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  1. Trial was too small to definitively compare combinations, but Moderna may have an edge. Mixing and matching COVID-19 vaccines for booster doses appears safe and as effective—if not more effective—than sticking with the same vaccine for a booster dose. That's according to preliminary data posted online Wednesday from a clinical trial run by the National Institutes of Health. The trial bolsters what some have long hoped: that mixing and matching vaccines could provide stronger, broader protection against the pandemic virus and all its variants. The trial was not large enough to definitively indicate which combination of vaccines offers the best protection. And the early results, available on a preprint server, have not yet been peer-reviewed. But the preliminary trial findings do hint that Moderna's mRNA vaccine may offer the strongest protection all around—backing up similar findings from earlier vaccine-effectiveness studies. The data also suggests that people who received the one-shot Johnson & Johnson vaccine may want to get a boost with one of the two mRNA vaccines, either Moderna's or Pfizer/BioNTech's. But most clearly, the study found that mix-and-match boosting increases protection and produces only similar side effects as boosting with the same vaccine. Or, in the authors words: "These data suggest that if a vaccine is approved or authorized as a booster, an immune response will be generated regardless of the primary Covid-19 vaccination regimen." Nine combinations For the study, researchers at various trial sites around the country recruited 458 people over the age of 18. Subjects were subsequently split into three groups of roughly 150 each. Those three groups had different initial vaccine regimens: either two doses of the Moderna vaccine, two doses of the Pfizer/BioNTech vaccine, or one shot of the Johnson & Johnson vaccine. From there, each of the three groups of 150 were split into three groups of 50, with each of the smaller groups getting different boosters. So, for example, among the 151 people who received a Moderna vaccine initially, 51 went on to receive a Moderna booster, 51 got a Pfizer/BioNTech booster, and 49 got a Johnson & Johnson booster. The booster doses were given between 12 and 29 weeks after the initial vaccinations. Next, researchers looked at the levels of binding and neutralizing antibodies the day of the booster shot (so before the boosters were able to kick in). The researchers checked those same levels 15 days later and 29 days later. Across all of the combinations, levels of binding antibodies rose between fourfold and 56-fold. They also looked carefully at neutralizing antibodies—the antibodies that bind to and prevent SARS-CoV-2 virus from infecting cells. In people who had received the same type of vaccine for their initial doses and their booster dose, neutralizing-antibody levels rose fourfold to twentyfold. In people who got different vaccines, neutralizing-antibody levels rose sixfold to 76-fold. The fold-changes strongly indicated that the booster doses increased protection across the board while mix-and-match perhaps have an edge. But the fold-changes can obscure some finer points. (You can see the whole table of results here, beginning on page 27) Looking at just the average antibody levels in each group, subjects who initially got the Johnson & Johnson vaccine started with some of the lowest neutralizing-antibody levels on day 1. Their geometric mean titers of neutralizing antibodies ranged from 7.6 to 9 on day 1. As such, they had the smallest and the largest fold-changes after the boosts. Members of the Johnson & Johnson group who got a Johnson & Johnson booster saw their neutralizing-antibody levels rise only fourfold after 15 days (to 31)—the smallest change across all of the groups. But people who got the Johnson & Johnson vaccine followed by a Moderna booster saw a 76-fold rise (to 676)—the largest change. Moderna’s edge Overall, people who got the Moderna booster had the highest neutralizing-antibody levels regardless of what vaccine they got initially. Their geometric mean titers of neutralizing antibodies ranged from 676 to 900 at day 15. The group with the mean of 900—the highest level reported in study—had received the Moderna vaccine for their initial and booster doses. People who had initially gotten the Pfizer/BioNTech vaccine saw their geometric mean titers of neutralizing antibodies rise from about 25 to 786 after a Moderna booster. People initially vaccinated with Moderna also had better starting levels of neutralizing antibodies compared to those seen in people initially vaccinated with the Pfizer/BioNTech vaccine. They had ranges of 58-89 and 19-25, respectively. People initially vaccinated and boosted with Pfizer/BioNTech vaccine saw their levels rise from 21 to 448. But that was still lower than the people initially vaccinated with Moderna and boosted with Pfizer/BioNtech—they saw levels rise from 58 to 678 after 25 days. The researchers noted that previous studies have estimated that a geometric mean titer of neutralizing antibodies at 100 or above correlates with vaccine efficacy of 90.7 percent against symptomatic disease. All of the groups met that threshold, except for the group that got a both a Johnson & Johnson primary dose and booster dose. In all, the study indicates that mixing and matching is a safe and effective way to bolster protection. Researchers will need to conduct larger studies to see if Moderna can maintain the lead it seems to have here, though. But the weak Johnson & Johnson results will provide plenty of fodder for debate when advisors for the Food and Drug Administration meet later this week to consider authorizing Johnson & Johnson booster doses. reader comments 89 Mix-and-match COVID boosters are as good—if not better than—all the same shots
