Results 24,551 to 24,575 of 41810
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08-05-2020, 01:13 PM #24551
Just saw this posted by a former client about a former client....
https://news.illinois.edu/view/6367/...V27Y54c7Q3uLT4
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08-05-2020, 01:15 PM #24552
Mail in voting also negates the GOP strategy of closing polling places where young, poor, and minority people vote and ending or decreasing early voting.
I guess a lot of GOP leaders are worrying that Trump smearing vote by mail will drive down Republican turnout more than Democratic. Hence Trump saying it's ok for Florida to vote by mail, but not anywhere else, because we all know how honest and reliable Florida's electoral system is. (Al Gore must be rolling in his grave.)
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08-05-2020, 01:26 PM #24553“I tell you, we are here on Earth to fart around, and don't let anybody tell you different.”
― Kurt Vonnegut, A Man Without a Country
www.mymountaincoop.ca
This is OUR mountain - come join us!
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08-05-2020, 01:27 PM #24554
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08-05-2020, 01:29 PM #24555
I don't buy the enthusiasm gap. The way the polling is done--yes Trump voters are more enthusiastic about voting for Trump than Biden voters are about voting for him. (I'm not enthusiastic at all about voting for Biden). But Biden voters are extremely enthusiastic about voting against Trump and if people have to stand in long lines to do it they will.
The most worrisome thing is that in swing states currently controlled by Republicans an electoral "mistrial" could be declared and the legislature and/or governor could appoint electors, ignoring the outcome of the vote. By the time that made it through the courts the electors would already have voted for Trump and the courts would be faced with overturning the results of the Electoral College vote.
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08-05-2020, 01:39 PM #24556
I agree that would be less than ideal, and I expect they don't want to hide their faces, either, right? I think there's a solution that should be explored for that circumstance: basically "sealing" the shield to the wearer's face with a filter. PM me if you're interested in really going into the weeds on that.
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08-05-2020, 01:39 PM #24557click here
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I see. Too bad. Also, I don't count subsidies as discount to the price. Money is money. If the government pays the $50/test, it's still about $50 too expensive to use daily. If 300 million do a daily test, that's $15B per day. $0.45T per month, less if we don't test weekends. Seems too expensive, though it's a little cheaper than the economic hit from Corona so far.
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08-05-2020, 01:45 PM #24558
I agree with you about the desire to vote against being stronger than the desire to vote for--definitely our present pattern. In the case of analyzing GOP tactics, though, these days hope is a plan, and they're not being led by people who want to look at that second layer.
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08-05-2020, 01:47 PM #24559
making voting easier is considered to benefit democrats because there are more registered democrats than republicans
if every democrat voted there would be far fewer or no republicans in office
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08-05-2020, 01:47 PM #24560
1 in 5.
. This week, 46% of Americans know someone who has tested positive for the coronavirus – half of whom (23% of all Americans) know someone in their community who has tested positive.
Almost one in five (18%) Americans know someone who has died from the coronavirus. Black (31%) and Hispanic (28%) Americans continue to be more likely to know someone who has died of coronavirus compared to white (13%) Americans.
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08-05-2020, 02:00 PM #24561
Thanks for posting. Wouldn't be my first choice of strategies to attack this thing for a few reasons. Producing and formulating the protein for therapeutic use could be challenging. It's a receptor which means it likes to live in cell membranes which cannot be part of the drug. So you have to produce a smaller portion of the protein that maintains comparable affinity (as the in tact receptor) for covid ... that could be very challenging. Second, if you put the decoy into humans, the possibility exists that you will bind up all the soluble angiotensin in your circulation and disrupt the intricate regulation of blood volume and pressure. Finally, the antibody therapies being developed by REGN should be every bit as effective as a decoy receptor. They will have optimized PK and a clear path for manufacturing, purification and regulatory.
