, table-turning, trumpet mediumship, materializations, sealed-letter reading and spirit photography. The skeptic Joseph McCabe documented many mediums who had been caught in fraud and the tricks they used in his book Is Spiritualism Based on Fraud? (1920).

Magicians have a long history of exposing the fraudulent methods of mediumship. Early debunkers included Chung Ling Soo, Henry Evans and Julien Proskauer. Later magicians to reveal fraud were Fulton Oursler, Joseph Dunninger, and Joseph Rinn. The researchers Trevor H. Hall and Gordon Stein have documented the trickery of the medium Daniel Dunglas Home. Tony Cornell exposed a number of fraudulent mediums including Rita Goold and Alec Harris.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Séance


text:
Naidu

Naidu (also spelled as Nayudu, Naidoo) is a Telugu title commonly used by various Telugu castes. 'Nayudu/Naidu' (నాయుడు) is a contraction of the Telugu word 'Nayakudu' (నాయకుడు) meaning leader, chief, headman. Telugu castes such as the Kapu/Balija Kamma, Gavara,  Golla,  Turpu Kapu, Velama, Boya etc. use the title.

In Coastal Andhra, the term Naidu primarily refers to Kapu caste.

Notable people
People bearing the title Naidu include:

 * Ama Naidoo, social activist from South Africa
 * Baddukonda Appala Naidu, politician, YSRCP leader
 * B. Munuswamy Naidu, former Chief Minister of Madras Presidency
 * Buchi Babu Naidu, Indian cricket pioneer known as the 'father of South Indian cricket'
 * Chandra Nayudu, India's first female cricket commentator
 * Chota K. Naidu, Telugu cinematographer
 * C. K. Nayudu, first captain of the Indian cricket team and one of India's greatest cricketers
 * C. S. Nayudu, represented India in Test cricket from 1934 to 1952
 * D. K. Adikesavulu Naidu, former chairman of Tirumala Tirupati Devasthanams
 * Dwaram Venkataswamy Naidu, Carnatic violinist
 * Daggubati Ramanaidu, Telugu film producer
 * Gali Muddu Krishnama Naidu, member of Telugu Desam Party
 * Galla Ramachandra Naidu, Indian industrialist, the founder of Amara Raja Group of companies
 * Gorle Sriramulu Naidu, former Minister, Congress Party, Andhra Pradesh
 * Grandhi Venkata Reddy Naidu, first Law Minister of Andhra Pradesh
 * G. D. Naidu, scientist, inventor and businessman, known as "Edison of India"
 * K. Govindaswamy Naidu, entrepreneur, founder of KG Group
 * Kamisetty Parasuram Naidu, Speaker of Pondicherry Assembly (1985–1989)
 * Kodi Rammurthy Naidu, bodybuilder, strongman, and wrestler
 * Kondapalli Pydithalli Naidu, former Member of Parliament; Telugu Desam Party leader
 * Kondapalli Appala Naidu, Telugu Desam Party leader
 * Kuppuswami Naidu, entrepreneur, founder of Lakshmi Mills
 * Kurma Venkata Reddy Naidu, former Chief Minister and Governor of Madras Presidency
 * K. Venkataswami Naidu, politician
 * Leela Naidu, Indian actress
 * M. Venkaiah Naidu, 13th Vice President of India
 * Nalla Reddi Naidu, former Member of Parliament
 * Naransamy Roy Naidoo, social activist in South Africa
 * Nimmala Rama Naidu, politician, Telugu Desam Party
 * N. Chandrababu Naidu, current Chief Minister of Andhra Pradesh, leader of Telugu Desam Party
 * P. Varadarajulu Naidu, Indian physician, politician, journalist and Indian independence activist
 * P. S. Govindasamy Naidu, educator, founder of PSG Group
 * P. V. Rangayya Naidu, former Director General of Police and member of the 10th Lok Sabha of India
 * Padmaja Naidu, freedom fighter
 * Palnati Brahmanaidu, minister of a small Andhra kingdom of Palnadu
 * Pathivada Narayanaswamy Naidu, former Minister, Andhra Pradesh
 * Pemmasani Ramalinga Nayudu, commander of a Vijayanagara military unit
 * Prakash Nayudu, sportsperson who represented Madhya Pradesh cricket team
 * Raghupathi Venkaiah Naidu, filmmaker widely known as the "father of Telugu cinema"
 * Raghupathi Venkataratnam Naidu, Indian social reformer and educationist
 * Ramesh Naidu, National Award-winning music composer
 * Sarojini Naidu, independence activist and poet known as "nightingale of India"
 * Sobha Naidu, classical dancer
 * Srihari S. Naidu, physician
 * S. R. A. S. Appala Naidu, politician; former MP and state minister
 * Thapi Dharma Rao Naidu, writer and journalist, winner of Sahitya Akademi Award
 * Thota Narasayya Naidu, freedom fighter
 * Vasireddy Venkatadri Nayudu, Amaravathi Raja

