Karla Sofen

Dr. Karla Sofen (also known as Moonstone, Meteorite, and Ms. Marvel) is a fictional character appearing in American comic books published by Marvel Comics. She first appeared in "Captain America" (vol. 1) #192, created by writer Marv Wolfman and artist Frank Robbins.
She is a former psychologist who got her powers from a fusion with a gravity stone designed by the alien Kree. The character has been depicted as both a supervillain and an anti-hero at various times in her publication history. She was a member of the Masters of Evil, Thunderbolts and the Dark Avengers, and in the latter group she temporally replaced Carol Danvers as Ms. Marvel.
Publication history.
The character first appeared as a gun moll of the villain Dr. Faustus in "Captain America" (vol. 1) #192. She later appeared in issue #228 of "The Incredible Hulk" where it was revealed that she was the psychiatrist of the former Moonstone, Lloyd Bloch, and that she tricked him into relinquishing the moonstone to her. She was later revealed to be a member of the shadowy organization known as the Corporation.
She appeared in Avengers as part of the supervillain team the Masters of Evil. During the disappearance of the Avengers and the Fantastic Four (after the Onslaught crossover), the Masters of Evil, Moonstone (as Meteorite) included, posed as the new hero team called the Thunderbolts. After 12 issues, their true identities were exposed. Moonstone returned to the Thunderbolts series in 2007's "Thunderbolts" #110, as the team's new field leader.
Moonstone was one of the Thunderbolts' characters that Brian Michael Bendis moved over to the Dark Avengers, where she took on the identity of Ms. Marvel, and she became the main character in the "Ms. Marvel" solo title in issue #38. She appeared as a regular character in the "Dark Avengers" series from issue #1 (March 2009) through issue #16 (June 2010).
Moonstone returned to the "Thunderbolts" in issue #144, after the Dark Reign era. She became part of a government program led by Luke Cage to reform villains. Joining them was Juggernaut, Ghost, Crossbones, and Man-Thing. She remained with the team after the title transitioned into "Dark Avengers" beginning with issue #175.
Moonstone was also a member of the third "Thunderbolts" team, which was relaunched as part of the aftermath of "". It was written by Jim Zub and drawn by Jon Malin, the team consists of Moonstone, The Winter Soldier, the Fixer, Atlas and MACH-V. The comic was cancelled after twelve issues due to the "Secret Empire" event.
Fictional character biography.
Origins.
Karla Sofen was born in Van Nuys, California. She grew up in the mansion of Hollywood producer Charles Stockbridge, as the child of the butler Karl Sofen. After her father's death, her mother Marion Sofen worked three jobs to put her daughter through college, and Karla vowed never to end up like her mother and that she would never put another's needs before her own. Despite building a successful practice as a psychologist and psychiatrist, Karla so disliked being dependent on her patients for income that she entered the super-criminal world as an aide to Doctor Faustus. Learning of Lloyd Bloch (a.k.a. the original Moonstone), she became the supervillain's psychologist and manipulated him into rejecting the source of his powers, an extraterrestrial gem of considerable power, which she then acquired and absorbed to gain the powers of Moonstone. She then battled the Hulk.
It has been revealed Karla murdered her mother by suffocating her and then set her house on fire. It has also been said that during Sofen's career as a psychologist, she convinced depressed patients to kill themselves while she watched, and was "instrumental in the therapeutic hospitalization of six more".
Masters of Evil.
Karla Sofen worked briefly for the Corporation, controlling the Hulk and manipulating General Thunderbolt Ross into a nervous breakdown. She battled Captain America, Falcon, Hulk and Quasar on behalf of the Corporation. She continued to pursue greater power, stealing Curt Connors's Enervator and fighting Spider-Man in the process.
Egghead recruited her for the third Masters of Evil and she fought the Avengers. However, her tenure was short-lived as she surrendered after the Masters of Evil's defeat. It wasn't long before she broke out of confinement at Project: Pegasus with Blackout, the Rhino and Electro, battling the Avengers and escaping into the Darkforce dimension with Blackout. She traveled to the Moon in search for more moon stone fragments, where she battled Dazzler and the Inhumans, and was then returned to Pegasus.
Later, Baron Helmut Zemo recruited Moonstone for the fourth Masters of Evil. She participated in the Masters' takeover of Avengers Mansion, but attempted to manipulate the mentally damaged Blackout to her side to take position of team leader from Zemo. She subsequently battled Captain Marvel, but this confrontation ended with her being temporarily paralyzed when she crashed into a cliff during the fight and broke her neck. Healed by the power of the stone, she then had a rematch with Captain Marvel. Moonstone later battled Volcana. She was twice targeted by the original Moonstone, now known as Nefarius, first while going to court, and then when he got imprisoned in the Vault. Eventually, she decided to serve out her prison term.
Thunderbolts.
When Baron Zemo formed a group of villains to masquerade as heroes, Moonstone was broken out of the Vault and she reluctantly returned to villainy as Meteorite, a member of the Thunderbolts.
Upon encountering a young victim of Arnim Zola's genetic manipulations, a youngster by the name of Jolt, Meteorite nudged Zemo into accepting her in the team. She soon became a mother figure to Jolt and used the enthusiasm to create a power-base inside the team, rallying the others behind her. Zemo exposed the true nature of the team, but Moonstone opposed Zemo, followed by MACH-1, Songbird and Jolt. Zemo had brainwashed the Fantastic Four and the Avengers, but the small team of Thunderbolts, with the help of Iron Man, was able to defeat Zemo and Techno. After the battle the Thunderbolts had decided to pay for their crimes, but they were unwittingly teleported to an alternate dimension.
In this world known as Kosmos, Moonstone led the team to safety from the Kosmosian army and eventually executed the Kosmosian Primotur to ensure their return to Earth. Inspired by Jolt, she made the Thunderbolts see that it would be preferable to work for their redemption as heroes, rather than to be in jail. After gaining fake identities for the team, she led them away from S.H.I.E.L.D. and the Lightning Rods, and she managed to defeat Graviton using her psychological skills, making Graviton see he was without a true goal and he was lacking vision. However, the Thunderbolts disagreed with her, for she merely thought of the present and did not care for the future consequences of her actions. When Hawkeye joined the team, claiming they would be pardoned if they followed the former member of the Avengers, she stepped down as leader.
Nightmares.
Soon after the Thunderbolts fought the new Masters of Evil, a veritable army of supervillains, and Moonstone decided to betray the team. But something inside of her snapped, and she defeated Crimson Cowl and returned to the team.
Graviton returned weeks later, having pondered Karla Sofen's words. Graviton took over the city of San Francisco, turning it into an island in the skies. The Thunderbolts attempted to stop this, but they were captured. Graviton offered Moonstone a place at his side, as a queen, but she laughed at this. As the youngest members of the team saved them, Moonstone wondered why she didn't take Graviton's offer.
During a mission against the Secret Empire, she became romantically involved with Hawkeye. In "Thunderbolts" #30, Hawkeye invited Moonstone and Songbird to come train with him. While Songbird refused, Karla accepted. During the fight, Hawkeye praised Karla for being a woman in athletic condition. Moonstone, however, turned the tables, complimenting the fact that Hawkeye trained four hours a day to maintain peak human physical performance. Using psychological deduction, she picked up on Clint's attraction towards her. At the end of the issue, Karla slowly undresses herself as she and Clint begin to kiss. Songbird then walks in on their moment of intimacy.
But as time went by, she became haunted by nightmares of an ancient Kree warrior woman, who whispered in her thoughts. Soon after, the team was targeted by Scourge killing Jolt. The death of the youngster hit Karla deeply. Subsequently, Citizen V asked for help against her own team, the V-Battalion, and the Thunderbolts agreed to do so, engaging the V-Battalion's operatives in battle. Karla was torn about fighting them, for they were heroes. She released a surge of her powers to stop the fight, making them all intangible, and fled, trying to find out what was wrong with her. Her first stop was Attilan, but the Inhumans were gone. She then searched the Fantastic Four's computers and found the answer she was looking for.
She flew under her own power to the Blue Area of the Moon, where she sought the Kree Supreme Intelligence and demanded the truth. The Supreme Intelligence revealed to her that the fragment she referred to as the "moonstone" was part of a Kree Lifestone, which was used to empower the Guardians of the Galaxy centuries ago. Ajes'ha the Kree warrior woman that haunted her dreams was the previous owner of the moonstone, whose memory was etched into it, and kept steering Karla into the path of heroism. The Thunderbolts managed to catch up with her, and so did Captain Marvel offering her help. Led by Captain Marvel, the Thunderbolts went to Titan, where Mentor and ISAAC attempted to remove the moonstone from Karla's body. After a serious discussion about Karla's potential to do good, Mentor allowed her to keep the gem but erased the memory of the previous owner, leaving Karla's mind, and by consequence, her decisions, to herself.
Uncertain loyalties.
Karla Sofen was soon contacted by Graviton who hired her as a tutor. In the following weeks, Karla helped Graviton understand and control his powers in ways he had not even dreamed, making him fall in love with her. Lifting hundreds of cities all over the world in a misguided attempt to reshape Earth into a semblance of his face, the Thunderbolts re-formed to stop him, only to find Karla at his side. In the end, she helped them stop Graviton. His power imploded, however, sending most of the Thunderbolts, including Karla, to Counter-Earth.
While trapped on Counter-Earth, Karla was given the task of reshaping the minds of the world's leaders, creating a new way of thought to ensure the survival of all. Soon after, Karla removed a second moonstone from that world's Lloyd Bloch (known as the Phantom Eagle), dramatically increasing her own powers. The Thunderbolts, along with Karla, eventually returned to their Earth.
"The Best Intentions".
When the Avengers later interfered in the Thunderbolts' plan to control the world's "transnormal energy", a failsafe was triggered; a device that Karla had planted in her private plot against Zemo. The stolen energy was funneled into her moonstones, further increasing her powers. Karla attempted to use this energy to flee, but the Thunderbolts and Avengers combined forces to stop her. In the end, Zemo ended up in possession of both moonstones and Karla was left comatose.
Since then, Zemo occasionally used her link to the moonstones to puppeteer her, but her mind remained shut down.
Return.
Later the Commission on Superhuman Activities brought her body to their facility, where she and Songbird became mentally linked through the moonstones' power. Karla Sofen came out of her coma, and now has the moonstones in her possession again.
Moonstone next became the field leader of the revamped Thunderbolts, sponsored by the government. The Director of this team, the semi-insane Norman Osborn, eventually turned to blackmail to force her to join, threatening to remove her moonstone and put her in a coma if she refused. Moonstone is seen as a ruthless if less-than-capable leader of the Thunderbolts—Songbird describing her as someone who simply tells people what to do rather than coordinating them as a group—on one of their first missions (capturing the renegade Jack Flag), she preferred to have the mission finish early so that she could have sex with one of the government agents, a point stressed by Songbird at their next briefing. She is fully behind the Thunderbolts' new role and that they must rely on public approval to stay employed, but clashes with her teammate Songbird and her employer Osborn. She revealed that she had been influencing S.H.I.E.L.D. agents to give Norman placebos rather than the usual medication, and also that when Osborn was gone she planned to 'accidentally' kill Songbird in the field and take over as leader. She is shot through the wrist by a crossbow bolt by American Eagle, pinning her to their jet and tearing some of her wrist away. Blinded by rage, she subsequently orders Bullseye to cripple American Eagle who instead cripples Bullseye.
The Thunderbolts encountered Nova having just returned to Earth after Annihilation and had a tangle with Diamondhead. Moonstone advised her team not to underestimate his high power level, which they did, when Nova singlehandedly held his own against the Thunderbolts and even survived Penance's hyperkinetic shockwave. Iron Man and S.H.I.E.L.D. arrived just in time to defuse the situation before federal and galactic authority could conflict any further.
When the psychic supervillains, Mind-Wave, Caprice, Bluestreak and Mirage, are imprisoned in the Thunderbolt's base, they use their powers to alter the Thunderbolts' minds. They force Moonstone to attack Doc Samson and Penance. Penance manages to repel her with a powerful energy blast. It is later mentioned that Moonstone survived, but her body needs a fortnight to stabilize before she can be submitted to nanosurgery.
