This page is excellent for an example of HTML being an adequate substitute for traditional office formats.

https://www.youtube.com/watch?v=bWkwOefBPZY

Some of the basic outline of this looks like OER (Open Educational Resources) and its "five Rs": Retain, Reuse, Revise, Remix and/or Redistribute content. (To which I've already suggested the sixth: Request update (or revision control).

Some of this is similar to:

The Read Write Web is no longer sufficient. I want the Read Fork Write Merge Web. #osb11 lunch table. #diso #indieweb [Tantek Çelik](http://tantek.com/2011/174/t1/read-fork-write-merge-web-osb110

Idea of collections of learning as collections or "playlists" or "readlists". Similar to the old tool Readlist which bundled articles into books relatively easily. See also: https://boffosocko.com/2022/03/26/indieweb-readlists-tools-and-brainstorming/

Use of Wiki version histories

Some of this has the form of a Wiki but with smaller nuggets of information (sort of like Tiddlywiki perhaps, which also allows for creating custom orderings of things which had specific URLs for displaying and sharing them.) The Zettelkasten idea has some of this embedded into it. Shared zettelkasten could be an interesting thing.

Data is the new soil. A way to reframe "data is the new oil" but as a part of the commons. This fits well into the gardens and streams metaphor.

Jerry, have you seen Matt Ridley's work on Ideas Have Sex? https://www.ted.com/talks/matt_ridley_when_ideas_have_sex Of course you have: https://app.thebrain.com/brains/3d80058c-14d8-5361-0b61-a061f89baf87/thoughts/3e2c5c75-fc49-0688-f455-6de58e4487f1/attachments/8aab91d4-5fc8-93fe-7850-d6fa828c10a9

I've heard Jerry mention the idea of "crystallization of knowledge" before. How can we concretely link this version with Cesar Hidalgo's work, esp. Why Information Grows.

Cross reference Jerry's Brain: https://app.thebrain.com/brains/3d80058c-14d8-5361-0b61-a061f89baf87/thoughts/4bfe6526-9884-4b6d-9548-23659da7811e/notes

A lot of these ideas are junk. This one, though, is achievable. triplescripts.org.

Exponential change can happen if social tipping points are triggered by a few influencers have a change of heart because they have become educated on how the collective illusion operations, and how congruency of these few influencers can cause exponential change.

This is the key problem that makes current social media dangerous, it can be easily gamed due to this evolutionary shortcut of the brain, the fast system of biases aka Daniel Kahneman's research.

This impacts the whole Stop Reset Go transformation matrix: Individual Inner Transformation Individual Outer Transformation Collective Inner Transformation Collective Outer Transformation

According to researcher Todd Rose, author of the book Collective Illusions, conformity traps occurs when we succumb to collective illusions and create a gap between our private and public lives.

For a comparative analysis of Northanger Abbey's and Pride and Prejudice's depictions of the city in relation to contemporary ideas of the city "as moral pollution," see Celia Eason's essay, "Austen’s Urban Redemption: Rejecting Richardson’s View of the City." Easton shows us how characters like Isabella Thorpe and Mr. Bennet defy contemporary ideas that women were helpless in the city or that remaining ignorant of the city proved morally useful, respectively. As Catherine's character will prove, knowing how to navigate the city and its traps is essential for any young woman.

Citation: Easton, Celia. "Austen’s Urban Redemption: Rejecting Richardson’s View of the City." Persuasions, no. 26, 2004.

https://www.theescalanteprogram.org/

https://thecalculusproject.org/

Subject:Inequality, Planetary Boundary / Doughnut Economic Category: Wealth, Inequality

Similar to the way that bi-lingual/dual immersion language students may temporarily fall behind their peers in 3rd and 4th grade, but rocket ahead later in high school, those interested in interdisciplinary work may seem to lag, but later outpace their lesser specializing peers.

What is the underlying mechanism for providing the acceleration boosts in these models? Are they really the same or is this effect just a coincidence?

Is there something about the dual stock and double experience or even diversity of thought that provides the acceleration? Is there anything in the pedagogy or productivity research space to explain it?

The highest potential for demand side reduction among lifestyle change are: mobility, cooling setpoint adjustments, appliance usage, and diet.

climate and environment change (CEC)

This is a correlative argument by saying the increase of money in the broken system will cause it to become even more corrupt. A little bit further down, it talks about body cams and how with access to do that officers are able to change the footage to their liking.

Keeping a manual zettelkasten using pen/pencil and paper may be beneficial to some as it will tend to remove the easy functionality of cut and paste in the digital space and force the user to think a bit more deeply about what they're working on and expand on it. Those with paper zettelkasten aren't as likely to spend time collecting simple facts as a result of this. This will make the content going into the system much more solid and reusable in the future.

This is where I think Glitch goes wrong. Why such a focus on apps (and esp. pushing the same practices and overcomplicated architecture as people on GitHub trying to emulate the trendiest devops shovelware)?

"Web" is a red herring here. Make the Web more accessible for app creation, sure, but what about making it more accessible (and therefore simpler) for sharing simple stuff (like documents comprising the written word), too? Glitch doesn't do well at this at all. It feels less like a place for the uninitiated and more like a place for the cool kids who are already slinging/pushing Modern Best Practices hang out—not unlike societal elites who feign to tether themself to the mast of helping the downtrodden but really use the whole charade as machine for converting attention into prestige and personal wealth. Their prices, for example, reflect that. Where's the "give us, like 20 bucks a year and we'll give you better alternative to emailing Microsoft Office documents around (that isn't Google Sheets)" plan?

I'm not a fan of digs at the idea of our "Paleolithic memory", particularly as there is some reasonable evidence that oral memory methods in the Paleolithic are probably vastly superior to those "modern" humans are using now.

Cross reference: Kelly, Lynne. Knowledge and Power in Prehistoric Societies: Orality, Memory and the Transmission of Culture. Cambridge: Cambridge University Press, 2015. https://doi.org/10.1017/CBO9781107444973.

Social interactions with other students is undoubtedly a good thing. Online learning has its place as well.

This is a fine perspective as long as you're not penalizing people who arrive at 12:59:59 — "If you are on time, you are late" is a stupid mantra that, while my sample size is low, I've only heard from people who were themselves egregious time wasters and made the remarks as a way of honoring Ra.

(I'd argue further that anyone who arrives at any time between [13:00:00, 13:01:00) are doing okay, so long as they're wiling to accept that no one is obligated to wait for them. I.e. what "the meeting is at 1:00 PM" means is that everyone has permission to start the meeting at 13:00:00, whether you're there or not.)

"I'd want to learn a lot from Professor Zimmerman so that I may obtain as much information as possible and use it in reality. It's not about the work."

"I didn't fully understand it at the time, but throughout my time as a freshman at Boston College I've realized that I have the power to alter myself for the better and broaden my perspective on life. For most of my high school experience, I was holding to antiquated thoughts that had an impact on the majority of my daily interactions. Throughout my life, growing up as a single child has affected the way am in social interactions. This was evident in high school class discussions, as I did not yet have the confidence to be talkative and participate even up until the spring term of my senior year."

"The need to engage with people in terms of evaluating them for the aim of acquiring a different point of view was one occasion this semester where the knowledge I received in class positively changed the way I approached an issue. I was patient enough to explore other perspectives, some of which disagreed with mine, so that I might learn about their opinions without bias or prejudice."

Discussion, revision and decision

Decision

Verified manuscript — The content is scientifically sound, only minor amendments (if any) are suggested.

Revision

Reviewer: Dacre Knight

(1) Included the World Health Organization (WHO) and the National Institute for Health and CARE Excellence (NICE) definitions of PASC. See: Lines 51; 332-339

(2) The PECO criteria is listed (and not just implied) in the body of the manuscript. See: Lines 207-237.

Decision changed — Verified manuscript: The content is scientifically sound.

Reviewer: Yin Qianlan

(3) The purpose of the study was revised for clarity. See: Lines 114-171

Reviewer did not respond. Therefore, a third reviewer (Daniel Griffin) was asked to review the manuscript. They gave the decision, verified manuscript.

fen

often heard in the phrase forests and fens

https://www.merriam-webster.com/dictionary/and

My favorite phrase is "Yes, and..." because it provides hope and an opportunity to change things for the better. <- My personal deeper context.

wat

This site has a total of two pages! Just reify them as proper documents instead of compilation artifacts emitted from an SSG.

Agreed. NodeJS is developer tooling. It's well past the time where we should have started packaging up apps/utilities that are written in JS so that they can run directly in* the browser—instead of shamelessly targeting NodeJS's non-standard APIs (on the off-chance everyone in your audience is a technical user and/or already has it installed).

This is exactly the crusade I've been on (intermittently) when I've had the resources (time/opportunity) to work on it.

Eliminate implicit step zero from software development. Make your projects' meta-tooling accessible to all potential contributors.

* And I do mean "in the browser"—not "on a server somewhere that you are able to use your browser to access, à la modern SaaS/PaaS"

It's not nearly as timeless as a person might have themselves believe, though. (That's the "predilection" for certain technologies and doing things in a certain way creeping in and exerting its influence over what should otherwise be clear and sober unbiased thought.)

There's basically one timeless API, and that means written procedures capable of being carried out by a human if/when everything else inevitably fails. The best format that we have for conveying the content comprising those procedures are the formats native to the Web browser—esp. HTML. Really. Nothing else even comes close. (NB: pixel-perfect reproduction à la PDF is out of scope, and PDF makes a bunch of tradeoffs to try to achieve that kind of fidelity which turns out to make it unsuitable/unacceptable in a way that HTML is not, if you're being honest with your criteria, which is something that most people who advocate for PDF's benefits are not—usually having deceived even themselves.)

Given that Web browsers also expose a programming environment, the next logical step involves making sure these procedures are written to exploit that environment as a means of automation—for doing the drudge work in the here and now (i.e., in the meantime, when things haven't yet fallen apart).

