1. Last 7 days
    1. De analyse met behulp van partiële correlaties

      Een partiële correlatie gebruik je om de samenhang tussen twee variabelen X en Y te onderzoeken, terwijl je de invloed van een derde variabele Z constant houdt. Zo kun je beter beoordelen of X en Y nog steeds samenhangen als je rekening houdt met die mogelijke verstorende factor.

      Het lijkt dus sterk op de elaboratietechniek van hiervoor. Het verschil is vooral dat je hier werkt met correlatiecoëfficiënten en variabelen op intervalniveau, in plaats van met tabellen.

    2. tijdsvolgordeproblemen

      Als X en Y samenhangen, is niet altijd duidelijk welke variabele de oorzaak en welke het gevolg is. Als motivatie en schoolprestaties samenhangen, kan motivatie tot betere prestaties leiden, maar betere prestaties kunnen iemand ook gemotiveerder maken.

      Kort: je weet niet zeker of X → Y of Y → X.

    3. Causaliteit in correlationeel onderzoek

      Bij correlationeel onderzoek kun je aantonen dat twee variabelen samenhangen, maar niet zomaar dat de ene variabele de andere veroorzaakt. Dit komt vooral door het tijdsvolgordeprobleem en het derde-variabeleprobleem.

    4. centrale tedentiematen

      Dit is een derde manier om te onderzoeken of groepen van elkaar verschillen. Je berekent bijvoorbeeld het gemiddelde van verschillende groepen en vergelijkt die gemiddelden.

      Bijvoorbeeld:

      Groep A → gemiddeld cijfer 7,8 Groep B → gemiddeld cijfer 6,3

      Vervolgens kun je statistisch toetsen of dat verschil waarschijnlijk een echt verschil is of door toeval kan zijn ontstaan. In de tekst wordt hiervoor bijvoorbeeld variantieanalyse genoemd.

      Kort: je vergelijkt centrale waarden, zoals gemiddelden, van verschillende groepen.

    5. overige coëfficiënten

      Een associatiemaat drukt de samenhang tussen twee variabelen uit in één getal. Welke associatiemaat je gebruikt, hangt af van het meetniveau van de twee variabelen. Daarom staat bovenaan die tabel met bijvoorbeeld nominaal, ordinaal en interval/ratio.

      Je hoeft vooral het idee erachter te begrijpen:

      Associatiemaat = getal dat aangeeft hoe sterk twee variabelen samenhangen.

      Hoe interpreteer je zo'n getal?

      Sommige associatiematen, zoals C en λ (lambda), lopen van 0 tot 1:

      0 = geen samenhang 1 = perfecte samenhang

      Andere maten, zoals Pearsons r en Spearmans rangcorrelatie, lopen van -1 tot +1:

      0 = geen samenhang +1 = perfecte positieve samenhang -1 = perfecte negatieve samenhang

      Een positieve samenhang betekent bijvoorbeeld:

      Meer motivatie ↔ betere schoolprestaties.

      Een negatieve samenhang kan bijvoorbeeld zijn:

      Meer stress ↔ minder slaap.

      Bij een negatieve samenhang gaat de ene variabele dus omhoog terwijl de andere omlaag gaat.

    6. Randomiseren

      Bij randomiseren bepaalt het toeval in welke groep iemand terechtkomt. De onderzoeker kiest dus niet zelf wie in de experimentele of controlegroep komt.

      Bijvoorbeeld: je hebt 100 leerlingen. Door loting komen er 50 in de groep met de nieuwe lesmethode en 50 in de controlegroep.

      Het doel hiervan is dat allerlei kenmerken, zoals motivatie, intelligentie en leeftijd, ongeveer gelijk over de groepen verdeeld raken.

      Kort: randomiseren = toeval bepaalt de groepsindeling.

      Belangrijk: randomiseren garandeert niet dat groepen perfect gelijk zijn. Zeker bij kleine groepen kunnen er toevallig toch verschillen ontstaan.

    7. 8.4 Randomiseren en matchen

      Als je wilt aantonen dat:

      X → verandering in Y

      moet je ervoor zorgen dat je groepen zo vergelijkbaar mogelijk zijn. Idealiter verschillen de groepen alleen in de onafhankelijke variabele X.

      Dus bijvoorbeeld:

      Groep A → krijgt behandeling Groep B → krijgt geen behandeling

      Verder wil je dat de groepen ongeveer gelijk zijn wat betreft bijvoorbeeld leeftijd, intelligentie, motivatie enzovoort.

      Dat kun je onder andere bereiken door randomiseren of matchen. Die begrippen zullen hierna verder worden uitgelegd.

    8. 8.3.8 Interactie van buitenexperimentele factoren

      Soms werken twee buitenexperimentele factoren tegelijkertijd en versterken ze samen het probleem. Daardoor wordt het nóg moeilijker om vast te stellen of X werkelijk verantwoordelijk is voor de verandering in Y.

      Je hoeft hier vooral te begrijpen: meerdere verstorende factoren kunnen gecombineerd optreden.

    9. 8.3.4 Regressie

      Regressie kan optreden wanneer je deelnemers selecteert omdat ze bij de eerste meting extreem hoog of extreem laag scoren. Bij een volgende meting zullen zulke extreme scores vaak vanzelf wat dichter bij het gemiddelde liggen.

      Bijvoorbeeld: je kiest alleen leerlingen die extreem slecht scoorden op een toets. Bij de tweede toets scoren ze gemiddeld beter. Dat hoeft niet volledig door de behandeling te komen; hun eerste extreem lage score kan deels toeval zijn geweest.

      Kort: regressie = extreme scores bewegen bij een volgende meting vaak richting het gemiddelde.

      ⚠️ Verschil met testing:

      Testing: de hele groep kan beter scoren doordat ze de test al kennen. Regressie: vooral belangrijk wanneer mensen zijn geselecteerd vanwege extreme scores.

    10. 8.3.3 History

      History betekent dat er tijdens het onderzoek een gebeurtenis plaatsvindt die invloed heeft op de resultaten, maar niets met de behandeling te maken heeft.

      Voorbeeld: je onderzoekt of een programma angst bij kinderen vermindert. Tijdens het onderzoek start de school toevallig óók een groot welzijnsprogramma. Als de angst afneemt, kan dat dus ook daardoor komen.

      Kort: history = een externe gebeurtenis tijdens het onderzoek beïnvloedt Y.

    11. 8.3.2 Testing

      Testing betekent dat een eerdere meting invloed heeft op een latere meting. Deelnemers kunnen bij de tweede meting bijvoorbeeld beter scoren omdat ze de test al kennen en weten wat ze kunnen verwachten, niet omdat de behandeling heeft gewerkt.

      Voorbeeld: je maakt twee keer dezelfde intelligentietest. De tweede keer scoor je hoger omdat je de soort vragen al kent.

      Kort: testing = de voormeting beïnvloedt de nameting.

    12. 8.2.1 De one shot case study

      Dit design zag je op de vorige pagina al:

      X → O

      Waarbij:

      X = onafhankelijke variabele / interventie O = observatie/meting van de afhankelijke variabele

      Dus:

      Je voert een behandeling uit en meet alleen daarna wat er gebeurt.

      Bijvoorbeeld:

      Nieuwe lesmethode (X) → toets maken (O)

      De leerlingen halen gemiddeld een 8.

      Kun je nu zeggen:

      "De nieuwe lesmethode zorgt voor goede cijfers"?

      ❌ Nee.

      Want je weet bijvoorbeeld niet eens hoe goed de leerlingen vóór de nieuwe lesmethode waren.

      Misschien haalden ze daarvoor óók al achten.

      Er is dus geen:

      voormeting ❌ controlegroep ❌

      Daarom is het heel moeilijk om andere verklaringen uit te sluiten.

    1. ch of the Da

      i like this one. and we need clever animation idea of under the sea teal backgroudn or wtv an email pill floats down and based on the agic shit it goes in the treasure chest, in the monitr or gets thrown awa and eated by a bigger fish, or somethign different everytime but esy to make and funny, but diffeernt every time ow it shows te to keep to monitor to suprpess at the very least.

      sometimes we use rme clean and rme insights info tomake decisions, someitmes only one or the other in order for ti o match the point of the post/caption. not sure ahout sonar rings? i was thinkign fishing, or somethign sinking under the in the sea and cleanup is expressed from how email disappears or where it goes.

    2. me Email. Two Verdicts. 10s split-screen loop · retention-first The lean, ruthless version. Same address, Keep on your core list, Suppress on a scrape, side by side. Engineered so the loop cannot resolve until the five-second mark, then loops clean to lift watch time.

      this one pops up a lot,

      the same email can get different verdict between one provide rand ours, because we check more things, or because of engagement info. but it can'd be disposable in one but not the other. does that make sense?

