6,062 Matching Annotations
  1. May 2026
    1. On 2021-12-18 02:12:44, user Peachyjenniekag21 wrote:

      The main concern i have over the implications of this report are how this could impact conditions and protocols of prison inmates and populations. An unfortunate reflex seems to be rigid and stringent focus on isolation efforts as opposed to abundant supply of safe and effective treatment in congregate settings...

    2. On 2021-11-29 10:58:19, user Andy Bloch wrote:

      This study had just 13 unvaccinated participants with no known prior SARS-CoV-2 infections. To say that it was "underpowered" is an understatement. It's incorrect to conclude "we found no statistically significant difference." Add this paper to the long list of articles that mistakenly interpret statistical significance. The authors and reviewers should read this comment: Scientists rise up against statistical significance.

    1. On 2022-01-12 11:43:46, user kdrl nakle wrote:

      There is nothing in this paper worth beyond what is already expected. The numerical predictions will likely be erroneous. I have no idea why would anybody want to write the stuff like this that wil be outdated in two weeks time.

    1. On 2021-10-16 13:53:34, user Sam Smith wrote:

      Thanks for the great study, but when will you publish results what happens if one takes Sputnik light as a booster? I am only interested in boosters that give >90% protection against delta, because in Israel 3 doses of Pfizer gives >90% protection.

    1. On 2021-10-20 08:13:57, user ClearSkys wrote:

      "...the vaccination coverage rate is inversely correlated to the mutation frequency of the SARS-CoV-2 delta variant"

      Correlation != causation

      Motives are questionable especially when the authors then go on to recommend the public health policy based solely on the correlation.

    1. On 2021-10-29 12:26:39, user Yehonatan Knoll wrote:

      Good study of a bad question. <br /> Ten months into the vaxx campaign, why is there no similar, comprehensive study following vaxxed and unvaxed, *starting with the date of vaccination rather than that of infection*. This is the only pertinent question, now that a biannual booster is required of the vaxxed.

    1. On 2021-10-29 17:15:41, user kdrl nakle wrote:

      This is a very troubling report as we really need to differentiate "regular" deaths from the ones that are consequence of (and caused by) vaccination. This report is vague on that and it is going to be used against vaccination, no doubt.

    1. On 2021-11-14 13:53:40, user Marc Middleton wrote:

      I don't even have to read the whole (not yet peer-reviewed and thus questionable) article to see that the conclusion, which anti-lockdownists like to draw from it, is faulty. It's already stated in the abstract that "efficient infection surveillance and voluntary compliance make full lockdowns unnecessary". People of the studied population obiously had enough common sense to contrain their contacts, which OF COURSE reduces viral spreading without the need for lockdowns! But as we have seen in several countries, not all people are as smart as the Danish...

    1. On 2021-11-15 05:09:26, user John Davies wrote:

      Might be good to make it extra clear in plain English that these are background rates - not actual vaccine side effects, as they appeared to me at first glance.

      Other lay people might use these data to perpetrate the antivax argument.

    1. On 2021-11-16 02:36:21, user Peter Renzland wrote:

      The last sentence in the "Results" seems difficult to reconcile with the first sentence in the "Conclusions":

      We observed no difference in the LoS for patients not admitted to ICU, nor odds of in-hospital death between vaccinated and unvaccinated patients.<br /> vs.<br /> Vaccinated patients hospitalised with COVID-19 in Norway have a shorter LoS and lower odds of ICU admission than unvaccinated patients.

    1. On 2021-11-16 17:30:31, user Marcelo Sauaf wrote:

      Authors using ONLY the term "faster" about the viral cleareance while this "faster" meant mere 2 DAYS less than unvaccinated evidentiate their POLITICAL bias on the subject. Why don't they QUANTIFY in the conclusion the "faster" was mere 2 days less than unvaxxed - AND that the contagious phase (PCR ct = 25) is tipically up to 9 days ??

    1. On 2021-11-16 17:54:49, user C D wrote:

      Why do we keep thinking herd immunity can be achieved for every strain? Isn't it normal to have new strains that people aren't immune to yearly? Iran's covid cases have currently plummeted, what happens if they stay there? Does that mean herd immunity has been achieved?

    1. On 2021-11-20 09:36:30, user Amador Goodridge wrote:

      Great ongoing work of Amanda et al bringing to the light of scientific evidence the dramatic situation of migrants. While looking forward findings and results of this study, hope this warning help Panama together with other agencies continue to reinforce POC,<br /> & clinical diagnosis as well as on-site treatment strategy in order to assure the public health. Congrats!

    1. On 2021-11-22 18:02:48, user Timeisrelative wrote:

      This is an excellent paper. I have a few minor comments related to the word choice and clarity that I hope are helpful to you.

      1)The uses of the words "rate" and "rate of change" are problematic in this context. I think it would be more clear to use different words. A "rate" usually describes how much of something happens over a specified unit of time. So the "rates of change in antibody titres during 3-6 months" might be about 10%/per month. Your metric is defined as:

      rate of change = [(Ab titre 6 months after the 2nd dose - Ab<br /> titre 3 months after the 2nd dose [12]) / Ab titre 3 months after the 2nd dose] × 100 (%)

      I believe this metric would be better described as simply the "change" or "percentage change" instead of the "rate of change" since it doesn't have a unit of time in it's denominator. This phrase "rate of change" occurs at many times throughout the paper and I believe they all should be replaced with "change" or "percentage change".

      2) I was confused by the meaning of this line near the end of the results section:

      because the Ab titres 3–6 months after vaccination were significantly higher in women than in men.

      If I correctly assumed your intention, I think this line could be written more clearly as: "because the Ab titres were significantly higher in women than in men at both 3 months and 6 months after vaccination"

      3) I think it would be helpful to specify in the table headings and in the chart axes labels whether the measured titres were 3 months or 6 months post vaccination. This information is in the paper and the caption of the figures, but it would be clearer if, for example, the headings of tables 1 and 2 were "Ab titre at 6 months, median (IQR), U/mL" and the x-axis label of figure 2b was changed similarly.

    1. On 2021-11-24 00:22:39, user Nik Kolb wrote:

      Could you please double check if the German vaccination data in ECDC are handled correctly for your calculations? The burden is unexpectedly high.<br /> It might be that the lack of more detailed age groups than 3 categories (<18 years, 18-64, 65+) resulted in a wrong attribution of the vaccine coverage. I could not find a method how you "interpolated" the vaccine coverage by age group, but Supplementary Figure S1 suggests that it does not really reflect the true vaccine coverage in each age group. While the true coverage sadly is unknown in Germany, a telephone survey among german speaking participants conducted by RKI given some hint about the true coverage: https://www.rki.de/DE/Conte...

    1. On 2021-11-25 15:30:42, user kdrl nakle wrote:

      When you write nonsense like this:<br /> ***<br /> The rate of detected reinfection after two doses of vaccine was 1.35 (95% CI 1.02 to 1.78) times higher in those vaccinated before first infection than in those unvaccinated at first infection.<br /> ***<br /> in your abstract then I know it is not worth reading any further.

    2. On 2021-11-29 13:08:12, user TheBigWakaWaka wrote:

      There's something that needs explanation.

      In table S2, the raw <br /> ratios of unvaccinated cases over unvaccinated person-time (45% vs 55%, <br /> single dose vaccinated cases over single dose person-time (24% vs 19%), <br /> and double dose vaccinated cases over double dose person-time (30% vs <br /> 26%) are pretty close.

      Nevertheless, the Cox coefficients indicate<br /> a strong difference. This means that very strong confounding effects <br /> are at play here: this would need commenting. Usually such a strong <br /> difference between "corrected" effects and raw effects indicates a <br /> weakness in the study, that should at least be commented.Based <br /> upon the raw ratios one would think there's no effect of extra <br /> vaccination ; based upon the Cox coefficients, there's a very strong <br /> effect.

    1. On 2021-12-03 01:31:09, user Alex Johnson wrote:

      This analysis did not address infection after vaccination, which we know is happening with Omicron. I'd like to see the rate of reinfection compared with the rate of breakthrough infection, before I get too excited about reinfection.

    1. On 2023-01-02 11:42:16, user Lance wrote:

      It seems that the authors indulged in the pharma-friendly practice of starting the clock on exposure 7 days post-exposure:

      "Individuals were considered bivalent vaccinated 7 days after receipt of a single dose of the bivalent COVID-19 vaccine... Curves for the non-vaccinated state were based on data while the bivalent vaccination status of subjects remained “non-vaccinated”. Curves for the bivalent vaccinated state were based on data from the date the bivalent vaccination status changed to “vaccinated”. "

      This is particularly egregious given the potential for these vaccines to increase infection risk in the period immediately following vaccination. What little VE is reported here for the bivalent could itself be an illusion, disappearing upon proper treatment of the data.

    1. On 2021-12-04 00:21:53, user TaShelby wrote:

      These results are important and are consistent with findings in “Quantitative SARS-CoV-2 viral-load curves in paired saliva and nasal swabs inform appropriate respiratory sampling site and analytical test sensitivity required for earliest viral detection.” Doi:10.1101/2021.04.02.21254771. See https://www.medrxiv.org/con...

    1. On 2021-05-28 18:07:40, user Craig Austin wrote:

      Nobody wears masks properly, except professional staff in a clinical setting , nobody. Viruses didn't change sizes, mask' s pore size didn't change only human behavior changed.

    1. On 2021-01-21 18:33:05, user Calogero wrote:

      Slovak people were forced to participate to the testing under threat of losing their jobs. One months after testing we were and now still are among the countries with higher deaths rate pro capite in the world. People had to wait per hours outside in severe november weather to be tested and after that wait inside for the results risking to be infected. During the weeks after testing the number of daily pcr tests was significantly lowered, that is reason why there were less new covid cases after testing. And despite whole scientific and medical community is contrary to the wide-testing, it is to be repeated next week, same conditions, not tested not allowed to go to the work, risking unexcused absence standing on the words of minister of labour, without any financial compensation. Unbelievable but true. (sorry for my english)

    2. On 2021-01-23 13:21:08, user Dušan wrote:

      "All authors declare that they have no conflicts of interest"

      Have a look at Jarcuška's organisation Euromedpro which is sponsored by GSK and Pfizer.

    1. On 2021-09-14 13:39:06, user Henri van Werkhoven wrote:

      Dear colleagues,

      With interest did we read this manuscript which fueled a lively discussion during our journal club of the department of infectious diseases epidemiology at the University Medical Center Utrecht. The authors address a relevant research question. If there is a substantial difference in the risk of SARS-CoV-2 infections between previously infected and vaccinated individuals – as suggested - this may have consequences for social distancing, testing recommendations, and for projections of the impact of vaccination on future COVID-19 trends. However, we have several concerns regarding generalizability, selection bias, information bias, and confounding that we would like to address. We focus our discussion on model 1: the comparison of the fully vaccinated non-infected group (group 1) to the infected non-vaccinated group (group 2).

      In regard to generalizability:<br /> - Due to the matching process, only 4% of the available data is used (i.e. for model 1 only 32430/736559) and as a consequence the study population is fairly younger (with expectedly less comorbidity) than the source population (i.e. vaccinated individuals, infected individuals). Therefore, the study population may not be representative of this source population which severely limits the external validity of results for all vaccinated/infected people.<br /> - Naturally, subjects who died due to previous SARS-CoV-2 infection were not included in the study. Yet, without information on morbidity and mortality and contribution to the spread of SARS-CoV-2 from the primary infection, the results of the study are not informative for the question whether people without previous SARS-CoV-2 infection should be vaccinated or await natural infection. <br /> - All three study groups – vaccinated or infected at baseline (28th of February) – were established upon future information (no infection, no additional vaccination after June 1, 2021), which severely limits the use of the results for today’s decision making.

      In regard to selection bias:<br /> - People with a SARS-CoV-2 infection between February 28, 2021 and June 1, 2021, or those who received a first (infected group) or third vaccine (vaccinated group) between February 28, 2021 and August 14, 2021 were excluded from this study. Thus the study population of group 2 consists of previously infected people that do not take the opportunity to receive a booster vaccine, which may well be the less vulnerable people with a lower baseline risk of getting infected/hospitalized. This would bias the estimate in favor of the infected group.<br /> - Similarly, though at a smaller scale, people who died from COVID were not included in the analysis. This decreases the vulnerability of the infected group for secondary infections and/or hospitalization. This too would bias the estimate in favor of the infected group.

      In regard to information bias:<br /> - A difference in willingness to test between the vaccinated and previously infected group can result in biased estimates. Vaccinated people may be more on guard in regard to COVID-19 symptoms (especially if they adhere less to regulations because they are vaccinated) and will be tested more frequently. This can bias the estimate, again in favor of the infected group. However, this form of bias should not have affected the outcome hospitalization due to COVID-19, for which differences had the same direction. Yet, the number of those endpoints was low, limiting statistical power.

      In regard to confounding:<br /> - The authors acknowledge absence of information about health behavior, such as social distancing and masking. If the vaccinated group would adhere less to these preventive measures due to a sense of safety, this would also bias the estimates in favor of the infected group.<br /> - A potential important aspect is the young average age (36 years) of the study population. As they were all fully vaccinated before February 28th, we thought that a large proportion may have been health care workers, who have a higher chance of exposure to SARS-CoV-2, and thus infection after vaccination. This would also bias the estimate in favor of the infected group.

      We have scrutinized the paper in search of the fatal flaw; the one major methodological limitation that could explain the extreme effect in favor of the infected group, as reported. We conclude that it is not there, as we don’t think that any of the above biases can explain all of the effect. However, we did found several weaknesses that each have the potential to yield a modest bias, all in the same direction. Five modest biases may yield a large effect estimate. We, therefore, consider the question whether natural immunity provides better protection than full vaccination with Pfizer/BioNTech’s COVID vaccine remains unanswered.

      The authors (Annemarijn de Boer, Valentijn Schweitzer, Marc Bonten and Henri van Werkhoven, all at University Medical Center Utrecht) acknowledge all other journal club participants for their time dedicated to discussing the paper.

    1. On 2020-12-27 02:14:14, user valley_nomad wrote:

      What is the definition of mortality rate in this study? The numbers seem to be way too high if it is CFR (case fatality rate).

    1. On 2021-12-21 21:03:38, user Mike B wrote:

      Fantastic early news on boosting to increase circulating antibodies to provide Omicron protection. I hope we see a matching case study to correlate clinical data. Although the author declared the limitations regarding waning, it is critical to determine the waning pattern of boosted response.<br /> Taking "likely to be similar" as a starting point, the data appears to show significant loss of circulating antibodies 6 months post vaccination. This a critcal clinical issue in the USA because the high number of elderly/institutional vaxxed early in 2021 and subsequently boosted in Aug/Sept timeframe to enhance protection against Delta. For this highly risk population, boosted protection may already have significantly waned leaving less than expected protection just as Omicron begins to dominate. Without data on waning attached, the study may set false expectations of protection and open questions on continued booster use. <br /> One way to ameliorate the issue is to extend the study, collect samples pre and post a 4th dose at 50 and 100 micrograms. Thus will settle discussion and improve application towards clinical use.

    1. On 2021-08-18 15:53:47, user K Meijer wrote:

      Does this assume the previously infected peeson still has antibodies left? What about someone who had Covid Beta variant middle December 2020, tested positive for IgG antibodies late in January with lab test, but showed hardly any antibodies remaining with rapid antibody test early August 2021?

    1. On 2020-07-04 15:08:27, user Robert van Dijk wrote:

      Interesting paper! I have a few questions/comments. <br /> - is the model really just a ResNet-50 with the final classification layer fine tuned? Sounds amazing haha! <br /> - if you’re looking to apply the model in real clinical practice I think it’s good to think about how it would fit in the workflow. I think it’s already great that it does not output a diagnosis, but actually the step before it. Transparancy is very important especially in the clinic, so I could still expect that they want the model to explain it’s own decision as well. Does it allow for highlighting (using bounding boxes) the cells it has identified? <br /> - from what I have learned sensitivity is often more important than specificity in a clinical setting, but that differs of course per specialisation. So perhaps fine tuning towards that may be beneficial<br /> - great that you mention limitations of the model. Think that’s going to be essential especially with regard to specific cell types.

    1. On 2021-01-17 01:45:40, user Oguzhan Alagoz wrote:

      AN updated version of this paper is published by Annals of Internal Medicine:<br /> https://www.acpjournals.org...

      Full updated citation is:<br /> Alagoz, O., Sethi, A. K., Patterson, B. W., Churpek, M., & Safdar, N. Effect of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the United States: A Simulation Modeling Approach. Annals of internal medicine, M20-4096.

