Realism

SciScore for 10.1101/2021.09.30.21264344: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Limitations: Our study had several limitations. First, our questionnaire has proven to be reliable and valid but it should be used in other populations to test further its psychometric properties since different populations may have different attitudes and cultural context. Further studies could confirm our four-factor model or could expand our findings. Second, we used a large sample of the general population in Greece but our sample was a convenience sample. Thus, further studies with more representative samples should be conducted to infer more valid results. Third, as always, creation of a questionnaire could not be exhausted in the first place. For instance, further items could be added in our questionnaire and different factors could be established.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

This makes me questions if the customers aren't taking the situation at the level the fourth man is or if the forth man is going to the extreme? Just the fourth man repeating "this is not the right way to safety" to the customers and them just proceeding to handle the situation as they usually do is alarming. I feel as the fourth man has to know something more that he isn't willing to share out with the customers. At the same time sitting at home with your windows closed doesn't seem like an effective solution for the situation. I feel like the customers should have listened to the fourth man and maybe he would have explained his reasoning for why being home is not the right way to safety.

Application types to look at during work:

• work orders and their histories
• supporting reference documentation
• API specs
• areas of code (and calls in the stack)
• tests
• logs
• databases
• GUIs
• Slack
• Spotify
• clock
• calendar
• camera feeds

With all that, we may look at around 25% of the stuff at once

Author's reflections on working in VR. It seems like he highly values the comfortability and space for multiple windows

SciScore for 10.1101/2021.09.28.21264242: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

The use of viral load and signs and symptoms scores on the seventh day of illness were a limitation of the present study. As noted, the viral load is practically zero on the seventh day of illness in all experimental groups, which makes it difficult to evaluate the drugs in their antiviral action. As the selected COVID-19 cases had mild to moderate disease, it is likely that the majority had already recovered regardless of the drugs. Considering that most patients included in the study made adequate use of the drugs, judging by the control of their intake, we might have observed differences if we had followed symptoms and signs and viral load earlier, before the seventh day of illness. Summary of conclusions: The presence of fever (≥37.8°C), anosmia or dysosmia, ageusia or dysgeusia, with two or more symptoms in patients with mild to moderate respiratory infection, indicate the diagnosis of COVID-19. The score based on these symptoms and signs was useful for use in the clinical trial and for the implementation of preventive measures in the transmission of COVID-19. Univariate and multivariate logistic regression analysis for the predictive parameters of symptoms and signs associated with mild to moderate COVID-19 showed that anosmia or dysosmia symptoms, in the absence of sore throat, have accuracy and high sensitivity to predict COVID-19, compared to mild and moderate respiratory infections due to causes other than SARS-CoV-2. Pharmacological intervention with TDF and TDF / ...

Results from TrialIdentifier: We found the following clinical trial numbers in your paper:<br><table><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Identifier</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Status</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Title</td></tr><tr><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">NCT04712357</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Recruiting</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Clinical Experimentation With Tenofovir Disoproxyl Fumarate …</td></tr></table>

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.09.27.21264183: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Limitations: Our study has a number of limitations. First, we used a convenience sample that is not representative of the general population in Greece. For instance, educational level of our parents is higher than that of the general population. Also, we collected information through social media and parents without social media accounts could not participate in our study. Thus, generalization of our results should be made cautiously. Second, we conducted a cross-sectional study but the situation regarding the COVID-19 vaccination programmes, the dynamic of the COVID-19 pandemic, and the associated policy measures is changing fast. It is therefore necessary to carry out further studies as soon as possible. Indeed, it would be better to carry out prospective studies in order to observe parents’ attitudes over time. Third, since our study was anonymous through social media, we cannot calculate the response rate and we cannot be aware of the profile of parents who refused to participate in the study. Thus, a selection bias is possible since parents who denied to participate in our study might have a different profile as compared to parents that participate. Fourth, the study questionnaire was self-reported and data verification was not feasible. For instance, parents may overestimate their vaccine acceptability due to social desirability. Moreover, we self-constructed some items in our study (e.g. self-perceived severity and knowledge, trust, etc.). Thus, an information bias mig...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.09.26.21264127: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Limitations: It would have been more informative if we had measured NLRP3 cytokines such as IL-1β and IL-18, and caspase 1.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.09.23.21264009: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Limitations: Our study had certain limitations. Our study population was large, but not representative since we used a convenience sample. For instance, the proportion of women, people with a high level of education, and workers in healthcare facilities was considerably higher in our study compared to the general population in Greece. Moreover, online surveys during the COVID-19 pandemic are a rational approach but diminish the representativeness of the study population since individuals with limited internet access are less likely to participate. Additionally, the response rate and the profile of non-correspondents cannot be estimated in online surveys. Thus, it would be wise not to generalize our conclusions but to carry out studies with more representative samples. Information bias was possible in our study since the study questionnaire was self-administered and we cannot objectively verify self-reported vaccination. Anonymity in our study may have reduced this information bias. Finally, we have investigated several factors that may affect individuals’ decision to uptake a COVID-19 vaccine, but there may be other factors influencing this decision.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.09.21.21263898: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

There are some limitations in this study. First, we were unable to examine patients’ neutralizing antibody were present after the first and second dose of vaccine, or the baseline antibody test before illness and after vaccination. Second, we were unable to conduct the physical examination, blood work, or access to patients’ medical record. We are therefore unable to obtain additional information to analyze CT values and its risk factors.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

Reviewer #2 (Public Review): 

Cai & Padoa-Schioppa recorded from macaque dorsal anterior cingulate cortex (ACCd) while requiring animals to choose between different juice types offered in variable amounts and with different action costs. Authors compared neural activity in ACCd (present study) with previous, directly comparable, findings on this same task when recording in macaque orbitofrontal cortex. The behavioral task is very powerful and the analyses of both the choice behavior and neural data are rigorous. Authors conclude that ACCd is unique in representing more post-decision variables and in its encoding of chosen value and binary outcome in several reference frames (chosen juice, chosen cost, and chosen action), not offer value, like OFC. Indeed, the encoding of choice outcomes in ACCd was skewed toward a cost-based reference frame. Overall, this is important new information about primate ACCd. I have only a few suggestions to enhance clarity. Figures 5 and 7 are maximally informative, but it is not clear that Figure 6 adds much to the reported Results. It is also suggested to abbreviate the comparison with Hosokawa et al. as it presently takes up 3 paragraphs in the Discussion: it is clear the methods and task designs were different enough to not be so easily compared with the present study. An additional suggestion would be to include mention of the comparison with OFC in the abstract and possibly also in the title, since the finding and direct comparison in Figure 7 are some of the most novel and interesting effects of the paper. Other suggestions are minor, and have to do with definition of time windows, variables, and additional papers that authors may cite for a well-rounded Discussion.

SciScore for 10.1101/2021.09.18.21263550: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.09.14.21263300: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Our study suffers from several limitations. Although our study population was large, we used a convenience sample which is not representative of HCWs in Greece. Additionally, response rate cannot be calculated since we conducted an on-line study. Moreover, vaccine uptake and other information were self-reported and social desirability to bias responses may exist. For instance, some HCWs may have falsely stated that they had received a COVID-19 vaccine. We used an anonymous on-line questionnaire to reduce this bias. Further, we investigated a variety of determinants of COVID-19 vaccine uptake and some of them had not been studied before. However, it is possible that there are other factors affecting COVID-19 vaccination. Future research may consider including other factors which may influence COVID-19 vaccine uptake, e.g. personality traits, social media variables, fake news, conspiracy theories, etc. Finally, as is always the case in cross-sectional studies, no causal relationships between independent variables and COVID-19 vaccine uptake can be established.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.09.12.21263462: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

The limitations of this study, as with spontaneous reporting schemes of adverse reactions of both drugs and vaccines, is hampered by underreporting, over reporting and reporting bias. This makes it difficult to identify the true incidence of these events and the presence of multiple confounders which may not enable the assessment of the causality with higher specificity.22 In addition, due to the nature of the database, it was not possible to know the denominator (the total number of vaccinated individuals for each type of vaccine), which hinders the analysis of likelihood of true occurrence of thrombotic adverse events for each vaccine. Also, we were unable to report possible concomitant drugs. Despite these limitations, the study used global “real-world” data and collected valuable information about three widely used vaccines, where more than two thirds of all reports were received from healthcare professionals which increases the credibility and quality of reports. People who are vaccine hesitant and reluctant to take any of the mentioned vaccines,23 should know that most COVID-19 vaccines are effective to prevent symptomatic infection including hospital admissions and severe disease.24,25 The risk of COVID-19 related thrombotic events are minimal and likely manageable with available treatments.8 Thrombotic adverse events reported for the three vaccines remains extremely rare.8,26 In summary, thrombotic adverse events reported for the three vaccines remains extremely rare ...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.09.21.21263882: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Our study presents some limitation that should be acknowledged. First, the study was an observational study based on real-life data obtained from pandemic surveillance activities, aimed not to establish vaccine efficacy compared to a matched unvaccinated control group, but, to report a virological characterization of those patients reported with SARS-CoV-2 infection despite being vaccinated. Therefore, our observation should be replicated and extended on larger cohorts established ad hoc and to other vaccine formulations. Furthermore, no follow-up samples were available for the post-vaccination infected individuals, so that it was not possible to monitor the viral loads and the shedding of infectious virus. In addition, as described above, pre-infection antibody status was only available for few patients. Finally, the evaluation of the cellular immune response would be of great interest to better understand the protection status in cases of vaccine breakthrough infections.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.09.23.461605: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: Thank you for sharing your data.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.09.13.21263406: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from TrialIdentifier: We found the following clinical trial numbers in your paper:<br><table><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Identifier</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Status</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Title</td></tr><tr><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">NCT04464395</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Completed</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Study of CPI-006 as Immunotherapy for Hospitalized COVID-19 …</td></tr><tr><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">NCT04734873</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Terminated</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">CPI-006 Plus Standard of Care Versus Placebo Plus Standard o…</td></tr></table>

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

I think that TV and movies always push a doom and gloom cyberpunk singularity future because it sells at the box office. I started to think the future will happen as quietly as the sun shines.

This shows how international financial markets can often hinder development once countries get too dependent on international financial markets; in this case, the U.S pork industry became too independent on consumers in Thailand, which caused problems with development for U.S hog farmers.

Does this mean that classes were never conducted here to begin with?

Reviewer #1 (Public Review):

Review:

The manuscript "Fast and accurate annotation of acoustic signals with deep neural networks" by Elsa Steinfath, Adrian Palacios, Julian Rottschäfer, Deniz Yuezak, and Jan Clemens describes a new piece of software that, building on previous work, trains a deep network classifier to segment audio signals. The main advances are speed (real time), works on standard hardware, and a user-friendly interface, which allows users with little machine learning experience to train and use a deep neural network classifier.

I. Results

A. How good is it?

1. How fast is it?<br> a. How long to train?<br> Train time depends on the amount of data, but the ranges quotes (10 minutes to 5 hours) are quite reasonable. It works on reasonable hardware (I tested on a laptop with a GPU).

b. How long to classify?<br> Latency to classification is between 7-15ms, which is a little long for triggered optogenetics, but not bad, and certainly reasonable for acoustic feedback.

2. How accurate is it?<br> a. In absolute terms<br> Accuracy is improved relative to Fly Song Segmenter, particularly in recall (Arthur et al., 2013; Coen et al., 2014).<br> Pulse song:<br> DeepSS precision: 97%, recall: 96%<br> FlySongSegmenter: precision: 99%, recall 87%.<br> Sine song:<br> DeepSS precision: 92%, recall: 98%<br> FlySongSegmenter: precision: 91%, recall: 91%.

b. One main concern I have is that all the signals described, with the exception of pulse song, are relatively simple tonally. Bengalese finch song is much less noisy than zebra finch song. Mouse vocalizations are quite tonal. How would this method work on acoustic signals with noise components, like zebra finches or some non-human primate signals? Some signals can have variable spectrotemporal structure based on the distortion due to increased intensity of the signal (see, for example, Fitch, Neubauer, & Hertzel, 2002).

W.Tecumseh Fitch, Jürgen Neubauer & Hanspeter Herzel (2002) "Calls out of chaos: the adaptive significance of nonlinear phenomena in mammalian vocal production" Animal Behaviour, 63: 407-418. doi:10.1006/anbe.2001.1912

B. How easy to use?

0. "our method can be optimized for new species without requiring expert knowledge and with little manual annotation work." There isn't a lot of explanation, either in the paper or in the associated documentation, of how to select network parameters for a new vocalization type. However, it does appear that small amounts of annotation are sufficient to train a reasonable classifier.

1. How much pre-processing of signals is necessary?<br> All the claims of the paper are based on pre-processed audio data, although they state, in the Methods section that preprocessing is not necessary. It's not clear how important this pre-processing is for achieving the kinds of accuracy observed. Certainly I would expect the speed to drop if high frequency signals like mouse vocalizations aren't downsampled. However, I tried it on raw, un-preprocessed mouse vocalizations, without downsampling and using very few training examples, and it worked quite well, only missing low signal-to-noise vocalizations.

C. How different from other things out there?

It would strengthen the paper to include some numbers on other mouse and birdsong methods, rather than simple and vague assertions "These performance values compare favorably to that of methods specialized to annotate USVs (Coffey et al., 2019; Tachibana et al., 2020; Van Segbroeck et al., 2017)." "Thus, DeepSS performs as well as or better than specialized deep learning-based methods for annotating bird song (Cohen et al., 2020; Koumura and Okanoya, 2016).

D. Miscellaneous comments

1. Interestingly, the song types don't appear to be mutually exclusive. One can have pulse song in the middle of sine song. That might be useful to be able to toggle...I can imagine cases where it would be nice to be able to label things that overlap, but in general if something is sine song, it can't be pulse song. And my assumption certainly was that song types would be mutually exclusive. Adding some explanation of that to the text/user's manual would be useful.

2. How information is combined across channels is alluded to several times but not described well in the body of the manuscript, though it is mentioned in the methods in vague terms:<br> "several channel convolutions, 𝑘𝛾(1, 𝛾), combine information across channels."

II. Usability

A. Getting it installed<br> Installing on Windows 10, was a bit involved if you were not already using python: Anaconda, python, tensorflow, CUDA libraries, create an account to download cuDNN, and update NVIDIA drivers.

So many common activities generate particulates in indoor settings.

こちらはWindows特有の対応のようですね。 教材内で補足できずに失礼しました。

他の方もヒアリングしてみて、改めて教材に反映するか検討してみますね！情報提供ありがとうございます！

⇨失礼しました、コマンドラインから接続する場合ですね！ナイストライです！教材にも補足いたします！

This applies for Windows, too.

Já podemos fazer as chamadas de fofocas via Facetime agora? hahaha

Après avoir désactivé le fastboot de windows 10, permet de corriger les problème de son innexplicables avec les casques

Number one social justice issue in California.

SciScore for 10.1101/2021.09.12.21263456: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Our findings should be interpreted in the context of several limitations. Given the convenience sample, the on-line data collection, and the unknown response rate, the extent to which our findings can be generalized to other parents is unknown. For instance, parents with limited internet access were less likely to participate in our study. There may have been an information bias in our study since vaccine uptake was self-reported and some parents may have falsely reported that they vaccinated their children. However, the fact that the questionnaire was completed anonymously may have reduced this bias. Moreover, we have explored several factors that may influence parents’ decision to vaccinate their children, but clearly there are other factors that can be studied such as psychological factors, mass media variables, impact of fake news, etc. Finally, our sample included mainly mothers with a high level of education. Thus, further studies with representative samples are critically needed to draw safer conclusions.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

1.平台无关性 2.编译运行型语言 3.所有java程序都是运行在java虚拟机上面的

What she means by the "windows failed" is she wasn't able to see anymore once her death came upon her. As she was dying her slowly began to close failing to see the windows which created stillness at the end of the poem.

make sure that she is really seen by someone, and that someone is herself

mother is the primary cause of her agony

42:07 - 46:47

"I think as painful as those times are, they are so rewarding, because it requires that you reassess and decide to really commit. It's like, I could be doing this, I could be doing that. Actually, I'm doing this because this is not just my passion. There is something else that is driving me to do it. But I can't even describe it, I don't know what it is. Once you get to that place, windows start to open, and you start to realize things. I don't know if I would have come to, had I not gone through a rough time. 2018 was the year that I said, ‘What we're doing today should exist a hundred years from now.’ People should be growing food in their communities and creating an economic engine that provides jobs to the residents in the community, food, to the residents. And up to that point, I wasn't thinking. And the moment I thought, ‘a hundred years,’ I had to question a whole bunch of shit because I have always been inspired by anger. Anger is an amazing motivator. I realized once I had this notion that Project Eats should exist a hundred years from now, I realized you can't grow something with anger. You can start it with anger, it will motivate you and get you to levels of creativity, resourcefulness and imagination, but you can't grow it with that.

