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Wife

A wife is a female partner in a continuing marital relationship. The term continues to be applied to a woman who has separated from her partner, ceases to be applied to such a woman only when her marriage has come to an end, following a recognized divorce or the death of her spouse. On the death of her partner, a wife is referred to as a widow, but not after she is divorced from her partner; the rights and obligations of a wife in relation to her partner and her status in the community and in law vary between cultures and have varied over time. The word is of Germanic origin, from Proto-Germanic *wībam, "woman". In Middle English it had the form wif, in Old English wīf, "woman or wife", it is related to Modern German Weib, Danish viv and may derive from the Indo-European root ghwībh- "shame. The original meaning of the phrase "wife" as "woman", unconnected with marriage or a husband/wife, is preserved in words such as "midwife" and "fishwife". In many cultures, marriage is expected that a woman will take her husband's surname, though, not universal.

A married woman may indicate her marital status in a number of ways: in Western culture a married woman would wear a wedding ring but in other cultures other markers of marital status may be used. A married woman is given the honorific title "Mrs", but some married women prefer to be referred to as "Ms", a title, used when the marital status of a woman is unknown. A woman on her wedding day is described as a bride after the wedding ceremony, while being described as a wife is appropriate after the wedding or after the honeymoon. If she is marrying a man, her partner is known as the bridegroom during the wedding, within the marriage is called her husband. In the older custom, still followed, e. g. by Roman Catholic ritual, the word bride means fiancée and applies up to the exchange of matrimonial consent. "Wife" refers to the institutionalized relation to the other spouse, unlike mother, a term that puts a woman into the context of her children. In some societies historically, a concubine was a woman, in an ongoing matrimonially oriented relationship with a man who could not be married to her because of a difference in social status.

The term wife is most applied to a woman in a union sanctioned by law, not to a woman in an informal cohabitation relationship, which may be known as a girlfriend, cohabitant, significant other, mistress etc. However, a woman in a so-called common law marriage may describe herself as a common law wife, de facto wife, or a wife; those seeking to advance gender neutrality may refer to both marriage partners as "spouses", many countries and societies are rewording their statute law by replacing "wife" and "husband" with "spouse". A former wife whose spouse is deceased is a widow; the status of a wife may be terminated by annulment, or the death of a spouse. In the case of divorce, terminology such as former-wife or ex-wife is used. With regard to annulment, such terms are not speaking, because annulment, unlike divorce, is retroactive, meaning that an annulled marriage is considered to be invalid from the beginning as if it had never taken place. In the case of the death of the other spouse, the term used is widow.

The social status of such women varies by culture, but in some places, they may be subject to harmful practices, such as widow inheritance or levirate marriage. In some cultures, the termination of the status of wife made life itself meaningless, as in the case of those cultures that practiced sati, a funeral ritual within some Asian communities, in which a widowed woman committed suicide by fire on the husband's funeral pyre; the legal rights of a wife have been since the 19th century, still are, in many jurisdictions subject to debate. This subject was in The Subjection of Women. Many societies have given sets of rights and obligations to husbands that have been different from the sets of rights and obligations given to wives. In particular, the control of marital property, inheritance rights, the right to dictate the activities of children of the marriage, have been given to male marital partners. However, this practice was curtailed to a great deal in many countries in the twentieth century, more modern statutes tend to define the rights and duties of a spouse without reference to gender.

Among the last European countries to establish full gender equality in marriage were Switzerland, Greece and France in the 1980s. In various marriage laws around the world, the husband continues to have authority. Traditionally, still in some parts of the world, the bride or her family bring her husband a dowry, or the husband or his family pay a bride price to the bride's family, or both are exchanged between the families; the purpose of the dowry has varied historically. In some cultures, it was paid not only to support the establishment of a new family, but als

Spontaneous Broadway

Spontaneous Broadway is an advanced long-form improvised performance, based on audience suggestions. The audience submits titles of songs that have never been written, the performers choose suggestions to create songs, the audience votes through acclamation on their favorite song, used as the core of a brand new Broadway musical; the format received a favorable review from The New York Times when it premiered in New York in 1995. Though not required or encouraged by improv professionals, elements of humor surface in the performance because of the surprising and playful nature of improvisation and its use of typical Broadway stereotypes; the performers' songs are supported by an onstage musician or band that improvises the music in the style of typical show tunes. The format was created in New York City at Freestyle Repertory Theatre and has been performed by a number of different companies around the US, it is performed by BATS theatre in San Francisco, The Mop & Bucket Co. in Schenectady NY, at several colleges around the country, including Stanford.