Secret Invasion.
Moonstone is among four Thunderbolts members present during an attack on Thunderbolts Mountain by a renegade Skrull sleeper agent Khn'nr taking the form of Captain Marvel but has refused to follow programming and has pledged to defend the human race. During the battle, Khn'nr reveals that her stone is of Kree origin, and uses his energy-controlling abilities to shut it down. When the Thunderbolts attack and board a Skrull ship, the Swordsman confronts a group of them with the newly returned Andrea von Strucker. Moonstone painfully immobilizes Swordsman, and suggests an alliance to the Skrulls and Andrea. Andrea turns out not to be a Skrull, however, and attacks Moonstone, although Bullseye kills Andrea from behind. Bullseye tries to kill Moonstone as well, although she becomes intangible, and she threatens Bullseye in order to keep in line.
Later, Bullseye tries to kill Songbird under Osborn's orders. Songbird manages to get into the Zeus aircraft, and blows up part of the Thunderbolts' mountain headquarters. Moonstone survives because Bullseye had warned her to go intangible, and walks away saying "to Hell with this team". Moonstone was also among the fighters in the climactic battle against the Skrulls on Central Park, which ended as Osborn shot dead the alien Veranke.
Dark Reign.
Norman Osborn approaches Moonstone while Karla Sofen is meditating and offers her a spot on the Dark Avengers. She is given the codename of Ms. Marvel as well as the original costume (reclaimed from Ultra Girl) after Carol Danvers (aka the original Ms. Marvel) refuses to follow Osborn. The costume is also scratched heavily by Tigra, causing an embarrassing exposure in front of the press. On this member of the Dark Avengers' first mission, Ms. Marvel is seen attacking which blasts Morgana le Fay off a dragon, causing Morgan to die in the present. After defeating Morgana, Moonstone flirts with Noh-Varr, and then eventually seduces and sleeps with him. While watching a televised interview that Norman is conducting, Karla tells Noh-Varr that the Dark Avengers are all criminals. This prompts Noh-Varr to leave the group. She would also get closer to Daken, saving him from the rubble after an explosion caused by the Fantastic Four, and following him to a Japanese restaurant to find out more about Daken's hidden personality traits.
As Karla takes on the Ms. Marvel mantle, she goes out patrolling and comes across some men robbing an armored car. After killing the men, Karla goes back to the Avengers Tower where Osborn informs her the Dark Avengers all have to undergo psychiatric evaluations and wants her to go first, wanting her professional opinion of Dr. Gerald Wright's skills. Dr. Wright turns out to be a psychic who wanted to kill the Dark Avengers for finding out they were criminals. However, Karla gets an upper hand on him as Wright gets overwhelmed discovering Karla had killed her mother and hated being seen as a criminal and a failure, and seemingly chokes Wright to death.
After being told by Norman to find A.I.M., Karla sorts through the original Ms. Marvel's A.I.M. leads and takes out an A.I.M. cell in Atlanta, Georgia. There she finds baby M.O.D.O.C.'s, enhanced to warp reality. They communicate with her telepathically, telling her that they need Ms. Marvel to save them. It is unclear if they are controlling her, or if she genuinely cares about them, but Karla takes them back to her room in the Avengers Tower for safe keeping. Almost immediately her room is blown apart by a strange yellow being, provoking Karla's rage. With the aid of Venom, Noh-Varr and Osborn, Karla manages to defeat the mysterious being and after a meeting with the Dark Avengers, the babies are moved to Thunderbolts' Mountain where they are stolen by Deadpool on behalf of A.I.M.
Later while flying through the city, Karla comes across a green version of Ms. Marvel's lightning bolt on the side of a building. Karla goes back to the Avengers Tower where Osborn informs her Deadpool stole the baby M.O.D.O.C.'s. Karla goes to confront him in Los Angeles. After defeating him, Karla comes across the New Avengers and four of the mysterious beings, each one a different color in an underground A.I.M. base. Trying to save the babies, Karla is too late to reach them as Spider-Man hooks them up to a machine. The four mysterious beings then merge and reform the original Ms. Marvel. Refusing to let her title be taken away, Karla attempts to pound Danvers, but strangely, no matter what she hits Danvers with, Danvers survived each and every blow. Eventually, it is discovered that Danvers has a counterpart named Catherine Donovan that in close proximity allows Danvers to be invulnerable. Donovan is subsequently killed by Osborn and is revealed to be a creation of the Storyteller whose persona then habits Karla's body as she is fighting Danvers. While trapped in her own body, Sofen is forced to confront her own identity and retakes her Moonstone mantle. As Moonstone, Sofen is able to expel Donovan's consciousness which merges with Danvers upon exit, thus making Ms. Marvel whole again. However, during their battle, Carol uses her own powers to remove the moonstone from Sofen, depowering her in the process. She tells Sofen that she learned a great deal about her while in her mind and offers her a chance at redemption. Knowing she will die in 72 hours without the moonstone's support, Carol hides it at the gravesite of Sofen's mother and gives her the opportunity to reexamine her life and stand against Osborn. Sofen finds the moonstone at her mother's grave, in a fury she smashes the headstone marking it and leaves.
Karla is sent out by Osborn to help quell the riots in San Francisco along with the other Dark Avengers and H.A.M.M.E.R. Outside the Castro Theatre, she takes out Nekra and Frenzy much to the surprise of Karma, Armor, and Bling. Later she comes into conflict with Rogue, accusing her of attacking an unconscious H.A.M.M.E.R. agent and viciously attacks her, though Rogue manages to trick her and escape. Karla is later informed of Trance's situation by H.A.M.M.E.R. agents and goes to confront her. After taking out Gambit and Danger, she gets into another fight with Rogue. Trance pulls herself together and attacks Karla. Under Rogue's orders, Trance and Gambit manage to successfully take down Karla before teleporting off with Pixie. During the final fight on Utopia, Karla takes on Nekra, Frenzy and Bling. She comes to Osborn's side telling him if they want to win, they'll have to kill them all but the whole world is watching and if they kill one, they'll have to kill them all and nobody comes back from committing genocide live on TV.
Alongside the Dark Avengers, Moonstone confronts Molecule Man in his hometown Dinosaur, Colorado, and an Absorbing Man which had harnessed the Cosmic Cube's powers.
Moonstone flirts with Bullseye, stating that she thinks Bullseye is a creep but finds "Hawkeye" attractive. Karla is caught having sex with Bullseye in the Avengers Tower meeting room in front of H.A.M.M.E.R. agents. This act is perceived as an act of rebellion from Karla against Osborn's rule over the Dark Avengers. Norman sends Victoria Hand to deal with the situation. Hand confronts Moonstone and Bullseye with a group of H.A.M.M.E.R agents. Moonstone disobeys Hand's orders, which prompts Hand to take out an alien weapon to shoot Moonstone, knocking her unconscious.
She is part of the team when they go look for Noh-Varr in Manhattan, after Sentry found him.
Prior to the attack on Asgard, Moonstone is approached by Mac Gargan, telling Karla of waking up 'sticky' after dreams and was wondering if she could help Venom. At first, she looks disgusted at Gargan's attempts to approach her. While this is happening, Daken walks up to her and calls her 'sweetheart'. Karla wraps her arm around Gargan's arm and spurns "Wolverine" in the process.
During Asgard's siege, Moonstone is seen helping Osborn defeat Thor. She is seen being chased away from the scene by Maria Hill. Moonstone turns intangible to avoid the bullets. Moonstone is one of the on-lookers when Sentry tears Ares in half. Moonstone is standing besides Osborn when the New Avengers, Young Avengers, and Nick Fury led by Steve Rogers arrive to assist the Asgardians. Rogers hits Osborn with the shield as Karla retreats back, prompting her to say "Well, I sure as @#$% saw this coming!". Karla engages in personal combat with Carol. Karla wins the exchange when Osborn interferes into the fight by blasting Danvers with an energy beam in the back. When Osborn is defeated by Rogers and Tony Stark, and reverts to the Green Goblin persona, Karla and Bullseye are seen in the distance. Both of them come to the realization that it would be a good time to leave the battle.
Moonstone, along with the other members of the Dark Avengers, are arrested by the Avengers. After Rogers does away with Osborn, Moonstone and Bullseye take the opportunity to attempt an escape. Danvers gives chase to Moonstone, only to have Karla fire on with an energy blast. When it seems she has escaped, Stark appears and punches her, knocking her out. At the same time, Bullseye is struck down by Luke Cage, sending the two villains falling unconscious to the ground, thus ending Moonstone's involvement.
Return to the Thunderbolts.
Moonstone was confirmed as a member of the second Thunderbolts team, which was formed in the aftermath of Siege.
Luke Cage visitsed the women's section of the Raft, where he recruited Moonstone to be a member of the Thunderbolts once again. Moonstone claimed that "It is about time" someone came by to recruit her for the Thunderbolts, and that her "costume should be pressed". Moonstone's recruitment upset Songbird, but was insisted upon by higher authorities. After the members were selected, a test was given to see where the loyalties lay among the team. Moonstone showed to be one of the few who helped out Cage and the rest of the support team. During missions, Karla passively flirted with Cage, though she was rebuked by him and the rest of the team tried to manipulate him. She later stated that she genuinely respected his heroism.
During the "" storyline, Moonstone was an inmate of Pleasant Hill, a gated community established by S.H.I.E.L.D. Using the powers of , S.H.I.E.L.D. turned Moonstone into a baker that specializes in making cupcakes. Baron Zemo and Fixer restored her memory, she helped to assault a S.H.I.E.L.D. outpost that was used as Pleasant Hill City Hall.
Following the Pleasant Hill incident, Moonstone briefly joined up with Winter Soldier's incarnation of the Thunderbolts with the goal to prevent S.H.I.E.L.D. from continuing the Kobik Project. During an argument with Winter Soldier, Kobik lunged through Moonstone's chest, tearing out the Moonstone object and incapacitating Karla, she eventually gets the Moonstone back.
Moonstone later joined the Thunderbolts into fighting Baron Helmut Zemo's incarnation of the Masters of Evil which ended with the Thunderbolts defeated.
During the "Opening Salvo" part of the "Secret Empire" storyline, Moonstone defected to the Masters of Evil after Winter Soldier was sent back in time to World War II and Kobik was shattered. She assisted in gathering the pieces of Kobik.
Powers and abilities.
Moonstone's powers are derived from a Kree gravity stone (found on Earth's moon) which is charged with unknown energy and bonded to her nervous system.
She can use the stone to fly, and to become intangible so as to pass through solid objects (while intangible she is immune even to some magic-based attacks). She can project laser-like energy beams from her hands (able to penetrate steel plates), and has also shown the ability to discharge non-coherent light omni-directionally in a blinding flash. Additionally, her bond with the stone grants her superhuman strength, stamina, speed and reflexes, as well as sufficiently enhanced healing to even recover from a broken neck with enough time.
During the period when Moonstone had absorbed a second gravity stone, she displayed the ability to control gravitational forces, enabling her to move and otherwise manipulate matter, to create force fields, to increase gravity around a target and crush it, to generate miniature black holes, and even to transport objects through dimensional rifts. She no longer possesses the second stone, and is currently at her original power level.
Moonstone is vulnerable to astrally-projected beings and energy forms even while in her intangible state. It was revealed that Moonstone's gravity stone is also connected to her own life-force. If she is separated from it for more than a period of 72 hours, she would die without its support.
In addition to the powers she wields by virtue of her bond with the gravity stone, Karla Sofen has extensive knowledge of psychology and psychiatry, and has an M.D., specializing in psychiatry. She often uses this expertise to manipulate those around her for personal gain. However, she has often shown that she is not as skilled as she would like to believe, resulting in her being outmanipulated by more experienced manipulators.
Other versions.
Moonstone appears alongside the Thunderbolts in the "Dead Days" one-shot of the Marvel Zombies mini-series using her alias of Meteorite. She attacks Thor, pouncing on him but is stunned with a blast of lightning and then destroyed when Thor smashes her head.
In the miniseries "Old Man Hawkeye", Moonstone was a member of the Thunderbolts who betrayed and killed the Avengers, and hid herself in the Canadian Rockies after disagreements with Baron Zemo. 45 years later, she is met by Hawkeye and Kate Bishop in a village where Karla is worshipped for her immense powers, with her body severely decayed by the alien artifact that is the source of her powers. After a short discussion, Moonstone attempted to kill the Hawkeyes, but they managed to overload her moonstone, causing it to explode and kill Karla and her followers.