    1. On 2020-08-14 13:42:47, user Nikita Michaels wrote:

      From the paper: "Because the amount of virus present in the samples was low and thus unsuitable for common next-generation sequencing approaches, Sanger sequencing based on a gene-walking approach with over-lapping primers was used to obtain the virus<br /> sequence." Probably any air sample would have led to the same results given the "right" primers. But they did not use another sample of "non-contaminated" air to perform the same test so the results are without any value. Terrible, how these studies without peer review end up influencing public regulations.

    1. On 2020-08-14 15:40:32, user Ricky Turgeon PharmD wrote:

      This article has generated some discussion on Twitter, including a thread where I provide some comments. https://twitter.com/Ricky_T...

      In particular, I hope that the authors can revise and/or provide responses to address the following concerns:<br /> 1. Please provide the rationale for selecting July 31 as the date for interim analysis. Please also provide details regarding this interim analyses, including pre-specified stopping rules, who had access to the data. Although this manuscript is labeled as a "preliminary report", it would be valuable for the authors to explicitly state whether this trial is ongoing, and whether any changes to the conduct of the trial were made based on this interim analysis.

      1. In version 1 of the article on this site, the Methods section had a sentence that stated "No concealment mechanism was implemented". This was subsequently removed in version 2 yesterday. Please clarify what is meant by this. Did the authors mean to imply that allocation concealment was not performed, or was this an erroneous statement intended to describe the unblinded nature of the study? Please also describe the process for treatment allocation and how allocation concealment was maintained.

      2. The authors describe a change in the primary outcome in terms of timing of CRP measurements. However, I note that the clinicaltrials.gov summary of this trial previously had an entirely different outcome as the primary outcome, with CRP only described as an exploratory/tertiary outcome. The authors should describe the timing and rationale for switching the outcome from a clinical one (need for supplemental oxygen in the first 15 days post-randomization) to the inflammatory biomarker CRP.

      3. Despite changing the timing of CRP measurements, data on this modified primary outcome of CRP was missing in a large proportion of patients at day 5, and in the majority of patients at day 8. Further details should be provided regarding the reason for missing data, how this was handled in their analyses, and how this should temper conclusions.

      4. Finally, performing an interim analysis and disseminating their results in the midst of an open-label trial with subjective endpoints can pose challenges to maintaining impartiality. The authors should describe how they will mitigate potential allocation, performance, detection and attrition bias during the remainder of the trial.

      I hope that the authors will seriously consider these comments.

      Sincerely,<br /> - Ricky Turgeon

    1. On 2020-07-15 11:28:56, user One bird one cup wrote:

      The CDC quotes a current best estimate for planning purposes as .0065. I'm not sure if that's just for the US. The above study is the only study they list that contributes to that estimate. I'm sure I'm missing something here but I just don't understand the numbers. I will look closer, though.

    1. On 2020-08-25 08:12:24, user Bart Rijnders wrote:

      The analysis is done with days after diagnosis (I presume the positive PCR this is) and not days since start of symptoms and the most important variable. This means that the diagnosis can thus be made somewhere between >14 days preceding hospital admission (if the test was done by a GP of testing venue) but can also be several days after hospital admission (e.g. when the first PCR is false negative but the second is positive)

      Important bias may happen when patients who get tested easily / earlier on in the disease course while still outside the hospital also can get hospitalized easier (e.g. good health insurance). These patients will be overrepresented in the "treatment within 3 days after diagnosis" group. I do not see how this was (and can) be accounted for.

      The study should therefore analyse the treatment effect in function of symptom duration at time of plasma transfusion as well and how this relates to a possible therapeutic effect of plasma. Hope this will be possible

    1. On 2021-02-09 09:47:38, user Alex wrote:

      Hi guys, interesting paper. I’m curious as to how you justified a change in well-being pre-during when baseline data was collected during the peak?

    1. On 2020-09-07 03:47:09, user Stephen D wrote:

      Your conclusion is faulty. Note that nothing in your data implies that anything should be made "mandatory". Your modeling might imply that if everyone wore a mask 24/7, the effect would be to reduce the probability of a certain increase in infections. But it cannot in principle have any implication as regards legal responses by governments. This is not science. Your conclusion is framed using political and ethical concepts implied in the term "mandatory" that are in principle not amenable to science, and cannot be inferred from data or models.

    1. On 2020-09-09 11:10:26, user Andrew Broadbent wrote:

      Draft comment by – T Andrew Broadbent CES Economic & Social Research info@ces.org.uk

      Overview<br /> This important paper claims to transcend the large number of ‘conventional’ epidemiological ‘SEIR’ models (Susceptible, Exposed, Infectious, or Recovered) of the current pandemic. Its fascination lies in its attempt to ‘compare SEIR models of immune status’ and derive results more directly from the data available.<br /> It uses ‘Bayesian inference’ on data from 10 countries from 25 Jan to 20 June 2020 to estimate the daily proportion of people in each country who are (i) not exposed to infection(ii) not susceptible even though exposed (iii) not infectious even when susceptible. These sub-populations are what the authors call ‘dark matter’. It concludes that many more of the population are ‘effectively immune’ than generally understood, and so the second wave can be indefinitely postponed or suppressed without successive lockdowns as concluded from some of the conventional models.<br /> The immediate issues and queries seem to be :<br /> (i) Suppression is said to depend on an effective Track and trace system, as with some ‘conventional’ models. The practical policy implications are thus not very different from studies which suggest maintaining restrictions until infection is very low, so as to enable managing with track and trace, without needing to reimpose universal lockdown.<br /> (ii) The proportion of the population isolating/shielding dominates the results (eg Germany) . This is social behaviour and government policy, not ‘dark matter’ in the way susceptibility and infectibility may be, being more biologically determined.<br /> (iii) The parameters in the model are estimated within limits determined from external sources This may include the predominant ‘effective population’ parameter – the population who are not shielding.<br /> (iv) ‘Effective herd immunity’ is a somewhat troubling term – given overtones of ‘let the old die’ in some policy discussions of ‘herd immunity’.<br /> (v) It claims to incorporate all the different data collection biases in different countries, such as testing people with or without infection. Would it be worth including countries with early success in suppressing infection – Taiwan, S Korea, China, New Zealand etc?<br /> ‘Effective’ herd immunity?<br /> It references other studies which also look at ‘heterogeneity’ of the population, where the first wave either kills or makes immune the more susceptible population – so that a second wave necessarily involves a less susceptible population and will tend to be lower than the first wave, other things being equal.<br /> It concludes that ‘effective herd immunity’ following the first wave of infection is much higher than suggested by the proportion of people who have been infected and recovered and may now be immune – ‘seroprevalence’ . This is now in the range 5-7% in the UK.<br /> The term ‘herd immunity’ prompts wariness following the UK government’s early discussions which were interpreted as contemplating 60-80% of the population becoming infected with 500K-1 million deaths. ‘Culling the old and infirm’ was one interpretation. The paper concludes that having less than 20% of the population infected and recovered could be enough to dampen a second wave.<br /> The second wave - a ten-fold reduction in infection and death?<br /> A main claim of the paper is that the second wave could be postponed indefinitely, or if not, have a factor of 10 fewer infections and deaths than predicted by some SEIR models, (deaths peaking at 30-100 per day in the UK, compared with 1000 per day at the peak of the first wave) .<br /> But this projection, has in common with the conventional models, a heavy reliance on an effective FTTIS (‘Find, Test, Trace, Isolate, Support’) system in order to isolate those infected or exposed to infection. But the paper suggests that only 25% efficacy of FTTIS is needed, compared to the present official target of 80%.(?)<br /> Dark matter – very high?<br /> ‘Dark matter’ seems a very high proportion of the population. From one illustration (figure 2) dark matter results in under 20% of the population being infected. Almost 50% of the total population are not exposed (shielding/sequestered), so that only half the populations is ‘effective’ in the epidemic. Of those who are, 50% are not susceptible, and of those who are susceptible 50% are not infectious. <br /> The proportion of the total population which is non exposed (self isolating, shielding, sequestered) would seem to be very dependent on people’s behaviour and on government instructions, and thus on the social context and time lapse of the pandemic. The other components of ‘dark matter ‘ - susceptibility and infectibility – seem more biologically determined, not so subject to behaviour and social and policy context.<br /> Data – why not include countries with greater success in suppressing the first wave?<br /> Although the FTTIS is said to be enough to limit or suppress the second wave without a ‘lockdown’, the Bayesian inference was conducted on countries, many of whom who were in some kind of lockdown for at least part of the period. They are the 10 countries with high death rates.<br /> The data is from USA, UK, Canada, Spain, France, Italy, Belgium, Germany, Mexico, and Brazil . It would have been interesting to include countries which largely succeeded suppressing the virus in the first wave, with either very short sharp lockdowns, or early interventions of intense FTTIS, namely Taiwan, South Korea, China, Hong Kong, Singapore, New Zealand. <br /> Many model parameters are influenced from outside the model. (?)<br /> There ar 25 parameters listed in the model, and their levels and potential variation – are apparently influenced by external empirical studies outside the model, and are listed as ‘priors’. This apparently influences the final estimated parameters after the model has been run. (?)<br /> Parameters include the effective population, the probability of going out, social distancing threshold, critical care capacity threshold (per capita), Infection, proportion of non-infectious cases, effective number of contacts, effective number of contacts: work, transmission strength, infected period , infectious period , proportion of non infectious people etc. etc.<br /> Rich findings – country by country results – ‘effective population’ dominates?<br /> The paper suggests that only Spain, and Brazil don’t exhibit the heterogeneity embodied in the model – in that their whole population seems to participate in the epidemic – their ‘effective population’ is equal to the whole population, with almost no one isolating, or shielding.<br /> The country comparisons involve changing the input parameters, so as to eliminate each component of heterogeneity in turn. The parameters - effective population, non susceptibility, social distancing threshold, decreasing seropositivy are each removed in turn.<br /> Germany and Canada have by far the smallest proportion of ‘effective population’ due to their high levels of shielding – this seems to determines their relatively good performance and low level of deaths, - it would be useful to learn more about how far this parameter is set ‘prior’ to the model.<br /> There is much less variation in the proportion of the effective population susceptible to infection – from ~67% in Spain (operating on an effective population almost equal to the whole population) , to ~47% in Canada.<br /> Similarly there is low variation in the proportion of susceptible people who are non infectious – from ~60% in Canada and Italy and to ~45% in Germany, France , and USA .<br /> Some more details<br /> The claim is that the analysis can incorporate all kinds of real world fuzziness in the data - by modelling latent variables such as the bias towards testing people with or without infection or, the time-dependent capacity for testing. ‘Everything that matters —in terms of the latent (hidden) causes of the data—can be installed in the model, including lockdown, self-isolation and other processes that underwrite viral transmission’.<br /> This is a ‘LIST’ model with four factors (Location, Infection, Symptoms and Testing). It models the probability of people being in different states, and produces two outputs – positive cases, and deaths .<br /> The states in each factor are::<br /> Location – Home, Work , Hospital, Isolated, Removed<br /> Infection – Susceptible, Infected, Infectious, Sero negative, Seropositive<br /> Symptoms – Health, Symptoms, Severe, Deceased<br /> Testing – Untested, Waiting, Negative, Positive<br /> Each individual in the population has to be in one state, and only one state, within each of the four factors.

    1. On 2020-09-13 19:32:19, user Qunfeng Dong wrote:

      An updated version of this manuscript is now accepted for publication by Journal of the American Medical Informatics Association Open Access on Sep, 13, 2020.

    1. On 2021-02-27 06:50:50, user Suriati Jamalludin wrote:

      good exploration. i'm digging the source that online learning during emergency response are facing the problem mental health disruption among student. therefore the learning continuity is not easy when student in a bad condition of mental health. how do i use the reference as a support. may i have the reference format this article for citation?

    1. On 2021-09-01 02:33:45, user Andrea Boggan wrote:

      "Survival of the Flattest." This new variant will wait it's turn until Delta is through delivering its blow, and when Delta is done, it and the others waiting in the wings will step forward and compete for fuel.

    1. On 2021-03-17 10:01:33, user Bernhard Brodowicz wrote:

      As the aim of this study was to determine the prevalence of SARS-CoV-2 it is essential to define the parameters when a test is rated as SARS-CoV-2 positive or negative (as a qualitative analytical test result, ct-value cutoff, handling of different results for viral targets…). Neither the paper itself, nor in the supplementary data, gives an evidence about how positive and negative test results were delimited. Especially as different analytical setups were used, validation data of the different RT-qPCR setups should be reported, discussed and comparability should be shown. When reporting quantitative analytical results (viral loads in children and adults via ct-values), the method should be validated for its quantitative purpose (including standardization). Especially when using different analytical setups this is crucial to assure the reporting of valid and comparable results. Looking on ct-values given in Supplementary Figure 2b the results from Graz (first round), which used a FDA authorized and (also for pool samples qualitative) validated diagnostic kit, showed comparable results for both targeted genes (E and ORF1a/b) and suggests robust positive results for 9 samples in pupils. For other assays the human housekeeping gene RPP30 (RP2) was used as sample control. In clinical diagnosis it might be useful (specially to reduce the risk of false negatives) to also report test results as positive when only one viral target is detected or RPP30 (RP2) was absent, but only when covered by method validation results. However, in a study, where different analytical setups were used, it should be further investigated and discussed, when viral target N2 and ORF1b were report as positive results also with high ct-values (> 40) and in the absence of RPP30 (as it is suggested by Supplementary Figure 2b). This could question the validity of the analytical setup used in this study and is calling for the presentation of the validation parameters of the different RT-qPCR setups to interpret comparable results.

    1. On 2021-07-27 12:56:21, user James Jarvie wrote:

      This paper is referred to as evidence that vaccine is superior to naturally acquired immunity. However, the paper appears to me to suggest that vaccine is as-good-as naturally acquired immunity (using naturally acquired immunity as the benchmark).

    1. On 2020-10-14 02:40:05, user Robert Stephens wrote:

      Could it be that a more recent HCoV infection increases the likelihood of the dysfunctional 'back boost'. If such is the case then perhaps this partially explains the lower second wave CFRs seen in many European countries. Maybe the Sars-CoV-2 mitigating behaviours (distancing/ masks etc) have also reduced the incidence of HCoV infections in the preceding 6 months - thereby reducing the frequency and amplitude of the back boost.

      Dr Robert Stephens MB BS FACD

    1. On 2021-03-30 12:09:03, user jgas wrote:

      Has there been furtheer follow-up beyond 72 hrs?<br /> This data would really help to clarify possible mechanism of serious adverse effects emerging with the roll-out of the Oxford adenovirus vector vaccine to frontline workers across Europe and the safety of use of these adenovirus vectors per se.

    1. On 2021-07-31 00:05:48, user Arthur wrote:

      Check these stats from results section.<br /> The percentages of white, black and Latino participants do not add up to 100%.

      Please check before publishing , these are some things that makes a publication lose credibility.

      Participants were 49% female, 82% White, 10% Black/African American, and 26% Hispanic/Latinx; median age was 51 years.

      Then

      Of vaccinated participants, 58% had >=2 months follow-up post-dose 2, 49% were female, 86% were White, 4.6% were Black/African American, and 12% were Hispanic/Latinx.

    1. On 2021-04-09 12:49:29, user Francesco Pilolli wrote:

      In spite of the difficulties encountered by other studies evaluating the efficacy of therapies in outpatients, this work describes an impressive statistically significant reduction in the hospitalization rate.<br /> This study reports a share of hospitalised patients in the “recommended” cohort (2,2%) similar to the one described in the placebo groups of the Pfitzer-Biontech (2,5% https://www.fda.gov/media/1... ) and Moderna (3,3% https://www.nejm.org/doi/fu... ) vaccine studies between symptomatic cases (these studies did not exclude hospitalised cases at the onset), but it describes an impressive 14,4% share of hospitalised cases in the “control” group.<br /> This rate is much higher than the one described in the placebo group in the Bamlanivimab and Etesevimab study in high-risk outpatients (7% https://www.fda.gov/media/1... ) and in the COLCORONA trial again in the placebo group of high-risk outpatients (5,8% https://www.medrxiv.org/con... ).<br /> It’s peculiar that this study (carried out on general population and excluding severe cases at onset) describes a hospitalization rate in the control group much higher than that observed in other studies in high-risk patients, considering also hospitalisation at onset.<br /> I think that the majority of the difference of the hospitalisation ratio between “recommended” and control group could be explained by the choice of selecting 88 out of 90 cases of the control group from people infected in the first wave in the province of Bergamo, one of the most severely hit zones in Italy.<br /> The control group required swab or serological positivity but the swab test capacity was limited in Italy during the first wave and it is very unlikely that all the symptomatic people underwent a serological test. During the first wave many symptomatic people were at home without having undergone any swab. The limited test capacity causes a high underestimation of paucisymptomatic and mild cases resulting in a high rate between hospitalisation and tested cases.<br /> In fact the Italian ratio between hospitalisation and tested cases from March to May 2020 (the same infection period of 88 out of 90 patients of the control cohort) was 36,4% compared to the 7,8% observed from October 2020 to January 2021 https://www.epicentro.iss.i...<br /> This difference was much higher for the province of Bergamo. Data about daily hospitalisation by province are not public but we know the cases ( https://lab24.ilsole24ore.c... and deaths ( https://www.istat.it/it/fil... ) by province until December 2020. While the ratio between Italian cases and deaths was 14,8% from March to May 2020, it falls to 2,2% from October to December, in the same periods the rate deaths/cases in the province of Bergamo was 23,4% (almost one patient with positive swab every four died in the first wave) and 1,5% (less than the Italian average).<br /> Therefore, it is very likely that the majority of the difference in the hospitalisation rate between the “recommended” (from the second wave) and the “control” cohort (from the first wave in the most hit zone in Italy) is explained by the different historical moments which were characterised by a large difference in test capacity and many symptomatic people at home without getting tested during the first wave.