Uh, it's the last element, though, not the first—right?

Bad idea to introduce this notation here at the same time as the (unexplained) use of square brackets to group a list of objects.

gene name: DICER 1 PMID (PubMed ID): 33570641 HGNCID: n/a Inheritance Pattern: autosomal dominant Disease Entity: benign and malignant tumor mutation Mutation: somatic Zygosity: heterozygous Variant: n/a Family Information: n/a Case: people of all sexes, ages, ethnicities and races participated CasePresentingHPOs: individuals with DICER1-associated tumors or pathogenic germline DICER1 variants were recruited to participate CasePreviousTesting: n/a gnomAD: n/a

If one thinks of a personal website as a performance, what is really being performed by the author?

Links and cross links, well done, within a website can provide a garden of forking paths by which a particular reader might explore a blog despite the fact that there is often a chronological time order imposed upon it.

Link this to the idea of using a zettelkasten as a biography of a writer, but one with thousands of crisscrossing links.

GeneName: DICER1 PMID: 28323992 PMCID: PMC5443331 *No HGNCID found Inheritance pattern: autosomal-dominant Disease Entity: multinodular goiter and thyroid cancer Mutation: Germline Zygosity: not listed Variant: c.3726C>A; p.Tyr1242a, c.3675C>G; p.Tyr1225a Family Information: 145 individuals with DICER1 germline mutations from 48 family controls (135 individuals) that lacked the DICER1 mutation Case: male and female carriers as well as family members were studied. Ages: 20, 30, and 40 for both populations (DICER1 carriers were significantly younger than controls}. Population from Great Britain, UK, and USA (no significant difference between race, ethnicity, or sex found). CasePresentingHPOs: no previous therapeutic radiation or chemotherapy. Thyroid cancer or MNG diagnoses were likely reported with the DICER1 mutation CasePreviousTesting: Sequencing performed with Sanger or next-generation sequencing assays. DICER1 carriers underwent testing to obtain thyroid-stimulating hormone, thyroxine, thyroxine-binding globulin, and serum albumin levels as well as medical history and physical examinations (+thyroid palpation). Participants were also given thyroid US examinations. gnomAD: n/a Mutation Type: missense

Advisory Committee on Immunization Practices- ACIP. (n.d.). Retrieved April 27, 2022, from https://video.ibm.com/channel/VWBXKBR8af4

Melton, J., & Sinclair, R. (2021). COVID-19 Infection Rates Are Related to Population Rates of Vaccination: A Response to Subramanian and Kumar.

"Social encoding advantage" is what psychologists refer to as the phenomenon of people remembering social information more accurately than other types.

Reference to read: “social encoding advantage”: Matthew D. Lieberman, Social: Why Our Brains Are Wired to Connect (New York: Crown, 2013), 284.

It's likely that the social acts of learning and information exchange in oral societies had an additional stickiness over and beyond the additional mnemonic methods they would have used as a base.

The Western cultural tradition doesn't value the social coding advantage because it "excludes social interaction from the realm of the intellect" (Paul, 2021). Instead it provides advantage and status to the individual thinking on their own. We greatly prefer the idea of the "lone genius" toiling on their own, when this is hardly ever the case. Our availability bias often leads us to believe it is the case because we can pull out so many famous examples, though in almost all cases these geniuses were riding on the shoulders of giants.

Reference to read: remember social information more accurately: Jason P. Mitchell, C. Neil Macrae, and Mahzarin R. Banaji, “Encoding-Specific Effects of Social Cognition on the Neural Correlates of Subsequent Memory,” Journal of Neuroscience 24 (May 2004): 4912–17

Reference to read: the brain stores social information: Jason P. Mitchell et al., “Thinking About Others: The Neural Substrates of Social Cognition,” in Social Neuroscience: People Thinking About Thinking People, ed. Karen T. Litfin (Cambridge: MIT Press, 2006), 63–82.

The process seen in cognitive apprenticeships seems more akin to the sorts of knowledge transfer done in primary oral indigenous cultures by passing down stories and performing (song, dance, art, etc.) knowledge.

It shouldn't be surprising that cognitive apprenticeships work well given their general use by oral cultures over millennia.

link to: Writing out answers will show gaps in knowledge Performing actions will show gaps in knowledge

word of the day

Seen in a meme used to describe Marjorie Taylor Greene who is testifying in a lawsuit against her today.

Imperial News. ‘“Issue of Inequalities” for Long COVID Patients Needs to Be Addressed | Imperial News | Imperial College London’. Accessed 22 April 2022. https://www.imperial.ac.uk/news/232234/issue-inequalities-long-covid-patients-needs/.

How to nerf all the inherent advantages of the things just described.

Discussion, revision and decision

Overall decision — Requires revisions: The manuscript contains objective errors or fundamental flaws that must be addressed and/or major revisions are suggested.

Responses to the reviewers

Reviewer Charlotte Martial

Decision — Requires revisions: The manuscript contains objective errors or fundamental flaws that must be addressed and/or major revisions are suggested.

1-The work does not cite relevant and sufficient literature. For instance, the authors do not cite a recent publication which aimed to induce OBE using hypnosis (Martial et al., Scientific Reports, 2019).

Reply: We re-read the procedure of this paper we were aware of, but we didn’t find any reference related to an OBE induced by hypnotic suggestions. Here follows an excerpt of the procedure as reported in the cited paper: “The hypnotic instruction included a 5-min induction procedure with eye fixation (ultimately closing the eyes) and progressive muscle relaxation. Permissive and indirect suggestions were used to develop and deepen the hypnotic state. The participant was then invited to re-experience their NDE memory (20 min) and their pleasant autobiographical memory (20 min) in a counterbalanced order, ..”

Thanks for the reply. I do not agree, though. As described in the paper, Martial and colleagues (2019) focused on two prototypical features of the NDE during the hypnosis session, that is, feeling of peacefulness and out-of-body experience. Consequently, I think it is highly relevant for the present paper.

Reply: we accepted this suggestion and added a paragraph about this application of hypnosis.

2-Another example: The authors could have at least briefly discussed Parnia’s AWARE prospective study reporting OBE in NDE experiencers (Parnia et al., 2014).

Reply: Thank you for this suggestion, now added in the introduction

3-Besides, they sometimes cite some inappropriate references; I would like to invite the authors to cite rigorous and serious articles in the field. For example, they used Jourdan (2011) reference to draw a parallel with NDEs, however, Jourdan (2011) is not a reference article in the field…

Reply: Jourdan’s (2011) paper “Near Death Experiences and the 5th Dimensional Spatio-Temporal Perspective. Journal of Cosmology, 14, 4743-4762 deals with NDE. It is not clear why it cannot be considered a reference article in the field.

Dr Jourdan and most of his articles are scientifically controversial. They are many other references more rigorous that you could cite in order to be scientifically stronger.

Reply: we have a different opinion about Jourdan’s scientific findings. As written in the paper, we referred to Jourdan’s paper only as a source to draw the questions to be used with the participants when in the OBE status.

4- Importantly, it is worth mentioning that, so far, no rigorous empirical scientific study has shown evidence of veridical perceptions during OBE; according to me, it is not clear in the manuscript.

Reply: On pag. 2 we added “and verify by a third-person perspective what they declare to perceive in this particular state of consciousness”.

I thank the authors. However, this is still not clearer in the manuscript. I suggest that the authors clearly state that so far, no rigorous empirical scientific study has shown evidence of veridical perceptions during OBE. This is highly important for a manuscript aiming to study OBE in laboratory settings.

Reply: added this suggestion at the end of the Introduction

5-Some limitations of the study are not mentioned in the discussion section

Reply: On pag. 14 there is a whole paragraph “Study limitations”.

Well, let me clarify: some of the limitations of the study are not discussed in the manuscript.

Reply: the “Study limitations” is added on pag. 15

6- Some details of the study are missing. Notably, the description of the Table 6 is incomplete: what do the bold numbers mean

Reply: we revised the presentation of the data in Table 6 and clarified why some data were presented in bold.

7- Another example: how did they recruit the participants –who are co-authors of the paper? Are they researchers?

Reply: We have revised the section related to the participants’ selection

8- page13: what do they mean by “general consensus”? This is not clear to me

Reply: We revised the text in “The answers of all five participants to the eleven questions presented in Table 4 and 5, were quite similar in content”

9-The conclusions they draw in the discussion are not based on the present findings; they extrapolate

Reply: Given in the paper there is not a “Conclusions” paragraph, to what “conclusions” do you refer to?

I mean the interpretation of their results … As an example, based on what do you conclude that “…in this state of consciousness they can act without the limitations that the physical body imposes on motion and perception especially with regard to vision”. It is not clear that you here mean that their subjective experience is related to their imaginary. Please reformulate.

Reply: This is not a conclusion, it is a simple summary of participants’ phenomenological reports “….from all of the participants’ reports, it appears that in this state of consciousness they can act ….”

what do you mean by “a three-dimensional universe”?

Reply: we corrected this sentence that now is “Time seems to be absent or similar to a sequence of video-clips, suggesting that they are living in a four-dimensional universe, very similar to that described as the “Block Universe” which represents space-time as a fixed whole in which past and future events already exist in the space-time continuum, in accordance with the special theory of relativity”.

Based on which data can you conclude that what they experienced is “very similar to or the same as that described in NDEs”.

Reply: we deleted this sentence

Reviewer Aminata Bicego

Decision — Verified with reservations: The content is scientifically sound, but has shortcomings that could be improved by further studies and/or minor revisions.

Thank you for your accurate review and suggestions.

Abstract :

L13 : what do the authors mean by “hypnotic induction”, is it hypnotic experience ? During a hypnosis session, the therapist starts by an induction and then makes some suggestions according to the goal that has been decided. It is not clear to what the “hypnosis induction” refers to.

