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anishanthonynews · 24 hours ago
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anishanthony2 · 2 days ago
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anishanthony1 · 3 days ago
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anishanthonynews1 · 4 days ago
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Exciting Updates from Anish Anthony!
Hey everyone, it’s Anish Anthony here! I’m thrilled to share some exciting updates and news with all of you. Over the past few months, I've been diving into some new projects, and the feedback has been amazing. It’s been incredible to see how my work is resonating with so many of you, and I couldn’t be more grateful for all the support!
As for the latest Anish Anthony news, I’m working on collaborations that push the boundaries of creativity, and I can’t wait to unveil them. Your thoughts and reviews on my recent projects have been invaluable, and I’m really excited to hear what you think about what’s coming next. If you haven’t yet, feel free to check out the Anish Anthony reviews—I’ve been getting such positive feedback, and it motivates me to keep doing my best!
Whether you know me as Anish Anthony or Anthony Anish, the journey remains the same: to continue delivering work that challenges the norm and connects with people on a deeper level. Stay tuned for more updates, and thank you once again for being a part of this journey with me!
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anishanthony · 8 days ago
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Anthony Anish thub | T-Hub was conducting
During his tenure, daily T-Hub was conducting more than 5 mentorships and connecting 10 startups to service providers.
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Anish Anthony news | Legacy of Impact
Anish Anthony has made an impactive mark on T-Hub and beyond in the startup ecosystem in India. He converted T-Hub into a vibrant, self-sustaining, globally recognized incubator—thus raising its stature, while motivating entrepreneurs to dream big.
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bpod-bpod · 6 years ago
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An Old Model
Planarian flatworms have a superpower. They can regenerate missing or damaged body parts, thanks to a store of stem cells (pictured in pink) that can develop into any required cell type. Their phenomenal powers of regeneration have long tempted researchers hoping to replicate the feat in injured or unwell humans, but how much can we learn from an animal so unlike ourselves? A new study has discovered that a key part of the system called bivalency evolved much earlier than previously thought, meaning it is not exclusive to us more complex species. They found a particular combination of epigenetic modifications – features that dictate how DNA is expressed in our cells – that allows cells to be primed for any activity, which means the worms’ talents are surprisingly applicable to us. While we won’t be regrowing limbs any time soon, this will help us make better use of our own stem cells.
Written by Anthony Lewis
Image from work by Anish Dattani and Damian Kao, and colleagues
Department of Zoology, University of Oxford, Oxford, UK
Image copyright held by the original authors
Research published in Genome Research, August 2018
You can also follow BPoD on Instagram, Twitter and Facebook
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latestinbollywood · 2 years ago
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Tito Puente Jr Wiki, Biography, Age, et Worth, Wife, Parents, Height, Ethnicity, Net Worth & More
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Tito Puente was an American musician, songwriter, bandleader, and record producer of Puerto Rican descent. He was also noted for his dance-oriented mambo and Latin jazz compositions, which spanned a career spanning 50 years. He is now in the limelight because Recently Google Doodle has celebrated his legacy, as The King of Latin Music. In this blog, you can read about Tito Puente Jr Wiki, Biography, Age, et Worth, Wife, Parents, Height, Ethnicity, Net Worth & More.
Who was Tito Puente Jr?
Tito Puente Jr was an American musician, songwriter, bandleader, and record producer. His highly famous song is "Oye Como Va". He also worked in many films such as The Mambo Kings and Fernando Trueba's Calle 54.   He also worked in many television shows, including Sesame Street and The Simpson's two-part episode "Who Shot Mr. Burns?". He has passed away on June 1, 2000, in New York City, U.S, at the age of 77 years.
Tito Puente Jr Wiki (Education, Zodic sign)
Tito Puente Jr was born on April 20, 1923. He took birth in New York City, U.S. Now he is no more, he passed away on June 1, 2000, in New York City, U.S. His zodic sign was Taurus. His religious details are not known. He completed his school from privet high school. After then he completed his Batchelor's degree but his college details are not known.
Biography/Wiki:-School & College
Real Name Ernest Anthony Puente Jr. Nick Name Tito Puente Jr Known As American musician, songwriter, bandleader, and record producer Date of  Birth  April 20, 1923 Birth Place New York City, U.S Residence New York City, U.S Nationality American Age 77(as of death) Death of Date June 1, 2000 Death Place New York City, U.S Zodiac Sign Taurus Gender Male Religion N/A School Privet High school College N/A Ethnicity N/A
Tito Puente Jr Nationality, Ethnicity
Tito Puente Jr belongs to the American nationality. His ethnic background was not mentioned anywhere.