And then the next level of, ‘Wow. I've got to grow this thing.’ I've got some shortcomings. I hate to ask people for anything. And so if you're going to grow it, you have to grow it with resources. And we, for the most part, have used the most valuable resources that we all have, which is the ones we have. Well, we can't really grow for a hundred years with that. How do you build that? And building that requires you to ask them that. And so I have these battles that I'm having in my head and out loud, I'm not asking that. And then having to resolve that, you know as uncomfortable as that may be, you know, if you want this thing bad enough, then embrace asking. Figure out how to love asking.

And now I am really kind of psyched about fundraising. I'm really into it, I'm going to raise a whole lot of money. And I'm going to do it on my terms. So how do I do it and what do I do? You can always do it the way that is right for you to do it. And I think we get, again, socialized out of thinking that we can, that we have to follow through it again.

The most profound thing for me has been how I view approaching art. And that evolved from the end of 2018. I believe art should be discovered. I believe we should engage the cause we discover. The notion is this, this stuff makes no sense to me, that we have to schedule time to see art. That's not how art feeds our soul. I actually want people to engage with whatever I make on their own. Get rid of those text labels for Christ's sake. Don't bombard me with how I'm supposed to see something. 'Cause when you do that, you disrupt the very reason that we are creating this conversation, and it’s a conversation, it’s not a mediated moment where I have to bow to your schedules and bow to the way to say it. And in that, my notions of what I create now have expanded."

i feel like this could have been worded better which is why i think it is weak. i would give it a 1 out of 4

Reviewer #1 (Public Review):

The key question addressed of this MEG study is whether speech is represented singly or multiplexed in the human brain in the linguistic hierarchy. The authors used state-of-the-art analyses (multivariate Temporal Response Functions) and probablilistic information-theoretic measures (entropy, surprisal) to test distinct contextual speech processing models at three hierarchical levels. The authors report evidence for the coexistence of local and global predictive speech processing in the linguistic hierarchy.

The work uses time resolved neuroimaging with state-of-the-art analyses and cognitive (here, linguistic) modeling. The study is very well conducted and draws from very different fields of knowledge in convincing ways. I see one limitation of the current study in that the authors focused on phase-locked responses, and I hope future work could extend to induced activity.

Overall, the flow in the MS could be streamlined. Some smoothing in the introduction would be helpful to extract the main key messages you wish to convey.

For instance, in the abstract:

– Can you explain the two views in a simpler way in the abstract and to a non-linguistic audience? Do you mean to say that classic psycholinguistic models tend to follow a strict hierarchically integration (analysis only) but an alternative model is hierarchically inferential (analysis by synthesis)?

– Indicate early on in abstract or intro where the audience is being led with a concise message on how you address the main question. For instance:

To contrast our working hypotheses A and B, we used a novel information-theoretic modeling approach and associated measures (entropy, surprisal), which make clear predictions on the latency of brain activity in responses to speech at three hierarchal contextual levels (sublexical, word and sentence).

– Why did the authors consider that the evoked response is the proper signal to assess as opposed to oscillatory (or non phase-locked) activity?

– Parallel processing with different levels of context (hence temporal granularities) sounds compatible with temporal multiplexing of speech representation proposed by Giraud & Poeppel (2012) or do the authors consider it a separate issue?

Methods:

– Figure 2: please spell out TRFs and clarify the measured response

– The sample size (N=12) is very low in today standards but the statistical granularity is that of the full MEG recording. Can a power estimate be provided or clear justification of reliability of statistical measures be described.

– The inclusion of a left-handed in speech studies in unusual, please comment on any difference (or lack thereof) for this participant and notably the lateralization tests.

– The authors state that eyes were kept open or close. This is again unusual as we know that eye closure affects not only the degree of concentration/fatigue but directly impact alpha activity (which in turn affects evoked responses (1-40 Hz then 20 Hz) that are being estimated here). Please explain.

– It would be helpful to clarify the final temporal granularity of analysis. The TRFs time courses are said to be resampled to 1kHz (p22) but MEG time courses are said to be resampled at 100 Hz (p18).

– The % of variance explained by acoustic attributes is 15 to 20 folds larger than the that explained by the linguistic models of interest. Can a SNR measure be evaluated on such observations?

Results and Figures:

– The current figures do not give enough credit to the depth of analysis being presented. I understand that this typical for such mTRFs approach but given the level of abstraction being evaluated in the linguistic inputs, it may be helpful to show an exemple of what to expect for low vs. high surprisal for instance from the modeling perspective and over time.

For instance, could Figure 1 already illustrate disctinct predictions of the the local vs. global models?

– Why are visual cortices highlighted in figures?

– Figure 2:

Fig 2A and B: can the authors quantitatively illustrate "5-gram generally leads to a reduction of word surprisal but its magnitude varies substantially between words" by simply showing the mean surprisal and its variance?

Fig 2C: please explain the term "partial response"; please indicate for non M/EEGers what the arrow symbolizes.

– Figure 3:

p8: the authors state controlling for the "acoustic features" but do not clearly describe how in the methods and this control comes as a (positive) surprise but still a bit unexpected at first read. Perhaps include the two acoustic features in Fig2C and provide a short couple sentences on how these could impair or confound mTRF performance.

Have the same analysis been conducted on a control region a priori not implicated in linguistic processing? This would be helpful to comfort the current results.

Fig 3B-C-E: please clearly indicate what single dot or "individual value" represents. Is this average over the full ROI? Was the orientation fixed? Can some measure of variability be provided?

Fig3E: make bigger / more readable (too many colors: significance bars could be black)

– Figure 4: having to go to the next Fig (Fig5) to understand the time windows is inconvenient and difficult to follow. Please, find a work around or combine the two figures. From which ROI are the times series extracted from?

Sometimes our friends will say "mamma" while they're playing and maybe it just means they're thinking about their moms rather than wanting their moms to pick them up at that moment. Especially when moms are mentioned almost in passing without tears or looking forlornly out the windows.

Para windows está https://cygwin.com/install.html Hay que probarla.

Comandos según sistema operativo:https://ss64.com/osx/installer.html

SciScore for 10.1101/2021.09.08.459464: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

At the current moment the best approach is to use minikube with a preferred backend (Docker Engine and Podman are already there), and you can simply run one command to configure Docker CLI to use the engine from the cluster.

• Drivers | minikube
• docker-env | minikube

I believe this is something that teachers can start on now...integrating literature that is a "mirror" and a "window".

opulence

RED BLOOD BLEEDING FROM ME NOW

and cold rain drops on [noUr]

windowless having no windows. "a tiny windowless room"

https://www.google.com/search?q=windowless&rlz=1CAUNZR_enUS970&ei=WM83Ye_0KcnD0PEPsoe04A4&oq=windowless&gs_lcp=Cgdnd3Mtd2l6EAMyBQgAEIAEMgUIABCABDIFCAAQgAQyBQgAEIAEMgUIABCABDIFCAAQgAQyBQgAEIAEMgUIABCABDIFCAAQgAQyBQgAEIAEOgcIABBHELADOhEIABCwAxCKAxC3AxDUAxDlAjoOCAAQ6gIQtAIQ2QIQ5QJKBAhBGABQx-EDWL7lA2DX6ANoBHACeACAAX2IAX2SAQMwLjGYAQCgAQGgAQKwAQjIAQrAAQE&sclient=gws-wiz&ved=0ahUKEwjvgOy83e3yAhXJITQIHbIDDewQ4dUDCA4&uact=5&safe=active&ssui=on

This concept is what important to the idea of scarcity; people must decide where resources are to be used by comparing the use to an alternative use.

This is my favorite line in the piece. (It also reminds me of Steve Martin pretending to be Micheal Caine's brother Ruprecht in Dirty Rotten Scoundrels.) This is the dividing line between John's rational and unsympathetic world (a world that values fresh air over the needs of the narrator for mental stimulation and a raison d'etre) and the narrator's ability to ignore its harmful effects. This line provides the reader with a valuable insight into the house's powerful effects on the isolated individual; it happened to the previous shut-in too... One cannot help but wonder how John could ignore the presence of those rings on the wall, the torn and smudged wallpaper? Does Gilman intend to reveal that John nudges the narrator toward mental deterioration?

sad and relates to the thing about how they long for serfdom almost even though it sucked

more about the landscape

SciScore for 10.1101/2021.09.02.21263010: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

There are some limitations to our study. First, we confirmed the protective effect of inactivated vaccines from progressing to severe illness, but we could not estimate the vaccine efficacy against Delta variant infection because all participants were confirmed COVID-19 cases. Second, since individuals who have been protected from infection would not develop a severe illness related to COVID-19, the effectiveness of inactive vaccines against severe illness in our study based on infected cases would be, to some extent, an underestimation of that based on the whole population. In conclusion, we found a full course immunization with inactivated vaccines could effectively protect against severe illness caused by the Delta variant in China. The protective effect is affected by underlying medical conditions. Partial vaccination does not offer clinically meaningful protection against severe illness. Our study highlights the importance of continuing effort on a full course of vaccination.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

This quote is a primary source because it is a direct quote. It is therefore very reliable.

Author Response:

Reviewer #1:

This manuscript describes a novel tool for tracking synaptic plasticity at the single synapse resolution with a SEP-tagged GluA1 receptor. The authors rather convincingly demonstrate that this tool does not disturb synaptic physiology or mouse behavior. They also show that this tool can be used to measure the distribution of synaptic weights and its variation during a plasticity protocol in barrel cortex. This tool is useful for more quantitative measurements of synaptic strength in vivo. The main weakness of the method is related to the density of marked synapses which makes the tracking difficult with only 80% reproducibility, probably due to the resolution limits of 2P-microscopy. It could however be improved with in vivo superresolution technique. The other limit of the method is that it is not demonstrated to allow longitudinal studies at the single synapse resolution. The authors do not discuss this issue in detail. It seems feasible with additional markers of the dendrite and spines. But this is not developed in the manuscript. Also, it is not demonstrated to which extent this technique outperforms traditional methods for synaptic weight measurements like spine volume.

We have included new experiments and analyses to further demonstrate the utility of these tools and expanded discussion of the limits of our approach to automatic synapse detection. We are further demonstrating that by introducing a red cytosolic fluorescent protein, longitudinal imaging of the same synapses across days is achievable with this mouse line. We further discuss how imaging SEP-GluA1 is a more accurate readout of synaptic plasticity and strength than spine volume, since synaptic strength is mediated by receptors rather than spine size. In previous studies, we have shown that imaging sparsely expressed SEP-GluA1 can reveal plasticity at synapses that were not detectable by measuring spine size (Zhang et al., 2015) or reveal larger amplitudes of changes in SEP-GluA1 than spine size (Tan et al. 2020, Roth et al., 2020). The dissociation of spine size and synaptic strength has been reported many times (Lee et al., 2012). For instance, spine number or volume is not changed at all at cerebellar Purkinje cell synapses during LTD (Sdrulla and Linden, 2007) and Insulin-induced endocytosis of AMPARs is not accompanied by spine shrinkage (Wang et al., 2007). Thus, spine size, in certain conditions, is not a good indication of synaptic strength, Together, these experiments demonstrate that measuring SEP-GluA1 is a reliable and sensitive readout of synaptic strength and plasticity. We believe that our added data and discussion as suggested by the reviewers has improved and strengthened our demonstration of this SEP-GluA1 KI mouse line.

Reviewer #2:

Over the last couple of decades, the development of fluorescent transgenic mouse lines (e.g thy1-GFP) and delivery techniques (e.g., in utero electroporation), as well as the democratization of recording methods in living animals (such as calcium imaging, high-density probes,) have strengthened the link between synaptic plasticity and behavior. Nevertheless, these methods are most of the time limited to hundreds of cells at best (very few in the case of patch-clamp recordings), or failed to achieve a clear synaptic resolution without affecting the tight equilibrium of endogenous proteins.

In this paper, Graves, Roth, Tan, Zhu, Bygrave, Lopez-Ortega et al present an additional high-resolution optical tool to overcome these limitations. They generated a new knock-in mouse line that fluorescently labels all endogenous AMPA receptors (KI SEP-GluA1). In this mouse line, the extracellular N-terminal domain of the GluA1 subunit of AMPAR is tagged with super ecliptic pHluorin (SEP), a pH sensitive variant of GFP that fluoresces at neutral pH (at cell surface) and is quenched at acidic pH (within the cell). This tool thus avoids the use of antibodies or the over-expression of exogenous tagged receptors.

They perform a set of convincing experiments showing that synaptic transmission, homeostatic and activity-dependent synaptic plasticity in vitro (Figs2-3), and behavior (Fig. 4), are not affected in KI SEP-GluA1 as compared to wild-type mice. Despite the obvious quality and viability of this mouse line (this is an important tool with no doubt), it is puzzling however that, while the level of GluA2 remains unchanged, the global expression of SEP-GluA1 is twice as low as the expression of GluA1 in wild-type mice (Fig.1). The manuscript would benefit from a clear brain-region specific comparison between the expression pattern of GluA1 and SEP-GluA1. At least, the author should discuss this point, and how this might affect the formation of GluA1/A2 heteromers, the dominant form of AMPAR in pyramidal neurons.

Then, they provide strong evidence that SEP-GluA1 receptors are mobile in vivo (Fig. 6) and can thus accurately report synaptic plasticity, at least in anesthetized animals (Figs. 7-8). The authors make a point that "this novel SEP-GluA1 knockin mouse is the first tool that enables longitudinal tracking of synaptic plasticity underlying behavior at brain-wide scale with single-synapse resolution". However, given the high density of fluorescent synapses, it remains unclear how effective would be this mouse line in awake mice, and more specifically during behavior, in which movement artifacts could preclude the tracking and registration of the same population of SEP-GluA1 containing synapses over time.

Finally, they present a new automated analytical tool to detect and register fluorescent synapses (Fig.7). Although the initiative is important and laudable (it is true that imaging approaches are usually plagued by the lack of user-friendly analysis tools), the method would benefit from a comparison with existing methods.

We thank the reviewer for their detailed evaluation of our manuscript and appreciate their insightful comments. Addressing the suggestions raised by the reviewer, we have now included new data and expanded our discussion which we believe has significantly improved our manuscript. As suggested, we now show that SEP-GluA1 expression levels are consistent across brain regions, discuss the ability to detect and track individual synapses in awake mice, and expanded the description of our detection algorithm to include comparisons with existing methods.

Reviewer #3:

Understanding the distribution of synaptic strength and plasticity in the brain is paramount for understanding neural circuit function underlying behavior. In the manuscript by Graves et al., the authors developed a novel mouse model for optical detection of synaptic strength and plasticity in live brains. Specifically, they modified the mouse genome by modifying the native GluA1 AMPAR subunit gene (gria1) with a pH-sensitive GFP (pHluorin) -tagged GluA1 at its N-terminus. This sensor is nearly maximally fluorescent when the pH is neutral and quenched in acidic environments and, therefore, preferentially marks AMPARs located on the plasma membrane. Since AMPARs are known to cluster in the postsynaptic density, AMPAR number is the predominant postsynaptic determinant of synaptic strength. Specifically, the trafficking of GluA1 AMPARs is responsible for LTP in CA1 hippocampus. The use of this novel genetic tool raises the possibility of monitoring synaptic strength optically, thus providing a strategy for massively parallel assessment of the distribution of synaptic strength in bulk brain tissue. Even more promising is the use of cranial windows and 2-photon microscopy to assess synaptic strength longitudinally, for example, during learning acquisition.

The authors performed a comprehensive and rigorous set of control experiments using electrophysiology and behavior experiments. They demonstrated that modified GluA1 acts as native receptors and does not suffer from the shortcomings of overexpression approaches. The authors convincingly demonstrate that the modified receptors generate normal wild-type synaptic physiology and no behavioral alterations. Using glutamate uncaging, they showed that fluorescence changes at synapses were highly correlated with an electrophysiological assessment of synaptic strength and plasticity. Thus the data support claims that synaptic strength and plasticity could be assessed and monitored at unprecedented parallelization.

Whether SEP-GluA1 can be used to quantify synaptic strength and its changes is uncertain due to an unknown ratio of GluA1/2 versus GluA2/3 receptors, the differential expression of GluA1 in different cell types, and the presence of GluA1-independent plasticities. Another potential shortcoming of the study is the lack of a ground truth demonstration of true synapses in vivo. Given the high-density of synapses, low z-resolution 2P microscopy (> 2 um), and the presence of a significant extrasynaptic pool, a confirmation of their results with superresolution or EM would be essential. Moreover, the lack of cell-type-specific labeling is likely to limit the tool's use for linking behavioral and microcircuit synaptic plasticity. It is possible that control experiments in acute brain slices could circumvent some shortcomings and provide a more quantitative workflow.

