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Txzen

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Posts posted by Txzen

  1. 44 minutes ago, We’reTexas said:

    Now we’re talking. But that’s probably a little too far for tourists. I didn’t mean to start a redwoods fight, but I just find SF tourism confusing in that many of the tourist places are adjacent to superior places but are inexplicably absent of tourists. I love people experiencing my city, but just wish they could experience the best of it. Like, Ghirardelli Square is packed, but Ft Mason is just over the hill. There are mobs at Lombard Street, but a few blocks over Ina Coolbrith offers arguably the best view of the city. Battery Spencer and the whole Hawk Hill drive? Avoid the traffic and hike off Rodeo Beach. Muir Woods is certainly beautiful when not crowded, but as someone who hikes Marin weekly it’s not where I go for my redwoods fix. 

    Shut the fuck up, Donny, and let all the tourists go to Muir. 
     

    Rodeo beach is a desolate wasteland. Don’t go there. 

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  2. On 6/12/2022 at 10:43 AM, We’reTexas said:

    Well, you should go to Reinhardt Redwood Park in the East Bay, but if you really want to hike through redwoods in Marin you can totally avoid the clusterfuck of the main Muir entrance and park off the Panoramic Highway (or take the Dipsea Trail) and take trails through redwoods with none of the crowds. Just a local’s tip.  

    Or anywhere on the Peninsula - La Honda, Purissima, Heritage Grove, Portola…

     

  3. Warwick is great, if maybe a little on the commercialized side. We stayed on the grounds overnight in an area where they have cabins by the river. Food was forgettable but the experience was great - they had some extra activities for the guests there and you get early admission. 

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  4. That Peak Design bag is the shit though - I use it all the time. Great for active trips where I'm lugging a camera and electronics but also want to maybe pack my helmet, cycling shoes, etc.

    Just enough pockets, love that it has a full zip access from the part that has the back straps - that way when you lay it down you can access your stuff and not get the part that touches you dirty from the dreck of a 3rd-world airport or the great outdoors. Deep secure side pockets, fits over the handle of a rolling bag, hidden waist band, laptop sleeve, side and top quick carry straps... It's super technical but doesn't shout that I'm backpacker. Darn near everything Peak Design makes is great (tech pouches, capture clip, etc.). It's the largest you can carry on for international regulations, and even though it's basically one big space it can fill up quickly. 

    Ode to my PD 45L. I've taken it all around the world at this point. Great bag. 

    https://www.peakdesign.com/products/travel-backpack/?variant=11530908172332

     

  5. 23 hours ago, Murfdogg21 said:

    I’m not sure what your point is by posting those studies in reply to my post. I was not debating the risks of Covid-19, even a mild case of it. I was stating that my highly vitamined, triple Moderna vaxxed, late 30s wife and I experienced similar symptoms in intensity and duration as my unvaccinated 4 year old and several unvaccinated 30s/40s we know. This is clearly not universal, but in science and medicine you should consider the minority results as well. I have mentioned previously that I have minor concerns about safety, but they weren’t enough that my wife and I ever seriously considered not getting vaccinated. I am still on the fence about kids younger than 5, maybe a bit older, and now that my kids have recovered from one bout of Covid I might kick their vaccination decision down the road 6-12 months. I’m sure you’ll have some aloof cunt comment to this too, like you do every time I post on this thread. 

    I actually came here to post that study (which had just published) just because it challenged even my assumption of minimal risk to those with no comorbidities, and spoke to your question as to the efficacy of vaccination for not-at-risk populations. 

    I'm not an aloof cunt, I'm a sarcastic one. Well, maybe aloof in that I don't know who the fuck you are, as outside of a few people who post decent scientific info here I don't pay attention to the names of those who routinely post the usual crap (unfounded vaccine safety concerns, statements of steamrolled development, 'I know people who were never vaxxed and we had the same outcome', etc.). If I always post in response to you, well, FAFO I guess. 

     

  6. 2 hours ago, Murfdogg21 said:

    As stated much earlier in the thread, I am a medical scientist and not anti-vax, but I have had legitimate safety concerns about how the mRNA vaccines were steam rolled through, as well as being statistically certain that this kind of vaccination has any efficacy impact on non-at-risk populations. Unvaccinated friends in area had nearly the same symptoms and duration as my wife and me. Who the hell knows. Olds and fats should still get vaccinated though. 

    Curious what 'medical scientist' means, as this is...an interesting opinion not at all grounded on the facts.

    New study looking at 150k people in the VA - even a mild case has impacts on heart health, regardless of comorbitities. So that's fun.