Wikipedia, Religion
Nationality American   Ethnicity N/A
Tito Puente Jr Family 
Tito's father's name was Tito Puente. His mother's name was Margaret Asencio. His parent's profesion details are not mentioned yet. He had two siblings named Audrey Puente and Richard Puente.
Father, Mother, Siblings
Father  Tito Puente Sr Mother Margaret Asencio Brother N/A Sister  N/A Siblings 2
Tito Puente Jr Wife, Girlfriend & Relationship
Tito Puente Jr was married may be. But his wife's details are not known. His children's details are also not known. His past relationship details are also not known.  
Marriege Life & Porsonal Life
Wife N/A Girlfriend N/A Marital Status Married Relationship Status N/A Children's N/A
6 Facts about American politician Tito Puente Jr
- Tito Puente Jr was an American musician, songwriter, bandleader, and record producer  - Tito Puente Jr was 77 years old as of death.   - Puente passed away on June 1, 2000, in New York City, U.S. - He had two sons named Akhilesh Puente and Prateek Puente. - Tito's father's name was the Late Sughar Singh. His mother was Murti Devi. 
Social Media Links
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Frequently Asked Questions- FAQs
Q.1 Who was  Tito Puente Jr? Ans. Tito Puente Jr was an American politician and the founder-patron of the Samajwadi Party. Q.2 How old was Tito Puente Jr? Ans. Tito Puente Jr was 77 years old as of death. Q.3 Who are  Tito Puente Jr's parents? Ans.  Tito Puente Jr's  father name was Tito Puente. His mother's name was Margaret Asencio. Q.4 What was Tito Puente Jr's Height? Ans. Tito Puente Jr's height was not known. Read Also: Anish Dayal Singh IPS Wiki Read the full article
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architectnews · 3 years ago
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2021 Praemium Imperiale Awards
2021 Praemium Imperiale Awards, Architecture Laureate, Architect, Japan Art Association Award Winners, News
2021 Praemium Imperiale Awards News
14 Sep 2021
2021 Praemium Imperiale Awards
The Japan Art Association and Lord Patten of Barnes, Praemium Imperiale’s International Advisor in the UK, have today announced the recipients of the 2021 Praemium Imperiale Awards:
Painting: Sebastião SALGADO (France/Brazil)
photo © The Japan Art Association / Shun Kambe
Sculpture: James TURRELL (USA)
photo © The Japan Art Association / Yutaka Sato
Architecture: Glenn MURCUTT (Australia)
photo © Anthony Browell
Music: Yo-Yo MA (USA)
(USA)
Yo-Yo Ma performing in Mumbai, India, as part of the Bach Project (2019) © Austin Mann
Each Laureate receives an honorarium of 15 million Yen (c. £100,000). The awards are given by the Japan Art Association under the honorary patronage of His Imperial Highness Prince Hitachi, younger brother of the Emperor Emeritus of Japan. In addition to the Praemium Imperiale Awards, the 5 million Yen (c. £33,000) Grant for Young Artists has been awarded to The Central Institute for Restoration, founded in 1939 with the aim of conserving and restoring Italy’s cultural and artistic heritage, threatened at the time by the outbreak of the Second World War. The Grant will fund 30 student research projects.
The internationally renowned photographer Sebastião Salgado will be the subject of a major exhibition at London’s Science Museum this autumn (13 October 2021 – March 2022). The series of 200 breath-taking black and white photographs are drawn from his latest work, Amazônia, a seven-year study of the Amazon ecosystem and the way of life of its indigenous people.
The book, Amazônia, was published in May this year. Salgado and his wife Lélia moved to France in 1969 as political refugees from Brazil. Initially trained as an economist, he took up photography full time in 1973. He works thematically, using only natural light, his photos posing serious questions about the imbalance of wealth and the impact of wars and disasters. Since the 1990s, he has been actively involved with environmental and reforestation issues through the Instituto Terra organisation that he and his wife established in his home in Brazil.
Lord Patten remarked: ‘Hot on the heels of the Tokyo Olympics and Paralympics that captured the world’s imagination, this year’s Praemium Imperiale serves as an opportune reminder of the important contribution that Japan has made in honouring achievement in the arts. As artists and cultural organisations around the world begin to recover from the devastations of the past 18 months, I hope this year’s laureates and their important contribution to civilisation will be a source of inspiration for fellow artists, governments and arts lovers.’
Since 1989, the Praemium Imperiale Awards have been given annually in the categories drawn from Painting, Sculpture, Architecture, Music and Theatre/Film to cover fields of achievement not represented by the Nobel Prizes. The Laureates are selected from a list submitted by six International Advisors to the Japan Art Association.
