text: Crosby decided to leave the series part way through the first season, due to the underdevelopment of her character, Tasha Yar. She later said about the situation in an interview with the official "Star Trek" website, "I was miserable. I couldn't wait to get off that show. I was dying". Roddenberry agreed to her request to leave, and she returned in the episode "Yesterday's Enterprise". Another change to the cast, this time after the end of the first season, was the firing of McFadden, who played Dr. Crusher, from the show. This was later attributed to the actions of Hurley and once he left the crew, she returned to the role at the start of the third season.


title: Star Trek: The Next Generation (season 1)

text: "Star Trek: The Next Generation" was released into broadcast syndication, meaning that it was hosted on multiple television stations without going through a broadcast network. At the time this was relatively unheard of, although "The Original Series" had become successful following release on syndication after an initial run on NBC. In advance of the first airing of the pilot, "Encounter at Farpoint", the show had been sold in 171 markets. There were concerns at the time that such a method of broadcasting would negatively impact the ratings received by the series, with Justman suggesting that the payoff would be worth it due to the lack of interference from a potential network.


text: "Encounter at Farpoint" received Nielsen ratings of 15.7 percent, and it was granted a commitment for a further 24 one hour episodes following the broadcast. The pilot was the highest rated episode of the first season; the lowest rated episode of the first season was "The Last Outpost", the fourth episode broadcast, which received ratings of 8.9 percent. Three episodes later, "" was broadcast, which received a rating of 12.7 percent, the highest for the season other than the pilot. As of the period between September 6 and January 3, the show was only outranked in the Nielsen Ratings by "Wheel of Fortune" and "Jeopardy!" for shows released directly into syndication, and it became the highest rated syndicated series by the end of the first season, which prompted several other series to be released directly into syndication.


text: Although it was highly anticipated, when the series was initially broadcast, the response was lukewarm from fans and reviewers. John J. O'Connor reviewed the first episode for "The New York Times", and simply hoped that the action and pace would increase in the episodes aired after the pilot. Other critics of "Encounter at Farpoint" were more positive; Don Merrill, writing for "TV Guide" said that the show was a "worthy successor to the original". Jill L. Lanford for "The Herald Journal" said that it was a resurrection of a "legend" and was reminiscent of "The Original Series" episodes "" and "The Squire of Gothos". She added that it was the "perfect vehicle to introduce the crew", and a "perfect start". There was also some initial criticism of the casting, with Tom Shales of "The Washington Post" saying Patrick Stewart was a "grim bald crank who would make a better villain", and Jonathan Frakes "verges on namby-pamby". Mark Jones and Lance Parkin, in their book "Beyond the Final Frontier : An Unauthorised Review of Star Trek", said the first season "often felt like an uneasy politically correct attempt to recreate one of the sixties' least politically correct shows."


text: While critics approved of certain elements of the show such as the design of the new "Enterprise", the early episodes after the pilot were received negatively. "The Naked Now", the second episode of the season, was based on the original series episode "The Naked Time". This resulted in some fans, and former "Star Trek" writers, becoming concerned that the series would continue to "re-hash" old plots. "" has been seen in hindsight as being racist, with Stewart later saying that the cast and crew were embarrassed by it. Mark A. Altman felt that "The Next Generation" during the first season was a missed opportunity to address issues relevant to modern life, which he said that "The Original Series" had done successfully in the sixties. He called some episodes "trite", and suggested that elements were straight rehashes of previous plots with only some names and scenarios changed. Marina Sirtis remarked while promoting "" that in the beginning "they bloody hated us".


text: Reviewing the series as part of the DVD release in 2002, Marc Bernardin for "Entertainment Weekly" said of season one, that it was "almost hard to believe ... just how bad much of it was". He thought that the first season was too similar to the end of the "cheesy" original series but said that it "succeeded where it needed to: It introduced viewers to the characters who would carry the torch through six more seasons", and gave it a score of B+. Tor.com reviewer Keith DeCandido was less positive, feeling that it "earned" its reputation as the poorest of "The Next Generation" seven seasons because "the episodes were uneven, poorly plotted, ineptly scripted, and acted by actors who were still trying to figure their characters out". He gave it a score of 5 out of 10. The season has been given an 80% "fresh" rating by review aggregator website Rotten Tomatoes.


text: "Star Trek: The Next Generation" received seven nominations at the 40th Primetime Emmy Awards. Chris Haire, Doug Davey, Jerry Clemans and Alan Bernard were nominated for "Outstanding Sound Mixing for a Drama Series" for work on the episode "Where No One Has Gone Before". Edward R. Brown was nominated for "Outstanding Cinematography for a Series" for "The Big Goodbye".


text: The makeup teams on the show were nominated for two episodes for "Outstanding Achievement Makeup for a Series", for the episodes "Coming of Age" and "", winning the award for the latter episode. William Ware Theiss won the award "Outstanding Costume Design for a Series" for "The Big Goodbye", while the team working on "11001001" won the Emmy for "Outstanding Sound Editing for a Series".


text: "The Big Goodbye" also won a Peabody Award. The series' premiere episode, "Encounter at Farpoint" was nominated for "Best Dramatic Presentation" at the 1988 Hugo Awards. Wil Wheaton was nominated for "Best Young Actor Starring in a Television Drama Series" at the 9th Youth in Film Awards for his portrayal of Wesley Crusher.


text: In the following table, episodes are listed by the order in which they aired, and may not necessarily correspond to their production codes.


text: The episodes of the first season of "The Next Generation" had each been released individually and in pairs before being released as a season long box set. This first release came on DVD, but following further work to update the releases into high-definition video and onto Blu-ray disc, "Encounter at Farpoint" was among those episodes included on a preview disc released in January 2012. A full season release on region-free Blu-ray followed at the end of July.


title: Dirty Sexy Money

text: Dirty Sexy Money is an American prime time drama television series created by Craig Wright. It ran on ABC from September 26, 2007, to August 8, 2009. The series was produced by Berlanti Television and ABC Studios. Wright served as an executive producer alongside Greg Berlanti, Bryan Singer, Matthew Gross, Peter Horton, and Josh Reims, with Melissa Berman producing.


title: Dirty Sexy Money

text: The series revolves around lawyer and family man Nick George, portrayed by Peter Krause. When Nick's father mysteriously dies in a plane crash, he agrees to take his position as the Darling family's lawyer, while trying to discover who committed the murder. The Darlings, the richest family in New York, constantly rely on Nick to solve their problems. Nick struggles to balance his morals and family life while dealing with the demands of the Darlings.


title: Dirty Sexy Money

text: The series revolves around Nick George, whose whole life has been lived in the shadow of the Darling family, but as an adult he's leading a simple life as an idealistic lawyer, until his father's suspicious death. The wealthy Darlings of New York have asked him to take over his father's job as their personal lawyer, but the money that will allow him the freedom to be an do-gooder is only part of the picture. That same money pulls him into the dubious doings of the Darling clan.


title: Dirty Sexy Money

text: Due to the cancellation of the show, the running plot line of the mystery of Dutch George will never be solved. Craig Wright told the "Los Angeles Times" that had the series lasted, Juliet would have been arrested after getting into a situation like that of Patty Hearst, later teaching drama at a boarding school in Connecticut, marrying the school's soccer coach and having kids.


title: Dirty Sexy Money

text: The series premiered in the United States on September 26, 2007, on ABC following the "Grey's Anatomy" spin-off, "Private Practice", airing on Wednesday nights at 10:01 P.M. Eastern/9:01 P.M. Central.


title: Dirty Sexy Money

text: On November 16, 2007, ABC ordered a full 22-episode season for the show, making it the first show to receive a full season order since the WGA writers' strike began on November 5, 2007. However, in the end, the first season comprised only 10 episodes due to the strike. "Dirty Sexy Money: The Complete First Season", a three-disc DVD set including all 10 original episodes and exclusive bonus features including bloopers, audio commentary, deleted scenes, and featurettes,


title: Dirty Sexy Money

text: and more, was released on September 16, 2008. The second season premiered on October 1, 2008, ten months after the first-season finale.


title: Dirty Sexy Money

text: On November 20, 2008, ABC decided not to order any additional episodes for the 2008–2009 TV season. On December 10, 2008, Billy Baldwin appeared on NBC's Today Show asking for fans to support the show by watching the show and by visiting the ABC website and sending nice messages of support to the ABC executives. He said the show was not canceled, but on hiatus until ABC knew how the midseason replacement shows fared. All cast and sets continued to be contracted and on hold. The last scheduled episode of "Dirty Sexy Money" aired on December 17, 2008, while four episodes remained unaired in the USA though they were broadcast elsewhere.


title: Dirty Sexy Money

text: After "Dirty Sexy Money" was officially canceled, ABC announced the series would return on Saturday, July 18, 2009, at 10:00 P.M. Eastern/9:00 P.M. Central. The final episode, "The Bad Guy", aired on August 8, 2009, and the second season came out on DVD on August 18, 2009.


title: Dirty Sexy Money

text: The series premiered in the United Kingdom on March 21, 2008, at 9 P.M. on Channel 4. "Dirty Sexy Money" was on hiatus due to the WGA writers' strike as of January 9, 2008, the date on which replacement series "Cashmere Mafia" assumed the time slot. "Men in Trees", which has a total of 11 filmed unaired episodes available, assumed the slot on February 27, 2008, potentially for the balance of the spring season.


title: Dirty Sexy Money

text: The show will be broadcast on Turner Network Television in Spain, Studio 23 in Philippines, Dizimax in Turkey and Nelonen in Finland. The series is being broadcast on the satellite/cable channel TNT in Spain since January 2008.


title: Dirty Sexy Money

text: In Canada, CTV first aired the show on Sundays at 10 P.M. (four days after ABC), then it moved to 7 P.M. CTV then moved the show to its secondary A system effective October 24, 2007 where it airs it in simulcast Wednesdays at 10 P.M.


title: Dirty Sexy Money

text: In Australia, the Seven Network began airing Season One on Monday February 11, 2008 at 9:30 P.M. Season Two began on December 2, 2008, initially at 9:30 P.M., but due to low ratings, it was pushed back to 11:30 P.M. The Seven Network in Australia has aired all episodes of Season 2 that were unaired in the USA. Also Kanal 5 in Sweden aired the episodes, the last one on March 18, 2009.


title: Dirty Sexy Money

text: In the United Kingdom, Channel 4 began airing the episodes on Friday, March 21, 2008, at 9:00 P.M. Channel 4 began airing the second season on March 8, 2009, on E4 in the 11 o'clock timeslot. Because of its cancellation in the US and low ratings for its first season in the UK there will be no new shows on Channel 4 for the foreseeable future. However, Season 2 commenced airing on E4 in a new time slot. For Season One it aired Tuesday nights at 9:00 P.M., whereas for Season Two it aired on Sunday nights at 11 P.M. between March 8 and May 31, 2009, including the four episodes not yet shown in the US.


