445 Matching Annotations
  1. Jan 2022
    1. Peer review report

      Reviewer: Hurng-Yi Wang Institution: Institute of Ecology and Evolutionary Biology, National Taiwan University email: hurngyi@gmail.com


      Section 1 – Serious concerns

      • Do you have any serious concerns about the manuscript such as fraud, plagiarism, unethical or unsafe practices? No
      • Have authors’ provided the necessary ethics approval (from authors’ institution or an ethics committee)? not applicable

      Section 2 – Language quality

      • How would you rate the English language quality? Medium quality

      Section 3 – validity and reproducibility

      • Does the work cite relevant and sufficient literature? No
      • Is the study design appropriate and are the methods used valid? No
      • Are the methods documented and analysis provided so that the study can be replicated? Yes
      • Is the source data that underlies the result available so that the study can be replicated? Yes
      • Is the statistical analysis and its interpretation appropriate? Yes
      • Is quality of the figures and tables satisfactory? No
      • Are the conclusions adequately supported by the results? No
      • Are there any objective errors or fundamental flaws that make the research invalid?

      Section 4 – Suggestions

      • In your opinion how could the author improve the study?

      • Do you have any other feedback or comments for the Author?

      Agarwal and Parekh analyzed 685 SARS-CoV-2 isolates collected during 27th Jan - 27th May 2020 from India and described the distribution of virus strains and mutations across the country. While the information might be valuable to some local readers, the results are mainly descriptive and the data are a bit out of date. In addition, I have the following comments.

      1. Some details of the methods are lacking. For example, the MUpro provides two methods, it is necessary to specify which method was used in the analysis. The confidence score of each prediction should also be provided. Besides, some results from I-Mutant and MUpro were conflicting, the authors may want to discuss the discrepancy.
      1. The “Analysis of the Mutational Profile of Indian Isolates” should be moved to Materials and Methods.
      1. The authors provided lengthy discussion about the effect of each mutation in some lineages, such as 20A and I/A3i. However, as these mutations are tightly linked, the effect of each individual mutation is difficult to access. It is possible that some of the mutations are just hitchhikers. They may want to address this alternative point.
      1. Several figures are confusing and lack detail. The diversity plots of Figure 3 and Figure 8 are hard to be precisely compared to the mutations that occurred among different plots. Phylogenetic trees, as well as their figure legends, are confusing, especially Figure 9 and Figure 10. For Figure 9, it is impossible to tell which mutation site had changed from C to T. For Figure 10, spots depicted in yellow are both position 29827 A>T and position 29830 G>T, green spot only notes as G, but A29827 is not mentioned in the figure. Furthermore, the mutation position of blue spot C cannot be found.
      1. Figure 9 and Figure 10 were not mentioned inside the text.
      1. The Top 10 mutations in PCA analysis are the mutations in 20A and I/A3i. It is reasonable to observed a clear association of the clusters with the clades. It is not clear, however, how these distribution correlate with lockdown, contact tracing and quarantine measures.

      Section 5 – Decision

      Requires revisions

    2. Peer review report

      Reviewer: Dr. Jyotsnamayee Sabat Institution: Regional VRDL, RMRC(ICMR). email: jyotsnasabat@yahoo.com


      Section 1 – Serious concerns

      • Do you have any serious concerns about the manuscript such as fraud, plagiarism, unethical or unsafe practices? No
      • Have authors’ provided the necessary ethics approval (from authors’ institution or an ethics committee)? not applicable

      Section 2 – Language quality

      • How would you rate the English language quality? Good quality

      Section 3 – validity and reproducibility

      • Does the work cite relevant and sufficient literature? Yes
      • Is the study design appropriate and are the methods used valid? Yes
      • Are the methods documented and analysis provided so that the study can be replicated? Yes
      • Is the source data that underlies the result available so that the study can be replicated? Yes
      • Is the statistical analysis and its interpretation appropriate? Yes
      • Is quality of the figures and tables satisfactory? Yes
      • Are the conclusions adequately supported by the results? Yes
      • Are there any objective errors or fundamental flaws that make the research invalid?

      No such application was observed.


      Section 4 – Suggestions

      • In your opinion how could the author improve the study?

      They have analysed it in-depth and presented nicely.

      • Do you have any other feedback or comments for the Author?

      I want to know how the representative sequences were selected for different states. Is it based on no of sequences submitted or positivity rate of a particular region.