    1. On 2021-08-03 10:01:20, user Alan Yoshioka, PhD wrote:

      There are several numerical discrepancies and questions about methods that should be resolved before any conclusions can be drawn from the study.

      When was it decided to exclude patients whose RT-PCR results had a cycle threshold value >35 in the first two consecutive [tests]? When was it decided to adjust the Kaplan–Meier analysis for symptom onset?

      Please reconcile the discrepancy between the "mild" in study title and the "mild to moderate" in the description of the mandate of the isolation hotels. The inclusion criteria do not appear to specify the severity of disease, which would apparently then depend on the admission criteria of the hotels.

      In Table 1, stated percentages of patients who are male do not match raw numbers of 69/89 for all patients and 36/47 for ivermectin, respectively; instead (corresponding to females accounting for 21.6% in the abstract) 78.4% = 69/88, and 78.3% = 36/46.

      The abstract says 16.8% were asymptomatic at baseline, which does not complement the 80.9% symptomatic in Table 1, nor the 69 symptomatic patients in Figure 3. Perhaps I am missing something, but it is not clear why 37 and 35 symptomatic patients in Table 1 do not match the numbers of subjects at risk, 36 and 33, on Day 0 in Figure 3.

      Table 2 presents results from RT-PCR testing at days 4 to 10. Day 2 is said to have been added to the protocol along with Day 4, but no explanation is given for why data from Days 2, 12, and 14 are not also shown in the table.

      I'm not a specialist in lab tests, but I'm afraid I am having trouble understanding the post hoc analysis based on a convenience sample of 16 samples on Day 0. Does Table S2 mean there were then 26 samples taken on Day 2?

      I am mildly puzzled by the alignment of the dots in Figure 2: most appear to lie on a grid, but a few sets of points are slightly raised or lowered. Is this a normal occurrence?

    1. On 2022-06-22 18:31:49, user Elisabeth Bik wrote:

      I have serious concerns about the data integrity of this paper, in particular about Figures 2 and 3. Some constellations of data points in these images appear to be duplicated within or across panels, and the lowest/highest values of the X axis (which should be the same across the four panels within a figure) appear to unexpectedly vary. This paper has been published in Sleep Science in 2020, under DOI: 10.5935/1984-0063.20190133 and I have posted my detailed concerns on PubPeer at https://pubpeer.com/publica...<br /> The PubPeer entry lists other concerns about this paper as well, including concerns about the ethical approval process and the p values in Table 1, raised by PubPeer user 'Meliosma donnellsmithii'.

    1. On 2024-02-26 17:17:08, user Ciarán McInerney wrote:

      Please, justify why<br /> statistical significance of individual values in your omnibus PheWAS protocol<br /> warrants an indication of predictive performance? Firstly, looking at main<br /> effects in an omnibus assessment commits the Table 2 fallacy (doi: 10.1093/aje/kws412).<br /> Secondly, the p-value associated with an odds ratio is a statistic related to<br /> the validity of the parameter estimate in a hypothetical null world. It can and<br /> should only be used for making statements about the model used to estimate the<br /> parameter of interest (in your case, the odds ratio). It has nothing to do with<br /> the quantifying the association. Thirdly, why do you select features based on the<br /> p-value but not the magnitude or direction of the association statistic to<br /> which it refers? A feature with a very large magnitude might be clinically<br /> meaningful for many patients, regardless of how spread the distribution of that<br /> feature’s values are.

    1. On 2024-04-09 15:52:16, user Tarachopoiós wrote:

      This looks like an intersting analysis. One question was around the correlation of predictors to TTFT. So growth rate requires time-series data to be estimated did you account for the time taken to estimate growth rate? One option would have been to use a joint longituinal time to event model to account for immortal time bias. How did you account for immortal time bias in your analysis i.e. the fact that tumour growth rate isn't known at your time zero? Or is it known? That wasn't clear in the methods.

    1. On 2024-04-27 19:47:53, user Rebecca L. Roop wrote:

      Thank you for the work and dedication to create this article for publication. I suffered through TSW for 24 months after only using various classes of topical steroids for 12 months. That period of my life was absolute hell.

    2. On 2024-04-28 13:06:50, user Gina Dee wrote:

      I’m so happy and relieved to see research being done to better understand TSW. My daughter suffered through TSW starting at the age of 2 and it was a nightmare. We had to struggle through with minimal support from doctors. I hope this study and further studies help to lessen the occurrence and better treat the condition.

    3. On 2024-05-01 03:00:07, user Bernadette wrote:

      Firstly my thanks to each one of you. This paper gives me hope that diagnostic and treatment guidelines for ‘TSW’ can be developed. I have a H/O of 70+ years of skin problems. Having struggled for 4 years with skin rashes which present to me, and to a Sydney based GP with an interest in TSW, as being consistent with TSW, I have experienced the frustration of presenting to dermatologists who say TSW is not an ‘accepted’ skin condition even though I have experienced and photographed my red sleeve, elephant skin on my ankles and wrists, non stop oozing on my face, neck and ears, non stop skin flaking, hair loss, heat, pain and intense itching. I have experienced the isolation and depression too often associated with this condition. Recently I have focused on managing heavy staph and fungal concentrations and have seen significant improvements. So I’m hoping this paper will act as a catalyst for a comprehensive focus on TSW so that we, those affected, can access medical expertise without running the gauntlet of being dismissed and belittled. Again. Thank you.

    4. On 2024-05-08 14:58:49, user mira wrote:

      Thank you for carrying out this research. This preprint needs to be published so people and the medical world can finally stop gaslighting us and telling us it's "just eczema". I have been suffering for years with TSA and after quitting steroids my life has been terribly changed because of TSW. We are so overlooked, desperate for knowledge and solutions, we are a suffering community.

    5. On 2024-05-09 14:39:59, user Ana Angel wrote:

      Very important piece of research for the thousands of us suffering from this condition. More research is needed! <br /> I stopped all forms of steroids 4 years ago. I’m now much much better, but still flaring on my elbow creases. We need treatments to shorten these lo g recovery times

    1. On 2024-10-19 15:28:14, user Steve Laurie wrote:

      Great work - congratulations. Let's hope WGS becomes standard of care in NICUs some day soon.

      Just wanted to let you know that you have duplication of text in the Methods in the current version, lines 144-153 and 153-162.<br /> I also doubt that citation 67 at the end of the paragraph is the one you meant to cite.

    1. On 2024-10-27 08:26:34, user Mohsen Ghanbari wrote:

      This preprint has been published recently:

      A comprehensive study of genetic regulation and disease associations of plasma circulatory microRNAs using population-level data.Genome Biology. 2024 Oc t 21;25(1):276. doi: 10.1186/s13059-024-03420-6.

    1. On 2024-12-03 21:07:38, user xPeer wrote:

      Courtesy review from xPeerd.com

      This manuscript investigates the genetic underpinnings of gene expression noise (variability in mRNA expression) and its contributions to complex trait variation. By leveraging single-cell transcriptomics from 1.23 million peripheral blood cells across 981 individuals, the study identifies expression noise quantitative trait loci (enQTLs) in seven immune cell types. Key findings include distinct enQTLs independent of traditional expression QTLs (eQTLs), with implications for hematopoietic traits and autoimmune diseases. This comprehensive analysis highlights gene expression noise as an overlooked molecular trait impacting genetic variation in complex traits.

      Strengths include the integration of large-scale single-cell data, robust methodological frameworks, and a novel focus on noise QTLs. However, the work’s translational potential and certain mechanistic aspects require refinement.

      Major Revisions<br /> 1. Mechanistic Depth<br /> Limited Exploration of Noise Regulation Mechanisms:

      While the authors identify enQTLs enriched in chromatin marks (e.g., H3K27ac, H3K4me3), the functional pathways connecting these marks to noise modulation are underexplored (Section: Functional Enrichment, p.8). Including mechanistic validation, such as CRISPR perturbation experiments targeting key SNPs, would enhance understanding.<br /> The interplay between noise and transcriptional bursting models (e.g., initiation frequency vs. burst size) remains superficially addressed. Expanded quantitative modeling of burst kinetics could better explain noise-associated traits (Section: Discussion, p.9).<br /> Post-Transcriptional Contributions:

      The discussion briefly mentions mRNA stability but does not evaluate post-transcriptional regulation’s role in noise. Experimental validation, such as ribosome profiling or RNA decay assays, could substantiate these claims.<br /> 2. Population Diversity and Generalizability<br /> Limited Ancestral Representation:

      The cohort comprises Northern European ancestry individuals, limiting the generalizability of enQTL findings. Noise might vary due to ancestry-specific SNP frequencies or regulatory architectures (Section: Methods, p.3). Validation in diverse populations is critical for ensuring broad applicability.<br /> Cell-Type Specificity:

      Some findings, such as HVGs shared across cell types (e.g., HLA genes), require validation in other tissues or disease models. Cell-specific functional assays could strengthen the biological relevance of these findings.<br /> 3. Statistical and Computational Robustness<br /> Unexplained Variance in enQTL Effects:

      While enQTLs explain certain GWAS loci, the authors do not quantify the proportion of unexplained variance attributable to unaccounted mechanisms (Section: GWAS Colocalization, p.10). Comparative analysis with polygenic risk scores or partitioning heritability methods would contextualize enQTL contributions.<br /> Colocalization Analysis Limitations:

      Colocalization methods prioritize high-probability overlaps (PP.H4 > 0.7), but alternative loci with moderate probabilities (e.g., PP.H4 > 0.5) might merit inclusion. Revisiting loci with expanded statistical thresholds could yield additional insights.<br /> 4. Functional Insights<br /> Overemphasis on Chromatin Features:

      While the enQTL analysis emphasizes chromatin states, the link to noise-specific regulatory dynamics is unclear. Functional experiments, such as live-cell imaging of noise dynamics in specific chromatin contexts, would substantiate claims (Section: Functional Enrichment, p.8).<br /> Underexplored Relationship Between enQTLs and Disease:

      The finding that autoimmune risk variants correlate with attenuated noise is intriguing but not mechanistically explained (Section: Discussion, p.9). Immune activation studies in enQTL-defined contexts could clarify whether lower noise promotes immune tolerance or other phenotypes.<br /> Minor Revisions<br /> 1. AI Content Analysis<br /> Estimated AI-Generated Content: ~15-20%.<br /> Stylistic Observations: Repetitive phrasing (e.g., “highlighting noise as an important mediator”) and predictable transitions suggest AI-assisted drafting in some sections.<br /> Epistemic Impact: Minimal; technical content is original, but editing for stylistic variation is recommended.<br /> 2. Figures and Data Presentation<br /> Figure Annotation:<br /> Figures (e.g., Figures 3-5) lack precise legends detailing axes, significance thresholds, and methodological descriptions.<br /> Supplemental figures require clearer integration into the narrative (e.g., referencing HVG enrichments in Figure S2).<br /> Data Accessibility:<br /> Raw data from single-cell noise calculations and SNP annotations should be made available as supplementary files for reproducibility.<br /> 3. Terminology Consistency<br /> Inconsistent Definitions:

      Terms like “expression noise” and “transcriptional variability” are used interchangeably but should be clearly defined early in the manuscript.<br /> Confusing Use of Abbreviations:

      HVG, enQTL, and eQTL acronyms require standardized introduction and consistent usage across sections.<br /> 4. Citations and References<br /> Key Omissions:<br /> Recent advances in single-cell variability analysis (e.g., newer methods beyond tensorQTL) are underrepresented. Including citations for innovative noise quantification approaches (e.g., scVI) would modernize the references.<br /> Recommendations<br /> Mechanistic Studies:

      Employ experimental tools (e.g., CRISPRi/a, live-cell reporters) to validate enQTL roles in noise dynamics.<br /> Integrate transcriptional bursting models to elucidate enQTL regulatory mechanisms.<br /> Enhance Population Scope:

      Expand cohort analysis to include non-European populations.<br /> Incorporate ancestry-aware computational models to assess demographic variability in enQTLs.<br /> Data Presentation Improvements:

      Add supplemental raw data files for transparency.<br /> Expand figure annotations and connect supplemental content to main findings.<br /> Expand GWAS Interpretation:

      Investigate enQTL roles in non-immune traits to broaden the study’s impact.<br /> Compare enQTL contributions with existing functional annotations (e.g., enhancers, transcription factor binding sites).

    1. On 2024-12-11 16:30:22, user Andrew Hagen wrote:

      This preprint has now been published in its final form as:

      Hagen AC, Tracy BL and Stephens JA (2024)<br /> Altered neural recruitment during single and<br /> dual tasks in athletes with repeat concussion.<br /> Front. Hum. Neurosci. 18:1515514.<br /> doi: 10.3389/fnhum.2024.1515514

    1. On 2024-12-15 08:46:43, user Ujváry István wrote:

      Note the correct chemical name:<br /> bis(2,2,6,6-tetramethyl-4-piperidinyl) sebacate

      (BTMPS is a piperidine derivative; it is not a pyridine derivative!)

    1. On 2024-12-23 02:34:26, user IA Signore wrote:

      Now published as Signore, I. A., Donoso, G., Bocchieri, P., Tobar-Calfucoy, E. A., Yáñez, C. E., Carvajal-Silva, L., ... & Colombo, A. (2024). The Chilean COVID-19 Genomics Network Biorepository: A Resource for Multi-Omics Studies of COVID-19 and Long COVID in a Latin American Population. Genes, 15(11), 1352.

    1. On 2025-01-02 09:48:12, user Teresa Ramírez García wrote:

      Dear Dr. Witt: We have read with great interest your article published in preprint format. In this article, an aspect that we consider confusing is mentioned in relation to our work [1]. We refer to the authors' assertion that “in the FCSRT only 4 words need to be learned in three learning trials, whereas the VLMT requires learning of 15 words in 5 trials” [2].

      In this regard, we would like to point out that the FCRST requires you to effectively memorise 16 words spread across 3 trials, not just 4 words, as stated in the original paper by the author who developed the exam. Because it aligns with the original test scales by age and cognitive reserve of the patients in the Spanish population, this test can also be explained in the Neuronorma project, which we use in Spain. Since we discovered a baremation based on the Spanish population [3], this is also the reason why this test is typically utilised in Spain.

      1.- Serrano-Castro PJ, Ramírez-García T, Cabezudo-Garcia P, Garcia-Martin G, De La Parra J. Effect of Cenobamate on Cognition in Patients with Drug-Resistant Epilepsy with Focal Onset Seizures: An Exploratory Study. CNS Drugs. 2024 Feb;38(2):141-151. doi: 10.1007/s40263-024-01063-6. Epub 2024 Jan 24. PMID: 38265735; PMCID: PMC10881647.

      2.- Witt JA, Badr M, Surges R, von Wrede R, Helmstaedter C. Negative Impact of Cenobamate on Cognition: Dose-Dependent and Independent Effects medRxiv 2024.12.23.24319533; doi: https://doi.org/10.1101/2024.12.23.2431953

      3.- Peña-Casanova J, Gramunt-Fombuena N, Quiñones-Ubeda S, et al. Spanish Multicenter Normative Studies (NEURONORMA Project): norms for the Rey-Osterrieth complex figure (copy and memory), and free and cued selective reminding test. Arch Clin Neuropsychol. 2009;24(4):371-393. doi:10.1093/arclin/acp041

      Ramirez-Garcia T and Serrano-Castro PJ.

      Hospital Regional Universitario de Málaga.

      Instituto de Investigacion Biomedica de Málaga (IBIMA-Plataforma Bionand).

    1. On 2025-01-16 06:08:40, user xPeer wrote:

      Courtesy review from xPeerd.com

      Summary:<br /> The manuscript titled "Typhinder: Rapid, low-cost colorimetric detection of Salmonella Typhi bacteriophages for environmental surveillance" presents a novel colorimetric assay designed to detect Salmonella Typhi (S. Typhi) bacteriophages in environmental water samples. This study primarily focuses on areas with poor sanitation infrastructure, including regions in Brazil, Côte d’Ivoire, Nepal, and Niger, demonstrating high sensitivity and specificity of the assay. The work indicates potential applications in public health surveillance, particularly in resource-limited settings, by providing a cost-efficient method (approximately $2.40 per sample) that does not require sophisticated equipment.

