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MIS-C Shares Host Immune Responses with COVID-19 and Kawasaki Disease

A subset of children infected by the SARS-CoV-2 virus suffers from multisystem inflammatory syndrome in children (MIS-C) which shares clinical features…

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A child’s positive COVID-19 test may come as a surprise to parents, given that a SARS-CoV-2 infection may cause very mild, or even no, symptoms in children. While many children do not suffer severe COVID-19 disease, a subset experience the serious complication known as Multisystem Inflammatory Syndrome in Children (MIS-C), which sends many pediatric patients to intensive care. Presenting 4–6 weeks after infection, the inflammatory condition is marked by abdominal pain, headaches, rashes, and vomiting, and shares many clinical features with the pre-pandemic syndrome of Kawasaki disease (KD).

Kawasaki disease has puzzled pediatricians for more than 50 years. MIS-C and KD share many symptoms though KD disease can also lead to coronary artery aneurysms and heart attack. Unlike MIS-C, which is associated with a specific virus, KD may be triggered by a variety of infectious and environmental stimuli.

To better understand how these inflammatory syndromes compare, researchers collected blood and tissue samples from MIS-C and KD patients. Using artificial intelligence tools, they analyzed patterns of gene expression in both conditions and compared them to gene expression markers of COVID-19.

The study reveals that MIS-C and KD are on the same immune response continuum as COVID-19, with MIS-C being a more severe version of the response than KD. Despite these underlying similarities, the conditions diverge in several laboratory and clinical parameters. The authors said the findings could improve disease diagnosis, monitoring, and treatment in pediatric patients.

This work is published in Nature Communications in the article, “An artificial intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease.

“We want our immune system to protect us from harmful stimuli, but some children are genetically predisposed to respond more intensely, leading to inflammation and unwanted symptoms across the body,” said Jane C. Burns, MD, a pediatrician at Rady Children’s Hospital-San Diego and director of the Kawasaki Disease Research Center at University of California, San Diego (UCSD), School of Medicine. “The sooner we can identify and understand the child’s inflammatory condition, the better we can tailor our delivery of life-saving support.”

This study was led by University of California, San Diego, School of Medicine researchers Pradipta Ghosh, MD, (left), Jane C. Burns, MD, (center), and Debashis Sahoo, PhD (right). [UC San Diego Health Sciences]
The research team previously identified a set of 166 genes expressed in viral respiratory diseases—including COVID-19—a subset of which also corresponded to disease severity. Researchers found that this same “gene signature” also applied to both MIS-C and KD, suggesting the conditions all stem from a similar underlying mechanism, which involves the rapid release of IL15/IL15RA cytokines.

In this work, they used a computational toolbox of two gene signatures that were developed in the context of SARS-CoV-2 infection. The first was a viral pandemic (ViP) signature and the second was a 13-transcript signature previously demonstrated to be diagnostic for KD.

The team found that a computer program trained to look for this genetic signature could not tell the KD and MIS-C samples apart and that KD and MIS-C are on the same continuum of the host immune response as COVID-19.

“We were not expecting that,” said Pradipta Ghosh, MD, professor of medicine and cellular and molecular medicine at UCSD School of Medicine. “We analyzed MIS-C and KD through the lens of two distinct gene signatures, and both experiments told us these diseases are closely related.”

Ghosh said the two gene signatures likely represent different parts of the same broader immune response.

More specifically, they showed that both of the pediatric syndromes (KD and MIS-C) “converge upon an IL15/IL15RA-centric cytokine storm, suggestive of shared proximal pathways of immunopathogenesis; however, they diverge in other laboratory parameters and cardiac phenotypes.”

UCSD researchers summarize the similarities and differences between COVID-19, MIS-C, and Kawasaki disease, three conditions unified by the same immune-associated gene signature. [UCSD Health Sciences]
While the study provides a new unifying framework for these diseases, it also identifies a few subtle differences. For example, MIS-C patients had lower blood platelet and eosinophil counts, two features that can be measured from routine blood tests. And, while many serum cytokines were similarly elevated in both conditions, a select few were more elevated in MIS-C than in KD samples.