      Section 5 – Decision

      Verified manuscript

    3. Peer review report

      Reviewer: Parvin Abraham Institution: MIMS Research Foundation, Calicut, Kerala, India. email: parvinabraham@gmail.com


      Section 1 – Serious concerns

      • Do you have any serious concerns about the manuscript such as fraud, plagiarism, unethical or unsafe practices? No
      • Have authors’ provided the necessary ethics approval (from authors’ institution or an ethics committee)? not applicable

      Section 2 – Language quality

      • How would you rate the English language quality? High quality

      Section 3 – validity and reproducibility

      • Does the work cite relevant and sufficient literature? Yes
      • Is the study design appropriate and are the methods used valid? Yes
      • Are the methods documented and analysis provided so that the study can be replicated? Yes
      • Is the source data that underlies the result available so that the study can be replicated? Yes
      • Is the statistical analysis and its interpretation appropriate? Yes
      • Is quality of the figures and tables satisfactory? Yes
      • Are the conclusions adequately supported by the results? Yes
      • Are there any objective errors or fundamental flaws that make the research invalid? Please describe these thoroughly. No

      Section 4 – Suggestions

      • In your opinion how could the author improve the study?

      The dataset is only from 27th Jan – 27th May 2020. Maybe they can include more Numbers.

      • Do you have any other feedback or comments for the Author? No

      Section 5 – Decision

      Verified manuscript

    1. Peer review report

      Reviewer: Dr. : Peter Dahlberg Institution: SLAC national laboratory email: pdahlb@slac.stanford.edu


      Section 1 – Serious concerns

      • Do you have any serious concerns about the manuscript such as fraud, plagiarism, unethical or unsafe practices? No
      • Have authors’ provided the necessary ethics approval (from authors’ institution or an ethics committee)? not applicable

      Section 2 – Language quality

      • How would you rate the English language quality? Low to medium quality. I have added several comments to section 4 as suggested edits.

      Section 3 – validity and reproducibility

      • Is the reason for developing a new method explained? Yes
      • Is the description of the method technically sound? Yes
      • Are sufficient details provided so that the method can be replicated? No
      • Is the source data that underlies the result available so that the study can be replicated? not applicable
      • Is quality of the figures and tables satisfactory? Yes
      • Are the conclusions adequately supported by the results? No
      • Are there any objective errors or fundamental flaws that make the research invalid? Please describe these thoroughly. No

      Section 4 – Suggestions

      • In your opinion how could the author improve the method?

      The manuscript describes the progressive refinement method for sparse recovery. This approach uses minimal RAM while producing a finely discretized output for high density 3d fluorescence localizations. Furthermore, the approach does not require the PSF to be translationally independent. This is an assumption that is often made that simplifies the computation, but does not account for field dependent aberrations. There are several comments that I believe would improve what is overall strong manuscript. The most serious of which is addressed in 1a below.

      1. The two main claims of the manuscript are that the PRIS method requires less RAM than a brute force approach and that the algorithm functions for spatially varying PSFs. Neither of these claims are supported directly by the text or figures. a. Perhaps I missed it, but there were no field dependent aberrations in the simulations. If this is the case, how exactly has it been demonstrated that the approach works well for a spatially varying PSF? Because this is a central claim of the PRIS method, I think it is worth implementing. b. The authors describe a scenario of brute force solving of the inverse problem requiring 152.6 GB, while I have no doubt that the PRIS approach would require less RAM, the authors do not make it clear how much less. While I know that the reduction will depend on the exact implementation and the data at hand, a rough comparison of the RAM requirements would be helpful for the reader.

      2. Following algorithm 1, the authors introduce the “shrink” operator. A one line description would be helpful of what this operator does. As I understand it, it is a threshold of the output to keep the data output sparse.

      3. Following algorithm 1 and 2, the authors describe the use of “kicking.” They do a nice job of giving a brief description of what the “kicking” does (improve the convergence speed), but I am concerned because neither algorithm 1 or 2 shows kicking. The kicking is wrapped up in another conditional statement that is not shown in either algorithm. This is confusing for the reader. Perhaps a parenthetical should be added stating that the kicking is not shown in the algorithm.

      4. The code for the PRIS method should be made available publicly, both so the results can be replicated and also so that others can use the approach.

      • Do you have any other feedback or comments for the Author?

      Additionally, I have some minor text/figure edits

      1. In the title, the acronym PRIS is defined as “progressive refinement method on sparse recovery” however in the text it is “progressive refinement method for sparse recover” I think the wording in the text is correct.

      2. 5th paragraph of the introduction: “In principal” should be “In principle”

      3. Paragraph preceding section 3: “in case if a species” I think should read “in case a species”

      4. Throughout the figures, dark red, dark green, and dark blue are used over black and this is very difficult to see. For example, dashed red line in figure 2 on the right hand side, the cy5 and cy3 labels in figure 7, the dark blue box in figure 8.

      5. Throughout the figures there are also a lot of small symbols used. For example, Figure (a)-4 there are small (red?) marks on top of a red heat map. These are extremely difficult to see clearly.

      6. Figure 6c, it is very challenging to see differences in the distributions of points. I think this data would be better represented if additional histograms were shown.