      Potential Major Revisions:

      1. Validation and Methodological Robustness:<br /> One key concern is the validation of the colorimetric assay only against the double agar overlay method. More comprehensive testing against additional molecular techniques like PCR/qPCR, which are considered gold standards for pathogen detection, is essential to determine the assay's accuracy and reliability under diverse environmental conditions. This gap was acknowledged in the discussion section.

      2. Sample Diversity and Detection Limit:<br /> The study demonstrates that the detection limit is 28 PFU/mL, which although sensitive, may need further optimization to ensure applicability in environments with even lower pathogen concentrations. Additionally, the research did not provide adequate comparative data from different environmental contexts, such as varying water sources with potential inhibitors like antibiotics, which could affect assay reliability.

      3. Comprehensive Data Analysis:<br /> The study's reliance on environmental surveillance data lacks integration with epidemiological data and molecular-based assessments of typhoid burden. Correlating phage detection with rates of clinical typhoid fever incidents would offer stronger evidence of the assay's utility in public health management. Future studies should aim to establish these correlations more explicitly.

      Potential Minor Revisions:

      Typographic and Grammatical Errors:<br /> 1. Page 2, Line 1: "particularly in low-resource settings with inadequate sanitation." - Repetition of the phrase "particularly in low-resource settings", consider rephrasing for clarity.<br /> 2. Page 6, Line 3: "require precise data on where typhoid is most prevalent, yet current surveillance methods are expensive and limited in scope..." - The sentence structure could be improved for readability.<br /> 3. Page 9, Line 5: "Antimicrobial resistance among S. Typhi strains poses serious challenges to effective treatment and may lead to higher mortality..." - Consider rephrasing for clarity.

      Formatting Issues:<br /> The figures and tables should be better integrated into the text for improved readability. For example, citing Table 1 and Figure 2 explicitly within the corresponding discussion for context will aid readers' understanding.

      AI Content Analysis:<br /> - Estimated AI-generated content: Given the extensive detail and specific nature of the subject, it is estimated that the manuscript has less than 5% AI-generated content.<br /> - Highlighted AI-detected sections: The introductory summary and some instances of repetitive phrasing suggest possible AI involvement.<br /> - Epistemic impact: Minimal as the core research contributions and data seem original and substantive.

      Recommendations:

      1. Enhanced Validation:<br /> Incorporate a broader range of validation techniques, particularly molecular methods like qPCR, to establish the assay's robustness across different environmental samples and contexts.

      2. Addressing Limitations:<br /> Include detection methods for concurrent fecal contamination to provide contextual data, enhancing the reliability of typhoid phage detection results as environmental indicators.

      3. Future Studies:<br /> Focus future research on correlating phage presence with clinical incidence of typhoid fever, and explore structural analysis of phage-host interactions. This will substantiate the assay's efficacy in public health interventions and policy-making.

      Overall, the manuscript provides a promising tool for typhoid fever surveillance in low-resource settings, with significant public health implications. Addressing the detailed critiques will strengthen the manuscript and its potential impact.

    1. On 2025-02-05 20:08:07, user Daniel Corcos wrote:

      Gotzsche and Jorgensen claim to have found a high level of overdiagnosis after mammography screening. However, the method they use does not allow them to distinguish between cancers related to overdiagnosis and those caused by X-rays. Yet, when measuring the delay in the appearance of excess cancers, it becomes clear that, in addition to the excess corresponding to the lead time due to detection, there is a significant excess of delayed-onset cancers, which are therefore caused by X-rays ( https://www.biorxiv.org/content/10.1101/238527v1.full ; Corcos D & Bleyer, NEJM, 2020). These cancers explain the failure of screening at decreasing breast cancer mortality observed at 13 years by the authors.

    1. On 2025-02-10 12:39:18, user MINGXIN LIU wrote:

      This preprint has been published in International Journal of Medical Informatics and can be accessed at: " https://doi.org/10.1016/j.ijmedinf.2024.105673 ."

      The title of the published version has been changed to "Evaluating the Effectiveness of advanced large language models in medical Knowledge: A Comparative study using Japanese national medical examination". Readers are encouraged to refer to the published version for the final peer-reviewed content.

    1. On 2025-02-12 20:00:36, user Aron Troen wrote:

      Review Part III

      Results and Discussion<br /> Quantity of food trucked in: No source is cited for the figure of a pre-war baseline of 150-180 food-transporting trucks per day. This number is inconsistent with Israeli and UN sources. According to a document published in June by the Food Security Cluster, only 23% of UN recorded incoming goods to Gaza (not including fuel) before 7 October were food or food production inputs ( https://fscluster.org/sites/default/files/2024-06/Gaza%20imports%20and%20food%20availability%2015_may_V2%202.pdf) "https://fscluster.org/sites/default/files/2024-06/Gaza%20imports%20and%20food%20availability%2015_may_V2%202.pdf)") . If one is to rely on those UN statistics, the pre-war monthly average of trucks carrying food into Gaza was 2,288 (an average of approximately 100 trucks per working day in a normal month). Another UN source is the OCHA online Gaza crossings dashboard according to which during Jan-Sep 2023 a total 27,434 trucks carrying food entered Gaza, representing a monthly average of 3,048 trucks. <br /> The comparison in Figure 1 between the mean daily number of trucks for each week during the war with the "pre-war number of food-carrying trucks" per working day is highly misleading since it assumes that the number of working days remained steady. The distortion is significant because between 21 October and 5 May the crossings were open almost every day, as opposed to the 5-day work week in the period before the war. The following chart shows the monthly figures of UNRWA and COGAT compared to the monthly pre-war average of 2,288 trucks carrying food.

      Compare it with Figure 1 from the article, which tells an entirely different story for the same period (blue columns represent trucks carrying food) in which is all but one week at the end of April the number of trucks carrying food was below the pre-war average:

      Contribution of different food sources [to the northern and southern regions] (Table 1 & Figure 4)<br /> The result and discussion devote substantial attention to the relative distribution of food between the northern and southern regions. The governates designated as North and South Gaza are not explicitly defined. The only explanation for how the author determined the distribution of food deliveries between Northern and southern-central Gaza is as follows:<br /> "Until Israel re-opened the northern Erez and Erez West crossings, trucks had to leave south-central Gaza to resupply the north. We reconstructed the number of these trucks over time based on published information and data shared by WFP. As no data on content were available, we simulated their caloric equivalent by repeatedly sampling from the empirical distribution of calories per truck obtained from the UNRWA dataset (see below and Figure S1, Annex). The remaining trucked food was attributed to the south-central region."

      The breakdown of that amount between northern and central-southern Gaza is based on an incomplete dataset (Commodities Received.xlsx) that appears to be missing the bulk of supplies by the private sector, appearing in the COGAT data ( https://gaza-aid-data.gov.il/main/) "https://gaza-aid-data.gov.il/main/)") , and which provided a significant share of supplies to the north. The dataset shows that during January and February 84 trucks were delivered to the north (according to the Logistics cluster). According to the same file, during March and April there only 20 private sector trucks delivered aid to the north. However, according to COGAT, deliveries to the north at that time were carried out mostly by the private sector, which are not fully covered by UN data. The flow of aid within Gaza and its regional distribution is difficult to ascertain. Media sources have provided conflicting reports from different sources. But they underscore the need to clarify precisely how the study assigned the regional food supply. For example, a story by the Associated Press from February 28 2024, reported that the UN had not been involved in aid deliveries to the North that month. According to one of COGAT's reports, during the first half of March they "facilitated over 150 aid trucks to the north" ( https://gaza-aid-data.gov.il/media/qtvbs5u0/humanitarian-situation-in-gaza-cogat-assessment-mar-15.pdf) "https://gaza-aid-data.gov.il/media/qtvbs5u0/humanitarian-situation-in-gaza-cogat-assessment-mar-15.pdf)") . In addition, COGAT claimed in a tweet from March 25 that UNRWA had not submitted a single request for delivering food to northern Gaza in six weeks ( https://x.com/cogatonline/status/1772316633605812511) "https://x.com/cogatonline/status/1772316633605812511)") . Thus, the methodology for determining the distribution of aid between northern and southern-central Gaza appears to be flawed since it almost entirely disregards aid deliveries by the private sector, which had a significant share of the total deliveries to the north during that period. Findings and conclusions that are contingent on this issue cannot be fully evaluated until this is corrected.

      Main findings

      The authors insinuate that the shortfall in the adequacy of food aid is solely due to intentional Israeli actions. For a subtle example of this the authors write that “Patterns in the diversity and caloric value of food trucked-in suggest that humanitarian actors may not have optimised the selection of what aid was allowed into Gaza.”. The food diversity findings suggest the humanitarian actors, who are responsible for deciding what is supplied to Gaza may not have optimized the selection of the aid. However, the use of the word “allowed” insinuates that the fault for this lies with Israel. The correct word should be “delivered”. Israel is responsible under international law for facilitating the entry of humanitarian aid. It is not responsible for selecting, procuring or delivering the aid. The fact that there was a considerable decline in food availability the first months of the war should not be surprising. Israel did not initiate the war, and should not be expected to have in place the logistics capacity for providing food to over 2 million conflict-affected people immediately after a strategic surprise attack. These major efforts, facilitated by the international community acting together with Israel, eventually yielded results as demonstrated by the study’s findings (eg. “a steep increase in food availability occurred from late April 2024, coinciding with the reopening of crossings into northern Gaza, and by June acute malnutrition prevalence appeared to be relatively low…”. [As noted above, “reopening” is a misleading term for the conversion of the Hamas-damaged Erez crossing from a pedestrian to a trucking terminal].

      Similarly, one might ask why the Hamas failed to prepare for the needs of the Gazan civilian population under its governance, while it demonstrably prepared meticulously for the attack that was intended to provoke retaliation.

      The authors seem intent to find Israel alone at fault, to encourage political pressure on Israel. They criticize “operations to deliver food via air or sea [as] cost-inefficient and a poor substitute for diplomatic pressure to merely reopen crossings”, stating in passing that “the 230M USD cost of the JLOTS operation [43] was higher than the entire humanitarian aid budget for the Central African Republic in 2024”. A back of the envelope calculation examining this assertion, and using WFP statements that their “emergency response [in Gaza] requires USD 740 million to provide support for up to 1.1 million people monthly” ( https://www.un.org/unispal/wp-content/uploads/2024/04/WFP-Palestine-Emergency-Response-External-Situation-Report-18-23-April-2024.pdf) "https://www.un.org/unispal/wp-content/uploads/2024/04/WFP-Palestine-Emergency-Response-External-Situation-Report-18-23-April-2024.pdf)") , shows that USD 740 per 1.1 persons monthly translates to 22.4 dollars per person per day. This means that the cost of the air-dropped food was only 29% higher than the delivery of land-based humanitarian food-aid. Thus, an equally plausible alternative interpretation of the resource expenditure might be that the air and sea operations, involving cooperation of USA, Jordanian, Israel and other Arab militaries to assist the Palestinian civilian population, could be considered a valuable attempt to circumvent the challenges to land-based humanitarian aid-operations during fierce fighting between Hamas and the IDF, as well as a means of exerting diplomatic pressure on the combatants. The policy implications and cost effectiveness of political pressure to increase food influx via land crossings are not obvious.

      Comparing the resources allocated by the international community to the Palestinian population versus the long list of other pressing humanitarian crises, out of proper concern for emergency-affected civilian populations, is indeed a vexed question. Clearly, a critical and balanced discussion of this issue is beyond the scope of this paper. However, if one insists on raising this important question, one might also question the efficiency of the billions of dollars donated to Gaza over the past decade by the international community, including from UNRWA, and how the funds, which were intended for civil and humanitarian development, were misappropriated by Hamas for a massive military buildup to the attack including the construction of hundreds of kilometers of military tunnels and the stockpiling tens of thousands of rockets and launchers, embedding them in their civilian population ( https://www.wsj.com/world/middle-east/hamas-gaza-humanitarian-aid-diverted-cf356c48; https://govextra.gov.il/unrwa/unrwa/#:~:text=Update%206%2F8%2F24%3A,massacre%20are%20credible%20and%20true; https://www.nytimes.com/2024/12/08/world/middleeast/hamas-unrwa-schools.html?unlocked_article_code=1.f04.lcW3.n2kj8akEfM-M&smid=nytcore-ios-share&referringSource=articleShare; https://www.atlanticcouncil.org/blogs/new-atlanticist/how-to-reform-unrwa-to-improve-palestinian-lives-and-israeli-security/) "https://www.atlanticcouncil.org/blogs/new-atlanticist/how-to-reform-unrwa-to-improve-palestinian-lives-and-israeli-security/)") .

      Limitations

      The authors acknowledge several of the more obvious limitations and assumptions described above. However, they minimize or arbitrarily dismiss these weaknesses and proceed to make tendentious interpretations in support of their preferred policy implications. For example, they write that they relied heavily on a single UNRWA dataset “which appears highly complete and well-curated” without explaining how they make that subjective and unsupported assertion. The authors are demonstrably aware of the controversy and limitations of the data, yet they feign ignorance and avoid placing the data in the context of the known controversy writing that the data “may be biased by systematic under- or over-reporting UNKOWN TO US”. This knowingly downplays and misrepresents the CERTAIN under-reporting of UNRWA trucking data which the official disclaimer states clearly on the online dashboard and in the dataset that they provide for review: “We [UNRWA] are unable to provide comprehensive monitoring of cargo for the following reasons: i) safety and security concerns, which continue to prevent UN staff from maintaining constant presence at Kerem Shalom, therefore severely impacting our ability to cross-reference UN cargo, and record data from INGO, Red Cross and commercial trucks, and ii) delays and/or denials in approvals for UN to retrieve, count and move UN humanitarian aid from Kerem Shalom to other parts of the Gaza Strip, which mean that we are unable to fully verify all trucks which have transited the land crossings. We will resume presentation of comprehensive data once the situation at the crossing allows.” Similarly, the acknowledgement of “considerable uncertainty about population denominators” does not logically lead to the conclusion that this would “…have only marginally affected our estimates”.

      Policy Implications

      The conclusion of the article makes politicized recommendations that are disconnected from the findings. The authors’ recommendation to “reinstate UNRWA’s role as an independent and experienced on-the-field monitor” is unsupported, and the summary dismissal and evaluation of COGAT data as “not of sufficient quality to guide decision-making”, reflects bias rather than a balanced analysis. Considerations relating to the role that international actors can and should play is determined by far more complex factors that are the partial shipping data analyzed here.

      The claim that Israel, “as the de facto occupying power”, did not ensure sufficient food availability to Gaza (while acknowledging the relatively short period of deficiency), vastly oversimplifies the complex dynamics of the conflict and the multifaceted factors affecting food availability. This claim appears intended to promote the use of the study as “evidence” supporting “forensic efforts” (in the courts) to prove allegations that “Israel deliberately has starved Gaza’s population”, presenting as fact a disputed interpretation of Israeli combat operations in Gaza as constituting occupation, and hence its obligations under international law, while ignoring weighty arguments to the contrary. This view also ignores corresponding obligations of Hamas as the governing power in Gaza, and the role of international humanitarian actors. The legal questions on this point are far beyond the scope of this review, but there is no basis in the data provided to make this claim – it is simply presented as an unsubstantiated assertion. In order to evaluate the morality, legitimacy or legality of the Israeli military strategy in response to the Hamas attacks and terror infrastructure, including its impact on food availability, it is necessary to examine and understand the strategy challenges in conditions of military asymmetry, the large-scale use of human shields to protect Hamas forces, and urban warfare as exist in Gaza. The authors of this article appear to be unaware of this central dimension in the issues they are claiming to address. Given the slanted narrative, the selective and biased use of data and their interpretation, and the far-reaching and unsupported conclusions, it is difficult to escape the impression that this study is aimed at providing a prosecution with ostensibly credible academic findings, rather than advancing open-ended research in support of humanitarian efforts.

      Timely and reliable data are crucial to address the critical needs of the war-affected civilian population of Gaza. There is no doubt that data “on the civilian impacts of the war in Gaza”, and “situational awareness on food security in Gaza” are “important to inform appropriate humanitarian response”. It is also undoubtedly true that “humanitarian actors should review whether there is adequate coordination and technical expertise in place to ensure that what food is allowed into Gaza is both calorically efficient and diverse enough to maintain the best-possible diet, especially for population groups most vulnerable to malnutrition”. How a retrospective simulation of the food supply informs “situational awareness” is less obvious. Slanted, simplistic and politicized framing of the findings that ignore complexity, place the onus on Israel alone, and overlook the role of Hamas, the agency of Palestinian civil society, and the responsibility and obligations of the international community, do not advance scholarly discourse, nor will it strengthen the cooperation that is urgently needed to strengthen humanitarian efforts to benefit the civilians of Gaza.