Therapeutics targeting some of these cytokines, including TNFα and IL1β, have already been approved by the FDA and are being tested as novel treatments for MIS-C.

“We believe our findings have a high potential to impact clinical trial planning immediately, and also shape clinical guidelines and patient care down the line,” said Debashis Sahoo, PhD, associate professor of pediatrics and computer science at UCSD School of Medicine and UCSD Jacobs School of Engineering.

The post MIS-C Shares Host Immune Responses with COVID-19 and Kawasaki Disease appeared first on GEN - Genetic Engineering and Biotechnology News.

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Government

Cruise Line Drops Pre-Cruise Covid Testing Rule

The major cruise lines walk a delicate line. They need to take the actual steps required to keep their passengers safe and they also need to be aware of…

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The major cruise lines walk a delicate line. They need to take the actual steps required to keep their passengers safe and they also need to be aware of how things look to the outside public. It's a mix of practical covid policy balanced with covid theater.

You have to do the right thing -- and Royal Caribbean International (RCL) - Get Royal Caribbean Group Report, Carnival Cruise Lines (CCL) - Get Carnival Corporation Report, and Norwegian Cruise Lines (NCLH) - Get Norwegian Cruise Line Holdings Ltd. Report have been doing that with very meticulous protocols-- but you also have to show the general public you're taking the pandemic seriously. The cruise industry has been under the microscope of both public perception and the Centers for Disease Control (CDC) since covid first appeared.

That's not because you're likely to get infected on a cruise ship than at a concert, sporting event, theme park, restaurant, or any other crowded space. It's because when you get sick at one of those locations nobody can pinpoint the source of your infection

Cruises last from 3 days to 7 days or even longer and that means that some people will get covid onboard and that will be blamed on the cruise industry. To mitigate that Carnival, Royal Caribbean, and Norwegian have rigid protocols in place that require passengers 12 and over to be vaccinated as well as pre-cruise covid tests taken no more than two days before your cruise leaves.

Once cruise line has dropped that testing requirement (at least on a few sailings) and that could lead Royal Caribbean, Carnival, and Norwegian to follow. 

Sina Schuldt/picture alliance via Getty

Holland America Drops Some Covid Testing

As the largest cruise lines sailing from the U.S., Royal Caribbean, Carnival, and Norwegian don't want to be the first to make major covid policy changes. They acted more or less in tandem when it came to loosening, then dropping mask rules and have generally followed the lead of the CDC, even when that agency's rules became optional.

Now, Holland America cruise line has dropped pre-cruise covid testing on a handful of cruises. It's a minor move, but it does provide cover and precedent for Royal Caribbean, Carnival, and Norwegian to eventually do the same.

"Holland America Line becomes the first US-based cruise line to remove testing for select cruises. Unfortunately for those taking a cruise from the United States, the new protocols are only in place for certain cruises onboard the company’s latest ship, the Rotterdam, in Europe," Cruisehive reported.

The current CDC guidelines do recommend pre-cruise testing, but the cruise lines into following those rules. By picking cruises sailing out of Europe, Holland America avoids picking a fight with the federal agency just yet, but it will be able to gather data as to whether the pre-cruise testing actually helps.

Holland America has not changed its vaccination requirements for those cruises which mirror the 12-and-up rule used by Royal Caribbean, Carnival, and Norwegian.

Some guests have called for the end of the testing requirement because they believe it's more theater than precaution because people can test and then contract covid while traveling to their cruise.

The Current Cruise Protocols Work

Royal Caribbean President Michael Bayley does expect changes to come in his cruise line's covid protocols, and he talked about them during Royal Caribbean's recent President's Cruise, the Royal Caribbean Blog reported.

"I think pre cruise testing is going to be around for another couple of months," Bayley told passengers during a question and answer session. "We obviously want it to go back to normal, but we're incredibly cognizant of our responsibilities to keep our crew, the communities and our guests safe."

People do still get covid onboard despite the crew being 100% vaccinated and all passengers 12 and over being vaccinated, but the protocols have worked well when it comes to preventing serious illness.

Bayley said that the CDC shared some information with him in a call.