    1. engaged 52% Gone quiet 31% At risk 17%

      we should focus on vlidation (rme clean) not rme insights the insihgts is the report audit part, the validation is cleaning, which mayb mean we change aniamtion content above)

    1. そのため、負荷をかけるためのPythonスクリプト

      「クライアントを別プロセスにする理由」と「負荷をかける理由」は別の話な気がするのですが、「測定結果への影響を避ける」→「負荷をかける」いう因果関係に読めてしまいます。以下は分けて説明した方がよいかなと思いました。(因果関係があるならスルーしてください;)

      ・別プロセスにする → 測定への影響を減らすため ・1,000リクエスト送る → 十分な負荷をかけて性能差を見るため

    2. 次の3種類の処理を比較します。

      下のコードは、この3種類に関するコードは載っていないので、最初に下記コードの説明、run_nulitiの引数の説明があるとよいと思いました。

    3. 。

      表の意味がすんなり入って来なかったです。 「XXの状況によって最初に検討する方法(設計?)を表にまとめると....」のような文章があると読みやすいと思いました。

    4. 1つのイベントループと複数イベントループの実行モデル

      「仕事の分割」というのが粒度としてよくわかりませんでした。タスクの意?

  2. www.researchsquare.com www.researchsquare.com
    1. ail does not send you a list of who complained. The tools cannot give you a true compl

      name more thang mail (and in backgroudn show usage worldwide of inboxes, then how many die evry year and then how much of your list you arent' even getting data from , so you spam rate is acual bigger if you actual ratio epr procvider

      )

    2. an Uber rating. Riders score you, you never see who gave you one star, but your score quietly slips and suddenly fewer cars show up. Your recipients rate you the very same

      too many comparisons, do we need ths one?

    3. ing whether it is real and reachable, is the one signal that does not lie. That is the part we d

      is this smooth enough the part we do? or maybe the part i obsess about because its somethign i can actualyl control in a snese

    4. I wish it worked that

      doens'T sound natural... well alot of thigns dont' but i gues this is like sentence order imporatntce. and then we can make it smoother after? like make sentence flow better?

    5. mn. A healthy tree drops its leaves every year. A list that never sheds anything is not healthier, it is just hoarding.

      remove. we can visualize this if we want but we donT' have to show it?

    6. This is the good kind of list, the people who chose you. We are never talking about lists you bought or scraped, only the people who actually want your emails.

      we donT' want to say this. we donT know who is in the audience and col emailers we want them to, WE don'T just go saying it sokay . there is a difference. we can remove not worth it

    1. His life isn't draining into mine. It's moving with mine.

      让男主说,有种3D环绕的感觉,修改台词,变成那种很庄严的共享生命的誓言。

    2. That’s a Sanctified Round. Lucian, that gun kills your kind — MOVE!

      话有点多,怎么不紧张,这个时候看到男主被瞄准,很紧张,感觉话有点多;

    3. EPISODE 33

      对话会有些多,但是保留男主的打斗画面,做的像魔法世界一点,吸血鬼的瞬移,猎人的魔法枪,都做的炫酷一点

    1. Author clarification: This “Withdrawn” status applies only to the original medRxiv preprint. During subsequent peer review, some numerical and statistical results were revised, and the corrected version was published in the Journal of Medical Virology (DOI: 10.1002/jmv.27209). The published journal article has not been withdrawn or retracted. Readers should refer to and cite the peer-reviewed version of record.

    1. eLife Assessment

      The study presents a valuable conceptual framework by classifying pattern-forming gene subnetworks into three established categories. By meticulously enumerating and simulating various network topologies, the authors provide a systematic catalog of these patterning motifs. However, the supporting evidence remains incomplete, as the mathematical generalizations rely on simplified assumptions that may not hold in more complex or realistic scenarios.

    2. Reviewer #1 (Public review):

      Summary:

      The authors tackle a long-standing question in developmental theory: given a gene-regulatory network that includes extracellular signaling, which topologies are even capable of transforming an initial spatial profile into a genuinely new pattern? Building on the classical reaction-diffusion framework in one dimension, but imposing biologically motivated constraints, they prove that every one-signal sub-network must be either Hierarchical (H), self-activating (L+), or self-inhibiting (L-). They further demonstrate that only three composite classes of full networks - pure H, a coupled L+ L- "Turing" pair, and an L- module fed by an intracellular positive loop ("noise-amplifying")-can create non-trivial spatial transformations. Analytical criteria and illustrative simulations are provided, together providing a closed taxonomy, which is supposed to be relevant for real systems.

      Strengths:

      - Useful classification framework. Reducing a vast number of possible gene circuits to three canonical pattern-forming motifs is a valuable organizing insight for both theorists and experimentalists.

      - Practical interpretability. Given a reaction network diagram, one can now decide (assuming the model applies to real systems) whether spatial patterning is even possible, saving experimental effort on in silico screens that could never succeed.

      Weaknesses:

      - Theoretical limitations in the application of Linear Stability Analysis (LSA): I remain uncertain about the framework's reliance on LSA as a necessary condition for non-trivial pattern transformation, especially for large initial perturbations ("spikes"). The revised manuscript itself states that spike amplitudes must be sufficiently small for the linearization to hold. In the rebuttal, the authors argue that large spikes can nevertheless be treated because their influence is initially small outside the spike. However, linear stability of a homogeneous steady state only describes the response to infinitesimal perturbations around that state; it does not generally exclude finite-amplitude perturbations from entering a different nonlinear basin of attraction and producing a heterogeneous stationary state, e.g., as in subcritical Turing patterns. Thus, I do not think the rebuttal establishes the stronger claim that a linearly stable network cannot produce a non-trivial pattern regardless of nonlinear terms.

      - Presentation: The manuscript remains difficult to follow. The argument is distributed across many named requirements and topology classes, long prose descriptions of network structures, and repeated cross-references to the Supplementary Information. Given that the main contribution is a conceptual classification, I think the logical hierarchy should be considerably easier to reconstruct.

      Discussion:

      The study offers a solid conceptual organization of pattern-forming networks. However, the theoretical bridge between infinitesimal linear stability and macroscopic, non-linear pattern emergence still presents some uncertainties. The way the current framework formally treats large initial perturbations leaves some questions open regarding its broad analytical applicability to real biological tissues.

    3. Author response:

      The following is the authors’ response to the previous reviews.

      Public Reviews:

      Reviewer #1 (Public review):

      Summary:

      The authors tackle a long-standing question in developmental theory: given a gene-regulatory network that includes extracellular signaling, which topologies are even capable of transforming an initial spatial profile into a genuinely new pattern? Building on the classical reaction-diffusion framework in one dimension, but imposing biologically motivated constraints, they prove that every one-signal sub-network must be either Hierarchical (H), self-activating (L+), or selfinhibiting (L-). They further demonstrate that only three composite classes of full networks - pure H, a coupled L+ L- "Turing" pair, and an L- module fed by an intracellular positive loop ("noise-amplifying")-can create non-trivial spatial transformations. Analytical criteria and illustrative simulations are provided, together providing a closed taxonomy, which is supposed to be relevant for real systems.

      Strengths:

      (1) Useful classification framework. Reducing a vast number of possible gene circuits to three canonical patternforming motifs is a valuable organizing insight for both theorists and ---experimentalists.

      (2) Practical interpretability. Given a reaction network diagram, one can now decide (assuming the model applies to real systems) whether spatial patterning is even possible, saving experimental effort on in silico screens that could never succeed.

      Weaknesses:

      (1) After the resubmission, I still have concerns regarding the formal definition of "non-trivial transformations" (P1/P2) and its application to noisy or multi-dimensional systems. The criteria rely on counting "new" critical points (maxima/minima). In their response, the authors argue that the diffusion operator instantly smooths discontinuous white noise, allowing critical points to be properly defined. However, this very smoothing process passively generates a landscape of new, smooth local extrema from the initial noise. Consequently, trivial diffusive regularization could inadvertently fulfil the criteria for a "non-trivial" transformation, leaving the definition conceptually problematic.

      That is indeed the case: diffusion alone can generate new concentration maxima and minima; but these would be transient unless there are some self-activatory loops (as we detail over the article). If these concentration maxima and minima are transient in time, they do not count for pattern transformation. In the two version of the article we explicitly stated (in P1 in the introduction when defining pattern transformation) that we only consider resulting patterns that are stable in time. This implies that the concentration maxima and minima that may transiently arise from diffusion alone do not count for the definition of pattern transformation. In the current new version (the third) and after the reviewer’s suggestion, we insist (in red text) that the new concentration maxima and minima need to be stable in time (i.e. non-transient).