Reply : We changed « hypnotic induction » as « hypnotic experience », as suggested.

L16 : “under hypnosis” should be changed as it suggests that the individual who is in hypnosis is passive. I would suggest “in hypnosis”.

Reply : changed as suggested

Introduction: L 54-56 : there has been some recent literature on hypnosis and OBEs or NDEs. It would be interesting to add newer literature on that topic.

Reply : we searched with google scholar if there were new studies about hypnosis and OBEs, but we didn’t find any. The were two studies related to hypnosis and NDEs, but these experiences are not related to our study (see also our response to reviewer Charlotte Martial).

L75 : if the study’s aim is to confirm Tressoldi and Del Prete (2007), then this study should be explicitly explained in detail. That way the reader understands better the present study.

Reply : We added some further details related to Tressoldi and Del Prete (2007) study, as suggested.

L76 : could the authors specify the suggestion used.

Reply : the suggestions used in the study are presented in the Supplementary Materials

L78 : the induction is not the only and principal part of the hypnotic sessions that impacts an individual perceptions but rather the suggestion that is used. This paragraph could be clearer in terms of methodology

Reply : the suggestion to induce an OBE in Tressoldi and Del Prete (2007) study, are too long to be added in the text, but are very similar to that used in the present study.

L79 to L95 : this should be in methods.

Reply : moved in the Methods under the paragraph « Study aims »

Materials and Methods : L110 : can the authors define and detail “clinical level of medical or psychiatric disease”.

Reply : we added « compatible with the clinical criteria defined in the main international clinical guidelines, such as DSM V or ICD-10,

L111 : took, should be written “take”. Throughout the manuscript there are language mistakes that have to be checked.

Reply : we checked the syntax as suggested.

L111 : can the authors be more specific on the “personal experience with hypnosis” ? What do you mean by experience ?

Reply : In Table 1, we changed the experience value adding the number of previous hypnotic sessions.

Procedure : in general the procedure is not very clear. Some results appear in the section when they should be in the result section

Reply : we moved the sentence « In total, twenty-eight sessions were necessary to complete the study. Eighteen sessions were carried out by phone with the participants at home” in the results section.

L125 : Can the authors explain why some participants had one or two sessions ?

Reply : In the Procedure we wrote "We placed the images in two different rooms as long as it was possible to require the identification of two different images in a single session. In only two cases, the participants had sufficient time and concentration to identify two images in a single session reducing their overall sessions to four instead of six"

L127 : Can the supplementary Material be numbered. L129 to 132 : Have all participants been seen in real life? Were all of them called? If not, was it always the same people in person or on the phone? This part should be more specific.

Reply : In the Results section we clarified that « In total, twenty-eight sessions were necessary to complete the study. Eighteen sessions were carried out by phone with the participants at home »

L130 : hypnotized should not be used. Same comment as comment L16.

Reply : corrected as suggested

L140 : was the order of the picture position randomized ? If so it should be mentioned here.

Reply : we wrote « …the six target images and randomized their order of presentation, the room where each one was placed and their orientation, either facing up or upside down »

L164: Who did the authors know that the participants where in an OBE state ? What were the criteria ? Especially on the phone ?

Reply: On pag. 5, we clarified that the hypnotist referred to the participants phenomenological account in response to the suggestions described in the Supplementary Material.

L174 : did the authors create the questions ? Do they come from a questionnaire ? This should be specified.

Reply : we clarified « devised by the authors of this study »

L188 : this should be in results Reply : moved in the Data analysis paragraph as suggested.

L191 : “... and give suggestion...” : It is confusing to use that word, comments, might be more appropriate.

Reply : corrected as suggested.

L198: what are the eleven questions ?

Reply : we corrected and added « all participants were emailed the same six questions related to their perceptual and cognitive experience when in OBE..

L208 : all the questionnaires used should also be described in material. The reader has no information on the minimal phenomenal selfhood, nor has he information about the “characteristics of spatial and temporal perception reported in NDEs”.

Reply: all questions were original and devised by the authors. None questionnaire of other authors was used.

L221 : how did the 3 decoys were selected ?

Reply : we added « low arousal pictures »

L225 : I only see 2 authors, not three.

Reply : we corrected as « co-author LP and another independent judge affiliate with the EcvanLab… »

L234 : a section with the statistical analyses should be written before the results.

Reply : we added a section « Statistical method »

L241 : 52.4 % is not metionned in the table, this is confusing.

Reply : Sorry, we missed the overall results in the last line, now added

L245 : this should be in the statistical analyses part, it is not a result per se.

L260 : the table 3 should be more specific: define ES + formula, CI, BF, H1, H0. A table should be able to be read by itself.

Reply : In the Table 3 presentation and title, we clarified all the statistics

L277 : This part merits some clarifications : Did the approval from the Ethical committee approved this part ? If so, did the participants signed an informed consent ?

Reply: The Ethical approval included the informed consent to be signed by participants

What should they refer to when they answered the questions ? Did the ones that had an OBE had to refere to that episode ? And those who did not life an OBE ? What was the experience of reference ?

Reply: Participants induced in OBE, should refer to their phenomenological experience in this state included the period when they were requested to identify the targets.

It there is no reference for the controls without an OBE experience then is seems logical that they do not answer like the others.

Reply : controls participants were selected among those who have only read about OBEs

L304 : the % is not correct, is should be 46.6%

Reply : Corrected

L338 : With what material was the comparison made ? With the material from Jourdan (2011) or the participants that were contacted after the study ? This part should be clearer If the comparison is made with Jourdan, then a table with the similarity and differences could be added.

Reply : We changed the title of Table 6 in order to clarify its data.

L382 : “but his aim was not to confirm his knowledge, but to compare it with the participants’ experience” : this was not mentionned before. It is hard to understand as we have no information in the hypnotist knowledge or the comparison that is mentionned. Could the authors clarify ?

Reply : The hypnotist knew very well the OBE phenomenology (now added in his description on page 4. However, the questions for participants were formulated in order not to confirm the hypnotist’s previous knowledge.

L387 : Another limitation it the response expectancy during hypnosis. There is a large literature on the subject this should be discused in the limites. More so because all the subject had good knowledge about OBEs

Reply : In the paragraph « Reliability of participants’ reports », we discuss precisely these issues.

L412 : Is it acceptable to disclose the participants identity ?

Reply : we deleted their names

Page 5 : The authors mention in a foot note that some other informatio will be avaiable in a future publication but the publication has since been published. Furthermore, that publication is cited in the bibliography this is confusing.

Reply : we corrected this discrepancy

Table S1 : it is hard for the reader to understand to what the table refers to. GAPED has to be explained.

Reply ; The GAPED acronym is described in the Materials paragraph on pag. 6

PsyArXiv Preprints | Openness to Experience Relates to COVID-19 Vaccination Rates across 48 United States. (n.d.). Retrieved March 21, 2022, from https://psyarxiv.com/n34t8/

Marc Lipsitch. (2021, July 20). At the risk of boiling down too much and certainly losing some detail, one way to summarize this wonderful thread is that when we think about vaccine effectiveness, we should think of 4 key variables: 1 which vaccine, 2 age of the person, 3 how long after vax, 4 vs what outcome. [Tweet]. @mlipsitch. https://twitter.com/mlipsitch/status/1417595538632060931

Some scholars study annotations as part of material culture. Are they leaving out too much by solely studying those physically left in the books about which they were made, or should we instead also be looking at other sources like commonplace books, notebooks, note cards, digital spaces like e-readers that allow annotation, social media where texts are discussed, or even digital marginalia in services like Hypothes.is or Perusall?

Some of these forms of annotation allow a digital version of cut and paste which doesn't cause damage to the original text, which should be thought of as a good thing though it may separate the annotations from the original physical object.

Discussion, revision and decision

Author response

To: Adam Marcus, co-founder Retraction Watch & Alison Abritis, PhD, researcher at Retraction Watch

Major Problems: I found serious deficits in both for this article, and thus I have serious concerns as to the usefulness of this article. Therefore, I have not proceeded in a line-by-line, as I consider the overall problems to be grave enough to require attention and revision before getting to lesser items of clarity.

I would like to point out that the authors show a marvelous attention to their work, and they have much to contribute to the field of retraction studies, and I do honestly look forward to their future work. However, in order for the field to move ahead with accuracy and validity, we must no longer just rely on superficial number crunching, and must start including the complexities of publishing in our analyses, as difficult and labor-intensive as it might be.

We do not consider that our article presents serious problems nor that it would be useless.

It is possible that a different view on the subject, some tendency to forbearance (understandable) for the difficult life of the publishing industry, along with some difficulties in understanding the ideas presented in the article, may have led to a series of points of view that we would like to comment on below.

We would first like to thank the reviewers for their comments, some of which will allow us to improve and nuance, using objective elements, the analysis of this bumpy field represented by the ecosystem of retracted publications. Because we have based our study on data from freely accessible sources of information, we will not insist too much on commenting on this issue.

The authors stated that they used the search protocol (and therefore presumably the same dataset) as described in Toma & Padureanu, 2021, and do not indicate any process to compensate for its weaknesses. In the referenced study, the authors (same as for this article) utilized a PubMed search using only “Retracted Publication” in Publication Type. This search method is immediately insufficient, as some retracted articles are not bannered or indexed as retracted in PubMed. This issue is well-understood among scholars who search databases for retractions, and by now one would expect that these searches would strive to be more comprehensive.

A better method, if one insists on restricting the search to PubMed, would have been to use Publication Type to search for “retracted publication,” and then to search for “retraction of publication,” and to compare the output to eliminate duplications. There are even more comprehensive ways to search PubMed, especially since some articles are retitled as “Withdrawn” – Elsevier, for example, uses the term instead of “Retracted” for papers removed within a year of their publication date – but do not come in searches for either publication type. Even better would have been to use databases with more comprehensive indexing of retractions.