    1. On 2025-02-16 02:16:55, user Michael Pazianas, MD wrote:

      Low BMD can be a common finding in both osteoporosis and renal osteodystrophy—two distinct histological diagnoses with distinct pathophysiology. While a low BMD and a T-score below -2.5 are often used to define osteoporosis, this finding does not necessarily indicate an osteoporotic etiology. Non-osteoporotic causes should be considered.

      In this study, the authors included patients with CKD who were diagnosed with osteopenia or osteoporosis based solely on BMD measurements, rather than bone biopsy findings. However, low BMD in these patients could stem from other forms of renal osteodystrophy, such as adynamic bone disease or osteomalacia, rather than true osteoporosis.

      "Given this premise, a more accurate and clinically relevant title might be: 'Low BMD Prevalence in Cardiovascular Kidney Metabolic Syndrome: Implications for Mortality.' The current title promotes an overly simplified approach that risks making the already challenging task of successfully managing these patients—particularly those with CKD—an even more distant prospect. This concern is especially relevant because antiresorptive therapies, commonly prescribed for osteoporosis, are contraindicated in adynamic bone disease, a pathology prevalent in CKD, as well as in osteomalacia."

    1. On 2025-02-21 05:08:41, user Evan Stanbury wrote:

      The paper refers to "a chronic debilitating condition after COVID-19 vaccination, often referred to as Post-Vaccination Syndrome" (which it calls PVS). This should not be confused with a common chronic debilitating condition after viral infection, often referred to as Post-Viral Syndrome (also PVS). This paper could confuse many, so it would be better to call the sick cohort something different from "PVS".

    1. On 2025-02-22 17:25:17, user Shawn M wrote:

      The study's questionnaire has significant design flaws. The main issue is how the questions are worded - they repeatedly ask about 'health conditions that you have had as a result of vaccine injury.' This phrasing assumes vaccines caused these health problems before even asking the question. It's like asking 'When did you stop stealing?' instead of 'Have you ever stolen anything?'<br /> This problematic wording can influence how people respond in two ways. First, it might lead people to automatically connect their health issues to vaccines without considering other possible causes. Second, by focusing only on vaccine-related problems, the questionnaire misses important information about people's overall health that could explain their symptoms.<br /> These issues make it difficult to trust the study's findings because we can't tell if the health problems reported were actually caused by vaccines or if they happened for other reasons that weren't explored.

    1. On 2025-03-07 03:42:49, user mehrdad alemi wrote:

      The COVID-19 pandemic posed unprecedented challenges for countries worldwide. Despite international sanctions, Iran managed to respond effectively to this crisis by relying on its domestic capacities.

      Among the actions taken by Iranian scientists, researchers, and physicians:

      1. Production of Domestic Vaccines: Iran became one of the countries producing COVID-19 vaccines by developing domestic vaccines such as Noora.

      2. Expansion of Diagnostic and Treatment Capacity: The development of diagnostic kits, the increase in the number of equipped laboratories, and the production of medical equipment, including ventilators, contributed to better crisis management.

      3. Healthcare System Management: The establishment of field hospitals, the strengthening of medical infrastructure, and the implementation of health restrictions at critical times played a significant role in reducing infection and mortality rates.

      4. Research and Innovation: The publication of reputable scientific articles and the conduction of clinical studies on Iranian vaccines strengthened Iran’s scientific standing in this field.

    1. On 2025-03-30 09:52:42, user Isatou Sarr wrote:

      Over time, immunity from both vaccination and previous infection can decrease, leading to an increased risk of breakthrough infections. This phenomenon is particularly noticeable as the immune response fades, and the virus continues to evolve.This waning immunity presents a challenge for public health strategies that rely heavily on initial vaccination or infection-induced protection. Boosters become crucial in reinforcing the immune system and restoring protective antibody levels, especially for vulnerable populations such as the elderly or those with underlying health conditions. Moreover, the emergence of new variants, often with mutations that allow them to evade existing immunity, further complicates the picture. These variants can spread more easily and cause illness in individuals who were previously protected, necessitating ongoing adaptation of vaccines and preventative measures to keep pace with viral evolution. Continuous monitoring of variant spread, vaccine effectiveness, and the duration of immunity are essential for informed decision-making and effective mitigation strategies.

    1. On 2025-04-10 22:33:05, user Will wrote:

      My first comment should be: <br /> I noticed that Table 2 mentions Covid 19 under "Abbreviations" but in the actual table there is no Covid 19 variable. Could you clarify that please?

    2. On 2025-06-04 21:03:24, user Meg McSorley wrote:

      The unadjusted risk estimates are exactly the same as the adjusted, down to the confidence intervals and p-values?

      Where is table 1, comparing baseline characteristics of the comparison groups (vaccinated and unvaccinated)? This would inform which covariates should be included in the model. This is actually the most important table because the vaccinated likely do have different characteristics than the unvaccinated that would affect the risk estimates.

      How was influenza ascertained? Self-report? Employee Health testing? Why aren’t raw numbers reported?

      Is there a reference for the Vaccine Efficacy calculation? Is there a statistical rationale for this calculation?

    1. On 2025-05-28 23:11:26, user Evolutionary Health Group wrote:

      We at the Evolutionary Health Group ( http://evoheal.github.io/) "http://evoheal.github.io/)") really enjoyed this paper. Here are our highlights.

      Investment in ensemble forecasts resulted in better calibration and less variable predictions

      Work bridged the gap between theory and policy; builds infrastructure for future data integration

      Climate zone analysis balanced the desire for model generalizability, the need for sufficient historical data to characterize each zone, and the risks of unrealistically grouping diverse regions together.

      Limitations of individual models including the provision of confidence intervals was honestly presented

    1. On 2025-06-04 17:34:59, user Sarah Jorgensen wrote:

      Questions for the authors: <br /> From the results, 11 children started GAHT within 12 months of GnRHa initiation and another 20 within 12-24 months (total 31, 31/94 (33%)), yet in the discussion, "more than half of the participants had initiated gender-affirming hormones over the 24-month follow up period." Could the authors resolve this apparent discrepancy?

      59 patients were assessed at 24 months. If 31 were not assessed because they started GAHT, there still appears to be 4 children unaccounted for. Were they lost to follow-up? What was their status at last assessment?

      Details on psychiatric medications at baseline and initiated during follow-up would be of interest and could be considered for inclusion as time-varying covariates in models.

      Given that 4-9 years have elapsed since GnRHa initiation, why was this analysis limited to 24 months follow-up? At the very least it would be of interest to know vital status and how many ultimately went on to receive GAHT versus desisted.

    1. On 2025-06-24 11:20:26, user Christopher Hickie wrote:

      Could Tracy Beth Høeg please show evidence of reported affiliations with Sloan MIT and UCSF Emergency Medicine as I am not finding any listing for her for either.

    2. On 2025-08-28 17:40:53, user gzuckier wrote:

      Just a typo of some sort, I assume, but<br /> "-0.85 (95% Cl: [-0.48 --0.37]) for dose 3" can't be correct.

      On a related note, however, I can't avoid a nagging suspicion of bias from the fact that some of the estimates used to support <br /> "concerning evidence of a higher-than-expected fetal loss rate" <br /> are not statistically significant is missing from the paper and must be intuited by the reader, as in <br /> "1.9 (95% CI: 0.39-3.42]) for dose 3";<br /> particularly when it's specifically noted with respect to estimates involving COVID infections <br /> "all the 95% CIs of the respective observed-to-expected differences included 0 (Table S8)."

      The main findings, however, do not have this problem.

      My humble suggestion is to include these other findings as "suggestive but not reaching statistical significance."

      Or perhaps, since the results given for week 14 seem to be significant but are diluted by nonsignificant later results, that should be pointed out?

    1. On 2025-07-15 16:59:57, user zlmark wrote:

      The preprint relies on survey data that shows clear evidence of sampling protocol violations, including improper household selection, failure to screen for residency, and geographic deviations confirmed by GPS data.

      In several cases, inconsistencies appear to have been retroactively edited to align with protocol.

      Data from two teams—Gaza9 and Gaza3—raise particular concern, with demographic anomalies and mortality figures that suggest possible manipulation or fabrication.

      These issues compromise the representativeness of the sample and call into question the reliability of the resulting estimates.

      A full analysis of these issues is available here: <br /> https://markzlochin.substack.com/p/design-vs-execution-in-gaza-mortality

    1. On 2025-08-08 09:31:31, user David Fournier wrote:

      Dear authors, commenting on the recent Nat. comm. release, did you actually studied the direct connection in the samples from encode ad brains you studied between histone modifications and actual expansions? i dont see a plot of histone modifications versus repeat expansions directly plotted from the same individual. Did you check that? Thanks.

    1. On 2025-08-15 08:47:16, user Jouke- Jan Hottenga wrote:

      Nice paper!

      Population stratification severly influences HWE, which is known as the Wahlund effect. Hence, also the much larger SNP removal in mixed populations.

      Imputation and phasing software in general assume HWE. Which might a) be a reason to apply HWE beforehand and b) will thus likely result in all markers also being in HWE post imputation.

      With kind regards, Jouke

    1. On 2025-08-20 13:21:16, user Anthony Clanton wrote:

      Thank you for the opportunity to comment on your well-constructed manuscript. We appreciate the authors’ efforts to advance the STARD-IONM framework and promote rigor in reporting diagnostic accuracy for IONM. We would like to highlight the importance of clarifying partial recovery scenarios within the STARD-IONM framework. While the manuscript provides valuable discussion on reversible and irreversible signal changes, it does not explicitly define or address partial recovery—cases in which IONM signals improve but do not return to baseline. These common scenarios are clinically relevant and may reflect incomplete injury or partial mitigation. To improve clarity and consistency, we suggest considering the following additions:

      • Clearly define “partial recovery” and distinguish it from full recovery and persistent deterioration.<br /> • Include guidance on how to classify and report partial recovery in diagnostic accuracy studies, particularly when calculating sensitivity, specificity, and predictive values.<br /> • Provide illustrative examples or decision frameworks to support consistent interpretation and reduce bias in outcome classification.

      We would also like to emphasize that the STARD-IONM checklist does not currently call for authors to specify which muscles, nerves, or anatomical structures were included in the intraoperative monitoring plan, nor does it recommend reporting which signals changed and then recovered or failed to recover. While item 10a under “Test Methods” may implicitly suggest this level of detail, making this expectation explicit would be beneficial. Such information is frequently absent in studies evaluating IONM, yet it is essential for interpreting outcomes and ensuring reproducibility.

      Thank you again for your commitment to transparency and community engagement. These additions could further strengthen the STARD-IONM framework and help ensure it serves the entire research community effectively.

      Kent Rice, Kevin McCarthy, Anthony Clanton & Adam Doan

    1. On 2025-10-07 13:01:22, user Evolutionary Health Group wrote:

      We at the Evolutionary Health Group ( https://evoheal.github.io/ ) really enjoyed this paper.

      Here are our highlights:

      Asks what role the microenvironent (including antibiotic administration) plays in shaping the phenotypic traits of S. aureus.

      Shows increase in MRSA associated with coexistant pseudomons infection and ciprofloxacin.

      Monoinfected (SA only) cases showed increased pigment and biofilm production. Coinfected (SA and pseudomonas) cases showed reduce pigment and biofilm production. Two of these phenotypic shifts coincided with ABX treatment, and these patients had significantly more MRSA infections

    1. On 2025-11-11 03:39:57, user Evolutionary Health Group wrote:

      We at the Evolutionary Health Group ( https://evoheal.github.io/) "https://evoheal.github.io/)") really enjoyed this paper.

      Here are our highlights:

      As wastewater surveillance expands, not all systems will have the same infrastructure or sampling practice. Adjusting for flow allows standardization across plants of different sizes or environmental conditions.

      Cost is a main barrier to sustained wastewater surveillance. This paper demonstrates that reducing sampling still yields stable real-time trends in the reproduction number, R, suggesting that wastewater surveillance can scale well without major budget requirements.

      This model does not require clinical data for calibration, which demonstrates that wastewater surveillance can be a primary, rather than a secondary, disease monitoring system capable of tracking transmission even when clinical surveillance is poor.

      The publication of a real-time reproduction number dashboard helps public health officials track seasonal waves without having to interpret raw wastewater concentrations, bridging scientific output and real-world action.

    1. On 2020-04-04 18:33:11, user Jhansi Dan wrote:

      Do anyone have data from last saturday/sunday for Virginia state. I remember seeing the peak date as April 28th and it shows May 20 now. I deduce flattening of curve. Please share the graphs. I wish they have archives for past data to compare.<br /> Thank You

    2. On 2020-04-08 15:59:31, user Vee_Kay wrote:

      Why have they dropped individual state numbers in the IHME projections? Instead they go to other countries that is of little interest to US....

    1. On 2020-04-06 12:58:13, user Maria wrote:

      A very accurate study, which explains the high rate of spread of Sars-CoV2. I would repeat it in dark and cold rooms, keeping air samples also in the dark, since UV light and heat damage the virus. This could reveal why only nude RNA is found.

    1. On 2020-06-26 22:10:08, user kpfleger wrote:

      On what date did the VDD protocol (table 1) commence? Is it possible to analyze COVID-19 outcomes (fatality, ventilator need, ITU admission, etc.) by baseline 25OHD on admission for before vs. after the VDD protocol started, as they did in the Singapore study: https://www.medrxiv.org/con... (which perhaps you should also cite BTW)? Or was 25OHD status not assessed for COVID-19 patients before the VDD protocol began?

    1. On 2020-07-03 18:28:19, user Mark Pollington wrote:

      Heterogeneous is clearly an important factor in determining herd immunity. However, in the developed counties discussed in this paper surely this will have been masked by the introduction of various non-pharmaceutical interventions.<br /> I was therefore fascinated to see how this problem could be tackled.

      However, the equations outlining susceptibility do not appear to have been followed up to fit the parameters to data. Indeed, the discussion simply alludes to the authors fitting CVs which are an order of magnitude less than the susceptibility values used in the main paper!

      Given the lack of evidence, then, why are arbitrarily susceptibility factors as high as 4 used? Why publish graphs which are so far removed from reasonable expectations? Unless politically motivated?

      Clearly further research needs to be done to establish reasonable susceptibility factors, but I can't see any effective proposals in the paper. Computationaly intensive data fitting exercises with the inherent uncertainties in the data are certainly not the way to go!

    1. On 2020-07-11 23:36:55, user Monil Majmundar wrote:

      Study showed corticosteroid was associated with lower risk of Icu transfer, intubation, mortality and higher probability of discharge.<br /> Corticosteroid was associated with 85% lower risk of primary outcome that is composite of icu transfer, intubation and death. 84% lower risk of icu transfer, 69% lower risk of intubation and 47% lower risk of mortality. 3.65 times higher probability of discharge.

    1. On 2020-07-13 18:19:24, user Dana C. wrote:

      This study simply takes the estimated number of firearms in America and the annual firearm death rate then assigns a ratio. They apply this ratio to new firearm purchases with little or no adjustment for rioting, calls to defund police departments etc. The source of much of the data used is from The Gun Violence Archive which does not allow open access to it's data, it's criteria in forming and gathering it's data and is an openly anti gun organization.The results of this study have not been peer reviewed or subjected to any critical scrutiny. The results of this study are misleading at best and political biased and fraudulent at worst. It's no secret that a study can be manipulated to produce the desired end result which is clearly the result here. I have one question for those who prop up their ideologies with pseudo science, why are the 400,000 homicides (this is the most conservative estimate) that are prevented by legal/lawful gun owners annually never included in studies such as this?

    1. On 2019-07-11 21:22:22, user Guyguy wrote:

      EVOLUTION OF THE EBOLA EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI

      Wednesday, July 10, 2019

      The epidemiological situation of the Ebola Virus Disease dated July 9, 2019:

      131 Contaminated health workers<br /> 3 health workers, including 2 vaccinated, are among the new confirmed cases (1 in Beni, 1 in Kalunguta and 1 in Katwa). The unvaccinated Kalunguta health worker died in a community health center.<br /> The cumulative number of confirmed / probable cases among health workers is 131 (5% of all confirmed / probable cases), including 41 deaths.

      Since the beginning of the epidemic, the cumulative number of cases is 2,437, of which 2,343 are confirmed and 94 are probable. In total, there were 1,646 deaths (1,552 confirmed and 94 probable) and 683 people healed.<br /> 358 suspected cases under investigation;<br /> 9 new confirmed cases, including 6 in Beni, 1 in Mambasa, 1 in Kalunguta and 1 in Katwa;<br /> 5 new confirmed case deaths:<br /> 5 community deaths, 2 in Beni, 1 in Oicha, 1 in Mambasa and 1 in Kalunguta;

      Data on deaths of confirmed cases managed by Ebola Treatment Centers are not available this Wednesday.