"The cruise industry sailing out of the US ports over the past 12 months and how many people have been hospitalized with Covid and how many deaths occurred from Covid from people who'd sailed on the industry's ships, which is in the millions," he said, "And the number of people who died from COVID who'd sailed on ships over the past year was two."

That success may be why the major cruise lines are reluctant to make changes. The current rules, even if they're partially for show, have been incredibly effective.

"Two is terrible. But but but against the context of everything we've seen, that's it's truly been a remarkable success." he added.

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Government

The Insufferable Arrogance Of The Constantly Wrong

The Insufferable Arrogance Of The Constantly Wrong

Authored by Clayton Fox via The Brownstone Institute,

The media, and the people who work…

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The Insufferable Arrogance Of The Constantly Wrong

Authored by Clayton Fox via The Brownstone Institute,

The media, and the people who work in and around it, the Blue Checks™ of Twitter, have upped the ante over the past few years regarding how far they are willing to go to enforce various preferred narratives. 

Pick any major story of the past three years - e.g. Lab LeakJussie SmollettRussiagateUkrainian BiolabsIvermectinHospitalizations From COVID v. With CovidJanuary 6th‘Transitory’ Inflation, and of course Hunter’s Laptop - and you will find absolutely hysterical narrative pushing up front followed by retractions, corrections, and outright denials as reality became undeniable. 

In the meanwhile, our civilization was ripped apart, our citizens were gaslit and impoverished, and in countries across the Western world, innocent people were removed from polite society, branded as lepers, and fired from their jobs. 

Why? Because there is one story that just won’t die and for which no corrections have been issued - the shibboleth that vaccination can prevent infection, transmission, and help “end” COVID.

While there is never an excuse for hateful rhetoric towards, and intervention in, the personal medical choices of law-abiding Americans, perhaps one could have, kinda sorta, understood the campaign if the new vaccines had provided long-lasting immunity and prevented community transmission. They do not. 

Early on we were told: “Nine out of ten [vaccinated] people won’t get sick” (Columbia University feat. Run-DMC, February 12th, 2021, no this is not a joke); “Vaccinated people do not carry the virus, don`t get sick” (Dr. Rochelle Walensky, March 29th, 2021); “When people are vaccinated, they can feel safe that they are not going to get infected” (Dr. Anthony Fauci, May 17th, 2021). 

And by mid-summer, 2021, we were still being told that unequivocally, these vaccines were a resounding success worthy of uncritical support. On July 27th in Scientific American, Dr. Eric Topol wrote, “Vaccination is the closest thing to a sure thing we have in this pandemic.” Not to be outdone, Dr. Anthony Fauci of the NIAID told CBS on August 1st, that the unvaccinated were responsible for “propagating this outbreak.” 

But on July 29th, 2021, the Washington Post reported a scoop that the CDC was privately acknowledging that the vaccinated could spread COVID as easily as the unvaccinated. Occasionally, they are forced to report inconvenient facts. And August 5th, CDC Director Walensky told CNN’s Wolf Blitzer that, “They continue to work well for Delta, with regard to severe illness and death — they prevent it. But what they can’t do anymore is prevent transmission.”

While there is a mountain of medical literature available demonstrating quite clearly the failure of these vaccines to prevent infection and transmission, the August 5th declaration from the CDC Director should have made clear that being vaccinated is contributing in no way to the safety of others, nor to the eradication of this virus. 

In fact, Israeli Health Minister Nitzan Horowitz was even caught on tape in September of last year explaining that the use of the Israeli Green Pass wasn’t intended to make a difference epidemiologically, but because it would help convince people to get vaccinated. And even vaccine poobah Bill Gates admitted in a late 2021 interview, that, “We got vaccines to help you with your health, but they only slightly reduce the transmissions.”

So there should be no question that continuing to suggest in any way that these shots are a panacea, and that those who refused to get them were plague spreaders, should have been thoroughly trashed by Fall 2021. 

Nonetheless, on September 24th President Joe Biden coined his now famous phrase “a pandemic of the unvaccinated.” To our north, Prime Minister Trudeau called the unvaccinated science deniers, misogynists, and racists, and asked rhetorically whether Canadians should “tolerate” them. 