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08-05-2020, 02:03 PM #24562
Immunology lesson time folks. Expertly written for this crowd.
https://www.theatlantic.com/health/a...ystery/614956/
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08-05-2020, 02:59 PM #24563
Actually making the soluble ACE2 receptor proved to be dead easy, we obtained well over 300 mg/L of active materal without any expression optimization. The FL protein is ~805 aa but the membrane tether in the the C-terminal 100 aa and does not contribute to the binding site; the RBD binding site on ACE2 is also non-overlapping with the receptor's proteolytic domain for AngII cleavage. But making something functional is much easier than the path to clear regulatory for an injectable protein biological.
Soluble ACE2 has been floated as a complement to Angiotensin Receptor Blockers for ARDS as it does more than down-regulate AngII signaling, but actually promotes counter-effects mediated through Ang1-7/ATRII and MAS receptors. More than acting as a decoy for the virus, modulating the cytokine mileu may be crucial for allowing adaptive immune responses to trend toward resolution of infection instead of exacerbation.
RE: Mab's. From our own Spike-trimer immunizations, we got close to 20 Mab's clonally selected and purified that block RBD binding to ACE2 and show strong neutralization in conventional VNT assays. I would expect multiple groups putting forth Mab therapies in the next 6mos.
An assay based on ACE2/RBD blockade to measure neutralizing Ab's was just published last week in Nature Biotechnology. In their reported assay, neutralizing Ab's from SARS-1 patients were still present 17 yrs later. https://www.nature.com/articles/s41587-020-0631-zMove upside and let the man go through...
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08-05-2020, 03:25 PM #24564
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08-05-2020, 06:11 PM #24565
I'm with Huckbucket. It seems to me that the potential for a decoy ACE2 receptor to wreak havoc on the renin-angiotensin system is high. I think you would have to do a lot of animal studies to prove its safety before you could begin to test in humans for efficacy. Monoclonal Ab seems a lot cleaner.
A quick Pubmed search for ARBs for ARDS seems to show maybe benefit--retrospective, mortality rates the same with and without, but after survival analysis, whatever that is, better survival in the treated group. I don't follow the statistics.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786717/
Is there better data?
I don't see any clinical data on soluble ACE2 for ARDS.
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08-05-2020, 06:12 PM #24566
To think somewhere, some anti-vaxxer that lacks a highschool diploma is saying to themself, well based on my “research” this vaccine is dangerous! And I have the right to decide what I do with my body. #mybodymychoice
Thanks for what you do Mofro, Lego, Huck, and the rest of the scientists and medical community that is fighting this thing.
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08-05-2020, 06:25 PM #24567
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08-05-2020, 06:39 PM #24568
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08-05-2020, 06:46 PM #24569
It would seem that an unbalanced RAS may be an underpinning for inflammatory states.
Many animal studies have been conducted with hACE2 transgenics, and human studies per recent review, An update on ACE2 amplification and its therapeutic potential.
Human recombinant ACE2 has been evaluated in human subjects in limited clinical studies.The pharmacokinetics, pharmacodynamics, safety, and tolerability of hrACE2 were determined in healthy volunteers 71. This study was randomized, double-blind, and placebocontrolled. -In addition to showing good tolerability of hrACE2 (1-740 AA) by healthy human subjects, this study revealed a suppression of systemic Ang II levels both by single and repeated dosing of hrACE271. Since ACE2 has been implicated in animal models of acute lung injury68,72 it was postulated that administration of hrACE2 could attenuate acute lung injury in human subjects with ARDS73. In patients with acute respiratory distress syndrome (ARDS) hrACE2 (GSK2586881) was well tolerated 73. Human rACE2 caused a decrease of circulating Ang II levels 73 whereas angiotensin (1-5) and angiotensin (1-7) levels were increased and continued elevated for 48 h73. In this exploratory study registered under ClinicalTrials.gov, NCT01597635, surfactant protein D (SP-D) which is considered a beneficial biomarker contributing to normal surfactant structure and inhibition of inflammatory response was increased in hrACE2-treated subjects compared with placebo. However, hrACE2 infusions did not result in improvement in other physiological or clinical measures of ARDS in this small study and the trial was terminated early73.