      Furthermore, when extending the framework to 2D/3D, the manuscript assumes that starting from a central "spike" will robustly preserve radial symmetry, yielding concentric rings or shells. This overlooks the fundamental nature of macroscopic mean-field models like reaction-diffusion equations. The realization of the final multidimensional pattern depends strictly on the stability of the solution against ubiquitous perturbations (including angular modes) rather than solely on the deterministic symmetry of the initial condition. It remains unclear how the current framework accounts for spontaneous symmetry breaking in cases where these angular modes become unstable, challenging the assumption that radial symmetry will strictly dictate the outcome. We note that the authors' use of noise as an initial condition does not resolve this fundamental issue. Reaction-diffusion equations inherently describe mean-field dynamics, meaning that microscopic fluctuations are continuously present in any real system, regardless of whether explicit stochastic terms are written into the equations. Ultimately, if a symmetric mean-field solution is structurally unstable to these inherent fluctuations, it simply cannot be realized in nature.

      If we understood right the reviewer is saying that there are always fluctuations everywhere and that, thus, the spike initial pattern should also have noise everywhere. In the discussion (and partially in the introduction) we have now added a discussion (in red) on how the resulting patterns possible from such spike-with-noise initial pattern can actually be understood, to a large extent, from those of the homogeneous-with-noise and spike-without noise. In that case, as the reviewer suggests, the resulting patterns do not necessarily have radial symmetry. We have kept the results on spike initial patterns without noise because they are very helpful to understand the pattern transformations possible from spike-with-noise initial patterns. Moreover, as we discuss now, the spatial fluctuations that occur everywhere can be really small compared to the concentration in the spike and, thus, the spike initial pattern without noise can be a good approximation in some cases, at least worth considering.

      (2) Theoretical limitations in the application of Linear Stability Analysis (LSA): I remain uncertain about the framework's reliance on LSA to categorize macroscopic transformations, especially those arising from large initial perturbations (spikes). In their rebuttal letter, the authors justify this by assuming the perturbation remains small over a short time interval. However, because the study aims to describe stationary, asymptotic states, applying a linear approximation that relies on transient t->0 conditions to predict long-term global stability is not fully resolved.

      We are not trying to predict long-term stability and we never intended to. We never claimed that to be the case. We are interested in stable in time spatial patterns but the long-term stability of resulting patterns is not something we intend to see from the LSA. The LSA just provides a necessary (but not sufficient) condition for non-trivial pattern transformations: any network unable to sustain the growth of small perturbations (i.e., any linearly stable network topology) cannot lead to a non-trivial pattern transformation, regardless of the nonlinear terms in the reaction term f(g). From the previous suggestions by the reviewer it could be the case that he/she thinks that since there is always noise everywhere and all the time we can never apply the LSA or that it cannot be applied along time. In fact, we do not try to applied over time (that would make no sense for our purposes). The LSA is only applicable and only informative when applied to the initial pattern (that is at time 0) to see gene network that cannot transform initial patterns into other patterns. As we discuss in the previous version and we further stress in the current one (in red in the LSA), large spikes do not invalidate this approach. Even if the spike would be large, it would only affect cells outside the spike through the diffusion of gene products from the spike. Thus, if a small enough time is considered, large spikes can be considered as small concentration perturbations outside the spike and, thus, in the the worse case scenario our whole approach may not be applicable inside the spike but outside of it (that is reasonable since spikes are by definition narrow).

      Here it is important to stress that many things that used the LSA in the original version of the article do not used it in the current version of the article. In fact, in this article we address two main questions: (i) which gene network topologies can produce non-trivial pattern transformations; and (ii) what can we say about the stationary patterns they produce. We acknowledge that a linear stability analysis alone is not enough to fully characterize the long-term behavior of the system, and this is why we only use LSA as an aid to answer question (i).

      This was not clear enough in the first version of the article but it was explicitly stated in the last version (in the Gene network classification and Linear stability analysis section). This allows us to discard many topologies, but further analysis is still required to assess whether linearly unstable network topologies can actually produce non-trivial pattern transformations.

      It is in this further study that question (ii) comes to play. Here we do not rely on LSA, but instead impose a series of requirements (R1-R5) on the reaction term f(g) that constrain the nonlinear dynamics in a biologically motivated way that prevents pathological behaviors (particularly, boundedness of solutions (R4) and monotonicity of the reaction (R5)). These requirements enable the qualitative analysis of the different unstable network topologies in order to say some things about the possible stationary patterns. This is complemented with numerical simulations and quantitative analysis of some prototypical examples in the supplementary information.

      (3) In the previous round of the review, I suggested that a biomolecular sink, such as A+B -> AB reaction, could break the approach. In their response letter, the authors defend their approach by arguing that such reactions can be accommodated by their abstract constraints (R1-R5) as long as the signs of the Jacobian elements remain invariant. However, the problem I see here is not the sign of the interactions, but the severe loss of spatial homogeneity.

      When a macroscopic initial perturbation (a "spike" of morphogen) is introduced into a domain with a strong bimolecular sink, it will inevitably cause massive local depletion of the consumed substrate near the source. Consequently, the background state of the system will rapidly evolve into a profile with macroscopic spatial gradients long before any spontaneous pattern-forming instability takes over. Mathematically, this dictates that the system no longer possesses a homogeneous steady state, and the Jacobian matrix becomes explicitly space-dependent, which should break the classical LSA approach.

      This criticism seems to be intimately related to the previous one. If we understand correctly, the argument is that in a very non-linear system, such as in the sink described, the spike will rapidly lead to a local change in the concentration of other gene products and that then the LSA is not applicable. This is true but what we care about is whether the initial pattern (that is the system at time zero) is actually stable or not. We care about it because as we explain, pattern transformation is only possible if the perturbation in the initial pattern (spike or noise) is unstable. This is simply a necessary condition (an initial pattern may be unstable to perturbation and still not produce nontrivially transformations). So whether the system will be suitable for a LSA some time after the initial pattern, as the reviewer suggests, is not something we need to know for our classification. Related to the other comments the reviewer may be concerned with whether other perturbations occurring everywhere (and all the time), that is noise, may actually affect the possible resulting patterns (that we described in the new section of the discussion).

      We want to thank the reviewer for this clarification, as we believe we had not fully understood their concern in the previous round of review. In our framework, the bimolecular sink the reviewer suggests corresponds to a three-gene-product network where A and B mutually inhibit each other and both activate AB.

      First it is important to consider that unless something else is specified an A+B→AB system with homogeneous initial pattern (with or without noise) is just not stable: the A and B gene products will decay to zero concentration and AB to a maximal concentration (that would be homogeneous over space if there is no noise). Besides the final stable state is totally stable since with no A or B left the concentration of AB cannot change. We explicitly state in the article (in the LSA section) that we apply the LSA to systems that, when unperturbed, are stable. For other systems we just wait for the system to stabilize and then ask whether pattern transformation is possible from that state if there is some perturbation, where we can now apply a LSA). So strictly speaking the system the reviewer is suggesting is outside the scope of the article and indeed unsuitable for LSA. Nevertheless, the system the reviewer proposes cannot lead to non-trivial pattern formation, as we detail below.

      The reviewer does not specify whether A, B or AB diffuse, we then consider all possibilities. We also assume that A is the gene product in the spike.

      Case in which no molecule diffuses. In this case a spike of A will simply lead to a valley of B (since A reacts with B to deplete B), and a spike of AB in the exact same location of the spike (i.e., no non-trivial pattern transformation occurs). If there is noise, each small fluctuation in the concentration of A or B would lead to a similar fluctuation in AB. Notice this case does not lead to non-trivial pattern transformations (the peaks in the initial pattern and resulting pattern are in the same places). This latter situation in fact we explain in the “Pattern formations from homogeneouswith-noise initial patterns in H networks section.”

      Case in which AB diffuses. Since nothing is promoting the production of A and B, their concentration will inevitably decay to zero and since AB diffuses its concentration on the long-term will inevitably become homogeneous (irrespectively of which initial pattern there may be).

      Case in which only A diffuses. In this case the spike of A will initially lead to a valley of B (since A consumes B) and a peak of AB (since this consumption leads to AB). However, since for each molecule of AB a molecule of both A and B are required and the concentration of B is homogeneous (since B does not diffuse), having more of A around the spike would not lead to more AB in the peak than elsewhere. The concentration of AB would thus become homogeneous over time. The same applies if B is the only molecule that diffuses.