Lifetime reserve days

Lifetime reserve days are additional days that the United States health care system Medicare will pay for when a beneficiary is in a hospital for more than 90 days during a benefit period. Beneficiaries are limited to a total of 60 reserve days over the course of their life.


Mark Atkinson (scientist)

Mark Atkinson (born March 27, 1961) is a medical researcher best known for his contributions to research seeking to predict, prevent, and cure type 1 diabetes. He is the author of over 500 publications and is one of the world's most cited diabetes researchers.
Atkinson currently conducts research at the University of Florida College of Medicine, where he is Director for the Diabetes Institute at UF Health. He also is the Executive Director of the Network for Pancreatic Organ donors with Diabetes (nPOD) program.
Atkinson has also been widely cited for his humanitarian contributions, particularly his efforts to improve diabetes care, management, and access to medications and supplies in developing nations.
Background and education.
Mark Atkinson was born and raised in southeastern Michigan. He attended the University of Michigan – Dearborn where he received a bachelor of Science in microbiology in 1983. Atkinson next received a Ph.D. from the Department of Pathology at the University of Florida in 1987.
While at the University of Florida, Atkinson studied under diabetes researcher Dr. Noel Maclaren, who became his mentor and fostered Atkinson's interest in type 1 diabetes research. His work with Maclaren led Atkinson to develop his three goals of determining what causes type 1 diabetes, identifying a means to predict T1D, and developing a way to prevent and cure the disease.
Academic career.
Atkinson has been teaching and conducting research in the Departments of Pathology and Pediatrics at the University of Florida College of Medicine since 1988. He is currently the American Diabetes Association Eminent Scholar for Diabetes Research and the Jeffrey Keene Family Professor at the University of Florida, as well as the Director for the Diabetes Institute at that institution.
Type 1 diabetes research.
Atkinson's research activities have a broad scope, but most fall under the umbrella of preventing and curing type 1 diabetes. Specific areas of focus include disease prediction, the role of environment in the initiation of type 1 diabetes, stem cells and beta cell regeneration, pancreatic pathology, clinical trials seeking to prevent or reverse type 1 diabetes, the identification of markers of immunological tolerance, and devising ways to instill proper immunoregulation. Atkinson has been the recipient of funding awards from entities such as the National Institutes of Health, JDRF, the American Diabetes Association, and the Leona M. and Harry B. Helmsley Charitable Trust.
Research approaches.
Atkinson has conducted numerous studies that take different approaches to predicting, preventing, and curing type 1 diabetes. His earliest efforts focused on the use of autoantibodies, both anti-insulin and anti-glutamic acid decarboxylase (GAD), for that purpose. He was also amongst the first to describe cellular immune responses against GAD in both humans and the NOD mouse model of type 1 diabetes. He has extensively utilized NOD mice as a means to identify agents that could be translated to studies seeking to prevent or reverse type 1 diabetes but at the same time, has stated that such efforts need be approached with caution. His publication in the journal Nature Medicine noting the nearly 200 ways to prevent diabetes in that animal model elicited mixed responses from the research community.
Atkinson was one of the first to propose “combination therapies” to prevent or reverse the disease, as well as the repurposing of existing treatments and agents already approved for other diseases and conditions. Atkinson has led or contributed to clinical trials utilizing several types of interventions to stop the progression of or reverse type 1 diabetes, including prophylactic insulin, GAD, cord blood, cord blood plus Omega-3 FA, granulocyte colony-stimulating factor (GCSF), and anti-thymocyte globulin (ATG) plus GCSF.
Atkinson is currently leading an NIH funded clinical research trial aiming to assess immune function during different stages of type 1 diabetes. The goal is to learn more about the genetics and immune function of blood cells, diet, and viruses and how they relate to the progression of T1D.
Atkinson is also active in studies assessing the human intestinal microbiome, pancreatic pathology, human pancreatic weight and beta cell development, as well as improving methods of data management.
nPOD.
Atkinson is the Executive Director for the Network for Pancreatic Organ donors with Diabetes (nPOD) program, the world's largest "open access" biobank of human tissues from persons with or at varying levels of risk for type 1 diabetes. nPOD is funded by JDRF and The Leona M. and Harry B. Helmsley Charitable Trust.
Through nPOD, Atkinson and other collaborators support research utilizing transplant-grade human tissues obtained from organ donors, including pancreas, spleen, whole blood, serum, lymph nodes, pancreatic lymph nodes, thymus, skin and bone marrow. The goal is to better understand the causes of type 1 diabetes and identify potential approaches to curing the disease. Atkinson has directed nPOD since its founding in 2007, it has and continued to support over 250 different investigators in some 200 research projects in 20 countries worldwide.
Research collaborations.
In addition to nPOD, Atkinson participates in a number of other collaborative research efforts. He is one of ten members of the Brehm Coalition for Type 1 Diabetes Research, and one of four initial members of the Leona M. and Harry B. Helmsley Charitable Trust's Type 1 Diabetes Research Initiative. Atkinson also collaborates on a number of research initiatives with investigators around the globe as well as with his colleagues at the University of Florida's Diabetes Institute.
Atkinson also serves as Director of the Human Biomolecular Atlas Program (HuBMAP) at the University of Florida. HuBMAP's mission is to develop a 3-D map of the human body at a single-cell level.
Leadership and influence in the field.
Atkinson is the author of over 425 peer-reviewed publications as well as several book chapters. Expertscape ranks Atkinson as one of the ten most published diabetes researchers in the world, and with an all time h-index of 91, he is one of the most highly cited diabetes researchers in the world.
Atkinson provides leadership to numerous entities that focus on research and service to the type 1 diabetes community, and currently provides administrative or advisory service to JDRF, the American Diabetes Association, Diapedia, the National Institutes of Health (NIH), and the Immunology of Diabetes Society. He is a charter member of the NIH's Immune Tolerance Network Scientific Advisory Board, former Chair of the NIH's Human Islet Research Network (HIRN), and a steering committee member of NIH TrialNet.
Atkinson also formerly served as an Associate Editor for the journal "Diabetes". He now serves as ad hoc Editor-in-Chief for that journal as well as "Diabetes Care".
Commercial and industry work.
Along with his colleagues at the University of Florida Diabetes Institute, Atkinson is pursuing a vaccine strategy for preventing type 1 diabetes. The approach seeks to eliminate the autoimmune response directed at insulin that is present in patients with the disease by generating antigen-specific Tregs (regulatory T cells) in response to the antigens of interest rather than try to eliminate the autoreactive destructive cells. To further this line of research, Atkinson and other investigators started a spin-off company called OneVax, LLC. OneVax seeks to develop and commercialize a novel vaccine formula to prevent and/or reverse type 1 diabetes, incorporating biomaterials and polymers for applications including multicomponent and time-release drug delivery. Atkinson serves as CEO of OneVax.
Humanitarian interests.
Atkinson has joined with other leaders calling for a means to provide insulin to 100 percent of the world's population who need it by 2022, the centennial anniversary of insulin availability. Atkinson also serves as an Advisory Board Member to the Life for a Child program.
Atkinson has served with the Haitian Foundation for Diabetes and Cardiovascular Diseases (Fondation Haitienne de Diabete et de Maladies Cardio-Vasculaires), overseen by Nancy Larco. Atkinson has traveled to Haiti to provide medical, dental, and educational assistance, including after the 2010 Haiti earthquake.
Atkinson and his wife co-founded a non-profit organization, Hope on the Move, for humanitarian causes, primarily related to providing medical and dental care to developing nations. Atkinson serves as secretary, treasurer and director of Hope on the Move.
Atkinson is the president of Insulin for Life-USA, a non-profit organization that collects insulin, test strips, and other diabetes management supplies and distributes them to needy individuals in developing nations as well as in the United States following natural disasters.