Encouraging but still very preliminary findings were drawn from a recent phase IIa, open label pilot study which suggested a potential therapeutic role for hrACE2 in pulmonary arterial hypertension 74. This study found a reduced plasma ACE2 activity in subjects with PH. This was inferred, from higher plasma Ang II to Ang (1-7) ratio however, the ratio is not specific as it can potentially be affected by changes in other enzymes that affect the conversion of Ang II to Ang (1-7). At baseline in subjects with PH, increased expression in six out of nine measured cytokines as compared with controls (interleukin (IL)-10, IL-1β, tumor necrosis factor (TNF)-α, IL-13, IL-8 and IL-4) was found. Reduced plasma superoxide dismutase 2 (SOD2), which is considered an anti-oxidant enzyme, and increased oxidant stress parameters were also observed74. After hrACE2, cytokines such as IL-10, IL-1β, IL-2 and TNF-α were decreased 2 hours after administration. Human rACE2 administration was reported to also beneficially influence SOD2 levels, and reduce plasma oxidant stress. These findings were based on a limited number of subjects. Further assessment of hrACE2 as a potential therapeutic in PH certainly will require larger studies. Table 2 provides a summary of studies so far that have used human soluble recombinant ACE2.
Agree that it is unlikely to move forward ahead of Mabs in terms of inducing virus neutralization. But those same cytokines that are induced by ACE2 depletion/ AngII enhancement are the cytokines that allow disruptive t cell responses that increase disease severity and can lead to sepsis/cytokine storm. RAS is active on lymphocytes too. Still much to learn.Move upside and let the man go through...
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08-05-2020, 07:44 PM #24570
I must say immunology has changed a lot since my last formal class. Glad I only administered them.and didn't have to decouple them.
I agree it is a constitutional right for Americans to be assholes...its just too bad that so many take the opportunity...iscariot
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08-05-2020, 09:25 PM #24571
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08-05-2020, 10:03 PM #24572
This has been a very fun page to read, thanks!
Originally Posted by blurred
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08-05-2020, 10:22 PM #24573
Just because one has an advanced degree in a science does not mean that they understand that stuff or are idiots.
There’s a “famous” immunology phd former researchers that now (mainly?) gives talks to the anti-vax folks.
A bunch of residents in Gainesville caught covid because they went to (or threw?) a house party.
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08-05-2020, 10:29 PM #24574
I've been following ARDS closely since I was a resident--the condition was first recognized in Vietnam casualties and a lot of the early research was done by surgeons, including my mentor Dr. Blaisdell. What has impressed me over the years is the number of pharmacological inventions that have been tried unsuccessfully. (Dr. Blaisdell's hypothesis that the condition was caused by platelet activation and could be treated by antiplatelet therapy. It couldn't.)
The human inflammatory response is incredibly complex and simplistic interventions often have unintended consequences. The one thing we know for sure is that to treat ARDS you have to successfully treat the underlying condition--in the case of Covid 19 that obviously means controlling the viral infection. If manufactured ACE2 receptor can do that the benefit might outweigh whatever ill effects it might have on the renin angiotensin system and the inflammatory response, just as dexamethasone seems to control the inflammatory response without the negative effect on the immune system negating its benefit. Still the response to dexamethasone is far from 100% and my suspicion is that the same will be true for any other pharmacologic intervention in the inflammatory cascade.
It's still not clear to me how much of the respiratory problems of Covid 19 are viral pneumonia, excessive inflammatory response, and/or secondary bacterial pneumonia. Can someone clarify for me?
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08-05-2020, 10:45 PM #24575I form the light, and create darkness: I make peace, and create evil: I the LORD do all these things. -אלוהים אדירים
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