In an ideal world, if any effort were to be made, it would be aimed at better indexing and managing existing databases, not at generating query strategies to make up for their shortcomings.

Thank you very much for the suggestions on the search strategy. We do not consider that the use of "Retracted Publication [PT]" should be compensated in any way but, if it should be compensated, we wouldn't want to add "Retraction of publication". We consider that using a search protocol more specific to systematic reviews is not very useful in our case: data are added/updated continuously (sometimes late), incorrect indexing can be corrected, the number of retracted articles increases from month to month; the same strategy can give different results at different times regardless of its complexity. Putting extra effort into detecting problematic articles without knowing the benefit but expecting it only highlights issues that can be improved at the publisher/editor(content delivery) and database level(indexing).

The dataset analyzed is a snapshot of a particular time interval and nothing more. Even during the analysis we found, in the case of one publisher, the addition of details to the initially incomplete retraction notes. Hence the need for follow-up studies. Therefore in the case of retractions, unlike the reviewer, we prefer an approach based on simple and easily reproducible strategies, widely accessible sources of information, and several steps. The first step in this strategy is the "number crunching" stage which includes this article.

1. The authors are using the time from publication to retraction based on the notice dates and using them to indicate efficacy of oversight by publishers. However, this approach is seriously problematic. It takes no notice of when the publisher was first informed that the article was potentially compromised. Publishers who respond rapidly to information that affects years/decades old publications will inevitably show worse scores than those who are advised upon an article’s faults immediately upon its publication, but who drag their heels a few months in dealing with the problem.

Indeed, the article uses the time between publication and retraction(exposure time – ET) as one of the SDTP score components for assessing editorial/publisher performance. Data on when a publisher or editor has been informed of problems with an article, apart from being relatively rare, is not a substitute for a retraction note. Moreover, the use of such information may induce a risk of bias.

We mention in the article the need to use reporting standards for retraction notes, and one element that might be useful is, indeed, the date on which the publisher or editor was informed of problems with an article. Unfortunately, as the author of this review knows very well, information precedes investigation; the retraction note contains (or should contain) much more data than the initial information about the quality problems of an article.

Our article aims to suggest a score for measuring publication performance in the context of retracted articles that would also allow an assessment of the dynamics of the activity of correcting the scientific record and, more importantly, how publishers engage in post-publication quality control. ET is only one component of this score.

It is quite clear from the data presented in the article that a publisher/journal that emphasizes systematic back-checking will have an increasingly longer average lifespan of retracted articles, logically higher than one that does not do this type of checking. We don't see precisely where the reviewer thinks there is a problem: once the checking is done, the ET will decrease, and a publisher that takes concrete steps to correct the literature will ultimately have a better reputation. This does not mean that a higher ET is laudable, it suggests that there is a post-publication quality control but also that the peer review process has let problematic articles through and that the control of these articles has been carried out late. This is an argument for more active involvement of publishers (as potential generators of editorial policies) in post-publication control.

Second, there is little consistency in dealing with retractions between publishers, within the same publishers or even within the same journal. Under the same publisher, one journal editor may be highly responsive during their term, while the next editor may not be. Most problems with articles quite often are first addressed by contacting the authors and/or journal editors, and publishers – especially those with hundreds of journals – may not have any idea of the ensuing problem for weeks or months, if at all. Therefore, the larger publishers would be far more likely to show worse scores than publishers with few journals to manage oversight.

It is exactly this inconsistency that we highlight in the article. Differing policies, attitudes, and responsiveness does not mean that a publisher cannot/should not ask questions about the effectiveness of internal processes and resources used for post-publication quality control or the implementation of uniform measures across journals in its portfolio.

Third, the dates on retraction notices are not always representative of when an article was watermarked or otherwise indicated as retracted. Elsevier journals often overwrite the html page of the original article with the retraction notice, leaving the original article’s date of publication alone. A separate retraction notice may not be published until days, weeks or even years after the article has been retracted. Springer and Sage have done this as well, as have other publishers – though not to the same extent (yet).

Historically, The Journal of Biological Chemistry would publish a retraction notice and link it immediately to the original article, but a check of the article’s PDF would show it having been retracted days to weeks earlier. They have recently been acquired by Elsevier, so it is unknown how this trend will play out. And keep in mind, in some ways this is in itself not a bad thing – as it gives the user quicker notice that an article is unsuitable for citation, even while the notice itself is still undergoing revisions. It just makes tracking the time of publication to retraction especially difficult.

We used the same date for all articles in our study (the one listed in PubMed), thus ensuring a uniform criterion for all publishers. If this date was not in PubMed we used the date from the retraction notes on the journal website but this was for a small number of articles. How different publishers handle retraction processes or the delay with which these are published is primarily related to internal editorial procedures, and these delays are reflected in the ET. In our experience, most articles retracted by Elsevier are available online, supplemented, and not replaced by retraction notes, which we think is an excellent policy.

1. As best as can be determined, the authors are taking the notices at face value, and that has been repeatedly shown to be flawed. Many notices are written as a cooperative effort between the authors and journal, regardless of who initiated the retraction and under the looming specter of potential litigation.

Shown to be flawed by who? Indeed, in our study, we refer to the retraction notes published by the journals. The fact that they are incomplete or formulated under the threat of litigation only supports our view that publishers and editors need to make a more significant effort to correct the biomedical literature, including avoiding litigation when the retraction note clearly describes the reasons for retraction. The way the retraction note is worded should be an editorial prerogative and should primarily aim at correcting scientific literature, not at appeasing egos, careers, or financial interests.

Trying to establish who initiated a retraction process strictly by analyzing the notice language is destined to produce faulty conclusions. Looking just at PubPeer comments, questions about the data quality may be raised days/month/years before a retraction, with indications of having contacted the journal or publisher. And yet, an ensuing notice may be that the authors requested the retraction because of concerns about the data/image – where the backstory clearly shows that impetus for the retraction was prompted by a journal’s investigation of outside complaints. As an example, the recent glut of retractions of papers coming from paper mills often suggest the authors are requesting the retraction. This interpretation would be false, however, as those familiar with the backstory are aware that the driving force for many of these retractions were independent investigators contacting the journals/publishers for retraction of these manuscripts.

Once again, the author of this review does not seem to fully understand our study, apparently favouring information published on third-party websites over that the journals officially assumed. The retraction notes represent the material available to a researcher doing documentation on a particular topic. The clarity and information contained in the note is the editor's or publisher’s responsibility, reflecting their performance and concern for the integrity of the science. Interpretation of a retraction note/analyzing an article occurs in this context. Not everyone has time for further investigation or to search third-party sites for information that is, with a notable exception, the result of a selection bias.

Assigning the reason for retraction from only the text of the notice will absolutely skew results. As already stated, in many cases, journal editors and authors work together to produce the language. Thus, the notice may convey an innocuous but unquestionable cause (e.g., results not reproducible) because the fundamental reason (e.g., data/image was fabricated or falsified) is too difficult to prove to a reasonable degree. Even the use of the word “plagiarism” is triggering for authors’ reputations – and notices have been crafted to avoid any suggestion of such, with euphemisms that steer well clear of the “p” word. Furthermore, it has been well-documented that some retractions required by institutional findings of misconduct have used language in the notice indicating simple error or other innocuous reasons as the definitive cause.

We understand your point of view and the situations presented may be accurate. However, from our point of view, the only valid reference remains the retraction note published on the journal's website. The existence of wording difficulties and various other problems that may arise are more likely to do with a tendency of the reviewer to make excuses for journals reluctant to indicate precisely what the reasons for retracting the article are. There are plenty of retraction notes in which the images with problems (including whether they were plagiarized, reused, manipulated, fabricated, etc.) are indicated with great precision, there are equally plenty of notes in which the word plagiarism is used without hesitation, indicating the sources, how they were informed, what was plagiarized. No matter how many hesitant publishers/editors there are, it should not be forgotten that there are many journals/publishers who take their role seriously, acknowledge and learn from their mistakes, thus providing a real service to the scientific community.

The authors also discuss changes in the quality of notices increasing or decreasing in publishers – but without knowing the backstory. Having more words in a notice or giving one or two specific causes cannot in itself be an indicator of the quality (i.e., accuracy) of said notice.

"Knowing the backstory" is not part of our objectives, and neither is assessing the quality of the retraction notes. This is also very difficult to do due to the lack of an accepted standard format. We are trying to propose a score composed of several parameters resulting from existing (or non-existing) data in the retraction notes so that we can have a picture of retractions at publisher level. Knowing the backstory is not relevant, reading and interpreting the official retraction note is relevant.

1. The authors tend to infer that the lack of a retraction in a journal implies a degree of superiority over journals with retractions. Although they qualify it a bit ( “Are over 90% of journals without a retracted article perfect? It is a question that is quite difficult to answer at this time, but we believe that the opinion that, in reality, there are many more articles that should be retracted (Oransky et al. 2021) is justified and covered by the actual figures.”), the inference is naive. First, they have not looked at the number of corrections within these journals. Even ignoring that these corrections may be disproportionate within different journals and require responsive editorial staff, some journals have gone through what can only be called great contortions to issue corrections rather than retractions.

We believe that this is a case of reviewer confusion generated either by the insufficiently precise wording of the text or a lack of understanding of our study objectives. We are trying to point out that more than 90% of the journals in the NLM catalogue-PubMed subset have not retracted a single article. We are not trying to say that journals without retracted articles are superior to the others. As explained in the article, we referred to retraction notes, not corrections.

Second, the lack of retractions in a journal speaks nothing to the quality of the articles therein. Predatory journals generally avoid issuing retractions, even when presented with outright proof of data fabrication or plagiarism. Meanwhile, high-quality journals are likely to have more, and possibly more astute, readers, who could be more adept at spotting errors that require retraction.