      Section 5 – Decision

      Requires minor revisions

    2. Peer review report

      Reviewer: Dr. Christopher H. Bohrer Institution: NIH/NCI email: bohrerch@nih.gov


      Section 1 – Serious concerns

      • Do you have any serious concerns about the manuscript such as fraud, plagiarism, unethical or unsafe practices? No
      • Have authors’ provided the necessary ethics approval (from authors’ institution or an ethics committee)? not applicable

      Section 2 – Language quality

      • How would you rate the English language quality? High quality

      Section 3 – validity and reproducibility

      • Is the reason for developing a new method explained? Yes
      • Is the description of the method technically sound? Yes
      • Are sufficient details provided so that the method can be replicated? No
      • Is the source data that underlies the result available so that the study can be replicated? No
      • Is quality of the figures and tables satisfactory? Yes
      • Are the conclusions adequately supported by the results? No
      • Are there any objective errors or fundamental flaws that make the research invalid? Please describe these thoroughly. No

      Section 4 – Suggestions

      • In your opinion how could the author improve the method?
      1. The approach is nice, but I really think they should highlight the advantage of their approach --- that is, perform a simulation with imperfect optics then apply the traditional methodologies as well as their own to show their superiority.

      2. The comparison to previous methodologies is nice, but the fact that they are different simulations with different parameters is a major problem --- for example, the photons used in their simulations are higher than used in the previous studies. Therefore, if they are going to compare, it should only be done if the methodologies were applied to the same data.

      3. A user guide with an example, walking through the specifics would aid this work greatly. For instance, it is unclear how one obtains the different matrices given their data --- though this is likely within the references. Additionally, if they want others to use the methodology, this is a must!

      4. Finally, though I don’t think they necessarily need to do this, but utilizing real experimental data to validate their approach would be nice. For instance, investigate the structure of the nuclear pore complex with the different methodologies --- a standard within the field.

      • Do you have any other feedback or comments for the Author? No

      Section 5 – Decision

      Requires revisions

    1. Peer review report

      Reviewer: Deyou Qiu Institution: Chinese Academy of Forestry. email: qiudy@caf.ac.cn


      Section 1 – Serious concerns

      • Do you have any serious concerns about the manuscript such as fraud, plagiarism, unethical or unsafe practices? No
      • Have authors’ provided the necessary ethics approval (from authors’ institution or an ethics committee)? not applicable

      Section 2 – Language quality

      • How would you rate the English language quality? High quality

      Section 3 – validity and reproducibility

      • Does the work cite relevant and sufficient literature? Yes
      • Is the study design appropriate and are the methods used valid? Yes
      • Are the methods documented and analysis provided so that the study can be replicated? Yes
      • Is the source data that underlies the result available so that the study can be replicated? Yes
      • Is the statistical analysis and its interpretation appropriate? Yes
      • Is quality of the figures and tables satisfactory? Yes
      • Are the conclusions adequately supported by the results? Yes
      • Are there any objective errors or fundamental flaws that make the research invalid? Please describe these thoroughly. No

      Section 4 – Suggestions

      • In your opinion how could the author improve the study? No
      • Do you have any other feedback or comments for the Author?

      The resolution of Fig 3 is not good, could you pls improve it?


      Section 5 – Decision

      Requires revisions

    1. Peer review report

      Reviewer: Max Shokhirev Institution: Salk Institute for Biological Studies email: maxshok@gmail.com


      Section 1 – Serious concerns

      • Do you have any serious concerns about the manuscript such as fraud, plagiarism, unethical or unsafe practices? No
      • Have authors’ provided the necessary ethics approval (from authors’ institution or an ethics committee)? not applicable

      Section 2 – Language quality

      • How would you rate the English language quality? High quality

      Section 3 – validity and reproducibility

      • Does the work cite relevant and sufficient literature? Some, but seems to be very limited in terms of biological literature.
      • Is the study design appropriate and are the methods used valid? Yes
      • Are the methods documented and analysis provided so that the study can be replicated? not applicable
      • Is the source data that underlies the result available so that the study can be replicated? Yes
      • Is the statistical analysis and its interpretation appropriate? Yes
      • Is quality of the figures and tables satisfactory? Yes
      • Are the conclusions adequately supported by the results? Yes
      • Are there any objective errors or fundamental flaws that make the research invalid? How could the author improve the study?

      The author has laid out a theoretical argument for senescence as a tradeoff between information capacity between epigenetic and non-epigenetic content.“A constraints-based theory of senescence: imbalance of epigenetic and non-epigenetic information in histone crosstalk.” This work is interesting, but is based on a superficial understanding of the biology underlying senescence/aging, makes several dangerous oversimplifications and assumptions, and does not provide any data or analysis to support the theory. I’ve laid out my comments for each section below:

      Sections 1.1-1.3

      The author only mentions the Hayflick limit as a biological reference for senescence. There is a very rich body of literature on senescence and aging that is completely overlooked here. The author should include additional references to reviews for senescence and aging to orient the reader to the complexity of these biological processes (e.g. PMC8658264, PMC7846274). Please clarify what you mean by senescence vs aging for both cells and individuals. Senescence is a natural biological process that cells/organisms use to turn off cell replication due to damage (e.g. telomere shortening, double-stranded breaks, etc.). Other cells can also facilitate this process through signaling (e.g. immune cells or contact inhibition). Aging is typically thought of as an organismal phenomenon, which is still poorly understood but is theorized to include tradeoffs (as you describe in section 1.2). It is also accepted that aging is cell, tissue, and organism specific. Since you talk about senescence and aging across both biological scales, it is important to define exactly what your theory pertains to.