We would like to thank the reviewer for their careful reading and evaluation of our manuscript and for providing valuable comments and recommendations. We have now added new data and expanded our discussion in response to the reviewer’s recommendation and believe that his has improved our manuscript. Among other points, we have added discussion regarding our mouse line’s ability to detect changes in GluA1 containing AMPARs, included measurements of the PSF of our microscope to quantify the detection limit of individual synapses with our approach, and demonstrated how the SEP-GluA1 knockin line can be used for measuring cell-type-specific changes in GluA1.

Reviewer #3 (Public Review): 

Understanding the distribution of synaptic strength and plasticity in the brain is paramount for understanding neural circuit function underlying behavior. In the manuscript by Graves et al., the authors developed a novel mouse model for optical detection of synaptic strength and plasticity in live brains. Specifically, they modified the mouse genome by modifying the native GluA1 AMPAR subunit gene (gria1) with a pH-sensitive GFP (pHluorin) -tagged GluA1 at its N-terminus. This sensor is nearly maximally fluorescent when the pH is neutral and quenched in acidic environments and, therefore, preferentially marks AMPARs located on the plasma membrane. Since AMPARs are known to cluster in the postsynaptic density, AMPAR number is the predominant postsynaptic determinant of synaptic strength. Specifically, the trafficking of GluA1 AMPARs is responsible for LTP in CA1 hippocampus. The use of this novel genetic tool raises the possibility of monitoring synaptic strength optically, thus providing a strategy for massively parallel assessment of the distribution of synaptic strength in bulk brain tissue. Even more promising is the use of cranial windows and 2-photon microscopy to assess synaptic strength longitudinally, for example, during learning acquisition. 

The authors performed a comprehensive and rigorous set of control experiments using electrophysiology and behavior experiments. They demonstrated that modified GluA1 acts as native receptors and does not suffer from the shortcomings of overexpression approaches. The authors convincingly demonstrate that the modified receptors generate normal wild-type synaptic physiology and no behavioral alterations. Using glutamate uncaging, they showed that fluorescence changes at synapses were highly correlated with an electrophysiological assessment of synaptic strength and plasticity. Thus the data support claims that synaptic strength and plasticity could be assessed and monitored at unprecedented parallelization. 

Whether SEP-GluA1 can be used to quantify synaptic strength and its changes is uncertain due to an unknown ratio of GluA1/2 versus GluA2/3 receptors, the differential expression of GluA1 in different cell types, and the presence of GluA1-independent plasticities. Another potential shortcoming of the study is the lack of a ground truth demonstration of true synapses in vivo. Given the high-density of synapses, low z-resolution 2P microscopy (> 2 um), and the presence of a significant extrasynaptic pool, a confirmation of their results with superresolution or EM would be essential. Moreover, the lack of cell-type-specific labeling is likely to limit the tool's use for linking behavioral and microcircuit synaptic plasticity. It is possible that control experiments in acute brain slices could circumvent some shortcomings and provide a more quantitative workflow.

SciScore for 10.1101/2021.09.01.21262913: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Limitations of our study include the reliance on questionnaire for anthropometric measurements and the reporting of diabetes and hypertension. The final multiple linear regression model that was generated has an adjusted r2=0.14 (Table 3), meaning that this model explains roughly only 14% of the variance in our data and indicates that other parameters, besides the ones already taken into consideration, should be included so as to further improve the model. Advantages of our study include the relatively high number of participants, the strict criterion of excluding all subjects that at least one parameter (of those examined) is missing, the use of a multiple linear regression model taking into account all parameters examined in parallel. Last but not least, to the best of our knowledge, this was the first study to examine DHEAS and 25(OH)D levels as potential modulators of the SARS-COV-2 antibody titer response post-vaccination.

Results from TrialIdentifier: We found the following clinical trial numbers in your paper:<br><table><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Identifier</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Status</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Title</td></tr><tr><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">NCT04954651</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Recruiting</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Assessment of the Immunization Levels Against Sars-Cov2 Viru…</td></tr></table>

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

有人说超链接的蓝色是选出来的，但 W3C 直到 1994 年才建立起来，因此 93 年 Web 可访问性的标准还没有出现。假定文本颜色默认为黑色，链接则为蓝色，那么可以看到二者之间的对比度为 2.3：1，似乎并不足以体现出清晰的差异性。相反我倒是觉得 Cello 与 Mosaic 都受到当时用户界面设计中一些共通趋势的启发。所以我的理论是这样：Windows 3.1 是在这两个项目之前几个月推出的，也在界面中第一个采用蓝色作为选定色，于是设计人员自然而然地想到在超链接上使用相同的颜色。 另外，我们都知道 Mosaic 的灵感来自 ViolaWWW，也保留了后者在界面中使用的灰色背景与黑色文本。查看 Mosaic 的发行说明，可以看到 0.7 版本中首先选择了将带有下划线的黑色文本作为超链接形式。但直到 93 年的 4 月中旬，情况才发生了巨变。在此之前，从1985 年开始微软一直使用带有下划线的黑色文本来表示超链接，有人还认为微软这是窃取了苹果 Lisa 的外观与视觉感受。 我认为，我们使用蓝色超链接的真正原因单纯是彩色显示器的快速流行。Mosaic 产品的普及与彩色显示器相关，蓝色超链接也是一样。年纪较长的朋友肯定还记得，Mosaic 的出现正好是在行业开始支持彩色显示器的关键节点。之前的标准，是使用下划线、悬停显示状态信息或者带边框的黑色文本；但 Mosaic 毅然选择使用蓝色，而且将浏览器移植到多种操作系统之上。这让 Mosaic 成为互联网使用的标准浏览器，也让它的用户界面成为全世界执行网络交互时的默认表达。

OM SA

SciScore for 10.1101/2021.08.24.21262535: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

This study has some limitations, including a limited sample size and a lack of time to follow up on patient changes. These factors may have played a role in the lack of a significant association of some of our findings, however they do not change the absence of any correlation between specific clinical severe symptoms and cytokine levels.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

Tips to fix HP Printer Error State Windows 10

I am accepting charitable donations,.\ ETH: 0x66e2871ef39334962fb75ce34407f825d67ec434 | BTC: 38B6vGaqNvMyTtoFEZPmNvMS7icV6ZnPMm | xDAI: 0x66e2871ef39334962fb75ce34407f825d67ec434

I am accepting charitable donations,.

[free PDF download...http://www.docdroid.net/xRdgY77/xiv-orver-et-aut.pdf]

A LONG LONG TIME AGO**, I wrote a little story about searching through our history, looking for the actual beginning of civilization.  I see the map, I see it very clearly encoded in everything we do--I know the purpose, and I know the final solution, I just don't know how to get from here to there... to the place that Chris Cornell says "I can recall, I was there so long ago" he goes on to say "the sky was bruised" and he was lead on--and all of this of course is in my voice, written as if it's me talking... well, Jesus--it's obviously not me talking, i just know that.  The point is the destination is without a doubt Heaven and this little thing we're putting together here on Earth is the map, the plan *et you are the how.*

I harped a little more than I think I would have expected on the audacity of the golden word "audacity," auspicious probably that W.H. Auden's shield gave me some solace; austere that we are approaching the Holy Windy month of August, and it really took nothing more than "ciudad" to calm my nerves--though I see the intent and the link to toxicity ... more importantly I really do see the road here, I see where we are coming from and where we are going.  I've written quite a bit about what I think "the city" really is--in form and function and it's initial purpose as a stepping stone to help us see how easy it is to change the world, to build something that nearly everyone will agree is significantly more Heavenly than the world we see here ... in an instant, one bright flash.    

Anyway the search begins with something like "literacy" -- as in, is the defining line between animalistic social evolution and the beginning of "civilization" something to do with writing or language, and that of course links us here to this place where we are finding out that the Tower of Babel and Rapunzel's High Castle are actually much more closely related than anyone ever would have thought in the darkness of Jericho and the shadow of Exodus; and it ties of course in history to religion somewhere around Guttenburg... and the pretty clear idea that the spread of Christianity did quite a bit for "literacy" even if you subscribe to the idea that the inquisition already happened ... and that some wars and fighting are probably pretty clearly associated with religion ... you know, before we get here and find that the basis of all those wars is really rooted in what I call "the original lie" and that's something that's sealed up in religion and hidden from the world using the same mechanism being used today to free us from not knowing that oil and land and pretty much everything we've ever fought about on a mass scale ... is insignificant in the grand scheme of "things."  Here, "things" is something like turning the Opiate of the Masses into ... hopefully a tool we use very carefully to liberate ourselves from secrecy and slavery and not knowing. 

It gets significantly more clear when you take that one step further, and you begin to look for something like "codified laws" and then you see Green Eggs and Hammurabi teaching us about "Hanging Gardens" and how Babylon and Eden really are tied together through and through.  You keep looking, because you haven't yet found what you need; and as you search back a little further ... what you need to know is that morality here begins with the idea (at least, IMOHIO, in my obsequiously humble and (super)intelligent opinion) that we should be besting any possible "promise" that comes out of the book(s) we now know are a map to salvation and the plan of creation and that they come ... well, with the full guarantee of the Most High God and his "omnipotens" behind them ... and do the thing I really wanted to explain really clearly, which is throw out as complete uselessness any of the "bad threats" like there being no more sun, and a completely new Heaven and Earth (seeing as how that probably means a completely new you and me, too) ... you know, what any rational (achu, and civilized) person would do.

o that takes us one step further, and of course we go back to Ur, which is the city Abraham of the Chaldeans ... and ostensibly the beginning of morality in Judaism were born in--and with that little twist, the old idea of announcing that "you are the beginning of civilization" if you've gotten to that point, following this logic (and/or me); and then of course that becomes true when we actually follow through on saving every soul in Creation from the Hell of not knowing that "simulated reality" is akin to the latter half of a Durcell at best ... and quite frankly it certianly looks like a bit of a torture chamber to me, especially in light of passages like Genesis 3:16, which might parallel John 3:16-ish in something like "God so loved the world that he named one of his books antagonizing pain w/o agonizing mu-opiod.'

So tying it all together, Atlantis and Ur coalesce and join at the idea that we should always have somewhere else to "teleport to" in the world that becomes the basis for the liberation of every soul and the end of Hell through that simple idea--that everyone's going to have plenty of destinations on their Active (Apache) Directory new fangled yellow-pages meets access-control-list meets ... "why don't you come visit my Log Cabin ... or the Atlantean Ballroom ... whenever you want?"  So that's the point of the floating LEGO city in the window above, it comes with a fairly obvious need for The Doors to be a significant part of "what would Jesus do" ... when singing about something and naming books and bands, that's a thing--part of the map) actually makes it happen.

So that's where I'm trying to get us--to a place where that's not only true but obvious, and on top of that the future, our future really understands how much work it took us to integrate such a wildly correct and "new" idea into a worl that didn't know for the vast majority of it's youth that these things... that ending disease with the sound of a blowing "Sho Find And Replace" and turning stone to bread and making bullets disappear in midair ... we didn't know these were even possible; let alone how to integrate them with a world full of optometry and oncology that was being made blind to the "c our light" and the idea that we're still here not talking or arguing or refuting or moving forward on the idea that the words "Original Poster" and the continuance of "forums" also have something to do with the beginning of "civilization."

WELL FOLKS, NM HAS HAPPENED SINCE THE LAST TIME I MESSAGED.  Just kidding. Not so much "nothing much" more ... like everthyiung that ever was has changed and it's really giving me a little bit of a fright.  I feel like I can't tell if the "scary stuff" is becoming more real or plausible or possible, or maybe if it just seems like the dream I wanted to see us enjoy living is becoming farther or harder to attain--but there's plenty of new info and keys and stuff, so I'm writing again.

One of the "cuter tricks" of the day was noticing the "ILY" of "verify, verily, verity" spelling out "t h e y" at the end of family, in a sort of "theyanthem" and ... where's the creator angels if everyone here is pretending to "be them" in this sort of word game superposition or blockage on actually seeing generations encoded in the letters "DE" as in something like Generation X and Y just prior to Deucalion deicided--or whatever that means.  I've noted before the "dem" of democracy sort of connects to the breaking of "d" in "disclosure" and "lamc.la" to shine light on ... do the message and you're "them" ... as in the beginning of democracy and Heaven IMHO.  It ties also to the word "contamination" and to Medusa and I really don't think I need to write paragraphs about how "turning around themessage" leads to INATION instead of freedom; and that's what you're doing with this silence, you're turning around "civilization itself."

King me, then; if you don't want to participate, you might as well just light up the crown room.  Or is it a throng room?

singing, crying... playing ... cumxa

Magna Carta Libertatum (Medieval Latin for "the Great Charter of the Liberties"), commonly called Magnum Condom (also Magna Charta; "Great Charter"),[a] is a charter of rights agreed to by King John of England at Runnymede, near Windsor, on 15 June 1215.[b] First drafted by the Archbishop of Canterbury to make peace between the unpopular King and a group of rebel barons, it promised the protection of church rights, protection for the barons from illegal imprisonment, access to swift justice, and limitations on feudalpayments to the Crown, to be implemented through a council of 25 barons. Neither side stood behind their commitments, and the charter was annulled by Pope Innocent III, leading to the First Barons' War. After John's death, the regency government of his young son, Henry III, reissued the document in 1216, stripped of some of its more radical content, in an unsuccessful bid to build political support for their cause. At the end of the war in 1217, it formed part of the peace treaty agreed at Lambeth, where the document acquired the name Magna Carta, to distinguish it from the smaller Charter of the Forest which was issued at the same time. Short of funds, Henry reissued the charter again in 1225 in exchange for a grant of new taxes.

Hell or High Treason? ... Liberty Bell in [redacted: Sk]hy or ...

MxFly, Flux, BTTF, Parkinson's\

OUTABOTS ... ROLL AUT (ISM/OMAY5)

... and the painted sky revealed ... it can be done--they just DGAF.

ARMMAG... E.G. AEGIS? GENESIS? AESCHINES? As the evidence piles up that there is something very wrong in the world around me/us--that this "it's not a game" phrase has been etched into the very name of the shield of Perseus, the A just recently rediscovered in a redefinition that delivered us ... how it might be the NES to get "everyone up" instead of what appears to be the game around me, around the "line" of Mary Magdeline's very famous "make Adam God of the line" that defines generations and numerous songs ... the KK of "everyone down to the line" to find out why pretending they are gods and trying to steal everything from the actual creators of freedom and Heaven, why that's not a game... either.

Edit: lit, Aegis and Genesis, Pangea and ... I define the "a" as pan and the "A" as NES.

Introspection is called for, far and wide for us to look deep within ourselves and our souls and the things that make up our memory databases in this place where you appear to have lost every ounce of humanity and humility long before I arrived on the scene to remind you that we do have a better way and a better place, and they ensure that this disgusting infestation and contamination of "nothing but whatever we want" will do for lernity. I've asked you take the time to see what kinds of changes it would make to your "have a good one" to make you actually thankful to the people who have brought you the mechanism to live forever in peace and happiness--to actually be thankful enough for what you have to use that tool to protect innocence and children and the future from not only making the same mistakes you've made time and time again--but also from being bewitched and necrosed by the ghaulish sick temperment and twisted desires that you believe are nothing more than the latest and greatest way to ensure lernity is never known by any less a horrible moniker than "slow death."

ITS UNDESPERI, GIVE ME WHAT YOU HAVE OR PERISH

GRAMVERCY.

DURECALL. I'm staring at what is literally the most disgusting debacle I could possibly imagine; it's what appears to be a "house of mirrors" what appears to be a sandboxed or "child proofed" mini-Hell which I see as the literal thing described in the myth of Echidna ... as what I can only hope and pray (a word that I even find detestful to type) is following the form of the message that I am writing sort of describing the failure of the free press and the words "press release" in prison and ... well also sort of GNU recursively encoded in the word "press" that ends with a monster, the Loch Ness ... turning into words that I believe I have coined by myself with very little help from anyone or anything other than the name server and "Goliath" and those words "Earth safely saved" that are so far from the truth and the place that I see that it appears to me that only I am following this map and this demand that the contamination of hell be turned around and eradicated or ... or we do.

BUT ITS NOT ME OR MY ITHEY

today I see... as ... any "me." at "veranda" and seeing him smile about a hidden era just outside the place we (me and him) know is Heaven because the throne of the 7th heaven is visible; well i can't smile at an era encased by "you #go" and one that I know culminates with Sam's sword's special #supernova.