    Nature : Heart-disease risk soars after COVID — even with a mild case

    Spoiler

    Even a mild case of COVID-19 can increase a person’s risk of cardiovascular problems for at least a year after diagnosis, a new study1 shows. Researchers found that rates of many conditions, such as heart failure and stroke, were substantially higher in people who had recovered from COVID-19 than in similar people who hadn’t had the disease.

    What’s more, the risk was elevated even for those who were under 65 years of age and lacked risk factors, such as obesity or diabetes.

    “It doesn’t matter if you are young or old, it doesn’t matter if you smoked, or you didn’t,” says study co-author Ziyad Al-Aly at Washington University in St. Louis, Missouri, and the chief of research and development for the Veterans Affairs (VA) St. Louis Health Care System. “The risk was there.”

    Al-Aly and his colleagues based their research on an extensive health-record database curated by the United States Department of Veterans Affairs. The researchers compared more than 150,000 veterans who survived for at least 30 days after contracting COVID-19 with two groups of uninfected people: a group of more than five million people who used the VA medical system during the pandemic, and a similarly sized group that used the system in 2017, before SARS-CoV-2 was circulating.

    People who had recovered from COVID-19 showed stark increases in 20 cardiovascular problems over the year after infection. For example, they were 52% more likely to have had a stroke than the contemporary control group, meaning that, out of every 1,000 people studied, there were around 4 more people in the COVID-19 group than in the control group who experienced stroke.

    The risk of heart failure increased by 72%, or around 12 more people in the COVID-19 group per 1,000 studied. Hospitalization increased the likelihood of future cardiovascular complications, but even people who avoided hospitalization were at higher risk for many conditions.

    “I am actually surprised by these findings that cardiovascular complications of COVID can last so long,” Hossein Ardehali, a cardiologist at Northwestern University in Chicago, Illinois, wrote in an e-mail to Nature. Because severe disease increased the risk of complications much more than mild disease, Ardehali wrote, “it is important that those who are not vaccinated get their vaccine immediately”.

    Ardehali cautions that the study’s observational nature comes with some limitations. For example, people in the contemporary control group weren’t tested for COVID-19, so it’s possible that some of them actually had mild infections. And because the authors considered only VA patients — a group that’s predominantly white and male — their results might not translate to all populations.

    Ardehali and Al-Aly agree that health-care providers around the world should be prepared to address an increase in cardiovascular conditions. But with high COVID-19 case counts still straining medical resources, Al-Aly worries that health authorities will delay preparing for the pandemic’s aftermath for too long. “We collectively dropped the ball on COVID,” he said. “And I feel we’re about to drop the ball on long COVID.”

     

    The paper : Long-term cardiovascular outcomes of COVID-19

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  7. 15 hours ago, Dontshootrude said:

    Here is an excellent article on the manufacturing process of Paxlovid that will give you a sense of how incredibly powerful Pfizer's manufacturing capability is.

    https://www.science.org/content/blog-post/making-paxlovid

    That's a fun read. I spent about a decade doing small molecules in oncology for a large pharma. I'm on the biology side, so my chemistry knowledge is a bit on the 'I slept at a Holiday Inn last night' level, but after a while you do learn some of the salient points. Always enjoyed sitting in with the chemistry team, all wearing 3D glasses while they rotate around the pocket on the kinase we were targeting, overlaying how all the chemical variants they made grew or reached into hydrophobic areas or made contact with key amino acid residues. Space age.

    I think a lot of small molecules that make it to market probably have similar issues as paxlovid. One thing he didn't mention that I saw was multiple chiral centers. Each time you make that reaction, you have multiple outputs and sometimes only one spacial orientation has the properties you need. The odds are almost never 50:50, and invariably the stuff I worked on always needed the one product that was 20% of the reaction. That's a nuisance in the preclinical stage and a colossal issue at the commercial stage.

    There's a lot of work as these programs move to IND to ensure that the chemical synthesis doesn't utilize some process which isn't scalable.

    I know industry gets a bad rap, but I hope that's due to the business/marketing side. The science is incredible, and I'm constantly fascinated by how much work goes in to make these drugs at scale - whether it's small molecule, biologics, or even cell therapy.

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  8. 1 hour ago, Lobo said:

    I'm sure this was answered far upthread, but gotta ask again.  

    After close-contact alerts in September and October (I was double-vaxxed back then), my IgM & IgG were both negative at two clinical/PCR tests.  Did some at-home tests in November and December before family gatherings, including getting boosted.  But after another close-contact in January, I've been tested twice this month in a clinical setting with PCR as well.  Now, my IgM is still negative, but both results have flipped to IgG-Positive.  What would cause the IgG flip from negative to positive?  

    Not a B cell guy, but the natural progression of antibody class switching upon antigen exposure is for a first transient production of IgM and then a second prolonged IgG production. My guess would be that your vaccination already ‘switched’ B cell production from IgM to IgG, and any secondary exposure would likely only trigger a profound IgG production. 