      Section 1.4

      The author posits that senescence is an imbalance in information contents of histone post-translational modifications around transcription start sites. This is just one level of regulation, albeit an important one. The author seems to completely overlook many other types of regulation (e.g. microRNA, lincRNAs, metabolic/energetic constraints, non-proximal regulation at enhancers, higher ordered structure of the chromatin, post-translational regulation of proteins, and etc.). How can all of these other important levels of regulation fit into this theory? All have been implicated in senescence/aging in some form or another. The author further suggests that histone crosstalk information content can be decomposed into two unrelated components: epigenetic and non-epigenetic. The non-epigenetic component is described as “hologenic information content,” which stems from a previously published work by the author. Non-epigenetic is confusing in this context since really this is information content that stems from the synergies of individual cells to form a whole, e.g. the emergent information content that comes from many cells working together (or at least this is how I understand the underlying theory). This information content is important for the general maintenance and survival of the organism. The author should clarify this point further, since this seems to be one of the fundamental assertions being made in the paper. For example, bringing in the descriptions used in section 2, can further clarify these central points. In addition, the author states: “ Moreover, the sum decomposition in Eq. 1 implies that the growth in magnitude (bits) of the hologenic (i.e., non-epigenetic) component must be accompanied by a decrease in magnitude of the epigenetic component.” This is not necessarily true, since signaling is a separate biological process from the regulation of gene expression. In other words, both can increase or decrease simultaneously. For example, a healthy non-senescent immune cell can upregulate very specific transcriptional programs that lead to very complex signaling and extra-cellular interactions. You can argue that both represent an increase in information content for both the epigenetic and non-epigenetic “hologenic” components. In addition, as cells naturally senesce they are programmed to turn off cell-cycling while upregulating autophagy and repair processes. They may not upregulate extracellular signaling at this time, which would seem to contradict the author’s theory/statement. In this case, the simplification that all cells are the same is dangerous because it overlooks the tradeoff of information contents between cells. It also ignores important repair pathways (senescence being one of them), to deal with cells that have dysregulated their natural processes over time. It also overlooks the important action of immune cells that work to get rid of cancer and poorly-functioning cells. Also, it seems crosstalk, correlation, capacity, and content, are used interchangeably. Please clarify that these are all the same, or use one of these terms to avoid confusion.

      Section 1.5

      The author provides a general approach for measuring the log of the ratio of epigenetic and non-epigenetic capacities for a particular histone modification at three positions (i,j,k), and for some measured abundance of mRNA Y. Since we typically measure abundance of a particular modification genome-wide, and the mRNA level for tens of thousands of genes, how would a realistic equation look like (i.e. one that has 10k mRNA levels, and 10k histone positions)? In addition, the author does not explain how to combine correlations across multiple histone modifications. Please expand this section to make it relevant for real-world genome-wide measurements since this will be important for falsifying the theory. Since public datasets are available (e.g. the aging atlas https://doi.org/10.1093/nar/gkaa894), the author should show an example of how a dataset might be used to falsify or demonstrate the theory in more detail.

      Section 2.1

      The author uses correlation of the log ratio of the epigenetic and non-epigenetic content with age as a readout of “reassignment” of crosstalk/contents, arguing that for cancer cells this correlation should be essentially zero. This seems like an oversimplification of the “reassignment” process since senescence may occur in phases across the age of a cell/organism, and since there might be both increases and decreases in the log ratio of contents due to natural biological processes and variability. Would it not be better to measure the sum of changes in the log ratio or the difference between the log ratios at different ages?

      In addition, the biological age of a cell/tissue/organism can vary. For example, stem cells may have negligent aging, while other cells might age relatively quickly. Again, the author should clarify the context of age: are we measuring strictly chronological age correlation? Should we consider different correlations for each cell/tissue in the organism? What about tradeoffs in information content between cell types and tissues? In other words, it is unclear how the theory should be applied to biological systems.

      Section 2.2

      The author argues that senescence is an emergent property of the loss of information content for epigenetic histone crosstalk and an increase in information content of “hologenic” information content (e.g. cell signaling and anti-tumor signaling). I believe this premise does not stem from the reality of biological systems (see my comments for section 1.4). Also, this section seems to be contradicting the author’s conclusions and is very confusing. The author seems to argue that there is both more AND less constraint at the multi-cellular level (organismal)? Please clarify or remove this section.