      Case in which A and B diffuse and AB does not. In this case the spike of A will lead to a peak of AB. This would deplete B around the spike but since B can diffuse, new molecules of B would arrive and lead to a further growth in the peak of AB. As a result a stable peak of AB will form (even if A and B will ultimately decay to zero), just around the initial spike of A and both A and B will decay to zero (so no new peaks or valleys form and thus, no non-trivial pattern transformation).

    1. Case 1

      Case#:1, 44-year-old man

      DiseaseAssertion: Stargardt disease

      FamilyInfo: no known family history of an ocular disease

      CasePresentingHPOs: HP:0007663, HP:0007793, HP:0012045, HP:0000603

      CaseHPOFreeText: gradual, relatively recent decreased visual acuity in the right eye, some pigment mottling in both maculae and ‘fish-tail'-like retinal flecks, central relative scotoma

      CaseNotHPOs:

      CaseNotHPOFreeText:

      Genotyping Method: “Analysis of the entire coding region of the ABCA4 gene”

      PreviouslyPublished: NR

      Variant: NM_000350.3:c.191C>T

      ClinVar:2733951

      CAID:CA341285580

      SupplementalData:

    1. 534-05STGD2461 T→AW821RMissense4139 C→TP1380LMissense5682 G→CNoneSilent5814 A→GNoneSilent

      Case#: Family AR534 Proband 05

      DiseaseAssertion: Stargardt

      FamilyInfo: Three paternal cousins are affected with STGD, with onset between the ages of 8 and 10 (unaffected het parents). The proband’s parents reported no visual impairment (father has P1380L/wt, mother has W821R/wt), but the paternal grandmother had been diagnosed previously with age-related macular degeneration at age 68 (het for P1380L). Subsequently, she developed hemorrhagic detachment of the macula, and a diagnosis of exudative AMD was made at age 74

      CasePresentingHPOs:

      CaseHPOFreeText: central visual impairment at age 11, retinal atrophy of the macula and a few peripheral flecks, A dark choroid was observed on fluorescein angiography,

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: Direct DNA sequencing of the 50 exons and flanking intronic regions of ABCR. Heteroduplex analysis

      PreviouslyPublished: n/a

      Variant: c.2461T>A (p.W821R); c.4139C>T (p.P1380L). Phase confirmed. Also has 2 synonymous variants (c.5682G>C and c.5814A>G)

      ClinVar: 7904

      CAID: CA129033

      SupplementalData: n//a

    1. P023 ABCA4 20 c.3035_3037delACA p.Asn1012Ile ATP-binding domain novel deletion – DCABCA4 24 c.3547G>T p.Gly1183Cys – reported – – –ABCA4 46 c.6289C>T p.Pro2097Ser ATP-binding domain novel missense probablydamagingDC

      Case#: Patient #P023, Korean

      DiseaseAssertion: stargardt

      FamilyInfo: n/a

      CasePresentingHPOs:

      CaseHPOFreeText: no individual phenotype information, group only

      CaseNotHPOs:

      CaseNotHPOFreeText:

      PreviouslyPublished: n/a

      Variant: exome sequencing: c.6289C>T p.Pro2097Ser; c.3547G>T p.Gly1183Cys; c.3035_3037delACA p.Asn1012Ile

      ClinVar: CA341277622

      CAID: 2202780

      SupplementalData: n/a

    1. In this study, we summarized the phenotypic and genotypic characteristics of 129 Chinese patients with ABCA4-RD.

      paper not publicly available, but is said to contain this variant based on LOVD entry. requested from library.

      Update: Received paper from library. 1 proband in Figure 1 has this variant, but cannot access the supplementary info to see the individual phenotype information. Affected maternal aunt with homozygous c.4605_4606ins-non-segregation.

    1. In case 71674, diagnosed with arRD, along with a recurrent nonsense mutation (p.Trp663*, HGMD Accession = {"type":"entrez-nucleotide","attrs":{"text":"CM003370","term_id":"909078994","term_text":"CM003370"}}CM003370), a novel splice-site variant was identified (c.2160 + 1 G > T) (Fig. 3a). This variant is predicted to lead to skipping of exon 14 in the ABCA4 transcript. The patient inherited one mutant allele from each parent.

      Patient 71674: Female, Swiss, 13 years old. bi-allelic variants in ABCA4, diagnosed with Retinal dystrophy DD: Retinitis pigmentosa

      Figure 3: Segregation analysis performed on family samples GenotypingMethod: Whole exome sequencing performed on HiSeq2000 and NextSeq500 (252 genes)

      Multiple Variants: VPS13B NM_017890.4:c.897 8A>G:p.Asn2993Ser Heterozygous CM041280

      PCDH15 NM_001142763.1:c. 4329_4337del:p.Pro 1446_Pro1448del Heterozygous

      DHX38 NM_014003.3:c.366 2C>T:p.Thr1221Met Heterozygous

      USH1G NM_173477.4:c.310 A>G:p.Met104Val Heterozygous

    1. Additionally, one novel change in exon 12 (p.Val552Ile) was found in one STGD patient by means of the dHPLC technique. This variant was detected in two alleles out of 200, suggesting a polymorphism.

      Case#: Aguirre-Lamban Unlabeled Proband, Spanish

      DiseaseAssertion: STGD

      FamilyInfo: n/a

      CasePresentingHPOs:

      CaseHPOFreeText: "Diagnosis of STGD was determined according to a bilateral central vision loss with a beaten-bronze appearance and/or the presence of orange-yellow flecks in the retina from the posterior pole to the mid-periphery; typical dark choroid observed by fluorescein angiography; and normal to subnormal electroretinograms (ERGs)."

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: ABCR400 microarray, direct sequencing, dHPLC, haplotype analysis

      PreviouslyPublished: n/a

      Variant: c.1654G>A p.Val552Ile, interpreted as non-pathogenic, suggested to be a polymorphism

      CAID: CA239745

      SupplementalData: n/a

    1. 16P36M198426217–50.300.10 P37F198913817–40.22

      Case#: Family 16, P37, female, Netherlands 13yo at onset

      DiseaseAssertion: Stargardt

      FamilyInfo: 1 affected sibling with same genotype

      CasePresentingHPOs:

      CaseHPOFreeText: visual acuity: OD=0.22, FAF images consistent with STGD1

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: Sanger

      PreviouslyPublished: n/a

      Variant: c.5196+1137G>A; c.859-506G>C

      ClinVar: 438100

      CAID: CA26843511

      SupplementalData:

    1. Souradip C

      PMID:35973334

      Gene: ABCA4

      HGNC ID: 34

      Case#: 18-year-old sister II.3

      Variant splice-site variant NC_000003.11(NM_016247.3):c.1239 + 1G > T [Chr3:100972539C > A

      FammilyInfo two-generation north Indian family with three members affected with Stargardt-like macular dys trophy

      CasePresentingHPOs:ow vision and difficulty in night vision, with symptoms starting in the early second decade of life, which progressed slowly over time

      PedrigreeIn the results section is mentioned

      CaseHPOFreeText:NA

      CaseNotHPOs:Na

      CaseNotHPOFreeText:NA

      Genotyping Method:2.3. Validation of identified variant by Sanger sequencing

      PreviouslyPublished:NA

    1. Case 2A 19-year-old female referred for consultation for difficulty reading, particularly in dim light. She was clinically diagnosed with STGD 3 month prior, after complaining of gradual difficulty in focusing. Family history was not significant for ocular disease. Visual acuity measured 20/40 OD and 20/150 OS. Slit-lamp examination was unremarkable with normal anterior segments and applanation tensions of 14 mmHg OU. Funduscopic exam revealed bilateral central atrophy, multiple fleck lesions, multiple clumps of yellowish deposits at the level of the retinal pigment epithelium in the posterior pole surrounded with some pigment clumping, and no evidence of atrophy of the retinal pigment epithelium. Autofluorescence imaging revealed multifocal atrophic lesions involving the central macula and peripheral hyperautofluorescent flecks OU. The peripapillary regions demonstrated atrophic flecks OU without confluent atrophy (Figure 2, A and B). Genotyping revealed homozygous ABCA4 mutations, P1380L and P1380L.Open in a separate windowFig. 2Case 2. STGD mutations P1380L and P1380L. A, Autofluorescence OD. B, Autofluorescence OS show multifocal hypoautofluorescent (atrophic) lesions involving the central macula OU and peripheral hyperautofluorescent flecks OU. The peripapillary regions have atrophic flecks OU but there is not confluent peripapillary atrophy.