title: Dirty Sexy Money

text: In Latin America, the series began broadcasting on February 12, 2008, on the AXN channel, season 2 will begin broadcast on February 3, 2009.


title: Dirty Sexy Money

text: In South Africa, the series began in December and the full series has been aired on the local satellite or analog channel M-Net. M-Net has broadcast the remaining episodes of Season 2 which followed on from the Organ Donor episode which aired on January 29, 2009. The series aired on Thursday nights at 8:30 p.m. with a repeat on Sundays at 2:00 p.m. The season finale has aired on February 5, 2009.


title: Dirty Sexy Money

text: In Israel, the series was launched under the name "Money, Darling" on July 7, 2008, on Yes Stars Drama. Season 2 premiered on February 16, 2009, with all 13 episodes confirmed to air consecutively, including those not aired in the US.


title: Dirty Sexy Money

text: In Hong Kong, the series was premiered Thursday nights at 10:30 P.M. on July 17, 2008, on the mainly English free-to-air network TVB Pearl with bilingual audio in both English and Cantonese and widescreen on the same channel in Digital. Series 2 is due to air on March 26, 2009, at the same time-slot. Same as the rest of the world, Hong Kong also aired the unaired episodes before the US on May 28, 2009, starting with the thanksgiving recap episode "The Facts".


title: Dirty Sexy Money

text: In Russia, the show premiered on 1TV in summer 2008. Two seasons were shown in summer of 2009. The series launched under the name "Dirty Wet Money". In 2012 the show was aired late at nights on Domashny channel.


title: Dirty Sexy Money

text: In Greece, the show premiered on cable FOX Life in February 2009 and season 2 premiered in October 2009. The show also will premiered on ANT1 on 2010.


title: Dirty Sexy Money

text: In France, the show premiered on Canal+ pay TV in 2008 and the second season was aired from 2009 until Feb 11, 2010.


title: Dirty Sexy Money

text: In Slovenia, the show's 1st season aired on Mondays on POP TV, It reaired on POP TV's new sister channel POP BRIO in September 2010, after the reruns the 2nd season premiered in the same time slot (Monday–Friday at 10 P.M.).


title: Dirty Sexy Money

text: In Republic of Macedonia, the show aired Sundays at 12:00 P.M. in 2008 on A1 television, and later on Fox Life.


title: Dirty Sexy Money

text: Using publicity from Paris Hilton's jail sentence controversy, ABC placed full-page advertisements in the "Los Angeles Times" and "The New York Post" that read: ""We love Paris. The Darling Family."" Later, an airplane towing a banner with the same message flew above the downtown courthouse on June 8 during Hilton's subsequent hearing. The network has also placed fake advertisements on popular gossip blog Perezhilton.com on August 6, 2007 "denouncing" the diva-like behavior of Samaire Armstrong's character, Juliet Darling, among others.


title: Dirty Sexy Money

text: The song "Beautiful, Dirty, Rich" by singer Lady Gaga was used during advertisements for the show. Clips from the show were also used in an alternate version of the music video


title: Dirty Sexy Money

text: Walt Disney Studios Home Entertainment released both seasons on DVD in Regions 1, 2 and 4 in 2008/2009. The region 1 releases have been discontinued and are now out of print.


title: Dirty Sexy Money

text: On February 9, 2012, it was announced that Lionsgate Home Entertainment had acquired the rights to the series and plan on re-releasing it. Seasons 1 and 2 was re-released on May 1, 2012.


title: Immunosuppressive drug

text: Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system.


title: Immunosuppressive drug

text: In pharmacologic (supraphysiologic) doses, glucocorticoids, such as prednisone, dexamethasone, and hydrocortisone are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes.


title: Immunosuppressive drug

text: Glucocorticoids suppress cell-mediated immunity. They act by inhibiting genes that code for the cytokines Interleukin 1 (IL-1), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, and TNF-alpha, the most important of which is IL-2. Smaller cytokine production reduces T cell proliferation.


title: Immunosuppressive drug

text: Glucocorticoids also suppress the humoral immunity, causing B cells to express smaller amounts of IL-2 and IL-2 receptors. This diminishes both B cell clone expansion and antibody synthesis.


title: Immunosuppressive drug

text: Glucocorticoids influence all types of inflammatory events, no matter their cause. They induce the lipocortin-1 (annexin-1) synthesis, which then binds to cell membranes preventing the phospholipase A2 from coming into contact with its substrate arachidonic acid. This leads to diminished eicosanoid production. The cyclooxygenase (both COX-1 and COX-2) expression is also suppressed, potentiating the effect.


title: Immunosuppressive drug

text: Glucocorticoids also stimulate the lipocortin-1 escaping to the extracellular space, where it binds to the leukocyte membrane receptors and inhibits various inflammatory events: epithelial adhesion, emigration, chemotaxis, phagocytosis, respiratory burst, and the release of various inflammatory mediators (lysosomal enzymes, cytokines, tissue plasminogen activator, chemokines, etc.) from neutrophils, macrophages, and mastocytes.


title: Immunosuppressive drug

text: Cytostatics inhibit cell division. In immunotherapy, they are used in smaller doses than in the treatment of malignant diseases. They affect the proliferation of both T cells and B cells. Due to their highest effectiveness, purine analogs are most frequently administered.


title: Immunosuppressive drug

text: The alkylating agents used in immunotherapy are nitrogen mustards (cyclophosphamide), nitrosoureas, platinum compounds, and others. Cyclophosphamide (Baxter's Cytoxan) is probably the most potent immunosuppressive compound. In small doses, it is very efficient in the therapy of systemic lupus erythematosus, autoimmune hemolytic anemias, granulomatosis with polyangiitis, and other immune diseases. High doses cause pancytopenia and hemorrhagic cystitis.


title: Immunosuppressive drug

text: Methotrexate is a folic acid analogue. It binds dihydrofolate reductase and prevents synthesis of tetrahydrofolate. It is used in the treatment of autoimmune diseases (for example rheumatoid arthritis or Behcet's Disease) and in transplantations.


title: Immunosuppressive drug

text: Azathioprine (Prometheus' Imuran), is the main immunosuppressive cytotoxic substance. It is extensively used to control transplant rejection reactions. It is nonenzymatically cleaved to mercaptopurine, that acts as a purine analogue and an inhibitor of DNA synthesis. Mercaptopurine itself can also be administered directly.


title: Immunosuppressive drug

text: By preventing the clonal expansion of lymphocytes in the induction phase of the immune response, it affects both the cell and the humoral immunity. It is also efficient in the treatment of autoimmune diseases.


title: Immunosuppressive drug

text: Among these, dactinomycin is the most important. It is used in kidney transplantations. Other cytotoxic antibiotics are anthracyclines, mitomycin C, bleomycin, mithramycin.


title: Immunosuppressive drug

text: Antibodies are sometimes used as a quick and potent immunosuppressive therapy to prevent the acute rejection reactions as well as a targeted treatment of lymphoproliferative or autoimmune disorders (e.g., anti-CD20 monoclonals).


title: Immunosuppressive drug

text: Heterologous polyclonal antibodies are obtained from the serum of animals (e.g., rabbit, horse), and injected with the patient's thymocytes or lymphocytes. The antilymphocyte (ALG) and antithymocyte antigens (ATG) are being used. They are part of the steroid-resistant acute rejection reaction and grave aplastic anemia treatment. However, they are added primarily to other immunosuppressives to diminish their dosage and toxicity. They also allow transition to cyclosporin therapy.


title: Immunosuppressive drug

text: Polyclonal antibodies inhibit T lymphocytes and cause their lysis, which is both complement-mediated cytolysis and cell-mediated opsonization followed by removal of reticuloendothelial cells from the circulation in the spleen and liver. In this way, polyclonal antibodies inhibit cell-mediated immune reactions, including graft rejection, delayed hypersensitivity (i.e., tuberculin skin reaction), and the graft-versus-host disease (GVHD), but influence thymus-dependent antibody production.


title: Immunosuppressive drug

text: As of March 2005, there are two preparations available to the market: Atgam, obtained from horse serum, and Thymoglobuline, obtained from rabbit serum. Polyclonal antibodies affect all lymphocytes and cause general immunosuppression, possibly leading to post-transplant lymphoproliferative disorders (PTLD) or serious infections, especially by cytomegalovirus. To reduce these risks, treatment is provided in a hospital, where adequate isolation from infection is available. They are usually administered for five days intravenously in the appropriate quantity. Patients stay in the hospital as long as three weeks to give the immune system time to recover to a point where there is no longer a risk of serum sickness.


title: Immunosuppressive drug

text: Because of a high immunogenicity of polyclonal antibodies, almost all patients have an acute reaction to the treatment. It is characterized by fever, rigor episodes, and even anaphylaxis. Later during the treatment, some patients develop serum sickness or immune complex glomerulonephritis. Serum sickness arises seven to fourteen days after the therapy has begun. The patient has fever, joint pain, and erythema that can be soothed with the use of steroids and analgesics. Urticaria (hives) can also be present. It is possible to diminish their toxicity by using highly purified serum fractions and intravenous administration in the combination with other immunosuppressants, for example, calcineurin inhibitors, cytostatics, and corticosteroids. The most frequent combination is to use antibodies and ciclosporin simultaneously in order to prevent patients from gradually developing a strong immune response to these drugs, reducing or eliminating their effectiveness.


title: Immunosuppressive drug

text: Monoclonal antibodies are directed towards exactly defined antigens. Therefore, they cause fewer side-effects. Especially significant are the IL-2 receptor- (CD25-) and CD3-directed antibodies. They are used to prevent the rejection of transplanted organs, but also to track changes in the lymphocyte subpopulations. It is reasonable to expect similar new drugs in the future.


title: Immunosuppressive drug

text: Muromonab-CD3 is a murine anti-CD3 monoclonal antibody of the IgG2a type that was previously used to prevent T-cell activation and proliferation by binding the T-cell receptor complex present on all differentiated T cells. As such it was one of the first potent immunosuppressive substances and was administered to control the steroid- and/or polyclonal antibodies-resistant acute rejection episodes. As it acts more specifically than polyclonal antibodies it was also used prophylactically in transplantations. However, muromonab-CD3 is no longer produced, and this mouse monoclonal antibody has been replaced in the clinic with chimeric, humanized, or human monoclonal antibodies.