      Section 2.3

      Senescence as transcriptional overregulation is vague. Here the author is arguing that as epigenetic constraint decreases, you have a decrease in precision (e.g. loss of regulation), but then you have a competing global or hologenic increase in constraints, which constrains the expression of genes for the overall benefit of the organism. A shift toward global constraint.

      Section 2.4

      This seems to be describing an illustrative real-world example? This section is incredibly specific and again only focuses on one possible mechanism and does not include any measured data or analysis. Please preface this section to explain that this is just one of many possible examples. Again, it will be good to provide other examples looking at other aspects of aging biology (not just histone modifications).

      Section 2.5-2.9,3

      This seems to be a general discussion. It would be easier to organize these sections into one discussion section for added clarity. Again, I would recommend not talking about sweeping statements like “Senesensce’s ultimate cause” and “Can senescence be stopped?” since this theory only addresses one small aspect of the biology underlying aging and senescence and does not address the heterogeneity of aging. These topics are controversial and should be addressed very carefully to avoid alienating the biological community.


      Section 4 – Decision

      Revisions required

    2. Peer review report

      Reviewer: Charles A. Schumpert Institution: University of South Carolina email: schumpca@email.sc.edu


      Section 1 – Serious concerns

      • Do you have any serious concerns about the manuscript such as fraud, plagiarism, unethical or unsafe practices? No
      • Have authors’ provided the necessary ethics approval (from authors’ institution or an ethics committee)? not applicable

      Section 2 – Language quality

      • How would you rate the English language quality? High quality

      Section 3 – validity and reproducibility

      • Does the work cite relevant and sufficient literature? Yes
      • Is the study design appropriate and are the methods used valid? Yes
      • Are the methods documented and analysis provided so that the study can be replicated? not applicable
      • Is the source data that underlies the result available so that the study can be replicated? Yes
      • Is the statistical analysis and its interpretation appropriate? Yes
      • Is quality of the figures and tables satisfactory? Yes
      • Are the conclusions adequately supported by the results? Yes
      • Are there any objective errors or fundamental flaws that make the research invalid? Please describe these thoroughly.

      Overall the manuscript is written brilliantly and provides excellent context to the audience about a complex theoretical biological concept. No flaws can be found, although one could argue against a few of the points in the assumptions used to construct the theory, there’s nothing illogical or irrational.


      Section 4 – Suggestions

      • In your opinion how could the author improve the study?

      The writing of the paper makes it easy to read, which can sometimes be a challenge with theoretical biology manuscripts. Potentially adding a bit more context on the various theories of aging may help demonstrate the marriage of the ideas into the theory he constructed.

      • Do you have any other feedback or comments for the Author? No

      Section 5 – Decision

      Verified manuscript

    1. Edouard Mathieu. (2022, January 17). Update: Switzerland now reports deaths by booster status. Compared to unvaccinated people, the COVID mortality rate is: • 9x lower after full vaccination • 48x lower after a booster [From our post with @maxcroser on death rates by vaccination status: Http://ourworldindata.org/covid-deaths-by-vaccination] https://t.co/ozWueyHO2k [Tweet]. @redouad. https://twitter.com/redouad/status/1482991873190936576

    1. BNO Newsroom. (2021, December 30). BREAKING: U.S. reports 400,000 new coronavirus cases, the biggest one-day increase on record, with some states yet to report [Tweet]. @BNODesk. https://twitter.com/BNODesk/status/1476348049404436485

    1. Ariel Karlinsky. (2022, January 2). Russia at 1.04 MILLION excess deaths since March 2020, which is about 240% higher than their reported COVID-19 deaths. This is 1st place worldwide (for countries with data) in absolute excess mortality, 2nd place on per capita terms and 9th on p-score. #poptwitter #epitwitter https://t.co/aLBRRht3z2 [Tweet]. @ArielKarlinsky. https://twitter.com/ArielKarlinsky/status/1477531141510946818

    1. Hugh Pym. (2022, January 11). While U.K. daily reported cases fall, COVID deaths (379) up to 28 days after a positive test have sadly hit the highest level since February last year. [Tweet]. @BBCHughPym. https://twitter.com/BBCHughPym/status/1480959960653737992

    1. Tigran Avoundjian. (2022, January 3). Increases in hospitalizations routinely lag behind cases by a week (sometimes more). Deaths have an even longer lag. On 12/30, we had seen a 56% increase in 7-day hospitalization counts, and today we are seeing an 81% increase week-to-week. We have already passed the Sept peak. [Tweet]. @avoundji. https://twitter.com/avoundji/status/1478092404091588608

    1. Kayla Simpson. (2022, January 3). The COVID data coming out of NYC jails is...beyond staggering. Today’s report shows a 7-day avg positivity rate of 37%, w/502 ACTIVE INFECTIONS. With a ~5K census, that means that nearly one in ten people in DOC has an ACTIVE infection. Crisis on crisis. Https://hhinternet.blob.core.windows.net/uploads/2022/01/CHS-COVID-19-data-snapshot-2020103.pdf [Tweet]. @KSimpsonHere. https://twitter.com/KSimpsonHere/status/1478114046360657926