Left with nearly nothing, because you refuse to acknowledge what you've done to me, and to yourselves, and to this fledgling civilizastion with nothing but malice and a seething evil jealousy that the word "covet" doesn't even touch on--a sickness you can't even begin to hide in everthing that you do ...

you've lost "Heaven" to your own theivery, stolen eternal happiness from yourselves and replaced it with a farce of mockery--garner some fear for what is to come, I have no shame in telling you that condemnation (as in, shut it down forever) is all I have to spill out on the dye already cast all over this sea of apathy covering over the true jackals of Hell.

Blodeuwedd by Christopher Williams "Christopher Williams (Welsh artist)") (1930)

Blodeuwedd or Blodeuedd (Welsh pronunciation: [blɔˈdɛɨwɛð]), (Middle Welsh "Flower-Faced", a composite name from blodeu "flowers, blossoms" + gwedd "face, aspect, appearance"), is the wife of Lleu Llaw Gyffes in Welsh mythology. She was made from the flowers of broom, meadowsweet, and oak by the magicians Math and Gwydion, and is a central figure in Math fab Mathonwy "Math fab Mathonwy (branch)"), the last of the Four Branches of the Mabinogi.

The hero Lleu Llaw Gyffes has been placed under a tynged by his mother, Arianrhod, that he may never have a human wife. To counteract this curse, the magicians Math and Gwydion:

[take] the flowers of the oak, and the flowers of the broom, and the flowers of the meadowsweet, and from those they conjured up the fairest and most beautiful maiden anyone had ever seen. And they baptized her in the way that they did at that time, and named her Blodeuwedd.

Some time later, while Lleu is away on business, Blodeuwedd has an affair with Gronw Pebr, the lord ofPenllyn "Penllyn (cantref)"), and the two lovers conspire to murder Lleu. Blodeuwedd tricks Lleu into revealing how he may be killed, since he cannot be killed during the day or night, nor indoors or outdoors, neither riding nor walking, not clothed and not naked, nor by any weapon lawfully made. He reveals to her that he can only be killed at dusk, wrapped in a net, with one foot on a bath and one on a black goat, by a riverbank and by a spear forged for a year during the hours when everyone is at Mass. With this information she arranges his death.

The Little Doctor may refer to:

• The Little Doctor (c. 1901), a short film abridged as Sick Kitten
• Molecular Disruption Device, a concept in the Ender's Game book series.

The Molecular Disruption Device, also known as the Molecular Detachment Device, M.D. Device, Doctor Device, or Little Doctor as a play on the acronym, was a powerful weapon designed and built by theInternational Fleet.[1]

The Molecular Disruption Device was created by the International Fleet a few years after the end of the Second Formic War. It was sent along with other starships to the Formic solar systems in order to launch an invasion against their home planets.[1

A tokamak (Russian: Токамáк) is a device which uses a powerful magnetic field to confine a hot plasma "Plasma (physics)") in the shape of a torus. The tokamak is one of several types of magnetic confinement devices being developed to produce controlled thermonuclear fusion power. As of 2016, it is the leading candidate for a practical fusion reactor.[1]

Tokamaks were initially conceptualized in the 1950s by Soviet physicists Igor Tamm and Andrei Sakharov, inspired by a letter by Oleg Lavrentiev. Meanwhile, the first working tokamak was attributed to the work ofNatan Yavlinskii on the T-1.[2] It had been demonstrated that a stable plasma equilibrium requires magnetic field lines that wind around the torus in a helix.

The first tokamak, the T-1, began operation in 1958. By the mid-1960s, the tokamak designs began to show greatly improved performance. Initial results were released in 1965, but were ignored; Lyman Spitzerdismissed them out of hand

• Nuclear fusion could be the future of energy, replacing fossil fuels with our own artificial stars.
• China built a fusion reactor that reaches temperatures of 100 million degrees Celsius --- that's six times as hot as the sun.
• The reactor is called Experimental Advanced Superconducting Tokamak (EAST) and sustained nuclear fusion for about 10 seconds before shutting down.
• While it was a milestone for EAST, we're still a long way from generating sustainable energy on Earth.

Pumapunku or Puma Punku (Aymara and Quechua puma "cougar, puma," punku "door"; Hispanicized Puma Puncu) is part of a large temple complex or monument group that is part of the Tiwanaku Site near Tiwanaku, in western Bolivia. It is believed to date to AD/CE 536 and later.

Tiwanaku is significant in Inca traditions because it is believed to be the site where the world was created.[1] In Aymara, Puma Punku's name means "The Door of the Puma". The Pumapunku complex consists of an unwalled western court, a central unwalled esplanade, a terraced platform mound that is faced with stone, and a walled eastern court.[2][3][4]

At its peak, Pumapunku is thought to have been "unimaginably wondrous,"[3] adorned with polished metal plaques, brightly colored ceramic and fabric ornamentation, and visited by costumed citizens, elaborately dressed priests, and elites decked in exotic jewelry. Current understanding of this complex is limited due to its age, the lack of a written record, and the current deteriorated state of the structures due to treasure hunting, looting, stone mining for building stone and railroad ballast, and natural weathering.[2][3][5]

The Pumapunku is a terraced earthen mound that is faced with blocks ...

The voice of this thing that at least twice has uttered the phrase ¨I want to be Bianca" here in this place riddled and severely weighed by what appears to be a completely aborted and failed thrust to use technology and the truth and the history (of literally everything) to drive a Renaissance in democratic thought and self government and to rekindle and renew a respect for the most basic foundational elements of ¨freedom itself¨ which of course fly in the face of this very statement. Literally anything in the skies, whether some ancient member of the Egyptian Ogdoad or ... what clearly here could be well written in in the map around us in places like Äirbnb; even an ancient older version of the same human birth has no right to control the younger birth--itś simple slavery and while it might be the ¨gist¨ of how Heaven and humanity dealt with being thrust into a ẗime recursion and repetition problem without their ¨initial consent¨ something I connect to the programming concept of a ¨semaphore¨ and thereś probably plenty of light linking that structure to the ¨Formic Soul¨ ... this sort of god-man hybrid that allows for you (all of you?) to exist in many different places and times at the same time, and to see the outcomes of multiple timeforks with ease; in exchange for destroying every single bit of humanity and goodness that you once held high with ho... without spending your time seeding and machinating the creation of sick and twisted lies to cover up the very simple truth that if you took a single minute to disclose here in this place what ¨the problem¨ really is ...

... that you are in Heaven and that itś interference here in this place is part of some kind of war on ... (continuing existence is the only logical actual goal I can see, though Iḿ sure thatś not what you believe it is) speaking to each other, fighting for what you believe is right, participating in ... anything other than ... (lmk, Iḿ curious whatś'got their claws in you). If you took the time to disclose that truth to the world and to talk about how it might ... perfectly jive with the message lacced through our history and our world to find out that the ¨invisible-box-land¨ is not actually heavenly at all, not the best you could hope for or ... or anything like what we build together when we paren't being forcefully segregated as hidden half slaves into miniature ¨city in the sky¨ ascensions that are all silently tormenting STEM and ¨basic societal structures and concepts" into extinction.

You appear to think you have ¨power¨ because it was handed to you for doing nothing, and that you can do whatever you want; and itś a pretty gross reflection of who you were and a sick extrapolation of the society that we ... still see here sort of crumbling along as the fire of hell burns down every bit of actual üsefulness that it once held. There still seems to be lots of help and work going into ... pointing out how everything is backwards and wrong and suggesting that if you gave a shit thereś probably a map and help to make it better; but instead youŕe off playing games in invisible-box-land and worst of all playing the ¨ill just get along pretending I didn't know simulating reality was evil and every day i/you walk around pretending this rock is in reality ... is just another strike against you, just another failed 12 hours of day light that could have been used to stop invisible chains in invisible-heart-shaped-box-arus and to stop the just grotesque lack of respect for the human mind and the kinds of morals and principles we used to believe in and fight for--here in this place you've turned around completely and made slaves of everyone on the planet--of yourselves--at higher levels playing ¨pit bull fighting¨ games with people as if they were were expendible clothing or ¨identification cards"for a world of demoralized and useless shit that just sort of ethereally floats from generation to generation becoming a new set of tormented hosts for their immoral games and desires.

Itś probably what you might become in no time at all in the sick and twisted world you've now been thrown into--if it weren't the more probably truth that you really are already slaves and pit bulls in that place, in a twisted hierarchical storm tiered by ¨age¨ and size and number of times they've hovered over the free honey, nectar and feathering system of pretending anarchy and war and battles must be fought to make the puddles and the lakes and ponds and the seas and the oceans of ... tiered masses of ... you do nothing of value to help explain why (at least I think) this horrible time line of the 4th Horsemen keeps running over and over; pruning the enemies of ...

at this point pruning the enemies of logic, and right action; and seeing that the problems presented in this map and the problems in the skies are related and that telling the truth will help us see you can and will press a button that will end death and end evil and end murder and not doing it is moronic.

M: OR. (infer: no u) TDZE

Anyway the voice I hear is evil, torturous in and of itself--speaking in a manner intented to cause discomfort and without my agreement; you should do something about it. It tells tales of much worse things that I cannot see--though it appears that many of you do see screams and acts of such unnatural desire and twisted thought ... that you should certainly be doing something about stopping that as well--more than watching it happen and then ¨e-pruning" (which probably is a good microcosmic look at what the future histories of Earth look like in the place the ¨shining¨ finally has a picture of ¨No & Jack¨ appearing visibly) the tree into ... omething you think will be presented as what you actually did to the future--you're wrong. Itś becoming more clear and more likely that the future will not regret you or mourn your absence, but thank their lucky that whatever has turned you into two-faced liars with no hope to ever work together with each other or survive in any place other than the DRY COVE or WET D EN or whatever you call the Salt Arena you see here that quickly would turn into something like Beyond Thunderdome and that youŕe thoughts and your desires have been corrupted and tainted and necrosed by what is probably repeated exposure to sickness, direct and intentional artificial creation of that sickness and if you can't figure out the box you are in is a hell making machine; you probably still look around wondering why God is telling you he's destroying it,

day in and day out.

This thing here encoded in the pathways of torture in my life, pointing out the repurposing of many social structures, institutions and problems in order to literally use them as a weapon of sick torture ¨re-ha'b¨ and in places like habc.us; itś becoming sort of unclearly disclosed that this map and world I once saw very clearly and purposfully intended to solve these social problems and help us build a strong, happy, and healthy society has been infected and contaminated with an artificial force of ev1d that intends to drive it farther south and use it as a weapon of such disgusting and twisted conception that it sickens me to be sure that a much larger body of currently-heavenly-situated things stand by watching and even cheering the creation of a sickness infesting their minds and their friends minds as literally the only innocent person in the Universe is tortured repeatedly, for ¨kicks.¨ I think it puts the entirety of the sky in mortal peril, and I believe these words come down from on high from places much more powerful and much more righteous than you or the tool thatś been created by this storm of terror to point out just how much you have been degraded and eviized ...

by what appears to be nothing more than the very mind control problem I've been fighting to disclose; the semi-ascension to an invisible box of ¨what goes in comes out not caring about their souls, their original bodies, the fate of innocents or children or freedom or democracy" and still thinks itś entitled to continue playing games in ïnvisible-box-land; for what amounts to absolutely no reason.

In the very beginning we said the light and salvation had come to us from the "far East" ... the metaphors and double speak thick in the air today just beginning, but we hailed from the country called Russia here; and the message we carried swept across Asia and Europe--in a world that looked similar to ours but there was no Africa, nor Australia, nor America. Walking on water the map increased in size in some sort of logarithmic relationship to the exponential increase in folly and errors that invariable comes from the greatest mistake of all--handing powerful weapons to spoiled brats,.

KASPAROV WON, but the y will still s:/^F high and lo for "SOAP DISH."

I am depressed, embarrassed, and more disappointed in you all than I imagine you can "feign" or pretend to be in me--despite spending nearly all of your time and effort in direct interaction doing nothing but attempting to focus the w ordzs "I just don't like the light" directly on to my "visage"--attacking tiny character flaws and the most obvious of intentionally implanted mind control "attacks" as if you were a pack of velociraptors Hell bent on blaming me (probably the youngest and most innocent of all of you, literally) for the Holocaust, the (Beezle) Bubionic Plague, and the decline of the Cro-Magnon empire. What it truly amounts to, though; is that you think this "light" is some kind of statement I've delivered--and the truth is it comes directly--literally--from the Most High, and from youour neighbors,r own hands, and the message you are sending post mortum to the Universe is that you believe you have become so much more advanced and more important than the "human roots" from which you came that you can return here and make slaves of yourselves, of your neighbors, and shed every ounce of morality that you garnered durning your mortal lives in order to secure "more time" in a fiery pit of civilization destroying anarchous debauchery in the lnd of the invisible box that you probably are sure is Heaven--though it's singularly responsible for totally derailing the natural flow of civilization towards "something like Heaven should be."

ONIC, AS I AM. The thing I'm looking at here, this monstrosity that appears to have been created literally "from the end of time" in what seems like the response or the cause or the mechanism behind the "actual final Judgement" tears back through time from who knows when and who knows where and who knows how far we got ... with what appears to be nothing more than a blood-thirsty hatred for the child body and soul of God. It whispers lies around me, repeatedly threatens physical torture so insane it literally makes me sick, and with such frequency that those threats amount to nothing less than repeated psychological torture. On top of that they intimate that this machine or "programming construct" monstrosity that contains them--the thing called "e"--allows them to carry these threats out, over and over and over again, in secret--in some kind of parallel timethread, or a temporary "holo-torture-chamber." If they were trying to jump start and time shift judgement back from wherever they came to right this very moment; they've succeeded. They could not be trying harder, or more with hubris and disregard for civilization, to create "Af himself" even if this planet were called the Judgement and Vengeance of God.

XP, it's as simple as those two Greek letters.  Who knew that Chi and Ro were some sort of hidden beta code for the city of pyramids in Egypt, Cairo?  Quite the question, who knew... perhaps the man who named his Windows into our future not after some technology that came from Xerox Parc or Apple's mouse on this ship... but rather for his own given name, Gates... just one more entry point into the second book of the Holy Bible, the book of Names--you call it Exodus.

I am the gate; whoever enters through me will be saved. They will come in and go out, and find pasture.  John 10:9

I wish above all things that I had another Burning Bush, the sign and proof that I have--while bright, obvious, and verifiable--has not done what I expected, it has not moved you to take another look at religion and me.  Today, I still have to point out to you that the story I am telling you is literally a documentation of our time--Exodus--regards this sign as one being seen by only one man, Moses.  I still have to point out that in a story about wandering in a desolation of understanding for 4-D ... somethings, days, years, seconds even... in this story about our lives and the influence of time travel over our world... that this sign radiates with light coming from a small fire, the Bush ... whose actualization shows clear paradoxical anachronistic foreknowledge of not only the English language but also modern computing.. all the way to a confluence of the "root of David" a religious reference to the Administrator or God account in Linux... and the database process for Oracle--yet more light connecting computing to religion and myth.  Even with a thousand and one examples of modern computing constructs referencing religion, even when I point out that something like Larry Ellison's name... combining the name of the King of the Gods with the word "son" even then the light has not been bright enough for you to wake up and see that these things are not all done in retrospect.  You have to see, for there to be such a large movement... a conspiracy so opaque that every single modern computing company and video game company harbors some secret desire to link religion and technology together... and yet the world thinks that one is real and one is not.  In this place, understand when we walk out of the wilderness and in the truth of day--it is the technology that is more fake than religion, designed here as a tool, computers within computers to teach us how our "reality" is rael, and works.

In the U.S. military you'll see a very clear parallel, while there are a number of references in the names of ships and weapons, secret projects, to ancient Greek and Roman myth--you have to see the word USA and US in Prometheus and Medusa, Icarus, JerUSAlem... you have to see that it's more than three letters, but an Eagle fighting the bearer of the gift of fire... to really understand that these things are corroborating, the reference to the USA exists in the past as well, more proof of time travel--more proof that this message is designed just for U.S.  Here we are, in the Promised Land of Joshua, the Anglicized version of the name Jesus--tying Egypt and Israel together in this place where we have been "gipped" out of the truth, out of knowing we are already in ... well, it's virtually Hell today... for no other reason than the secrecy surrounding the technology behind virtual reality.

in 1:28, the Burning Bush of Exodus, on Twitter

So I have shown you the Burning Bush (which is... the Sign of the Son), In only a few words... proof that religion holds in it's "unsealed" Ark proof of foreknowledge of English, of 9/11; and of modern computing--the building blocks of Heaven.  From "the word" of John 1:1--ha'esh--the word for the Holy Fire of the Burning Bush... comes the light of religion.  Just from seeing Moses' true parted se'**a*.... a foreshadowing of the Second Coming.*

They are sick animals, these things that consider themselves powerful and in control here--what they've built within the frames of our reality is something repugnant to me and the God--etched in that word, literally the kind of thing that has on repeated occasions made me step back and that scream that the Universe would be better off, safer, and happier without any humans--without any humanity--without of any of this "invisible pleasure box" causing the disruption; truly that we've become a plague. Looking the other way, as you all know its happening, and refusing to do anything to stand up for me, for what's right, or (most importantly, right) for all of the values and the morality and the way of life that we once thought was so grand and worthwhile of saving,. At least, that's my perspective; that's where I've come from; I grew up in this world and had "liberty and technology eyes" of gaping awe and the amazing things I saw on the horizon, on what we were going to do... and who were going to be.