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  9. On 1/18/2022 at 8:41 AM, Brisketexan said:

     

    2 -- I've had this question before: the flu vaccine is updated based on the expected strain every year.  It doesn't have a long-term approval process (that is, we don't need an EUA for each year's flu vaccine, even though it was developed and rolled out in less than a year).  What is the mechanism/system for that, and could that be applied to the MRNA VOID vaccines?  That is, if enough of the delivery system remains the same, and only a few things are altered to address a new strain, does that get some sort of expedited review like the flu shot (presumably) gets each year?  I'm genuinely curious -- I don't know how that works.

    tl;dr - the WHO sets global recommendations, the FDA chairs an advisory committee to pass that recommendation on to manufacturers, then standard lot release assays verify the effectiveness. And yes, I could totally see this happen for COVID strains. The question is will manufacturing be able to keep up with strain emergence. That said I'm still amazed we do this every year in f-ing eggs (which was a prime issue during the H1N1 variant year as it also took out the egg production).

    An overview of the regulation of influenza vaccines in the United States

    Spoiler

    To maintain effectiveness, the composition of seasonal influenza vaccines must be reviewed and updated periodically to include the most current HA antigens expressed by circulating influenza wild‐type viruses. This is a complex, lengthy process that requires extensive collaboration among influenza manufacturers, vaccine regulators, and global public health laboratories. The process begins with the recommendations, coordinated globally by the World Health Organization (WHO), for the virus strains to be included in the vaccine.4 The WHO recommendations for the Northern Hemisphere, which are based on recent global surveillance data available each February, provide a guide to national public health authorities and vaccine manufacturers for the development and production of influenza vaccines for the following winter influenza season. However, as noted in the WHO recommendations, it is the responsibility of each national regulatory authority to approve the composition and formulation of the vaccines used in that country. Each year, soon after the WHO Northern Hemisphere vaccine recommendations are finalized, the FDA convenes its Vaccines and Related Biological Products Advisory Committee (VRBPAC), typically in late February or early March, to recommend the virus strains that should be included in FDA‐licensed influenza vaccines for the next winter influenza season in the United States.

    In the United States, licensed influenza vaccine manufacturers must submit a supplement to their license for review and obtain FDA approval before the updated version of the influenza vaccine containing new virus antigens can be distributed. Such supplements to inactivated and recombinant protein seasonal influenza vaccines do not require additional clinical data specific for the new strain. Supplements to the licensed live influenza virus vaccine require a study in approximately 300 adults prior to approval of the new strain to verify adequate attenuation. Manufacturing of influenza vaccine takes place over an approximately 6‐month time frame beginning prior to the VRBPAC strain selection and lasting until mid‐summer, when the trivalent or quadrivalent vaccine is formulated, filled, and distributed. The manufacturing timelines are tight and the process of producing influenza vaccine involves many sequential steps and overlapping processes. Even with technologic advancements, each of these steps and processes still requires time to complete, and there is limited flexibility in the timelines for manufacturing.

    Candidate vaccine viruses, which have been adapted for high growth in embryonated eggs and verified by a WHO Collaborating Center as antigenically like the recommended vaccine strain, are provided to manufacturers to generate “seed viruses” for inactivated seasonal influenza vaccine production. The availability of a “high‐yield” candidate vaccine virus is a key step in manufacturing, because poorly growing viruses extend the time needed for producing a sufficient amount of vaccine antigen. Manufacturers' “seed viruses,” which have been passed several more times to improve growth in their production systems, are tested by the FDA in an HI assay to ensure they remain antigenically similar to the recommended vaccine strain. Candidate vaccine viruses used for manufacturing live attenuated influenza vaccines conform to the same WHO/VRBPAC recommendations, but are tested for antigenic identity at the WHO Collaborating Center at the CDC.

    Production of each vaccine antigen to be included in the vaccine takes place sequentially over several months until late May, and in fact, production of at least one antigen usually begins at risk before the strain recommendations are finalized. In parallel with antigen production, FDA develops and calibrates reagents that are necessary for testing the potency and identity of each of the antigens included in inactivated and recombinant vaccines. The reagents are provided to the vaccine manufacturers and used by both manufacturers and FDA for testing, quality control, and release of the new formulation of the licensed seasonal influenza vaccines. Standardized reagents ensure that inactivated vaccines produced by multiple manufacturers contain the same amount of HA antigen for each of the recommended virus strains. During the vaccine production process, manufacturers of inactivated and recombinant influenza vaccines submit 3‐5 lots of monovalent vaccine produced for each strain for concurrence potency testing by the FDA. This process assures harmonization of the potency assay and is designed to minimize the chances of discrepancies between the potency assigned by the manufacturer and lot release testing done by the FDA for the final formulated vaccine that could result in delay of vaccine distribution. Although preparation of potency reagents has not delayed the production and availability of seasonal influenza vaccines in the United States, timely reagent production is challenging and always a potential bottleneck in influenza vaccine production.5