      Case#: Hwang Case 2, female, 19yo at report, 18yo at onset

      DiseaseAssertion: Stargardt

      FamilyInfo: Family history was not significant for ocular disease

      CasePresentingHPOs: HP:0007663, HP:0500087, HP:0011507

      CaseHPOFreeText: difficulty reading, particularly in dim light; gradual difficulty in focusing. Visual acuity measured 20/40 OD and 20/150 OS. bilateral central atrophy, multiple fleck lesions, multiple clumps of yellowish deposits at the level of the retinal pigment epithelium in the posterior pole surrounded with some pigment clumping, and no evidence of atrophy of the retinal pigment epithelium. Autofluorescence imaging revealed multifocal atrophic lesions involving the central macula and peripheral hyperautofluorescent flecks OU. The peripapillary regions demonstrated atrophic flecks OU without confluent atrophy (Figure 2, A and B).

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: Genotyping was performed by the ABCR400 microarray followed by direct sequencing to confirm identified variants.

      PreviouslyPublished: n/a

      Variant: P1380L homozygous

      ClinVar: 7904

      CAID: CA129033

      SupplementalData: n/a

    1. A 25-year-old White man presented with bilateral central vision loss due to foveal lesions consisting of vitelliform fluid.

      Case#: Patient 1, male, Caucasian, onset at 20yo, USA

      DiseaseAssertion: ABCA4

      FamilyInfo: No family history of retinal disease.

      CasePresentingHPOs: HP:0007677, HP:0030603, HP:0030500, HP:0030636, HP:0004328, HP:0012372

      CaseHPOFreeText: Bilateral central vision loss, progressive decline in visual acuity (20/60 both eyes), foveomacular vitelliform lesions with fluid accumulation, optical gap lesions progressing to cavitated appearance after fluid resorption, thinning and abnormal reflectivity of photoreceptor layers, near-infrared autofluorescence abnormalities in lesion-adjacent regions

      CaseNotHPOs: HP:0000510, HP:0000511

      CaseNotHPOFreeText: No generalized rod or cone dysfunction on full-field electroretinogram, EOG findings not consistent with bestrophinopathy (Arden ratio 1.62)

      Genotyping Method: Exome sequencing

      PreviouslyPublished: None

      Variant: NM_000350.3(ABCA4):c.5882G>A (p.Gly1961Glu), NM_000350.3(ABCA4):c.4139C>T (p.Pro1380Leu)

      ClinVar: ClinVarID:7888, ClinVarID:7904

      CAID: N/A

      SupplementalData: N/A

    1. RP-087M30c.6397T>Cp.C2133RD1D2D322.80Y

      Case#: Sporadic RP Patient 087, male, Chinese, 30yo at report

      DiseaseAssertion: RP

      FamilyInfo: n/a, sporadic case

      CasePresentingHPOs:

      CaseHPOFreeText: "The sporadic RP patients generally showed pubertal night blindness, restricted peripheral vision, progressive vision loss, overall bone-spicule pigmentation of the retina, attenuation of retinal vessels, and the flattening of the rod and cone ERG responses."

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: WES with Sanger sequencing confirmation

      PreviouslyPublished: no

      Variant: c.6397T>C p.(C2133R)

      ClinVar: 2021273

      CAID: CA341277387

      SupplementalData:

    1. STGD in 48 patients (55%) was explained by recessive ABCA4 mutations (supplemental table S2). Only 22 patients could be solved using previously known STGD causing mutations. However, we identified 35 novel mutations in ABCA4 contributing to the diagnosis of 25 STGD patients. This contained 10 novel mutations leading to amino acid substitutions already known to cause disease and mutations known to cause diseases other than STGD. In addition, we identified 13 novel nonsense mutations. The remaining 12 novel mutations are well justified, and novel mutations were either completely absent or extremely rare in controls.

      Case#: Patient #133, Chinese

      DiseaseAssertion: Stargardt

      FamilyInfo: n/a

      CasePresentingHPOs: n/a "Diagnosis of STGD was based on the clinical manifestations" is all that is stated

      CaseHPOFreeText: n/a

      CaseNotHPOs: n/a

      CaseNotHPOFreeText: n/a

      PreviouslyPublished: n/a

      Variant: c.6289 C>T p.(P2097S); c.4605_4606insT p.(V1535fs)

      ClinVar: 2202780

      CAID: CA341277622

      SupplementalData: info found in table S2

    1. The Akhada

      I could use this approach in my Community Photo Essay by photographing normal routines and objects instead of only the most obvious activities in my community. Small details like where people work, the things they use, or how they interact could help an outsider understand what being part of the community actually feels like.

    2. Unlike your stereotypical teenage girls, said Siksha, the students don’t spend much time on boys or fashion. “No point doing that when all we wear are T-shirts and shorts.” They all sport matching crew cuts, given to them when they arrive.

      An outsider might initially see their similar clothing and haircuts without understanding why they look alike. The writing gives those details more meaning because they become signs of belonging to the academy and show how the girls share a lifestyle that is centered around wrestling.

    3. Unlike your stereotypical teenage girls, said Siksha, the students don’t spend much time on boys or fashion. “No point doing that when all we wear are T-shirts and shorts.” They all sport matching crew cuts, given to them when they arrive.

      An outsider might initially see their similar clothing and haircuts without understanding why they look alike. The writing gives those details more meaning because they become signs of belonging to the academy and show how the girls share a lifestyle that is centered around wrestling.

    4. neha Sharma, 16, persuaded her parents to send her to the academy because she missed her older sister, who was training to be a wrestler. “I felt lost without her,” she said.

      This part changes the story from being mostly about wrestling and training to being about relationships and belonging. It helps show that the academy is more than a place where they practice a sport because the girls have also created a community and support system.

    5. “There are no friends on the mat,”

      I thought this was interesting because an outsider might assume that competing against each other would hurt their friendships. Instead, the girls understand that competition on the mat is separate from their relationships outside of it. This seems like an unwritten rule that members of their community understand.

    6. After the warm-up, their training varies. Cardio days can mean a cross-country run or stair climbing. On sports days, they play handball or basketball. Strength-building days are the most demanding of all: The girls must drag blocks of wood across the field or pull themselves up several meters of gnarly ropes.

      This photo shows how disciplined and structured their daily routine is. Having the girls running together instead of focusing on one person also makes them look like a team and shows that training is something they experience as a community.

    1. CHORUS: oh can't you ask a younger man

      Q: The Chorus can directly speak to onstage characters? What is it's role when it does? Is it acting as a single charcater?

    2. the man from Argos fled

      E: After Œdipus's death, Eteocles and Polyneikes agree to shared the throne, alternating who ruled each year. But at the end of the first year, Eteocles exiled Polyneikes, and he (Polyneikes), fled to the city of Argos. He gained the favor ofthe city's king, married the King's daughter, and raised an army(of the Argive), to attack Thebes, and reclaim his rights, one champion for each gate. At the seventh gate, the familial curse was fulfilled, and both killed each other at the same time.(https://www.britannica.com/topic/Seven-Against-Thebes)

    3. for death is longdeath is very longyou go on worrying about the gods oflife

      O: Antigone shows foresight, and emphasizes the importance of the afterlife in her eyes, where it is eternal compared to the limited time mortals have on Earth.

    1. The glitter of her jewels rose to meet it,

      all the jewels and riches spoken about in this passage are examples of the envy, evil, and human desires that comes after the story of Adam and Eve that is told in Paradise lost. the story of adam and eve also relates to the waste land because they lose the garden of eden after trying the forbidden fruit just as the waste land deals with the issues of lost fertility in the land in England due to industrialization.

    1. he offered lavish details of the land’s bountiful resources, countered biased views of Native Americans as simple savages and nomads by describing the Powhatan confederacy, and advocated strong leaders and leadership for maintaining colonies.

      His evidence towards what he found in new-virginina and what he observed while looking around

    1. Main navigation Home

      The main navigation or the drop down menus have both good and bad practice in my opinion. It follows the understandable principle well because it is very easy to follow and organized in terms of where the site is taking you. However, it could also be considered bad practice in terms of following the operable principle. This is because it may be hard to precisely navigate these menus if someone has motor impairments.

    2. ARIA stands for Accessible Rich Internet Applications Suite. It defines a way to make Web content and Web applications more accessible to people with disabilities.

      This is a good example of the robust principle, as the website uses assistive technology to help screen readers navigate the website.

    3. Canada.ca Accessibility Standards Canada Accessibility statement

      The "breadcrumbs" are a good example of the understandable and operable principles. It is understandable because users don't have to have the entire website layout in their head, and can easily identify where they are in the website. Its also operable because users can easily go back and fourth through the hierarchy.

    4. This site will work to meet the guidelines from Web Content Accessibility Guidelines 2.1 AA. This sets a higher standard.

      Important information to the reader is all written in text. This is good practice under the perceivable principle as the site does not solely rely on visual cues.

    5. Accessibility statement

      Good example of the robust principle. The page uses different level of headers so that the information is organized. Accessibility statement is at the top labeled as header one.