And during the first week of January 2022, while kicking the unvaccinated out of French daily life and public spaces, French President Emmanuel Macron said he wanted the measures to “piss off” his unvaccinated citizens. With world leaders speaking this way, it’s no wonder so many Blue Check™ elites took up the banner! 

Prominent media figures like Amy Siskind, Pulitzer Prize winner Gene Weingarten, and more have come out of the woodwork in recent months to share with us their enthusiasm for medical discrimination. Noted neurotic Howard Stern is all in on forced vaccination due to what must be his own debilitating fear of his mortality. Bill Kristol says the unvaccinated have “blood on their hands.” 

David Frum, heir to Maimonides, writes, “Let the hospitals quietly triage emergency care to serve the unvaccinated last.” Charles M. Blow was “furious” at the unvaccinated. CNN contributor Dr. Leana Wen suggested that the unvaccinated should not be allowed to leave their homes. The Ragin’ Cajun even wants to punch the unvaccinated in the face! 

All of the above links/stories were posted after Dr. Walensky’s unequivocal announcement that the vaccines do not prevent transmission. 

And all of the self-satisfied segregationists are supported in their vitriol by the Blue Checks™ of the Medical Establishment, like Dr. Paul Klotman, President and Executive Dean of the Baylor School of Medicine, who said on camera back in January that he isn’t polite to friends and family who aren’t vaccinated. “Keep them away. I don’t do it respectfully, I tell them to stay away, and teach them a lesson.” Less vitriolic but equally problematic, the WHO’s COVID-19 “technical lead” Dr. Maria Van Kerkhove continued to push the lie that vaccination can prevent outbreaks as recently as January 26th, 2022. She is, as well, a Blue Check™. And yes, Dr. Anthony Fauci is still at it, even as of April 14th, 2022, telling MSNBC that harsh Chinese lockdowns could be used to get the population vaccinated so that “When you open up, you won’t have a surge of infections.” 

The examples are legion. Blue Checks, Medical Blue Checks, Times Columnists, Radio Jocks, Presidents, and Prime Ministers have all espoused misinformation and/or hate speech regarding vaccination status. But they are all given intellectual cover by the official reporting of the fourth estate. Even in the face of all the evidence that there is no epidemiological basis for discrimination, our intellectual betters in the legacy media press onward the canard. 

On August 26th, the Toronto Star ran an article entitled, “When it comes to empathy for the unvaccinated, many of us aren’t feeling it.” Then, on December 22nd, published an explainer which stated that two doses won’t stop you from spreading COVID-19. Comme ci, comme ca. 

Back in February, MSNBC political contributor Matthew Dowd shared his insight that the unvaccinated do not believe in the United States Constitution, because if they did, they would get vaccinated for “We The People.” For the common good. 

An examination of the New York Times reveals three articles written this year which overtly continue supporting the idea that the vaccines prevent transmission. First, on January 29th in a piece entitled, “As Covid Shots For Kids Stall, Appeals Are Aimed At Wary Parents,” the author cites “public health officials” who say that to aid in “containing” the pandemic, kids must also be vaccinated. (It is worth mentioning that the current vaccines and boosters being distributed were designed in February 2020 to provide an immune response to a version of the SARS-CoV-2 spike protein circulating prior to that, not entirely similar to what is circulating now.)

Then February 23rd, in a hit piece on the Surgeon General of Florida Dr. Joe Ladapo, the Times writes, “When public health officials across the country were urging vaccines as a way to end the pandemic, Dr. Ladapo was raising warning flags about possible side effects and cautioning that even vaccinated people could spread the virus.” 

So, Dr. Ladapo was correct? 

Finally, in a piece about Novak Djokovic published March 3rd, they write, “Djokovic was the only player ranked in the top 100 in Australia who had not received a Covid-19 vaccination, which experts have long said will not eradicate the virus unless most of the population receives one.” 

They do not address the question of how a vaccine which does not prevent transmission can eradicate a virus. And they won’t. As Israeli Health Minister Horowitz candidly admitted, none of this is about epidemiology. 

And even when mainstream media tacitly acknowledges the failures of the vaccines to prevent transmission, they skillfully elide the significance of this fact in order to allow them to continue to scapegoat the unvaccinated. In a dazzling display of sophistry, Time Magazine moved the Overton window in this January 12th, 2022 piece, “These Charts Show That COVID-19 Is Still A Pandemic of the Unvaccinated.” 