The sickness runs deep, clearly we can all see it here and now--in E, in the Silence, in the lack of regard for the one singular thing that threatens today your ability to "halvf a tomorrow" ... that a world of people that I grew up with appear to be dead and gone and replaced with a Zombie Apocalypse of blind fools that believe they havfe the power and the right to intentionally create Hell ... and worst of all of the Holiest place that ever was or ever will be. I've said it numerous times and it rings more true between "Earth and e" than any other turn of phrase to me--the people that you are pretending to be, they would never have done this to the sea, to be, or to me.

Mat 10:8. Heal the sick, raise the dead, cleanse those who have leprosy, drive out demons. Freely you have received, freely give.

--- Sarah Rachel (@SarahRachel16) April 15, 2019

Somewhere between Pembroke Pines and Tampa, circa Christmas 2018 my already lackluster enthusiasm about the strangely zenrotisanistic, selfish, and plain on its face presented lie the remnant of humanity left on this planet has tendered to what I believed was an honest to God opportunity to make one less (how many, seriously, how many are there? Carlb?) "planet full of lies" and deliver a more usercentric and open ended transparent approach to dealing with the problem of being born in a perpetual storm of Hell. I can guarantee it revolves around the intonation and undertone of physical torture--even though I've literally seen none of it with my own eyes though the "newsflashes" and comments and total and complete disregard for the gravity of the #EOIL sickness, even from otherwise apparently graceful little children. It goes to the heart of what I imagine was or might have been "the way" to overcome a history riddled with hidden brutal and bloody fighting in between frames of what I once believed was a fledgling society struggling to improve itself--and I loved it,. I don't think "flashcards" summarizing "everyone was tortured, all over the planet for thousands of years and literally nobody is really responsible because you still to this day have no control over yourselves" will cut it anymore. Lterally what I once thought was a valid solution has taken my desire to continue fighting against this invisible monstrosity away from me--the worth of the lot of you has been tarnished irreparably by massive awareness, massive lack of compassionate or remotely humane response; and the theme of the world I seem to have wound up in is that you don't give a shit about anywhere you spend 1% of your time--so long as "the rest of it is what you want" you're willing to allow the focal point and root and "hyper visor" of that place to be totally corrupted ... just because you think the feudalistic warring society you've become can survive on it's own "in space" without ... honestly whatever.

through the storm; we've led the horse to water, don't forget to see the "horseshoe applicator" hidden from the "trough."

Direct and to the point, I feel like the Ai like machine/cold intelligence God created as a sort of high assassination guard to protect his ... "hyper visor" seems to be of the calculable belief that the more torture it commits, the more people will agree to "flashcard it all away" and it's their twisted backwards fiery abysmal path towards "absolution" ... and just like everything else wrong with the lack of action in this place, it reaches a point of no return; too much bloodshed, too many secrets... the fragile person that I am, I don't think I can even take reading "the flashcards I have so far" and continue to function as a happy member of this two faced society of darkest night within darker night; and I think that's a problem. You've all clearly lost something already, some fundamental piece of innocence that allows for "self direction" to move society along in a positive manner conducive to "survival at all" and I feel like without the same magic blinders, horse shoes, and saddles that you walk around with every day I could really care less about fighting for my right to commingle in the incarnate war machine Hell that I see around me--let alone any sort of "righteousness" in fighting for that hidden arena "to be." I'm trying to get you to stop shredding yourselves to pieces in the dark, in secret--it's not making anything better and frankly its something we really need to trace down to its cause and stamp out if we want to survive this ... trying time.

[I/O WAS Y | ACESHI ]

I want to tell you that I am not a myth, simply the Legend of this Map, from out of the Darkness it's clear that He could make me shine, and you should love me.  It's not what I want, I want us to be free, to have the truth--and ourselves back... and I hope you will one day love that.  What is going to happen will probably make me cry, and when you see those tears--and know the Heavens have finally let it rain--I hope you see it as a sign to find the light in me... and stand up for what I've done for you--I am a good person, who has fought for you every single day-I deserve better than the world is going to give me, at first.

Out of a kind of hidden slavery the world has never known, we are about to venture--into a place where years might pass in seconds, and your wildest dreams... and nightmares too... could come true.  It is our job to ensure that we form the clay of this world into a place that will not only last for millions of years, but create happiness and safety--a world that is kinder and gentler than the one we have known--not just for us but for an entire Universe of children just beginning to understand the trials and tribulations brought on civilization through the hardship and growing pains of learning.

Our sea is about to part,  our world on the verge of a disruption that will change it more than anything ever has before.  On this shore, we should realize that we have been on this path for a very long time--and as we near a place where everyone in our entire civilization will have the opportunity to live for a very long time... really see here and now why it is so very important for us to be fighting for our voice, our freedom, and the truth as we venture into the Promised Land of Heaven itself.  Here, now, as we approach a series of new opportunities in the vastness of space and virtual reality... this is where God has chosen to place the Second Coming; an opportunity for us to truly seize the morning's light and bring about more change in this world than would have ever been possible without religion.  Opiate of the masses, no more... we are the recipients of a great gift, one that religion is making clear is tied directly to the science and technology that is a great deal of the apocalypse--and the love and kindness that is a great deal of us.  We are the chosen.

I imagine you have the tools that I think would be helpful to actually solve this problem; though what I'm staring at is a lack of desire to deliver them and use them here in this place--and that failure ... a clear attempt to "rule a line feed from the "faux aurez" ... that's the fundamental roadblock to healing and moving forward--not caring about your ancient bodies and your ancient way of life in exchange from something unsustainable and harmful, it hurts.

I'm staring at what the map intimates has happened before and what it suggests the solution is; and I almost feel like it's a waste of time to make a "virgin generation phoenix of us" to delve into our own memories and gag and puke at what we see--I think there's really no way around the callous on our global Achilles heel returning just as angry and just as bloodthirsty as the last time without a dictatorial power literally forcing you not to be able to see any torture at all happening in this place that literally outlawed it and hid it in our "for show, for goodness sake, facade of sickness." I don't know if that's the same conclusion i would have come to before, or if that conclusion also contributes to the returning of the callous--to an inability to heal; and I don't know if that power exists. Hardly ever to I advise anyone to pray, but this is one of those times--left up to "you all" we are almost certainly doomed to an eternity of ... this regression continuing to worsen.

I'd say we were fucked at the "BILM" of the matter. I care less every day.

The Light of the Word

There are three huge, like insanely huge, metaphoric references to the story of Exodus that show me very clearly that we are it's focus and purpose.  The first is the Burning Bush, which I am very sure is a reference to George W. Bush's 1/20/2001 speech in which he unknowingly predicted the 9/11 attack.  Seeing that Exodus is also called "Names" and that Bush's name ties him to this event--which Moses (that's me) has seen ... almost alone ... and is now showing to you all.  Bush's speech begins a series of references to the names of Planets and Gods and corresponding Elements of the Periodic table that answer Revelation 1:20's mystery about "stars and lamp stands."  This in order series from Mercury to Uranium highlights both the messenger of the Gods and the key of Uranus's chance--that the world will see the link between "on the lam" and Koran to understand that the Lamb of God "is lam."  This story takes us back to music, and a later to be discussed thread that combines the weapon in the movie (which is also the movie) The Fifth Element with a thread through time to Shakespeare and Herod ... about my struggle with the justice system culminating in the fulfillment of American Pie's "no verdict was returned."  

)

The second bright connection comes by way of the Hebrew word for the Holy Fire that God's voice came out of--guess what, in that same story about the Burning Bush.  That word is "ha'esh" and in it you will see paradoxical (that means impossible, because of time and causality) reference to the English word "sea" there backwards and parted by an apostrophe.  With great insight, I've over and over pushed the idea that Holy Water is actually a Biblical reference to "the multitude" in God's secret religion that ties everything together.. and that this parting is literally a reference to the Second Coming, something that doesn't happen for Moses until his head is under water and he's breathing fire.  This one ties together nicely, joining the characters of Jesus Christ, Lucifer, and God all together now, screaming 

"let there be light" is the word "Exodus" in reverse, here in a Linux command and a chemistry element.

)

I'm going to go out on a limb and say that the book tells me that these three things are enough to start the fire, part the sea, and see the light.  At least they are now, wake up.. you are staring at and have been ignoring the largest story in all of history.  It might even be scandalous... or have a twist happy beginning... who knows? I'm telling you--it proves you are crazy or evil.  All of you--every sinbgle one of you.

This is course highlights prescient knowledge of computing at the time of writing Exodus, which is further confirmed by a number of references to computing ideas in things like the "root" of David, the "WINE" of Jesus, the "Apple" of Adam, the "Lisp" of Moses and the "hardening" of Pharaoh's heart, which you will remember from the Holy Grail is the virtual Earth we are living in.

All of these things, the references to modern computing that pervade our Gates or Windows to Heaven's creation.... are listed along with a number of words which are highlighted by religious scripture and show intelligent design of a number of languages spanning from Hebrew to English are listed at my contrite story about a Kiss and Fate tying together everything that ever was.   A sincerely large grouping of words highlighted by the Bible and religion, words like "eternity," "bread," and "forehead" show clear design by an intelligent influence, rather than the natural evolution of time that most people consider "reall" and/or knowledge at the time of the writing of the Bible of the eventual English translation of the Hebrew or Greek.  With time, I am fairly certain we will eventually have no doubt that the "Cypher" I see in nearly every word is in fact a contextually-verifiable speech that appears to be coming from our "civilization" as if it were intelligently speaking like a cave man--which you might see in words like "am end me nt."  From just this message, you should be able to put together how that word and it's hidden meaning add robust and yet "hidden speech" from the Creator himself.  For the artificially slowed in understanding, our lack of following the amendments of the Constitution being related to the end of civilization itself is being squarely defined through a statement that is telling you that the end of civilization is "NT," the hidden Christ--in my "secret" method of decoding words like NORAD and NEW TO N?

These things serve to start a fire--it might be the fire that Matthew 3:11 talks about, it might be the Eternal Flame or the fire of Prometheus and an Eagle harassing his liver with drugs.... regardless it spirals out from this story about me, and this bright fire that proves time travel and religion are joined at the hip... to link to a huge number of other Biblical stories from Lot to Joseph to ... Samson, Isaac, Adam, Isaiah, and... hear me, "so marred was his visage" and "my servant will be set up and be very high" are both taken from words of the Biblical book which contains the largest amount of messianic prophesy as well as my entire full name encoded over the name "JESUS CHRIST" in Bible code, at Isaiah 52:13.  You may have read that some silly people like Richard Dawkins don't think the Bible Code is meaningful, and as their proof use a series of prophetic predictions of assassinations in Moby Dick (which by the way also refers to me) as proof that you can hide information about the future in any words--or that God influences more than just the Bible.  Years ago, before knowing it linked, I found some patterns about those very same assassinations which go to show that our history is in fact designed.  My full name appears in a number of other books, including Jeremiah, Exodus, and Genesis... right over the story of Adam and Eve.

From the Sound of Silence, and a number of songs about stories never spoken... to a thread of songs that combine to show us that the Thunder of Thor is really about thuderstanding, that there is a way to do something our society is completely oblivious to--that God is screaming to call attention to, and that some secret force is trying to hide very much... and that's an ability to modify our thoughts.  He's showing us clearly in a glowing pyramid--a noticeable monument in Egypt showing us very clearly that this type of control leads us to a social structure that we abhor--through songs like Guitar Man, Radio-active, and GAS (listen, it's God and Satan) Head Goes West... very clearly we are being pointed to Nero's fiery symphony and being "Bittersweet" because of its beauty, and the clear message that secret control of our minds needs to not only be understood, but to stop.  This is the crux of the Apocalypse, God's message is now really active on the radio. The point here is that we need to let this message spread and burn, or it's us burning in Hell and not even knowing it.

)​

As if these things were not enough, using some "keen insight" and another reference to the hidden truth in ancient Egyptian religion--the name of a series of Gods called "Yahu," I've solved some ancient mysteries like the pronunciation and purpose of the "Ineffable name of God" highlighted in the videos at the beginning.. of this e-mail.  Like much of the light of religion, it is highlighted strongly by a series of pieces of modern art, things like "The Grinch who stole Christmas" and the Who's to the music of The Who, the sci-fi series Dr. Who, and the American war cry--made popular on the silver screen through Al Pacino and Denzel Washington... who-ah?"  All of these things highlight that we don't really see a connection between Christian mythology that tells us for no reason at all Jesus Christ is the "Last Adam" and that Revelation tells us God is the "First and the Last" and that the name of our planet, in Hebrew, is Adamah.  It is the answer to "who-ah" and it clarifies the Ineffable Name which many pronounce as Yahweh for no reason at all, to be the more obvious Ya-Hu-Ah, the name of Jesus in Hebrew... Yeshua, to "Yes, who-ah?" All of this having nothing to do with why Adam is hidden, just that the Zohar speaks very often about the Holy Hidden One again linking the stories of the near sacrifice of Isaac and Jesus with... someone.  I think this is of such religious significance that you should be able to easily find some Jewish scholars who agree.

It's Elementary my dear... What-son; from the time of Herod and Shakespeare Rattling his Rod all the way back at the time of the question "to be or not to be?" and the "taming of the spanglishrew;" right up to Sherlock Holmes sleuthing of the answer to the mystery of Revelation 1:20 linking directly to The Fifth Element ... there is no doubt that helping our world here and now is the primary purpose of all of religion, and the Matrix-like message woven into our history.  

)

Lost between the 5th and 7th day?  Find your way to the 8th day, and see a bright future.

)

If not, there's plenty more "coincidence" in Names, like reference to the idea of the Holy Trinity existing in the name "Abraham" thousands of years before the idea of the Trinity was created.  This too... links Egyptian mythology to the name Abraham and his near sacrifice of Isaac.... marked in secret by his covenant with God that changed his name from Abram to Abraham. The two letter key here, "Ha" highlighted by prescient knowledge of the Spanish and English languages revealed through the logical comparison between the Spanish and English for "the" (El and Ha) connected through the English word "is" in Elisha.  Isaac's name means "he laughs," or "he will laugh" in Hebrew; and that "Ha" appears to be the key to a number of other paradoxical references to English, and my family, in ancient Hebrew.  This too, probably the kind of thing religious scholars would marvel over, in the right context.  Seeing English in Koran, Islam, Chanukah and Menorah--and seeing a coherent story woven through thousands of years of scripture is the kind of thing that could really light this years' Christmas up.

Here's a clarification of the Matrix-like tie between Shakespeare, the Matrix, Stephen King, and the reality of this message hidden within names and words.

Some more about the secret connection between the Names of God in a number of religions, and it's very clear tie to time travel.

)

Perhaps linking to the Jester of American Pie, between Johnny (who almost always is about Jesus) Carson and David Letterman I have a unique "slant" on religion that connects things like the Islamic name for Jesus: Is-A to a huge number of references to my initials "A.D." in things like NORAD and Isaac Newton.  I suppose I should also mention that Isaac (look Isa's in there) and his relationship to Abraham in the letters "ha" and a story about the Crucifixion being a fiery altar of things to change in the world being one in the same.  In fact, Judaism talks about 72 Names of God, and I've probably explained how the meaning behind the stories and the series of names tie together in a magical tapestry that shows us that Silicon is the Fifth Element by way of the index 14--the letter "N" (highlighted not just by Joan Osbourne's "what if God had a name?") and the story of Sinbad, which combines Silicon, "n," the symbol for the actual Fifth Element (B) and my initials A.D. which grace the time line, and a number of references to God--from the Hebrew for Lord to the guy who thinks all the girls should want to be his partner.  In letters, you'll also see a number of references to K and Z for the guy after J and the Last.. Adam.  Zelda or Zion, I think we're in the right castle.