    1. .Ultrasonido abdominal Evaluación por imagen de órganos y estructuras del abdomen. Puntos: -Valoración de órganos abdominales -Estudio diagnóstico no invasivo -Apoyo en la detección de alteraciones .Ultrasonido Doppler Vascular Estudio del flujo sanguíneo en venas y arterias mediante tecnología Doppler. Puntos: -Evaluación del flujo sanguíneo -Valoración arterial y venosa -Estudio de circulación en distintas regiones .Ultrasonido obstétrico Evaluación por imagen durante el embarazo para valorar el desarrollo fetal. Puntos: -Seguimiento del embarazo -Valoración del desarrollo fetal -Evaluación mediante ultrasonido obstétrico .Ultrasonido ginecológico Estudio por imagen enfocado en la valoración de órganos y estructuras pélvicas. Puntos: -Valoración ginecológica por imagen -Evaluación de estructuras pélvicas -Apoyo diagnóstico ginecológico

    2. Ubicación y AtenciónConsultorio Médico EspecializadoUres Km 3.5, San Pedro El Saucito, 83305 San Pedro el Saucito, Son.+52 (55) 5678-9012 / +52 (55) 5678-9013dr.jluis.delatorre@gmail.comLun - Vie: 08:00 - 19:00 hrsSábados: 08:00 - 14:00 hrsAtención con previa cita reservadaVer ubicación en Google Maps

      Revisar info

    3. Servicios y FormaciónUltrasonido Obstétrico Genético y EstructuralEcografía Doppler FetoplacentariaPerfil Biofísico y Marcadores CromosómicosDiplomado en Ultrasonografía Médica ContinuaTalleres Prácticos Hands-On para Especialistas

      Retirar esto

    1. Rapport d'Analyse Factuelle, Zététique et Épistémologique

      Source analysée : Émission Face À L'Actu (Le Crayon, 22 septembre 2026) – « Une prof de prépa et un prof de primaire parlent de l'école publique » (Intervenants : Madeleine de Jessey, professeure en classe préparatoire littéraire / Mohamadou, professeur des écoles).


      1. Résumé des Thèses

      L'échange s'articule autour des résultats du classement PISA et de la dégradation perçue du niveau des élèves français. Deux approches s'opposent et se complètent :

      • Thèse de Madeleine de Jessey (Conservatrice / Rationaliste pédagogique) : L'effondrement des performances (lecture, écriture, grammaire) découle de l'abandon de l'enseignement explicite, du recul de la grammaire/dictée dès le primaire, de méthodes de lecture non strictement syllabiques (présence de « mots outils » dits globaux) et d'une formation initiale défaillante des enseignants.

      La solution réside dans des réformes structurelles sur le long terme : labellisation des manuels (100 % syllabiques), retour aux méthodes explicites et évaluations nationales régulières.

      • Thèse de Mohamadou (Pragmatique / Constructiviste de terrain) : La baisse mesurée par PISA reflète un décalage entre les outils d'évaluation traditionnels et l'évolution des profils d'élèves/sociétale.

      Il impute la crise aux instabilités politiques (changements permanents de ministres/programmes), au manque de formation continue, au climat de violence institutionnelle subie par les enseignants, au rôle des écrans et aux inégalités familiales/socio-économiques.

      Il défend une pédagogie différenciée et progressive.


      2. Extraction et Vérification (Le Cœur du Debunking)

      Définition des Strates de Valeur (pour l'analyse du niveau et des diplômes) :

      1. Valeur Instrumentale (Légale) : Ce que le titre/diplôme autorise ou garantit juridiquement (droit de passage, équivalence administrative).

      2. Valeur Relative (Économique) : Ce que la compétence ou le titre apporte sur le marché du travail par rapport à l'effort investi.

      3. Valeur Distinctionnelle (Symbolique) : Ce que le titre/niveau véhicule en termes de prestige et de statut social.


      Tableau de Fact-Checking et d'Analyse Argumentative

      | Affirmation / Chiffre | Verdict | Analyse (Donnée vs Message) | Crédibilité | | --- | --- | --- | --- | | « La France est 27e sur 91 en compréhension de l'écrit, perd 18 points en PISA 2025... un tiers des élèves est en difficulté de lecture. » [00:03:54] | 🟠 VRAI MAIS TROMPEUR | Fait : Les scores PISA récents confirment une baisse moyenne continue des résultats de la France en compréhension de l'écrit.<br>

      <br>Manipulation : Omission de la structure des données.

      Le déclin moyen cache un accroissement massif de l'écart-type socio-économique.

      La France reste l'un des pays où le milieu d'origine des parents prédit le plus le score de l'élève.

      L'agrégation sous une moyenne nationale crée un biais de généralisation (la baisse touche de manière disproportionnée les milieux défavorisés).<br>

      <br>Réalité Scientifique : La baisse PISA n'est pas uniforme : elle résulte principalement de la dégradation des résultats du quartile inférieur socio-économique, corrélée à la ségrégation résidentielle et scolaire.<br>

      <br>

      <br>Strates de valeur (Compétence de lecture) :<br>

      <br>- Instrumentale : Garantie légale faible pour la poursuite d'études sans remédiation.<br>

      <br>- Relative : Pénalisation lourde sur le marché du travail qualifié.<br>

      <br>- Distinctionnelle : Perte du statut d'alphabétisation fonctionnelle avancée pour une partie de la population. | 6/10 | | « Quand on compare la même dictée donnée en 1987 et aujourd'hui, les élèves d'aujourd'hui font deux fois plus de fautes. » [00:05:15] | 🟢 VRAI | Fait : Études réitérées de la DEPP (Ministère de l'Éducation nationale) sur la même dictée en 1987, 2007, 2015 et 2021 : le nombre moyen de fautes est passé de 10,7 à 19,4.<br>

      <br>Manipulation : Le chiffre est exact et l'interprétation du recul en orthographe grammaticale est valide.

      Toutefois, le message omet le paramètre de la réduction globale du volume horaire dédié au français au primaire (-1,5h à -2h par semaine en moyenne depuis les années 1980).<br>

      <br>Réalité Scientifique : Consensus scientifique sur la baisse nette de la maîtrise de l'orthographe grammaticale (accord sujet-verbe, accord du participe passé), transversale à toutes les catégories sociales, liée au temps consacré à l'enseignement formel du code. | 9/10 | | « Seulement 5 % des professeurs des écoles utilisent une méthode de lecture 100 % syllabique. » [00:22:50] | 🟠 VRAI MAIS TROMPEUR | Fait : Statistique issue de rapports/enquêtes d'évaluation sur les manuels de CP (notamment les synthèses du Conseil scientifique de l'Éducation nationale - CSEN).<br>

      <br>Manipulation : Fausse dichotomie entre « méthode mixte/globale » et « méthode syllabique ».

      Une méthode introduisant quelques « mots outils » fréquents (ex: dans, est, avec) dès le début du CP n'est pas une « méthode globale » destructrice.

      Les neurosciences de la lecture (Stanislas Dehaene / CSEN) préconisent le décodage systématique (phonème-graphème), mais reconnaissent que l'immense majorité des méthodes actuelles sont à dominante syllabique combinée.<br>

      <br>Réalité Scientifique : Ce qui compte scientifiquement est le déchiffrabilité précoce et le débit combinatoire, et non l'exclusion absolue de quelques mots invariables indispensables à la syntaxe. | 5/10 | | « Quasiment 50 % des élèves de 5e ont un niveau insuffisant en français. » [00:00:00] | 🟠 VRAI MAIS TROMPEUR | Fait : Données issues des évaluations nationales de début de 5e (DEPP). Environ 45 à 50 % des élèves ne maîtrisent pas satisfaisamment les automatismes de la langue.<br>

      <br>Manipulation : Équivocation sur le terme « insuffisant ». La note de cadrage mesure la maîtrise de compétences spécifiques standardisées, et non un « illettrisme » total.

      Présenter ce chiffre comme un effondrement global induit une panique morale.<br>

      <br>Réalité Scientifique : Il existe une fracture marquée entre la compréhension orale/lexique usuel (plutôt préservés) et la maîtrise de la syntaxe complexe et de l'orthographe (en nette difficulté). | 6/10 | | « Plus d'un cinquième (1/5) des enseignants sont harcelés par d'autres enseignants au sein de l'institution. » [00:31:01] | 🟡 HORS CONTEXTE | Fait : Propos attribués aux travaux du sociologue Éric Debarbieux sur le climat scolaire et la souffrance au travail.<br>

      <br>Manipulation : Généralisation à partir d'enquêtes sur le climat relationnel dans certains établissements.