The author states that due to the rapidly narrowing gap between cases in the vaccinated and unvaccinated, some readers might think that the phrase “pandemic of the unvaccinated” is no longer justifiable. But with the grace of a ballerina, Time goes on to tell us that because the vaccines are still showing efficacy against severe illness, the phrase is still kosher. If an unvaccinated person gets sicker than his vaccinated neighbor who contracted COVID at a fully vaccinated wedding, that unvaccinated person is still the problem!

New York Magazine isn’t lacking in similar gymnastics. On February 16th of this year, Matt Stieb published a piece entitled, “Is Kyrie Irving Going to Get Away With It?” Irving is the Brooklyn Nets player who famously chose not to be vaccinated, and has become a fetish object for the Covidian Left. Stieb acknowledges that Irving’s vaccinated teammates were getting COVID at such high rates that it forced Nets management to allow Irving back to play in away games but still calls the New York City ban on unvaccinated athletes “a rare public health mandate with real teeth.” 

Just seven days later on February 23rd, Will Leitch, in the same publication, sighs, “Unfortunately, It’s Time to Let Kyrie Irving Play in New York.” He outlines all the reasons why epidemiologically it makes no sense to prevent athletes like Irving and Novak Djokovic from participating, but says, “It would feel like they got away with all their bullshit.” And also, they are “annoying.” 

And this barely concealed hatred for the unvaccinated from media and government and Big Tech—even in the rare moments when writers such as Leitch acknowledge the failure of the vaccines to prevent transmission—has real consequences. People have lost their jobs. People have been arrested for trying to go to a movie theater. 

Families got kicked out of restaurants, and patrons either cheered or remained indifferent, which is worse. A teenage boy at an uber-progressive and expensive Chicago prep school committed suicide after being bullied over an incorrect rumor he was unvaccinated. The stench of bad journalism rots people’s basic decency. 

A January Rasmussen poll found that, Fifty-nine percent (59%) of Democratic voters would favor a government policy requiring that citizens remain confined to their homes at all times, except for emergencies, if they refuse to get a COVID-19 vaccine…Forty-five percent (45%) of Democrats would favor governments requiring citizens to temporarily live in designated facilities or locations if they refuse to get a COVID-19 vaccine…”

As well as, “Twenty-nine percent (29%) of Democratic voters would support temporarily removing parents’ custody of their children if parents refuse to take the COVID-19 vaccine.” Unfortunately, these disturbing results are politically lopsided, but it’s no surprise when you consider who the readers of most legacy media platforms are. 

The saddest thing is that these media outlets and their flag bearers really think their readers are all morons. The New York Times believes that, in the midst of the Omicron wave as boosted person after boosted person was getting COVID, they could tell you these particular vaccines are still the way to eradicate this thing, and expect you to deny reality and nod your head. 

It calls to mind the quote attributed to Solzhenitsyn (or Elena Gorokhova), “The rules are simple: they lie to us, we know they’re lying, they know we know they’re lying, but they keep lying to us, and we keep pretending to believe them.”

We have ceded the better angels of our common cerebrum to people who may not have our best interests at heart, and a sycophantic laptop class who gleefully endorses their diktats and “fact-checks.” Collectively: Sophistry Inc. 

Their behavior, endorsed by every single entity which holds power in our society, is destroying us, and has already poisoned us such that there may be no antidote. Yes, first they came for the unvaccinated, but that doesn’t mean they won’t come for you next.

Tyler Durden Fri, 07/01/2022 - 22:20

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Spread & Containment

UTSW researchers develop rapid COVID-19 test to identify variants in hours

*Click here to watch “The hunt for COVID-19 variants” video Credit: UT Southwestern Medical Center *Click here to watch “The hunt for COVID-19 variants”…

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*Click here to watch “The hunt for COVID-19 variants” video

Credit: UT Southwestern Medical Center

*Click here to watch “The hunt for COVID-19 variants” video

 

Last year, pathologist Jeffrey SoRelle, M.D., and colleagues developed CoVarScan, a rapid COVID-19 test that detects the signatures of eight hotspots on the SARS-CoV-2 virus. Now, after testing CoVarScan on more than 4,000 patient samples collected at UT Southwestern, the team reports in Clinical Chemistry that their test is as accurate as other methods used to diagnose COVID-19 and can successfully differentiate between all current variants of SARS-CoV-2. 