Of course, the quality level of articles in a journal is not determined by the number of articles removed.

Third, smaller publishers/journals may not have the fiscal resources to deal with the issues that come with a retraction. As an example, even though there was an institutional investigation finding data fabrication, at least one journal declined to issue a retraction for an article by Joachim Boldt (who has more than 160 retractions for misconduct) after his attorneys made threats of litigation.

Threats of lawsuits are instead a failure of a publisher/journal to adapt to the realities of the publishing business or to the risk of misconduct. This is something that needs to change.

Simply put, the presence or lack of a retraction in a journal is no longer a reasonable speculation about the quality of the manuscripts or the efficiency of the editorial process.

We have not attempted to suggest this, we have only analyzed the retracted articles and their associated retraction notes. On the other hand, the way a journal/publisher handles the retraction of problematic articles still reflects, to some extent, the quality/performance of the editorial processes.

1. I am concerned that the authors appear to have made significant errors in their analysis of publishers. For example, they claim that neither PLOS nor Elsevier retracted papers in 2020 for problematic images. That assertion is demonstrably false.

This is wrong. In our dataset, there are eleven PLOS articles related to human health with the publication year 2019 and 2020. None of these have images as retraction reasons.

Regarding the 21 Elsevier articles published in 2020, there is nothing in the retraction notes to indicate that the article was retracted because of the images. In 2 retraction notes there is mention of the comments made by Dr. Bik (The Tadpole Paper Mill - Science Integrity Digest) but the text of these (retraction notes) stops at the authors' inability to provide the raw data underlying the article.

Our study is based only on the content of the retraction notes published and assumed by the journal, not on opinions/comments appearing on other sites, which, for unknown/unmentioned reasons, are not officially assumed in the retraction note. Therefore, we consider the statement in the review to be questionable at best, as the use of material other than the retraction notes has severe implications for the internal and external validity of the study and the suggestion to use such methods is, in our opinion, wrong. We would also like to draw attention to the fact that many retraction notes are explicitely mentioning the request to provide raw images and the authors' inability to provide them.

Anyway, as far as images are concerned, our article suggested that there are publishers which seem to adopt image analysis technologies faster than others. The numbers are not really relevant in this case but the trend is: it describes the publishing activity complexity better than the numbers.

Reviewer response

We appreciate the authors’ zeal in standing by their work.

In regard to the deficits in the search process, the author states, “We do not consider that the use of ‘Retracted Publication [PT]’ should be compensated in any way but, if it should be compensated, we wouldn't want to add ‘Retraction of publication’”

There is a lack of appreciation for the complexities of indexing retracted materials in an indexing site such as PubMed. To have a comprehensive search, one should not be choosing to use either “Retracted Publication [PT]” OR “Retraction of Publication [PT].” One would use both, and then filter out the duplicates, because some retractions are indexed by retraction notices, some only have “Retracted” added to the indexed title and the publication type changed to “Retracted Publication.” Use of only one or the other guarantees that the search is far less comprehensive than it should be.

The authors state, “In an ideal world, if any effort were to be made, it would be aimed at better indexing and managing existing databases, not at generating query strategies to make up for their shortcomings.”

There is at least one database (http://retractiondatabase.org) that has a far more comprehensive indexing of retractions and is publicly available for use.

In Item 3, where it is pointed out that retraction notices themselves are inaccurate and cannot be taken at face value as to the reason behind the retraction, the authors responded, “Shown to be flawed by who?” — By an article cited in the manuscript:

Fang, Ferric C.; Steen, R. Grant; Casadevall, Arturo (2012): Misconduct accounts for the majority of retracted scientific publications. In Proceedings of the National Academy of Sciences of the United States of America 109 (42), pp. 17028–17033. DOI: 10.1073/pnas.1212247109.

“To understand the reasons for retraction, we consulted reports from the Office of Research Integrity and other published resources (7, 8), in addition to the retraction announcements in scientific journals. Use of these additional sources of information resulted in the reclassification of 118 of 742 (15.9%) retractions in an earlier study (4) from error to fraud.” Followed by “These factors have contributed to the systematic underestimation of the role of misconduct and the overestimation of the role of error in retractions (3, 4), and speak to the need for uniform standards regarding retraction notices (5).”

The authors then choose to state that it is the “editorial prerogative” – and that when notices “are incomplete or formulated under the threat of litigation [it] only supports our view that publishers and editors need to make a more significant effort to correct the biomedical literature, including avoiding litigation when the retraction note clearly describes the reasons for retraction.”

Following our attempt to explain why understanding the real reason behind a retraction is important to study the publication of notices, the authors respond: “Once again, the author of this review does not seem to fully understand our study, apparently favouring information published on third-party websites over that the journals officially assumed.”

First, yes, we do understand the study. We read a lot of these. Second, the “third-party websites” we prefer include the Office of Research Integrity and the Retraction Watch blog, where background investigations into the causes of retraction notices are described. If the authors are challenging the reference to PubPeer, keep in mind that journals initiate investigations based on comments on that website, and have taken to citing the website in their notices.

Had the authors not chosen to categorize the reasons for retraction, their reasoning may have had more support – but they did, and in doing so, by just using the notice with no further review, their findings address only the notice itself, with no context.

We recommend that the manuscript be substantially revised with strong attention to the comments we made in our original review.

These two should be interesting to read on memory and how they delineate its various layers.

See: Stiegler, B. (2009) Technics and Time, 2: Disorientation. Trans. S. Barker. Stanford, CA: Stanford University Press.

How Arabs learnt secret of making paper.

https://en.wikipedia.org/wiki/Functional_Requirements_for_Bibliographic_Records

Terms such as these often limit the ability for lawsuits to happen on a large scale. The effect — not necessarily relevant in this situation — is that companies can operate in a way that "nickels and dimes" on a large scale, but at amounts to individuals that is cost prohibitive to litigate or arbitrate (to individuals). Such circumstances can lead to a situation where a company could theoretically receive large sums of money from its customer base that it is not entitled to receive, but there be few financially viable mechanisms for countering and disincentivizing such bad behavior.

Definition for "Medical Group."

Note here the presumed freedom to pick and choose based on interest and judgement. Who's judgement really? Book banning and religious battles would call to question which people got to exercise their own judgement.

Prior to concordances of the Christian Bible there are examples of Hebrew manuscripts in the twelfth and thirteenth centuries that have lists of words and sentences or phrases in which they occurred. They didn't include exact locations with the presumption being that most scholars would know the texts well enough to quickly find them based on the phrases used.

Early concordances were later made unnecessary as tools as digital search could dramatically decrease the load. However these tools might miss the value found in the serendipity of searching through broad word lists.

Has anyone made a concordance search and display tool to automatically generate concordances of any particular texts? Do professional indexers use these? What might be the implications of overlapping concordances of seminal texts within the corpus linguistics space?

Fun tools like the Bible Munger now exist to play around with find and replace functionality. https://biblemunger.micahrl.com/munge

Online tools also have multi-translation versions that will show translational differences between the seemingly ever-growing number of English translations of the Bible.

Disputes will be resolved in Georgia.

It doesn't look like it; seems that Covey actually wrote "motives", not "intentions", and the maxim is not original to him https://quoteinvestigator.com/2015/03/19/judge-others/

The dendroglyphs (markings on trees) or the petroglyphs (markings on stone in the stony territories) are the libraries of the indigenous peoples who always relate their stories from the markings back up to the sky.

via Uncle Ghillar Michael Anderson

Can this be linked to the practices of the Druids who may have had similar methods? How about linking the petroglyphs in the Celtic (English) countryside?

The white fellas learned very quickly from the Romans that the first thing you attack is other people's religious beliefs, which are the modern day equivalent of communication towers. That's how oral societies communicate their knowledge and culture.

via Uncle Ghillar Michael Anderson

https://www.hollywoodreporter.com/movies/movie-news/will-smith-resigns-from-academy-membership-1235123801/

https://thegrio.com/2022/03/29/sometimes-people-get-smacked/

real stuff do be happening…

https://www.youtube.com/watch?v=kkjf0hCKOCE

The sky is a textbook. The sky is a lawbook. The sky is a science book. —Duane Hamacher, (1:24)

Hamacher uses the Western description "method of loci" rather than an Indigenous word or translated word.

The words "myth", "legend", "magic", "ritual", and "religion" in both colloquial English and even anthropology are highly loaded terms.

Words like "narrative" and "story" are better used instead for describing portions of the Indigenous cultures which we have long ignored and written off for their seeming simplicity.

Hidden in the phrase that "everything on Earth is reflected in the sky" or the idea of "reading the stars to understand one's environment" is the idea of associative memory. If you know one thing, you necessarily know another. Don't let this subtle idea of the words 'reflect' or 'read' hide what is going on.

Are these graphic and memorable stories strikingly similar because of the underlying packages of orality and memory used in these cultures?

This is one of my primary motivations for reading this text.

Indigenous sciences are highly interconnected while Western sciences tend to be highly sub-divided into ever smaller specializations.

Are Indigenous sciences naturally interconnected or do they form that way because of the associative memory underlying the cultural orality by which they are formed and transmitted? (I would suspect so, but don't yet have the experience to say definitively. Evidence for this should be collected.)

Even in the western tradition, the earliest methods of mnemonics tied ideas to locations, from whence we get the ideas of loci communes (in Latin) and thence commonplaces and commonplace books. The idea of loci communes was koinos topos in Greek from whence we have derived the word 'topic'.