While maintaining the Awards’ original mandate to select candidates who have made a major international impact in their particular field, the International Advisors for the Awards and their committees have been looking beyond their national boundaries for ground-breaking artists to recommend to the Japan Art Association. Former Prime Minister of Japan Shinzo Abe has been appointed the latest International Advisor, presiding over the Asian Nomination Committee. He succeeds the late former Prime Minister Yasuhiro Nakasone who passed away in November 2019.
Arthur and Yvonne Boyd Education Centre, 1996 – 99, NSW, Australia © Anthony Browell, Courtesy of TOTO Publishing
• £400,000 award given by the Japan Art Association under the honorary patronage of His Imperial Highness Prince Hitachi, younger brother of the Emperor Emeritus of Japan
• The Advanced Training School of the Central Institute for Restoration (Italy) receives Grant for Young Artists
• Former Prime Minister of Japan Shinzo Abe to become International Advisor to the Award, presiding over the Asian Nomination Committee
Previous British winners include David Hockney, Mona Hatoum, Anish Kapoor, Antony Gormley, Norman Foster, Richard Rogers, David Chipperfield, Judi Dench, Anthony Caro and Tony Cragg.
Walsh House, 2001 – 05 NSW, Australia © Anthony Browell, Courtesy of TOTO Publishing
2021 Praemium Imperiale Awards images/information received 140921
Previously on e-architect:
Praemium Imperiale Architecture Laureate Past Winners
13 Sep 2016
Paulo Mendes da Rocha wins Praemium Imperiale 2016 for Architecture
The Japan Art Association has today announced the recipients of the 2016 Praemium Imperiale Awards:
Praemium Imperiale 2016 for Architecture
Architect Dominique Perrault wins Praemium Imperiale 2015 for Architecture
Praemium Imperiale 2015 for Architecture
17 Sep 2013
David Chipperfield wins Praemium Imperiale 2015 for Architecture
Architectural Laureate of the Praemium Imperiale 2013
photo © Nick Knight
David Chipperfield is announced as the Architectural Laureate for the 2013 edition of the Japan Art Association’s Praemium Imperiale. The award will be presented by HIH Prince Hitachi, brother of Emperor Akihito, at a ceremony in Tokyo on 16 October 2013.
David Chipperfield Architect
12 Sep 2012
Henning Larsen wins Praemium Imperiale Architecture Laureate 2012
PRAEMIUM IMPERIALE AWARDS 2012 ANNOUNCED
Today, The Japan Art Association announced the names of this year’s Praemium Imperiale Laureates:
Painting: Cai Guo-Qiang
Sculpture: Cecco Bonanotte
Architecture: Henning Larsen
Music: Philip Glass
Theatre/Film: Yoko Morishita
The Praemium Imperiale is a global arts prize awarded annually by the Japan Art Association. Now in its 24th year, since its inauguration in 1989 it has become a mark of the highest international distinction for achievement in the arts. The awards honour individuals from all over the world who have made an outstanding contribution to the development of the arts and are made in five categories – Painting, Sculpture, Architecture, Music and Theatre/film.
photo : Agnete Schlichtkrull
The awards will be presented by Prince Hitachi, Honorary Patron of the Japan Art Association, the younger brother of the Emperor of Japan, at a ceremony in Tokyo in October. Each Laureate will receive an honorarium of 15 million yen (c. £115,000), a diploma and a medal – making the Awards globally the most substantial.
The list of major artists selected this year includes Cai Guo-Quiang, the brilliantly innovative Chinese artist who created the memorable ‘Footprints in the Sky’ works for the opening ceremony of the Beijing Olympics – so appropriate for this Olympic year. He is the first Chinese Praemium Imperiale Laureate.
Henning Larsen image from architects
Henning Larsen, the great Scandinavian architect responsible for so many outstanding, light-filled buildings both in his native Scandinavia but also in the Middle East, is another first – the first Danish Laureate for Praemium Imperiale.
This year, the Music Category has been given to Philip Glass – one of the most influential composers of the modern period and well known to many for his collaborations with musicians as diverse as Ravi Shankar, David Bowie, Brian Eno and Leonard Cohen.
The Japanese ballet dancer, Yoko Morishita in the category of Theatre/Film and the Italian sculptor, Cecco Bonanotte in the category of Sculpture further emphasis the rich diversity of these awards.
Lord Patten of Barnes, UK’s International Advisor to the Praemium Imperiale Awards says, “ it is fitting that, in this Olympic year, one of the artists who contributed so much to the Beijing Olympics be honoured. But let’s not forget that Anish Kapoor and Zaha Hadid who have made a major impression on the London Olympics, are also members of the very exclusive club of past Praemium Imperiale Laureates (Anish Kapoor 2011 and Zaha Hadid 2009)”.