title: Naidu


text:
Nightingale of India

Nightingale of India may refer to:

 * Sarojini Naidu, political activist and poet (1879–1949)
 * Lata Mangeshkar, playback singer and occasional music composer (1929–2022)

title: Nightingale of India


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Fractal dimension

In mathematics, a fractal dimension is a term invoked in the science of geometry to provide a rational statistical index of complexity detail in a pattern. A fractal pattern changes with the scale at which it is measured. It is also a measure of the space-filling capacity of a pattern, and it tells how a fractal scales differently, in a fractal (non-integer) dimension.

The main idea of "fractured" dimensions has a long history in mathematics, but the term itself was brought to the fore by Benoit Mandelbrot based on his 1967 paper on self-similarity in which he discussed fractional dimensions. In that paper, Mandelbrot cited previous work by Lewis Fry Richardson describing the counter-intuitive notion that a coastline's measured length changes with the length of the measuring stick used (see Fig. 1). In terms of that notion, the fractal dimension of a coastline quantifies how the number of scaled measuring sticks required to measure the coastline changes with the scale applied to the stick. There are several formal mathematical definitions of fractal dimension that build on this basic concept of change in detail with change in scale: see the section Examples.

Ultimately, the term fractal dimension became the phrase with which Mandelbrot himself became most comfortable with respect to encapsulating the meaning of the word fractal, a term he created. After several iterations over years, Mandelbrot settled on this use of the language: "...to use fractal without a pedantic definition, to use fractal dimension as a generic term applicable to all the variants."

One non-trivial example is the fractal dimension of a Koch snowflake. It has a topological dimension of 1, but it is by no means rectifiable: the length of the curve between any two points on the Koch snowflake is infinite. No small piece of it is line-like, but rather it is composed of an infinite number of segments joined at different angles. The fractal dimension of a curve can be explained intuitively by thinking of a fractal line as an object too detailed to be one-dimensional, but too simple to be two-dimensional. Therefore, its dimension might best be described not by its usual topological dimension of 1 but by its fractal dimension, which is often a number between one and two; in the case of the Koch snowflake, it is approximately 1.2619.

Introduction

A fractal dimension is an index for characterizing fractal patterns or sets by quantifying their complexity as a ratio of the change in detail to the change in scale. Several types of fractal dimension can be measured theoretically and empirically (see Fig. 2). Fractal dimensions are used to characterize a broad spectrum of objects ranging from the abstract to practical phenomena, including turbulence,  river networks, urban growth,  human physiology,  medicine, and market trends. The essential idea of fractional or fractal dimensions has a long history in mathematics that can be traced back to the 1600s, but the terms fractal and fractal dimension were coined by mathematician Benoit Mandelbrot in 1975.