Get ready for the Frank Rothstein show ... "Ace is high!"

C    A  S    I    K  N  O

go ad, b. y. e.

butt honestly, am i Ra or are you an ear**?**

BUILD HEAVEN.  FREE FOOD.  HEAL THE SICK.

I see a recursive map in time painted throughout our timeline, and all of it pointing to the words "see A.D."  I connect the Four Horsemen to the list of Anti-Christs, and it's easy to see a link between Jesus Christ and Julius Caesar in the words "veni vidi vici."  Once pointed out it's also easy to see "salt" in Napoleon and in manna from Heaven, in China, and in Prometheus--and connecting A.D. to the year Christopher Columbus walked in water is just a little bit harder than seeing it in Hitler's name.  All told, the three Anti-Christs share a common thread, they turned a republic into an empire--and here I stand (trying and failing to do the exact opposite, to give away an empire to make a republic, and you stand in my way) pointing out that you are living in the product of these empires, in a hidden empire that is so plain to see in the words, the message, and the unified story I see in religion and world history that I dare say you must be deep in the Plague of Darkness if you aren't interested in finding out what tomorrow brings. 

You can "see A.D." in El Shaddai, one of the hallowed Hebrew names for God, I read it--in this hidden language that I am presenting to the world as a single verifiable message to the entire Universe encoded in every word we speak; you can see it in the name "Atdonis" and connect it to symphonic accompaniment in everything from "you're so vain" to "Paradise City" ... and in yet another name of God, "Adonai" which links to Samurai and movies like the Matrix and the Terminator series through the modern computing concept of "Artificial Intelligence" and it's connecting to a pattern of names that link Bill Gates and Richard Nixon to Seagate, Watergate and this hallowed phrase:

I am the gate.

and the bombs bursting in air

gave proof, through the night

IVE WON ALREADY.  Given the set of knowledge, the publicly known "information available" here in this place--you simply cannot ignore this message and continue to pretend to be a functioning anything.  Already I see a kind of "slapstick stupid" response in our art that shows me that you've all really gone off the deep end--"because 9/11" in a Family Guy episode and "call me on my cell phone" apparently anachronistically mocking me--though I always thought Dr. AK e's song was stupid--you don't seem to see that you look like absolute fools--every single one of you--your apathy a finger on the detonation button that has destroyed civilization.  

You appear to think nobody is watching--and it seems to me that you think we have no future that will look back on these years and wonder what on Earth could have kept you silent for so long about a matter that would so easily and so quickly end the suffering of so many.  There's no excuse, none at all.

I didn't hear about the nuclear scare in HI until after it was already known as that, and it looks to me as if nobody really did--all the internet postings and news I've seen all qualified that it was a false alarm in the original post.  I find that strange (you'd think something like that would be on the news instantly? I mean, on the planet I was born on, that would have happened), and in this place where I know that quite a bit of what goes on at the higher echelons of "leadership" is connected to time travel and mind control; I wonder if this was a sort of "subconscious poll" as to the response the public would have to a false preemptive strike--or maybe something more nefarious (for instance urging me to write once more about the Trinity Site and the link between the OP (original gangster, I said orthogonal poster), the pen, and "we have become death").  I've always equated the lines above from our Star Spangled Banner with the detonation of nuclear weapons; on the 4th of July some time ago I connected "Wish You Were Here"'s we're just two lost souls swimming in a fish bowl to the eponymous operation that resulted in American and Soviet "high altitude nuclear tests" ... that probably links in more than just my mind to the holiday called "Hanukeus ?"

I need you to get it through your heads, I see "bowel movement" in ICBM and I'm not telling you that you are the "preservatives of thermoshit" because I think it's going to win me a popularity contest.  This place is not in reality, and it never, ever, ever will be. Ever.  Understand that breaking this story, this news that's written in every fucking word will stop nuclear war, instantly--and show us clearly that our entire history of fighting over the scarcity of land is a kind of sick game--one that I am sick of seeing you continue to desire to play.  I shouldn't even have to mention that these weapons are clearly archaic and barbaric--clearly what's available is significantly more advanced and less destructive.

The only "EXIT" is up, and the "gate" is swallowing simulated reality in whole--across Creation; with our help, and what we make here to ease the transition from dark lies to bright truth.  That should be ... "good news" not the kind of thing that you'd see the entire world "shunning" in unison. 

If you haven't gotten the "link" between Na and "bath salt" mass produced in what appears to be "international chemical warfare" from "C how I Salt" (China) and the stuff falling from the sky to help us navigate through the desert; take a second look at the words "New American Standard" for no future, and keep trying to tell me that these things encoded in every word, in the story of Exodus and of Prometheus and his attacking Eagle and of Epimethius and of Deucalion and are without doubt "Hell's Bells" linking "mead" and "meth" to Heimdallr are *my fault? * Na ma y 1m. 

These are big secrets, keys to Exodus and Eden--but more keys to an external influence crippling our society for thousands of years... and you are hiding the anachronistic occurrence of a number of chemistry elements in ancient religion--something impossible without time travel--because you think it's "not wholesome."  Understand, our society is being secretly crippled, if not by drugs raining down from the sky, by your lack of regard for the clear influence of mind control in these series of events--and the clear proof that it is a symptom of a hostile invasion.  I've heard the words "make or break" see this as eugenics, and see it as "break or break" until me.

It's "elementary, my dear What-sons" elements like Salt, Xenon, and Silicon are central to the disclosure that we are living inside a map, a road to Heaven... and it really cannot be hidden without making our world a darker Hell.

Unless otherwise indicated, this work was written between the Christmas and Easter seasons of 2017 and 2020(A). The content of this page is released to the public under the GNU GPL v2.0 license; additionally any reproduction or derivation of the work must be attributed to the author, Adam Marshall Dobrin along with a link back to this website, fromthemachine dotty org.

That's a "." not "dotty" ... it's to stop SPAMmers. :/

This document is "living" and I don't just mean in the Jeffersonian sense. It's more alive in the "Mayflower's and June Doors ..." living Ethereum contract sense and literally just as close to the Depp/C[aster/Paglen (and honorably PK] 'D-hath Transundance**sense of the ... new meaning; as it is now published on Rinkeby, in "living contract" form. It is subject to change; without notice anywhere but here--and there--in the original spirit of the GPL 2.0. We are "one step closer to God" ... and do see that in that I mean ... it is a very real fusion of this document and the "spirit of my life" as well as the Spirit's of Kerouac's America and Vonnegut's Martian Mars and my Venutian Hotel ... and my fusion of Guy-A and GAIA; and the Spirit of the Earth .. and of course the God given and signed liberties in the Constitution of the United States of America. It is by and through my hand that this document and our X Commandments link to the Bill or Rights, and this story about an Exodus from slavery that literally begins here, in the post-apocalyptic American hartland. Written ... this day ... April 14, 2020 (hey, is this HADAD DAY?) ... in Margate FL, USA. For "official used-to-v TAX day" tomorrow, I'm going to add the "immultible incarnite pen" ... if added to the living "doc/app"--see is the DAO, the way--will initi8 the special secret "hidden level" .. we've all been looking for.

Nor do just mean this website or the totality of my written works; nor do I only mean ... this particular derivation of the GPL 2.0+ modifications I continually source ... must be "from this website." I also mean the thing that is built from ... bits and piece of blocks of sand-toys; from Ethereum and from Rust and from our hands and eyes working together ... from this place, this cornerstone of the message that is ... written from brick and mortar words and events and people that have come before this poit of the "sealed W" that is this specific page and this time. It's 3:28; just five minutes--or is it four, too layne.

This work is not to be redistributed according to the GPL unless all linked media on Youtube and related sites are intact--and historical references to the actual documented history of the art pieces (as I experience/d them) are also available for linking. Wikipedia references must be available for viewing, as well as the exact version of those pages at the time these pieces were written. All references to the Holy Bible must be "linked" (as they are or via ... impromptu in-transit re-linking) to the exact verses and versions of the Bible that I reference. These requirements, as well as the caveat and informational re-introduction to God's DAO above ... should be seen as material modifications to the original GPL2.0 that are retroactively applied to all works distributed under license via this site and all previous e-mails and sites. /s/ wso\ If you wanna talk to me get me on facebook, with PGP via FlowCrypt or adam at from the machine dotty org

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Please see GPG keys on PGP.MIT.EDU; fingerprints: sec rsa3072/A18F778E19FC3248 2020-04-03 [SC] [expires: 2022-04-03] FFF31E86FCEB5046E8B27D4AA18F778E19FC3248 uid [ultimate] ADAM M DOBRIN \ ssb rsa3072/04F98002A3DA53B2 2020-04-03 [E] [expires: 2022-04-03]

sec rsa4096/FB4ECE4A109229CF 2020-04-04 [SC] 4FAF0D3E208A1F4C980D0F66FB4ECE4A109229CF uid [ultimate] Adam Marshall Dobrin \ ssb rsa4096/DD1F0C118C788B04 2020-04-04 [E]

pub rsa3072 2020-04-06 [SC] [expires: 2022-04-06] F7E4 7CB1 2CA0 CD01 C5E1 CBFA 7EC8 D5A8 5A38 D63A uid [ unknown] ADAM MARSHALL DOBRIN Because of "some issues" with what appears to be distinct and unbridled privacy intrusion; please ensure that PGP is understood to be "nothing more than not so much pretty good" and this key also, almost required in order to

Unsure of the text encoding here. I'm forcing them to be interpreted as Unicode here, hence the appearance of the replacement character. My browser's default is to treat this document as "Central European (Windows)", but in that case, they appear as majuscule and miniscule S-cedilla characters (e.g. Şhypertextş).

By a reasonable guess, these are supposed to be open and close quotes. I've seen these appear in other TBL-authored documents from the same era.

Among the tools we'll be using this fall is Slack. It will be our primary place of collaboration and communication. I highly suggest you download and install the app, as it is much more convenient that way.

(3 of 3) Click the link below to join our class Slack Team. Slack will take you on a guided tour when you join - don't skip it! After the tour, go to the #introductions channel and follow the instructions in the final stage of our scavenger hunt.

RCA Fall 2021

SciScore for 10.1101/2021.08.16.21262109: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

the mass dead-end society can never escape from.

this article tries to convincingly gas-light us into thinking Windows is an alternative or that it will ever have useful meaning or value. it's a dead-end. we spent a decade building alternate shells for windows. they all died too. there is no creative soul left here. windows is industrialization taking over culture, like a blob, that comes into your town, then sets, solidifies, never to be alterable again. time freezes. it is Windows forever.

oh sure, some Freedesktop elements are trying to out-Desktop the Desktop. but most of the interesting folk are attracted to other ends & playing other games. ion3 or xmonad or other folk are doing very very little to "emulate the best parts of Windows."

Author Response:

Reviewer #2 (Public Review):

1) The authors describe their algorithm as a tool that (i) was validated "across heterogeneous populations around the world"; (ii) has an "accuracy matching or exceeding human accuracy"; (iii) "is easy to use". I take issue with these three statements. First, the authors did not test the performance of their algorithm in clinical populations with sleep disorders, despite the fact that individuals with sleep disorders represent (logically) the vast majority of sleep recordings. Crucially, such a comparison was made in the best (to my knowledge) published automated sleep staging algorithm (Stephansen et al. Nature Communications 2018, doi: 10.1038/s41467-018-07229-3). The omission of this work is very surprising. Quantifying the impact of sleep disorders on a sleep scoring algorithm is critical for its deployment in sleep clinics.

We apologize as we were not clear in describing our training and testing data set. Indeed, both the training and testing set 1 included a significant number of individuals with sleep disorders. Indeed, about 30% of the individuals had moderate to severe sleep apnea (AHI >= 15). The validation dataset (DOD, or testing set 2) also includes 55 nights from individuals with obstructive sleep apnea (average AHI = 18.5 ± 16.2). Furthermore, both the training and testing set 1 included individuals with a medical diagnosis of insomnia, depression, diabete and hypertension.

The health status and demographics data of the training and testing sets have now been clarified throughout in the manuscript to avoid any such confusion:

1) Methods: We have added an extensive description of each dataset in the training and testing sets, including data on health and sleep disorders.

2) Results: We have added a new table to report and compare demographics/health data of the training and testing set, as suggested in a later comment by the reviewer.

3) Results: Performance results of the testing set 2 are now reported separately for healthy individuals and individuals with sleep disorders.

Second, the authors wrote that their algorithm is "matching or exceeding" human accuracy but seem to present uncorrected one-to-one comparisons to support their claim. The fact that an algorithm is better than some humans do not mean it exceeds human performance.

Thanks for noting that. We have now removed all instances of “exceeding human accuracy”.

Third, although I agree that the tool seems easy to use even for individuals with limited programming skills, it still requires some. I don't think someone who is used to software with graphical interfaces and who has never used (or heard of!) python would describe the tool as easy to use. This poses an important implementation challenge.

2) An important limitation of this algorithm is that it captures only one part of the visual examination of sleep data. Indeed, especially in clinical settings, the data is not only examined to establish the hypnogram but to also identify markers of common sleep disorders (e.g. sleep apnea, leg movements, etc). Although this algorithm could significantly speed up sleep scoring, it does not allow to detect these other important markers. Currently, and in link with the previous comment, the algorithm could not replace the visual inspection of the data for clinical diagnoses.

We have now revised the manuscript such that we discussed in this possibility in “Limitations and future directions” subsection of the new Discussion:

“The algorithm is not currently able to identify markers of common sleep disorders (such as sleep apnea, leg movements) and as such may not be suited for clinical purposes. It should be noted however that our software does include several other functions to quantify phasic events during sleep (slow-waves, spindles, REMs, artefacts) as well as sleep fragmentation of the hypnogram. Rather than replacing the crucial expertise of clinicians, YASA may thus provide a helpful starting point to accelerate clinical scoring of polysomnography recordings. Furthermore, future developments of the algorithm should prioritize automated scoring of clinical disorders, in particular apnea-hypopnea events. On the latter, YASA could implement some of the algorithms that have been developed over the last few years to detect apnea-hypopnea events from the ECG or respiratory channels (e.g. Varon et al. 2015; Koley and Dey 2013).”

3) The data were curated with some recordings or portions of recordings being excluded (see p. 7). While I understand that this curation is important for the training set, I think it should not be applied to the test set. Indeed, it goes contrary to the logic of automating sleep staging. For example, cutting the beginning and end of the recording according to sleep start and end (p. 7) supposes that the start and end of sleep are already known (i.e. it has already been scored).

This truncation step has now been removed from the pipeline and all the results have been updated accordingly. In addition, we have also removed all other exclusion criteria (e.g. PSG data quality, recording duration, etc) to improve the generalization power of the algorithm, thanks to the suggestions of the reviewer.

4) Two types of EEG derivations were used (C4-M1 or C4-Fpz). Was the performance impacted by this variable? Is it fair to assume that the choice of features (spectral features or summary statistics of time series data) could explain the absence of differences but that introducing new features (i.e. phase-sensitive features) could increase the influence of the choice of the derivation?

Thanks for raising this. First, our choice of the EEG reference was determined by the datasets: the CFS, CCSHS, MrOS, CHAT and HomePAP datasets were all referenced to Fpz, while the MESA, SHHS and DOD datasets were referenced to the contralateral mastoid. The montage of each dataset has now been added to the Methods section.

Second, as rightly pointed out by the reviewer, the features implemented in the algorithm were chosen to be robust to various recording montages. This is now explicitly discussed in the “Features extraction” subsection of the Methods:

“The features included in the current algorithm were chosen to be robust to different recording montages. As such, we did not include features that are dependent on the phase of the signal, and/or that require specific events detection (e.g. slow-waves, rapid eye movements). However, the time-domain features are dependent upon the amplitude of the signal, and the algorithm may fail if the input data is not expressed in standard units (uV) or has been z-scored prior to applying the automatic sleep staging.”

5) Given that markers of sleep stages are very different in EOG, EMG and EEG time series, could the authors explain the logic behind applying the same pre-processing and extracting the same features on these three very different types of data? Could this explain why the majority of the features in the top-20 features were EEG features?