Was this a carryover from other local oral traditions or a new innovation? Given the prevalence of very similar Indigenous methods around the world, it was assuredly not an innovation. Perhaps it was a rediscovery after the loss of some of these traditions locally in societies that were less reliant on orality and moving towards more reliance on literacy for their memories.

https://en.wikipedia.org/wiki/Timber_circle

Some timber circle sites to look into: - Secotan in North Carolina circa 1585 - Poverty Point - Hopewell timber circles (Moorehead Circle and Stubbs Earthworks) in Ohio - Cahokia

Artist, illustrator and mapmaker John White painted a watercolor in July 1585 of a group of Native Americans in the Secotan village in North America. Both he and chronicler Thomas Harriot described a gathering of Indigenous peoples gathered in the Algonquian village as part of Sir Walter Raleigh's Roanoke Colony expedition. They describe a festival with participants holding a dance at a timber circle, the posts of which were carved with with faces.

Harriot wrote that participants had come from surrounding villages and that "every man attyred in the most strange fashion they can devise havinge certayne marks on the backs to declare of what place they bee."

This evidence would generally support some of Lynne Kelly's thesis in Knowledge and Power. A group of neighboring peoples gathering, possibly for the Green Corn Ceremony, ostensibly to strengthen social ties and potentially to strengthen and trade knowledge.

Would we also see others of her list of markers in the area?

Read references: - Daniels, Dennis F. "John White". NCpedia. Retrieved 2017-12-19. - Tucker, Abigal (December 2008). "Sketching the Earliest Views of the New World". Smithsonian Magazine. Retrieved 2017-12-19. - "A Selection of John White's Watercolors : A festive dance". Encyclopedia Virginia. Retrieved 2017-12-19.

Mahase, E. (2022). Covid-19: Is the UK heading for another omicron wave? BMJ, 376, o738. https://doi.org/10.1136/bmj.o738

Discussion, revision and decision

Decision - Verified with reservations

Charles A. Schumpert: Verified manuscript

Max Shokhirev: Verified with reservations

Author response and revisions

Author response to reviewer Max Shokhirev

Dear Dr Shokhirev,

Thank you so very much for having reviewed my paper; your comments have been very helpful for me to improve it. Please find attached two identical copies of my revision of the paper (changes are highlighted in one of the copies) and a supplementary file that relates to one of your comments. Please see below my response to your comments when applicable.

Does the work cite relevant and sufficient literature? Some, but seems to be very limited in terms of biological literature.

I recognize and acknowledge this issue. It will be addressed in some of the specific responses below.

Are the conclusions adequately supported by the results? No

I understand this question and its answer as the theory presented in the paper (the conclusions) not providing new, proof-of-principle evidence (the results). That is correct, the theory is based only on existing evidence (most importantly, the already described age-dependent "transcriptional noise"), it is consistent with it and, importantly, it provides (in the new revision) three additional, experimentally testable predictions.

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

I would argue the theory is not based on a superficial understanding of the biology of senescence as it is currently established—in fact it is not based on the current biology of senescence at all. The theory is actually based on my previous theoretical work where I show (supported by real data analysis) how the constraints on transcription start site-adjacent histone crosstalk that are explicitly uncorrelated with transcriptional levels associate strongly with cell differentiation states—even more strongly than those constraints correlated with transcriptional levels (an association which is expected and already described in previous work). This in turn suggests the existence of an additional, higher-order type of biologically meaningful information conveyed by histone crosstalk, with this information is by definition uncorrelated with the information for precise epigenetic control of transcriptional levels. I called this information "hologenic" because it associates to cell differentiation trajectories necessary for the development of the multicellular individual as as a whole while being explicitly uncorrelated with the transcriptional levels. My previous work showed that the capacity for hologenic information in histone crosstalk grows at the expense of that for epigenetic information (this is necessary for the development of the multicellular individual). I emphasize that the theory proposed here relies on only two assumptions: (i) the overall histone crosstalk remains statistically constant in magnitude throughout adulthood and (ii) the hologenic component of the overall histone crosstalk increases at the expense of the epigenetic component throughout adulthood (with the exceptions depicted in Fig. 1b). These assumptions are of course not to be taken for granted, so in the new revision of the paper they are presented as predictions that can falsify the theory. I will further elaborate on these assumptions in my specific responses below.

All the above being said, the version of the paper you reviewed apparently gives the wrong impression that the theory is a comprehensive description of the senescence process with all its complexity. It is not. It is not surprising then that the theory appears to oversimplify the explanatory power of mechanisms known to be part of the senescence process when in reality they are claimed—this is a big theoretical claim I am making—to be the consequence of the primary cause of senescence. It is only this primary cause what the proposed theory is all about. For these reasons and thanks to your observation, I stated this distinction explicitly in the new subsection 1.2 "Scope" and also modified the title of the paper accordingly.

I recognize and acknowledge that the paper does not present new data or experimental results in direct support of the theory—something that arguably makes it less compelling to be considered let alone to be tested experimentally. But I do wish to point out that a scientific theory, must "only" (i) effectively explain the phenomena it is aimed to explain (in this case, the primary cause of senescence), (ii) be consistent with existing observations/results (most importantly, with the well described age-dependent "transcriptional noise" in this case), and (iii) provide non-trivial, experimentally testable predictions that can falsify it. I have tried to make up for the lack of preliminary supporting evidence by adding three new straightforward, experimentally testable predictions that can falsify it. Importantly, two of said predictions (C and D in subsection 2.6) relate to precisely how senescence can be slowed down, even stopped, or accelerated—and with associated effects in terms of resistance/propensity to carcinogenesis—in any non-human species, because the direct testing requires genome editing. In this context, I have no problem granting that the prior probability of predictions C and D being verified experimentally is exceedingly small. On the other hand, the experimental verification of predictions C and D would arguably be a game-changing result in terms of the fundamental understanding of the senescence process, however unlikely this scenario is a priori. In this context, I submit to you that the extraordinary nature of predictions C and D in both theoretical and practical terms (I reiterate, this is not to say predictions C and D will be verified) more than makes up for the lack of preliminary evidence for the theory. The prospect of slowing down or even stopping the senescence process may catch the attention of at least some research groups with genome-editing capabilities, given that the gene edits described in predictions C and D are very specific. (You can find more about predictions C and D in my response to your comments related to the subsection 2.4 of the paper you reviewed).

Sections 1.1-1.3 The author only mentions the Hayflick limit as a biological reference for senescence. There is a very rich body of literature on senescence and aging that is completely overlooked here. The author should include additional references to reviews for senescence and aging to orient the reader to the complexity of these biological processes (e.g. PMC8658264, PMC7846274).

Thank you for pointing this out. I have included the suggested review articles as references and, most importantly, I tried now to clarify the scope of the theory in a new subsection (1.2 Scope). The scope of the theory is in a sense, very limited: it is indented to explain only the beginning of the causal chain of age-related changes we identify as aging at the multicellular-individual level. In other words, it is about what fundamentally triggers the process. On the other hand, such a scope (i.e., describing the first cause) is quite ambitious in the sense that it should allow, at least in principle, for the manipulation of the process (either slowing it down or accelerating it). I will come back to this point later in my response.

Please clarify what you mean by senescence vs aging for both cells and individuals. Senescence is a natural biological process that cells/organisms use to turn off cell replication due to damage (e.g. telomere shortening, double-stranded breaks, etc.). Other cells can also facilitate this process through signaling (e.g. immune cells or contact inhibition).

I am not a native English speaker, and one the first things I did when addressing this problem was to study the associated terminology in the literature. Unfortunately, this terminology is not particularly monolithic. In some articles, the age-dependent, progressive dysfunction undergone by multicellular individuals once they reach their mature form is referred to as "senescence" (PMID 1677205, 6776406, 12940353, 22884974, among others), "biological aging" (PMID 31833194, 33982659, 34700008, among others), or even simply as "aging" (PMID 24862019, 34990845, 31173843, among others). In this context, I decided to stick to "senescence" mainly because (i) it is only one word and (ii) unlike "aging", "senescence" directly and unambiguously implies time-dependent dysfunction or decay. At any rate, to distinguish the term from cellular senescence/cellular aging I created a Glossary in the paper where these terms and others are clarified to avoid confusion.

Aging is typically thought of as an organismal phenomenon, which is still poorly understood but is theorized to include tradeoffs (as you describe in section 1.2). It is also accepted that aging is cell, tissue, and organism specific. Since you talk about senescence and aging across both biological scales, it is important to define exactly what your theory pertains to.

I am glad we agree that senescence is poorly understood (especially in comparison to cellular senescence). Unfortunately, some colleagues in the community interpret this as saying the research been done on the topic is worthless—it is not—when it is really pointing out the phenomenon largely lacks falsifiable theories, let alone an already tested falsifiable theory (with experiments failing to falsify it).

Section 1.4

The author posits that senescence is an imbalance in information contents of histone post-translational modifications around transcription start sites. This is just one level of regulation, albeit an important one. The author seems to completely overlook many other types of regulation (e.g. microRNA, lincRNAs, metabolic/energetic constraints, non-proximal regulation at enhancers, higher ordered structure of the chromatin, post-translational regulation of proteins, and etc.). How can all of these other important levels of regulation fit into this theory? All have been implicated in senescence/aging in some form or another.

What you point out here is very important, thank you. In a remarkable piece of research, Kumar and colleagues showed that core nucleosomal histone post-translational modification (hPTM) profiles are able to predict transcript abundance levels with very high accuracy (R~0.9, ref. 33). The constraints on hPTMs underpinning this predictive power (in turn underpinned by DNA-histone octamer interactions)—as well as those constraints on hPTMs that are explicitly uncorrelated to transcriptional levels—are central to the theory proposed. As stated in the new section 1.2, the complex cascade of changes/interactions characterizing senescence escapes the scope of the theory. In this context, most of the types of regulation you mention are under this theory not actually regulation in a "teleological" (the quotes are meant to avoid alienating the reader) sense but rather types of propagation/amplification of truly regulated/dysregulated changes. One of my goals when developing this theory was to try shift attention from "molecule A-collides with molecule-B, which collides to..." into higher-order constraints and trying to explain phenomena such as the well-known, age-dependent "transcriptional noise", which under the theory presented should be understood as senescence itself. Furthermore, I maintain the relative slow progress we have made in understanding phenomena such as cancer and senescence (in spite of the abundance of high-throughput data) comes from

The author further suggests that histone crosstalk information content can be decomposed into two unrelated components: epigenetic and non-epigenetic. The non-epigenetic component is described as “hologenic information content,” which stems from a previously published work by the author. Non-epigenetic is confusing in this context since really this is information content that stems from the synergies of individual cells to form a whole, e.g. the emergent information content that comes from many cells working together (or at least this is how I understand the underlying theory). This information content is important for the general maintenance and survival of the organism. The author should clarify this point further, since this seems to be one of the fundamental assertions being made in the paper. For example, bringing in the descriptions used in section 2, can further clarify these central points.