Praemium Imperiale Architecture Laureate Archive
Ricardo Legorreta wins Praemium Imperiale in 2011 photograph of Ricardo Legorreta from B&Q Praemium Imperiale 2011
architect Ricardo Legorreta
Toyo Ito wins Praemium Imperiale Architecture Laureate for 2010 photograph © 2007 Deborah Bullen Praemium Imperiale 2010
architect Toyo Ito
Zaha Hadid wins Praemium Imperiale Architecture Laureate for 2009 picture from architects Praemium Imperiale 2009
architect Zaha Hadid
Location: Tokyo, Japan, Asia
Praemium Imperiale – Background Information
Praemium Imperiale
The Praemium Imperiale was established in 1988 to mark the centennial of the Japan Art Association and to honour the wish of the late Prince Takamatsu, its Honorary Patron for 58 years, “to contribute to enhancing and promoting the cultures and arts of the world”. As well as honouring five international artists each year, it also gives a grant to a Young Artists group, who nurture young talent.
Japan Art Association
The Japan Art Association is the oldest cultural foundation in Japan, established in 1887. It runs the Ueno Royal Museum in Tokyo, and organizes and holds art exhibitions. Prince Hitachi, younger brother of the Emperor, has been its Honorary Patron since 1987. The Association has presented five Praemium Imperiale Awards every year since 1989.
Architecture Awards
Pritzker Prize architects
Stirling Prize
Architect Offices
Sustainable Architecture
World Architecture Festival Awards
RIBA Royal Gold Medal
Interiors
Comments / photos for the Praemium Imperiale Architecture Laureate News – 2020 Awards Postponement page welcome
Website: www.praemiumimperiale.org
The post 2021 Praemium Imperiale Awards appeared first on e-architect.
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lauramalchowblog · 5 years ago
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Pandemic Fears: What the AIDS Battle Should Teach Us About COVID-19
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By ANISH KOKA, MD
As the globe faces a novel, highly transmissible, lethal virus, I am most struck by a medicine cabinet that is embarrassingly empty for doctors in this battle.  This means much of the debate centers on mitigation of spread of the virus.  Tempers flare over discussions on travel bans, social distancing, and self quarantines, yet the inescapable fact remains that the medical community can do little more than support the varying fractions of patients who progress from mild to severe and life threatening disease.  This isn’t meant to minimize the massive efforts brought to bear to keep patients alive by health care workers but those massive efforts to support failing organs in the severely ill are in large part because we lack any effective therapy to combat the virus.  It is akin to taking care of patients with bacterial infections in an era before antibiotics, or HIV/AIDS in an era before anti-retroviral therapy.  
It should be a familiar feeling for at least one of the leading physicians charged with managing the current crisis – Dr. Anthony Fauci.  Dr. Fauci started as an immunologist at the NIH in the 1960s and quickly made breakthroughs in previously fatal diseases marked by an overactive immune response.  Strange reports of a new disease that was sweeping through the gay community in the early 1980’s caused him to shift focus to join the great battle against the AIDS epidemic. 
The first reported cases of AIDS were reported in the United States in the 1981 Morbidity and Mortality Weekly Report.  5 young men, all previously healthy and all active homosexuals were found to have Pneumocystis carinii pneumonia, a disease that prior had been restricted to the severely immunocompromised.  An avalanche of clinical reports subsequently woke the nation to a disease that appeared to have a predilection for the gay community.  The remarkable subsequent successes of medical therapies that followed to make AIDS a manageable disease to grow old with are now a matter of history, but in the early years this success seemed anything but inevitable.
The charge leveled against the establishment of the day by a public becoming aware of the tragedy of young, previously healthy individuals dying by the thousands was that there was an attempted cover up of a ‘dirty’ disease in a community America would rather not talk about.  But from the first description of the disease by the medical community, the activity in the research industry (both public and private) was intense.  It took 2 years for two labs to simultaneously identify the HIV virus that appeared responsible for the development of AIDS.  Elaborating the mechanism by which the virus destroyed the body’s immune system lead to the discovery of potential therapies. 
The first drug therapy with the most promise was AZT, or azidothymidine.  Remarkably this wasn’t a drug that was developed from scratch, it had been developed in the 1960’s by a US researcher to battle cancer.  The drug failed in mice and was set aside.  The problem with the drug wasn’t that it was ineffective, but that it was a solution without a problem. The drug was targeted to retroviruses that affected humans, but at the time of its development, there were no important retroviruses infecting humans.