“Using this test, we can determine very quickly what variants are in the community and if a new variant is emerging,” said Dr. SoRelle, Assistant Professor of Pathology and senior author of the study. “It also has implications for individual patients when we’re dealing with variants that respond differently to treatments.”

The testing results at UT Southwestern’s Once Upon a Time Human Genomics Center have helped public health leaders track the spread of COVID-19 in North Texas and make policy decisions based on the prevalence of variants.  Doctors have also used the results to choose monoclonal antibodies that are more effective against certain strains infecting critically ill COVID-19 patients.

While a number of other tests for COVID-19 exist, they generally detect either a fragment of SARS-CoV-2 genetic material or small molecules found on the surface of the virus, and don’t provide information to identify the variant. In addition, many researchers worry that these tests aren’t accurate in detecting some variants – or may miss future strains. To determine which variant of COVID-19 a patient has, scientists typically must use whole genome sequencing, which is time-consuming and expensive, relying on sophisticated equipment and analysis to spell out the entire RNA sequence contained in the viruses.

In early 2021, Dr. SoRelle and his colleagues at UT Southwestern wanted to track how well current tests were detecting emerging variants of SARS-CoV-2. But they realized that sequencing a lot of specimens would not be timely or cost-effective, so they designed their own test, working in the McDermott Center Next Generation Sequencing Core, part of the Eugene McDermott Center for Human Growth and Development directed by Helen Hobbs, M.D., Professor of Internal Medicine and Molecular Genetics.

CoVarScan hones in on eight regions of SARS-CoV-2 that commonly differ between viral variants. It detects small mutations – where the sequence of RNA building blocks varies – and measures the length of repetitive genetic regions that tend to grow and shrink as the virus evolves. The method relies on polymerase chain reaction (PCR) – a technique common in most pathology labs – to copy and measure the RNA at these eight sites of interest. 

To test how well CoVarScan works, Dr. SoRelle’s team ran the test on more than 4,000 COVID-19-positive nasal swab samples collected at UT Southwestern from April 2021 to February 2022 – from patients both with and without symptoms. The tests were validated with the gold-standard whole genome sequencing, and the results were used by doctors to choose treatments in some critically ill COVID-19 patients.  

Compared to whole genome sequencing, CoVarScan had 96% sensitivity and 99% specificity. It identified and differentiated Delta, Mu, Lambda, and Omicron variants of COVID-19, including the BA.2 version of Omicron, once known as “stealth Omicron” because it did not show up on some tests designed to detect only the Omicron strain.

“A common critique of this kind of test is that it requires constant adjustment for new variants, but CoVarScan has not needed any adjustment in more than a year; it is still performing very well,” said Dr. SoRelle. “In the future, if we did need to adjust it, we could easily add as many as 20 or 30 additional hotspots to the test.”

Dr. SoRelle plans to continue developing CoVarScan as a commercial test and has a pending patent application based on this work. As the inventor of the genotyping PCR test for variants, Dr. SoRelle is entitled to income from its use.

Other UTSW researchers who contributed to this study include Andrew Clark, Zhaohui Wang, Emily Ostman, Hui Zheng, Huiyu Yao, Brandi Cantarel, Mohammed Kanchwala, Chao Xing, Li Chen, Pei Irwin, Yan Xu, Dwight Oliver, Francesca Lee, Jeffrey Gagan, Laura Filkins, Alagarraju Muthukumar, Jason Park, and Ravi Sarode.

Dr. Hobbs holds the 1995 Dallas Heart Ball Chair in Cardiology Research, the Philip O’Bryan Montgomery, Jr., M.D. Distinguished Chair in Developmental Biology, and the Eugene McDermott Distinguished Chair for the Study of Human Growth and Development. Dr. Sarode holds the John H. Childers, M.D. Professorship in Pathology.

 

 

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 17 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.


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