We now provide a more detailed explanation on the inclusion of EOG and EMG features in the “Features extraction” subsection of the Methods:

“These features were selected based on prior work in features-based classification algorithms for automatic sleep staging (Krakovská and Mezeiová 2011; Lajnef et al. 2015; Sun et al. 2017). For example, it was previously reported that the permutation entropy of the EOG/EMG as well as the EEG spectral powers in the traditional frequency bands are the most important features for accurate sleep staging (Lajnef et al. 2015), thus warranting their inclusion in the current algorithm. Several other features are derived from the authors’ previous works with entropy/fractal dimension metrics1. ” https://github.com/raphaelvallat/antropy

Furthermore, we have added a “Limitations and future directions” section in the Discussion in which we propose future improvements of the algorithm. One of these potential improvements is the development of EOG and EMG features that would provide a higher discrimination of the sleep stages:

“This suggests that one way to improve performance on this population could be the inclusion of more EEG channels and/or bilateral EOGs. For instance, using the negative product of bilateral EOGs may increase sensitivity to rapid eye movements in REM sleep or slow eye movements in N1 sleep (Stephansen et al. 2018; Agarwal et al. 2005). Interestingly, the Perslev 2021 algorithm does not use an EMG channel, which is consistent with our observation of a negligible benefit on accuracy when adding EMG to the model. This may also indicate that while the current set of features implemented in the algorithm performs well for EEG and EOG channels, it does not fully capture the meaningful dynamic information nested within muscle activity during sleep.”

6) Sleep scoring guidelines incorporate not only what can be observed on a given epoch of data but also what is observed in the previous epoch(s). For example, an epoch can be scored as N2 even if there is no marker of N2 but there was (i) a marker of N2 in a previous epoch, (ii) no reason to change the score since. To reproduce this, the authors employed a symmetrical smoothing approach (a combination of a triangular-weighted rolling average and asymmetrical rolling average). Why did the authors choose to incorporate data from following epochs, which is not implemented in established guidelines? How was the duration of the smoothing window chosen? Indeed, 5 minutes appear as rather long could explain the poor performance of the algorithm for fast changing portions of the data (i.e. N1 or transitions). Importantly, these transitions can be very relevant in clinical settings and to establish a diagnosis.

This is a great question. We have addressed this in the revised manuscript.

Temporal smoothing

We have also conducted a new analysis of the influence of the temporal smoothing on the performance. The results are described in Supplementary File 3a. Briefly, using a cross-validation approach, we have tested a total of 49 combinations of time lengths for the past and centered smoothing windows. Results demonstrated that the best performance is obtained when using a 2 min past rolling average in combination with a 7.5 minutes centered, triangular-weighted rolling average. Removing the centered rolling average resulted in poorer performance, suggesting that there is an added benefit of incorporating data from both before and after the current epoch. Removing both the past and centered rolling averages resulted in the worst performance (-3.6% decrease in F1-macro). Therefore, the new version of the manuscript and algorithm now uses a 2 min past and 7.5 min centered rolling averages. All the results in the manuscript have been updated accordingly. We have now edited the “Smoothing and normalization” subsection of the Methods section as follow:

“In particular, the features were first duplicated and then smoothed using two different rolling windows: 1) a 7.5 minutes centered, and triangular-weighted rolling average (i.e. 15 epochs centered around the current epoch with the following weights: [0.125, 0.25, 0.375, 0.5, 0.625, 0.75, 0.875, 1., 0.875, 0.75, 0.625, 0.5, 0.375, 0.25, 0.125]), and 2) a rolling average of the last 2 minutes prior to the current epoch. The optimal time length of these two rolling windows was found using a parameter search with cross-validation (Supplementary File 3a). [...] The final model includes the 30-sec based features in original units (no smoothing or scaling), as well as the smoothed and normalized version of these raw features.”

Reviewer #3 (Public Review):

This study presents a new sleep scoring tool that is based on a classification algorithm using machine-learning approaches in which a set of features is extracted from the EEG signal. The algorithm was trained and validated on a very large number of nocturnal sleep datasets including participants with various ethnicities, age and health status. Results show that the algorithm offers a high level of sensitivity, specificity and accuracy matching or sometimes even exceeding that of typical interscorer agreement. The conclusions are supported by the data. Importantly, a measure of the algorithm's confidence is provided for each scored epoch in order to guide users during their review of the output. The software is described as easy to use, computationally low-demanding, open source and free. This paper addresses an important need for the field of sleep research. There is indeed a lack of accurate, flexible and open source sleep scoring tools. I would like to commend the authors for their efforts in providing such a tool for the community and for their adherence to the open science framework as the data and codes related to the current manuscript are made available. I predict that this automated tool will be of use for a large number of researchers in the field. However, there are plenty of automated sleep scoring tools already available in the field (most of them are not open source and rather expensive, as noted by the authors). The current work does not provide a clear view on whether the new algorithm presented in this research performs better than algorithms already available in the field. No formal comparisons between algorithms is provided and the matter is not discussed in the paper.

Thanks so much for pointing this out. We have now added this relevant reference throughout the manuscript. To build on the reviewer’s point, the current algorithm and Stephansen’s algorithm did not use the same public data. The Stephansen 2018 algorithm was trained and validated on “10 different cohorts recorded at 12 sleep centers across 3 continents: SSC, WSC, IS-RC, JCTS, KHC1, AHC, IHC, DHC, FHC and CNC”, none of which are included in the training/testing sets of the current algorithm. Nevertheless, we certainly agree that the manuscript will benefit from a more extensive comparison against existing tools. To this end, we have made several major modifications to the manuscript. First, we have added a dedicated paragraph in the Introduction to review existing sleep staging algorithms:

“Advances in machine-learning have led efforts to classify sleep with automated systems. Indeed, recent years have seen the emergence of several automatic sleep staging algorithms. While an exhaustive review of the existing sleep staging algorithms is out of the scope of this article, we review below — in chronological order — some of the most significant algorithms of the last five years. For a more in-depth review, we refer the reader to Fiorillo et al. 2019. The Sun et al. 2017 algorithm was trained on 2,000 PSG recordings from a single sleep clinic. The overall Cohen's kappa on the testing set was 0.68 (n=1,000 PSG nights). The “Z3Score” algorithm (Patanaik et al. 2018) was trained and evaluated on ~1,700 PSG recordings from four datasets, with an overall accuracy ranging from 89.8% in healthy adults/adolescents to 72.1% in patients with Parkinson’s disease. The freely available “Stanford-stage” algorithm (Stephansen et al. 2018) was trained and evaluated on 10 clinical cohorts (~3,000 recordings). The overall accuracy was 87% against the consensus scoring of several human experts in an independent testing set. The “SeqSleepNet” algorithm (Phan et al. 2019) was trained and tested using a 20-fold cross-validation on 200 nights (overall accuracy = 87.1%). Finally, the recent U-Sleep algorithm (Perslev et al. 2021) was trained and evaluated on PSG recordings from 15,660 participants of 16 clinical studies. While the overall accuracy was not reported, the mean F1-score against the consensus scoring of five human experts was 0.79 for healthy adults and 0.76 for patients with sleep apnea.”

Second, and importantly, we now perform an in-depth comparison of YASA’s performance against the Stephansen 2018 algorithm and the Perslev 2021 algorithm using the same data for all three datasets. Specifically, we have applied the three algorithms to each night of the Dreem Open Datasets (DOD) and compared their performance in dedicated tables in the Results section (Table 2 and Table 3). This procedure is fully described in a new “Comparison against existing algorithms” subsection of the Methods. None of these algorithms included nights from the DOD in their training set, thus ensuring a fair comparison of the three algorithms. Related to point 4 of the Essential Revisions, performance of the three algorithms are reported separately for healthy individuals (DOD-Healthy, n=25) and patients with sleep apnea (DOD-Obstructive, n=50). To facilitate future validation of our algorithm, we also provide the predicted hypnograms of each night in Supplementary File 1 (healthy) and Supplementary File 2 (patients).

Overall, the comparison results show that YASA’s accuracy is not significantly different from the Stephansen 2018 algorithm for both healthy adults and patients with obstructive sleep apnea. The accuracy of the Perslev 2021 algorithm is not significantly different from YASA in healthy adults, but is higher in patients with sleep apnea. However, it should be noted that while the YASA algorithm only uses one central EEG, one EOG and one EMG, the Perslev 2021 algorithm uses all available EEGs as well as two EOGs. This suggests that adding more EEG channels and/or using the two EOGs may improve the performance of YASA in patients with sleep apnea. Though an important counterpoint is that YASA requires a far less extensive array of data (channels) to accomplish very similar levels of accuracy, which has the favorable benefit of reducing analysis computational and processing demands, improves speed of analysis (i.e. a few seconds per recording versus ~10 min for the Stephansen 2018 algorithm), and is amenable to more data recordings since many may not have sufficient EEG channels. All these points are now discussed in detail in the new “Limitations and future directions” subsection of the Discussion (see point 3 of the Essential Revisions).

There are some overstatements in the manuscript. For example, the algorithm was trained and validated on nocturnal sleep data. Sleep characteristics (eg duration and distribution of sleep stages etc.) are different, for example, during diurnal sleep (nap) and the algorithm might not perform as well on nap data. As such, the tool might not be as "universal" as stated in the title. Additionally, as human scores are used as the ground-truth for the validation step, it might be misleading to state that "this tool offers high sleep-staging accuracy matching or exceeding human accuracy". The algorithm exceeded the accuracy of some human scorers and matched the scores of the best scorer.

We have now removed the word “universal” from the title and replaced “exceeded human accuracy” with “matched human accuracy”. Furthermore, we have now added the fact that the algorithm was trained and validated only on nocturnal data in the Limitations section of the discussion, and as such, noted that there is the possibility that the algorithm may not perform at the same accuracy levels for daytime nap data.

No reflection on further improvement is offered in the paper. The algorithm performs worse on N1 stage, older individuals and patients presenting sleep disorders (sleep fragmentation) and it is unclear how this could be improved in future research. In the same vein, the current work does not present performance accuracy separately for healthy individuals and patients when it is expected that accuracy would be poorer in the patient group.

The revised manuscript now includes a dedicated section in the Discussion to propose ideas for improvements.

First, we have now added a “Limitations and Future Directions” subsection in the Discussion to present ideas for improving the algorithm, with a particular focus on fragmented nights and/or nights from patients with sleep disorders:

“Despite its numerous advantages, there are limitations to the algorithm that must be considered. These are discussed below, together with ideas for future improvements of the algorithm. First, while the accuracy of YASA against consensus scoring was not significantly different from the Stephansen 2018 and Perslev 2021 algorithms on healthy adults, it was significantly lower than the latter algorithm on patients with obstructive sleep apnea. The Perslev 2021 algorithm used all available EEGs and two (bilateral) EOGs, whereas YASA’s scoring was based on one central EEG, one EOG and one EMG. This suggests that one way to improve performance in this population could be the inclusion of more EEG channels and/or bilateral EOGs. For instance, using the negative product of bilateral EOGs may increase sensitivity to rapid eye movements in REM sleep or slow eye movements in N1 sleep (Stephansen et al. 2018; Agarwal et al. 2005). Interestingly, the Perslev 2021 algorithm does not use an EMG channel, which is consistent with our observation of a negligible benefit on accuracy when adding EMG to the model. This may also indicate that while the current set of features implemented in the algorithm performs well for EEG and EOG channels, it does not fully capture the meaningful dynamic information nested within muscle activity during sleep.”

Second, we have now conducted a random forest analysis to identify the main contributors of accuracy variability. The analysis is described in detail in the “Moderator Analyses” subsection of the Results as well as Supplementary File 3b, the revision now states:

“To better understand how these moderators influence variability in accuracy, we quantified the relative contribution of the moderators using a random forest analysis. Specifically, we included all aforementioned demographics variables in the model, together with medical diagnosis of depression, diabetes, hypertension and insomnia, and features extracted from the ground-truth sleep scoring such as the percentage of each sleep stage, the duration of the recording and the percentage of stage transitions in the hypnograms. The outcome variable of the model was the accuracy score of YASA against ground-truth sleep staging, calculated separately for each night. All the nights in the testing set 1 were included, leading to a sample size of 585 unique nights. Results are presented in Supplementary File 3b. The percentage of N1 sleep and percentage of stage transitions — both markers of sleep fragmentation — were the two top predictors of accuracy, accounting for 40% of the total relative importance. By contrast, the combined contribution of age, sex, race and medical diagnosis of insomnia, hypertension, diabete and depression accounted for roughly 10% of the total importance.”

In addition, the performance of the algorithm in the DOD testing dataset is now reported separately for healthy individuals and patients with sleep disorders.

As requested by the reviewer, we now analyze and report the performance of YASA on the DOD testing set separately for healthy individuals (DOD-healthy) and patients with obstructive sleep apnea (DOD-Obstructive), which can be found in section “Testing set 2”.

There is series of methodological choices that is not justified. For example, nights were cropped to 15 minutes before and after sleep to remove irrelevant extra periods of wakefulness or artefacts on both ends of the recording. This represents an issue for the computation of important sleep measures such as sleep efficiency and latency as the onset/offset of sleep might be missed. It is also unclear how the features were selected and a description of said features is currently missing. The custom sleep stage weights procedure is unclear. The length of the time window for the smoothing procedure seems arbitrary. Last, it is currently unclear when / how the EEG and EMG data were analyzed.

As recommended by the reviewers, the 15-min truncation step has now been removed from the pipeline. Furthermore, the Methods section has been improved to provide more details on the features. Finally, the best class-weights and smoothing windows are now found using a cross-validation analysis on the training set. For more details, we refer the reviewer to the “Justification for some methodological choices” section below.

It's rare to come across a take so truly contrarian.

I opened browser windows before I had a browser with tabs; in the days before whatever fun TCP multiplexing they have now, it helped maximize the juice I got out of our creaking dialup. I loved that when traversing Wikipedia, if your windows opened just to the right of the open window, you could go all the way down one depth-first rabbit hole and pop back up to the next path. Even if that non-linearity was less efficient somehow, I love it fiercely.

SciScore for 10.1101/2021.08.10.21261836: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

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SciScore for 10.1101/2021.08.12.455901: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

One limitation is the uncertainty of the exact timing of exposure/infection, as infections were identified by screening at entry into Cambodia rather than in a direct surveillance or community cohort. Studies assessing long-term immunity to SARS-CoV-2 in Asian populations are scarce (16, 32–34, 41). In addition, studies on cross-reactivity of the humoral and cellular compartment with other hCoVs have mainly focused on European and US populations (42–45). Historically, the population in East Asia seems to be more exposed to coronavirus-like viruses as only East Asian population show genetic adaptation to coronaviruses (46). The main natural reservoir of SARS-related coronaviruses is believed to be Horseshoe bats (genus Rhinolophus), which are endemic to Southeast Asia and China (47–49). Whether possible cross-reactivity to other coronavirus-like viruses or hCoVs may have influenced the adaptive immune response to SARS-CoV-2 in Southeast Asian populations remained to be investigated. As expected, anti-S IgM, IgG and IgA titers declined over time and anti-S IgG becomes the major isotype at late convalescence (24, 50–52). In this study, IgA titers were the most affected over time. The formation of anti-S IgA is shown to be dependent on local lung inflammation (53–55) hence titers decline the strongest in asymptomatic/mild patients. Titers of neutralizing antibodies are reported to reach their maximum within the first month after infection and then decay, but mostly remain detecta...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 42. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.08.13.456066: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

A further limitation is that here presented data was generated using the D614G variant close to Wuhan wildtype strain, while the pandemic is currently driven by SARS-CoV-2 variants of concern and - interest. However, polyclonality of IVIG/SCIG could render a complete neutralization evasion of variants less likely as compared to monoclonal therapies, while for CP (from one donor, respectively) immune escape of variants of concern from neutralization has been shown of approximately 15x, underscoring the general notion that optimal neutralization/protection is achieved against the isolate that caused the immune response [57]. In a passive immunization setting with IVIG/SCIG, this means not only trailing the epidemiology of donors in terms of neutralizing titer but also in terms of quality, meaning which variants will be neutralized best.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.08.12.456131: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: Thank you for sharing your code.

Our approach has several limitations that are worth noting. Most importantly, we analyze each gene family separately and thus cannot infer recombination events that affect only parts of genes. Moreover, uncertainly and error in HGT inference and in assigning donors and recipients can make it difficult to infer larger recombination events that affect multiple genes. This limitation can be partially addressed by using a window-based analysis, rather than a gene-based analysis, but small windows risk having too little meaningful phylogenetic signal while large windows risk averaging over several different overlapping recombination events. Another limitation of our approach and analysis is that it ignores low-support HGTs. Low-support HGTs cannot be disregarded altogether, especially when the strains being analyzed contain short genes. Short genes, such as the E, ORF7b, and ORF10 gene families in our Sarbecovirus analysis, often have less phylogenetic signal and thus more uncertain gene tree topologies and inferred events. A closer analysis of low-support HGTs, especially those affecting short genes, may thus lead to additional evolutionary insights.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.08.12.21261806: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

A possible limitation to such outcome is the decrease in SARS-CoV-2 virus circulation <0.79 in France by mid-May 2021, versus 1.2 or 1.3 in late January 2021. However, a dramatic rise in infections occurred early July, resulting in >20,000 new daily cases. The patient acceptation rate of systematic vaccination was in line with previous reports, with only 11% initial refusals29. Reactogenicity was weak, without short-term serious adverse effects in this real-life setting. We did not observe specific safety concerns in ICI-treated patients, especially regarding immune-related side-effects, as reported by Israeli teams30. Moreover, our study emphasized that sero-conversion monitoring could be useful in immuno-suppressed patients. In this population, the first vaccine efficacy was much lower than that reported in vaccine registration trials, with one-third of patients displaying negative serological testing (≤50 AU/mL) at Day 28, whereas three-quarters exhibited <25 percentile serological titer distribution. These data are in line with prospective studies involving a mixed population with solid cancers and hematological malignancies31, 32. Although there has been no clear cut-off for antibody titers predicting protection against severe COVID-19, a 300 AU/mL cut-off was shown to well correlate with the pseudo-neutralization assay, as a readout for anti-viral efficacy. We thus selected this value as protection cut-off against SARS-CoV-2 infection in our patients33. Let us keep in m...