    1. Meaghan Kall. (2022, January 3). ⚠️ Warning on death data on https://coronavirus.data.gov.uk NHS England has not reported hospital deaths since 1 January. The backlog will be reported Wednesday. Data are incomplete yesterday, today and tomorrow. Expect a bigger number reported on Wednesday. [Tweet]. @kallmemeg. https://twitter.com/kallmemeg/status/1478049788159569929

  2. Dec 2021
    1. Dr Duncan Robertson. (2021, December 15). Cases on the dashboard exclude reinfections.And there are a lot of reinfections as far as Omicron is concerned h/t @AlistairHaimes and @Peston And this is only cases reported today—Not from infections today With a 2-day doubling time for Omicron, this isn’t great https://t.co/fU2RLhshtn [Tweet]. @Dr_D_Robertson. https://twitter.com/Dr_D_Robertson/status/1471156538681315336

  3. Nov 2021
  4. Oct 2021
    1. mirtazapine is used to treat akathisia probably because of its antagonistic property at H1 postsynaptic receptors and dopaminergic action in the frontal cortex.

      That's an interesting hypothesis. I wouldn't have thought histamine was involved. Though, histamine being a stimulant, it also makes some sense. I'd have thought the primary mechanism is serotonin blockade, which would work in part by dopamine dis-inhibition as mentioned here.

  5. Sep 2021
    1. Users think every Webpack tool/config problem is a problem with a specific package and opens an issue asking for support on the package instead of Webpack. In the past year alone, I’ve had to deal with hundreds of Webpack issues on my repos.
  6. Aug 2021
  7. Jul 2021
  8. Jun 2021
    1. Deepti Gurdasani on Twitter: “I’m still utterly stunned by yesterday’s events—Let me go over this in chronological order & why I’m shocked. - First, in the morning yesterday, we saw a ‘leaked’ report to FT which reported on @PHE_uk data that was not public at the time🧵” / Twitter. (n.d.). Retrieved June 27, 2021, from https://twitter.com/dgurdasani1/status/1396373990986375171

    1. Thompson, M. G., Burgess, J. L., Naleway, A. L., Tyner, H. L., Yoon, S. K., Meece, J., Olsho, L. E. W., Caban-Martinez, A. J., Fowlkes, A., Lutrick, K., Kuntz, J. L., Dunnigan, K., Odean, M. J., Hegmann, K. T., Stefanski, E., Edwards, L. J., Schaefer-Solle, N., Grant, L., Ellingson, K., … Gaglani, M. (2021). Interim Estimates of Vaccine Effectiveness of BNT162b2 and mRNA-1273 COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Health Care Personnel, First Responders, and Other Essential and Frontline Workers—Eight U.S. Locations, December 2020–March 2021. MMWR. Morbidity and Mortality Weekly Report, 70(13), 495–500. https://doi.org/10.15585/mmwr.mm7013e3

  9. May 2021
    1. Gobeil, P., Pillet, S., Séguin, A., Boulay, I., Mahmood, A., Vinh, D. C., Charland, N., Boutet, P., Roman, F., Most, R. V. D., Perez, M. de los A. C., Ward, B. J., & Landry, N. (2021). Interim Report of a Phase 2 Randomized Trial of a Plant-Produced Virus-Like Particle Vaccine for Covid-19 in Healthy Adults Aged 18-64 and Older Adults Aged 65 and Older. MedRxiv, 2021.05.14.21257248. https://doi.org/10.1101/2021.05.14.21257248

  10. Apr 2021
  11. Mar 2021
    1. However, since you haven't yet provided any details about how you built with Qt (Qt isn't officially supported, so you must have used a third party derivative of vim), and you haven't provided any detailed information about what error messages or malfunctions you're having with python-complete, it's not really possible to tell you how to fix the problem and get vim working with Qt.
    1. Patricio R Estevez-Soto. (2020, November 24). I’m really surprised to see a lot of academics sharing their working papers/pre-prints from cloud drives (i.e. @Dropbox @googledrive) 🚨Don’t!🚨 Use @socarxiv @SSRN @ZENODO_ORG, @OSFramework, @arxiv (+ other) instead. They offer persisent DOIs and are indexed by Google scholar [Tweet]. @prestevez. https://twitter.com/prestevez/status/1331029547811213316

  12. Feb 2021
    1. Nick Brown. (2020, November 27). A researcher reads an online news article about a family suicide in another country and writes it up more or less verbatim as a ‘case report’, with a spurious reference to homicide. WTF @wileyglobal? 10.1111/ppc.12686 News article (trans by Google in pic): Https://t.co/uPZeRPN4jg https://t.co/tHW1XQGRyl [Tweet]. @sTeamTraen. https://twitter.com/sTeamTraen/status/1332413218271195137