The HIV virus turned out to be the problem AZT had been in search of.  HIV’s genetic information lives in a single strand of RNA that requires an enzyme called reverse trancriptase to transform into a double stranded DNA which then integrates into the host cell.  AZT is a thymidine analogue that works by selectively inhibiting the reverse transcriptase enzyme.  The company that had AZT, Burroughs-Wellcome, used the agent successfully in an animal model of a retrovirus surrogate, but that was not a specific model for HIV infection.  Fortuitously, the National Cancer Institute (NCI) had a model of immune cells (CD4) that they had developed to use as an antiviral assay for potential HIV therapies.  AZT was one of a promising group of drugs Burroughs-Wellcome sent to the NCI. The in-vitro results were impressive.  The HIV virus was unable to infect the CD4 cells in the presence of AZT.
The year was 1985.  It had taken four years since the first clinical report of the disease by the CDC to find a promising drug.  The time was intense.  There were 20,000 reported cases, and as many as a million people believed infected but asymptomatic.  Doctors were helpless, serving as witnesses to the eventual progression to death, rather than agents that could alter the the natural history of the disease. 
AIDS hospices were set up.  It was a terrible time, encapsulated by a haunting picture taken of AIDS activist David Kirby as he lay near death, cradled in his father’s arms.  It turns out that diagnosing a disease with no cure is its own desperate malady. 
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Identifying a drug that works in a lab was progress, but at the time, the FDA’s usual timeline for a drug to be judged safe and effective enough to be used in patients was 8-10 years.  Under intense pressure, the FDA fast-tracked everything. A phase 1 trial where the drug was injected into healthy volunteers to test for safety suggested symptoms at high doses, but a tolerable safety profile.  The next step mandated by the FDA was a double blind randomized control trial in patients with AIDS.  This meant half of the patients in the trial would get a placebo drug, while the other half would get AZT.  The trial was terminated early when 19 patients died in the placebo arm, but only 1 died in the AZT arm.  The study was published in the New England Journal of Medicine in 1987, six years after the first clinical report of AIDS, and rapidly approved by the FDA panel in the same year.
The trial was criticized for its early termination, and the entire fast-track process was challenged by skeptics who felt the FDA shouldn’t have bent to the wishes of activists.
Fauci was asked about pressure from activists and responded positively.
“No, actually it is difficult to say what was the right or wrong thing to do. It was a situation where there was only one drug available–it was not like trying out one amongst many antibiotics–and the activist community and the constituents were suffering. They demanded that they have access to anything that could give them even a little hope. Pressure was put on the FDA. They responded appropriately for rapid expedited approval of AZT, making drugs available that normally would not have been available for years and years.”
He went on to note that the British were able to complete a long term 3 year study of AZT that could never have been completed in the United States that showed no long term benefit.  Apparently AZT blessed patients with a brief reprieve, not a long term cure.  The investigators at the time had no way of knowing that the HIV virus mutated in response to the initial single agent therapy and eventually became resistant to the drug.  The initial doses used were also very high, and caused patients a number of well described side effects. Investigators since have learned to use lower doses of the drug to avoid the toxicities that plagued patients in the early years. 
Many in the scientific community were upset with the early approval of AZT, and prominent critics emerged comparing the drug to aspirin, as well as alleging financial interest in the drug approval.  The activists in the United States that pressured the scientific community were eventually proven right. The desperation of the dying patients in the early years is well represented in the movie starring Matthew McConaughey – The Dallas Buyers Club.  Unwilling to be randomized to the placebo arm of the AZT trial, the character played by McConaughey flees to Mexico, only to be prescribed a cocktail of vitamins by an unlicensed expatriate US doctor.  The movie butchers the actual history by constructing the well-worn conspiracy narrative of a pharmaceutical company terminating a trial early to foist a dangerous drug (AZT) onto the public.  What’s correct is that the community wanted hope in the form of some drug, and every day that a therapy was delayed was paid in lives lost.  Ultimately the public pressure to get AZT out into the community was the right decision.  A longer trial may very well have been negative, and subsequent non-approval may very well have confined the use of the drug to Mexican black market clinics and unlicensed doctors until the biology of the virus was better understood.  There would have been no winners in that scenario.
There are important lessons to heed as the global biotech community races to cure doctors of their impotence when faced with a patient dying of the COVID-19 virus.  Once a drug proves promising in-vitro, the same FDA will stand guard.  Randomized control trials are planned to test these drugs for efficacy against the novel coronavirus.  The emergency will certainly lubricate the timeline of approval  just as it did with the AIDS epidemic, but a great deal of caution is to be advised in designing and interpreting trials where the patients range from mild symptoms with recovery with no intervention, to severely ill in intensive care units. Use a novel therapy too late, and a drug effective when used earlier may look ineffective.  Used too early in the process, and any positive effect may be washed away by the mild natural history of the disease in most.