title: Immunosuppressive drug

text: The muromonab's mechanism of action is only partially understood. It is known that the molecule binds TCR/CD3 receptor complex. In the first few administrations this binding non-specifically activates T-cells, leading to a serious syndrome 30 to 60 minutes later. It is characterized by fever, myalgia, headache, and arthralgia. Sometimes it develops in a life-threatening reaction of the cardiovascular system and the central nervous system, requiring a lengthy therapy. Past this period CD3 blocks the TCR-antigen binding and causes conformational change or the removal of the entire TCR3/CD3 complex from the T-cell surface. This lowers the number of available T-cells, perhaps by sensitizing them for the uptake by the epithelial reticular cells. The cross-binding of CD3 molecules as well activates an intracellular signal causing the T cell anergy or apoptosis, unless the cells receive another signal through a co-stimulatory molecule. CD3 antibodies shift the balance from Th1 to Th2 cells as CD3 stimulates Th1 activation.


title: Immunosuppressive drug

text: Muromonab-CD3 can cause excessive immunosuppression. Although CD3 antibodies act more specifically than polyclonal antibodies, they lower the cell-mediated immunity significantly, predisposing the patient to opportunistic infections and malignancies.


title: Immunosuppressive drug

text: Interleukin-2 is an important immune system regulator necessary for the clone expansion and survival of activated lymphocytes T. Its effects are mediated by the trimer cell surface receptor IL-2a, consisting of the α, β, and γ chains. The IL-2a (CD25, T-cell activation antigen, TAC) is expressed only by the already-activated T lymphocytes. Therefore, it is of special significance to the selective immunosuppressive treatment, and research has been focused on the development of effective and safe anti-IL-2 antibodies. By the use of recombinant gene technology, the mouse anti-Tac antibodies have been modified, leading to the presentation of two chimeric mouse/human anti-Tac antibodies in the year 1998: basiliximab (Simulect) and daclizumab (Zenapax). These drugs act by binding the IL-2a receptor's α chain, preventing the IL-2 induced clonal expansion of activated lymphocytes and shortening their survival. They are used in the prophylaxis of the acute organ rejection after bilateral kidney transplantation, both being similarly effective and with only few side-effects.


title: Immunosuppressive drug

text: Like tacrolimus, ciclosporin (Novartis' Sandimmune) is a calcineurin inhibitor (CNI). It has been in use since 1983 and is one of the most widely used immunosuppressive drugs. It is a cyclic fungal peptide, composed of 11 amino acids.


title: Immunosuppressive drug

text: Ciclosporin is thought to bind to the cytosolic protein cyclophilin (an immunophilin) of immunocompetent lymphocytes, especially T-lymphocytes. This complex of ciclosporin and cyclophilin inhibits the phosphatase calcineurin, which under normal circumstances induces the transcription of interleukin-2. The drug also inhibits lymphokine production and interleukin release, leading to a reduced function of effector T-cells.


title: Immunosuppressive drug

text: Ciclosporin is used in the treatment of acute rejection reactions, but has been increasingly substituted with newer, and less nephrotoxic, immunosuppressants.


title: Immunosuppressive drug

text: Calcineurin inhibitors and azathioprine have been linked with post-transplant malignancies and skin cancers in organ transplant recipients. Non-melanoma skin cancer (NMSC) after kidney transplantation is common and can result in significant morbidity and mortality. The results of several studies suggest that calcineurin inhibitors have oncogenic properties mainly linked to the production of cytokines that promote tumor growth, metastasis and angiogenesis.


title: Immunosuppressive drug

text: This drug has been reported to reduce the frequency of regulatory T cells (T-Reg) and after converting from a CNI monotherapy to a mycophenolate monotherapy, patients were found to have increased graft success and T-Reg frequency.


title: Immunosuppressive drug

text: Tacrolimus (trade names Prograf, Astagraf XL, Envarsus XR) is a product of the bacterium "Streptomyces tsukubensis". It is a macrolide lactone and acts by inhibiting calcineurin.


title: Immunosuppressive drug

text: The drug is used primarily in liver and kidney transplantations, although in some clinics it is used in heart, lung, and heart/lung transplantations. It binds to the immunophilin FKBP1A, followed by the binding of the complex to calcineurin and the inhibition of its phosphatase activity. In this way, it prevents the cell from transitioning from the G into G phase of the cell cycle. Tacrolimus is more potent than ciclosporin and has less pronounced side-effects.


title: Immunosuppressive drug

text: Sirolimus (rapamycin, trade name Rapamune) is a macrolide lactone, produced by the actinomycete bacterium "Streptomyces hygroscopicus". It is used to prevent rejection reactions. Although it is a structural analogue of tacrolimus, it acts somewhat differently and has different side-effects.


title: Immunosuppressive drug

text: Contrary to ciclosporin and tacrolimus, drugs that affect the first phase of T lymphocyte activation, sirolimus affects the second phase, namely signal transduction and lymphocyte clonal proliferation. It binds to FKBP1A like tacrolimus, however the complex does not inhibit calcineurin but another protein, mTOR. Therefore, sirolimus acts synergistically with ciclosporin and, in combination with other immunosuppressants, has few side effects. Also, it indirectly inhibits several T lymphocyte-specific kinases and phosphatases, hence preventing their transition from G to S phase of the cell cycle. In a similar manner, Sirolimus prevents B cell differentiation into plasma cells, reducing production of IgM, IgG, and IgA antibodies.


title: Immunosuppressive drug

text: IFN-β suppresses the production of Th1 cytokines and the activation of monocytes. It is used to slow down the progression of multiple sclerosis. IFN-γ is able to trigger lymphocytic apoptosis.


title: Immunosuppressive drug

text: Prolonged use of opioids may cause immunosuppression of both innate and adaptive immunity. Decrease in proliferation as well as immune function has been observed in macrophages, as well as lymphocytes. It is thought that these effects are mediated by opioid receptors expressed on the surface of these immune cells.


title: Immunosuppressive drug

text: A TNF-α (tumor necrosis factor-alpha) binding protein is a monoclonal antibody or a circulating receptor such as infliximab (Remicade), etanercept (Enbrel), or adalimumab (Humira) that binds to TNF-α, preventing it from inducing the synthesis of IL-1 and IL-6 and the adhesion of lymphocyte-activating molecules. They are used in the treatment of rheumatoid arthritis, ankylosing spondylitis, Crohn's disease, and psoriasis.


title: Immunosuppressive drug

text: These drugs may raise the risk of contracting tuberculosis or inducing a latent infection to become active. Infliximab and adalimumab have label warnings stating that patients should be evaluated for latent TB infection and treatment should be initiated prior to starting therapy with them.


title: Immunosuppressive drug

text: TNF or the effects of TNF are also suppressed by various natural compounds, including curcumin (an ingredient in turmeric) and catechins (in green tea).


title: Immunosuppressive drug

text: Mycophenolic acid acts as a non-competitive, selective, and reversible inhibitor of Inosine-5′-monophosphate dehydrogenase (IMPDH), which is a key enzyme in the "de novo" guanosine nucleotide synthesis. In contrast to other human cell types, lymphocytes B and T are very dependent on this process. Mycophenolate mofetil is used in combination with ciclosporin or tacrolimus in transplant patients.


title: Immunosuppressive drug

text: Fingolimod is a synthetic immunosuppressant. It increases the expression or changes the function of certain adhesion molecules (α4/β7 integrin) in lymphocytes, so they accumulate in the lymphatic tissue (lymphatic nodes) and their number in the circulation is diminished. In this respect, it differs from all other known immunosuppressants.


title: Immunosuppressive drug

text: A common side-effect of many immunosuppressive drugs is immunodeficiency, because the majority of them act non-selectively, resulting in increased susceptibility to infections, decreased cancer immunosurveillance and decreased ability to produce antibodies after vaccination. There are also other side-effects, such as hypertension, dyslipidemia, hyperglycemia, peptic ulcers, lipodystrophy, moon face, liver and kidney injury. The immunosuppressive drugs also interact with other medicines and affect their metabolism and action. Actual or suspected immunosuppressive agents can be evaluated in terms of their effects on lymphocyte subpopulations in tissues using immunohistochemistry.


title: Ketoprofen

text: Ketoprofen is one of the propionic acid class of nonsteroidal anti-inflammatory drugs (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin.


title: Ketoprofen

text: Ketoprofen is generally prescribed for arthritis-related inflammatory pains or severe toothaches that result in the inflammation of the gums.


title: Ketoprofen

text: Ketoprofen can also be used for treatment of some pain, especially nerve pain such as sciatica, postherpetic neuralgia and referred pain for radiculopathy, in the form of a cream, ointment, liquid, spray, or gel, which may also contain ketamine and lidocaine, along with other agents which may be useful, such as cyclobenzaprine, amitriptyline, acyclovir, gabapentin, orphenadrine and other drugs used as NSAIDs or adjuvant, atypical or potentiators for pain treatment.


title: Ketoprofen

text: Trial is been going on for using this drug along with ibuprofen for management of lymphedema . Animal trial and some human trials has been shown significant improvement over placebo control. Dr Stanley G Rockson, of Stanford University is leading these researches.


title: Ketoprofen

text: A 2013 systematic review indicated "The efficacy of orally administered ketoprofen in relieving moderate-severe pain and improving functional status and general condition was significantly better than that of ibuprofen and/or diclofenac." A 2017 Cochrane systematic review investigating ketoprofen as a single-dose by mouth in acute, moderate-to-severe postoperative pain concluded that its efficacy is equivalent to drugs such as ibuprofen and diclofenac.


title: Ketoprofen

text: There is evidence supporting topical ketoprofen for osteoarthritis but not other chronic musculoskeletal pain.


title: Ketoprofen

text: In October 2020, the U.S. Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in fetuses that result in low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy.


title: Ketoprofen

text: Ketoprofen undergoes metabolism in the liver via conjugation with glucuronic acid (glucuronidation) by UGT enzymes, hydroxylation of the benzoyl ring by the CYP3A4 and CYP2C9 enzymes, and reduction of its ketone moiety (a carbonyl functional group, i.e. with carbon-oxygen double bond) by carbonyl reducing enzymes (CREs). Ketoprofen is used for its antipyretic, analgesic, and anti-inflammatory properties by inhibiting cyclooxygenase-1 and -2 (COX-1 and COX-2) enzymes reversibly, which decreases production of proinflammatory prostaglandin precursors.


title: Ketoprofen

text: The patches have been shown to provide rapid and sustained delivery to underlying tissues without significantly increasing levels of drug concentration in the blood when compared to the traditional oral administration.


title: Ketoprofen

text: Ketoprofen has one stereogenic center in the side chain and hence exists as mirror-image twins. Majority of the profens are marketed as racemic mixtures. For most of the NSAIDs the pharmacological activity reside in the (S)-enantiomers with their (R)-enantiomer of virtually inactive. An interesting observation about most profens including ketoprofen is that they undergo unidirectional metabolic inversion, chiral inversion, of the (R)- acid to its (S)-mirror-image version with no other change in the molecule.


title: Ketoprofen

text: Ketoprofen was available over-the-counter in the United States in the form of 12.5 mg coated tablets (Orudis KT and Actron), but this form has been discontinued. It is available by prescription capsules.