    1. Report: This price didn't exist on the store This price did show on the store but the game could not be bought This was a very short price made by a mistake (glitch)
  13. Jan 2021
    1. When there are imperfections, we rely on users and our active community to tell us how the software is not working correctly, so we can fix it. The way we do that, and have done for 15 years now, is via bug reports. Discussion is great, but detailed bug reports are better for letting developers know what’s wrong.
  14. Dec 2020
  15. Nov 2020
    1. @hypothes.is

      be careful : because you store the page title, when we make annotation on a personal website that stores personal informations in title, hypothes.is users can retieve those informations.

      for example, here I can see that jbarnett mail is jeankap@gmail.com.

      and i can see his mail's title.

      I will find a report option that would be better than this current annotation.

  16. Oct 2020
    1. The President's efforts to influence the investigation were mostly unsuccessful, but that is largely because the persons who surrounded the President declined to carry out orders or accede to his requests.

      So the better judgement of others has apparently kept Trump out of trouble?

    2. if we had confidence after a thorough investigation of the facts that the President clearly did not commit obstruction of justice, we would so state. Based on the facts and the applicable legal standards, we are unable to reach that judgment. Accordingly, while this report does not conclude that the President committed a crime, it also does not exonerate him.

      TL;DR

      This summary is not what Trump or even Barr have been indicating in their communications.

      Barr's statement on the day of the release of the redacted report: https://www.youtube.com/watch?v=7aHPFh2HfSM

    3. Under OLC's analysis, Congress can permissibly criminalize ce1tain obstructive conduct by the President, such as suborning perjury, intimidating witnesses, or fabricating evidence, because those prohibitions raise no separation-of-powers questions. See Application of 28 U.S.C. § 458 to Presidential Appointments of Federal Judges, 19 Op. O.L.C. at 357 n.11. The Constitution does not authorize the President to engage in such conduct, and those actions would transgress the President's duty to "take Care that the Laws be faithfully executed." U.S. CONST. ART IT, §§ 3. In view of those clearly permissible applications of the obstruction statutes to the President, Franklin's holding that the President is entirely excluded from a statute absent a clear statement would not apply in this context.

      Since the DoJ won't indict a sitting president, here's a direct suggestion of what Congress could do.

    1. “every courageous and incisive measure to solve internal problems of our own society, to improve self-confidence, discipline, morale and community spirit of our own people, is a diplomatic victory over Moscow worth a thousand diplomatic notes and joint communiqués. If we cannot abandon fatalism and indifference in the face of deficiencies of our own society, Moscow will profit.”

      Perhaps the best defense against active measures is a little bit of activism of our own

  17. Sep 2020
    1. Blokland, I. V. van, Lanting, P., Ori, A. P., Vonk, J. M., Warmerdam, R. C., Herkert, J. C., Boulogne, F., Claringbould, A., Lopera-Maya, E. A., Bartels, M., Hottenga, J.-J., Ganna, A., Karjalainen, J., Study, L. C.-19 cohort, Initiative, T. C.-19 H. G., Hayward, C., Fawns-Ritchie, C., Campbell, A., Porteous, D., … Franke, L. H. (2020). Using symptom-based case predictions to identify host genetic factors that contribute to COVID-19 susceptibility. MedRxiv, 2020.08.21.20177246. https://doi.org/10.1101/2020.08.21.20177246

  18. Aug 2020
  19. Jul 2020
    1. Mulligan, M. J., Lyke, K. E., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S. P., Neuzil, K., Raabe, V., Bailey, R., Swanson, K. A., Li, P., Koury, K., Kalina, W., Cooper, D., Fonter-Garfias, C., Shi, P.-Y., Tuereci, O., Tompkins, K. R., Walsh, E. E., … Jansen, K. U. (2020). Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report. MedRxiv, 2020.06.30.20142570. https://doi.org/10.1101/2020.06.30.20142570

  20. Jun 2020
    1. Report A report relays the results of your research in an organized manner. A report is written from the perspective of someone who already knows the answers.

      Definition of a report

  21. May 2020
  22. Apr 2020
  23. Mar 2020
    1. The differences between the report and Mr. Barr’s description of it “cause the court to seriously question whether Attorney General Barr made a calculated attempt to influence public discourse about the Mueller report in favor of President Trump despite certain findings in the redacted version of the Mueller report to the contrary,” wrote Judge Walton, an appointee of President George W. Bush.

      Serious indictment of Barr.

  24. Oct 2019
    1. A former union boss jailed over receiving a coal exploration licence from his friend, former NSW Labor minister Ian Macdonald, was an "entrepreneur" who found a "willing buyer" in the disgraced politician, a court has heard.

      This is a flawed proposition and both misleading and deceptive in relation to the subject matter, considering its prominence in a court media report of proceedings which largely centre on the propriety or otherwise of an approvals process.