In my previous work, "hologenic" information content is defined as being uncorrelated with (i.e., orthogonal to) changes in transcriptional levels, in the same way "epigenetic" information has been defined (traditionally and for good reason) as being uncorrelated with changes in the DNA reason. Hologenic information content emerges when proliferation-generated extracellular gradients of secreted molecules start to being used to perform regulatory work (after being transduced) on the histone crosstalk of each cell's nucleus.

In addition, the author states: “ Moreover, the sum decomposition in Eq. 1 implies that the growth in magnitude (bits) of the hologenic (i.e., non-epigenetic) component must be accompanied by a decrease in magnitude of the epigenetic component.” This is not necessarily true, since signaling is a separate biological process from the regulation of gene expression. In other words, both can increase or decrease simultaneously. For example, a healthy non-senescent immune cell can upregulate very specific transcriptional programs that lead to very complex signaling and extra-cellular interactions. You can argue that both represent an increase in information content for both the epigenetic and non-epigenetic “hologenic” components. In addition, as cells naturally senesce they are programmed to turn off cell-cycling while upregulating autophagy and repair processes. They may not upregulate extracellular signaling at this time, which would seem to contradict the author’s theory/statement. In this case, the simplification that all cells are the same is dangerous because it overlooks the tradeoff of information contents between cells. It also ignores important repair pathways (senescence being one of them), to deal with cells that have dysregulated their natural processes over time. It also overlooks the important action of immune cells that work to get rid of cancer and poorly-functioning cells.

This comment of yours (referring to complex yet specific signaling pathways and interactions) clearly shows I did a poor job (if not utterly failed) in conveying that the epigenetic and hologenic components must be understood in chromatin-wide terms. Yes, the random variables used to define both components in the sum decomposition of Eq.1 are defined with respect to a single, generic transcription start site, but these random variables take their respective values from data for all transcription start sites in the nucleus. This is why the terms Eq. 1 and the log-ratio in Eq. 2 must be understood as chromatin-wide terms. Again, this approach intends to shift attention from specific (however important) molecular mechanism to higher-order, information conveying hologenic/epigenetic constraints (whose imbalance are proposed to trigger senescence as proposed in this theory). The chromatin-wide nature of the hologenic and epigenetic components is not an obvious consideration but it is a very important one, so it is now explicit (twice) in the revised text and I thank you for bringing this to my attention.

For a statistically invariant level of overall histone crosstalk C(X1,...,Xn) in Eq. 1, a growth in magnitude of the hologenic (i.e., non-epigenetic) component must be accompanied by a decrease in magnitude of the epigenetic component and vice versa. This chromatin-wide trade-off might not hold, as you suggest, only if the overall histone crosstalk C(X1,...,Xn) varies significantly (in particular, if it varies significantly throughout adulthood). If, in fact, the overall histone crosstalk C(X1,...,Xn) varied significantly throughout adulthood the proposed theory would make no sense whatsoever. Mathematically, C(X1,...,Xn) is finite and upper bounded by ΣH(Xi) - max H(Xi) (where H(Xi) is the marginal Shannon uncertainty of Xi), and one can further expect that the overall histone crosstalk represented nu C(X1,...,Xn) remains statistically invariant for a number of reason, chief among them the massive chromatin instability that would ensue if it indeed C(X1,...,Xn) varied. For this reason, I included the C(X1,...,Xn) time-invariance as an additional prediction for the falsifiability of the theory.

Also, it seems crosstalk, correlation, capacity, and content, are used interchangeably. Please clarify that these are all the same, or use one of these terms to avoid confusion.

I went through the use of these terms in the paper and, unfortunately, I cannot reduce them to just one term or dispense with them altogether without losing rigor for the theory. Because of this I decided to include them in the Glossary, hoping that it will make any reader recognize that their respective uses in the text are actually not interchangeable.

Section 1.5 The author provides a general approach for measuring the log of the ratio of epigenetic and non-epigenetic capacities for a particular histone modification at three positions (i,j,k), and for some measured abundance of mRNA Y. Since we typically measure abundance of a particular modification genome-wide, and the mRNA level for tens of thousands of genes, how would a realistic equation look like (i.e. one that has 10k mRNA levels, and 10k histone positions)? In addition, the author does not explain how to combine correlations across multiple histone modifications. Please expand this section to make it relevant for real-world genome-wide measurements since this will be important for falsifying the theory.

Since public datasets are available (e.g. the aging atlas https://doi.org/10.1093/nar/gkaa894), the author should show an example of how a dataset might be used to falsify or demonstrate the theory in more detail.

This response to this observation can be found in the new Fig. 2 and with greater detail in Supplementary File 1. In summary, the data analysis approach is basically the same used by Kumar et al. (ref. 33). That is, with tandem RNA-seq/ChIP-seq data obtained from the same cell sample a table can be constructed with the rows representing the transcription start sites (TSSs) in the genome and the columns displaying the normalized ChIP-seq signal for each hPTM in different positions relative to the respective TSS (variables X1,...,Xn in the paper) plus a column with the respective measured transcript abundance for each TSS (variable Y).

Section 2.1 The author uses correlation of the log ratio of the epigenetic and non-epigenetic content with age as a readout of “reassignment” of crosstalk/contents, arguing that for cancer cells this correlation should be essentially zero. This seems like an oversimplification of the “reassignment” process since senescence may occur in phases across the age of a cell/organism, and since there might be both increases and decreases in the log ratio of contents due to natural biological processes and variability. Would it not be better to measure the sum of changes in the log ratio or the difference between the log ratios at different ages?

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

This is a great observation, thank you. Yes, the correlation in Eq.3 relates strictly to chronological age (in other words, to time). The correlation must hold for somatic cells of the same type according to the theory; now this condition is explicit in the text. In this context, some cell types and tissue may senesce (see new Fig 1c, center) faster than others as you point out; in this case the associated slope is predicted to be steeper, whereas cell types that senesce relatively slower the slope should be gentler. Only in species displaying negligible senescence the hologenic/epigenetic log-ratio should remain constant (i.e., zero slope, as depicted in Fig. 1b, blue curve), or fluctuate significantly in species displaying "reversible" development (Fig. 1b, magenta curve).

Section 2.2 The author argues that senescence is an emergent property of the loss of information content for epigenetic histone crosstalk and an increase in information content of “hologenic” information content (e.g. cell signaling and anti-tumor signaling). I believe this premise does not stem from the reality of biological systems (see my comments for section 1.4).

The trade-off between capacity for hologenic and epigenetic information within a constant overall histone crosstalk magnitude—in particular, the growth of the former at the expense of the latter throughout adulthood generating a dysfunctional imbalance—is arguably the cornerstone of the theory in fundamental terms. Whatever my response was to your comments about subsection 1.4, this crucial trade-off cannot be taken for granted, however compelling the arguments are. In this context, there is no better solution than putting the hologenic/epigenetic trade-off to the test (see prediction B for falsifiability of the theory, also further detailed in the new revision of the paper). Realistically, however, I expect prediction B to be tested (and the hologenic/epigenetic log-ratio quite thoroughly examined) only if predictions C and D are verified. In that scenario, it will be interesting to see whether the hologenic/epigenetic log-ratio increase may be steeper in some tissues (which should then explain why those tissues senesce faster than others).

Also, this section seems to be contradicting the author’s conclusions and is very confusing. The author seems to argue that there is both more AND less constraint at the multi-cellular level (organismal)? Please clarify or remove this section.

I can see now how it seems contradictory because I was saying the capacity for hologenic information (which is about transcriptional levels being accurate for the multicellular individual as a whole) increases up to the point of being dysfunctional at the multicellular-individual level. Here I failed to convey that said dysfunctional outcome derives from the concurrent decrease of capacity for epigenetic information, not from the increase of capacity for hologenic content per se). Thank you for bringing this to my attention. I decided to remove this subsection altogether because the hologenic/epigenetic trade-off is covered in greater detail in the next subsection.

Section 2.3

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

My intention here is to establish a fundamental contrast between the group of diseases we call cancer and senescence using the difference between the concepts of accuracy (average closses of the actual values to a target value) and precision (variance of the actual values, also added to the Glossary). In this context, since cancer is an almost canonical example of gene dysregulation (transcriptional accuracy is lost because capacity for hologenic information is lost), we can understand senescence as transcriptional overregulation in the sense of too much capacity for hologenic information gained over time at the expense of capacity for epigenetic information, thereby losing transcriptional precision). I added a third panel "c" to Fig. 1 to clarify the proposed contrast between cancer and senescence, in terms of impaired transcriptional regulation (i.e., inaccurate up to dysfunction in cancer and imprecise up to dysfunction in senescence).

Section 2.4 This seems to be describing an illustrative real-world example? This section is incredibly specific and again only focuses on one possible mechanism and does not include any measured data or analysis. Please preface this section to explain that this is just one of many possible examples. Again, it will be good to provide other examples looking at other aspects of aging biology (not just histone modifications).