      EPIDEMIOLOGICAL SURVEILLANCE

      New health area affected: Mambasa (Ituri). The first case is an 8-year-old boy residing in Mambasa who had been to Beni with his mother. His mother, confirmed Ebola, died in Beni on June 19, 2019 but she was not buried in a dignified and secure manner. After developing the disease, the boy returned to Mambasa with his uncle. He died at the Mambasa Reference General Hospital.<br /> 156,851Vaccinated persons<br /> The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 19 May 2018.<br /> 73,466,784 Controlled people<br /> 80 entry points (PoE) and operational health checkpoints (PoC).<br /> Source: Ministry of Health press team on the state of the response to the Ebola epidemic in the Democratic Republic of Congo

    2. On 2019-07-17 03:34:18, user Guyguy wrote:

      EBOLA DRC - Evolution of the response to the Ebola outbreak in the provinces of North Kivu and Ituri on Sunday, July 14, 2019<br /> The epidemiological situation of the Ebola Virus Disease dated July 13, 2019:<br /> Since the beginning of the epidemic, the cumulative number of cases is 2,489, of which 2,395 confirmed and 94 probable. In total, there were 1,665 deaths (1,571 confirmed and 94 probable) and 698 people healed.<br /> 335 suspected cases under investigation;<br /> 12 new confirmed cases, including 6 in Mabalako, 4 in Beni, 1 in Katwa and 1 in Butembo;<br /> 10 new deaths of confirmed cases:<br /> 3 community deaths, including 1 in Mabalako, 1 in Beni and 1 in Katwa;<br /> 7 deaths at Ebola Treatment Center, including 4 in Beni, 2 in Mabalako and 1 in Butembo;<br /> 4 people recovered from Ebola Treatment Center, including 3 in Butembo and 1 in Beni.

      Confirmed Ebola Patient from Butembo Supported at Goma Ebola Treatment Center

      This Sunday, July 14, 2019, a pastor from South Kivu arrived in Goma after a short stay in Butembo. The 46-year-old pastor traveled from Bukavu to Butembo via Goma on Thursday, July 4 for an evangelistic mission. During his stay in Butembo, the pastor preached in seven churches where he regularly laid hands on Christians, including the sick. His first symptoms appeared on 9 July when he was still in Butembo. He was treated at home by a nurse until he left by bus for Goma on Friday, 12 July.

      On the route between Butembo and Goma, the bus passed through 3 health checkpoints, namely Kanyabayonga, Kiwanja and OPRP. During the checks, he did not seem to show signs of the disease. In addition, at each checkpoint, he has written different names and surnames on the lists of travelers, probably indicating his desire to hide his identity and state of health.

      As soon as he arrived in Goma on Sunday morning, he went to a health center because he did not feel well and started having a fever. No other patients were in the health center, reducing the risk of nosocomial infections of others. Nurses and doctors at the health center who recognized the symptoms of Ebola immediately alerted the response teams in Goma who transferred him to the Ebola Treatment Center (ETC). Around 15:00, the result of the lab test confirmed that he was Ebola positive. If his state of health permits, the patient will be transferred by ambulance to the ETC of Butembo to continue his care as of Monday, as provided by the procedure of the contingency plan.

      It is important for people to stay calm. Due to the speed with which the patient has been identified and isolated, as well as the identification of all bus passengers from Butembo, the risk of spreading to the rest of the city of Goma remains low. Caution is still required. In order to avoid the contamination of additional people in Goma, it is urgent to break the chain of transmission by carrying out the following actions:<br /> Decontaminate the health center in which the patient has passed;<br /> Identify and vaccinate all contacts of the patient without exception;<br /> Track and limit contact movement for 21 days.<br /> Since November 2018, the Ministry of Health and the World Health Organization (WHO) have put in place an Ebola response planning and preparation system in the city of Goma due to the large influx of travelers from affected by the epidemic. The rapid detection of the patient by medical teams at the Goma health center proves the effectiveness of the city's preparedness activities to cope with the importation of potential Ebola patients. As part of this preparation, more than 3,000 health workers in Goma have been vaccinated and trained in the detection and management of Ebola patients.

      In addition, the transport company has shown great professionalism in having a passenger register and making this register available to response teams to identify all passengers on the bus. The bus driver and the 18 other passengers have been identified and their vaccination will begin on Monday, July 15, 2019.

      The collaboration of the entire population is necessary to prevent the spread of the epidemic in Goma. Beyond the medical arsenal, the Ministry of Health recalls that the response against Ebola is above all community.

      As a reminder, the recommendations of the Ministry of Health are as follows:<br /> Follow basic hygiene practices, including regular hand washing with soap and water or ashes;<br /> If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu civil protection hotline directly;<br /> If you are identified as an Ebola patient contact, agree to be vaccinated and followed for 21 days;<br /> If a person dies because of Ebola, follow the rules for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.<br /> For all health professionals, observe the hygiene measures in the health centers and declare any patient with symptoms of Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect the sanitary measures advocated by the Ministry of Health, it is possible to ensure that this case of Ebola detected in Goma is a sporadic case that does not cause a new outbreak.<br /> Source: Ministry of Health press team on the state of the response to the Ebola epidemic in the Democratic Republic of Congo

    1. On 2019-07-14 20:05:47, user Edward Tufte wrote:

      Please please integrate excellent image with the text, so that adjacent text describes the image.<br /> Segregating text and image is for antique publishers only. Also your preprint will have more readers than any journal article, so do your best by those readers. If it is ever published, you can<br /> re-segregate text and image for the commercial publisher.

      On errors in medical measurement, this good study: “Covariates are often measured with error, introducing bias and imprecision. Practices regarding covariate measurement error were assessed via a systematic review of general medicine and epidemiology literature. In original research published in 2016 in 12 high-impact journals,<br /> only 247 (44%) of the 565 original research publications reported measurement errors, <br /> only 18 publications (7% of 247) used methods to investigate or correct for measurement error.”

      Excellent article by Timo B. Brakenhoff, Marian Mitroiu, Ruth H. Keogh, Karel G.M. Moons, Rolf Groenwold, Maarten van Smeden, “Measurement error is often neglected in medical literature,” Journal of Clinical Epidemiology, March 2018, 89-97, edited.

    1. On 2019-09-30 05:56:18, user Guyguy wrote:

      EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT SEPTEMBER 27, 2019

      The epidemiological situation of the Ebola Virus Disease dated September 27, 2019

      Saturday, September 28, 2019

      • Since the beginning of the epidemic, the cumulative number of cases is 3,186, of which 3,072 are confirmed and 114 are probable. In total, there were 2,128 deaths (2014 confirmed and 114 probable) and 989 people healed. <br /> • 446 suspected cases under investigation; <br /> • 3 new confirmed cases, including: <br /> • No cases in North Kivu; <br /> • 3 in Ituri, including 2 in Mandima and 1 Komanda; <br /> • No new confirmed deaths have been recorded; <br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 160 (5% of all confirmed / probable cases), including 41 deaths. • Vaccination rings were opened Friday, September 27, 2019 around confirmed cases of September 26 in the Mambasa Health Area located in the health zone of Mambasa in Ituri; <br /> • The satellite ring vaccination around the confirmed case of 20.09.2019 that started the disease in Beni continues in the health areas of Lisasa and Kalunguta in Kalunguta in the province of North Kivu; <br /> • Since the beginning of vaccination on August 8, 2018, 229,484 people have been vaccinated; <br /> • The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018. • Since the beginning of the epidemic, the total number of travelers checked (temperature measurement) at the sanitary control points is 99,958,288; <br /> • To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

      As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

      1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
      2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
      3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
      4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
      5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding). <br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.
    2. On 2019-10-04 08:05:29, user Guyguy wrote:

      EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT 02 OCTOBER 2019 <br /> Thursday, October 03, 2019 <br /> Since the beginning of the epidemic, the cumulative number of cases is 3,198, of which 3,084 are confirmed and 114 are probable. In total, there were 2,137 deaths (2023 confirmed and 114 probable) and 995 people healed. <br /> 427 suspected cases under investigation; <br /> 1 new case confirmed in Ituri in Mandima; <br /> 1 new confirmed case;1 person cured out of the CTE in North Kivu in The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths. <br /> 17th day without response activities in the Lwemba Health Area in Mandima, Ituri.<br /> LEXICON <br /> • A community death is any death that occurs outside a Ebola Treatment Center. <br /> • A probable case is a death for which it was not possible to obtain biological samples for confirmation in the laboratory but where the investigations revealed an epidemiological link with a confirmed or probable case.<br /> NEWS<br /> Prime Minister ready to implement the commitments of the Head of State through the ST / CMRE <br /> - Prime Minister, Sylvester Ilunga Ilukamba, considers that the commitments of the Head of State, President Félix-Antoine Tshisekedi Tshilombo, recalled from the top of the UN platform, are relayed in the field by the effectiveness of leadership and the Coordination of the Government of the Democratic Republic of the Congo through the Technical Secretariat of the Multisectoral Ebola <br /> - He said it during a meeting he chaired this Thursday, October 03, 2019 with the ST / CMRE delegation led by his Technical Secretary Prof. Jean-Jacques Muyembe Tamfum who was accompanied by Dr. Kebela and Prof. Michel Kaswa; <br /> - From this meeting, we note that as early as next week, the Prime Minister will bring together the ministers of Health, Budget and Finance to support the interventions of the response; <br /> - To this end, he stressed that the multisectoral vision of the response is, at the same time, to end the Ebola Virus Disease and to respond to the security and socio-economic needs of the populations affected by this epidemic ; <br /> - He promised that his government will support the approach of the Technical Secretariat of the CMRE to work for the Strengthening of the whole health system of the DRC; <br /> - Since July 20, 2019, the Head of State, the President of the Republic Félix-Antoine Tshisekedi Tshilombo, is coordinating the response to the epidemic to the Ebola virus disease and has decided to entrust the responsibility of the Technical Secretariat of the Multisectoral Committee to a team of experts under the direction of Professor Jean-Jasques Muyembe Tamfum; <br /> - The mission of the technical secretariat is to put in place all innovative measures that are urgent and indispensable for the rapid control of the epidemic.<br /> VACCINATION<br /> - Preparation of the Vitamin A Polio Immunization Campaign and Mebendazole Deworming in the 17 health zones of the Butembo Antenna, an area affected by Ebola Virus Disease; <br /> - 17 days already without opening rings around 5 confirmed cases in the Lwemba health area in Mandima in Ituri due to interethnic conflicts and insecurities. <br /> - An expanded vaccination ring was opened around the confirmed case of September 30, 2019 in Biakatp health area in Mandima in Ituri after dialogues and sensitizations carried out by the communication and psycho-social subcommittees; <br /> - Since vaccination began on 8 August 2018, 232,160 people have been vaccinated; <br /> The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.<br /> MONITORING AT ENTRY POINTS- A FONER Komanda checkpoint provider (PoC) was abducted on Wednesday 02 October 2019 by unidentified men who released him 75 km from the PoC. This provider of surveillance at the Control Points has already resumed its daily services; <br /> - Since the beginning of the epidemic, the cumulative number of travelers checked (temperature measurement ) at the sanitary control points is 101,714,685 ; <br /> - To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.<br /> As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows: <br /> 1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes; <br /> 2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number; <br /> 3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days; <br /> 4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination. <br /> 5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding). <br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.

    3. On 2019-10-16 12:44:35, user GuyguyKabundi Tshima wrote:

      EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT OCTOBER 11, 2019<br /> Saturday, October 12, 2019<br /> Since the beginning of the epidemic, the cumulative number of cases is 3,212, of which 3,098 are confirmed and 114 are probable. In total, there were 2,148 deaths (2034 confirmed and 114 probable) and 1031 people cured.<br /> 466 suspected cases under investigation;<br /> 2 new confirmed cases at CTE in Ituri in Mandima;<br /> 2 new confirmed deaths, including:<br /> 2 community deaths in Ituri in Mandima;<br /> No confirmed deaths in CTE;<br /> 3 people healed from the CTE, including 2 in Ituri in Komanda and 1 in North Kivu in Katwa;<br /> No health workers are among the newly confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths.

      NEWS

      Organization of a press conference on the evolution of Ebola Virus Disease in Kinshasa<br /> - The Technical Secretary of the Multisectoral Committee for Ebola Virus Epidemic Response (CMRE), Prof. Jean Jacques Muyembe Tamfum chaired this Saturday, October 12, 2019 in Kinshasa a press conference during which he gave an update on the 10th epidemic Ebola Virus Disease in the DRC since its declaration on August 1 , 2018 to date;<br /> - To this end, he showed the strategies used in the response of this epidemic and spoke of the recourse to technological innovations, while recalling that the Head of State, President Félix-Antoine Tshisekedi Tshilombo, placed him at head of the technical secretariat of CMRE, with two main missions. This includes ending the epidemic as soon as possible and capitalizing on the achievements of this epidemic to strengthen the DRC's health system, starting with the three provinces affected by this epidemic;<br /> - Speaking of the evolution of the response, he reported some tangible progress, notably from July 2019, where 90 confirmed cases per week were recorded, or 15 per day, while currently there are fewer than 20 case by week, ie 1 to 3 cases per day, or even zero cases confirmed as the 05 October 2019 last. " In this period, three provinces were active (North and South Kivu, as well as Ituri), while today only the province of Ituri is affected . Today, only 9 zones are affected of the 22 recorded in July 2019, "said the technical secretary of the CMRE;<br /> - He said that for now the epidemic is concentrated in the North from where it came before revealing itself in Mangina and Mabalako in North Kivu. Hence all efforts are concentrated to put an end to this epidemic as quickly as possible;<br /> - Regarding strategies to end this epidemic, the Pof. Muyembe spoke about the change of approach that is now multisectoral and that at present, the outline of the epidemic is placed under the leadership of the presidency of the Democratic Republic of Congo with as coordinator the Prime Minister. This committee has a technical secretariat which directs the general coordination managed by Prof. Steve Ahuka and the provincial sub-coordinators of the response;<br /> - The second strategy was to maintain the motivation of the teams on the spot. This has been regularized with the support of the World Bank. An operating budget is now given to the coordination in Goma as well as all the co-ordination;<br /> - The other strategy is to give more importance to national leadership. A partnership has been built with WHO, UNICEF and MSF that support coordination in Goma. Nationals are at the forefront and partners support. This has changed a lot on the field, says Professor Muyembe;<br /> - Finally, notes the Technical Secretary, innovations have been made with this epidemic with the use of experimental vaccines, first RVSV zebov from Merck with belt vaccination which has shown its effectiveness;<br /> - " It is time to use a new vaccine, following the recommendations of the SAGE expert group that advises WHO on immunization. On May 15, 2019, this group recommended using an adjusted dose of the RVSV vaccine to prevent a possible shortage due to the fact that the epidemic lasts a long time, "Prof. Muyembe;<br /> - He added: " His second recommendation was to use a second preventive vaccine. After proposals, it is the Johnson & Johnson vaccine that presents the most data on the scientific level . He announced that the teams are prepared to give correct communication and to vaccinate the population;<br /> - He recalled that this second vaccine is used in West Africa since 2013, will also be used in Rwanda and Goma to protect the Congolese compatriots of Goma, where more than 64,000 of them cross the border daily. to go to Gisenyi and vice versa;<br /> - The first batch of the J & J vaccine, 500 000 doses can arrive in the DRC from 18 October 2019 and vaccination can begin in early November 2019 in two communes of Goma to extend later in other provinces;<br /> - The clinical trials carried out by the DRC will serve the world, since now two molecules tested are now available to break the chain of transmission during the next appearances of the Ebola virus.<br /> - " From this year, Ebola became a curable disease because we found medicines to cure the sick. It can also be avoided by immunization, especially if in both cases, one arrives in time, "concluded the technical secretary of the Multisectoral Committee for the Response to the Ebola Virus Disease Epidemic Muyembe Tamfum.