Fractal dimensions were first applied as an index characterizing complicated geometric forms for which the details seemed more important than the gross picture. For sets describing ordinary geometric shapes, the theoretical fractal dimension equals the set's familiar Euclidean or topological dimension. Thus, it is 0 for sets describing points (0-dimensional sets); 1 for sets describing lines (1-dimensional sets having length only); 2 for sets describing surfaces (2-dimensional sets having length and width); and 3 for sets describing volumes (3-dimensional sets having length, width, and height). But this changes for fractal sets. If the theoretical fractal dimension of a set exceeds its topological dimension, the set is considered to have fractal geometry.

Unlike topological dimensions, the fractal index can take non-integer values, indicating that a set fills its space qualitatively and quantitatively differently from how an ordinary geometrical set does. For instance, a curve with a fractal dimension very near to 1, say 1.10, behaves quite like an ordinary line, but a curve with fractal dimension 1.9 winds convolutedly through space very nearly like a surface. Similarly, a surface with fractal dimension of 2.1 fills space very much like an ordinary surface, but one with a fractal dimension of 2.9 folds and flows to fill space rather nearly like a volume. This general relationship can be seen in the two images of fractal curves in Fig.2 and Fig. 3 – the 32-segment contour in Fig. 2, convoluted and space filling, has a fractal dimension of 1.67, compared to the perceptibly less complex Koch curve in Fig. 3, which has a fractal dimension of approximately 1.2619.

The relationship of an increasing fractal dimension with space-filling might be taken to mean fractal dimensions measure density, but that is not so; the two are not strictly correlated. Instead, a fractal dimension measures complexity, a concept related to certain key features of fractals: self-similarity and detail or irregularity. These features are evident in the two examples of fractal curves. Both are curves with topological dimension of 1, so one might hope to be able to measure their length and derivative in the same way as with ordinary curves. But we cannot do either of these things, because fractal curves have complexity in the form of self-similarity and detail that ordinary curves lack. The self-similarity lies in the infinite scaling, and the detail in the defining elements of each set. The length between any two points on these curves is infinite, no matter how close together the two points are, which means that it is impossible to approximate the length of such a curve by partitioning the curve into many small segments. Every smaller piece is composed of an infinite number of scaled segments that look exactly like the first iteration. These are not rectifiable curves, meaning they cannot be measured by being broken down into many segments approximating their respective lengths. They cannot be meaningfully characterized by finding their lengths and derivatives. However, their fractal dimensions can be determined, which shows that both fill space more than ordinary lines but less than surfaces, and allows them to be compared in this regard.

The two fractal curves described above show a type of self-similarity that is exact with a repeating unit of detail that is readily visualized. This sort of structure can be extended to other spaces (e.g., a fractal that extends the Koch curve into 3-d space has a theoretical D=2.5849). However, such neatly countable complexity is only one example of the self-similarity and detail that are present in fractals. The example of the coast line of Britain, for instance, exhibits self-similarity of an approximate pattern with approximate scaling. Overall, fractals show several types and degrees of self-similarity and detail that may not be easily visualized. These include, as examples, strange attractors for which the detail has been described as in essence, smooth portions piling up, the Julia set, which can be seen to be complex swirls upon swirls, and heart rates, which are patterns of rough spikes repeated and scaled in time. Fractal complexity may not always be resolvable into easily grasped units of detail and scale without complex analytic methods but it is still quantifiable through fractal dimensions.

History
The terms fractal dimension and fractal were coined by Mandelbrot in 1975, about a decade after he published his paper on self-similarity in the coastline of Britain. Various historical authorities credit him with also synthesizing centuries of complicated theoretical mathematics and engineering work and applying them in a new way to study complex geometries that defied description in usual linear terms. The earliest roots of what Mandelbrot synthesized as the fractal dimension have been traced clearly back to writings about nondifferentiable, infinitely self-similar functions, which are important in the mathematical definition of fractals, around the time that calculus was discovered in the mid-1600s. There was a lull in the published work on such functions for a time after that, then a renewal starting in the late 1800s with the publishing of mathematical functions and sets that are today called canonical fractals (such as the eponymous works of von Koch, Sierpiński, and Julia), but at the time of their formulation were often considered antithetical mathematical "monsters". These works were accompanied by perhaps the most pivotal point in the development of the concept of a fractal dimension through the work of Hausdorff in the early 1900s who defined a "fractional" dimension that has come to be named after him and is frequently invoked in defining modern fractals.