Community-based rehabilitation

The aim of community-based rehabilitation (CBR) is to help people with disabilities, by establishing community-based medical integration, equalization of opportunities, and Physical therapy (Physiotherapy) rehabilitation programs for the disabled. The strength of CBR programs is that they can be made available in rural areas, with limited infrastructure, as program leadership is not restricted to professionals in healthcare, educational, Physiotherapy , Occupational therapy vocational or social services. Rather, CBR programs involve the people with disabilities themselves, their families and communities, as well as appropriate professionals. Some are doing their own works.
History.
In the beginning of the 1960s, efforts to establish rehabilitation centers in developing countries had taken hold in urban centers, but failed to provide support and assistance to disabled people in rural areas throughout the world. The response of world aid organizations was to shift funding from city-based hospitals to rural community programs. The first CBR pilot projects were launched in the 1960s, and their continuing success has led to CBR programs being adopted throughout Africa, Asia and [South America].
CBR Asia Pacific Network.
A CBR Network is a formal or informal relationship among CBR implementers/ practitioners or their organizations to promote and strengthen CBR. The strength of the network depends on the strength of individual or organizational members and the co-ordination and collaboration between members. It is expected that the benefits from the network will be greater than any individual's effort. To enrich CBR further for the benefit of the people with disabilities, their family, community and the country, a network of CBR practitioners/implementers/promoters is required at least at a national level, regional level and global level.
These networks need to be democratic, national CBR network members need to select their national executive body; e.g., CBR Afghanistan Network, CBR India Network, CBR Indonesia Network. President or the secretary of the national networks should represent the general body of the Regional Network; e.g., CBR Asia Pacific Network. General body of the CBR AP Network to elect their Executive body and representatives for CBR Global Network. While electing the executive body one must ensure that committee represents with competent and committed people. CBR is for all, richness and success of CBR depends on diversity and respecting that diversity. An ideal CBR committee should be of people from various background; e.g., people with disabilities (different impairment groups), academicians, people with different socio economic background, people coming from rural areas or representing vulnerable groups policy makers, practitioners, promoters, representative from public and private sectors. Gender and disability balance are the key of the success of any CBR Networks.
Around the world there are existing networks: large and small, formal and informal, active and inactive, etc. For example the CBR Africa Network is a large network covering one continent.
In 2001 during the first Africa Regional Conference on CBR in Kampala, Uganda, the CBR Africa Network (CAN) was created. It started with four action points:
There are other notable networks including the CBR South-Asia Network is a sub regional network and there exists across the world many National CBR Networks.
At present three larger continental (regional) networks are under development or expansion including the CBR Africa Network (CAN), CBR America Network (RED de RBC de las Américas y el Caribe) and the CBR Asia-Pacific Network. One of the main outcomes of the CBR Asia-Pacific Congress was to form the CBR Asia-Pacific Network.
The 1st CBR Asia Pacific Congress provided a great opportunity to form the general body of the CBR Asia-Pacific Network who eventually would meet and elect their executive body and take the CBR Asia-Pacific Network forward. The initial purpose of the CBR Asia-Pacific Network was to promote and strengthen CBR across the continent and in countries; mobilize resources, organize trainings and support information exchange.
Twenty-four country representatives have nominated and selected among CBR promoters/implementers/practitioners, including persons with disabilities, taking gender equity, organizational and regional diversity into consideration. The country representatives of the Network held their first meeting immediately after the Congress. Members present in the meeting have taken the responsibility to form the CBR Asia-Pacific Network, draft a constitution, draw a future plan of actions and take it forward (as a continuation of dialogue) with support from the Asia-Pacific Center on Disability (APCD) as the secretariat of the Network.


Bernard Kouchner

 Bernard Kouchner (born 1 November 1939) is a French politician and physician. He is the co-founder of Médecins Sans Frontières (MSF) and Médecins du Monde. From 2007 until 2010, he was the French Minister of Foreign and European Affairs in the center-right Fillon government under president Nicolas Sarkozy, although he had been in the past a minister in socialist governments. In 2010, "The Jerusalem Post" considered Bernard Kouchner the 15th most influential Jew in the world. Since 2015 Kouchner is workstream leader for the AMU (Agency for the Modernisation of Ukraine), where he contributes his expertise in healthcare.
Early life.
Kouchner was born in Avignon, to a Jewish father and a Protestant mother. Kouchner's paternal grandparents were Russian-born Jews who escaped the pogroms by immigrating to France, but perished decades later in Auschwitz.
Career.
Kouchner began his political career as a member of the French Communist Party (PCF), from which he was expelled in 1966 for attempting to overthrow the leadership. On a visit to Cuba in 1964, Kouchner spent the night fishing and drinking with Fidel Castro. In the protests of May 1968, he ran the medical faculty strike committee at the Sorbonne.
Co-Founder of Médecins Sans Frontières and Médecins du Monde.
Kouchner worked as a physician for the Red Cross in Biafra in 1968 (during the Nigerian Civil War). His experience as a physician for the Red Cross led him to co-found Médecins Sans Frontières (Doctors Without Borders) in 1971, and then, due to a conflict of opinion with MSF chairman Claude Malhuret, he established "Doctors of the World" ('Médecins du Monde') in 1980. Kouchner worked as a humanitarian volunteer during the Siege of Naba’a refugee camp in Lebanon in East Beirut during the Lebanese Civil War taking risks that "other foreign aid workers weren’t, even worked closely with the Shia cleric Imam Musa al-Sadr".
Career in government.
From 1988, Kouchner began his government career in Socialist governments, though he was not always a member of the French Socialist Party. He became "Secrétaire d'état", a lower position in the Cabinet, for Humanitarian Action in 1988 in the Michel Rocard cabinet, then Minister of Health under Pierre Bérégovoy in 1992, during Mitterrand's presidency.
Member of the European Parliament, 1994–1997.
Kouchner continued his political career in the European Parliament from 1994 to 1997. During the time, he chaired the Committee on Development and Cooperation and served on the Subcommittee on Human Rights. In addition to his committee assignments, he was a member of the Parliament's delegation for relations with the People's Republic of China.
Together with Judge Andrée Ruffo, Kouchner established the International Bureau for Children's Rights (IBCR), a non-governmental organization based in Montreal, in 1994.
Minister of Health, 1997–1999.
When Lionel Jospin became Prime Minister in 1997, Kouchner became Minister of Health for the second time. He held the office until 1999.
UN Representative in Kosovo, 1999–2001.
On 15 July 1999, pursuant to Security Council Resolution 1244, UN Secretary General Kofi Annan nominated Kouchner as the second UN Special Representative and Head of the United Nations Interim Administration Mission in Kosovo (UNMIK). During 18 months, he led UN efforts to create a new civil administration and political system replacing the Serbian ones, and to rebuild the economy shattered by the Kosovo War. Thus, municipal councils were elected at local level by the end of 2000. He was replaced on 21 January 2001 by Danish Social Democrat Hans Hækkerup. Later, he was awarded an honorary doctorate by the University of Pristina for his services to Kosovo.
Minister of Health, 2001–2002.
Kouchner became at this time Minister of Health for the third time, until the 2002 elections.
Candidate for UN positions.
In 2005, Kouchner was a candidate for the position of United Nations High Commissioner for Refugees (UNHCR), but lost the appointment in favor of former Portuguese Prime Minister, António Guterres, who was nominated by then-UN Secretary-General Kofi Annan.
In 2006, Kouchner was also a candidate to become Director-General of the World Health Organization. He lost before the final election round, and (Hong Kong) Chinese candidate Margaret Chan was later elected.
In 2007, the European Commission appointed Kouchner as its representative on the International Independent Group of Eminent Persons (IIGEP), a group of individuals nominated by international donor countries and the government of Sri Lanka, vested with a wide mandate to observe all investigations and inquiries conducted by and on behalf of the Commission of Inquiry into alleged human rights abuses in Sri Lanka.
Minister of Foreign Affairs, 2007–2010.
After the election of Nicolas Sarkozy as President of France in 2007, Kouchner was appointed Minister of Foreign Affairs in Prime Minister François Fillon's government, even though Kouchner supported Sarkozy's Socialist rival Ségolène Royal during the campaign. He has since been expelled from the Socialist Party for his acceptance of the post.
Kouchner was dismissed in the November 2010 Fillon cabinet reshuffle.
Political positions.
On the U.S.-led invasion of Iraq.
Kouchner is a longtime advocate of humanitarian intervention. In early 2003, he pronounced himself in favour of removing Saddam Hussein as President of Iraq, arguing that interference against dictatorship should be a global priority, and continued to say that now, the focus should be on the actual people themselves, and that they are the only ones who could answer "yes" or "no" to war.
In a 4 February 2003 editorial with Antoine Veil in "Le Monde", entitled "Neither War Nor Saddam", Kouchner said that he was opposed to the impending War in Iraq, and, as the title suggests, to the remaining in power of Saddam Hussein, the removal of whom should be accomplished via a concerted UN, preferably diplomatic, solution. He later became a fierce critic of how the occupation was subsequently conducted.
On Europe.
Kouchner is a well-known pro-European. He supported the ratification of the Lisbon Treaty when it was threatened to be rejected by the Irish in referendum. In the run up to the referendum in the Republic of Ireland on the ratification of the Treaty of Lisbon, Kouchner warned that any "No" vote towards the treaty would be detrimental to Ireland and the Irish economy. He also commented that "It would be very, very awkward if we were not able to count on the Irish, who have often counted on Europe". His comments were dismissed as "unhelpful" by leading Irish politicians, and some media commentators have suggested that his remarks may have galvanised the "No" campaign in the run up to the rejection of the Lisbon Treaty on 13 June 2008.
In 2012, Kouchner co-signed the George Soros call for a strengthening of the European prerogatives as an answer to the eurozone crisis.
Comments on Iran nuclear situation.
In September 2007, Kouchner's public comments on the Iranian nuclear situation attracted much attention and controversy. In an interview on 16 September 2007, he said, "We will negotiate until the end. And at the same time we must prepare ourselves [...] for the worst...The worst, it's war". He stated that France was committed to a diplomatic resolution and that no military action was planned, but that an Iranian nuclear weapon would pose "a real danger for the whole world".
Iranian officials criticized the comments as "inflammatory". The chief UN nuclear inspector Mohamed ElBaradei, the head of the International Atomic Energy Agency indirectly responded to Kouchner by characterizing talk of attacking Iran as "hype", saying the use of force should only be considered as a last resort and only if authorized by the UN Security Council.
"I would not talk about any use of force", he said. On 18 September 2007, Kouchner attempted to respond to criticisms. In comments to newspaper "Le Monde", he stated, "I do not want it to be said that I am a warmonger! [...] My message was a message of peace, of seriousness and of determination. [...] The worst situation would be war. To avoid that, the French attitude is to negotiate, negotiate, negotiate, without fear of being rebuffed, and to work with our European friends on credible sanctions."
Comments on a unity government for Zimbabwe.
On 1 July 2008, France assumed the presidency of the Council of the European Union. In his capacity as the French foreign minister, he commented after the African Union summit, that The European Union would only recognise a Zimbabwe unity government headed by Morgan Tsvangirai not Robert Mugabe.
Use of condoms to prevent AIDS in Africa.
Kouchner denounced statements by Pope Benedict XVI claiming that condoms promoted AIDS, saying they were "the opposite of tolerance and understanding".
Life after politics.
After leaving politics, Kouchner took on a variety of positions, including the following:
Personal life.
Kouchner has three children (Julien, Camille and Antoine) by his first wife, Évelyne Pisier, a professor of law, and one child, Alexandre, by his present wife Christine Ockrent, a journalist and author.