title: Ketoprofen

text: Ketoprofen is also available as a 2.5% gel for topical application, and it is also available as a patch for topical analgesia and anti-inflammatory action. However, the gel is not sold in the United States.


title: Ketoprofen

text: Brand names in Australia are Orudis and Oruvail. It is available in Japan in a transdermal patch Mohrus Tape, made by Hisamitsu Pharmaceutical. It is available in the UK as Ketoflam and Oruvail, in Ireland as Fastum Gel, in Estonia as Keto, Ketonal, and Fastum Gel, in Finland as Ketorin, Keto, Ketomex, and Orudis; in France as Profénid, Bi-Profénid, Toprec, and Ketum; in Italy as Ketodol, Fastum Gel, Lasonil, Orudis and Oki; in Poland as Ketonal, Ketonal active, Ketolek, in Serbia, Slovenia and Croatia as Knavon and Ketonal; in Romania as Ketonal and Fastum Gel; in Mexico as Arthril; in Norway as Zon and Orudis; in Russia as ОКИ (OKI), Fastum Gel and Ketonal; in Spain as Actron and Fastum Gel; in Albania as Oki and Fastum Gel and in Venezuela as Ketoprofeno as an injectable solution of 100 mg and 150 mg capsules.


title: Ketoprofen

text: In some countries, the optically pure ("S")-enantiomer (dexketoprofen) is available; its trometamol salt is said to be particularly rapidly reabsorbed from the gastrointestinal tract, having a rapid onset of effects.


title: Ketoprofen

text: Ketoprofen is a common NSAID, antipyretic, and analgesic used in horses and other equines. It is most commonly used for musculoskeletal pain, joint problems, and soft tissue injury, as well as laminitis. It is also used to control fevers and prevent endotoxemia. It is also used as a mild painkiller in smaller animals, generally following surgical procedures.


title: Ketoprofen

text: In horses, it is given at a dose of 2.2 mg/kg/day. Studies have shown that it does not inhibit 5-lipoxygenase and leukotriene B4, as originally claimed. It is therefore not considered superior to phenylbutazone as previously believed, although clinical signs of lameness are reduced with its use. In fact, phenylbutazone was shown superior to ketoprofen in cases of experimentally-induced synovitis when both drugs were used at labeled dosages.


title: Ketoprofen

text: Ketoprofen, when administered intravenously, is recommended for a maximum of five days of use. Its analgesic and antipyretic effects begin to occur one to two hours following administration. The most common dosage is 1 mg/ lb, once per day, although this dosage may be lowered for ponies, which are most susceptible to NSAID side effects.


title: Ketoprofen

text: Experiments have found ketoprofen, like diclofenac, is a veterinary drug causing lethal effects in red-headed vultures. Vultures feeding on the carcasses of recently treated livestock develop acute kidney failure within days of exposure.


title: Bill DeMott

text: William Charles DeMott II (born November 10, 1966) is an American retired professional wrestler and road agent and trainer. He is best known for his appearances with World Championship Wrestling (WCW) as Hugh Morrus and World Wrestling Federation/Entertainment (WWF/E) under his real name. DeMott also performed as Crash the Terminator in both Extreme Championship Wrestling (ECW) and Japan.


title: Bill DeMott

text: Generally used as a jobber to the stars in WCW, he attained championship success during the promotion's dying days in late 2000 and early 2001, holding the WCW United States Heavyweight Championship twice. After an unsuccessful stint as a performer in WWE, DeMott retired from in-ring competition and transitioned into the role of a trainer for the company's "Tough Enough" program, on which he became known for using a rough, controversial style in handling trainees, as well as WWE's developmental territories Deep South Wrestling, Florida Championship Wrestling, and NXT; after working for WWE a total of 10 years between 2001 and 2015, he resigned from the company.


title: Bill DeMott

text: William Charles DeMott II was born on November 10, 1966, in Ridgewood, New Jersey. He grew up in Paramus, New Jersey, graduating from Paramus High School in 1983.


title: Bill DeMott

text: DeMott was trained by Johnny Rodz in his New York City wrestling school beginning in 1988. From there he began working at small independent promotions using the name Big Sweet Williams. In 1992 DeMott began wrestling for the Americas Wrestling Federation and started using the name Crash the Terminator. Under this name he found some success, first capturing the AWF World Heavyweight Title from Steve Strong in Puerto Rico, before moving on to the Japanese promotion W*ING and winning their World Tag Team Championship with Mr. Pogo. In 1993, while competing in W*ING, DeMott won a 16-man tournament to be crowned their World Heavyweight Champion.


title: Bill DeMott

text: When DeMott returned to the United States, he wrestled for Extreme Championship Wrestling for a short time under his Crash the Terminator name. On February 21, 1994 DeMott received a tryout match with the World Wrestling Federation at a Monday Night Raw taping at Poughkeepsie, NY. He also had matches over the next two days at taping for WWF Superstars of Wrestling and Wrestling Challenge. He then went to Pennsylvania Championship Wrestling, where he won the latter promotion's World Heavyweight Championship upon winning a battle royal. Crash's final ECW appearance came on May 13, 1994, in a TV victory against AJ Powers, which aired on June 7.


title: Bill DeMott

text: In 1995, DeMott was signed to a World Championship Wrestling (WCW) contract at the behest of Kevin Sullivan who had been impressed by him. He debuted in dark matches as The Man of Question and The Laughing Man, a strange gimmick that saw him wearing a singlet covered in question marks and laughing frequently. He made his television debut as a member of The Dungeon of Doom as "The Laughing Man" Hugh Morrus (a pun on the word humorous) on the November 18, 1995 episode of WCW Saturday Night in a vignette inside the Dungeon, where Kevin Sullivan told his (kayfabe) father, The Master, that he was giving him something he never had: laughter, and that he was giving him "the man from the Isle of Nowhere."


title: Bill DeMott

text: Upon the dissolution of the Dungeon of Doom, Morrus was relegated to the undercard. He gained the distinction of being the first wrestler to lose a televised match to Bill Goldberg during the September 22, 1997 episode of "Nitro". As a part of the growing hardcore wrestling style in WCW, Morrus joined Jimmy Hart's First Family stable. Although the Family found success and received a push following a victory over their rivals The Revolution, the stable was suddenly disbanded.


title: Bill DeMott

text: At this time, DeMott took some time off from WCW. He returned in early 2000, utilizing the same name and ring attire, but squashing a number of wrestlers as an angrier version of himself. The angry Morrus gimmick came to a halt when Vince Russo and Eric Bischoff took over and aimed to take WCW in a new direction.


title: Bill DeMott

text: After getting on Russo's bad side (in kayfabe), Morrus was fired from his New Blood stable along with a number of other wrestlers. These ex-New Blood members (including Chavo Guerrero Jr. and Booker T) formed the comedic Misfits In Action stable, which saw its members adopt both military-themed names and attires. As the stable's leader, Morrus re-christened himself General Hugh G. Rection, and led the group in a feud against The Filthy Animals.


title: Bill DeMott

text: The group's comedic nature and the workrate of some of the wrestlers made the group immediate favorites with fans. Upon the introduction of the heel Team Canada, the Misfits In Action immediately began feuding with Team Canada, based over the patriotism both stables had for their respective countries. As the leader of the Misfits, Rection feuded with Team Canada's leader and United States Heavyweight Champion Lance Storm, with the two trading wins until Rection defeated both Storm and a turncoat "Hacksaw" Jim Duggan in a handicap match on October 29 at Halloween Havoc to win the title. Rection would soon lose the title back to Storm on the November 13 episode of "Nitro" before defeating Storm to regain the title on November 26 at Mayhem.


title: Bill DeMott

text: After his feud with Storm, the next night on "Nitro", DeMott stood in the ring and spoke to the fans. During this segment, the WCW locker room emptied and many wrestlers from backstage stood on the entrance way clapping for DeMott; Bill Goldberg grabbed the microphone and, fondly recalling his first opponent in WCW, said "Hey, Goldberg's streak had to start somewhere, my friend."


title: Bill DeMott

text: At Sin on January 14, 2001, Rection lost the United States Heavyweight Title to Shane Douglas. Following the title loss, the Misfits disbanded when Rection announced that they were honorably discharged, which led to Rection reverting to his Hugh Morrus name while the now former Misfits briefly feuded amongst each other. DeMott would then resume his pursuit of the United States Heavyweight Title until the World Wrestling Federation (WWF) bought out WCW.


title: Bill DeMott

text: When WCW was purchased by the WWF, DeMott signed a deal with the WWF and became part of The Invasion angle under his Hugh Morrus ring name as a member of The Alliance. Morrus made his WWF debut on the June 4, 2001 episode of "Raw" by attacking Edge. Aside from a pay-per-view match at Invasion on July 22 where he, Shawn Stasiak and Chris Kanyon defeated Big Show, Billy Gunn and Albert and an Intercontinental Championship match on the August 27 episode of "Raw" which he lost to Edge via disqualification, Morrus was relegated to wrestling on the company's secondary shows "Heat" and "Jakked" much like his fellow WCW alumni. In the September 29 episode of WWE Metal, Morrus made his first appearance at the show, where he takes on Billy Gunn, in a losing effort. When The Invasion ended at Survivor Series following Team Alliance's loss to Team WWF, Morrus was kayfabe fired by Vince McMahon. While off television, Morrus performed at house shows and worked in company's developmental territory Heartland Wrestling Association (HWA). During his time in the HWA, he teamed with Raven to defeat Lance Cade and Steve Bradley to win the Tag Team Champions on March 12, 2002, which they lost only three days later.


title: Bill DeMott

text: In April 2002, Morrus was drafted to the SmackDown! brand. He made his television return on the April 6 episode of "Jakked" alongside fellow WCW alumnus Chavo Guerrero Jr. and defeated The Hurricane and Funaki. Morrus was soon relegated to being a mainstay on "Jakked" and later "Velocity" until late July 2002, when he was legitimately injured in a motorcycle accident and had to take a leave of absence. During his time away, he became a trainer for the third season of Tough Enough", WWE's reality television show.


title: Bill DeMott

text: When he had sufficiently healed, Morrus made his return on the November 23 episode of "Velocity" under his real name. DeMott made his "SmackDown!" debut on December 5 as a heel, where he defeated Funaki in a squash match. The victory saw DeMott immediately receive a push that saw him squash several established wrestlers, including Funaki, Shannon Moore, Chuck Palumbo, Crash Holly, and Rikishi weekly on "SmackDown!". However, this came to an end soon and saw DeMott relegated back to "Velocity" beginning in February 2003. In May, DeMott made a face turn that also saw him tell knock-knock jokes as part of the turn. As the gimmick failed to get over, he remained on "Velocity" while continuing to win several squash matches. DeMott wrestled his last televised match on the June 14 episode of "Velocity", where he defeated fellow WCW alumnus Chris Kanyon. Later that month, DeMott retired from in-ring action, citing years of knee injuries. He then moved on to become the color commentator for "Velocity", beginning on the November 1 episode, and remained in that position until December 11, 2004.