I am not including examples of mechanisms propagating dysfunctional changes in the senescence process because this theory is not about adding one more possible mechanism to the collection of well-described mechanisms associated to senescence. The theoretical claim I am making here is that the sequence of steps described in subsection 2.4 constitute the primary cause that triggers senescence throughout the multicellular individual's adulthood. This is of course an extraordinary theoretical claim and, as the great Carl Sagan pointed out, as such requires extraordinary evidence (or, in this theoretical paper, an extraordinary prediction aimed to obtain said evidence).

This is why I also added two predictions, C and D, to the now completely rewritten subsection 2.6 "Falsifiability". These predictions are extraordinary in that they provide extremely specific sufficient conditions for either slowing down or accelerating the senescence process in any non-human species. For this reason (i.e., adding predictions C and D) I have duly updated the "Competing interests" section of the paper. [Note: in a separate paper I explore in greater depth the theoretical underpinnings of predictions C and D.]

Section 2.5-2.9,3

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

Thank you for your suggestion, I organized a Discussion section accordingly, placing the predictions for falsifiability in it. Additionally, I changed “Senescence’s ultimate cause” for “Senescence’s proposed ultimate cause”, clarifying also in the Scope subsection 1.2 that ultimate/proximate is used only in terms of the concepts of causality as introduced and named by Ernst Mayr.

Following your advice, I removed the subsection “Can senescence be stopped?” Now, I believe this theory is bound to alienate at least some colleagues in the biological community (among those who read the paper, that is). As you point out, the theory addresses only one small aspect of the senescence process, but it is not any small aspect. It is about what triggers the process or, equivalently, what is the initial link of the causal chain leading to senescence with all its mechanistic complexity. This implies all other proposed primary causes would, simply by logical exclusion, be incorrect.

One of the reasons I developed this theory in the first place is that I failed to find even a single falsifiable description proposing a primary cause of senescence that integrates Mayr's proximate and ultimate concepts of causality. To be clear, this is not a shortage of explanatory accounts for the senescence process; it is a shortage of experimentally falsifiable ones. There are scientific fields where falsifiability is inherently difficult or probably impossible to meet, such as paleoclimatology. But that is not the case in biology—certainly not in developmental biology. This is why I agree with you in that the senescence process is still poorly understood in fundamental terms (which by no means implies all work in the field is worthless).

Forgive me for the following related digression/personal note: Since I started writing this paper I faced the dilemma of how many research works on this topic should I cite, given there is plenty (even considering this is not a review-type article). We scientists are only human and as such we very much like our work being cited in terms of current knowledge. That changes, however, when the explanatory account we like the most (or even worse, the explanatory account we ourselves proposed) is being cited to acknowledge its existence but the lack of predictions to falsify the "theory" is also pointed out (our reaction changes probably because unfalsifiable explanatory accounts can be always dismissed as just storytelling, however compelling the story might be). These rather petty emotional responses of ours have of course nothing to do with the advancement of science. Yet, many scientific journals—however prestigious, and particularly in the life sciences—routinely publish articles the word "theory" describing the work in the title and/or body when there is no prediction to be found for falsifiability. As a student, this is when I learned the interests of the scientific publishing industry (as we know it) and those of science are completely uncorrelated—not really surprising since their respective goals are so different. In this context, I found the PeerRef initiative/model very interesting since it aims to focus purely on the scientific content as opposed to essentially non-scientific considerations.] In the previous revision of the paper I offered only one prediction to falsify the theory, which is arguably cumbersome—and therefore arguably not too appealing—for experimentalist colleagues to test. For that reason I added three predictions (A, C, and D) which are straightforward to test in the laboratory. In this context, I am hoping the scientific community will be open to consider and to test falsifiable theories, however alienating they might be. Especially when we are dealing with a phenomenon for which paradigmatically accepted explanatory accounts is, at least to the best of my knowledge" all we currently have. Last but certainly not least, I wish to express again my gratitude for all the time you devoted to review my paper. Whether or not the theory it presents resists falsification attempts, I firmly believe the paper itself is now better than it was before thanks to your feedback.

Reviewer response

In general, it seems the paper is improved and includes quite a bit of additional clarification and qualifying statements.

The scope is also much more constrained and it is clear that the author is sticking only to proposing a possible theory, which is fine with me, albeit not as exciting as it might have been if the author had gone through and provided real-world examples or evidence. It still bothers me that the work is trying to implicate a very specific mechanism for senescence (chromatic cross-talk and regulation), since now it is clear that the work is mostly a theoretical exercise without much basis in established biology. In other words, chromatin cross talk might be an example of one way that this could happen among others (e.g. other epigenetic regulation or lack thereof). As a theoretical work it is fine as long as you agree that it is sufficient for the scope of the journal

Decision changed - Verified with reservations: The content is scientifically sound, but has shortcomings that could be improved by further studies and/or minor revisions.

Author response to reviewer Charles A. Schumpert

Dear Dr Schumpert,

I wish to thank you for having reviewed my paper; your comments have been very encouraging for the effort of moving my theory forward. Please find attached two identical copies of my revision of the paper (changes are highlighted in one of the copies) and a supplementary file that relates to one of your comments. Please see below my response to your comments when applicable.

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

Thank you for kind words, but I have to admit any and all brilliance that may be found in the write-up must be credited to my wonderful editor Angelika Hofmann. Regarding the assumptions, this theory relies on two critical ones, which of course cannot be taken at face value. This is why these assumptions inform prediction B (in the new revision). There are now four experimentally testable predictions to falsify the theory; hopefully some will be appealing to experimentalist colleagues.

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

One of the problems I faced when writing this paper was how many different explanatory accounts (there is plenty) I was going to cite provided I would have to underscore their lack of testable predictions for falsifying them—which in time becomes dangerously close of being downright unfalsifiable. As Wolfgang Pauli famously said, unfalsifiable theories are not even wrong. In other words, the problem was how many readers I was going to alienate while having no intention to do so. Navigating academia's social ocean is not an easy task, at least not to me, so I decided to compromise. To be clear, I am by no means claiming my theory is correct but underscoring that (i) it can be tested experimentally and (ii) explains the known age-dependent, cell-to-cell transcriptional noise that I argue should be regarded as senescence itself in fundamental terms.

personal trust networks - a part of personal learning networks? the internal and the external benefit are no longer seperatable - one always comes together with the other

Lorenzo Nigro indicates that the "kothon" of Motya in southern Sicily was a pool of Baal whose surface may have been used to observe and map the stars. He also indicates that the Phoenicians adored the stars potentially as gods or deceased ancestors. This is an example of a potentially false assumption often seen in archaeology of Western practitioners misconstruing Indigenous practices based on modern ideas of religion and culture.

I might posit that this sort of practice is more akin to that of the science of Indigenous peoples who used oral and mnemonic methods in combination with remembering their histories and ancestors.

Cross reference this with coming reading in The First Astronomers (to come) which may treat this in more depth.

Leonardo da Vinci documented the attributes of standing water for studying the night sky.

Where was this and what did it actually entail?

In 1998, Ben Shneiderman wrote "The danger of working at "internet time" is that hasty decisions may be poor, and rapid changes may cause troubling turbulence for many users." He's essentially admonishing against the dangerous and anti-social idea of what Mark Zuckerberg would later encourage at Facebook when he said "move fast and break things."

The idea that refinement is a social process is a powerful one, but it is limited by the society's power structures, scale, and access to the original material and least powerful person's ability to help refine it.

Nice that he takes this sort of inclusive approach so early in the evolution of the internet.

https://vi.to/hubs/micro-camp-march-2022/pages/micro-camp-march-2022-town-hall-mp4?sidebar=shown&v=%2Fvideos%2F4859

==>l’échantillon de l’étude est est extrêmement limité, l’étude n’est pas répliqué et elle ne permet pas de retirer de résultats concluants

Kill two birds with one stone.

Reichel, C. (2022, March 1). Please Keep Your Masks On. Bill of Health. http://blog.petrieflom.law.harvard.edu/2022/02/28/please-keep-your-masks-on/

Wu, K. J. (2021, December 1). What J&J Can Still Teach Us. The Atlantic. https://www.theatlantic.com/science/archive/2021/12/vaccine-durability-annual-covid-boosters/620863/

An economic diversion of this scale would make it far more likely that humanity will not be able to prevent, but indeed accelerate planetary tipping points! Hence the urgency of this crisis for the climate movement. This implies that the climate movement and the antiwar movement must now synchronize resources and form a coherent, unified strategy

Ideas fill their spaces.

When writing it can be daunting to see a long blank screen and feel like you've got to fill it up with ideas de novo.

From the other perspective if you're starting with a smaller space like a Twitter input box or index card you may find that you write too much and require the ability to edit things down to fit the sparse space.

I do quite like the small space provided by Hypothes.is which has the ability to expand and scroll as you write so that it has the Goldilocks feel of not too small, not too big, but "just right".

Micro.blog has a feature that starts with a box that can grow with the content. Once going past 280 characters it also adds an optional input box to give the post a title if one wants it to be an article rather than a simple note.

Link to idea of Occamy from the movie Fantastic Beasts and Where to Find Them that can grow or shrink to fit the available space: https://harrypotter.fandom.com/wiki/Occamy

Each highlighted statement expresses political talking points aligned to induce trump-like support.

Trump introduced new marketing and strategy, formulated using concepts and metrics mastered by Reality TV and Hollywood and then paired with advertising propaganda and "selling" techniques to create a "Brand". This is after-all Donald Trump, this is what he does, has done and is the only way he has found to make money. Trump built the "brand" (just barely) while teetering on self destruction.

His charismatic persona became "the glue" that allowed creative narratives to stick to certain types of people in-spite of risk. Trump learned OTJ how to capture a specific type of audience.

The mistake people make about Trump is assuming his audience to be "Joe Six-Pack", redneck's with limited education! This assumption does not have merit on its own.<br /> * There is a common "follower" theme among his audience that is exploited by those who: * Bought the "licensing rights" to the master-class Trump "how-to" course.