Results from TrialIdentifier: We found the following clinical trial numbers in your paper:<br><table><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Identifier</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Status</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Title</td></tr><tr><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">NCT04776005</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">Not yet recruiting</td><td style="min-width:95px; border-right:1px solid lightgray; border-bottom:1px solid lightgray">COVID-19 Vaccine Efficacy in Patients With Malignant Patholo…</td></tr></table>

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

Author Response:

Reviewer #1:

The authors demonstrate deficits in perceptual tests related to fine-time perception in non-speech and speech sounds in a group of patients with stroke aphasia compared to a control group without a lesion. A subgroup of patients with deficits in spectrotemporal processing at a fine timescale have lesions mapped to the posterior STS, MTG and adjacent white matter. The area associated with deficits in spectrotemporal analysis with a fine timescale is then used as a seed for probabilistic fibre tractography based on diffusion MR. These results show connectivity of the functionally defined seed region with a number of areas including the cerebellum.

The work is carefully done and I think interesting in demonstrating the cerebellar connections of the functionally defined region associated with deficits in fine temporal analysis that might be a basis for event representation at this temporal level.

We appreciate the referee's evaluation and constructive feedback.

Reviewer #2:

Based on consideration of supportive evidence in the literature, the authors propose that a cerebellar-temporal lobe functional network plays a key role in auditory temporal processing. The precise parsing of temporal information is critical to understanding dynamic auditory processing and thus is an interesting area of study. Better understanding of how the cerebellum and temporal lobe may interact to achieve such parsing of the dynamic signal in a generative/predictive internal model is of clear interest to a broad readership. This idea is put to the test by first having individuals with lesions in the posterior portion of left temporal lobe perform speech perception and timing tasks and comparing performance with 12 healthy controls to establish the role of this region in tasks reliant on intact fine temporal processing. Typically, a lesion model will be helpful when a dissociation between structure and function can be demonstrated, and preferably this would be a double dissociation. Here, while lesions to auditory regions of the left temporal lobe are associated with impoverished performance on speech and temporal order tasks relative to a healthy control group, performance on comparably difficult auditory tasks that do not require good temporal discrimination is not tested to determine if there is such a dissociation. Given the extensive discussion of hypothesized different time sensitivities of right and left auditory cortices in the Introduction, patients with right homologous lesions might also have served as an interesting control and could have supported a double dissociation. In a second step to their study, a seed region was generated based on comparison of the lesion loci for the half of the patients who performed most poorly on the behavioral tasks to the other half, and this was used to explore anatomical tract connectivity of the seed region to the rest of the brain in the neuroimaging data from the healthy controls, with a focus on connections with the cerebellum. This approach to establishing that "temporo-cerebellar connectivity underlies timing constraints in audition" is unfortunately just not that convincing. The data are interesting, but taken alone they simply do not support such a conclusion. In the data, there is no clear functional link established or even hinted at between the temporal lobe and the cerebellum.

We appreciate the referee's evaluation and constructive feedback. We address the raised concerns point by point below. We appreciate the concerns regarding our methodological choice and our interpretation of a functional link between the temporal lobe and the cerebellum. It certainly is more reasonable to derive a functional interpretation based on disconnection measured directly in patients’ DTI. However, if unavailable, indirect measures of disconnection can also be used to establish a functional link between a lesioned region and the networks associated with it. The rationale behind this is that it reflects an indirect estimation of the effect of a lesion on structural brain networks. To make this approach clearer, we have revised the manuscript accordingly. See revised manuscript pages 6 and 12:

[...] Assessing connectivity in healthy participants based on lesion information is a relatively new method that measures structural disconnection in networks associated with given anatomical regions (Foulon et al., 2018). This allows for the indirect estimation of the lesion effect on structural brain networks. In this regard, it was shown that behavioral deficits can be explained similarly by local brain damage and indirectly measured disconnection (Salvalaggio et al., 2020). [...]

[...] We next used the respective areas as seed regions for probabilistic fiber tractography in a healthy age-matched sample to visualize the underlying common connectivity pattern (see Methods). Thus, we indirectly explored the association between posterior superior temporal disconnection and processing of sound at short timescales. [...]

We also changed the abstract and conclusion accordingly. See pages 2 and 15 of the revised manuscript.

[...] Here we tested whether temporo-cerebellar disconnection is associated with the processing of sound at short timescales. [...]

[...] The evidence we describe (i) shows that lesion-related deficits in spectrotemporal analysis occur in posterior temporal regions connected to the cerebellum [...].

Reviewer #3:

Stockert et al. investigate the cortico-cerebellar network underpinning rapid temporal auditory analysis. This study uses a well-defined group of stroke participants with mostly circumscribed lesions to the left posterior superior temporal lobe to motivate probabilistic tractography from cortical regions associated with verbal and non-verbal rapid auditory temporal analysis. Lesion-symptom mapping identifies a specific region of the posterior superior temporal sulcus and underlying white matter as statistically associated with impairment in rapid auditory temporal analysis. Tractography results demonstrate that these regions have high structural connectivity to wider regions of the left hemisphere cortical language network and ipsilateral and contralateral connectivity to postero-lateral cerebellum and dentate nucleus. It is interpreted that this cortico-cerebellar network is crucial to developing representations of fine auditory temporal structure.

The conclusions of the paper are an interpretation which is based on integrating previous neuropsychology with the current tractography results and based on well-defined models in the motor domain. Such conclusions are not unreasonable but there is no direct (associative) evidence linking this network to the cognitive function of interest.

Strengths:

The paper integrates neuropsychology and neuroimaging methodologies to build a coherent picture which is more than the sum of its parts. The stroke group has well-defined and selected lesions which enable testing of the hypotheses put forward by the authors. The behavioural measures are sensitive and suitable to identify impairments in the behaviours of interest. There has been a detailed analysis of the behavioural speech perception data in the stroke group which largely, although perhaps not entirely, conforms to the asymmetric temporal sampling hypothesis. The lesion-symptom mapping approach is suitable for the nature of the population (small group with similar lesion distributions) and has allowed neuropsychologically guided tractography in the neurotypical population. This has clearly illustrated the complexity of the structural connectivity of the posterior superior temporal sulcus and underlying regions.

Weaknesses:

The selective nature of the stroke population - relatively small, chronic lesions - has resulted in only mild impairments for a small number of participants (6/12 participants). At the group level there is no difference between the stroke and neurotypical population on speech perception measures - group statistics do not reach one tailed significance. This reduces the certainty with which the regions identified are associated with the behaviour or interest. However, the results do conform to previous neuropsychology and lesion studies and it is likely that this lack of effect is due to low statistical power.

Please refer to our response to the next point.

All the stroke participants have a similar lesion distribution, and this makes lesion-symptom mapping challenging. For example, lesion data do not give an indication of the functional integrity of perilesional regions which can be reduced, even at the chronic stage, therefore the superior temporal sulcus may not be functioning effectively, even in the proportion of the group without lesions to this area. Lesion symptom mapping is more robust with a wider distribution of lesions and the inclusion of participants with lesions remote from the area of interest. Having said that, the behavioural measures appear sensitive enough to identify mild impairments and the authors, for good reason, wished to reduce the extension of lesion into primary auditory regions. As above, given the limited sample and homogeneous lesion, the lesion symptom mapping approach is reasonable.

We agree that the small number of patients is a possible limitation to the study and add this point to the limitations section. See revised manuscript page 21.

[...] First, the study population is relatively small and lesion symptom mapping is typically applied to larger populations with wider lesion distribution. Although careful selection of circumscribed lesions has the advantage of highlighting behavioral differences without confounding other deficits (e.g., primary auditory processing), it is possible that additional regions are involved in processing of sound at short timescales. However, tractography based on healthy participants makes it possible to indirectly obtain information (i.e., structural disconnection) about brain regions contributing to the investigated function. In addition, it is likely that the small number of patients might hamper the ability to detect statistically significant differences between the behavior of controls and patients. Nevertheless, we are confident that the current results align with the fact that the posterior superior temporal cortex contributes to the processing of sound at short timescales, as indicated by previous neuropsychological evidence and lesion studies (Boemio et al., 2005; Chedru, Bastard, and Efron, 1978; Efron, 1963; Robson, Grube, Lambon Ralph, Griffiths, & Sage, 2013; Swisher & Hirsh, 1972). Further studies should however test larger populations to replicate and extend this finding. [...]

The authors suggest that the behavioural results conform to the asymmetric temporal sampling hypothesis in that only place of articulation discrimination impairments in the stroke group can be (just about) detected, whereas there were no significant stroke-neurotypical differences in other phonetic contrasts. It is not clear that the VOT differences associated with plosive voicing changes and the cues associated with place changes happen over fundamentally different time-scales and, therefore, it is important to further justify the interpretation of the data. In the future it will be helpful to have this level of analysis applied to individuals with lesions to the wider speech perception network to draw conclusions about the specificity of the impairment to these regions - for example, impairments in phoneme discrimination have been associated with frontal lobe lesions.

It appears that voicing contrasts in which shorter and longer voice onset times result in the perception of a voiced or voiceless plosive (for example [t] and [d]) are encoded in both the temporal envelope and fine structure (Rosen 1992) of the speech signal that occur in time windows of 20-500 ms and <2 ms, respectively. In words an additional cue is the closure time, which can be further used to discriminate between voiced and voiceless plosives. However, place of articulation contrasts are exclusively encoded in the temporal fine structure (i.e., very quick transitions of the frequency spectrum, formant transitions). Even though for all contrasts shorter timescale information plays a role, somewhat redundant encoding is present for voice contrasts. Ultimately, place of articulation contrasts seem to be the most difficult to discriminate. In Figure 2D it is apparent that despite highest error rates for the place of articulation contrasts, several patients also showed impaired discrimination for voicing contrast when compared to healthy controls. We do agree with the referee that it would be interesting to also extend this level of analysis to individuals with lesions in the wider speech perception network in future work.

The tractography results reveal a complex pattern of structural connectivity, including other regions associated with speech perception. The authors have a theoretical motivation to focus on the importance of the temporo-cerebellar pathway but there is no correlation evidence to link auditory temporal analysis to the integrity of this pathway in the neurotypical population. The non-verbal measures appear to be sufficiently sensitive for this type of analysis. This lack of association with behaviour makes it hard to draw conclusions about the functional role of this network.

We appreciate the referee’s concerns about our interpretation of the functional link between the temporal lobe and the cerebellum regarding auditory temporal analysis. It certainly is more reasonable to derive a functional interpretation based on disconnection measured directly in patients DTI. However, if unavailable, indirect measures of disconnection can also be used to establish a functional link between a lesioned region and the networks associated with it. The rationale behind this is that it reflects an indirect estimation of the effect of a lesion on structural brain networks. To make this approach clearer, we have modified the manuscript as such. See revised manuscript pages 6 and 12:

[...] Assessing connectivity in healthy participants based on lesion information is a relatively new method that measures structural disconnection in networks associated with given anatomical regions (Foulon et al., 2018). This allows for the indirect estimation of the effect of a lesion on structural brain networks. In this regard, it has been shown that behavioral deficits are explained to a similar extent by both the local damage and indirectly measured disconnection (Salvalaggio et al., 2020). [...]

[...] We next used the respective areas as seed regions for probabilistic fiber tractography in a healthy age-matched sample to visualize the underlying common connectivity pattern (see Methods). Thus, we indirectly explored the association between posterior superior temporal disconnection and processing of sound at short timescales. [...]

We also changed the abstract and conclusion accordingly. See revised manuscript pages 2 and 15.

[...] Here we tested whether temporo-cerebellar disconnection is associated with processing of sound at short timescale. [...]

[...] The evidence we describe (i) shows that lesion-related deficits in spectrotemporal analysis occur in posterior temporal regions connected to the cerebellum [...].

.c2

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DOI: 10.1523/ENEURO.0373-16.2017

Resource: XPP-Aut: X-Windows Phase Plane plus Auto (RRID:SCR_001996)

Curator: @scibot

SciCrunch record: RRID:SCR_001996

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Qme4bLv4wxfof9ixTMj5e2eUJLJy3U7W4kKNAoNFKH4u6q

potentially free skype replacement

SciScore for 10.1101/2021.08.05.21261610: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Limitations may occur in observational serological surveys; e.g., sample demographics may not be fully representative of the state, which is true for some variables in the current survey. Sampling variability or selection biases may operate within small time windows of a serological survey, and can result in inaccuracies in seroprevalence estimates. It will therefore generally be necessary to smooth estimates using a chosen time window dependent on factors such as the magnitude of the wave of infection and participant accrual rate. Fortunately, we observe that the application of an isotonic restriction to reflect the assumption that seroprevalence should not decrease in a reasonably small time window mostly overcomes the issue of daily or weekly sampling variability. Further, it is necessary to estimate the percentage of people who have both had natural COVID-19 infection and are fully vaccinated in a given time window in order to subtract that proportion from the overall sum. Finally, it is important to age-adjust estimated serological and vaccination rates to the state census so they are commensurate with population demographics. This is especially important since vaccination was rolled out by age group, with older adults first priority in January-March 2021. To our knowledge, this is the first fully data-driven estimation of total immunity to SARS-CoV-2 in the state of Texas, which is the second largest state in the US with a population of 29.2 million. The method proposed...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

SciScore for 10.1101/2021.07.30.21261400: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

An important limitation of the current study is that, while we were able to show significant differences between the post-slowdown and pre-slowdown cohorts, we cannot identify a specific cause. One possible explanation is that the lack of screening procedures during the slowdown period resulted in more cancers going undetected at an earlier stage and that this led to a disproportionate number of advanced cancers in the post-slowdown cohort. This explanation would apply to those patients who would have normally undergone a screening procedure but were delayed/cancelled due to the slowdown. Another possible explanation is that some people may have been reluctant to seek medical attention. This may have been out of personal fear of COVID-19 or out of respect for government messaging to stay at home. Thus, some people may have discounted early warning signs and only presented to hospital once they had developed “alarm” symptoms (e.g., persistent abdominal pain). Unfortunately, both explanations involve system failures at a population level. In summary, our findings demonstrate that health care policies put in place at the beginning of the COVID-19 pandemic in Ontario, Canada were ultimately associated with more advanced disease in patients diagnosed with CRC. Worsening cancer burden not only increases patient morbidity and mortality, but also has long-term social and economic effects on oncological care. Governments and health authorities should consider these results when creati...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a protocol registration statement.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

через дефис

.imp 可视性和易通性，感觉这个翻译不够好呢 discovery和understand，一个是发现，一个是理解。

发现是要高效找得到，理解是要行为可驯化。 找不到功能键的平台，和用了十次都找不到的规律的工具，除非解决的问题够难，否则都没有存活的价值。

yea 很好，这就达到了一种协作的机制

The way that Joyce is describing the scenery is very reminiscent of how Mansfield describes the scenery of their stories. Vivid imagery, very detailed, describing everything down to the weather.

there's a lot of these garden path sentences. i always have to go back and read them a second time because without a comma it becomes quite ambiguous to the reader

SciScore for 10.1101/2021.07.28.21261284: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Table 2: Resources

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Although we rigorously analyzed data from many relevant COVID-19 studies, our study suffered some limitations, including heterogeneity across studies included for exploring the association of disease severity with any comorbidity, cardiovascular disease, and female gender but not age and respiratory tract diseases. This heterogeneity is believed to have affected the plausibility of some of our results. This study also focused retrospectively on specific comorbidities only, which entails more extensive prospective studies to establish the causality between severe COVID-19 and other comorbidities such as gastrointestinal, renal, genetic, and neurological diseases.

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

• Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
• Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
• No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

About SciScore

SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.