See Fractal history for more information

Role of scaling

The concept of a fractal dimension rests in unconventional views of scaling and dimension. As Fig. 4 illustrates, traditional notions of geometry dictate that shapes scale predictably according to intuitive and familiar ideas about the space they are contained within, such that, for instance, measuring a line using first one measuring stick then another 1/3 its size, will give for the second stick a total length 3 times as many sticks long as with the first. This holds in 2 dimensions, as well. If one measures the area of a square then measures again with a box of side length 1/3 the size of the original, one will find 9 times as many squares as with the first measure. Such familiar scaling relationships can be defined mathematically by the general scaling rule in Equation 1, where the variable $$N$$ stands for the number of measurement units (sticks, squares, etc.), $$\varepsilon$$ for the scaling factor, and $$D$$ for the fractal dimension:

This scaling rule typifies conventional rules about geometry and dimension – referring to the examples above, it quantifies that $$D=1$$ for lines because $$N=3$$ when $$\varepsilon =\tfrac{1}{3}$$, and that $$D=2$$ for squares because $$N=9$$ when $$\varepsilon= \tfrac{1}{3}.$$

The same rule applies to fractal geometry but less intuitively. To elaborate, a fractal line measured at first to be one length, when remeasured using a new stick scaled by 1/3 of the old may be 4 times as many scaled sticks long rather than the expected 3 (see Fig. 5). In this case, $$N=4$$ when $$\varepsilon = \tfrac{1}{3},$$ and the value of $$D$$ can be found by rearranging Equation 1:

That is, for a fractal described by $$N=4$$ when $$\varepsilon =\tfrac{1}{3}$$, such as the Koch snowflake, $$D=1.26185 \ldots$$, a non-integer value that suggests the fractal has a dimension not equal to the space it resides in.

Of note, images shown in this page are not true fractals because the scaling described by $$D$$ cannot continue past the point of their smallest component, a pixel. However, the theoretical patterns that the images represent have no discrete pixel-like pieces, but rather are composed of an infinite number of infinitely scaled segments and do indeed have the claimed fractal dimensions.

D is not a unique descriptor

As is the case with dimensions determined for lines, squares, and cubes, fractal dimensions are general descriptors that do not uniquely define patterns. The value of D for the Koch fractal discussed above, for instance, quantifies the pattern's inherent scaling, but does not uniquely describe nor provide enough information to reconstruct it. Many fractal structures or patterns could be constructed that have the same scaling relationship but are dramatically different from the Koch curve, as is illustrated in Figure 6.

For examples of how fractal patterns can be constructed, see Fractal, Sierpinski triangle, Mandelbrot set, Diffusion limited aggregation, L-system.

Fractal surface structures
The concept of fractality is applied increasingly in the field of surface science, providing a bridge between surface characteristics and functional properties. Numerous surface descriptors are used to interpret the structure of nominally flat surfaces, which often exhibit self-affine features across multiple length-scales. Mean surface roughness, usually denoted RA, is the most commonly applied surface descriptor, however numerous other descriptors including mean slope, root mean square roughness (RRMS) and others are regularly applied. It is found however that many physical surface phenomena cannot readily be interpreted with reference to such descriptors, thus fractal dimension is increasingly applied to establish correlations between surface structure in terms of scaling behavior and performance. The fractal dimensions of surfaces have been employed to explain and better understand phenomena in areas of contact mechanics, frictional behavior, electrical contact resistance and transparent conducting oxides.