      Le chiffre de 20 % regroupe sous le terme « harcèlement » une large palette d'incidents allant des conflits d'équipe récurrents aux tensions hiérarchiques, et non uniquement du harcèlement moral au sens juridique strict.<br>

      <br>Réalité Scientifique : Le mal-être enseignant est scientifiquement documenté, mais ses déterminants principaux sont le manque de reconnaissance, la perte de sens et les incertitudes organisationnelles, avant les conflits entre pairs. | 4/10 |


      3. Analyse Rhétorique et Biais (Zététique)

      Qu'est-ce que l'Indice d'Impact sur la Distorsion (IID) ?

      L'IID est un indicateur évalué sur une échelle de 1 à 10 qui mesure à quel point un biais ou un sophisme altère la vérité scientifique et déforme la réalité des faits :

      • 1 à 3 : Biais mineur (imprécision rhétorique n'affectant pas le fond).
      • 4 à 7 : Biais significatif (altère la perception et induit des jugements erronés).
      • 8 à 10 : Biais majeur (le raisonnement repose entièrement sur ce sophisme, invalidant scientifiquement la conclusion).

      Biais et Sophismes Identifiés

      A. Généralisation Hâtive / Anectodisme (Biais de confirmation)

      • Mécanisme : Opposer une expérience personnelle (« J'ai trois filles », « Dans mes classes je n'ai jamais vu ça ») à des données agrégées ou, inversement, utiliser une statistique spécifique pour qualifier l'intégralité d'une population.

      • IID : 7/10 (Biais significatif)

      • Impact : L'argumentation par l'anecdote (Madeleine citant sa situation de maman ou Mohamadou citant sa pratique en Val-de-Marne) neutralise la rigueur statistique et empêche d'identifier les régularités structurelles.

      B. La Fausse Dichotomie (« Ancienne méthode » vs « Pédagogisme moderne »)

      • Mécanisme : Réduire la crise de l'enseignement à un combat binaire entre le retour à l'instruction traditionnelle (grammaire rigide, dictée, effort) et les théories dites « pédagogistes » issues des années 1970.

      • IID : 8/10 (Biais majeur)

      • Impact : Ce cadrage masque la variable de confusion centrale : la dégradation socio-économique, la ségrégation spatiale et le financement inégal de l'école selon les territoires.

      Le débat focalise sur des guerres de méthodes éducatives là où les données montrent un poids prédominant du capital socio-culturel des familles.

      C. L'Omission de la Variable de Confusion Socio-Économique

      • Mécanisme : Discuter de la baisse de niveau (PISA, dictée) sans contrôler systématiquement par les variables de pauvreté, d'immigration récente ou d'exposition au numérique domestique.

      • IID : 9/10 (Biais majeur)

      • Impact : Attribuer la baisse de niveau uniquement aux méthodes pédagogiques ou aux ministres successifs constitue une erreur de raisonnement causale.

      En sociologie de l'éducation (Bourdieu, Passeron, Rochex), le niveau scolaire est très fortement corrélé à la composition socioprofessionnelle des établissements.

      D. Sophisme de la Motte Castrale (Motte-and-Bailey)

      • Position défendable (Motte) : « L'école doit garantir la maîtrise de la lecture syllabique et de l'orthographe fondamentale. »
      • Position extrême glissée (Castrale) : « 95 % des enseignants appliquent de mauvaises méthodes causant l'illettrisme de masse en France. »

      • IID : 6/10 (Biais significatif)

      • Impact : Madeleine de Jessey bascule régulièrement entre un consensus scientifique (l'efficacité de la méthode explicite) et une charge contre l'ensemble du corps professoral du primaire prétendument mal formé ou complice du déclin.


      4. Conclusion et Reconstruction Scientifique

      Reconstruction Rigoureuse de la Réalité Pédagogique

      Si l'on appliquait une démarche scientifique stricte aux mêmes données statistiques (PISA, DEPP, CSEN), la conclusion s'énoncerait ainsi :

      1. Sur la baisse des performances : La dégradation mesurée en orthographe et en compréhension de l'écrit est un fait incontestable et mesuré.

      Toutefois, ses causes sont multifactorielles :

      • Réduction nette du volume horaire annuel dédié au français au primaire sur 40 ans.

      • Poids prépondérant et croissant des inégalités sociales et territoriales dans le système éducatif français.

      • Effet de la concurrence attentionnelle (écrans domestiques, baisse du temps de lecture de loisir).

      • Sur les méthodes de lecture et de grammaire : La recherche en neurosciences cognitives (CSEN) établit la supériorité de l'enseignement explicite et combinatoire (syllabique).

      Cependant, la quasi-totalité des enseignants actuels utilisent des méthodes à dominante syllabique.

      La crise ne provient pas d'un « dogme de la méthode globale », mais de disparités d'application, de lacunes dans la formation continue des enseignants et du manque de temps dédié à la consolidation des automatismes.

      1. Sur la crise du système : L'instabilité des politiques ministérielles et la perte d'attractivité du métier (dévalorisation relative des salaires à Bac+5 et baisse du prestige distinctionnel) créent un épuisement du corps enseignant.

      La solution scientifiquement documentée ne réside ni dans la nostalgie d'une école d'antan mythifiée, ni dans la négation du déclin, mais dans une stabilisation des programmes sur le long terme, un investissement massif ciblé sur le primaire défavorisé, et la revalorisation de la formation initiale et continue des professeurs.

    1. Export to Excel and other systems

      Lots of overlap between this and the other articles in this section. Unclear what our goal here is with these articles.

      Would it be better to list out some commonly used reports? I'm not sure there's huge value in generic articles on reporting - the UI should be self-explanatory

    1. eLife Assessment

      The study presents a valuable dataset and analysis on two sympatric Mediterranean clingfishes which will be of interest to the fields of evolutionary genomics, population genetics and comparative phylogeography, and especially to marine biologists working on population connectivity. The comparative design provides solid evidence that contemporary connectivity is more predictable across species than deeper phylogeographic and demographic history. The analysis of the genomic data, which is still incomplete, would benefit from further work and clarification, particularly regarding the evidence for parallel genomic divergence.

    2. Reviewer #1 (Public review):

      Summary:

      This article taps into the very interesting phylogeographic situation of two sympatric species of clingfishes sharing the same distribution and environment around Crete and the island of Cythera. Basically, it shows that the population structures of these fishes are influenced in a parallel manner by seascape, low dispersal, and potentially drift or selection despite a different phylogeographic history. This parallelism is looked after in a detailed manner at the genome level. I am very enthusiastic about this extremely well-constructed and very cleverly designed study of this natural "common garden" evolutionary duplicate situation, something sufficiently rare to be underlined.

      The authors have produced complete genomes for the two species and their five population samples, from which they are able to conduct up-to-date data analyses. The text is clearly written, without too much jargon, and the options chosen for the various analyses and bioinformatic pipelines are sufficiently detailed so it is rather easy to follow what they've precisely done, something which is alas not that frequent in comparable studies.

      Strengths:

      The structural part of their study is really very convincing, with results showing that despite very small differences, the population structures of the two species conform quite well with what could be inferred from larval dispersal modeled according to passive particle drift. The parallelism is striking, despite minute differences, and despite quite different population sizes for the two species.

      Weaknesses:

      After that, the authors tried to identify a set of outlier loci whose distribution doesn't conform to the main population differentiation. This search for outliers is made according to classical methods based on Fst or its derivates, like the program PBS which compares the Fst values in trios on sliding windows along the genome. The study is well conducted, namely taking into account false positives and false discovery rates in a conservative manner.

      Assuming that some environmental variables differ between the five locations where they have samples, the authors hypothesized from this that similar environmental pressures give similar patterns, potentially affecting pro parte similar places in the genome of the two species. However, there is a blind spot in their analysis inasmuch as it seems that recombination and linkage are not taken into account. It is well known that recombination rates are very variable along the chromosomes, going from recombination hot spots to stretches of very low levels of crossovers. It is well known as well that a variety of phenomena like background, purifying, and sweep selection are quite sensitive to the recombination rates, this having important bearings on local variation of a series of variables like Fst, D, Pi... . Hence, their conclusions about a direct action of environmental pressures may largely be challenged, especially when it is to look for functionality of tightly linked genes, and should be taken as the last hypothesis to be retained when the others can be ruled out.

      There are probably sufficient levels of conservation and synteny in teleost fish and a sufficient number of species where recombination maps exist so that the authors can reconstruct a map for their species, at least partially, permitting to use methods explicitly taking recombination rate variation along the genome into consideration (like for instance DILS: Demographic inferences with linked selection 2021 Mol Ecol Res) to challenge their adaptationist conclusions, all the more given the fact that the question of the eventual nature of differential environmental pressures cannot be addressed with extant data.