Part of the discomfort for the medical community lies in an aversion to dead ends in these battles.  But as any detailed analysis of medical progress will clarify – the forward march of science is messy.  Thalidomide, the drug responsible for the FDA as we now know it, eventually found use in patients with multiple myeloma.
The current approach is also paternalistic to the extreme.  Patients dying of their disease may choose to enter a randomized control trial where they have a 50% chance of being placed on a “sugar pill”.  But I question the ethics of denying patients an active drug unless they choose to enter this flip-of-a-coin lottery.  As Fauci himself noted, the AIDS fight taught the NIH the importance of working with the community.
“When the gay activists were demonstrating, predominantly against the FDA but also against the NIH, and being very strident in their criticism, I challenged them. I said, “Okay, come on in, sit down, and let’s talk about it. What is it that you want?” That was when we developed relationships with them that are now very productive. We have activists who are important members of our advisory councils. We consult back and forth with them all the time. AIDS changed the way we do business at NIH in that, when appropriate, the constituencies play a major role in some of the policy and decision-making processes. You cannot just cave in and let people tell you how to do science the wrong way, but there is a lot you can learn from understanding how the disease is affecting a particular population, somewhat removed from the bench, and removed from the “ivory towers” that we have here.”
Science turns out to be an imperfect war waged with many casualties.  Patients aren’t soldiers to be conscripted into this war.  If people are to die, they deserve agency if they are to be part of the scientific enterprise. Patients and their doctors deserve the right to choose paths that end up being dead ends.  Our job as doctors shouldn’t be to lean into the dichotomonia of positive and negative randomized control trials that frequently guides FDA approval. The AIDS struggle shows the chinks in the armor of the regulatory framework that keeps us safe, but in doing so risks keeping us from effective therapies.  While it shouldn’t take grave threats of the scale of AIDS and COVID19 to lower barriers to treatments, it would be stupidity on the scale of the current pandemic to not adapt regulatory barriers to the problems faced.
What the world needs months ago is a therapy for patients stricken with COVID19.  This would completely alter the public health response.  No need to self quarantine, little need to test the mildly symptomatic since most get better, and cruises would become great again.  A COVID-19 illness would prompt the same response as someone found to be actively ill with tuberculosis – not fun for close contacts, but no chance 16 million people would wake up in Italy to a quarantine.
The story of AIDS is a story of human ingenuity that should inspire hope for the COVID-19 pandemic.  Effective therapies will take time. Patients will die, but the deaths will not be in vain. Skeptics will rightly cast doubt on claims of success. They will be right most of the time. Regulatory frameworks will be appropriately challenged by the desperate. Conflicts of interest will be raised to question data.  The process will be messy and documented in a hypercritical manner by the Monday-morning journalists of the day. It will seem hopeless. But we will prevail despite the long odds because in the end, it will be those that remember the patients at the center of the storm that will show us the way forward.
It is always darkest just before the dawn.
Anish Koka is a cardiologist in practice in Philadelphia. He can be reached on Twitter @anish_koka
The post Pandemic Fears: What the AIDS Battle Should Teach Us About COVID-19 appeared first on The Health Care Blog.
Pandemic Fears: What the AIDS Battle Should Teach Us About COVID-19 published first on https://venabeahan.tumblr.com
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kristinsimmons · 5 years ago
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Pandemic Fears: What the AIDS Battle Should Teach Us About COVID-19
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By ANISH KOKA, MD
As the globe faces a novel, highly transmissible, lethal virus, I am most struck by a medicine cabinet that is embarrassingly empty for doctors in this battle.  This means much of the debate centers on mitigation of spread of the virus.  Tempers flare over discussions on travel bans, social distancing, and self quarantines, yet the inescapable fact remains that the medical community can do little more than support the varying fractions of patients who progress from mild to severe and life threatening disease.  This isn’t meant to minimize the massive efforts brought to bear to keep patients alive by health care workers but those massive efforts to support failing organs in the severely ill are in large part because we lack any effective therapy to combat the virus.  It is akin to taking care of patients with bacterial infections in an era before antibiotics, or HIV/AIDS in an era before anti-retroviral therapy.  
It should be a familiar feeling for at least one of the leading physicians charged with managing the current crisis – Dr. Anthony Fauci.  Dr. Fauci started as an immunologist at the NIH in the 1960s and quickly made breakthroughs in previously fatal diseases marked by an overactive immune response.  Strange reports of a new disease that was sweeping through the gay community in the early 1980’s caused him to shift focus to join the great battle against the AIDS epidemic. 