    When all of the antigens that will constitute the trivalent or quadrivalent influenza vaccine have been produced, they are blended and the vaccine is formulated into standard dosages, filled, and finished by the manufacturers into final containers such as vials, syringes, and sprayers. Manufacturers submit their vaccine testing results, along with samples from each lot, to FDA for “lot release.” Typically, FDA approves the updated seasonal influenza vaccines with new labeling by the end of July, and as FDA releases specific lots, the manufacturers make these lots commercially available throughout the United States. The dating period, or expiry, of the vaccine is based on stability studies conducted by each manufacturer, but no final vaccine formulations in the United States are labeled with an expiry date that extends past June 30 of the prior winter influenza season. This chosen expiry date is well past the Northern Hemisphere influenza season and serves to avoid any possible confusion with the influenza vaccines produced for the subsequent influenza season.

     

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  10. Had to renew the passport for my minor child, so it was basically almost like a new passport application. 

    Needed birth certificate, and both parents to be there, etc. Did the whole thing at the post office branch (which even offered on-site pictures). 

    Appointment was on Dec 20th, and we paid for expedited service and express mail since we were nervous as we have a trip in February. Just received it today (January 6th). 17 days!

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  11. 19 hours ago, 956 Worldwide said:

    Lived in Poland for two years. Zubrowka and apple juice is called a szarlotka. It’s delicious and dangerous and the stuff a night out on the town in Warszawa is made of.

    Polish vodka talk not going away. 
     

    Also the alternative name for that cocktail is ‘tatanka’ (yes, from ‘Dances with Wolves’). 

  12. On 12/20/2021 at 6:33 AM, davidg said:

    Plumbing is easy, only gotta know 4 things:  Hot on the left/Cold on the right, Shit flows downhill, payday is Friday and don't bite your fingernails.  

    The rule of plumbing is that if it’s too loose, it leaks. If it’s too tight, it leaks. 
     

    Fuck plumbing. 

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  13. Just now, Murfdogg21 said:

    If you read my posts, it was about caution in juvenile patients, particularly infants and toddlers. The 7.4 billion doses with <12 months safety data haven’t been going into little ones. 
     

    Please do not insult my scientific chops if you don’t understand that the 3-D confirmation of the natural spike protein is dependent on its molecular interaction with the other proteins of the virus shell. Because the other proteins of the virus are not present in the output of the vaccine, the ingenious work was to insert other amino acids to create synthetic bonds that could accomplish the same 3-D confirmation without needing the neighboring proteins. 

    Nice way to deflect your premise about differences in mRNA translation between a 12 year old and an adult. Or the impact said age on some processing of a proline substitution. There are no chops to insult. 

  14. On 11/7/2021 at 1:37 PM, Murfdogg21 said:

    Posting legitimate science based concerns on here paints you as an anti-science trumpster, yet I continue. Saying this particular mRNA must be safe because we naturally have mRNA is about as valid logic as saying cholera, ricin, or botulinum are safe proteins because we have other proteins. Is it most likely safe for most people? Of course. Could there be unknown side effects that we don’t understand until years down the road? Certainly. Could the metabolism and cell/DNA/RNA replication differences between children (or even more so infants and toddlers when that day comes soon) and adults results in different reactions? I can’t say that’s impossible or even unlikely. This is a synthetic mRNA designed to create a representation of the 3D conformation of a spike protein, with different start and stop sequences and intermediate stabilizing elements included that are unnatural. If I were concerned, it would be more about the introduction of this mRNA in a young system than the lipid (aside from some allergic reaction to the carrier materials). Anyway, that’s why I originally posted that I would feel more comfortable with the little kids getting the J&J version today and until there is wide spread safety data and, although under different circumstances I might inject my kids with Pfizer (or Moderna), I would be more cautious than celebratory. 

    You know enough legitimate science to write a few words, but not remotely understand the meaning.

    Could cell replication, DNA replication and RNA replication be different between children and adults and thus cause a reaction with the vaccine? This doesn't even make any sense. Please point to the legitimate science supporting this concern.

    It's not 'designed to create a representation of a 3D conformation'. It's a message to make a string of amino acids which make up a protein. The '3D structure' is built by your own cell machinery. 

    Unnatural start and stop codons? Explain how this impacts the translated product, please. Intermediate stabilizing elements? 

    Approximately 7.4 billion doses administered as of today. 

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