      (3) Moreover, there is now a considerable amount of literature which deals with what is coined "islands of differentiation" or "islands of speciation" or "barriers loci". These genomic segments coincide very often with low recombination regions, and some of them are quite often shared in multiple pairs of closely related species. It seems that their experimental set up (several closely related species) is ideal to easily derive the landscape of genomic architecture of divergence in the genus, this permitting to see where the conserved islands of differentiation stand, how much they are conserved or not in the different species, and how this matches or not with their PBS peaks, and by the way, allowing a more direct comparison with similar landscapes published in other species. They have everything at hand, and this will be a very valuable addition to this article that could hence become a more fascinating paper.

    3. Reviewer #2 (Public review):

      Summary:

      The authors analyzed genetic population structure of two clingfish species in the eastern Mediterranean Sea. They used a genome-wide DNA sequence dataset representing several populations of both species and found general patterns of isolation that agree with likely patterns of dispersal and described parallel signatures suggesting genomic adaptation. The results support that similar species follow the same evolutionary trajectories when they evolve in the same ecological and geographical context and when meta -populations are subject to the same constraints with respect to dispersal.

      Strengths:

      The findings as such include a population genetic analysis of taxa for which data are lacking. Conclusions on population subdivision as well as genomic divergence suggestive of genomic adaptation are well supported. The analysis of the genetic data is according to established standards and useful.

      Weaknesses:

      The idea to apply drift simulations to study dispersal in pelagic fish larvae makes sense; I do however, wonder to what extent the neutral drift scenario applies to the species under study, as an earlier paper by the authors ( J Fish Biol 2020 Nov 3; 98(1): 64-88) emphasizes a strong near-coastal retention of larvae. Accordingly, the drift simulations are in agreement with the observed population structure, but I note that a simpler isolation-by-distance model and dispersal primarily along coastlines would equally agree with the data. A demonstration that drift simulations contribute to a refined model of population subdivision would require a denser sampling of populations and measures of drift between these. Ideally, this should include a demonstration that areas where drift is reduced coincide with genetic discontinuity in the absence of deeper areas of the sea. This is not to say that the approach as such is not interesting, but the conclusions towards this goal are not very well supported by data.

      One aspect in the study should be clarified: between-species gene flow is common between closely related species of fish. If this occurs, this would dramatically affect the interpretation of parallelism and convergent evolution at the genomic level. Hybridization should be ruled out or discussed. The two focal taxa are not sister taxa according to a phylogenetic tree (Figure 6) based on only a few genetic loci. Even if a more complete dataset is missing for most relevant taxa to recalculate this phylogeny, I would like to see an assessment of the degree of separation between the two taxa at a genome-wide level. The authors mention that the genetic variants that are subject to parallel evolution are not identical. This is promising and should be highlighted more in case hybridization is likely.

    4. Reviewer #3 (Public review):

      Summary:

      This manuscript asks whether biogeographic patterns are similarly predictable across temporal scales in two sympatric clingfishes (Gouania). By integrating oceanographic dispersal simulations, population genomics, mtDNA, and demographic inference, the authors find broadly concordant contemporary connectivity between species but less consistent deeper phylogeographic and demographic histories. The study addresses an interesting question, although several aspects of the genomic analyses and their interpretation need further attention.

      Strengths:

      The manuscript has a strong comparative design and an interesting biological system. Comparing sympatric species provides a useful framework for asking how consistently shared environmental processes translate into similar evolutionary patterns. The integration of oceanographic, population-genomic, phylogeographic, and demographic evidence across temporal scales is a particular strength. The most convincing result is that contemporary connectivity appears more predictable across species than deeper phylogeographic and demographic history.

      Weaknesses:

      The main new dataset is whole-genome resequencing of 85 individuals (46 G. orientalis, 39 G. hofrichteri) from five localities on Crete and Kythira. These reads were mapped to the chromosome-level Gouania willdenowi assembly (fGouWil2; publicly labeled as G. willdenowi but referred to throughout as the G. adriatica reference) produced by the Vertebrate Genomes Project (Rhie et al. 2021). No new reference genome was generated here, which limits the genomic contribution. Ideally, each focal species would have its own reference.

      Mapping both species to a third congener also creates an important reference-bias issue. Figure 6a places G. orientalis closer to the reference lineage than G. hofrichteri, so the more distant species is expected to map less well and yield fewer callable sites. That is the direction observed: G. hofrichteri yields nearly half as many called variants (3.17 M vs 5.82 M). This could reflect real diversity, differential mapping, or both. Per-species mapping rates, missingness, and callable-site counts should therefore be reported, and outlier comparisons repeated using sites callable in both species.

      Coverage is also low and uneven: 69 individuals were targeted at 5X and 16 at 15X. This is probably adequate for broad population structure, but more problematic for heterozygosity- and frequency-based statistics, as hard calls at ~5X can bias heterozygosity, nucleotide diversity, FIS, and nearly fixed variants. The single 15X G. orientalis from NNE-Mades, which has unusually high diversity and affects FST, illustrates the issue. Key results should therefore be checked using genotype likelihoods, common-depth downsampling, or the higher-coverage subset. Table S1 should also report realized depth and missingness and clarify the discrepancy with the Methods, which state that two individuals per population were sequenced at 15X. Agreement among PCA, admixture, and FST is not independent reassurance because all use the same hard-called genotype matrix (see Lou et al. 2021; Helmkampf et al. 2025).

      Much of the remaining dataset comes from previous studies or public resources: the COI sequences, four of five MSMC2 genomes, the VGP genome, and Copernicus currents. Thus, the main new contribution is the Crete-Kythira population-genomic dataset. The strongest result is that contemporary connectivity is broadly concordant between species, whereas deeper phylogeographic and demographic histories are less predictable. The geographic mismatch among datasets, however, limits direct comparisons across scales.

      The least secure result is parallel genomic divergence, which is emphasized in the title. The null model for parallel divergence is problematic. The enrichment test treats 29,039 windows as independent even though 60-kb windows overlap by 30 kb. Adjacent windows are therefore not independent, and both species also share the same reference architecture. The significance of 8 shared windows among 397 and 220 outliers may consequently be inflated. This should be tested with a null model that preserves genomic autocorrelation, such as non-overlapping blocks or permutations of larger genomic segments. Otherwise, the parallelism claim should be softened, particularly in the title.

      The gene-level analysis raises the same concern and also contains several inconsistencies. The background is 23,789 genes in the Methods, but 21,274 in Table S3; the Methods specify {plus minus}30 kb around window midpoints whereas Table S6 appears to use 120 kb; and the nearly fixed-variant analysis uses 45 and 8 genes in the Methods versus 52 and 14 in the Results/Table S3. These numbers need to be reconciled. I would also avoid placing much weight on a single shared tuba gene without an appropriate null model.

      The MSMC2 analysis uses one diploid genome per species but is interpreted as species-level demographic history. Because these genomes come from different localities and the manuscript itself shows substantial within-species structure, species and locality are confounded. These results should be framed as exploratory histories of the sampled genomes/populations unless additional individuals are analyzed.

      The link between oceanography and genomic connectivity is also mainly visual. Because this is a central aim, it should be tested quantitatively, for example by comparing a Lagrangian connectivity matrix with genetic distance while accounting for geographic distance. Similarly, the correlation between pairwise FST values across species should use a matrix-based permutation test rather than a standard Spearman p-value based on 10 non-independent comparisons. The Methods explicitly state that correlations between oceanography and population structure are tested, but no such analysis is reported.

      A few additional points need attention. The NNE-Mades G. orientalis is excluded from some analyses but retained in others despite strongly affecting results. The particle-drift model assumes passive 2D advection and omits larval behavior and vertical movement, which should be stated. Mitochondrial-nuclear discordance could also reflect stochasticity, introgression, or sex-biased dispersal. Finally, several inconsistencies need correction, including duplicate Figure S6/missing S7, four versus five populations in the Figure 2 caption, the ENA accession range, and several typos.

    1. Save it. Preset, then Save As. Name it, tick Public if the team should see it, and tick Load On Start if it should fill the dialog every time it opens.

      I've noticed these fake screenshots - we need real screenshots or videos

    1. Check the unposted transactions report

      I don't think this is an every day task - it's more of a an exceptional case that happens from an every day task. suggest it lives in teh reference section but is linked to from the 'post transactions to other systems' every day task article

    1. PRÓXIMAMENTETestimonios de PacientesEstamos reuniendo las experiencias de nuestros pacientes y alumnos para compartirlas próximamente en esta sección. Agradecemos su paciencia.

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