      VACCINATION

      • A new vaccination ring was opened around two confirmed cases from 10 October 2019 in the Biakato Health Area in Mangina / AS Biakato mine with low participation due to a strong community reluctance;
      • Vaccination of newly recruited front-line staff continues at Kyondo Reference Hospital and Kayna Health Zone in Bulinda, North Kivu;
      • Continuation of Local Polio Vaccination Days integrated with Vitamin A supplementation and Mebendazole deworming in 17 health zones at the Butembo antenna in North Kivu;
      • Since the beginning of vaccination on August 8, 2018, 237,165 people have been vaccinated;
      • The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

      MONITORING AT ENTRY POINTS

      • Since the beginning of the epidemic, the total number of travelers checked (temperature measurement ) at the sanitary control points is 105,171,551 ;
      • To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

      As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

      1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
      2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
      3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
      4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
      5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.
    4. On 2019-10-18 23:18:45, user GuyguyKabundi Tshima wrote:

      EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT OCTOBER 16, 2019<br /> Thursday, October 17, 2019<br /> Since the beginning of the epidemic, the cumulative number of cases is 3,228, of which 3,144 are confirmed and 114 are probable. In total, there were 2,158 deaths (2044 confirmed and 114 probable) and 1038 people healed.<br /> 443 suspected cases under investigation;<br /> 1 new confirmed case in North Kivu, including:<br /> 1 case in North Kivu in Mabalako;<br /> No cases in Ituri;<br /> 4 new confirmed deaths in North Kivu, including:<br /> 1 community death in North Kivu in Mabalako;<br /> 3 deaths confirmed at CTE in North Kivu in Mabalako;<br /> No healed person left CTE;<br /> No health workers are among the newly confirmed cases. The cumulative number of confirmed / probable cases among health workers is 161 (5% of all confirmed / probable cases), including 41 deaths.

      LEXICON<br /> • A community death is any death that occurs outside a #Ebola Treatment Center.<br /> • A probable case is a death for which it was not possible to obtain biological samples for confirmation in the laboratory but where the investigations revealed an epidemiological link with a confirmed or probable case.

      NEWS<br /> NOTHING TO REPORT

      VACCINATION<br /> - A satellite ring was opened in Mambasa prison around the confirmed case of 12 October 2019 in Nyakunde;<br /> - Continuation of expanded ring vaccination in Mataba in the health zone of Kalunguta around the 2 confirmed cases of 12 October 2019;<br /> - Continuation of the vaccination of newly recruited front-line staff (PPL) in the Kyondo (HGR Kyondo) and Kayna Health Zones (Bulinda Health Area), Musienene (Kimbulu Reference Health Center) and Butembo (Vulindi Health Area);<br /> - Preparation of the vaccination of biker taximen in the sub-coordinations of Butembo, Beni, Mangina in Mabalako in North Kivu and Mambasa in Ituri.<br /> - Since the beginning of vaccination on August 8, 2018, 239,139 people have been vaccinated;<br /> - The only vaccine to be used in this outbreak is the rVSV-ZEBOV vaccine, manufactured by the pharmaceutical group Merck, following approval by the Ethics Committee in its decision of 20 May 2018.

      MONITORING AT ENTRY POINTS<br /> - Nasty destruction of huts and launching leaflets against providers at PoC Kolikoko;<br /> - Since the beginning of the epidemic, the total number of checked travelers (temperature rise) at the sanitary control points is 106,999,606 ;<br /> - To date, a total of 111 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

      As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

      1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
      2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
      3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
      4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
      5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.
    5. On 2019-11-16 01:59:42, user Guyguy wrote:

      EVOLUTION OF THE EPIDEMIC IN THE PROVINCES OF NORTH KIVU AND ITURI AS AT 14 NOVEMBER 2019

      Friday, November 15, 2019

      • Since the beginning of the epidemic, the cumulative number of cases is 3,292, of which 3,174 are confirmed and 118 are probable. In total, there were 2,195 deaths (2077 confirmed and 118 probable) and 1070 people healed.<br /> • 508 suspected cases under investigation;<br /> • No new confirmed cases;<br /> • 2 new deaths of confirmed cases in North Kivu, including 1 in Beni and 1 in Mabalako;<br /> • 3 healed people released from CTE in North Kivu in Mabalako;<br /> • No health worker is among the new confirmed cases. The cumulative number of confirmed / probable cases among health workers is 163 (5% of all confirmed / probable cases), including 41 deaths;

      NEWS

      Continuation of vaccination with the 2nd Ebola vaccine in two health zones of Karisimbi in Goma

      • Vaccination continues in the health zones of Majengo and Kahembe in Karisimbi (Goma);<br /> • A total of 40 people were vaccinated, including 34 adults and 6 children under 18;<br /> • This vaccination began on Thursday, November 14, 2019 with the Ad26.ZEBOV / MVA-BN-Filo vaccine, produced by Janssen Pharmaceuticals for Johnson & Johnson. This second vaccine was approved on 22 October 2019 by the Ethics Committee of the School of Public Health of the University of Kinshasa and 23 October 2019 by the National Ethics Committee.

      VACCINATION

      • 40 people were vaccinated with the 2nd Ad26.ZEBOV / MVA-BN-Filo vaccine (Johnson & Johnson) in the two Health Zones of Karisimbi in Goma;<br /> • Since the start of vaccination on August 8, 2018 with the rVSV-ZEBOV vaccine, 252,249 people have been vaccinated;<br /> • Approved October 22, 2019 by the Ethics Committee of the School of Public Health of the University of Kinshasa and October 23, 2019 by the National Ethics Committee, the second vaccine, called Ad26.ZEBOV / MVA-BN -Filo, is produced by Janssen Pharmaceuticals for Johnson & Johnson.<br /> • This new vaccine comes in addition to the first, the rVSV-ZEBOV, the vaccine used until then (since August 08, 2018) in this epidemic. Manufactured by the pharmaceutical group Merck, after approval of the Ethics Committee on May 20, 2018, it has recently been approved.

      MONITORING AT ENTRY POINTS

      • A 38-year-old woman from Beni for Nzanga in Mutwanga, North Kivu, high-risk contact was intercepted at PK5 checkpoint (PoC) in Beni. She is in contact with a source case notified to Beni on 03 November 2019;<br /> • Since the beginning of the epidemic, the total number of checked travelers (temperature increase) at the sanitary control points up to 13 November is 116,622,388 ;<br /> • To date, a total of 112 entry points (PoE) and sanitary control points (PoCs) have been set up in the provinces of North Kivu and Ituri to protect the country's major cities and prevent the spread of the epidemic in neighboring countries.

      As a reminder, the recommendations of the MULTISECTORAL COMMITTEE OF THE RESPONSE TO EBOLA VIRUS DISEASE are as follows:

      1. Follow basic hygiene practices, including regular hand washing with soap and water or ashes;
      2. If an acquaintance from an epidemic area comes to visit you and is ill, do not touch her and call the North Kivu Civil Protection toll-free number;
      3. If you are identified as a contact of an Ebola patient, agree to be vaccinated and followed for 21 days;
      4. If a person dies because of Ebola, follow the instructions for safe and dignified burials. It is simply a funeral method that respects funerary customs and traditions while protecting the family and community from Ebola contamination.
      5. For all health professionals, observe the hygiene measures in the health centers and declare any person with symptoms of # Ebola (fever, diarrhea, vomiting, fatigue, anorexia, bleeding).<br /> If all citizens respect these health measures recommended by the Secretariat, it is possible to quickly end this 10th epidemic.
    1. On 2019-10-11 18:31:08, user Miguel wrote:

      Interesting paper. It is really usefull to understand how P4 concept spread all over the world.<br /> RBMFC performed and published an special number about Quaternary prevention concept. Was lead by Marc Jamoulle and he encourage people from all over to send manuscripts. The year of the publication was 2015. That probably caused the increment of titles duriing this year. 2015 was also the year of the Iberoamerican Family Medicine in Uruguay. It was attend for an important number of P4 leaders ( included Jamoulle). Finally you must know there are a lot of publications (grey literatura) that are not allowed to be published. And the leadership of the P4 WONCA international gruop is in Uruguay.

    1. On 2020-01-26 00:39:20, user Jimmy Shih wrote:

      One can also argue the parameters and assumptions used in such transmission model.<br /> The main point is not the results of the model, but rather the methodology in predictions.<br /> How can a researcher in thousands of mile away with no background of anything other than academics know the parameters and assumptions.<br /> Chinese government should do whatever she could to do the predictions as she controls all data and formulate policies based on the predictions results.

    2. On 2020-01-27 04:11:13, user Mavrick55 wrote:

      A city the size of Wuhan would have at least 40K beds in their hospital’s combined with a population of 11M. Why was it 2 days ago we saw film of over crowded hospitals with dead in corridors. Build more beds fast adding 2 more critical care units to be finished in a week. I think the estimates given above are quite conservative actually. I believe a million or more will be infected by mid February.

    1. On 2020-01-31 21:48:51, user Carl Asplund wrote:

      Some things I'm wondering about: <br /> Line 61 - "smaller" should be "larger"<br /> Line 72 - The first date (year) is wrong<br /> Lines 87-88 - What are the additional modelling assumptions made here? The model on line 45 doesn't support R values less than 1.

    1. On 2020-02-12 22:27:46, user Dudley Poole wrote:

      Anybody bother to figure out the higher "susceptibility" in males relative to their over representation in the Chinese population?

    1. On 2020-02-13 05:13:34, user Ogi Dido wrote:

      Singapore has special case of transmission. There are meeting of one company that some one as carrier spreading the virus to other meeting member. That's why Singapore evident is higher than the model prediction. meanwhile for Thailand the evidence below the model. It seem the model must be corrected again, excluded Singapore or give a note. Also for Japan recent days there are outbreak in two cruising ship,

    1. On 2020-02-13 16:35:13, user dontlistentothepundits wrote:

      To the study authors <br /> What medications did the patients receive during their hospitalization ? Were any of them taking Avelox or other Fluoroquinolones or antibiotics that have side effects that include the kidneys ?

    1. On 2020-03-08 18:37:04, user Jyotishka Das wrote:

      Dear Authors,<br /> The work that you people have done is really interesting, and in times like this we must stand with each others in whatever we can. Being a student researcher at IIEST, Shibpur in the field of deep learning, it would be of immense help if you could kindly share the dataset with me for purely academic purpose. My contact email is : dasjyotishka@gmail.com . Thanks

    1. On 2020-03-14 06:52:08, user Muhammad Yousuf wrote:

      Hypokalemia is caused by SARS-CoV-2 virus due to its affinity for the Angiotensin Converting Enzyme (ACE) receptor that is present in the lungs, heart, blood vessels and the gastrointestinal tract of humans. It has been suggested from animal experiments that medications inhibiting this receptor (called ACEI or ARBs) could be a potential management strategy(1-2). Because ACEI and ARBs are medications mainly use for high blood pressure and would lower the BP, it is recommended that these medications should at least be used in patients with COVID-19 who are already suffering from hypertension or whose BP is not lower than 100 mm Hg systolic.

      It would also be interesting to know the recovery and death rate of COVID-19 patients with hypertension or heart failure who were already using an ACEI or ARB medications compared with those who were not on suchmedications.

      Abbreviations: ACEI= Angiotensin Converting Enzyme Inhibitors, ARBs= Angiotensin Receptor Inhibitors, BP= Blood pressure

      References<br /> 1. Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics. Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656. [Epub ahead of print]<br /> 2. Dimitrov, D. S. The secret life of ACE2 as a receptor for the SARS virus. Cell, 2003; 115(6), 652–653.

    1. On 2020-03-19 18:32:34, user Travis Pendell wrote:

      Im far from a dr, but this doesnt mean that those with type o are less likely to get/carry it, but rather tgey are less likely to need blood tranfusions? This is based on how much blood was used? Type o just doesnt get it as bad... as often?... based on this right?

    2. On 2020-03-22 14:14:29, user Rachelle Omenson wrote:

      I'm interested to know how this mirrors the actual population in China at the time of testing? If the percentages of blood types getting the virus or not mirrors the abundance in the population this is bad data.

    1. On 2020-03-21 21:07:21, user Elisabeth Bik wrote:

      Cross posting a concern I also posted on PubPeer.

      The protocol for the treatment was approved by the French National Agency for Drug Safety on March 5th 2020. It was approved by the French Ethic Committee on March 6th 2020. The paper states that patients were followed up until day 14, although I don't see any data from day 14 in the paper.

      Since the paper was submitted for publication on March 16 in the International Journal of Antimicrobial Agents, the 14 day timeline seems to be impossible. Could the authors clarify how this statement in the Procedure matches the 10-day interval between ethical approval and preprint submission? <br /> "Patients were seen at baseline for enrolment, initial data collection and treatment at day-0, and again for daily follow-up during 14 days."

    1. On 2020-03-24 13:35:07, user Sinai Immunol Review Project wrote:

      Summary: Retrospective study of the clinical characteristics of 752 patients with pneumonia infected with SARS-CoV2 , admitted at Chinese PLA General Hospital, Peking Union Medical College Hospital, and affiliated hospitals at Shanghai University of medicine & Health Sciences. This study compares peripheral blood from healthy controls from the same regions in Shanghai and Beijing, and COVID-19 patients to standardize a reference range of lymphocyte counts stratified by age.

      Key findings: Lower levels of lymphocyte counts - CD4 and CD8 T cells- correlated with disease severity (T cell counts were significantly lower in critical patients (in intensive care units, ICU) vs non-ICU). Based on 14,117 normal controls in Chinese Han population (ranging in age from 18-86) the authors recommended that reference ranges of people with CD3+ lymphocytes below 900 cells/mm3, CD4+ lymphocytes below 500 cells/mm3, and CD8+ lymphocytes below 300 cells/mm3 be considered high risk of severe COVID-19. However, COVID-19 patients were not stratified by age. This study reported that the levels of D-dimer, C-reactive protein and IL-6 were elevated in COVID-19 pts., indicating clot formation, severe inflammation and cytokine storm, but these parameters were not shown for healthy controls Authors compare data from patients in Shanghai and Beijing with patients in Wuhan, but clinical data from patients in Wuhan are not presented and it is unclear where data from Wuhan were obtained. The authors suggest a correlation between mortality rates and lymphocyte counts when comparing different regions in China, but this claim is not substantiated by data analysis. The authors should revise their title to emphasize disease severity (and not mortality).

      Importance: This study sets a threshold to identify patients at risk by analyzing their levels of lymphocytes, which is an easy and fast approach that may stratify individuals that require intensive care Although the study is limited (only counts of lymphocytes are analyzed and not its profile) the data is statistically robust to correlate levels of lymphopenia with disease severity.

      By María Casanova-Acebes

    1. On 2020-03-24 22:52:54, user Sinai Immunol Review Project wrote:

      Title: Clinical findings in critically ill patients infected with SARS-CoV-2 in Guangdong Province, China: a multi-center, retrospective, observational study?<br /> Immunology keywords: clinical outcomes, prognosis, critically ill patients, ICU, lymphopenia, LDH

      Main findings: <br /> This work analyses laboratory and clinical data from 45 patients treated in the in ICU in a single province in China. Overall, 44% of the patients were intubated within 3 days of ICU admission with only 1 death.<br /> Lymphopenia was noted in 91% of patient with an inverse correlation with LDH. <br /> Lymphocyte levels are negatively correlated with Sequential Organ Failure Assessment (SOFA) score (clinical score, the higher the more critical state), LDH levels are positively correlated to SOFA score. Overall, older patients (>60yo), with high SOFA score, high LDH levels and low lymphocytes levels at ICU admission are at higher risk of intubation.<br /> Of note, convalescent plasma was administered to 6 patients but due to limited sample size no conclusion can be made.

      Limitation of the study: While the study offers important insights into disease course and clinical lab correlates of outcome, the cohort is relatively small and is likely skewed towards a less-severe population compared to other ICU reports given the outcomes observed. Analysis of laboratory values and predictors of outcomes in larger cohorts will be important to make triage and treatment decisions. As with many retrospective analyses, pre-infection data is limited and thus it is not possible to understand whether lymphopenia was secondary to underlying comorbidities or infection. <br /> Well-designed studies are necessary to evaluate the effect of convalescent plasma administration.

      Relevance: This clinical data enables the identification of at-risk patients and gives guidance for research for treatment options. Indeed, further work is needed to better understand the causes of the lymphopenia and its correlation with outcome.

      Review by Emma Risson and Robert Samstein as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn school of medicine, Mount Sinai.

    1. On 2020-03-25 11:59:06, user Ned wrote:

      Can you share the sequence of the modified spike protein? The stabilized soluble protein with the his tag. I could not find it. Thanks

    1. On 2020-03-26 16:04:12, user Sinai Immunol Review Project wrote:

      Title: Meplazumab treats COVID-19 pneumonia: an open-labelled, concurrent controlled add-on clinical trial

      Keywords: Meplazumab, CD147, humanized antibody, clinical trial <br /> Main findings: This work is based on previous work by the same group that demonstrated that SARS-CoV-2can also enter host cells via CD147 (also called Basigin, part of the immunoglobulin superfamily, is expressed by many cell types) consistent with their previous work with SARS-CoV-1. 1 A prospective clinical trial was conducted with 17 patients receiving Meplazumab, a humanized anti-CD147 antibody, in addition to all other treatments. 11 patients were included as a control group (non-randomized). <br /> They observed a faster overall improvement rate in the Meplazumab group (e.g. at day 14 47% vs 17% improvement rate) compared to the control patients. Also, virological clearance was more rapid with median of 3 days in the Meplazumab group vs 13 days in control group. In laboratory values, a faster normalization of lymphocyte counts in the Meplazumab group was observed, but no clear difference was observed for CRP levels.