The Spontaneous Broadway format was created by Kat Koppett in association with Freestyle Repertory Theatre in New York. Koppett is a 25-year improv veteran, having worked with Freestyle Repertory Theatre) and San Francisco's BATS Improv, she is co-director of the Mop & Bucket Company, an improv troupe based in the Capital District of New York State. Koppett runs a consulting business, appropriately named Koppett. In 1995, TheaterWeek Magazine named Kat one of the year's "Unsung Heroes" for her creation of Spontaneous Broadway, now performed by teams of actors all over the world. Significant contributions to the development of the format at Freestyle Rep. were made by Kenn Adams, Laura Livingston, Samuel D. Cohen. At the 2000 Melbourne Fringe Festival, the show began its life in Australia and won a special Fringe Award. Produced by musical director John Thorn and hosted by Russell Fletcher, many of Australia's finest comic improvisors have since performed the show around the country, including sell-out performances at the Sydney Opera House, The Famous Spiegeltent, at the Melbourne International Comedy Festival, receiving rave reviews and legions of repeat attendee fans

Cladribine

Cladribine, sold under the brand name Leustatin and Mavenclad among others, is a medication used to treat hairy cell leukemia, B-cell chronic lymphocytic leukemia and Relapsing-remitting Multiple Sclerosis. Its chemical name is 2-chloro-2'-deoxyadenosine; as a purine analog, it is a synthetic chemotherapy agent that targets lymphocytes and selectively suppresses the immune system. Chemically, it mimics the nucleoside adenosine. However, unlike adenosine it is resistant to breakdown by the enzyme adenosine deaminase, which causes it to accumulate in cells and interfere with the cell's ability to process DNA. Cladribine is taken up by cells via a transporter. Once inside a cell cladribine is activated in lymphocytes, when it is triphosphorylated by the enzyme deoxyadenosine kinase. Various phosphatases dephosphorylate cladribine. Activated, triphosphorylated, cladribine is incorporated into mitochondrial and nuclear DNA, which triggers apoptosis. Non-activated cladribine is removed from all other cells.

This means that there is little non-target cell loss. Cladribine is used for as a first and second-line treatment for symptomatic hairy cell leukemia and for B-cell chronic lymphocytic leukemia and is administered by intravenous or subcutaneous infusion. Since 2017, cladribine is approved as an oral formulation for the treatment of RRMS in Europe, UAE, Chile and Australia. Marketing authorization for RRMS and SPMS in the US was obtained in March 2019; some investigators have used the parenteral formulation orally to treat patients with HCL. It is important to note that 40% of oral cladribine is bioavailable orally, it used in combination with other cytotoxic agents, to treat various kinds of histiocytosis, including Erdheim–Chester disease and Langerhans cell histiocytosis,Cladribine can cause fetal harm when administered to a pregnant woman and is listed by the FDA as Pregnancy Category D. Injectable cladribine suppresses the body's ability to make new lymphocytes, natural killer cells and neutrophils.

At the dosage used to treat HCL in two clinical trials, 16% of people had rashes and 22% had nausea, the nausea did not lead to vomiting. In comparison, in MS, cladribine is associated with a 6% rate of severe lymphocyte suppression. Other common side effects include headache, sore throat, common cold-like illness and nausea As a purine analogue, it is taken up into proliferating cells like lymphocytes to be incorporated into DNA synthesis. Unlike adenosine, cladribine has a chlorine molecule at position 2, which renders it resistant to breakdown by adenosine deaminase. In cells it is phosphorylated into its toxic form, deoxyadenosine triphosphate, by the enzyme deoxycytidine kinase; this molecule is incorporated into the DNA synthesis pathway, where it causes strand breakage. This is followed by the activation of transcription factor p53, the release of cytochrome c from mitochondria and eventual programmed cell death; this process occurs over 2 months, with a peak level of cell depletion 4–8 weeks after treatmentWithin the lymphocyte pool, cladribine targets B cells more than T cells.

Both HCL and B-cell chronic lymphocytic leukaemia are types of B cell blood cancers. In MS, its effectiveness may be due to its ability to deplete B cells, in particular memory B cells In the pivotal phase 3 clinical trial of oral cladribine in MS, CLARITY, cladribine selectively depleted 80% of peripheral B cells, compared to only 40-50% of total T cells. More cladribine has been shown to induce long term, selective suppression of certain subtypes of B cells memory B cells. Another family of enzymes, the 5´nucleotidase family, is capable of dephosphorylating cladribine, making it inactive; the most important subtype of this group appears to be 5NCT1A, cytosolically active and specific for purine analogues. When DCK gene expression is expressed as a ratio with 5NCT1A, the cells with the highest ratios are B cells germinal centre and naive B cells; this again helps to explain. Although cladribine is selective for B cells, the long term suppression of memory B cells, which may contribute to its effect in MS, is not explained by gene or protein expression.

Instead, cladribine appears to deplete the entire B cell department. However, while naive B cells move from lymphoid organs, the memory B cell pool repopulates slowly from the bone marrow. Ernest Beutler and Dennis A. Carson had studied adenosine deaminase deficiency and recognized that because the lack of adenosine deaminase led to the destruction of B cell lymphocytes, a drug designed to inhibit adenosine deaminase might be useful in lymphomas. Carson synthesized cladribine, through clinical research at Scripps starting in the 1980s, Beutler tested it as intravenous infusion and found it was useful to treat hairy cell leukemia. No pharmaceutical companies were interested in selling the drug because HCL was an orphan disease, so Beutler's lab synthesized and packaged it and supplied it to the hospital pharmacy; this was the first treatment that led to prolon