title: Bill DeMott

text: When "Tough Enough 4" wrapped production, DeMott did not make a return to "Velocity". Instead, he became a full-time trainer for WWE and began working in the company's Deep South Wrestling developmental territory. DeMott also worked as a booker for DSW, although his direction in the promotion received criticism, most notably by former WWE developmental wrestler Kenny Omega, who soon requested to be released from his developmental contract due to poor treatment. DeMott was released from his WWE contract on January 19, 2007, with Tom Prichard taking his place as DSW's head trainer.


title: Bill DeMott

text: In March 2015, Devon Nicholson described an incident from 2006 that DeMott was involved with while he was head trainer for the WWE's Deep South Wrestling developmental territory. Nicholson described an incident in which Drew Hankinson was completely naked in the ring for a long period of time and gave naked stinkfaces to Zack Ryder and Melissa Coates while DeMott held jelly donuts over their faces. The wrestlers agreed to do this (with the other talent encouraging them) in order to get out of regular training for that day. DeMott refuted the notion that it was his idea, stating that the other trainees came up with because they wanted to skip the session.


title: Bill DeMott

text: After parting ways with WWE, DeMott competed for several independent promotions, including the Carolina Wrestling Association and the United Wrestling Federation. In addition to wrestling, he also began operating his own wrestling school called New Energy Wrestling School from 2009 to 2010 in McDonough, Georgia, while also running a brief series of wrestling events in Locust Grove, Georgia.


title: Bill DeMott

text: In 2011, WWE announced that DeMott would return to the company to perform as the head trainer on the revived "Tough Enough" series. Following the conclusion of "Tough Enough", DeMott replaced Tom Prichard as the head trainer for the Florida Championship Wrestling developmental territory on June 2, 2012. After FCW was rebranded into NXT, DeMott retained his position as the head trainer, and continued in that role when the WWE Performance Center was opened in 2013. He was featured as a trainer in the "WWE 2K15" video game.


title: Bill DeMott

text: DeMott resigned from WWE on March 6, 2015 following multiple online wrestling news reports of accusations of misconduct and abuse by a dozen-plus former WWE trainees (see below) -- allegations DeMott defiantly denied.


title: Bill DeMott

text: Several former FCW, DSW, and NXT employees previously working within or with the WWE developmental system made public allegations of misconduct by DeMott during his time as trainer, including accusing DeMott of making trainees perform dangerous drills, physically assaulting and bullying trainees, using homophobic and racial slurs amongst other derogatory terms, letting trainees train while naked, and condoning sexual harassment. These allegations were made by Kevin Matthews, Mike Bucci, Ivelisse Vélez, and Devon Nicholson in 2012, Chad Baxter and Chase Donovan in 2013, Curt Hawkins in 2014, as well as several wrestlers including Judas Devlin, Briley Pierce, Brandon Traven, Derrick Bateman, independent wrestler Terra Calaway, and All Elite Wrestling star Kenny Omega from late February to March 2015. Devlin and Traven stated they had submitted complaints to WWE management about DeMott in March 2013 when still WWE employees; they publicized those complaints in 2015. WWE released statements regarding some of the claims that came to light in 2013 and 2015, stating it had investigated the matter and had found no wrongdoing. Pierce questioned the thoroughness of WWE's investigations, saying WWE did not question him despite Pierce being one of the alleged victims. The allegations caused a strongly negative reaction on social media in March 2015, with the #FireDeMott hashtag trending on Twitter. On March 6, 2015, DeMott publicly denied the allegations on Twitter, but also announced his resignation from WWE "to avoid any embarrassment or damage" to the company.


title: Bill DeMott

text: During a May 2015 podcast with Vince Russo, Vélez asserted that her reporting DeMott's alleged misconduct in 2012 to WWE officials was the likely reason WWE released her (i.e., as retribution) shortly thereafter.


title: Bill DeMott

text: DeMott married his first wife, Rose Azzolino, in 1987. The marriage was annulled in 2004. They had two daughters: Casey, who was born two months premature on July 7, 1993, and Keri, who was born on January 9, 1995 and died in a car accident as a result of a drunk driver in Orlando, Florida on October 10, 2015.


title: Bill DeMott

text: DeMott married his second wife, Lacey Storey, on December 18, 2004. They have a son, William Charles DeMott III, who was born on November 2, 2008.


The 2022 United States Senate election in Connecticut was held on November 8, 2022, to elect a member of the United States Senate to represent the State of Connecticut.


title: 2022 United States Senate election in Connecticut

text: Democrat Richard Blumenthal was first elected to this seat in 2010 with 55.2% of the vote over Republican Linda McMahon. He was then re-elected in 2016 with 63.2% of the vote over Republican Dan Carter. Blumenthal ran for reelection to a third term in office and secured the 2022 nomination. Businesswoman Leora Levy won the Republican primary on August 9, 2022. Blumenthal won reelection, defeating Levy by about 15 points. The race simultaneously took place with the 2022 Connecticut gubernatorial election.


title: Rectus femoris muscle

text: The rectus femoris muscle is one of the four quadriceps muscles of the human body. The others are the vastus medialis, the vastus intermedius (deep to the rectus femoris), and the vastus lateralis. All four parts of the quadriceps muscle attach to the patella (knee cap) by the quadriceps tendon.


title: Rectus femoris muscle

text: The rectus femoris is situated in the middle of the front of the thigh; it is fusiform in shape, and its superficial fibers are arranged in a bipenniform manner, the deep fibers running straight () down to the deep aponeurosis. Its functions are to flex the thigh at the hip joint and to extend the leg at the knee joint.


title: Rectus femoris muscle

text: It arises by two tendons: one, the anterior or straight, from the anterior inferior iliac spine; the other, the posterior or reflected, from a groove above the rim of the acetabulum.


title: Rectus femoris muscle

text: The two unite at an acute angle and spread into an aponeurosis that is prolonged downward on the anterior surface of the muscle, and from this the muscular fibers arise.


title: Rectus femoris muscle

text: The muscle ends in a broad and thick aponeurosis that occupies the lower two-thirds of its posterior surface, and, gradually becoming narrowed into a flattened tendon, is inserted into the base of the patella.


title: Rectus femoris muscle

text: The neurons for voluntary thigh contraction originate near the summit of the medial side of the precentral gyrus (the primary motor area of the brain). These neurons send a nerve signal that is carried by the corticospinal tract down the brainstem and spinal cord. The signal starts with the upper motor neurons carrying the signal from the precentral gyrus down through the internal capsule, through the cerebral peduncle, and into the medulla. In the medullary pyramid, the corticospinal tract decussates and becomes the lateral corticospinal tract. The nerve signal will continue down the lateral corticospinal tract until it reaches spinal nerve L4. At this point, the nerve signal will synapse from the upper motor neurons to the lower motor neurons. The signal will travel through the anterior root of L4 and into the anterior rami of the L4 nerve, leaving the spinal cord through the lumbar plexus. The posterior division of the L4 root is the femoral nerve. The femoral nerve innervates the quadriceps femoris, a fourth of which is the rectus femoris. When the rectus femoris receives the signal that has traveled all the way from the medial side of the precentral gyrus, it contracts, extending the knee and flexing the thigh at the hip.


title: Rectus femoris muscle

text: The rectus femoris is a weaker hip flexor when the knee is extended because it is already shortened and thus suffers from active insufficiency; the action will recruit more iliacus, psoas major, tensor fasciae latae, and the remaining hip flexors than it will the rectus femoris.


title: Rectus femoris muscle

text: Similarly, the rectus femoris is not dominant in knee extension when the hip is flexed since it is already shortened and thus suffers from active insufficiency. In essence: the action of extending the knee from a seated position is primarily driven by the vastus lateralis, vastus medialis, and vastus intermedius, and less by the rectus femoris.


title: Rectus femoris muscle

text: In the other extreme, the muscle's ability to flex the hip and extend the knee can be compromised in a position of full hip extension and knee flexion, due to passive insufficiency.


title: Rectus femoris muscle

text: Rectus femoris strain, referred to as hip flexor strain, is an injury commonly at the tendon that attaches to the patella or in the muscle itself. The injury is usually a partial tear, but could be a full tear. The injury is caused by a forceful movement related to sprinting, jumping, or kicking and is common in sports like football or soccer. The rectus femoris is prone to injury, since it crosses both the knee and the hip. Symptoms include a sudden sharp pain at the front of the hip or in the groin, swelling and bruising, and an inability to contract the rectus femoris with a full tear.


title: Rectus femoris muscle

text: The Rectus femoris tendon can cause a fragment of anterior inferior ilac spine of the hip (AIIS) to avulse in what is known as an Avulsion fracture. This is due to forceful contraction of the muscle that generates a force greater than that which holds the bone together. This is a well recognized, but unusual sports injury that can affect young athletes.


title: Robin Olsen

text: Robin Patrick Olsen (; born 8 January 1990) is a Swedish professional footballer who plays as a goalkeeper for Premier League club Aston Villa and the Sweden national team.


title: Robin Olsen

text: Olsen's parents are Danish and he used to hold a Danish passport, but grew up in Sweden. He began his career playing for Malmö youth teams before moving to the academy of BK Olympic. At the age of 16 he joined IF Limhamn Bunkeflo and made his debut in the Swedish second tier of a year later.


title: Robin Olsen

text: In 2011, Olsen re-joined Malmö FF. He made his Allsvenskan debut on 1 October 2012 in an away fixture against Syrianska FC, when first choice goalkeeper Johan Dahlin was suspended, and kept a clean sheet as the match ended 2–0 in Malmö's favour. In the match on 5 April 2013 against Åtvidabergs FF Dahlin had to be substituted at half time for an injury and Olsen once again took his place. Olsen then managed to hold a clean sheet in the remaining part of the match as well as a further three matches before conceding a goal in stoppage time in his fourth match of the season in the away fixture against IFK Göteborg. Olsen kept Dahlin out of the starting eleven for some further matches before he was given the place on the bench once again. In total Olsen played 10 matches for Malmö FF during the league title winning 2013 season, an unusual feat for a second choice goalkeeper.


title: Robin Olsen

text: Prior to the start of the 2014 season the club sold Johan Dahlin, making Olsen the first choice goalkeeper. In the 2014 season, Olsen made 29 out of 30 league appearances and was a vital piece of the team that defended the clubs league title and qualified for the group stage of the 2014–15 UEFA Champions League. For his performances in the league Olsen was awarded Allsvenskan goalkeeper of the year. He was also nominated for Swedish goalkeeper of the year at Fotbollsgalan.