  2. Why Memory Optimizers and RAM Boosters Are Worse Than Useless Chris Hoffman @chrisbhoffman November 1, 2014, 4:04am EDT Many companies want to sell you “memory optimizers,” often as part of “PC optimization” programs. These programs are worse than useless — not only will they not speed up your computer, they’ll slow it down. Such programs take advantage of inexperienced users, making false promises about boosting performance. In reality, your computer knows how to manage RAM on its own. It will use RAM to increase your computer’s performance — there’s no point in having RAM sit empty. Is Your Computer’s RAM Filling Up? That’s Good! Memory optimizers are based on a misunderstanding. You may look at your computer’s RAM and see it filling up — for example, you may have 4 GB of RAM and see that 3 GB is full with only 1 GB to spare. That can be surprising to some people — look how bloated modern versions of Windows are! How are you ever going to run additional programs with so little memory available? In reality, modern operating systems are pretty good at managing memory on their own. That 3 GB of used RAM doesn’t necessarily indicate waste. Instead, your computer uses your RAM to cache data for faster access. Whether it’s copies of web pages you had open in your browser, applications you previously opened, or any other type of data you might need again soon, your computer hangs onto it in its RAM. When you need the data again, your computer doesn’t have to hit your hard drive — it can just load the files from RAM. Crucially, there’s no point in having RAM empty. Even if your RAM is completely full and your computer needs more of it to run an application, your computer can instantly discard the cached data from your RAM and use that space for the application. There’s no point in having RAM sit empty — if it’s empty, it’s being wasted. If it’s full, there’s a good chance it can help speed up program loading times and anything else that would use your computer’s hard drive. Notice that very little RAM is actually “free” in the screenshot below. The RAM is being used as a cache, but it’s still marked as available for any program that needs to use it. In the past, full RAM did indicate a problem. If you were running Windows Vista on a computer with half a gig of RAM, you could feel the computer constantly slowing down — it had to constantly read and write to the hard drive, using the hard drive’s page file as an inefficient replacement for RAM. However, modern computers generally have enough RAM for most users. Even low-end computers generally ship with 4GB of RAM, which should be more than enough unless you’re doing intensive gaming, running multiple virtual machines, or editing videos. Even if RAM was a problem for you, there’s no reason to use a memory optimizer. Memory optimizers are snake oil that are useless at best and harmful at worst. How Memory Optimizers Work When you use a memory optimizer, you’ll see your computer’s RAM usage go down. This may seem like an easy win — you’ve decreased RAM usage just be pressing a button, after all. But it’s not that simple. Memory optimizers actually work in one of two ways: They call the EmptyWorkingSet Windows API function, forcing running applications to write their working memory to the Windows page file. They quickly allocate a large amount of memory to themselves, forcing Windows to discard cached data and write application data to the page file. They then deallocate the memory, leaving it empty. Both of these tricks will indeed free up RAM, making it empty. However, all this does is slow things down — now the applications you use will have to get the data they need from the page file, reading from the hard drive and taking longer to work. Any memory being used for cache may be discarded, so Windows will have to get the data it needs from the hard drive. In other words, these programs free up fast memory by forcing data you need onto slower memory, where it will have to be moved back to fast memory again. This makes no sense! All it accomplishes is selling you another system optimization program you don’t need. If Windows needs RAM, it will push data to the page file or discard cached data, anyway. This all happens automatically when it needs to — there’s no point in slowing things down by forcing it to happen before it’s necessary. Like PC cleaning apps, memory optimizers are a scam. They appear to be doing something positive to people who don’t understand how memory management works, but they’re actually doing something harmful. How to Actually “Optimize” Your Memory If you do want to have more available RAM, skip the memory optimizer. Instead, try to get rid of running applications you don’t need — purge unnecessary programs from your system tray, disable useless startup programs, and so on. If you do need more RAM for what you do, try buying some more RAM. RAM is pretty cheap and it’s not too hard to install it yourself using one of the RAM installing guides available online. Just ensure you buy the correct type of RAM for your computer. Yes, memory optimizers can free up some of your PC’s RAM. However, that’s a bad thing — you want your computer to use its RAM to speed things up. There’s no point in having free memory. Source Old article, but still very relevant!
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