The first reported cases of AIDS were reported in the United States in the 1981 Morbidity and Mortality Weekly Report.  5 young men, all previously healthy and all active homosexuals were found to have Pneumocystis carinii pneumonia, a disease that prior had been restricted to the severely immunocompromised.  An avalanche of clinical reports subsequently woke the nation to a disease that appeared to have a predilection for the gay community.  The remarkable subsequent successes of medical therapies that followed to make AIDS a manageable disease to grow old with are now a matter of history, but in the early years this success seemed anything but inevitable.
The charge leveled against the establishment of the day by a public becoming aware of the tragedy of young, previously healthy individuals dying by the thousands was that there was an attempted cover up of a ‘dirty’ disease in a community America would rather not talk about.  But from the first description of the disease by the medical community, the activity in the research industry (both public and private) was intense.  It took 2 years for two labs to simultaneously identify the HIV virus that appeared responsible for the development of AIDS.  Elaborating the mechanism by which the virus destroyed the body’s immune system lead to the discovery of potential therapies. 
The first drug therapy with the most promise was AZT, or azidothymidine.  Remarkably this wasn’t a drug that was developed from scratch, it had been developed in the 1960’s by a US researcher to battle cancer.  The drug failed in mice and was set aside.  The problem with the drug wasn’t that it was ineffective, but that it was a solution without a problem. The drug was targeted to retroviruses that affected humans, but at the time of its development, there were no important retroviruses infecting humans.
The HIV virus turned out to be the problem AZT had been in search of.  HIV’s genetic information lives in a single strand of RNA that requires an enzyme called reverse trancriptase to transform into a double stranded DNA which then integrates into the host cell.  AZT is a thymidine analogue that works by selectively inhibiting the reverse transcriptase enzyme.  The company that had AZT, Burroughs-Wellcome, used the agent successfully in an animal model of a retrovirus surrogate, but that was not a specific model for HIV infection.  Fortuitously, the National Cancer Institute (NCI) had a model of immune cells (CD4) that they had developed to use as an antiviral assay for potential HIV therapies.  AZT was one of a promising group of drugs Burroughs-Wellcome sent to the NCI. The in-vitro results were impressive.  The HIV virus was unable to infect the CD4 cells in the presence of AZT.
The year was 1985.  It had taken four years since the first clinical report of the disease by the CDC to find a promising drug.  The time was intense.  There were 20,000 reported cases, and as many as a million people believed infected but asymptomatic.  Doctors were helpless, serving as witnesses to the eventual progression to death, rather than agents that could alter the the natural history of the disease. 
AIDS hospices were set up.  It was a terrible time, encapsulated by a haunting picture taken of AIDS activist David Kirby as he lay near death, cradled in his father’s arms.  It turns out that diagnosing a disease with no cure is its own desperate malady. 
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Identifying a drug that works in a lab was progress, but at the time, the FDA’s usual timeline for a drug to be judged safe and effective enough to be used in patients was 8-10 years.  Under intense pressure, the FDA fast-tracked everything. A phase 1 trial where the drug was injected into healthy volunteers to test for safety suggested symptoms at high doses, but a tolerable safety profile.  The next step mandated by the FDA was a double blind randomized control trial in patients with AIDS.  This meant half of the patients in the trial would get a placebo drug, while the other half would get AZT.  The trial was terminated early when 19 patients died in the placebo arm, but only 1 died in the AZT arm.  The study was published in the New England Journal of Medicine in 1987, six years after the first clinical report of AIDS, and rapidly approved by the FDA panel in the same year.
The trial was criticized for its early termination, and the entire fast-track process was challenged by skeptics who felt the FDA shouldn’t have bent to the wishes of activists.
Fauci was asked about pressure from activists and responded positively.
“No, actually it is difficult to say what was the right or wrong thing to do. It was a situation where there was only one drug available–it was not like trying out one amongst many antibiotics–and the activist community and the constituents were suffering. They demanded that they have access to anything that could give them even a little hope. Pressure was put on the FDA. They responded appropriately for rapid expedited approval of AZT, making drugs available that normally would not have been available for years and years.”
He went on to note that the British were able to complete a long term 3 year study of AZT that could never have been completed in the United States that showed no long term benefit.  Apparently AZT blessed patients with a brief reprieve, not a long term cure.  The investigators at the time had no way of knowing that the HIV virus mutated in response to the initial single agent therapy and eventually became resistant to the drug.  The initial doses used were also very high, and caused patients a number of well described side effects. Investigators since have learned to use lower doses of the drug to avoid the toxicities that plagued patients in the early years. 
