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But an analytical result with a Ct value of 45 is scientifically and diagnostically absolutely meaningless (a reasonable Ct-value should not exceed 30). All this should be communicated very clearly. It is a significant mistake that the Corman-Drosten paper does not mention the maximum Ct value at which a sample can be unambiguously considered as a positive or a negative test-result. This important cycle threshold limit is also not specified in any follow-up submissions to date.
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I think this is something the consortium needs to answer. Your criticism about the PCR test in general and the Corman/Drosten assay in specific, got completely falsified by the availability of seroprevalence data. We now have dozens of well designed and well conducted studies available all over the world which unambiguously demonstrate that PCR greatly UNDERestimated the real number of SARS CoV2 infections by a number of 4 to 20. The above link to Meidcal Journal Of Aust says the virus was taken from a Wuhan man arriving in Australia ill, with the virus. It was examined by EM for morphology and found to be corona like.
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Intriguingly, our study also shows that the UPR is hyperactivated in Nrf1-deficient cells. Taken together, our data suggest that the ability of BET inhibitors to attenuate Nrf1-mediated proteasome bounce-back response could in part explain their ability to exacerbate the UPR triggered by proteasome inhibition. Next, as controls under our treatment conditions, we examined the mRNA levels of FOXM1, TERT, BCL2, and AURKB which are some of the target genes of BET proteins .
New Zealand conducted between 2000 and 4000 PCR tests during May – August with a positivity rate between 0.001 and 0.1%, noteworthy during winter season when other resp viruses circulate. Even in the unlikely event that all of those mentioned results are false positives, a false positive rate of anything higher than 0.5% can practically be excluded in routine use. As mentioned, the more likely scenario is that the false positive rate is actually below 0.1%. .) The cT value already has been corrected by drosten in an interview to a recommendation to cT ~30. But as this differs between labs, it should not be taken too precise, but validated by the labs.
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Interestingly, in contrast to proteasome genes, we observed a modest decrease in BET target genes in response to CFZ alone . These genes also exhibited a decrease after treatment with BET inhibitor alone, and depending on the cell type, registered a further decline with CFZ + BET inhibitor . In addition to triggering apoptosis, proteasome inhibitors also invoke certain cytoprotective pathways such as the heath-shock response , autophagy , and transcription factor Nrf1-mediated proteasome ”bounce-back” response . Overall, the interplay between the cytotoxic and cytoprotective effects elicited by the proteasome inhibitors determines the cell fate. Please see my comments addressing this for other questions proposed on this thread.
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After serious protests, the government now says AG positive results will be validated by PCR tests and 3 rounds of this “non mandatory” testing by Christmas. It turns out that two authors of the Corman-Drosten paper, Christian Drosten and Chantal Reusken, are also members of the editorial board of this journal . Hence there is a severe conflict of interest which strengthens suspicions that the paper was not peer-reviewed. It has the appearance that the rapid publication was possible simply because the authors were also part of the editorial board at Eurosurveillance. This practice is categorized as compromising scientific integrity.
The tests could also be used to screen people in communities where time, trust and resources are in short supply. Without providing strong experimental evidence, but rather ignoring scientific publications and real life observations that don’t fit your expectations you won’t be taken serious in the scientific community. I want to point out that PCR testing is conducted similarly around the world due to the usage of commercially available kits and high-throuput systems due to the massive number of tests being conducted each day around the world. The review is certainly a good job that delves into some critical issues that we knew existed, especially the number of cycles. But I wouldn’t call the test “essentially useless”. In such a situation, false positives are better than false negatives.
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- We provide compelling evidence of several scientific inadequacies, errors and flaws.
- In conclusion, the design of the RdRp assay is for sure not the best .
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Therefore, the confusing unspecific description in the Corman-Drosten paper is not suitable as a Standard Operational Protocol. These unspecified positions should have been designed unequivocally. Reliable and accurate PCR-test protocols are normally designed using between 100 nM and 200 nM per primer . In the Corman-Drosten paper, we observe unusually high and varying primer concentrations for several primers . For the RdRp_SARSr-F and RdRp_SARSr-R primer pairs, 600 nM and 800 nM are described, respectively. Similarly, for the N_Sarbeco_F and N_Sarbeco_R primer set, they advise 600 nM and 800 nM, respectively .
Yet history has shown, time & again, that once staunchly-held beliefs, based on “formal education”, are often later proven wrong. I’ve included a link to a table I created using that data. No testing being done at any venue in Tompkins County is testing for “infectious particles”. That type of testing is principally done in research settings. It is uncommon in diagnostic testing for viral diseases to use culture of viri.
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1) The different WHO methods were published within 1 to 4 weeks of each other. The Chinese protocol only days after the Charité protocol. That was at a time when the pandemic even hasn’t reached Europe or the US. Eurosurveillance is an independet scientific journal with confidential peer-review process. Its respective editorial policy abides to the standards of the International Committee of Medical Journal editors and other editorial associations .
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