Examples
The concept of fractal dimension described in this article is a basic view of a complicated construct. The examples discussed here were chosen for clarity, and the scaling unit and ratios were known ahead of time. In practice, however, fractal dimensions can be determined using techniques that approximate scaling and detail from limits estimated from regression lines over log vs log plots of size vs scale. Several formal mathematical definitions of different types of fractal dimension are listed below. Although for compact sets with exact affine self-similarity all these dimensions coincide, in general they are not equivalent:

 * Box counting dimension: D is estimated as the exponent of a power law.
 * $$D_0 = \lim_{\varepsilon \to 0} \frac{\log N(\varepsilon)}{\log\frac{1}{\varepsilon}}.$$

 * Information dimension: D considers how the average information needed to identify an occupied box scales with box size; $$p$$ is a probability.
 * $$D_1 = \lim_{\varepsilon \to 0} \frac{-\langle \log p_\varepsilon \rangle}{\log\frac{1}{\varepsilon}}$$

 * Correlation dimension: D is based on $$M$$ as the number of points used to generate a representation of a fractal and gε, the number of pairs of points closer than ε to each other.
 * $$D_2 = \lim_{M \to \infty} \lim_{\varepsilon \to 0} \frac{\log (g_\varepsilon / M^2)}{\log \varepsilon}$$

 * Generalized or Rényi dimensions: The box-counting, information, and correlation dimensions can be seen as special cases of a continuous spectrum of generalized dimensions of order α, defined by:
 * $$D_\alpha = \lim_{\varepsilon \to 0} \frac{\frac{1}{\alpha-1}\log(\sum_{i} p_i^\alpha)}{\log\varepsilon}$$

 * Higuchi dimension
 * $$D = \frac{d\ \log(L(k))}{d\ \log(k)}$$

 * Lyapunov dimension
 * Multifractal dimensions: a special case of Rényi dimensions where scaling behaviour varies in different parts of the pattern.
 * Uncertainty exponent
 * Hausdorff dimension: For any subset $$S$$ of a metric space $$X$$ and $$d\geq 0$$, the d-dimensional Hausdorff content of S is defined by
 * $$C_H^d(S):=\inf\Bigl\{\sum_i r_i^d:\text{ there is a cover of } S\text{ by balls with radii }r_i>0\Bigr\}.$$
 * The Hausdorff dimension of S is defined by
 * $$\dim_{\operatorname{H}}(X):=\inf\{d\ge 0: C_H^d(X)=0\}.$$

 * Packing dimension
 * Assouad dimension
 * Local connected dimension
 * Degree dimension: describes the fractal nature of the degree distribution of graphs.

 * Parabolic Hausdorff dimension

Estimating from real-world data
Many real-world phenomena exhibit limited or statistical fractal properties and fractal dimensions that have been estimated from sampled data using computer based fractal analysis techniques. Practically, measurements of fractal dimension are affected by various methodological issues, and are sensitive to numerical or experimental noise and limitations in the amount of data. Nonetheless, the field is rapidly growing as estimated fractal dimensions for statistically self-similar phenomena may have many practical applications in various fields including astronomy, acoustics, geology and earth sciences, diagnostic imaging, ecology, electrochemical processes, image analysis, biology and medicine, neuroscience, network analysis, physiology, physics, and Riemann zeta zeros. Fractal dimension estimates have also been shown to correlate with Lempel-Ziv complexity in real-world data sets from psychoacoustics and neuroscience.

An alternative to a direct measurement, is considering a mathematical model that resembles formation of a real-world fractal object. In this case, a validation can also be done by comparing other than fractal properties implied by the model, with measured data. In colloidal physics, systems composed of particles with various fractal dimensions arise. To describe these systems, it is convenient to speak about a distribution of fractal dimensions, and eventually, a time evolution of the latter: a process that is driven by a complex interplay between aggregation and coalescence.

title: Fractal dimension