      Using a market analogy mischaracterises the process involved in seeking and gaining approval for a proposal based on an innovative occupational health and safety concept.

      In this case, the Minister was the appropriate authority under the relevant NSW laws.

      And while Mr Maitland could indeed be described as a "entrepreneur", the phrase "willing buyer" taken literally in the context of the process to which he was constrained, could contaminate the reader's perception of the process as transactional or necessitating exchange of funds a conventional buyer and seller relationship.

      Based on evidence already tendered in open court, it's already known Mr Maitland sought both legal advice on the applicable process as well as guidance by officials and other representatives with whom he necessarily engaged.

      But the concept of finding a "willing buyer", taken literally at it's most extreme, could suggest Mr Maitland was presented with multiple approvals processes and to ultimately reach his goal, engaged in a market force-style comparative assessment of the conditions attached to each of these processes to ultimately decide on which approvals process to pursue.

      Plainly, this was not the case. Mr Maitland had sought advice on the process and proceeded accordingly.

      The only exception that could exist in relation to the availability of alternative processes could be a situation silimilar to the handling of unsolicited proposals by former Premier Barry O'Farrell over casino licenses which were not constrained by any of the regular transparency-related requirements including community engagement, notification or competitive tender.

      Again, this situation does not and could not apply to the process applicable to Mr Maitland's proposal.

      The misleading concepts introduced from the outset in this article also represent an aggravating feature of the injustice to which Mr Maitland has been subjected.

      To be found criminally culpable in a matter involving actions undertaken in an honest belief they were required in a process for which Mr Maitland both sought advice process and then at no stage was told anything that would suggest his understanding of the process was incorrect, contradicts fundamental principles of natural justice.

  25. Jul 2019
    1. (The Gates and Hewlett Foundations and Chan Zuckerberg Initiative are among the many funders of The Hechinger Report.

      An important disclosure here, given a paragraph or two above:

      This story was published in partnership with The Hechinger Report, a nonprofit independent news organization focussed on inequality and innovation in education.

    2. This story was published in partnership with The Hechinger Report, a nonprofit independent news organization focussed on inequality and innovation in education.
  26. Apr 2019
    1. 28 C.F.R. § 600.8(c)

      PART 600—GENERAL POWERS OF SPECIAL COUNSEL can be found here: https://www.govinfo.gov/content/pkg/CFR-2016-title28-vol2/pdf/CFR-2016-title28-vol2-part600.pdf

      Part (c) reads:

      (c)Closing documentation. At the conclusion of the Special Counsel's work, he or she shall provide the Attorney General with a confidential report explaining the prosecution or declination decisions reached by the Special Counsel.

    1. One of the biggest questions of the past two years — something that fueled the news coverage, the federal investigation and congressional scrutiny — is why so many people around Mr. Trump lied, misled and changed their stories
  27. washburnmail-my.sharepoint.com washburnmail-my.sharepoint.com
    1. The United States is a land of stark contrasts. It is one of the world’s wealthiest societies, a global leader in many areas, and a land of unsurpassed technological and other forms of innovation. Its corporations are global trendsetters, its civil society is vibrant and sophisticated and its higher education system leads the world. But its immense wealth and expertise stand in shocking contrast with the conditions in which vast numbers of its citizens live. About 40 million live in poverty, 18.5 million in extreme poverty, and 5.3 million live in Third World conditions of absolute poverty.4It has the highest youth poverty rate in the Organization for Economic Cooperation and Development (OECD), and the highest infant mortality rates among comparable OECD States. Its citizens live shorter and sicker lives compared to those living in all other rich democracies, eradicable tropical diseases are increasingly prevalent, and it has the world’s highest incarceration rate, one of
  28. Mar 2019
    1. What's possible with personalized learning: an overview of personalized learning for schools, families, and communities. This 32 page PDF is included in part due to its credibility and also to its breadth. The focus is personalized learning in schools. All ages are considered and there is a discussion of 'what personalized learning means for teachers.' It is sufficiently readable and rather attractively presented for a report. rating 5/5

    1. New Media Consortium Horizon Report This page provides a link to the annual Horizon Report. The report becomes available late in the year. The report identifies emerging technologies that are likely to be influential and describes the timeline and prospective impact for each. Unlike the link to top learning tools that anyone can use, the technologies listed here may be beyond the ability of the average trainer to implement. While it is informative and perhaps a good idea to stay abreast of these listings, it is not necessarily something that the average instructional designer can apply. Rating: 3/5

    1. n. The shifting nature of the instructor—from transmitter of knowledge to facilitator and curator—has accelerated the need for strategically planned faculty support and a reevaluation of the role of teaching and instruction. The

      Support for Open Pedagogy / Open Education Practices

  29. Feb 2019
    1. Interactions of tomato and Botrytis genetic diversity: Parsing the contributions of host differentiation, domestication and pathogen variation

      This article has a Peer Review Report

  30. Jan 2019