Guillaume Bigot

Guillaume Bigot (June 2, 1502 - c. 1550) was a writer, doctor, humanist, and poet in French and Latin. His "Christianae philosophiae Praeludium" ("Prelude to Christian Philosophy") was published in Toulouse in 1549. Its four books are devoted to the physiology of the human body, and to different aspects of the soul. It has a long preface, addressed to Cardinal Jean du Bellay, in which Bigot defends himself against his detractors.


Kee Chang Huang

Kee Chang Huang (July 22, 1917 in Canton, China – November 25, 1998) was a Distinguished Professor at the University of Louisville.
He attended Sun Yat-sen University, receiving his medical degree in 1940. He was a research fellow in pharmacology at the Chinese National Institute of Health for six years before joining the faculty of the National Shanghai Medical School in 1946. In 1949, he left China to enter graduate school at the Columbia University College of Physicians and Surgeons. After receiving a Ph.D. in physiology in 1953, he was recruited by the University of Louisville as a Research Associate in Pharmacology, rising through the ranks to become Professor of Pharmacology in 1963. During his tenure he was awarded the Fulbright Professorship twice and the Distinguished Professorship by the University of Louisville and the Tianjim Medical College of China.
He is the author of three books, "Absorption, Distribution, Transformation and Excretion of Drugs", "Outline of Pharmacology", and "The Pharmacology of Chinese Herbs", and many research papers. He retired from the University in 1989, but remained active in research.


Andy S. Jagoda

Andy S. Jagoda, M.D., is an American author and Professor and Chair Emeritus of the Department of Emergency Medicine at Mount Sinai Hospital in New York City. He has edited and authored 14 books, including "The Good Housekeeping Family First Aid Book" () and the textbook "Neurologic Emergencies" (). He is an editor of the 9th edition of "Rosen’s Emergency Medicine" ().
Jagoda is recognized nationally for his involvement in medical education and his expertise in the area of neurologic emergencies, including traumatic brain injury.
Education, military and professional careers.
Jagoda received his medical degree from Georgetown University in 1982. He completed a residency in emergency medicine at the joint program of Georgetown/George Washington/Maryland Institute for Emergency Medical Services System in 1985.
As a doctor in the United States Navy, Jagoda completed two tours in the Middle East, first during the Iran-Iraq War, and then again during Desert Storm/Desert Shield. He earned a Navy Achievement Medal for leading a resuscitation augmentation medical team in 1988 and in 1991 received the Navy Commendation Medal for meritorious service on the USNS Comfort. In 1990, he earned the rank of lieutenant commander. He was later made Assistant Professor at the Department of Military Medicine/Emergency Medicine at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. He was honorably discharged from the navy in 1991.
After his military service, Jagoda joined the faculty of George Washington University, then the University of Florida. He joined the staff at Mount Sinai Medical Center in 1995, earning the rank of Professor of Emergency Medicine with tenure in 2000. In 2009, he was named Chair of the Department of Emergency Medicine.
Jagoda is Editor-in-chief of Emergency Medicine Practice and an editorial board member of the Annals of Emergency Medicine. He is a member of the Executive Committee of the Brain Attack Coalition at the National Institute of Neurological Disorders and Stroke (part of the National Institutes of Health) and of the Executive Board of the Foundation for Education and Research on Neurologic Emergencies (FERNE). He is also on the advisory board of the Indian Head Injury Foundation and of the Brain Trauma Foundation where he also serves as the EMS Director. He is past chair of the Clinical Policies Committee of the American College of Emergency Physicians (ACEP), where his work with the committee for 14 years facilitated the evolution from a consensus-based process to an evidence-based process and promoted ACEP’s practice guideline methodology both nationally and internationally. He has organized evidence-based symposiums in Italy, the Netherlands, and Chile and co-organized the first Joint ACEP/Italian Congress on Emergency Medicine (in Torino). He is currently the ACEP's ambassador to Italy.
Jagoda is an active member of the Society for Academic Emergency Medicine and the New York Academy of Medicine.