title: Robin Olsen

text: Olsen signed a four-year contract with Greek team PAOK F.C. on 1 July 2015, with a transfer fee of nearly €650,000 being paid to Malmö.


title: Robin Olsen

text: On 26 January 2016, Olsen would join F.C. Copenhagen on loan for six months, to cover for the injured Stephan Andersen. F.C. Copenhagen wanted to make the loan move permanent, and on 24 May 2016 Olsen signed a four-year contract with the club for a transfer fee of almost €600,000.


title: Robin Olsen

text: In July 2018, Olsen signed a five-year contract with the Italian club A.S. Roma with a reported fee worth up to €12,000,000, replacing the outgoing Alisson. He marked his debut for the team with a clean sheet in a 1–0 away victory against Torino F.C. on 19 August 2018. Olsen was eventually replaced by veteran Antonio Mirante by interim manager Claudio Ranieri towards the end of the season. In total, Olsen made 35 appearances in his sole season at Roma, conceding 58 goals and keeping just seven clean sheets.


title: Robin Olsen

text: In August 2019, Olsen joined Cagliari Calcio on a season-long loan. On 25 November 2019, Olsen was sent off in an away game against U.S. Lecce for pushing Gianluca Lapadula, who in turn had pushed Olsen for kicking the ball away. Both players were sent off, received a fine of €10,000, and Olsen was suspended for the next four Serie A matches.


title: Robin Olsen

text: He played his first game for Everton on 1 November, away from home in the league against Newcastle United, in place of Jordan Pickford who had played 120 consecutive league games prior to that fixture. Everton lost the game 2–1.


title: Robin Olsen

text: Olsen played his second game for Everton on 16 December 2020, away from home in the league against Leicester City. Everton won the game 0–2 with Olsen keeping a clean sheet. Olsen also kept a clean sheet in his last game for Everton against Brighton & Hove Albion 12 April 2021. The goalkeeper impressed on the occasions he stepped into the side in place of Jordan Pickford. Despite Carlo Ancelotti's initial desire to bring the 31-year-old to Goodison Park on a permanent basis, the surprise exit of the Italian in the summer seemingly scuppered any hope of that taking place. While Everton instead brought both Asmir Begovic and Andy Lonergan to Merseyside to provide back-up to Pickford, Olsen opted to move to Sheffield United on loan.


title: Robin Olsen

text: On 31 August 2021, Olsen joined Championship side Sheffield United. He made his debut on 14 September 2021, in a 2–2 draw against Preston North End. Olsen picked up an injury while on international duty in mid-November and did not play after that.


title: Robin Olsen

text: On 18 January 2022, Olsen was recalled from his Sheffield United loan, in order to join Aston Villa on loan for the remainder of the 2021–22 season.


title: Robin Olsen

text: On 22 May 2022, Olsen made his first appearance for Aston Villa in a 3–2 away defeat to Manchester City on the final day of the season. The match was significant in the race between City and Liverpool, the three points leading to Manchester City winning the Premier League title. Amidst the post-match celebrations, Olsen was assaulted during a pitch invasion by Manchester City fans. Manchester City released a statement saying that "the club has launched an immediate investigation and once identified, the individual responsible will be issued with an indefinite stadium ban."


title: Robin Olsen

text: On 4 June 2022, Olsen signed for Aston Villa on a permanent basis, for an undisclosed fee rumoured to be in the region of £3m. On 29 October 2022, he made his first appearance since signing for Villa permanently in a away defeat to Newcastle United, coming off the bench to replace Emiliano Martínez, who had suffered a suspected concussion.


title: Robin Olsen

text: Olsen was eligible for international play for both Denmark and Sweden. When he came to Malmö FF he said that he would prefer to play for Denmark but in 2014 he opted to play for Sweden according to Danish international coach Morten Olsen. On 15 January 2015, he made his debut for Sweden in a friendly fixture against the Ivory Coast.


title: Robin Olsen

text: In May 2016, Olsen was called up for Sweden's squad for UEFA Euro 2016, as back-up keeper for Andreas Isaksson. After Sweden's early exit from the tournament, Isaksson retired and Olsen became Sweden's first-choice goalkeeper.


title: Robin Olsen

text: In May 2018 he was named in Sweden's 23-man squad for the 2018 FIFA World Cup in Russia. At the 2018 World Cup, Olsen started in all five games for Sweden as they were eliminated by England in the quarter final.


title: Robin Olsen

text: In March 2021, Olsen and his family were threatened with a machete by a masked gang during a raid on their home in Altrincham, Greater Manchester. The gang stole jewellery and a luxury watch during the burglary.


title: British Cyprus

text: British Cyprus was the island of Cyprus under the dominion of the British Empire, administered sequentially from 1878 to 1914 as a British protectorate, from 1914 to 1925 as a unilaterally annexed military occupation, and from 1925 to 1960 as a Crown colony. Following the London and Zürich Agreements of 19 February 1959, Cyprus became an independent republic on 16 August 1960.


title: British Cyprus

text: Cyprus was a territory of the Ottoman Empire, lastly as part of the Vilayet of the Archipelago, since it was conquered from the Republic of Venice in 1570–71.


title: British Cyprus

text: A British protectorate under nominal Ottoman suzerainty was established over Cyprus by the Cyprus Convention of 4 June 1878, following the Russo-Turkish War, in which the British occupied the island as a consequence of the Ottoman Empire's actions throughout the duration of the war. Cyprus was then proclaimed a British protectorate and was informally integrated into the British Empire. This remained in place until 5 November 1914, when after the Ottomans joined the Central Powers, in turn entering World War I, Britain declared the complete annexation of Cyprus into the British Empire, albeit under a military administration status. The Crown Colony of Cyprus was proclaimed a decade later, in 1925, after Britain's annexation of Cyprus was verified twice, firstly in the Treaty of Sèvres in 1920, then confirmed again in the Treaty of Lausanne in 1923.


title: British Cyprus

text: King Paul of Greece declared that Cyprus desired union with Greece in 1948. A referendum was presented by the Orthodox Church of Cyprus in 1950, according to which around 97% of the Greek Cypriot population wanted the union. The Greek petition and enosis became an international issue when it was accepted by the United Nations.


title: British Cyprus

text: The Cyprus Emergency was a military action that took place in Cyprus from 1955 to 1959. The Cyprus Emergency primarily consisted of a campaign by the Greek Cypriot military group EOKA to remove the British from Cyprus so it could be unified with Greece.


title: British Cyprus

text: Signed on 19 February 1959, the London and Zurich Agreements started the process for the constitution of an independent Cyprus. The United Kingdom granted independence to Cyprus on 16 August 1960 and formed the Republic of Cyprus. Archbishop Makarios III, a charismatic religious and political leader, was elected as the first president of independent Cyprus. As part of the independence agreement, the United Kingdom retained possession of the Sovereign Base Areas of Akrotiri and Dhekelia as a British Overseas Territory.


title: British Cyprus

text: In March 1961 at the 1961 Commonwealth Prime Ministers' Conference, Cyprus became an independent republic in the Commonwealth of Nations, and Archbishop Makarios III became both a Commonwealth head of state and a Commonwealth head of government.


title: Kaikala Satyanarayana

text: Kaikala Satyanarayana (born 25 July 1935) is an Indian actor, producer, director, and politician who predominantly worked in Telugu cinema. He appeared in over 750 films and served as the Member of Parliament in the 11th Lok Sabha representing Machilipatnam constituency from Telugu Desam Party. He is the recipient of the 2011 Raghupathi Venkaiah Award, and 2017 Filmfare Award for lifetime achievement in Telugu cinema.


title: Kaikala Satyanarayana

text: Kaikala Satyanarayana was born on 25 July 1935 to Kaikala Laxmi Narayana from Kavutaram village in Krishna district. Having completed his primary education in Gudlavalleru and intermediate education in Vijayawada, Satyanarayana graduated from Gudivada College.


title: Kaikala Satyanarayana

text: Kaikala was first noticed by D. L. Narayana, who offered him a role in his film "Sipayi Koothuru" directed by Changayya in 1959. Though it did not do well at the box office, he was noticed for his resemblance to N.T. Rama Rao. They found him as a prospective candidate to play dupe to NTR. Satyanarayana aptly fitted that place. He played dupe to NTR in several movies. NTR offered Satyanarayana a role in his film "Apoorva Sahasra Siraccheda Chintamani" in 1960, directed by S. D. Lal. Satyanarayana played the role of a prince.


title: Kaikala Satyanarayana

text: B. Vittalacharya cast him in a negative role in "Kanaka Durga Pooja Mahima". He fit the role to the T; from then on, Satyanarayana grew to infinite bounds in establishing himself in villain roles. Satyanarayana established "Rama Films" production house and made films such as "Kodama Simham" (1990), "Bangaru Kutumbam" (1994), and "Muddula Mogudu" (1997). He went on to appear in over 750 films.


title: Kaikala Satyanarayana

text: In 1996, he stepped into politics with TDP winning Lok Sabha elections from Machilipatnam constituency.


title: Atrazine

text: Atrazine is a chlorinated herbicide of the triazine class. It is used to prevent pre-emergence broadleaf weeds in crops such as maize (corn), soybean and sugarcane and on turf, such as golf courses and residential lawns. Atrazine's primary manufacturer is Syngenta and it is one of the most widely used herbicides in the United States, Canadian, and Australian agriculture. Its use was banned in the European Union in 2004, when the EU found groundwater levels exceeding the limits set by regulators, and Syngenta could not show that this could be prevented nor that these levels were safe.


title: Atrazine

text: At least two significant Canadian farm well studies showed that atrazine was the most common contaminant found. , atrazine was the most commonly detected pesticide contaminating drinking water in the U.S. Studies suggest it is an endocrine disruptor, an agent that can alter the natural hormonal system. However, in 2006 the U.S. Environmental Protection Agency (EPA) had stated that under the Food Quality Protection Act "the risks associated with the pesticide residues pose a reasonable certainty of no harm", and in 2007, the EPA said that atrazine does not adversely affect amphibian sexual development and that no additional testing was warranted. EPA's 2009 review concluded that "the agency's scientific bases for its regulation of atrazine are robust and ensure prevention of exposure levels that could lead to reproductive effects in humans". However, in their 2016 Refined Ecological Risk Assessment for Atrazine, it was stated that "it is difficult to make definitive conclusions about the impact of atrazine at a given concentration but multiple studies have reported effects to various endpoints at environmentally-relevant concentrations." EPA started a registration review in 2013.


title: Atrazine

text: The EPA's review has been criticized, and the safety of atrazine remains controversial. EPA has however stated that "If at any time EPA determines there are urgent human or environmental risks from atrazine exposure that require prompt attention, we will take appropriate regulatory action, regardless of the status of the registration review process."