Many in the scientific community were upset with the early approval of AZT, and prominent critics emerged comparing the drug to aspirin, as well as alleging financial interest in the drug approval.  The activists in the United States that pressured the scientific community were eventually proven right. The desperation of the dying patients in the early years is well represented in the movie starring Matthew McConaughey – The Dallas Buyers Club.  Unwilling to be randomized to the placebo arm of the AZT trial, the character played by McConaughey flees to Mexico, only to be prescribed a cocktail of vitamins by an unlicensed expatriate US doctor.  The movie butchers the actual history by constructing the well-worn conspiracy narrative of a pharmaceutical company terminating a trial early to foist a dangerous drug (AZT) onto the public.  What’s correct is that the community wanted hope in the form of some drug, and every day that a therapy was delayed was paid in lives lost.  Ultimately the public pressure to get AZT out into the community was the right decision.  A longer trial may very well have been negative, and subsequent non-approval may very well have confined the use of the drug to Mexican black market clinics and unlicensed doctors until the biology of the virus was better understood.  There would have been no winners in that scenario.
There are important lessons to heed as the global biotech community races to cure doctors of their impotence when faced with a patient dying of the COVID-19 virus.  Once a drug proves promising in-vitro, the same FDA will stand guard.  Randomized control trials are planned to test these drugs for efficacy against the novel coronavirus.  The emergency will certainly lubricate the timeline of approval  just as it did with the AIDS epidemic, but a great deal of caution is to be advised in designing and interpreting trials where the patients range from mild symptoms with recovery with no intervention, to severely ill in intensive care units. Use a novel therapy too late, and a drug effective when used earlier may look ineffective.  Used too early in the process, and any positive effect may be washed away by the mild natural history of the disease in most.
Part of the discomfort for the medical community lies in an aversion to dead ends in these battles.  But as any detailed analysis of medical progress will clarify – the forward march of science is messy.  Thalidomide, the drug responsible for the FDA as we now know it, eventually found use in patients with multiple myeloma.
The current approach is also paternalistic to the extreme.  Patients dying of their disease may choose to enter a randomized control trial where they have a 50% chance of being placed on a “sugar pill”.  But I question the ethics of denying patients an active drug unless they choose to enter this flip-of-a-coin lottery.  As Fauci himself noted, the AIDS fight taught the NIH the importance of working with the community.
“When the gay activists were demonstrating, predominantly against the FDA but also against the NIH, and being very strident in their criticism, I challenged them. I said, “Okay, come on in, sit down, and let’s talk about it. What is it that you want?” That was when we developed relationships with them that are now very productive. We have activists who are important members of our advisory councils. We consult back and forth with them all the time. AIDS changed the way we do business at NIH in that, when appropriate, the constituencies play a major role in some of the policy and decision-making processes. You cannot just cave in and let people tell you how to do science the wrong way, but there is a lot you can learn from understanding how the disease is affecting a particular population, somewhat removed from the bench, and removed from the “ivory towers” that we have here.”
Science turns out to be an imperfect war waged with many casualties.  Patients aren’t soldiers to be conscripted into this war.  If people are to die, they deserve agency if they are to be part of the scientific enterprise. Patients and their doctors deserve the right to choose paths that end up being dead ends.  Our job as doctors shouldn’t be to lean into the dichotomonia of positive and negative randomized control trials that frequently guides FDA approval. The AIDS struggle shows the chinks in the armor of the regulatory framework that keeps us safe, but in doing so risks keeping us from effective therapies.  While it shouldn’t take grave threats of the scale of AIDS and COVID19 to lower barriers to treatments, it would be stupidity on the scale of the current pandemic to not adapt regulatory barriers to the problems faced.
What the world needs months ago is a therapy for patients stricken with COVID19.  This would completely alter the public health response.  No need to self quarantine, little need to test the mildly symptomatic since most get better, and cruises would become great again.  A COVID-19 illness would prompt the same response as someone found to be actively ill with tuberculosis – not fun for close contacts, but no chance 16 million people would wake up in Italy to a quarantine.
The story of AIDS is a story of human ingenuity that should inspire hope for the COVID-19 pandemic.  Effective therapies will take time. Patients will die, but the deaths will not be in vain. Skeptics will rightly cast doubt on claims of success. They will be right most of the time. Regulatory frameworks will be appropriately challenged by the desperate. Conflicts of interest will be raised to question data.  The process will be messy and documented in a hypercritical manner by the Monday-morning journalists of the day. It will seem hopeless. But we will prevail despite the long odds because in the end, it will be those that remember the patients at the center of the storm that will show us the way forward.
It is always darkest just before the dawn.
Anish Koka is a cardiologist in practice in Philadelphia. He can be reached on Twitter @anish_koka
The post Pandemic Fears: What the AIDS Battle Should Teach Us About COVID-19 appeared first on The Health Care Blog.
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