Carl Wheezer


Mesoblast

Mesoblast Limited is an Australian-based regenerative medicine company. It seeks to provide treatments for inflammatory ailments, cardiovascular disease and back pain. The company is led by Silviu Itescu, who founded the company in 2004.
Mesenchymal lineage cells.
The company is developing a range of regenerative products derived from its proprietary mesenchymal lineage cells. This includes Mesenchymal Precursor Cells (MPCs) and Mesenchymal Stem Cells (MSCs). It is the hope of Mesoblast that these cells will behave like their natural counterparts, when injected into a patient. Such behavior would require the cells to survive in a patient's body, despite the action of the immune system, which functions to destroy anything that is foreign.
Use.
In the laboratory, highly purified and immunoselected MPCs and the culture expanded MSCs secrete trophic factors that have multiple potential actions. It is hoped that Mesenchymal lineage precursors will retain the ability of their natural counterparts. They have the ability to detect injury and inflammation and respond to local stimuli and signals from the injured tissue by releasing a wide range of biomolecules (growth factors, chemokines, enzymes etc.) that induce the body's own tissue to grow and regenerate, effectively repairing the injury. Which specific factors are released by mesenchymal precursors in any given tissue presumably depends on the signals they encounter from the damaged tissue itself. For example, with back pain, the MPCs are injected into the damaged disc in the hope that it will regenerate it.
Research and development.
Mesoblast is developing products in four major areas.
Back pain.
Mesoblast's investigational product candidate MPC-06-ID is being developed to target the population of patients suffering from moderate to severe chronic low back pain due to moderately degenerated discs.
2010.
In Mesoblast's annual report from August 2010, the company first announced positive results of preclinical trials showing radiographic and pathologic disc regeneration with MPC-06-ID. Mesoblast said they were in the process of completing an Investigational New Drug (IND) submission to the United States FDA to commence Phase 2 clinical trials in patients with low back pain due to disc degenerative disease.
2011.
On June 29, 2011, Mesoblast announced that it received clearance from the Food and Drug Administration to begin a Phase 2 trial with its MPC cells for treatment of disc degenerative disease. This trial is primarily designed to assess the safety and efficacy of the cells.
2012.
Osiris sold its MSC drug and patents to Mesoblast Ltd. With the potential of $100 million, the first $35 million in consideration, approximately 43% was paid to Osiris in Mesoblast common shares with the balance paid in cash. Product royalties start in low-single digits and will grow to 10% on revenues exceeding $750 million.
2014.
In January 2014, Mesoblast announced positive results of the Phase 2 trial for back pain treatment. It included 100 patients with moderate to severe back pain that were evaluated in a randomized, placebo controlled study. Patients were treated across 13 sites in the US and Australia. The results showed that 69% of patients given a 6 million dose of MPCs and 62% given an 18 million dose experienced a more than 50% reduction in low back pain at 12 months. This compares to around 35% for the controls. Patients underwent the outpatient injection for a single painful degenerated lumbar level and evaluated for safety and efficacy over a total of 36 months to evaluate long-term treatment effects. Other key findings included improvements in function and disc stability.
The participating sites were Arizona Pain Specialists, UC Davis Spine Center, the Spine Institute, IPM Medical Group, Inc., Denver Spine, Rocky Mountain Associates in Orthopedic Medicine, P.C., Emory University School of Medicine, Carolina Neurosurgery and Spine Associates, Central Texas Spine Institute, Richmond Bone and Joint Clinic, Memorial Hermann Medical Group, Washington Center for Pain Management, The Center for Pain Relief, Inc. and Monash Medical Centre of Victoria, Australia.
In August 2014, Mesoblast announced in its 2014 results and corporate strategy that the Food and Drug Administration granted approval to advance to an MPC Phase 3 trial for chronic lower back pain.
In November 2014, in Japan, the Pharmaceuticals, Medical Devices and Other Therapeutic Products Act (PMD Act) took effect. This Act established a pathway for expedited approval in Japan for regenerative medical products. Japan's new policy requires an early stage clinical trial (i.e. Phase I or small Phase II) at the minimum to confirm safety of the therapy and provide evidence of efficacy. Rather than requiring that the therapy then be evaluated in subsequent trials before making it available to patients, Japan's new law will allow for a “conditional approval” enabling the product to be brought to market, and for the product to obtain reimbursement in an accelerated manner. Conditional approval does not mean that the regulatory approval process is over. It simply allows the therapy to be made available to patients earlier in the process, and for the sponsor company to begin commercialization and obtain reimbursement.
As a result, Mesoblast announced they would leverage existing Phase 2 clinical trial results for Tier 1 and Tier 2 product candidates. Tier 1 includes MPC cells for back pain. Conditional approval would last seven years.
In March 2014, Circulation Journal published results of a clinical trial using MPC's as adjunctive therapy for patients with a Ventricular Assist Device. 50% of patients with MPC therapy achieved temporary weaning from LVAD compared to 20% of the control group at 90days.
2015.
On January 14, 2015, Mesoblast confirmed Phase 3 had already begun. The company also provided projected timeframes. Mesoblast anticipates patient enrollment completion in mid-2016, an interim analysis in mid-2016 and top-line data in mid-2017.
The objective of the Phase 3 clinical program will be to confirm the positive outcomes seen in the Company's Phase 2 clinical trial where product candidate, MPC-06-ID, demonstrated the potential to provide durable improvement in pain and function for patients who suffer with CDLBP due to degenerative disc disease. The primary endpoint in the Phase 3 program will seek to confirm the treatment benefit seen in Phase 2 for MPC-06-ID against saline control using a composite of durable improvement in pain and function.
On February 10, 2015, Mesoblast was granted a key patent by the United States Patent and Trademark Office (USPTO) covering its proprietary Mesenchymal Precursor Cell (MPC) technology for use in the treatment of degenerated intervertebral discs. Granted US patent number 8,858,932 provides Mesoblast with exclusive commercial rights through to June 2029. There is also potential for patent term and regulatory exclusivity extensions which would provide longer term protection.
On March 19, 2015, Mesoblast announced that it has been selected by the Japan External Trade Organization (JETRO) as the only regenerative medicine company worldwide to receive fast track access to potential investment incentives across all levels of government in Japan. Mesoblast will receive a specially tailored market and government incentive roadmap aimed at providing a more attractive business environment. Mesoblast Chief Executive Silviu Itescu welcomed the recognition from the Japanese Government.
“Japan is a major market for our cell-based therapeutics and offers near-term potential for product approvals and revenues. The selection of Mesoblast by JETRO as the only regenerative medicine company to receive investment priority status will guide the strategic direction of our commercial plans in Japan, in conjunction with our current and future strategic partners.”
On April 8, 2015, Mesoblast announced it intended to expand the Phase 3 clinical program of its product candidate MPC-06-ID in the treatment of chronic low back pain due to degenerative disc disease to include sites in the European Union (EU). This announcement came shortly after a positive meeting with the European Medicines Agency (EMA). The discussions with EMA occurred as part of combined scientific and reimbursement advice under an EU pilot program known as Shaping European Early Dialogues (SEED). The SEED pilot program was established to facilitate early dialogue between EMA, European Health Technology Assessment (HTA) reimbursement bodies, and selected companies with late-stage clinical development programs. Mesoblast's product candidate MPC-06-ID is one of only seven medicines accepted for the SEED program.
On September 20, 2015, Mesoblast's Annual Report stated that Phase 3 would actually consist of two clinical trials. The first trial, initiated in December 2014, has been recruiting candidates across multiple sites in the United States. No start date was mentioned for the second trial. The two studies will be double-blinded, and include approximately 330 patients each. The composite primary end point of pain relief and improved function consists of a 50% reduction in lower back pain. This is measured by VAS and a 15-point improvement in Oswestry Disability Index (ODI) at both 6 and 12 months, with no intervention at 12 months and will be used in the Phase 3 program.
On December 17, 2015, as part of the first quarter report, Mesoblast announced they anticipated patient enrollment completion for the first of two trials for phase 3 by third quarter, or mid-2016. No information was given about the second trial.
2016.
In February 2016, as part of Mesoblast's second quarter (ending December 31, 2015) and first half financial results, the company reported that recruitment for the phase 3 back pain trial was progressing well across the United States. For the first time, information was provided regarding the second trial. Mesoblast outlined key milestones that included the first trial's results to be completed by the 4th quarter of 2016, or June 30, 2016. The second trial's results should be complete by the 4th quarter of 2017, or June 30, 2017.
In August 2016, as part of Mesoblast's Annual Report, Mesoblast reported that the current 360 patient Phase 3 trial was recruiting well across US sites.
In addition, Mesoblast noted that the FDA has provided written guidance that included use of a composite primary endpoint is acceptable for approval, agreed thresholds for pain (50% decrease in VAS) and function (15 point improvement in ODI), two time points (12 and 24 months) for meeting pain and functional improvement criteria and no intervention at the treated level of the spine through 24 months. Mesoblast stated they intend to conduct an interim analysis in the Phase 3 trial in Q1 CY 2017.
In December 2016, Mesoblast and Mallinckrodt Pharmaceuticals entered into an agreement to exclusively negotiate a commercial and development partnership for MPC-06-ID in the treatment of chronic low back pain due to disc degeneration.
2017.
In early 2017, the U.S. government website that lists Mesoblast's study provided key milestones. The estimated study completion date is February 2020. The estimated primary completion date will be February 2019. This is the final data collection date for primary outcome measure. The only way these dates might change is if Mesoblast's solution for lower back pain is granted Fast Track status from the FDA. This would reduce the FDA's review process from 10 months to 6 months. It would also provide a streamlined rolling review process (completed sections of the Biologics License Application, BLA, can be submitted for FDA review as they become available, instead of waiting for all to be completed).
In March 2017, Mesoblast announced positive results of their 36-month follow-up of their randomized, placebo-controlled, 100 patient Phase 2 trial. A single intra-discal injection of 6 million MPCs resulted in meaningful improvements in both pain and function that were durable for at
least 36 months. “The sustained benefits on pain and function over three years seen with a single injection of Mesoblast’s cell therapy have the potential to transform the treatment paradigm for chronic low back pain due to disc degeneration,” said trial investigator Dr Hyun Bae, Professor of Surgery and Director of Education at the Cedars Sinai Spine Center, and Director of the Spine Institute in Los Angeles, CA. “Instead of replacing or fusing the disc, there is mounting compelling evidence that we can use this regenerative medicine to heal the disc. We are fast approaching this inflection point in the treatment of low back pain, which is particularly important in view of the epidemic of opioid abuse."
In May 2017, Mesoblast noted in the 3rd Quarter report that they target patient enrollment completion of the Phase 3 back pain trial by the end of 2017.
 In October 2017, Mesoblast confirmed that they still anticipated patient enrollment completion by the end of 2017.<ref name="http://www.mesoblast.com">http://www.mesoblast.com/</ref>
During the November 16, 2017 CEO Presentation to Annual General Meeting, Mesoblast said patient enrollment completion slipped to 1st quarter 2018.
2018.
On March 29, 2018, Mesoblast announced it had completed patient enrollment for its Phase 3 trial. Mesoblast Chief Executive Dr. Silviu Itescu said, "There is an urgent need to provide an effective treatment for patients suffering from chronic low back pain due to degenerative disc disease, a population which today accounts for 50% of prescription opioid usage. If the Phase 3 results demonstrate durable improvement in pain and function, MPC-06-ID has the potential to make a major difference in patients with this serious medical condition."
In addition to Mesoblast's announcement, other key milestones were delayed as well. On the U.S. government website, the estimated primary completion date was delayed from February 2019 to October 2019. The estimated study completion date also slipped from February 2020 to October 2020.
On August 29, 2018, Mesoblast reported its Annual and Fourth Quarter results. Included was a brief mention of the Phase 3 trial for back pain. Mesoblast reported that a total of 404 patients across 48 sites are being followed for evaluation of treatment related improvement in pain and function over two years.
2019.
Study completion dates for Mesoblast's solution for chronic low back pain were delayed again. On the U.S. government website for clinical trials, the estimated primary completion date slipped from October 2019 to March 2020. In addition, the estimated study completion date also slipped from October 2020 to March 2021. In total, the estimated primary completion date has been delayed over one year, as its original date was February 2019 and now is March 2020. The estimated study completion date originally was February 2020 and is now March 2021.
During the company's half year financial results in February, Mesoblast reported that a key milestone for the second half of 2019 would be that all patients will complete their 12-month assessment for safety and efficacy.
2020.
In October, it was reported that Mesoblast is expected to receive results from its chronic heart failure and phase three lower back pain trials by the end of the 2020. Additionally, Mesoblast and its partner Grünenthal GmbH are collaborating for a confirmatory phase three trial in Europe.
2021.
On March 31st, Mesoblast reported half-year results. Results from Phase 3 trial of rexlemestrocel-L (MPC-06-ID) in 404 patients with chronic low
back pain (CLBP) due to degenerative disc disease (DDD) showed that a single injection of rexlemestrocel-L + hyaluronic acid (HA) carrier may provide at least two years of pain reduction, with opioid sparing activity in patients using opioids at baseline. Mesoblast also reported significant and durable reductions in CLBP through 24 months were seen across the entire evaluable study population, and greatest pain reduction was observed in the pre-specified population with CLBP of shorter duration than the study median of 68 months. The results indicate that treatment benefit may be greatest when inflammation is high and before irreversible fibrosis has occurred in the intervertebral disc. Mesoblast announced they intend to meet with FDA to discuss a potential pathway for approval of rexlemestrocel-L in patients with chronic discogenic lower back pain based on the observed durable reduction in pain and opioid sparing activity in the CLBP Phase 3 trial.
Criticism.
Mesoblast's solution for back pain came under heavy criticism from competitor Regenexx in August 2015. Dr. Chris Centeno said the trial results were "spit shined" with confusing and misleading language, press releases for phases 1 and 2 did not include images of MRIs to prove that discs were regenerated and expressed doubts about maintaining cell quality while mass-producing cells. He also said the host's immune system removes the injected stem cells.
Centeno said: "Whenever you see a company drop key imaging results that are needed to impress insurers (like positive MRI changes in the spine) you can almost bet that there are serious troubles brewing. Then when you observe that what should take a few sentences to describe whether or not the product helped pain and function actually takes an entire page of reported numbers sliced and diced 10 different ways, you know there are serious issues."
Rheumatoid Arthritis.
On January 11, 2016, announced results showing significant benefit in the first cohort of Rheumatoid Arthritis patients treated with MPC. After 12 weeks 47% of MPC treated patients and 60% of MPC treated patients(with prior failures of 1or 2 biologics) reached efficacy endpoints (compared to controls at 25% and 17%). Remission was observed at week 12 on 20% of MPC treated patients (0% in controls). On 24 March 2016
US patent 9,265,796
was granted for the use of Mesenchymal Precursor Cells (MPCs)for the treatment or prevention of a broad range of rheumatic conditions, including rheumatoid arthritis, osteoarthritis, psoriatic arthritis, ankylosing spondylitis, sacroiliitis, enteric arthritis, and reactive arthritis.
On January 22, 2016, very encouraging results of a Phase 2 clinical trial on 241 children with acute Graft-versus-host disease were reported, see Graft vs Host Disease, later.
Crohn's disease.
A Phase 3 multi-centered, double-blind, randomized, placebo-controlled trial is evaluating the safety and efficacy of Prochymal® in moderate to severe Crohn's Disease in patients who are resistant to traditional treatments. Preliminary data from two interim analyses planned under the protocol provided encouraging results.
Graft versus host disease.
On September 30, 2014, Mesoblast announced that its Japanese partner, JCR Pharmaceuticals Co Ltd (JCR), filed with the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) to receive approval for manufacturing, marketing, and product registration of the allogeneic or "off-the-shelf" Mesenchymal Stem Cell (MSC) product JR-031 for the treatment of acute graft versus host disease (GVHD) in children and adults.
During the 2015 financial year, Mesoblast's licensee, JCR Pharmaceuticals Ltd, filed for regulatory approval for its GVHD MSC-based product, JR-031, in children and adults in Japan. JR-031 was granted orphan drug priority review. If successful, it will be the first allogeneic cell-based product approved in Japan.
In January 2016, results of a Phase 2 clinical trial on 241 children with acute Graft-versus-host disease, that were not responsive to steroids, were announced. Survival rate was 82% (vs 39% of controls) for those who showed some improvement after 1 month, and in the long term 72% (vs 18% of controls) for those that showed little effect after 1 month. This trial used the MSC-100-IV product.
For the Phase 3 trial in the United States, for the pediatric indication, a 60-patient open label trial was initiated in the 2015 financial year. During the conduct of the pediatric Phase 3 trial, Mesoblast expects to have discussions with the FDA regarding the trial design for a potential Phase 3 trial to support approval of this product for adults with steroid refractory liver or gut GVHD.
On December 19, 2017, Mesoblast announced that the Phase 3 trial completed enrollment. In November 2016, the Phase 3 trial was successful in a pre-specified interim futility analysis of the
primary endpoint.
When the three pivotal trials met their primary endpoints, The Oncologic Drugs Advisory Committee met on August 13, 2020 to review the data supporting the Biologics License Application filed by Mesoblast. The FDA granted Mesoblast Priority Review and a decision by September 30, 2020.
Diabetic nephropathy.
On June 9, 2015, Mesoblast announced results from the Company's Phase 2 trial in patients with diabetic nephropathy showed that a single infusion of its intravenously delivered allogeneic mesenchymal precursor cell (MPC) product candidate MPC-300-IV was safe, reduced damaging inflammation, and preserved or improved renal function over at least 24 weeks. The results were presented at the late-breaking scientific sessions of the 75th annual meeting of the American Diabetes Association (ADA) that was held in Boston. The ADA annual meeting brings together approximately 14,000 participants, including clinicians and researchers from 124 countries.
COVID-19 Acute Respiratory Distress Symptoms.
Ryoncil was tested in a March 2020 pilot study at Mount Sinai Hospital in New York City on late-stage, ventilator-assisted Covid-19 patients suffering Acute Respiratory Distress Syndrome. Based on the results, the FDA approved a Phase 2/3 study on 300 patients at 30 sites around the U.S. The Cardiothoracic Surgical Trials Network, funded by the NIH, and Mesoblast (the owner of the product) commenced that trial on May 5, 2020.
Acquisitions, manufacturing and financing.
In December 2010, Mesoblast entered an agreement with US-based Cephalon to develop and commercialize novel adult Mesenchymal Precursor Stem Cell (MPC) therapeutics for degenerative conditions of the cardiovascular and central nervous systems.
In September 2011, Mesoblast entered an agreement with Swiss-based Lonza Group. Under the agreement Lonza will manufacture the stem cells in sufficient quantity to meet the global demand for Mesoblast's MPC cell products. Mesoblast will also have exclusive access to Lonza's Cell Therapy facilities in Singapore for the manufacture of allogeneic cell therapy, subject to certain exceptions.
In October 2013, Mesoblast acquired the entire culture-expanded mesenchymal stem cell (MSC) business of Osiris Therapeutics. Cost savings and other synergies are expected across personnel, capital expenditure, and manufacturing. As a result of this acquisition, Mesoblast also inherited a relationship with Japan-based JCR Pharmaceuticals Co. Ltd.
In May 2014, Mesoblast announced it would receive incentives from the Singapore Economic Development Board (EDB) for activities in Singapore related to manufacturing operations, as well as product development and commercialization.
In June 2015, Mesoblast received $5.8 million from the Australian Government for Research & Development (R&D) activities conducted during the 2014 financial year. The funds were provided to Mesoblast under the Government's R&D Tax Incentive Program, designed to support industry innovation.
In February 2016, Mesoblast's Licensee (JCR Pharmaceuticals Co., Ltd.) sold its first allogeneic cell product TEMCELL® HS Inj., for the treatment of acute graft versus host disease (aGVHD) in children and adults in Japan. TEMCELL is the first allogeneic cell therapy to be fully approved in Japan.
Financial performance.
Mesoblast is listed as MSB on the Australian Securities Exchange (ASX), as MESO on the NASDAQ, and as MEOBF on the ATC Markets.
The company reported its financial results in November 2020. As of September 30, 2020:


Lorna Breen

Lorna Margaret Breen (October 9, 1970 – April 26, 2020) was an American physician who was the emergency room director at NewYork-Presbyterian Hospital. She died by suicide in 2020, while taking a break with family in Charlottesville, Virginia during the coronavirus pandemic.
Early life.
Breen was born in Charlottesville, Virginia and raised in Danville, Pennsylvania. She graduated from Wyoming Seminary in 1988. She received a master's degree at Cornell University and attended Medical College of Virginia before doing a residency at Long Island Jewish Medical Center.
Career.
Breen worked in The Allen Hospital at the NewYork-Presbyterian, where during spring of 2020 she treated patients with COVID-19. She contracted the virus herself then went back to work after isolating for a week and a half. On a family break in Charlottesville, Virginia, she died by suicide on April 26, 2020. Her father said: "She was truly in the trenches of the frontline. She tried to do her job, and it killed her [...] Make sure she’s praised as a hero. Because she was, she’s a casualty just as much as anyone else who has died."


American Osteopathic Board of Dermatology

The American Osteopathic Board of Dermatology (AOBD) is an organization that provides board certification to qualified Doctors of Osteopathic Medicine (D.O.) who specialize in the medical and surgical treatment of disorders of the skin (dermatologists). The board is one of 18 medical specialty certifying boards of the American Osteopathic Association Bureau of Osteopathic Specialists approved by the American Osteopathic Association (AOA). It was established in 1945. The AOBD is one of two certifying boards for dermatologists in the United States. The other certifying authority is the American Board of Dermatology, a member board of the American Board of Medical Specialties. As of 2011, 396 osteopathic physicians held active certification with the AOBD. In addition to the fellows of the American Board of Dermatology, board certified osteopathic dermatologists are eligible for admission into the American Society for Mohs Surgery.
Board certification.
Initial certification is available to osteopathic dermatologists who have successfully completed an AOA-approved residency in dermatology, two years of practice, successful completion of clinical and written exams. Diplomates of the American Osteopathic Board of Dermatology requires osteopathic dermatologists to renew their certification every ten years to avoid expiration of their board certified status.
Subspecialties.
The AOBD also oversees examinations for osteopathic dermatologists that seek to subspecialize in the fields of Mohs micrographic surgery and dermatopathology.


Lateral dorsal nucleus of thalamus

The lateral dorsal nucleus is a nucleus of the thalamus. It is the most anterior of the dorsal lateral nuclei.
It acts in concert with the anterior nuclei of thalamus.
It receives significant input from several subdivisions of visual cortex, and has a primary output to parietal cortex on the dorsolateral cortical convexity, giving it access to limbic forebrain nuclei important for emotion and behavior functions.


Murray Matthewson

Murray Hugh Matthewson MB ChB (NZ) 1967, FRCS (Eng) 1973, MA (Cantab) 1985. (17 September 1944 – 3 August 2018) was an orthopaedic surgeon who specialised in the spine and hand. Recipient of The Gordon Taylor Prize, he was an examiner for The Royal College of Surgeons as well as a Life Fellow of Hughes Hall, University of Cambridge, Associate Lecturer in the Faculty of Clinical Medicine, University of Cambridge and president of the British Society for Surgery of the Hand 2003. He was Orthopaedic Surgeon to Cambridge University Rugby Club 1998–2005.