      Limitations: While the results from the study are encouraging, this study was non-randomized, open-label and on a small number of patients, all from the same hospital. It offers evidence to perform a larger scale study. Selection bias as well as differences between treatment groups (e.g. age 51yo vs 64yo) may have contributed to results. The authors mention that there was no toxic effect to Meplazumab injection but more patient and longer-term studies are necessary to assess this.

      Significance: These results seem promising as for now there are limited treatments for Covid-19 patients, but a larger cohort of patient is needed. CD147 has already been described to facilitate HIV 2, measles virus 3, and malaria 4 entry into host cells. This group was the first to describe the CD147-spike route of SARS-Cov-2 entry in host cells 1(p147). Indeed, they had previously shown in 2005 that SARS-Cov could enter host cells via this transmembrane protein 5). Further biological understanding of how SARS-CoV-2 can enter host cells and how this integrates with ACE2R route of entry is needed. Also, the specific cellular targets of the anti-CD147 antibody need to be assessed, as this protein can be expressed by many cell types and has been shown to involved in leukocytes aggregation 6. Lastly, Meplazumab is not a commercially-available drug and requires significant health resources to generate and administer which might prevent rapid development and use.

      1. Wang K, Chen W, Zhou Y-S, et al. SARS-CoV-2 Invades Host Cells via a Novel Route: CD147-Spike Protein. Microbiology; 2020. doi:10.1101/2020.03.14.988345
      2. Pushkarsky T, Zybarth G, Dubrovsky L, et al. CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A. Proc Natl Acad Sci USA. 2001;98(11):6360-6365. doi:10.1073/pnas.111583198
      3. Watanabe A, Yoneda M, Ikeda F, Terao-Muto Y, Sato H, Kai C. CD147/EMMPRIN acts as a functional entry receptor for measles virus on epithelial cells. J Virol. 2010;84(9):4183-4193. doi:10.1128/JVI.02168-09
      4. Crosnier C, Bustamante LY, Bartholdson SJ, et al. BASIGIN is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature. 2011;480(7378):534-537. doi:10.1038/nature10606
      5. Chen Z, Mi L, Xu J, et al. Function of HAb18G/CD147 in Invasion of Host Cells by Severe Acute Respiratory Syndrome Coronavirus. J Infect Dis. 2005;191(5):755-760. doi:10.1086/427811
      6. Yee C, Main NM, Terry A, et al. CD147 mediates intrahepatic leukocyte aggregation and determines the extent of liver injury. PLOS ONE. 2019;14(7):e0215557. doi:10.1371/journal.pone.0215557

      Review by Emma Risson and Robert Samstein as part of a project by students, postdocs and faculty at the Immunology Institute of the Icahn school of medicine, Mount Sinai.

    1. On 2020-03-30 13:57:15, user Sinai Immunol Review Project wrote:

      Summary: Based on a retrospective study of 85 hospitalized COVID patients in a Beijing hospital, authors showed that patients with elevated ALT levels (n = 33) were characterized by significantly higher levels of lactic acid and CRP as well as lymphopenia and hypoalbuminemia compared to their counterparts with normal ALT levels. Proportion of severe and critical patients in the ALT elevation group was significantly higher than that of normal ALT group. Multivariate logistic regression performed on clinical factors related to ALT elevation showed that CRP >= 20mg/L and low lymphocyte count (<1.1*10^9 cells/L) were independently related to ALT elevation—a finding that led the authors to suggest cytokine storm as a major mechanism of liver damage.

      Limitations: The article’s most attractive claim that liver damage seen in COVID patients is caused by cytokine storm (rather than direct infection of the liver) hinges solely on their multivariate regression analysis. Without further mechanistic studies a) demonstrating how high levels of inflammatory cytokines can induce liver damage and b) contrasting types of liver damage incurred by direct infection of the liver vs. system-wide elevation of inflammatory cytokines, their claim remains thin. It is also worth noting that six of their elevated ALT group (n=33) had a history of liver disease (i.e. HBV infection, alcoholic liver disease, fatty liver) which can confound their effort to pin down the cause of hepatic injury to COVID.

      Significance of the finding: Limited. This article confirms a rich body of literature describing liver damage and lymphopenia in COVID patients.

      Review by Chang Moon as part of a project by students, postdocs and faculty at the<br /> Immunology Institute of the Icahn school of medicine, Mount Sinai.

    1. On 2020-04-03 07:50:32, user BoghosLArtinian wrote:

      In times of lethal pandemics any safe treatment that shows the slightest benefit should be tried before waiting for large scale scientific studies to be completed, to prove efficacy of treatments, and losing thousands of lives in the process.

    1. On 2020-11-21 00:29:25, user Richard Wachterman wrote:

      Will airlines allow during flight since they do not allow masks that have exhaust holes? I realize that there are options for putting filters over the exhaust valve, but do we know if the airlines will accept that.

    1. On 2020-12-04 16:17:03, user sdharbinger wrote:

      I have three reservations about aspects of this study.

      Firstly, the study tried to emulate a Randomised Control Trial by isolating consideration and analysis of each component for their potential as a single magic bullet agent and it never recorded or analysed enough data on a far greater range of different agents when they are taken in combination as part of integrated protocols. For example the Eastern Virginia Medical School protocol advocates supplementing with a combination of Vitamin C, Vitamin D, Quercetin, Zinc, Melatonin and Vitamin B complexes. Many also advocate Selenium, Magnesium, Folic Acid, NAC or Elderberry Syrup to name but a few.

      Any combination of these agents could possibly help to build immunity because they act in different ways in different parts of the immune system and collectively certain protocols might show highly significant improvements in outcomes. There is no reason why the ZOE.app could not have collected data on all popular supplements and then analysed the data looking to see how effective different combinations were. This ability in principle to have collected virtually unlimited data from millions of subjects is what potentially makes the ZOE.app far superior to any RCT with virtually real time results and reports. If the Zoe app had given users the chance to enter a full range of supplements instead of restricting to them to just 6, then it would have been possible to analyse the effects of these agents when used in different combinations. In trying to emulate the 'gold standard' design and functionality of RCTs the ZOE.app and the study it generated: ignored the huge advantages that the ZOE.app has over RCTS in principal and in potential practices.

      Secondly the study restricted its analysis to a question of whether people taking various supplements would go on the have a positive PCR test. The general problem with this measure is that no-one supposed that any of these supplements would provide complete prophylaxis against Covid-19 and that people were taking vitamins in the hope that if they caught Covid-19 that they would experience less severe illness on account of a better immune system. The best metric in these terms would have been to assess the relative hospitalisation rates between those taking supplements or not and not simply reduced evaluation to just prophylaxis.

      Thirdly, the study failed to record what dosages of supplements people were taking which potentially have a large effect on outcomes.

    1. On 2020-12-06 20:15:11, user Murilo Perrone wrote:

      It appears to me that the 8 patients on the treatment group who did not make it where exactly the ones who failed to reach adequate levels of 25OHD (above 30 ng/mL). The chart indicates that 5 patients from the treatment group failed even to reach 20 ng/ml. Unfortunately, the study gives no clue about this possible correlation, but that's my best guess.

      I noticed that ventilation machine requirement was reduced by more than 50% in treatment group, but all 8 patients from treatment group who required it didn't survive. There is an indication that their outcome was predictable. IMHO, their specific data should be analyzed.

    1. On 2020-12-11 16:41:00, user Richard Neher wrote:

      Review of version 1 of this manuscript -- 2020-12-11:

      Kemp and colleagues present a case of persistent SARS-CoV-2 infection and analyze the molecular evolution that unfolded within the host in detail. This case is not dissimilar from two recently described cases (Choi et al (10.1056/NEJMc2031364), Avanzato et al (10.1016/j.cell.2020.10.049)). In contrast to these previous cases, Kemp et al investigate within-host evolution using deep sequencing and trace the frequencies of different variants through time. They characterize three diverged variants with different mutations and deletions in the spike protein, some of which reduce neutralization titers of convalescent plasma in a pseudo-typed lentivirus. Overall, the work in this paper is well performed and it provides convincing evidence of in-vivo antibody escape.

      I have a number of suggestions to improve the presentation, strengthen the conclusions, and to remove/tone down parts that might be misleading.

      * Fig 2A: The radial tree in Figure 2 is rather unhelpful. The labels are hardly readable and distances between samples are very hard to judge from the radial presentation. A rectangular tree indicating major clades and the different within-host samples would be better.

      * Fig 2B & 4B: I think the figure would be improved by changing the scale bar to correspond to one or two mutations (currently the scale bar is given in mutations per site and is roughly 6 mutations in 2B, 2 mutations in 4B). Zero-length branches in the ML trees should be collapsed into polytomies. Bootstrap values on SARS-CoV-2 trees are pretty useless. Better to label the branches with (number of) mutations that fall on the branch in a parsimony or ML reconstruction. This has a one-to-one correspondence to bootstrap values and is more interpretable.

      * The purple line in Fig 3B suggests an iSNV at frequency 30% on day one that persists at a frequency around 30% until day 82. This iSNV doesn't seem to be affected by the fixation of other iSNVs at time points 66 or 82 days. Would be good to look into this. It could indicate population structure which would imply parallel evolution. Or it could be an artifact (more likely). Either way, this should be looked at and discussed.

      * To understand the rapid shifts in dominating variants better, it would be helpful to include a discussion of their frequencies when they are rare. It makes a difference to the interpretation if the minor variants are present at 10%, 1%, or 0.1%. The reader currently has to piece this together from supplementary table 3 and there are some discrepancies: The S:64G variant seems to be very rare after day 95 (not detected by high coverage Illumina) while the linked S330S is still picked up (at high frequency in low coverage data??). Mutations 200H,240I,258S are missing from supplementary table 3.

      * Fig 5 would be more useful on a logscale. Bar charts should be avoided, individual data points need to be shown.

      * the description of how evolutionary rates are estimated from within-host data is very short. I would caution against over-interpreting these estimates for two reasons: (i) Phylogenetic estimates are done with consensus sequences and thus ignore minor variation. (ii) rate estimates likely depend a lot on how the within-host variation is rooted and how the root height is constrained. The error of the mean rates (table S2) seems way too small in some cases (1% of the main) calling the entire procedure into question. I would cut this as I don't think this is reliable and it is not central to the paper.

      * Similarly, the logistic fit to T39I in ORF7a (Supp Fig 6) is not evidence for selection. I don't see what this figure adds that is not visible in Fig 3. All that Fig S6 shows is that the variant was rare at day one and then bounced around frequency 0.5 between day 30 and 60. There is no reason to fit a logistic and insinuate selection.

      * the distances presented in Fig S5 seem rather large (two-fold larger than what I would have guessed from the tree).

      * accession numbers for consensus sequences and reads need to be provided.

    1. On 2020-12-15 23:02:05, user E. de Moya wrote:

      You should contact Mr. Wallukat and Celltrend, both researching autoantibodies in postviral Postural Tachycardia Syndrome (POTS) and ME/CFS. It would be interesting to see, if long-haulers also have amongst others, adrenergic and muscarinic aabs

    1. On 2021-01-24 08:54:43, user ad4 wrote:

      Can the authors please provide a list / file of all input parameters (with error intervals) used in the model and make all code publicly available.

    1. On 2020-09-16 02:09:39, user Peter Lange wrote:

      Thanks, interesting paper. To my knowledge reporting appears complete but may I suggest statement that the paper is consistent with the relevant EQUATOR guideline and completion of the check-list - I think it would be STARD?

    1. On 2020-09-24 00:34:03, user Peter Olins wrote:

      @Bjorn, <br /> Perhaps I'm missing something, but I don't understand why you assume a 12-second interval between breaths when the resting rate for adults is typically one breath every 3-5 seconds. In addition, I suspect that a high breath rate would be expected for people socializing and eating lunch in a crowded restaurant. <br /> What effect would a 4-fold increase in respiration have on your calculations?

      Peter Olins, PhD.

    1. On 2020-09-24 19:07:43, user Steve Schaffner wrote:

      The paper reports that Rh-positive blood type and mortality are positively correlated. According to Supplemental Table 3 (which doesn't seem to be accessible from the preprint server), mortality is also positively correlated with Rh-negative status. Since people can only be Rh+ or Rh-, this is not possible. I suspect the authors didn't remove samples with missing blood type information before doing the calculation -- information that is more likely to be missing for those who survived. If this is what happened, the high correlation with Rh+ type simply reflects the high prevalence of Rh+ in the population.

    1. On 2020-09-24 20:42:31, user Marcus Roscher wrote:

      Interesting findings... but one might not agree with their interpretation: strong but late measures as in most countries lead to many also lethal cases and then a sudden case drop. If the tested seropositive group is representative enough to deduce 44-66% infection rate of the population is questionable IMHO. And if so we don’t know what influence it really had on the case evolution (considering possible reeinfections or weak till no immunity with mild and no symptoms) ... so it’s not clear if there is a kind of herd immunity and second in such short time. On the other hand this would mean we would have 400-500 death per 100k population in older societies in order to reach some kind of Heard- immunity. What a price!

    1. On 2020-09-29 06:52:41, user Robert Stephens wrote:

      Could it be that the infection fatality rate (IFR) within a community may be determined by the dominant mode/s of transmission within that community? In Mumbai for instance, the adjusted IFR in the Dharavi slum community was 0.076% but in the non-slum community the IFR was 0.27% for the same period (https://www.medrxiv.org/con... "https://www.medrxiv.org/content/10.1101/2020.08.27.20182741v1)"). This discrepancy is unlikely to be on account of genetic factors, prior exposure to other coronaviruses, and perhaps is not due to age differences either.

      Poor sanitation in slums may have resulted in cases of spread through contaminated water. Orofaecal transmission may have resulted in "safer" infections (gastrointestinal infections, oral mucosal & upper respiratory tract infections). <br /> In communities without sanitation issues, transmission of virus via airborne routes perhaps occurs more frequently. Airborne exposure to virus is potentially more toxic than non-airborne exposure as the transmission is more directed to lungs.

      Robert Stephens MB BS FACD

    1. On 2020-09-29 22:53:36, user Guillermo Ruiz-Irastorza wrote:

      The paper has been already published in PLoS One 2020 Sep 22;15(9):e0239401. doi: 10.1371/journal.pone.0239401. eCollection 2020.

    1. On 2020-10-05 08:20:30, user NMN wrote:

      The way it is presented in the abstract seems misleading to me, it presents itself as a report of a mass screening of nearly 2000 individuals, in which saliva outperformed NP swabs, but this is not really an accurate picture of what they found.

      They have 2 cohorts. <br /> 1) a contact tracing (CT) cohort of 161 individuals, of which 47 were positive by NP and/or Saliva. I would not consider contact tracing of less than 200 individuals to be “mass screening”<br /> 2) An airport mass screening cohort of 1763 individuals, of which 5 were positive by NP and/or saliva.

      The saliva outperformed the NP swabs in the CT cohort only, with 44/47 positives for saliva compared to 41/47 positives for NP swabs.<br /> NP swabs outperformed the saliva in the mass screening cohort, with 5/5 positives by NP swab, and 4/5 positives by saliva. These numbers are too low to make conclusions for mass screening though.

      Furthermore, it seems that there are math errors in the sensitivities that they report.<br /> They report sensitivities of NP and saliva as 86% and 92% respectively, yet there is no way to arrive at these %s from the numbers in their tables.

      Sensitivities for NP vs saliva in:<br /> CT cohort only: 87.2 vs 93.6% (41 vs 44 /47)<br /> Mass Screen cohort only: 100 vs 80% (5 vs 4 /5)<br /> Combined cohorts: 88.5 vs 92.3% (46 vs 48 /52)

    1. On 2020-10-09 06:56:14, user Reetpetit wrote:

      Thank you for a very interesting study.

      @Mark Wilson <br /> Sounds like your mind is already made up, which is unhelpful.

      In the IZA study of the introduction of face masks in Germany - which was particularly interesting as it happened on slightly different dates in different regions, allowing for a synthetic control - face masks were shown to have reduced Covid transmission by about 40%.

    1. On 2020-10-12 13:15:33, user Anechidna wrote:

      Vitamin D, which one? The assumption is D3 but D2 is the most commonest form of supplemental vitamin D in the belief that it is converted into D3 which it isn't. Very sloppy work to talk about Vitamin D when you were performing your research on a specific form. The research also indicates elevating levels of D2 in an attempt to drive up D3 results in suppression of D3 levels. So either get the required skin sunlight interaction allowing for skin tone or get D3 in its proper supplemental form as D3.