title: Atrazine

text: Atrazine is a herbicide that is used to stop pre- and post-emergence broadleaf and grassy weeds in crops such as sorghum, maize, sugarcane, lupins, pine, and eucalypt plantations, and triazine-tolerant canola.


title: Atrazine

text: In the United States as of 2014, atrazine was the second-most widely used herbicide after glyphosate, with of it applied each year. Atrazine continues to be one of the most widely used herbicides in Australian agriculture. Its effect on corn yields has been estimated from 1% to 8%, with 3–4% being the conclusion of one economics review. In another study looking at combined data from 236 university corn field trials from 1986 to 2005, atrazine treatments showed an average of 5.7 bushels more per acre (~400 kg per hectare) than alternative herbicide treatments. Effects on sorghum yields have been estimated to be as high as 20%, owing in part to the absence of alternative weed control products that can be used on sorghum.


title: Atrazine

text: Atrazine was invented in 1958 in the Geigy laboratories as the second of a series of 1,3,5-triazines.


title: Atrazine

text: Atrazine is prepared from cyanuric chloride, which is treated sequentially with ethylamine and isopropylamine. Like other triazine herbicides, atrazine functions by binding to the plastoquinone-binding protein in photosystem II, which animals lack. Plant death results from starvation and oxidative damage caused by breakdown in the electron transport process. Oxidative damage is accelerated at high light intensity.


title: Atrazine

text: Atrazine's effects in humans and animals primarily involve the endocrine system. Studies suggest that atrazine is an endocrine disruptor that can cause hormone imbalance.


title: Atrazine

text: Atrazine has been found to act as an agonist of the G protein-coupled estrogen receptor 1. Atrazine has been shown to bind covalently to (chemically react with) a large number of mammalian proteins.


title: Atrazine

text: Atrazine contamination of surface water (lakes, rivers, and streams) in the U.S. has been monitored by the EPA and has consistently exceeded levels of concern in two Missouri watersheds and one in Nebraska. Monitoring of atrazine levels in community water systems in 31 high-use states found that levels exceeded levels of concern for infant exposure during at least one year between 1993 and 2001 in 34 of 3670 community water systems using surface water, and in none of 14,500 community water systems using groundwater. Surface water monitoring data from 20 high atrazine use watersheds found peak atrazine levels up to 147 parts per billion, with daily averages in all cases below 10 parts per billion.


title: Atrazine

text: Atrazine remains in soil for a matter of months (although in some soils can persist to at least four years) and can migrate from soil to groundwater; once in groundwater, it degrades slowly. It has been detected in groundwater at high levels in some regions of the U.S. where it is used on some crops and turf. The U.S. Environmental Protection Agency expresses concern regarding contamination of surface waters (lakes, rivers, and streams).


title: Atrazine

text: Atrazine degrades in soil primarily by the action of microbes. The half-life of atrazine in soil ranges from 13 to 261 days. Atrazine biodegradation can occur by two known pathways:


title: Atrazine

text: Rates of biodegradation are affected by atrazine's low solubility; thus surfactants may increase the degradation rate. Though the two alkyl moieties readily support growth of certain microorganisms, the atrazine ring is a poor energy source due to the oxidized state of ring carbon. In fact, the most common pathway for atrazine degradation involves the intermediate, cyanuric acid, in which carbon is fully oxidized, thus the ring is primarily a nitrogen source for aerobic microorganisms. Atrazine may be catabolized as a carbon and nitrogen source in reducing environments, and some aerobic atrazine degraders have been shown to use the compound for growth under anoxia in the presence of nitrate as an electron acceptor, a process referred to as a denitrification. When atrazine is used as a nitrogen source for bacterial growth, degradation may be regulated by the presence of alternative sources of nitrogen. In pure cultures of atrazine-degrading bacteria, as well as active soil communities, atrazine ring nitrogen, but not carbon are assimilated into microbial biomass. Low concentrations of glucose can decrease the bioavailability, whereas higher concentrations promote the catabolism of atrazine.


title: Atrazine

text: The genes for enzymes AtzA-C have been found to be highly conserved in atrazine-degrading organisms worldwide. In "Pseudomonas" sp. ADP, the Atz genes are located noncontiguously on a plasmid with the genes for mercury catabolism. AtzA-C genes have also been found in a Gram-positive bacterium, but are chromosomally located. The insertion elements flanking each gene suggest that they are involved in the assembly of this specialized catabolic pathway. Two options exist for degradation of atrazine using microbes, bioaugmentation or biostimulation. Recent research suggests that microbial adaptation to atrazine has occurred in some fields where the herbicide is used repetitively, resulting in more rapid biodegradation. Like the herbicides trifluralin and alachlor, atrazine is susceptible to rapid transformation in the presence of reduced iron-bearing soil clays, such as ferruginous smectites. In natural environments, some iron-bearing minerals are reduced by specific bacteria in the absence of oxygen, thus the abiotic transformation of herbicides by reduced minerals is viewed as "microbially induced".


title: Atrazine

text: In 2016, photolytic degradation with 254 nm ultraviolet was seen by the authors of a particular study as an efficient process, which could be used in pilot plants to reduce or eliminate compounds of the atrazine class or similar emerging contaminants, in effluents.


title: Atrazine

text: According to Extension Toxicology Network in the U.S., "The oral median Lethal Dose or for atrazine is 3090 mg/kg in rats, 1750 mg/kg in mice, 750 mg/kg in rabbits, and 1000 mg/kg in hamsters. The dermal LD in rabbits is 7500 mg/kg and greater than 3000 mg/kg in rats. The 1-hour inhalation LC is greater than 0.7 mg/L in rats. The 4-hour inhalation LC is 5.2 mg/L in rats." The maximum contaminant level is 0.003 mg/L and the reference dose is 0.035 mg/kg/day.


title: Atrazine

text: A September 2003 review by the Agency for Toxic Substances and Disease Registry (ATSDR) stated that atrazine is "currently under review for pesticide re-registration by the EPA because of concerns that atrazine may cause cancer", but not enough information was available to "definitely state whether it causes cancer in humans." According to the ATSDR, one of the primary ways that atrazine can affect a person's health is "by altering the way that the reproductive system works. Studies of couples living on farms that use atrazine for weed control found an increase in the risk of preterm delivery, but these studies are difficult to interpret because most of the farmers were men who may have been exposed to several types of pesticides. Little information is available regarding the risks to children, however "[m]aternal exposure to atrazine in drinking water has been associated with low fetal weight and heart, urinary, and limb defects in humans". Incidence of a birth defect known as gastroschisis appears to be higher in areas where surface water atrazine levels are elevated especially when conception occurs in the spring, the time when atrazine is commonly applied.


title: Atrazine

text: The World Health Organization's International Agency for Research on Cancer has classified atrazine as "not classifiable as to its carcinogenicity to humans" (Group 3).


title: Atrazine

text: In 2006, the EPA stated, "the risks associated with the pesticide residues pose a reasonable certainty of no harm".


title: Atrazine

text: In 2007, the EPA said, "studies thus far suggest that atrazine is an endocrine disruptor". The implications for children's health are related to effects during pregnancy and during sexual development, though few studies are available. In people, risks for preterm delivery and intrauterine growth retardation have been associated with exposure. Atrazine exposure has been shown to result in delays or changes in pubertal development in female rats; conflicting results have been observed in males. Male rats exposed via milk from orally exposed mothers exhibited higher levels of prostate inflammation as adults; immune effects have also been seen in male rats exposed in utero or while nursing. EPA opened a new review in 2009 that concluded that "the agency's scientific bases for its regulation of atrazine are robust and ensure prevention of exposure levels that could lead to reproductive effects in humans." Deborah A. Cory-Slechta, a professor at the University of Rochester in New York has said in 2014, "The way the E.P.A. tests chemicals can vastly underestimate risks." She has studied atrazine's effects on the brain and serves on the E.P.A.'s science advisory board. She further stated, "There's still a huge amount we don't know about atrazine."


title: Atrazine

text: A Natural Resources Defense Council report from 2009 said that the EPA is ignoring atrazine contamination in surface and drinking water in the central United States.


title: Atrazine

text: Research results from the U.S. National Cancer Institute's 2011 Agricultural Health Study concluded, "there was no consistent evidence of an association between atrazine use and any cancer site". The study tracked 57,310 licensed pesticide applicators over 13 years.


title: Atrazine

text: A 2011 review of the mammalian reproductive toxicology of atrazine jointly conducted by the World Health Organization and the Food and Agriculture Organization of the United Nations concluded that atrazine was not teratogenic. Reproductive effects in rats and rabbits were only seen at doses that were toxic to the mother. Observed adverse effects in rats included fetal resorption in rates (at doses > 50 mg/kg per day), delays in sexual development in female rats (at doses >30 mg/kg per day), and decreased birth weight (at doses >3.6 mg/kg per day).


title: Atrazine

text: A 2014 systematic review, funded by atrazine manufacturer Syngenta, assessed its relation to reproductive health problems. The authors concluded that the quality of most studies was poor and without good quality data, the results were difficult to assess, though it was noted that no single category of negative pregnancy outcome was found consistently across studies. The authors concluded that a causal link between atrazine and adverse pregnancy outcomes was not warranted due to the poor quality of the data and the lack of robust findings across studies. Syngenta was not involved in the design, collection, management, analysis, or interpretation of the data and did not participate in the preparation of the manuscript.


title: Atrazine

text: Atrazine has been a suspected teratogen, with some studies reporting causing demasculinization in male northern leopard frogs even at low concentrations, and an endocrine disruptor. A 2002 study by Tyrone Hayes, of the University of California, Berkeley, found that exposure caused male tadpoles to turn into hermaphrodites – frogs with both male and female sexual characteristics. However, this study has not been able to be replicated, and a 2003 EPA review of this study concluded that overcrowding, questionable sample handling techniques, and the failure of the authors to disclose key details including sample sizes, dose-response effects, and the variability of observed effects made it difficult to assess the study's credibility and ecological relevance. A 2005 study, requested by EPA and conducted under EPA guidance and inspection, was unable to reproduce Hayes' results.


title: Atrazine

text: The EPA's Scientific Advisory Panel examined relevant studies and concluded in 2010, "atrazine does not adversely affect amphibian gonadal development based on a review of laboratory and field studies". It recommended proper study design for further investigation. As required by the EPA, two experiments were conducted under Good Laboratory Practices (GLP) and were inspected by EPA and German regulatory authorities, concluding 2009 that "long-term exposure of larval "X. laevis" to atrazine at concentrations ranging from 0.01 to 100 μg/L does not affect growth, larval development, or sexual differentiation". A 2008 report cited the independent work of researchers in Japan, who were unable to replicate Hayes' work. "The scientists found no hermaphrodite frogs; no increase in aromatase as measured by aromatase mRNA induction; and no increase in vitellogenin, another marker of feminization."