Clonal deletion

Clonal deletion is the removal through apoptosis of B cells and T cells that have expressed receptors for self before developing into fully immunocompetent lymphocytes. This prevents recognition and destruction of self host cells, making it a type of negative selection or central tolerance. Central tolerance prevents B and T lymphocytes from reacting to self. Thus, clonal deletion can help protect individuals against autoimmunity. Clonal deletion is thought to be the most common type of negative selection. It is one method of immune tolerance.
Discovery and Function.
Frank Macfarlane Burnet proposed autoreactive cells would be terminated before maturation in order to prevent further proliferation in his study in 1959. There are millions of B and T cells inside the body, both created within the bone marrow and the latter matures in the thymus, hence the T. Each of these lymphocytes express specificity to a particular epitope, or the part of an antigen to which B cell and T cell receptors recognize and bind. There is a large diversity of epitopes recognized and, as a result, it is possible for some B and T lymphocytes to develop with the ability to recognize self. B and T cells are presented with self antigen after developing receptors while they are still in the primary lymphoid organs. Those cells that demonstrate a high affinity for this self antigen are often subsequently deleted so they cannot create progeny, which helps protect the host against autoimmunity. Thus, the host develops a tolerance for this antigen, or a self tolerance.
Location.
B and T lymphocytes are tested for their affinity for self MHC/peptide complexes before leaving the primary lymphoid organs and entering into the periphery. If they demonstrate high affinity for self-antigen, one method of preventing autoimmunity is through clonal deletion. This is where the lymphocyte would receive apoptotic signals from antigen-presenting cell (APCs). It is important to note that not all lymphocytes expressing high affinity for self-antigen undergo clonal deletion. B lymphocytes can also participate in light chain receptor editing, VH gene replacement, or be released and later undergo negative selection in the periphery. T lymphocytes can instead undergo clonal arrest, clonal anergy, and clonal editing. If autoreactive cells escape clonal deletion in either the thymus or the bone marrow, there are mechanisms in the periphery involving T regulatory cells to prevent the host from obtaining an autoimmune disease. However, for both B and T cells in the primary lymphoid organs, clonal deletion is the most common form of negative selection.
B Cells.
B cells demonstrating high affinity for self cells can undergo clonal deletion within the bone marrow. This occurs after the functional B-cell receptor (BCR) is assembled. It is possible for B cells with high self affinity to go undeleted because they require activation signals and stimulation from autoreactive T cells. Such T cells are often removed via clonal deletion, leaving autoreactive B cells unstimulated and unactivated. These B cells do not pose a threat, even in the periphery, because they cannot be activated without an autoreactive T cell to stimulate them.
T Cells.
Between 2% and 5% of T cells develop auto-reactive receptors. Most of these undergo negative selection by clonal deletion.
Thymic Cortex.
T cells that show a high affinity for self MHC/peptide complexes can undergo clonal deletion in the thymus. Thymic dendritic cells and macrophages appear to be responsible for the apoptotic signals sent to autoreactive T cells in the thymic cortex.
Thymic Medulla.
T cells also have the opportunity to undergo clonal deletion within the thymic medulla if they express high affinity for self MHC/peptide complexes. Positive selection occurs in the thymic cortex, which suggests it is possible for a cell to undergo positive selection within the cortex and then negative selection in the medulla via clonal deletion. Epithelial cells are responsible for clonal deletion within the medulla. These medullary epithelial cells express an autoimmune regulator (AIRE) which allows these cells to present proteins specific to other parts of the body to T lymphocytes. This helps eliminate autoreactive T cells that recognize a protein from a specific body part.
Complete vs. Incomplete Clonal Deletion.
Complete clonal deletion results in apoptosis of all B and T lymphocytes expressing high affinity for self antigen. Incomplete clonal deletion results in apoptosis of most autoreactive B and T lymphocytes. Complete clonal deletion can lead to opportunities for molecular mimicry, which has adverse effects for the host. Therefore, incomplete clonal deletion allows for a balance between the host’s ability to recognize foreign antigens and self antigens.
Methods of Exploitation.
Molecular Mimicry.
Clonal deletion provides an incentive for microorganisms to develop epitopes similar to proteins found within the host. Because most autoresponsive cells undergo clonal deletion, this allows microorganisms with epitopes similar to host antigen to escape recognition and detection by T and B lymphocytes. However, if detected, this can lead to an autoimmune response because of the similarity of the epitopes on the microorganism and host antigen. Examples of this are seen in "Streptococcus pyogenes" and "Borrelia burgdorferi." It is possible, but uncommon for molecular mimicry to lead to an autoimmune disease.
Superantigens.
Superantigens are composed of viral or bacterial proteins and can hijack the clonal deletion process when expressed in the thymus because they resemble the T-cell receptor (TCR) interaction with self MHC/peptides. Thus, through this process, superantigens can effectively prevent maturation of cognate T cells.


Dan W. Brown

Dan Wayne Brown (December 22, 1950 – May 11, 2021) was an American politician who served as a member of the Missouri Senate, representing the 16th district from 2011 to 2019. Brown also served in the Missouri House of Representatives from 2008 to 2010, representing the 149th district.
Personal history.
Dan Brown was born in Solo, Missouri, and was a graduate of Houston High School in Houston, Missouri. Brown received a Bachelor of Science degree in Agriculture and a Doctorate of Veterinary medicine from the University of Missouri. Brown had been a practicing veterinarian for over 33 years and continued his practice in addition to his legislative duties. He died at the age of 70 on May 11, 2021.
Political history.
Dan Brown first entered statewide politics in 2008 when he defeated Democrat Wayne Bledsoe and Constitution Party candidate Dennis E. Husted to win the district 149 seat.
After only one term in the House, Brown chose to run for State Senator in 2010, defeating incumbent Democrat Frank Barnitz to win the 16th district seat.
During the 96th General Assembly Senator Brown served on the following committees:
Organizations.
Senator Brown belonged to the following groups:


Physician self-referral

Physician self-referral is a term describing the practice of a physician ordering tests on a patient that are performed by either the referring physician himself or a fellow faculty member from whom he receives financial compensation in return for the referral. Examples of self-referral include an internist performing an EKG, a surgeon suggesting an operation that he himself would perform, and a physician ordering imaging tests that would be done at a facility he owns or leases.
The ability to self-refer is an incentive for physicians to order more tests than they otherwise might. In the United States, the Stark Law (specifically sections I and II) was designed to control self-referrals. However, the exceptions designed to allow necessary testing in physicians' offices have been exploited to circumvent the law. The in-office exception, which allows testing on equipment in the physician's office, has resulted in many physicians purchasing high-tech and expensive equipment such as CT scanners, MRI scanners, and nuclear scanners for their own offices.
The incentive for this practice is largely the result of rapidly declining reimbursements for what has been termed "cognitive" physician care, i.e. the time spent talking to a patient and determining what course of diagnostic testing or treatment would be best.
History.
One of the current areas of change in medicine lies in the location and interpreter of advanced imaging results, including MRIs, CT scans, PET scans, and ultrasounds. The trend for non-radiology physicians to evaluate their patients’ imaging results began more than thirty years ago. In the past, the majority of x-rays were interpreted by radiologists; today, it is very common for physicians to read them. The same trends are occurring for other imaging techniques.
Advanced medical imaging used to be provided only in hospitals and privately owned imaging centers, and, with some notable exceptions, were only evaluated by radiologists. An example of such an exception included the American Society of Neuroimaging, which, with its formation in 1975, incited neurologists to develop interest in the newest imaging techniques of the time to help evaluate their patients in non-invasive ways. Other specialists, such as cardiologists, neurosurgeons, and orthopedic physicians became more interested in using advanced imaging techniques as they continued to be refined and developed over the last two decades.
This change in the delivery of these services has resulted in the debate between radiologists and other medical specialists over the control and use of advanced medical imaging.
Historically, self-referral described the normal practice of a physician diagnosing a patient and then treating that individual if the treatment was within that doctor's scope of practice. However, several radiology authors have successfully used the term to describe the idea of self-referral for imaging services with the connotation that it is an undesirable and wasteful practice.
Economic incentives.
Self-referral has had the greatest influence on radiology. Normally, the revenue from imaging exams comes from two sources: the facility fee and the professional fee. The facility fee covers technical costs, such as use of the machine, while the professional fee is for the interpretation and consulting services provided by the physician. Physicians who own imaging machinery can derive profit by collecting both of these fees.
For example, when a patient is seen at a hospital and receives a CT scan, a technical fee is paid to the hospital to cover the cost of running the scanner, while the professional fee is charged by the radiologist for interpreting the results and documenting the findings. In self referral, however, a doctor seeing a patient in his office would recommend a test, often an echocardiography or nuclear cardiac imaging, that would be performed at his office and interpreted by him. Thus, the physician collects both the facility and professional fees.
Negative consequences.
The risk to the physician-owner for self-referring is minimal, since he can increase the volume of scans to any point necessary to ensure profitability. This is recognized by the machine vendors, who have moved aggressively to sell imaging machines to physicians who are not board-certified or specialized in radiology. One vendor of medical imaging equipment marketing to physicians states:
Increased costs.
There is a large volume research indicating that self-referral has a major effect on increasing medical costs in the US. David Levin estimated the cost of unnecessary self-referred imaging in 2004 to be, conservatively, $16 billion per year.
There are several examples showing that self-referral increases utilization and costs:
However, many of the studies on imaging have not taken into account the role of technological improvements in the increase of imaging over the last decade.
IOAS or in office ancillary services include a wide range of services. The provision allows physicians to offer services such as X-Ray, ultrasound and MRI. The practice is legal and ethical. Physicians have offered services in their offices such as X-Ray for decades. Studies show an increased use in ancillary services when the procedures are provided in their office. What the studies fail to show is the motivating factor. Assuming its financial, such motivation would violate the AMA's code of ethics. Other factors to consider are a faster diagnosis, less complex authorization and scheduling process, and the consolidation of medical records — all of which benefit the patient's treatment.
Quality.
Modern MRI scans are very complex and require specialist training to be properly interpreted. An editorial in the "Journal of the American College of Radiology" lamented:
Convenience.
Studies show patients benefit from IOAS through access to a wide range of diagnostic and therapeutic services sooner resulting in a quicker diagnosis. Furthermore, patients benefit from the cost savings an IOAS provides as do insurance companies. The myth that IOAS increases health care costs is perpetuated by the giant companies who own multiple clinics.
Self-referral is often defended for its convenience, though if the patient cannot be seen by the physician on the same day for imaging, the argument is negated.
AMA Position.
On two different occasions, the American Medical Association House of Delegates has said that medical imaging should be performed by all physicians who are trained and qualified, and not only by one specialty group such as radiology, claiming that a monopoly by a single specialty would lead to lower quality in health care segments dependent upon imaging as well as higher costs.
Attempts at resolution.
The Medicare Improvements for Patients and Providers Act of 2008 aims to use point-of-order and point-of-service online approval systems to eliminate the overutilization presented by self-referrals.