title: Atrazine

text: A 2007 study examined the relative importance of environmentally relevant concentrations of atrazine on trematode cercariae versus tadpole defense against infection. Its principal finding was that susceptibility of wood frog tadpoles to infection by "E. trivolvis" is increased only when hosts were exposed to an atrazine concentration of 30 mg/L and not to 3 mg/L.


title: Atrazine

text: A 2008 study reported that tadpoles developed deformed hearts and impaired kidneys and digestive systems when chronically exposed to atrazine concentrations of 10 ppm in their early stages of life. Tissue malformation may have been induced by ectopic programmed cell death, although a mechanism was not identified.


title: Atrazine

text: In 2010, the Australian Pesticides and Veterinary Medicines Authority (APVMA) tentatively concluded that environmental atrazine "at existing levels of exposure" was not affecting amphibian populations in Australia consistent with the 2007 EPA findings. APVMA responded to Hayes' 2010 published paper, that his findings "do not provide sufficient evidence to justify a reconsideration of current regulations which are based on a very extensive dataset."


title: Atrazine

text: A 2015 EPA article discussed the Hayes/Syngenta conflict to illustrate both financial and nonfinancial conflicts of interest. The authors concluded, "Statements by Hayes and Syngenta suggest that their scientific differences have developed a personal aspect that casts doubt on their scientific objectivity".


title: Atrazine

text: In 2012, Syngenta, manufacturer of atrazine, was the defendant in a class-action lawsuit concerning the levels of atrazine in human water supplies. Syngenta agreed to pay $105 million to reimburse more than one thousand water systems for "the cost of filtering atrazine from drinking water". The company denied all wrongdoing.


title: Atrazine

text: Prompted by the EU's 2004 ban, a regulatory review of the product in Canada by the PMRA was begun in 2015. On 31 March 2017 the review result was published and the PMRA decided to leave unchanged the product's registration. This was done because while the EU's ban was based on a legislated pollutant level of 0.1 μg/L, the Canadian regulations call for a home-grown "risk-based scientific approach in determining the risk to human health from pesticides in drinking water." The US drinking water standard of 3 μg/L is inferior to the Canadian standard of 5 μg/L. Both maximum pollutant levels in North America were not exceeded by the maximum pollutant level in Canadian data of 2.32 μg/L.


title: Alex Band

text: Alexander Max Band (born June 8, 1981) is an American singer, songwriter, musician, record producer and actor. He is best known for being the vocalist of Los Angeles rock band the Calling, having performed on their hit song "Wherever You Will Go", which topped the Adult Top 40 for 23 weeks, making it the second-longest-running number 1 in the chart's history and later named the number 1 song of the decade of the 2000s on the Adult Pop Charts by "Billboard" magazine.


title: Alex Band

text: Along with friend and fellow songwriter Aaron Kamin, lead guitarist of The Calling, they achieved success with the release of two studio albums; their debut album, "Camino Palmero", sold over 5 million copies worldwide and was certified Gold by RIAA, and their second album, "Two", sold over 1.5 million copies, achieving hits across the world with the singles "Our Lives", and "Things Will Go My Way".


title: Alex Band

text: As a solo artist, Alex Band is well known for providing the vocals and face to the top 5 hit "Why Don't You & I" with Carlos Santana in 2004. In 2008, he created his own record label, AMB Records, and released a five-song EP entitled "Alex Band EP". Band later released his debut full-length album, "We've All Been There", in June 2010 with "Tonight" being its lead single, which was used as the theme song for the 2010 World Cup. He released his second EP, "After the Storm", in 2012.


title: Alex Band

text: Alex Band was born in Los Angeles, California, into an entertainment family. His mother is Meda Band (nee Robertson), and his father, Charles Band, is a well-known horror film director. His grandfather Albert Band was also another well-known director. Band's father is Jewish and his mother is Christian. Both his parents were raised in Italy and they owned a castle in Giove, Umbria. Band explores spiritual themes in several of his songs, though he claims to be of no particular faith himself. Of the song "Please", Band said; "...I grew up with a Jewish father who didn't practice and a Christian mother whose only tie to Jesus was celebrating Christmas. Needless to say I had to find my own religion. And in this song I'm asking God what that should be...what should I believe? In a world so full of different religions and so many people fighting over whose belief is the correct one, it frustrates me to think that they all really boil down to the same thing."


title: Alex Band

text: At a young age, Band's parents divorced and his father remarried. He grew up with two of his half-brothers, Harlan and Zalman, and his sister, Taryn. In 2020, his younger half-brother Harlan died after battling with addiction for over a decade. After his parents' divorce, his mother moved to Germany where she remarried and still resides. Band was about 8 at the time. She had three sons after her move, who Band eventually met when he toured Germany. The single "Could It Be Any Harder" explains some of his feelings towards his mother's move.


title: Alex Band

text: Growing up, Band made small appearances in his father's films. He grew up on Camino Palmero street, which would later inspire his first album of the same name. He began playing guitar and songwriting at the age of 8. Musically, Band was influenced by Pearl Jam, Bon Jovi, Live, Train and U2. At the age of 14, he had a kokopelli tattooed on his wrist. This would later become a symbol for The Calling.


title: Alex Band

text: He soon formed his first band with friend and filmmaker, Jethro Rothe-Kushel, called "Maybe Solitude". Rothe-Kushel also directed his first music video for a song called "Dormant Prayer". After the band disbanded, Band met Aaron Kamin when Kamin was dating Band's sister. They both began writing songs and jamming as far back as 1996 and soon formed the band "Generation Gap" that consisted of him and Kamin, and a few much older musicians. At this stage, the band also had saxophonist, Benny Golbin, giving the songs a more jazzy sound reminiscent of Dave Matthews Band.


title: Alex Band

text: Eventually, Band and Kamin ditched the "Gap" lineup, and briefly switched their name to "Next Door", which itself was a nod to Ron Fair, a veteran music business executive and Band's neighbor.


title: Alex Band

text: Kamin and Band began focusing on songwriting more, and as Band's signature baritone voice began to mature, the duo began leaving demo tapes of new songs and ideas for Fair in his mailbox. They quickly found a similar sound amongst such ready-for-radio rock acts of the early 21st century as Matchbox Twenty, Third Eye Blind, Train, and Fastball.


title: Alex Band

text: By 1999, Fair was impressed enough by the demos to sign them to a record deal with RCA. They changed their name to The Calling, which reflected the band's renewed sense of purpose.


title: Alex Band

text: At the age of 15, Band signed with RCA Records with the band he had created with Kamin, now named The Calling. At this time, he dropped out of school, though he later received a diploma through home schooling. The Calling released their first single "Wherever You Will Go" to much acclaim. The song soon reached number 1 on the Billboard Hot AC charts for 23 weeks and peaked at number 5 on the Hot 100 charts as well as becoming an international hit. The band's first album "Camino Palmero" soon followed, peaking at number 36 on the Billboard Sales charts and eventually went Platinum. The band's next singles, "Adrienne" and "Could It Be Any Harder" soon followed, charting in the AC top 40.


title: Alex Band

text: However, by 2004, the second album titled "Two" failed to live up to expectations, charting at number 54 on Billboard Top 200. The album suffered from a lack of label support, though the singles fared slightly better. The first single, "Our Lives," was featured in the 2004 Olympics ceremony and charted at number 34 in the Billboard top 40. A final single, "Anything," performed decently with little promotion, charting at number 23 in the Adult Top 40.


title: Alex Band

text: After the lack of label support with "Two", the band announced a hiatus. On June 4, 2005, they performed their last concert to date in Temecula, CA.


title: Alex Band

text: On August 15, 2013, Alex Band reformed The Calling with new members. The band performed their comeback gig at Bally's Atlantic City on August 17. On August 18, Band was reportedly abducted by two men that robbed him, beat him severely, and dumped him on train tracks in Lapeer, Michigan. He was taken to an emergency room at a nearby hospital, where he was treated and released. After only a few shows, the group broke up again.


title: Alex Band

text: In October 2016, The Calling reformed with a new lineup and performed in Manila, Philippines the following month. The Australian company Unbreakable Touring announced that the band were to perform in areas such as Adelaide, Sydney, Brisbane, Melbourne and Fremantle along with the rock band Juke Kartel and newcomer Mike Waters, but this was later postponed due to visa issues. In July 2017 it was announced that The Calling would be joining Lifehouse as support acts for Live's Australian leg of their world reunion tour.


title: Alex Band

text: Band said in an interview with Australian music website "may the rock be with you" in November 2017 that The Calling will be releasing new music soon.


title: Alex Band

text: In February 2020 whilst speaking in a video interview with Welsh media outlet Steegcast, Band spoke of his plans for the future, including the plan to release new music as well as eventually releasing orchestral reworkings of some of The Calling's back catalogue.


title: Alex Band

text: In November 2005 it was announced Band had signed as a solo artist with Ron Fair as part of Geffen Records. A new album had been recorded and was said to be released in late 2007, but was delayed several times. Band left the Geffen label in 2008. Band also contributed the song "The Truth" to the soundtrack of the 2005 movie "Doll Graveyard" which was directed by his father.


title: Alex Band

text: During this time Band had a few releases. One of his songs titled, "It Doesn't Get Better Than This" for "" soundtrack. Band performed and co-wrote the song, "Coming Home" which was featured in the film, "The Final Season" in late 2007.


title: Alex Band

text: In October 2007 Band performed at the first Alex Band's Donate Life Rocks charity concert for "Donate Life America" in Los Angeles, CA. The concert was taped and will air on DISH Network. Band also taped an appearance on "" which filmed at the concert. The second Alex Band Donate Life concert was held in Richmond, VA on August 21, 2008. The first music video in his solo career was again directed by lifelong friend and director / producer, Jethro Rothe-Kushel, for a song called "Only One". On April 25, 2008 Band released a 5-song EP titled, "Alex Band EP". The EP contained four new songs in addition to the song "Coming Home". The EP is sold via his official fan site. A new version of the EP was created for his tour in Brazil. On May 13 it was announced that the track, "Only One" would be the official single, for Brazil only, with both single and video available through Band's official fan site.


title: Alex Band

text: Band expressed displeasure with the continued delayed release of his debut album. On April 16, 2008, Band announced via his official fan site that he had left Geffen and created his own label called AMB Records under which the album in the US will be released, after buying back the rights to the master tapes after Geffen had gone through major restructuring. Band states: I've been working on leaving my label for a while now, and moving to somewhere else to put this record out finally and give it the push it deserves... and I'm happy to announce that I will be putting the record out on my own! With help from good friends in the business and an amazing team, I'm putting together my own label. This gives me the freedom to make my own decisions, to invest in myself, and to do what I want, when I want. This is the way to go these days in the music business and I am so lucky to be able to do it. There are no firm details as to when exactly the record will be released, but I am doing everything in my power to make the process as speedy as possible. I will let you all know of course as soon as I find out more.